Compositions comprising coumarin or coumarin derivatives against cell senescence and skin ageing

Abstract

A composition for use in a method of treating a disease or disorder associated with cell senescence is described. The composition may comprise a derivative of coumarin or coumarin. Alternatively or additionally, the composition may comprise a plant extract comprising a derivative of coumarin or coumarin. Also described is a cosmetic method for preventing, minimising, or reducing cell senescence, the method comprising contacting the skin with such composition, wherein the method is not a method of treatment. Also described is a use of the composition for preventing, minimising, or reducing cell senescence.

Description

[0001]COMPOSITION BACKGROUND Epidermal thinning, whereby viable epidermis can lose involutions into the dermal layer, can cause skin to have an aged appearance. It may also cause medical problems, for example increased frequency of bruises and bleeding cuts. Loss of epidermal thickness can be attributed to loss of proliferative capacity of epidermal progenitor cells residing in the basal layer of the epidermis, and / or to increased cell senescence. Several compounds on the market claim to have anti-aging effects on skin, such as retinoids, niacinamide and ascorbic acid, but without specifically mentioning that they affect proliferative capacity of skin cells, such as keratinocytes. SUMMARY At its most general, the present invention relates to the use of a derivative of coumarin, or coumarin, to enhance cell viability by reducing, minimising, or preventing cell senescence. In some embodiments, the derivative of coumarin or coumarin is a derivative of coumarin. In some embodiments, the derivative of coumarin is osthole, or a related compound. Examples of a related compound may include, for example, a solvate of osthole. In such cases, the derivative of coumarin or coumarin may be osthole, or a solvate of osthole. Alternatively or additionally, the related compound may include a salt, or protected form (a protected form may include a prodrug, as appropriate) of osthole. The derivative of coumarin or coumarin may be provided as part of a plant extract. When the derivative of coumarin or coumarin is osthole, or a related compound, the osthole, or related compound, may be provided as part of a plant extract. Senescence may be defined as the loss of proliferative capacity of previously replicative cells. Such loss of proliferative capacity may arise as a result of stress signal activation. Some drug compounds are known which will prevent e.g. keratinocytes from senescing and prevent loss of proliferation. These may be suitable for medical purposes but may be less suitable or attractive for a cosmetic purpose. The present compounds may be naturally occurring or derived from naturally occurring compounds, such as natural plant extracts. Therefore, they may have suitability both in medical and cosmetic settings. Accordingly, in a first aspect, the present invention provides a composition for use in a method of treating a disease or disorder associated with cell senescence, the composition comprising: (a) a derivative of coumarin or coumarin; and / or (b) a plant extract comprising a derivative of coumarin or coumarin. In some embodiments, the derivative of coumarin or coumarin is osthole, or a salt, protected form, or solvate thereof. Accordingly, in some embodiments, the first aspect provides a composition for use in a method of treating a disease or disorder associated with cell senescence, the composition comprising: (a) osthole, or a salt, protected form, or solvate thereof; and / or (b) a plant extract comprising osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae. In some embodiments, the cell is a skin cell. The skin may be more exposed, and therefore more prone to certain kinds of medical problems such as bruising or cuts that can more typically have external causes, than other organs. In some embodiments, the disease or disorder is selected from a disease or disorder associated with thinning of a skin epidermal layer. In a second aspect, the present invention provides a method, such as a cosmetic method, for preventing, minimising or reducing cell senescence, the method comprising contacting skin cells with a composition comprising: (a) a derivative of coumarin or coumarin; and / or (b) a plant extract comprising a derivative of coumarin or coumarin wherein the method is not a method of treatment of the human or animal body. In some embodiments, the derivative of coumarin or coumarin is osthole, or a salt, protected form, or solvate thereof. Accordingly, in some embodiments, the second aspect provides a method, such as a cosmetic method, for preventing, minimising or reducing cell senescence, the method comprising contacting skin cells with a composition comprising: (a) osthole, or a salt, protected form, or solvate thereof; and / or (b) a plant extract comprising osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae, wherein the method is not a method of treatment of the human or animal body. In a third aspect, the present invention provides use of a composition comprising: (a) a derivative of coumarin or coumarin; and / or (b) a plant extract comprising a derivative of coumarin or coumarin, for preventing, minimising or reducing cell senescence. The use may be in vivo or ex vivo, such as in vitro. In some embodiments, the derivative of coumarin or coumarin is osthole, or a salt, protected form, or solvate thereof. Accordingly, in some embodiments, the third aspect provides use of a composition comprising: (a) osthole, or a salt, protected form, or solvate thereof; and / or (b) a plant extract comprising osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae, for preventing, minimising or reducing cell senescence. The use may be in vivo or ex vivo, such as in vitro. In some embodiments, the method of the second aspect and the use of the third aspect for preventing, minimising or reducing cell senescence is for preventing, minimising or reducing skin epidermal aging. The following embodiments are applicable to any of the first, second and / or third aspects, as appropriate. In some embodiments, the derivative of coumarin or coumarin encompasses more than one such compound, for example coumarin and one or more derivatives of coumarin, or more than one derivative of coumarin. In some embodiments, the derivative of coumarin or coumarin is osthole, or a solvate thereof. Accordingly, in some embodiments, the composition comprises (a) osthole, or a salt thereof, and / or (b) the plant extract comprising osthole, or a solvate thereof. In some embodiments, the method or use increases or promotes senescent cell proliferative capacity. In some embodiments, the method or use increases or promotes epidermal growth. In some embodiments, the method or use increases or promotes senescent cell proliferative capacity and epidermal growth. In this way, it may be possible to not only slow or prevent skin thinning but also promote skin thickening. In some embodiments, the method or use prevents, minimises, or reduces skin epidermal aging. In some embodiments, the method or use preserves, maintains, or improves skin epidermal thickness, function and / or quality. In some embodiments, the method or use prevents, minimises, or reduces skin epidermal aging and preserves, maintains or improves skin epidermal thickness, function and / or quality. In some embodiments, the skin is facial skin. The face may be more exposed than other areas of skin so that the cosmetic method may be particularly beneficial to facial skin. The face may be more exposed than other areas of skin so that the use may be particularly beneficial to facial skin from a medical perspective also. In some embodiments, the cell is an epidermal skin cell. The epidermis is an upper layer of the skin, so that application to the epidermal layer may be most straightforward. In some embodiments, the composition is administered topically. Topical application may be a straightforward application route, particularly if the cell is a skin cell. In some embodiments, the derivative of coumarin or coumarin is present in an amount of at least 0.005 μM in the composition. In some embodiments, the osthole, or salt, protected form, or solvate thereof, is present in an amount of at least 0.005 μM in the composition. In some embodiments, the plant extract is present in an amount of at least 5 μg / mL in the composition. Such quantities may provide particularly noticeable or desirable improvements in preventing cell senescence. In some embodiments, the plant extract is an Umbelliferae extract. In some embodiments, the plant extract is selected from an Angelica extract or a Cnidium extract. In some embodiments, the Angelica extract is an Angelica japonica extract. In some embodiments, the Cnidium extract is a Cnidium monnieri extract. Extracts from such sources may have particularly useful levels of osthole, or salts, protected forms, or solvates thereof. In some embodiments, the extract is or comprises an extract from the fruit of the plant. Extracts from the fruit of the plant, rather than other areas of the plant, may have particularly useful levels of osthole, or salts, protected forms, or solvates thereof. In some embodiments, the plant extract may comprise osthole, or a salt, protected form, or solvate thereof, and one or more further coumarin or coumarin derivative compounds. In some embodiments, the one or more further coumarin derivative compounds may be selected from xanthotoxin, bergapten, isopimpinellin and imperatorin. Such compounds may be found in plant extracts such as Cnidium monnieri. Such compounds may function in the same way as the osthole, or salt, protected form, or solvate thereof, or may enhance the effects observed by the present inventors of osthole, or salt, protected form, or solvate thereof. In some embodiments, the composition comprising osthole, or a salt, protected form, or solvate thereof (or plant extract comprising such) is provided in the form of a skin care product. In some embodiments, the skin care product is selected from skin / hand lotion, skin / hand cream, skin / hand gel, skin / hand ointment, skin / hand paste, skin toner, shaving gel, shaving cream, sunscreen, deodorant, antiperspirant, suntan lotion, after sun, aftershave, body oil, bath oil, bubble bath, and skin cleanser. Such forms may be particularly suitable vehicles for delivery of the osthole, and in particular for delivery of osthole to provide the effects described herein. These and other aspects and embodiments of the invention are described in further detail below. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a graph showing cell viability and proliferation in the presence of varying concentrations of osthole. Figure 2 is a graph showing cell viability and proliferation in the presence of varying concentrations of Cnidium monnieri extract. Figure 3 shows the results of a 3D assay of primary keratinocytes in the presence of (i) 0.1% DMSO; (ii) 5 mM Niacinamide (NAM); (iii) 5 μM osthole; and (iv) 25 μg / mL Cnidium monnieri extract carried out on a 39-year-old female. Scale bar represents 100 μm. Figure 4 shows the results of a 3D assay of primary keratinocytes in the presence of (i) 0.1% DMSO; (ii) 5 mM Niacinamide (NAM); (iii) 5 μM osthole; and (iv) 25 μg / mL Cnidium monnieri extract carried out on a 49-year-old male. Scale bar represents 100 μm. Figure 5 shows the variation in epidermis thickness (μm) with 0.1% DMSO; 5 mM Niacinamide (NAM); 5 μM osthole; and 25 μg / mL Cnidium monnieri extract for (i) 39- year-old female and (ii) 49-year-old male. Figure 6 shows a trend of increased LMNB1 expression with CME treatment with 0.1% DMSO; 5 mM Niacinamide (NAM); 5 μM osthole; and 25 μg / mL Cnidium monnieri extract. (i) shows results of LMNB1 expression; (ii) shows results of LMNB1 expression in K10 positive cells; and (iii) shows results of LMNB1 expression in K10 negative cells. Figure 7 shows graphs of (i) alamar blue signal intensity and (ii) nuclei count without Y27632; with Y27632; with 5 mM Niacinamide (NAM); and with 50 μM osthole after removal of Y27632. Figure 8 shows a graph of nuclei count without Y27632; with Y27632; with 50 μM osthole after removal of Y27632; and with varying concentrations of Cnidium monnieri extract after removal of Y27632. The dashed line shows the nuclei count with no Y27632, osthole or osthole-containing plant extract. Figure 9 (i) shows representative immunofluorescence images following full thickness skin culture. From left to right, the images show results of: incubation without Y27632; incubation with Y27632; incubation with 5mM NAM; incubation with 50 μM osthole; and incubation with 500 μg / mL Cnidium monnieri extract. Figure 9 (ii) shows the percentage of Ki67 positive cells present without Y27632; with Y27632; with 5 mM Niacinamide (NAM); with 50 μM osthole; and with 500 μg / mL of Cnidium monnieri extract (CME). Figures 10 and 11 show graphs indicating a decrease in cellular metabolism after removal of Y27632. (i) shows the results with osthole; and (ii) shows the results with Cnidium monnieri extract (CME). In (i) and (ii) the decrease in metabolism is reduced. DETAILED DESCRIPTION It is to be noted that any aspect of the invention may be combined with any other aspect of the invention unless the context demands otherwise. Any of the optional features of any one aspect may be combined, either singly or in combination, with any other aspect of the invention unless the context demands otherwise. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Methods and materials are described herein for use in the present disclosure; other suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. Methods described herein usually employ ambient temperature of a typical laboratory, which is typically between 20°C and 30°C, such as between 22°C and 26°C, such as around 23°C-25°C, at atmospheric pressure, unless a different condition is defined herein or is more usually employed in the art e.g. for a particular apparatus. Where embodiments discussed herein use the term “comprises” or the like, corresponding embodiments using the term “consists of” should be considered explicitly disclosed. The present invention generally describes compositions comprising a derivative of coumarin or coumarin for reducing, minimising, or eliminating cell senescence. In some embodiments, the coumarin derivative is osthole, or certain related compounds. In some embodiments the related compounds include salts, protected forms, or solvates of osthole, such as solvates of osthole. The compositions described herein may have a medical application. Accordingly, the composition may address or treat a disease or disorder associated with cell senescence. Such composition may comprise a derivative of coumarin or coumarin, such as osthole, or a salt, protected form, or solvate thereof. Such composition may comprise a plant extract comprising a derivative of coumarin or coumarin, such as osthole, or a salt, protected form, or solvate thereof. The plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae. The plant extract may be an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Euphorbiaceae and Apiaceae. Accordingly, in some embodiments the present invention provides a composition for use in a method of treating a disease or disorder associated with cell senescence, the composition comprising: (a) osthole, or a salt, protected form, or solvate thereof; and / or (b) a plant extract comprising osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae. In some embodiments, provided herein is a method for treating a disease or disorder associated with cell senescence, the method comprising contacting cells having senescent capacity with an effective amount of a composition comprising: (a) osthole, or a salt, protected form, or solvate thereof; and / or (b) a plant extract comprising osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae. In some embodiments, an effective amount of the composition provides a detectable reduction in cell senescence. Methods for detecting and quantifying cell senescence may include methods such as: visual methods, such as assessment of nuclei count, optical assessments of skin layer thickness, and / or or histological processing of skin; use of one or more cell senescence markers such as LMNB1; use of one or more proliferative cell biomarkers such as Ki67; and / or assessment of cellular metabolism. For example, assessing nuclei count may involve a method involving incubating cells with a test media for a suitable period, adding a visual aid, such as alamar® blue reagent, and fixing before assessing with an appropriate analysis equipment and / or software. Such assessment may involve use of a microscope. For example, an optical assessment of skin layer thickness may involve incubating a skin sample with a test media for a suitable period, staining with a reagent and fixing before assessing with an appropriate analysis equipment and / or software. Such assessment may involve use of a microscope. For example, a cell senescence marker may be included in a test media and / or used as part of a stain, or separately applied to a sample, and its quantity assessed with an appropriate analysis equipment and / or software. Such assessment may involve capturing and assessing immunofluorescence images, and / or use of a confocal laser scanning microscope. For example, a proliferative cell biomarker may be included in a test media and / or used as part of a stain, or separately applied to a sample, and its quantity assessed with an appropriate analysis equipment and / or software. Such assessment may involve use of immunofluorescence imaging and / or a confocal laser scanning microscope. For example, assessment of cellular metabolism may involve carrying out an appropriate assay and using brightfield imaging. Suitable assays and analysis techniques are described elsewhere herein. Detailed exemplary methods are provided elsewhere herein. In some embodiments, the method is an in vivo method. In some embodiments, the cell is an aged cell and the use prevents, reduces or minimises senescence in aged cells. An aged cell may show functional decline. An aged cell may show aging phenotypes such as senescence or loss of viability. An aged cell may be collected from a donor. An aged cell may be generated by subjecting a cell to one or more stressors (physical or chemical), and this may be done in vitro. In some embodiments, the cell is a skin cell. In some embodiment, the skin cell is a dermal skin cell, an epidermal skin cell, or a skin cell of the stratum. In some embodiments, the skin cell is an epidermal skin cell. In some embodiments, the epidermal skin cell is a keratinocyte. In some embodiments, the keratinocyte is a primary keratinocyte. In some embodiments, the cell is a K10-positive skin cell or a K10-negative skin cell. In some embodiments, the cell is a K10-negative skin cell. In some embodiments, the skin is skin on the head, such as on one or more of the face, mouth, neck, and scalp. In some embodiments, the skin is skin on one or more of the chest, back, arms, legs, and hands. In some embodiments, the treatment is treatment of a disorder causing thinning of the skin such as Gottron syndrome, Rothmund-Thomson syndrome, and epidermolysis bullosa, including epidermolysis bullosa simplex, dystrophic epidermolysis bullosa and junctional epidermolysis bullosa. In some embodiments, the treatment is a treatment of thinning of the skin arising from a condition associated with aging such as menopause, including premature aging as a result of e.g. smoking or pollutants or UV exposure. In some embodiments, the composition is administered to a subject in need of treatment. The subject in need of treatment (the patient) may be a mammal, such as a human. The subject in need of treatment may be an adult or juvenile, such as a human adult. Alternatively, the subject in need of treatment is a non-human animal used in laboratory research. In some embodiments, the treatment is administered by any convenient route of administration. In a preferred embodiment, the treatment is administered topically (i.e. at the site of desired action). In some embodiments, the treatment comprises administering a therapeutically-effective amount of the composition to a subject in need of treatment. It will be appreciated by one of skill in the art that appropriate dosages of the compositions described herein, can vary from patient to patient. Determining the optimal dosage will generally involve the balancing of the level of therapeutic benefit against any risk or deleterious side effects. The selected dosage level will depend on a variety of factors including, but not limited to, the activity of the particular derivative of coumarin or coumarin and plant extract, the route of administration, the time of administration, the rate of excretion of the derivative of coumarin or coumarin and plant extract, the duration of the treatment, other drugs, compounds, and / or materials used in combination, the severity of the disorder, and the species, sex, age, weight, condition, general health, and prior medical history of the patient. The amount of derivative of coumarin or coumarin and plant extract and route of administration will ultimately be at the discretion of the physician, veterinarian, or clinician, although generally the dosage will be selected to achieve local concentrations at the site of action which achieve the desired effect without causing substantial harmful or deleterious side-effects. Administration can be effected in one dose (application), continuously or intermittently (e.g., in divided doses at appropriate intervals) throughout the course of treatment. Methods of determining the most effective means and dosage of administration are well known to those of skill in the art and will vary with the formulation used for therapy, the purpose of the therapy, the target cell(s) being treated, and the subject being treated. Single or multiple administrations can be carried out with the dose level and pattern being selected by the treating physician, veterinarian, or clinician. The compositions described herein may have a cosmetic application. Accordingly, the composition may prevent, minimise or reduce cell senescence without being a method of treatment. For example, the composition may act to prevent cell senescence in aging skin wherein there is no disease or disorder causing the cell senescence aside from the aging process. Such compositions may comprise osthole, or a salt, protected form, or solvate thereof. Such compositions may comprise a plant extract comprising osthole, or a salt, protected form, or solvate thereof. The plant extract may be an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae. Accordingly, in some embodiments the present invention provides a cosmetic method for preventing, minimising or reducing cell senescence, the method comprising contacting the skin with a composition comprising: (a) osthole, or a salt, protected form, or solvate thereof; and / or (b) a plant extract comprising osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae, wherein the method is not a method of treatment. In some embodiments, the method is an in vivo method. In some embodiments, the method is an ex vivo method. In some such embodiments, the method is an in vitro method. Accordingly, in some embodiments the present invention also provides a use of a composition comprising: (a) osthole, or a salt, protected form, or solvate thereof; and / or (b) a plant extract comprising osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae, for preventing, minimising or reducing cell senescence. In the following, references to the composition refer to the composition as it may be used in any of the aspects described herein. Osthole is a part of the coumarin family of compounds. Thus, the present inventors believe that coumarins could have effects as exemplified herein for osthole. Coumarin has the chemical structure: The compositions herein may comprise a derivative of coumarin or coumarin. A coumarin derivative is a compound having the 2H-chromen-2-one core, where one or both of the coumarin rings is substituted. The core may be substituted at a carbon ring atom, such as at one or more of ring positions 3 to 8, such as 7 and / or 8. The benzene ring of the 2H-chromen-2-one core may be substituted, such as with one or two substituents, such as one. The heterocyclic ring of the 2H-chromen-2-one core may be substituted, such as with one or two substituents, such as one. The 2H-chromen-2-one core may be monosubstituted or disubstituted, such as disubstituted. The 2H-chromen-2-one core may have a furan ring fused to it. The furan may be fused to the benzene ring, and the carbon ring atoms at positions 6 and 7 of the core may participate in the furan ring system. The 2H-chromen-2-one core may be substituted with one or more, such as one or two, such as one, hydroxyl group. The derivative may have a molecular weight of at most 500, such as at most 400, such as at most 300. The derivative may have a molecular weight of at least 146, such as at least 150, such as at least 200. The derivative may be a salt, a protected form (such as a prodrug), or a solvate. The derivative may include up to three short-chain groups (such as groups containing C1-C6alkyl, alkenyl or alkylyl chains containing 0-2 heteroatoms selected from O, S and N(H), for example an -OH group and / or an -OMe group and / or a -CH2CHC(Me)2group and / or a -OCH2CC(Me)2group) attached to one or more of the coumarin rings. An exemplary derivative of coumarin is osthole. Accordingly, the compositions herein may comprise osthole, or a salt, protected form, or solvate thereof, such as osthole, or a solvate thereof. Osthole, also known as osthol, has CAS registry number 484-12-8. Osthole has the chemical structure: The osthole compound described herein may be provided in the form of a solvate (a complex of solute (e.g., compound, salt of compound) and solvent). Examples of solvatesinclude hydrates, for example, a mono-hydrate, a di-hydrate and a tri-hydrate. The ostholecompound described herein may be provided in desolvated form, for example, in dehydrated form. Other exemplary derivatives of coumarin include imperatorin, bergapten, xanthotoxin, isopimpinellin and umbelliferone. These have the structures shown below: Imperatorin Bergapten Xanthotoxin Isopimpinellin Umbelliferone In some embodiments, the composition may comprise a coumarin derivative compound selected from one or more of xanthotoxin, bergapten, isopimpinellin, umbelliferone and imperatorin, or a salt, protected form, or solvate of any of these (referred to “thereof” for brevity herein). In some embodiments, the composition comprises the one or more of xanthotoxin, bergapten, isopimpinellin, umbelliferone and imperatorin, or the salt, protected form, or solvate thereof, in addition to the derivative of coumarin or coumarin. In some embodiments, the composition comprises the one or more of xanthotoxin, bergapten, isopimpinellin, umbelliferone and imperatorin, or the salt, protected form, or solvate thereof, in addition to the osthole, or a salt, protected form, or solvate thereof. In some embodiments, the composition comprises one or more of the bergapten, imperatorin, umbelliferone and xanthotoxin or the salt, protected form, or solvate thereof. In some embodiments, the composition comprises one or more of the bergapten, imperatorin, and xanthotoxin or the salt, protected form, or solvate thereof. In some embodiments, the composition comprises one or more of bergapten and imperatorin, or the salt, protected form, or solvate thereof. In such embodiments, the at least one of xanthotoxin, bergapten, isopimpinellin, umbelliferone and imperatorin is the compound or a solvate thereof.The composition herein may comprise an effective amount, such as a therapeutically orcosmetically effective amount, of the coumarin or coumarin derivative compound described herein.In some embodiments, the composition herein comprises derivative of coumarin orcoumarin, such as osthole or a salt, protected form, or solvate thereof, in an amount of at least 0.0001 wt%, such as at least 0.0005 wt%, at least 0.001 wt%, at least 0.005 wt%, at least 0.01 wt%, at least 0.05 wt% or at least 0.1 wt% based on the total weight of the composition. In some embodiments, the composition herein comprises derivative of coumarin or coumarin, such as osthole or a salt, protected form, or solvate thereof, in an amount of up to 5.0 wt%, such as up to 4.9 wt%, up to 4.8 wt%, up to 4.7 wt%, up to 4.6 wt%, up to 4.5 wt%, or up to 4.0 wt% based on the total weight of the composition. In some embodiments, the composition herein comprises derivative of coumarin or coumarin, such as osthole or a salt, protected form, or solvate thereof, in an amount of between 0.0001 to 5.0 wt%, such as 0.005 to 4.5 wt%, 0.001 to 4.9 wt%, 0.005 to 4.8 wt%, or 0.1 to 4.0 wt% based on the total weight of the composition. In some embodiments, the composition herein comprises derivative of coumarin or coumarin, such as osthole or a salt, protected form, or solvate thereof, in an amount of at least 0.005 μM, such as at least 0.01 μM, at least 0.05 μM, at least 0.1 μM, at least 0.5 μM or at least 1.0 μM. In some embodiments, the composition herein comprises derivative of coumarin or coumarin, such as osthole or a salt, protected form, or solvate thereof, in an amount of up to 1 mM, such as up to 500 μM, up to 100 μM or up to 50 μM. In some embodiments, the composition herein comprises derivative of coumarin or coumarin, such as osthole or a salt, protected form, or solvate thereof, in an amount of from 0.005 μM to 1 mM, such as 0.01 μM to 1 mM, 0.1 μM to 500 μM, or 0.1 μM to 100 μM. Similar amounts of the bergapten, imperatorin, umbelliferone and xanthotoxin or the salts, protected forms, or solvate thereofs, can be considered. In some embodiments, the composition herein comprises a plant extract. The plant extract comprises osthole, or a salt, protected form, or solvate thereof. The plant extract may be an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae. The plant extract may be an extract from any suitable species of the family Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae. The plant extract may be an extract from any suitable species of the family Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Euphorbiaceae and Apiaceae. The plant extract may be an extract from any suitable species of the family Umbelliferae, Asteraceae, Rutaceae, and Fabaceae. The plant extract may be an extract from any suitable species of the family Umbelliferae, Asteraceae, and Rutaceae. The plant extract may be an extract from any suitable species of the family Umbelliferae. Suitable plant extracts may be commercially available, and may, for example, be purchased from BOC Sciences, Dermalab, Imaherb, Nutri herb, Targetmol, and Rainwood. In some embodiments, the plant extract is an Umbelliferae extract. In some embodiments, the plant extract is selected from an Angelica extract and a Cnidium extract. In some embodiments, the Angelica extract is an Angelica pubescens extract, such as Radix Angelicae pubescentis. In some embodiments, the Angelica extract is an Angelica japonica extract. In some embodiments, the Cnidium extract is a Cnidium monnieri extract. In some embodiments, the plant extract is an Asteraceae extract. In some embodiments, the plant extract is an Atractylodes extract. In some embodiments, the plant extract is a Sigesbeckia extract. In some embodiments, the Atractylodes extract is an Atracylodes lancea extract. In some embodiments, the Sigesbeckia extract is a Siegesbeckiae herba. In some embodiments, the plant extract is a Rutaceae extract. In some embodiments, the plant extract is a Citrus extract. In some embodiments, the Citrus extract is a Citrus aurantium extract. In some embodiments, the plant extract is a Clausena extract. In some embodiments, the Clausena extract is a Clausena lansium extract. In some embodiments, the extract is a Fabaceae extract. In some embodiments, the plant extract is a Cullen extract. In some embodiments, the Cullen extract is a Cullen corylifolium (Psoralea corylifolia) extract. In some embodiments, the extract is a Euphorbiaceae extract. In some embodiments, the plant extract is a Euphorbia extract. In some embodiments, the Euphoria extract is a Euphorbia fischeriana extract. In some embodiments, the extract is a Apiaceae extract. In some embodiment, the plant extract is a Peucedanum extract. In some embodiments, the plant extract is a Prangos extract. In some embodiments, the plant extract is a Seseli extract. In some embodiments, the Peucedanum extract is a Peucedanum osthruthium extract. In some embodiments, the Prangos extract is a Prangos ferulacea extract. In some embodiments, the Seseli extract is a Seseli gummiferum extract. The plant extract may be derived from any suitable part of the plant. Suitable parts of the plant include roots, stems such as rhizomes, leaves, flowers, fruits and seeds. Examples of suitable fruit extracts include Cnidium monnieri fruit extract, Citrus aurantium fruit extract, Prangos ferulacea fruit extract. Examples of suitable stem extracts include Atracylodes lancea stem extract and Peucedanum osthruthium stem extract, which may be a rhizome extract. Examples of suitable root extracts include Angelica japonica root extract, Radix Angelicae pubescentis root extract, Clausena lansium root extract, Euphorbia fischeriana root extract. Examples of suitable leaf extracts include Prangos ferulacea leaf extract. Examples of suitable seed extracts include Cnidium monnieri seed extract and Psoralea corylifolia seed extract. In some embodiments, the plant extract is selected from Cnidium monnieri extract, Citrus aurantium extract, Atracylodes lancea extract, Angelica japonica extract and Psoralea corylifolia extract. In some embodiments, the plant extract is a Cnidium monnieri extract. In some embodiments, the plant extract comprises osthole at a concentration of between 5 and 50 mg / g of extract, such as between 5 and 40 mg / g, between 5 and 30 mg / g, between 10 and 40 mg / g or between 10 and 30 mg / g of extract. In some embodiments, the plant extract comprises osthole at an amount of between 1.0-3.0 wt%, based on the total weight of the extract. In some embodiments, the osthole is present in the plant extract at an amount of between 1.0-2.5 wt%, such as 1.1-2.5 wt% or 1.2-2.5 wt%, based on the total weight of the extract. In some embodiments, the composition may comprise a coumarin derivative compound selected from one or more of xanthotoxin, bergapten, isopimpinellin, umbelliferone and imperatorin, or a salt, protected form, or solvate of any of these (referred to “thereof” for brevity herein). In some embodiments, the plant extract comprises the one or more of xanthotoxin, bergapten, isopimpinellin, umbelliferone and imperatorin, or the salt, protected form, or solvate thereof, in addition to the derivative of coumarin or coumarin. In some embodiments, the plant extract comprises the one or more of xanthotoxin, bergapten, isopimpinellin, umbelliferone and imperatorin, or the salt, protected form, or solvate thereof, in addition to the osthole, or a salt, protected form, or solvate thereof. In some embodiments, the plant extract comprises one or more of the bergapten, imperatorin, umbelliferone and xanthotoxin or the salt, protected form, or solvate thereof. In some embodiments, the plant extract comprises one or more of the bergapten, imperatorin, and xanthotoxin or the salt, protected form, or solvate thereof. In some embodiments, the plant extract comprises one or more of bergapten and imperatorin, or the salt, protected form, or solvate thereof. In such embodiments, the at least one of xanthotoxin, bergapten, isopimpinellin, umbelliferone and imperatorin is the compound or a solvate thereof. The plant extract herein may comprise an effective amount, such as a therapeutically or cosmetically effective amount, of the coumarin derivative compound described herein. In some embodiments, the bergapten is present in the plant extract in an amount of at least 0.1 mg per g of plant extract, such as at least 0.2 mg per g of plant extract, at least 0.5 mg per g of plant extract, or at least 1 mg per g of plant extract. In some embodiments, the bergapten is present in the plant extract in an amount of up to 10 mg per g of plant extract, such as up to 8 mg per g of plant extract, up to 6 mg per g of plant extract, or up to 5 mg per g of plant extract. In some embodiments, the bergapten is present in the plant extract in an amount of between 0.1 and 10 mg per g of plant extract, such as between 0.1 and 8 mg per g of plant extract, between 0.1 and 5 mg per g of plant extract, between 0.2 and 6 mg per g of plant extract, or between 0.5 and 5 mg per g of plant extract. In some embodiments, the isopimpinellin is present in the plant extract in an amount of at least 0.1 mg per g of plant extract, such as at least 0.2 mg per g of plant extract, at least 0.5 mg per g of plant extract, or at least 1 mg per g of plant extract. In some embodiments, the isopimpinellin is present in the plant extract in an amount of up to 10 mg per g of plant extract, such as up to 8 mg per g of plant extract, up to 6 mg per g of plant extract, or up to 5 mg per g of plant extract. In some embodiments, the isopimpinellin is present in the plant extract in an amount of between 0.1 and 10 mg per g of plant extract, such as between 0.1 and 8 mg per g of plant extract, between 0.1 and 5 mg per g of plant extract, between 0.2 and 6 mg per g of plant extract, or between 0.5 and 5 mg per g of plant extract. In some embodiments, the imperatorin is present in the plant extract in an amount of at least 0.5 mg per g of plant extract, such as at least 1 mg per g of plant extract, at least 1.5 mg per g of plant extract, or at least 2 per g of plant extract. In some embodiments, the imperatorin is present in the plant extract in an amount of up to 15 mg per g of plant extract, such as up to 14 mg per g of plant extract, up to 12 mg per g of plant extract, or up to 10 mg per g of plant extract. In some embodiments, the imperatorin is present in the plant extract in an amount of between 0.5 and 15 mg per g of plant extract, such as between 0.5 and 10 mg per g of plant extract, between 1 and 12 mg per g of plant extract, between 1.5 and 14 mg per g of plant extract, or between 2 and 10 mg per g of plant extract. In some embodiments, the xanthotoxin is present in the plant extract in an amount of at least 0.1 mg per g of plant extract, such as at least 0.2 mg per g of plant extract, at least 0.5 mg per g of plant extract, or at least 1 mg per g of plant extract. In some embodiments, the xanthotoxin is present in the plant extract in an amount of up to 10 mg per g of plant extract, such as up to 8 mg per g of plant extract, up to 6 mg per g of plant extract, or up to 5 mg per g of plant extract. In some embodiments, the xanthotoxin is present in the plant extract in an amount of between 0.1 and 10 mg per g of plant extract, such as between 0.1 and 8 mg per g of plant extract, between 0.1 and 5 mg per g of plant extract, between 0.2 and 6 mg per g of plant extract, or between 0.5 and 5 mg per g of plant extract. In some embodiments, the umbelliferone is present in the plant extract in an amount of at least 0.1 mg per g of plant extract, such as at least 0.2 mg per g of plant extract, at least 0.5 mg per g of plant extract, or at least 1 mg per g of plant extract. In some embodiments, the umbelliferone is present in the plant extract in an amount of up to 10 mg per g of plant extract, such as up to 8 mg per g of plant extract, up to 6 mg per g of plant extract, or up to 5 mg per g of plant extract. In some embodiments, the umbelliferone is present in the plant extract in an amount of between 0.1 and 10 mg per g of plant extract, such as between 0.1 and 8 mg per g of plant extract, between 0.1 and 5 mg per g of plant extract, between 0.2 and 6 mg per g of plant extract, or between 0.5 and 5 mg per g of plant extract. In some embodiments, a ratio (mg per g of plant extract) of bergapten to osthole is in the range 0.01 to 2, such as 0.05 to 1.5, or 0.06 to 1.2. In some embodiments, a ratio (mg per g of plant extract) of isopimpinellin to osthole is in the range 0.01 to 1, such as 0.05 to 0.5, or 0.06 to 0.3. In some embodiments, a ratio (mg per g of plant extract) of imperatorin to osthole is in the range 0.05 to 1, such as 0.08 to 0.8, or 0.1 to 0.7. In some embodiments, a ratio (mg per g of plant extract) of xanthotoxin to osthole is in the range 0.01 to 2, such as 0.05 to 1.5, or 0.06 to 1.2. In some embodiments, the plant extract may further comprise other compounds or components. The nature of these further compounds or components may depend on the plant from which the extract is obtained, and / or the part of the plant from which the extract is obtained. In some embodiments, the plant extract further comprises one or more selected from 2'- acetlyangelicin, oroselone, o-acetylcolumbianetin, hydroxycindimoside A, cnidimoside A, cnidimol D, auraptenol, 20-hydrate-deoxymeranin, phlojodicarpin, (E / Z) 7-methoxy-8-(3- methylbuta-1,3-dien-1-yl)-2H-chromen-2-one, (E / Z) 7-methoxy-8-(3-methylbuta-1,3-dien- 1-yl)-2H-chromen-2-one, karenin, columbianadin, cniforin A, and daucosterol. In some embodiments, the plant extract further comprises (i) 2'-acetlyangelicin, oroselone and o- acetylcolumbianetin; (ii) hydroxycindimoside A, cnidimoside A, cnidimol D, auraptenol, 20-hydrate-deoxymeranin, phlojodicarpin, (E / Z) 7-methoxy-8-(3-methylbuta-1,3-dien-1- yl)-2H-chromen-2-one, (E / Z) 7-methoxy-8-(3-methylbuta-1,3-dien-1-yl)-2H-chromen-2- one, karenin, columbianadin and cniforin A; and / or (iii) daucosterol. In some embodiments, the plant extract comprising these is an extract of Cnidium monnieri. In some embodiments, the plant extract comprising these is from the fruit, such as from the fruit of Cnidium monnieri. The plant extract may be prepared using any suitable extraction method. Suitable extraction methods include extraction using an organic extraction solvent. Suitable organic extraction solvents may include n-hexane, petroleum ether, ethanol, methanol, or mixtures of n-hexane or methanol with ethyl acetate. The organic extraction solvent may be or comprise n-hexane, ethanol or methanol. The organic extraction solvent may be or comprise ethanol. In some embodiments, the plant extract is an ethanolic extract. In some embodiments, the extraction process comprises ultrasonication. The contents of the plant extract may be analysed using any suitable method known in the art. For example, a pressurized capillary electrochromatography / UV method, or a HPLC- based method such Suitable extraction processes and methods of measuring the quantity of osthole therein may be found in the literature; for example, see Journal of Pharmaceutical and Biomedical Analysis 50 (2009), 695-702 and Food Chemistry 141 (2013), 1962-1971, which may be particularly relevant to extracts of Cnidium monnieri, as well as Z Naturforsch C J Biosci. 200964(1-2):56-62; J. Nat. Prod. 1998, 61, 347-350; J. Nat. Prod. 2014, 77, 1215-1223; J. Agric. Food Chem., 2008, 56, 5577-5581; J. Agric. Food Chem., 2011, 59, 4371-4377; Research in Pharmaceutical Sciences, 2009; 4(1): 19-23; Journal of Pharmaceutical and Biomedical Analysis 77 (2013) 71-75; and Journal of Chromatography B, 937 (2013) 18- 24, for other extracts. The plant extract may be used directly following the extraction procedure. In some embodiments, the plant extract may be further treated e.g. to increase the concentration of osthole optionally together with other compounds within the extract. The composition herein may comprise an effective amount, such as a therapeutically or cosmetically effective amount, of the plant extract described herein. The plant extract may be a dry extract. In some embodiments, the dry extract may be solubilised before incorporation into a composition. In some embodiments, the solubilisation includes addition of a solvent to the dry extract to form a solution. A Cnidium monnieri plant extract may comprise one or more of, such as all of, the following compounds of Table 1, at an amount in the range given. Table 1. Components of dry Cnidium monnieri plant extract Compound Concentration Range (mg / g) bergapten 1.1-3.41 imperatorin 2.95-7.25 osthole 0.5-16.31 2'-acetlyangelicin 4.07-6.13 oroselone 3.88-8.26 o-acetylcolumbianetin 3.89-7.86 In some embodiments, the amount of osthole of such plant extracts can be concentrated. In some embodiments, a concentrated amount of osthole will provide a plant extract having osthole in a concentration range more than 50%, such as 60%, 70%, 75%, 80%, 90%, 95%, 99% or 100% higher. Accordingly, a Cnidium monnieri plant extract may comprise one or more of, such as all of, the compounds of Table 1, but having osthole at a concentration of up to 32.62 mg / g, up to 30.99 mg / g, up to 29.36 mg / g, up to 27.73 mg / g, up to 26.1 mg / g, or up to 24.47 mg / g. In one example, a Cnidium monnieri plant extract may have osthole at a concentration of 0.95mg / g. Extraction of the plant material may be conducted using standard solvents such as ethanol or DMSO. To enhance extraction efficiency, methods such as prolonged ultrasonication and application of controlled elevated temperatures may be utilized. Following extraction, the sample is analyzed by gas chromatography-mass spectrometry (GC-MS). The separation of analytes can be achieved using a typical capillary column such as Rtx-5MS column and a standard carrier gas such as helium under optimized flow condition. The concentration of osthole in the extract is determined by comparison to known standards. The composition herein comprises the plant extract in any suitable amount to provide an effective amount of osthole, or salt, protected form, or solvate thereof. Accordingly, the amount of plant extract in the composition herein may depend on factors such as, for example, the amount of osthole in the plant extract used. In some embodiments, the composition herein comprises the plant extract at an amount of at least 0.005 wt%, such as at least 0.01 wt%, at least 0.05 wt% or at least 0.1 wt%, based on the total weight of the composition. In some embodiments, the composition herein comprises the plant extract at an amount of up to 10 wt%, such as up to 9.5 wt%, up to 9.0 wt% or up to 8.5 wt%, based on the total weight of the composition. In some embodiments, the composition herein comprises the plant extract at an amount of between 0.005 and 10 wt%, such as between 0.01 and 9.0 wt%, between 0.05 and 9.5 wt%, or between 0.1 and 8.5 wt%, based on the total weight of the composition. In some embodiments, the composition herein comprises the plant extract in an amount of at least 0.1 μg / mL, such as at least 1 μg / mL, at least 5 μg / mL or at least 10 μg / mL, based on the total amount of the composition. In some embodiments, the composition herein comprises the plant extract in an amount of up to 10 mg / mL, such as up to 5 mg / mL, up to 2 mg / mL or up to 1 mg / mL, based on the total amount of the composition. In some embodiments, the composition herein comprises the plant extract in an amount of between 0.1 μg / mL to 10 mg / mL, such as between 1 μg / mL and 2 mg / mL, between 5 μg / mL and 5 mg / mL, or between 10 μg / mL and 1 mg / mL. The compositions herein may be formulated for cosmetic or therapeutic uses. Accordingly, the composition may additionally comprise one or more pharmaceutically or cosmetically acceptable ingredients. Pharmaceutically cosmetically acceptable ingredients are those which, within the scope of sound judgment, are suitable for use in contact with the tissues of the subject in question (e.g., human) without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. Each ingredient must also be compatible with the other ingredients of the composition. In some embodiments, the composition comprises one or more ingredients selected from solvents, oils, surfactants, thickeners, humectants, and preservatives. Examples of suitable solvents includes water; mono-alcohols such as ethanol, isopropanol, benzyl alcohol, and phenylethyl alcohol; polyalcohols such as ethylene glycol, propylene glycol, butane-1,3-diol, mannitol, sorbitol, glycerol, and erythritol; and glycol ethers such as ethylene glycol monomethyl ether and diethylene glycol monomethyl ether. Examples of suitable oils include mineral oils, plant oils and waxes. Examples of suitable plant oils include algal oil, annatto oil, argan oil, almond oil, apricot kernel oil, avocado oil, babassu oil, Brazil nut butter, butter, cashew butter, castor oil, camellia oil, cheery kernel oil, cocoa butter, coconut oil, corn oil, cottonseed oil, fish oil, grape seed oil, gardenia oil, ghee, hazelnut oil, jatropha oil, jojoba oil, kokum oil, linseed oil, macadamia oil, maize oil, mango seed oil, mango butter, mineral oil, mink oil, olive oil, palm oil, palm kernel oil, peach kernel 5 oil, peanut butter, peanut oil, plum kernel oil, pomegranate oil, rapeseed seed oil, rice bran oil, rosehip oil, sal oil, sesame oil, shea butter, soybean oil, squalene, sunflower oil, teas seed oil, walnut oil. Examples of suitable waxes include bayberry wax, beeswax, carnauba wax (palm wax), candelilla wax, ceresin, jojoba butter, lanolin wax, montan wax, ozokerite, polyglyceryl-3- beeswax, polyglyceryl-6-pentastearate, Japan wax, microcrystalline wax, paraffin wax, isoparaffin, vaseline solid paraffin, squalene, oligomer olefins, synthetic candelilla wax, synthetic carnauba, and synthetic beeswax. Surfactants (surface-active agents) may act as dispersants or wetting agents. Examples of suitable surfactants include anionic surfactants, cationic surfactants, non-ionic surfactants, and amphoteric (zwitterionic) surfactants. Examples of suitable anionic surfactants include ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanolamine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, lauric monoglyceride sodium sulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium lauryl sulfate, potassium laureth sulfate, sodium lauryl sarcosinate, sodium lauroyl sarcosinate, lauryl sarcosine, cocoyl sarcosine, ammonium cocoyl sulfate, ammonium lauroyl sulfate, sodium cocoyl sulfate, sodium lauroyl sulfate, potassium cocoyl sulfate, potassium lauryl sulfate, triethanolamine lauryl sulfate, triethanolamine lauryl sulfate, monoethanolamine cocoyl sulfate, monoethanolamine lauryl sulfate, sodium tridecyl benzene sulfonate, and sodium dodecyl benzene sulfonate Examples of suitable cationic surfactants include behentrimonium chloride, cocotrimonium chloride, cethethyldimonium bromide, dibehenyidimonium chloride, dihydrogenated tallow benzylmonium chloride, disoyadimonium chloride, ditallowdimonium chloride, hydroxycetyl hydroxyethyl dimonium chloride, hydroxyethyl behenamidopropyl dimonium chloride, Hydroxyethyl cetyidimonium chloride, hydroxyethyl tallowdimonium chloride, myristalkonium chloride, PEG-2 oleamonium chloride, PEG-5 stearmonium chloride, PEG-15 cocoyl quaternium 4, PEG-2 stearalkonium 4, lauryltrimonium chloride; Quaternium-16; Quaternium-18, lauralkonium chloride, olealkmonium chloride, cetylpyridinium chloride, Polyquaternium-5, Polyquaternium-6, Polyquaternium-7, Polyquaternium-10, Polyquaternium-22, Polyquaternium-37, Polyquaternium-39, Polyquaternium-47, cetyl trimonium chloride, dilauryidimonium chloride, cetalkonium chloride, dicetyidimonium chloride, soyatrimonium chloride, and stearyl octyl dimonium methosulfate. Examples of suitable non-ionic surfactants include fatty alcohol ethoxylates such as octaethylene glycol monododecyl ether, and pentaethylene glycol monododecyl ether; alkylphenol ethoxylates (APEs or APEOs) such as Nonoxynol-4, Nonoxynol-7, Nonoxynol-9, Nonoxynol-14, Nonoxynol-15, Nonoxynol-18, and triton X-100; glycerol fatty acid esters such as glycerol monostearate, and glycerol monolaurate; sorbitol fatty acid esters such as sorbitan monolaurate, sorbitan monostearate, sorbitan tristearate, polysorbate (Tween) 20, polysorbate 40, polysorbate 60, and polysorbate 80. Examples of suitable amphoteric (zwitterionic) surfactants include cocamidopropyl hydroxysultaine, cocamidopropyl betaine, lauryl betaine, lauryldimethylamine oxide, and myristamine oxide. Examples of suitable thickeners (rheological modifiers) include gums such as alginates, carageenans, gum acacia, gum arabic, gum ghatti, gum karaya, gum tragacanth, guar gum; guar hydroxypropyltrimonium chloride, xanthan gum or gellan gum; cellulose derivatives such as sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxymethyl carboxyethyl cellulose, hydroxymethyl carboxypropyl cellulose, ethyl cellulose, sulfated cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxypropylmethyl cellulose, microcrystalline cellulose; agar; pectin; gelatin; starch and its derivatives; chitosan and its derivatives such as hydroxyethyl chitosan; synthetic polymers such as polyvinyl alcohol, PVM / MA copolymer, PVM / MA decadiene crosspolymer, poly(ethylene oxide) based thickeners; Humectants may act as hygroscopic agents, increasing the amount of water absorbed or retained by the composition. Examples of suitable humectants include acetamide MEA, ammonium lactate, chitosan and its derivatives, colloidal oatmeal, galactoarabinan, glucose glutamate, glerecyth-7, glygeryth-12, glycereth-26, glyceryth-31, glycerin, lactamide MEA, lactamide DEA, lactic acid, methyl gluceth-10, methyl gluceth-20, panthenol, propylene glycol, sorbitol, polyethylene glycol, 1,3-butanediol, 1,2,6-hexanetriol, hydrogenated starch hydrolysate, inositol, mannitol, PEG-5 pentaerythritol ether, polyglyceryl sorbitol, xylitol, sucrose, sodium hyaluronate, and sodium PCA. Examples of suitable preservatives includes methyl p-hydroxybenzoate, propyl p- hydroxybenzoate and sorbic acid. Methyldibromo glutaronitrile (MDBGN), benzyl alcohol, imidazolidinyl urea 1,3-bis (hydroxymethyl)-5,5-dimethyl-2,3-imidazolidinedione (DMDM hydantoin), methylchloroisothiazolinone and methylisothiazolinone, phenoxyethanol, and sodium benzoate. In some embodiments, the composition comprises one or more ingredients selected from emollients, anti-inflammatory agents, antioxidants and UV blocking agents. Examples of suitable emollients include fatty esters such as isopropyl myristate, isopropyl palmitate, caprylic / capric triglycerides, cetyl lactate, cetyl palmitate, hydrogenated castor oil, glyceryl esters, hydroxycetyl isostearate, hydroxy cetyl phosphate, isopropyl isostearate, isostearyl isostearate, diisopropyl sebacate, PPG-5-Ceteth-20, 2-ethylhexyl isononoate, 2-ethylhexyl stearate, C12 to C16 fatty alcohol lactate, isopropyl lanolate, and 2-ethyl-hexyl salicylate. Examples of suitable anti-inflammatory ingredients include cyclo-oxygenase (e.g., COX-1 or COX-2) or Lipoxygenase (e.g., LOX-5) enzyme inhibitors such as ascorbic acid, ascorbic acid derivatives, vitamin E, vitamin E derivatives, tocotrienol, rutin, quercetin, hesperidin (Citrus sinensis), hesperetin (Citrus sinensis), diosmin (Citrus sinensis), mangiferin (Mangifera indica), mangostin (Garcinia mangostana), cyanidin (Vaccinium myrtillus), astaxanthin (Haematococcus algae), lutein patula), lycopene (Lycopersicum esculentum), resveratrol (Polygonum cuspidatum), tetrahydrocurcumin (Curcuma longa), rosmarinic acid (Rosmarinus officinalis), hypericin (Hypericum perforatum), ellagic acid (Punica granatum), chlorogenic acid (Vaccinium vulgaris), oleuropein (Olea europaea), alpha-lipoic acid, glutathione, andrographolide (Andrographis paniculata), grapeseed extract, green tea extract, polyphenols, pycnogenol (pine bark extract), white tea extract, black tea extract, (Andrographis paniculata), carnosine, and niacinamide. Further examples of suitable anti-inflammatory composition can additionally be selected from horse chestnut extract (Aesculus hippocastanum extract), esculin, escin, yohimbine, Capsicum oleoresin, capsaicin, niacin, niacin esters, methyl nicotinate, benzyl nicotinate, ruscogenins (Butchers Broom extract; Ruscus aculeatus extract), diosgenin (Trigonel afoenumgraecum, fenugreek), emblica extract (Phyllanthus emblica extract), asiaticoside (Centella asiatica extract), Boswellia extract (Boswellia serrata), sericoside, visnadine, thiocolchicoside, grapeseed extract, ginger root extract (Zingiber officianale), piperine, vitamin K, melilot (Melilotus officinalis extract), glycyrrhetinic acid, ursolic acid, sericoside (Terminalia sericea extract), darutoside (Siegesbeckia orientalis extract), Amni visnaga extract, vine leaf extract (Vitis vinifera), apigenin, phytosan, luteolin. Examples of suitable antioxidant ingredients include ascorbic acid, ascorbic acid derivatives glucosamine ascorbate, arginine ascorbate, lysine ascorbate, glutathione ascorbate, nicotinamide ascorbate, niacin ascorbate, allantoin ascorbate, creatine ascorbate, creatinine ascorbate, chondroitin ascorbate, chitosan ascorbate, carnosine ascorbate, vitamin E, vitamin E derivatives, tocotrienol, rutin, quercetin, hesperidin (Citrus sinensis), hesperetin (Citrus sinensis), diosmin (Citrus sinensis), mangiferin (Mangifera indica), mangostin (Garcinia mangostana), cyanidin (Vaccinium myrtillus), astaxanthin (Haematococcus algae), lutein (Tagetes patula), lycopene (Lycopersicum esculentum), resveratrol (Polygonum cuspidatum), tetrahydrocurcumin (Curcuma longa), rosmarinic acid (Rosmarinus officinalis), hypericin (Hypericum perforatum), ellagic acid (Punica granatum), chlorogenic acid (Vaccinium vulgaris), oleuropein (Olea europaea), alpha- lipoic acid, niacinamide lipoate, glutathione, andrographolide (Andrographis paniculata), carnosine, niacinamide, Potentilla erecta extract, polyphenols, grapeseed extract, pycnogenol (pine bark extract), pyridoxine, magnolol, honokiol, paeonol, resacetophenone, quinacetophenone, arbutin and kojic acid. Examples of suitable UV blocking agents (sunscreen active agents) include octyl methoxycinnamate (ethylhexyl p-methoxycinnamate), octyl salicylate oxybenzone (benzophenone-3), benzophenone-4, menthyl anthranilate, dioxybenzone, aminobenzoic acid, amyl dimethyl PABA, diethanolamine p-methoxy cinnamate, ethyl 4-bis (hydroxypropyl) aminobenzoate, 2-ethylhexy 1-2-cyano-3,3-diphenylacrylate, homomenthyl salicylate, glyceryl aminobenzoate, dihydroxyacetone, octyl dimethyl PABA, 2-phenylbenzimidazole-5-sulfonic acid, triethanolamine salicylate, zinc oxide, titanium oxide, and mixtures thereof. Further components suitable for use in the composition may include fragrances, pH adjusters, pigments, odour absorbers, antimicrobial agents, antifungal agents, chelating agents, and saccharides. In some embodiments, the composition herein is formulated for topical use, such as for topical use on skin, and for topical use on human skin. The composition herein may be formulated as a solution, liquid, lotion, cream, emulsion, dispersion, gel, or paste. Examples of suitable emulsions include two-phase emulsions comprising an aqueous phase and an oil phase such as oil-in-water (O / W) and water-in-oil (W / O), as well as complex emulsions such as triple emulsions (O / W / O and W / O / W). The composition and formulations may be prepared by any methods well known in the art. Such methods include the step of bringing into association the osthole compound and / or plant extract with a carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly mixing the osthole compound and / or plant extract with a carrier (e.g., a liquid carrier, a finely divided solid carrier, etc.). The composition herein can be formulated as both cosmetic and pharmaceutical products. In some embodiments, there is provided a personal care product comprising a composition herein. Suitable personal care products include skin care products, hair care products, cleansing products, and cosmetic powders and liquids. Examples of suitable skin care products include skin / hand lotions, skin / hand creams, skin / hand ointments, skin / hand pastes, skin toner, shaving gels, shaving creams, sunscreens, deodorants, antiperspirants, suntan lotions, after sun, aftershaves, body oils, bath oils, bubble baths, and skin cleansers. Examples of suitable hair care products include conditioners, hair detangling lotion, styling gel, styling creams, styling waxes, styling lotions, mousses, spray gels, hair tonics, spritzes, and pomades. Examples of suitable cleansing products include liquid soaps, bar soaps, body washes, skin cleansers, and shampoos. Examples of suitable cosmetic powders and liquids include blusher, body powder, bronzing powder, eye shadow, foundation, face powder, lip powder, powder makeup, liquid bronzer, eyeliner, lip gloss, lipstick, and mascara. The compositions herein prevent, minimise or reduce cell senescence. The inventors believe that this is associated with the presence of osthole in the compositions. In some embodiments, the compositions can increase or promote senescent cell proliferative capacity. In some embodiments, the cells are skin cells. In some embodiments, the skin cells are on the head, such as on the face, mouth, neck, or scalp. In some embodiments, the skin is skin on the chest, back, arms, legs, or hands. In some embodiments, the compositions can increase or promote epidermal growth. In some embodiments, the compositions can prevent, minimise or reduce skin epidermal aging. In some embodiments, the composition can preserve, maintain or improve skin epidermal thickness, function, and / or quality. In some embodiments, a thinning of the epidermal layer is slowed, reduced, prevented or avoided. In some embodiments, the compositions can cause an increase in epidermal thickness of at least 0.5 μm, at least 0.75 μm, at least 1.0 μm, at least 1.5 μm, or at least 2 μm. In some embodiments, the compositions can cause an increase in epidermal thickness of at least 0.25%, at least 0.5%, at least 0.75% or at least 1%. That is, the epidermal thickness may increase by at least these amounts following treatment with a composition as described herein. In some embodiments, epidermal thinning is decreased over time by application of the present compositions. The extent of epidermal thinning reduction is expected to vary between individuals. In some embodiments, a decrease in epidermal thinning may be observed from as soon as 30s after application of the present compositions. In some embodiments, epidermal thinning may be decreased by up to 10%, such as up to 15% or up to 20%, within the first 60s following application of the present compositions. In some embodiments, epidermal aging includes epidermis showing a functional decline such as epidermal thinning. Epidermal aging may include aged epidermal cells, such as aged epidermal cells showing aging phenotypes such as senescence or loss of viability as described elsewhere herein. In some embodiments, the epidermal function that is improved is a protective function. In some embodiments, the protective function includes barrier function. In some embodiments, the protective function that is improved is the tendency of the epidermis to bruise or bleed or wrinkle, i.e. the epidermis has a reduced tendency to bruise or bleed or wrinkle. In some embodiments the protective function includes water retention capacity. In some embodiments the epidermal function that is improved is a regeneration activity. In some embodiments the epidermal function that is improved is a structural function, such as skin flexibility or firmness. In some embodiments, epidermal quality is assessed by considering epidermal integrity. In some embodiments, the epidermal integrity refers to the overall structural and functional integrity of the epidermis. In some embodiments the epidermal integrity does not include assessment of age associated decline. In some embodiments, proliferative capacity refers to the ability to grow or reproduce. In some embodiments, an increase in proliferative capacity of cells refers to the cell ability to reproduce, or to avoid cell senescence. In some embodiments, this is compared to a baseline control condition (e.g. stressed or aged cells). In some embodiments, the individual is in want of cosmetic treatment. Individuals in want of cosmetic treatment may have a condition associated with thinning of the skin, such as aged appearance of skin, wrinkled skin and the like. In some embodiments, the individual has a cosmetic condition selected from aged skin, such as aged facial skin. Aged skin, such as aged facial skin, may comprise aged cells as described elsewhere herein. Typical phenotypes of aged skin may also include one or more selected from thinning of the epidermis, flattening of the dermal-epidermal junction, loss of extracellular matrix components, appearance of fine lines or wrinkles, skin texture becoming dry or rough, loss of skin strength, loss of skin elasticity, and loss of skin firmness. In some embodiments, the cosmetic method is not a method of treatment. In some embodiments, the cosmetic method is not a method of treatment of the human or animal body by therapy. EXAMPLES Materials Dimethyl sulfoxide (DMSO) D2650 and Nicotinamide (NAM) N0636 were purchased from Sigma-Aldrich®. Osthole T2848 was purchased from Targetmol. Cnidium monnieri 5:1 was purchased from BOC Sciences®. Asian primary keratinocytes were obtained from the breast of a 33 years old Chinese female (12SKERA006), from the breast of a 31 years old Eurasian female (12SKERA011), from the abdomen of a 30 years old Indian female (17SKERA024), from the abdomen of a 64 years old Chinese female (17SKERA005), from the abdomen of a 62 years old Chinese female (18SKERA003) and from the breast of a 60 years old Chinese female (EBLKERA065). Normal human epidermal keratinocytes, adult (NHEK-AD) obtained from MatTek® were derived from 18 years old Caucasian female (K19000A), from 60 years old Black female (K13400A) and from 58 years old Hispanic female (K9210816A1). (a) 2D assay (primary keratinocytes) (i) Methods A test composition was added to the well of a 96 well plate to achieve a final concentration of 50 μM for osthole (1 μL of 5M stock solution made up in DMSO into 99 μL of culture media) or 31.25 μg / mL for Cnidium monnieri extract (1 μL of 3125 μg / mL stock solution made up in DMSO into 99 μL of culture media). Primary keratinocytes were seeded at 10 x 104cells per well (99 μL) in culture media without Y27632 and normal human epidermal keratinocytes (NHEKs) were seeded at 5 x 103cells per well (99 μL) in growth media. The cells were incubated for 3 days at 37°C with 5% CO2. Alamar® blue reagent was added (1 μL of 0.6 mM stock solution; 0.006 mM working concentration) and the cells incubated at 37°C for 1 hour. Alamar® blue fluorescence intensity was read at 560, 590 nm to determine the cell viability. The media was discarded, and the cells fixed at room temperature with 4% paraformaldehyde (Thermo Fisher, 28908) for 20 minutes. The media was discarded and replaced with NucBlue® Fixed Cell ReadyProbes (Invitrogen®, R37606) [2 drops per mL] for 20 minutes before quantification of cell nuclei with Operetta® high content analysis system. (ii) Results The results of the 2D assay (primary keratinocytes) are shown in Figs. 1 and 2. Fig. 1 shows a graph of nuclei count vs osthole concentration, where the osthole was added as a compound rather than as part of a plant extract. From left to right, the bars show: results without Y27632 and without osthole in the culture medium; results with Y27632 and without osthole in the culture medium; results without Y27632 and with 1 μM osthole in the culture medium; results without Y27632 and with 5 μM osthole in the culture medium; results without Y27632 and with 10 μM osthole in the culture medium; and results without Y27632 and with 50 μM osthole in the culture medium. Error bars are indicated. The asterisks indicate the P values, as follows: * < 0.05 ** < 0.01 *** < 0.001 **** < 0.0001 The graph demonstrates that the presence of osthole increased nuclei count compared to the baseline (first bar, without Y27632). Thus, it was concluded that the osthole increased cell viability and proliferation in primary keratinocytes. Fig. 2 shows a graph of nuclei count vs. Cnidium monnieri plant extract concentration, where the Cnidium monnieri plant extract comprises osthole. From left to right, the bars show: results without Y27632 and without Cnidium monnieri plant extract in the culture medium; results with Y27632 and without Cnidium monnieri plant extract in the culture medium; results without Y27632 and with 16 μg / mL Cnidium monnieri plant extract in the culture medium; results without Y27632 and with 31 μg / mL Cnidium monnieri plant extract in the culture medium; results without Y27632 and with 62 μg / mL Cnidium monnieri plant extract in the culture medium; and results without Y27632 and with 125 μg / mL Cnidium monnieri plant extract in the culture medium. Error bars are indicated. The asterisks indicate the P values, as follows: * < 0.05 ** < 0.01 *** < 0.001 **** < 0.0001 The graph demonstrates that the presence of the Cnidium monnieri plant extract increased nuclei count compared to the baseline (first bar, without Y27632). Thus, in combination with the results of Fig. 1, it was concluded that the osthole present in the Cnidium monnieri plant extract increased cell viability and proliferation in primary keratinocytes. (b) 3D assay (primary keratinocytes) (i) Methods Full thickness skin was established by Asian Skin Bank (A*SRL) with donor matched human primary fibroblasts and keratinocytes (donor 12-S-012 has no filaggrin mutation whereas donor 13-S-017 has K4022X filaggrin mutation). Primary fibroblasts were seeded on culture inserts coated with bovine collagen and incubated for two days. Primary keratinocytes were then seeded on the fibroblasts layer. After one day of incubation, the culture inserts were air-lifted. All incubations were done in 37°C with 5% CO2. Compounds treatment began on the day of air-lift and media were refreshed every alternate day. Full thickness skin was harvested 14 days post air-lift and fixed with 4% formaldehyde (Thermo Fisher, 28908). Histological processing was done by Advanced Molecular Pathology Laboratory in A*STAR. Hematoxylin and eosin images were captured on Olympus BX43 microscope and epidermis thickness was measured using ImageJ. Between 5-7 images were taken for each replicate (3 replicates per treatment condition) over the whole length of the 3D full thickness skin. The thickness of the epidermis layer (excluding the stratum corneum) for each image was calculated by determining the area of the epidermis layer and dividing the area by the length of the 3D full thickness skin in each image. The determined epidermal thickness for each replicate is the average (mean) thickness derived from each image. Statistical analysis was performed using one-way ANOVA® with the GraphPad Prism software. Paraffin-embedded sections were dewaxed, rehydrated and antigen retrieval was carried out by heat-induced antigen retrieval treatment in universal HIER antigen retrieval reagent (Abcam®, ab208572) or Tris-EDTA buffer pH 9.0 (Abcam®, ab93684). The sections were then permeabilized and blocked with animal-free blocker and diluent (Vector Laboratories, SP-5035-100) containing 0.1% Triton X-100 (blocking solution) for 1 hour at room temperature before incubation with primary antibodies overnight at 4°C. Primary antibodies used were: Lamin B1 (Abcam®, ab133741, 1:250) and K10 (Santa Cruz, sc53252, 1:200). Slides were washed in PBS and incubated in secondary antibodies (goat anti-rabbit IgG Alexa Fluor 488, Life Technologies®, A27034; goat anti-mouse Alexa Fluor 555, Life Technologies®, A28180) and DAPI (Dojindo®, D523) at a dilution of 1:1000 for 1 hour at room temperature before mounting in Fluoromount-G (Celestial Sphere, 0100-01). Quantification of Lamin B1 level in the full thickness skin was performed on at least 4 immunofluorescence images captured at random using Olympus FV3000 confocal laser scanning microscope. Images were analysed using ImageJ and statistical analysis was performed using one-way ANOVA® with the GraphPad Prism software. (ii) Results The results of the 3D assay (primary keratinocytes) are shown in Figs. 3 to 6. Fig. 3 shows microscope images of the skin of a 39-year-old female after treatment with (i) 0.1% DMSO; (ii) 5 mM NAM; (iii) 5 μM osthole; and (iv) 25 μg / mL Cnidium monnieri plant extract. Scale bar (shown only in Fig. 3 (iv), but applicable to all samples) is 100 μm. The top layer is the strateum, the middle layer is the epidermis, and the bottom layer is the dermis. Fig. 4 shows microscope images of the skin of a 49-year-old male after treatment with (i) 0.1% DMSO; (ii) 5 mM NAM; (iii) 5 μM osthole; and (iv) 25 μg / mL Cnidium monnieri plant extract. Scale bar (shown only in Fig. 4 (iv), but applicable to all samples) is 100 μm. The top layer is the strateum, the middle layer is the epidermis, and the bottom layer is the dermis. Fig. 5 shows graphs of the epidermis thickness (μm) for (i) Fig. 3 and (ii) Fig. 4. From left to right in each of (i) to (ii), the bars show: results after treatment with 0.1% DMSO; results after treatment with 5 mM NAM; results after treatment with 5 μM osthole; and results after treatment with 25 μg / mL Cnidium monnieri plant extract. Error bars are indicated. The asterisks indicate the P values, as follows: * < 0.05 ** < 0.01 *** < 0.001 **** < 0.0001 The absolute epidermal thickness values shown in Fig. 5 (i) are as follows: result after treatment with 0.1% DMSO: 79 μm; result after treatment with 5 mM NAM: 65 μm; result after treatment with 5 μM osthole: 81 μm; and result after treatment with 25 μg / mL Cnidium monnieri plant extract: 99 μm. Thus, Fig. 5 (i) shows that the epidermis thickness was lowest in the presence of 5 mM NAM, and slightly increased in the presence of 5 μM osthole compared to 0.1 % DMSO or 5 mM NAM. The epidermis thickness measured highest in the presence of 25 μg / mL Cnidium monnieri extract. The absolute epidermal thickness values shown in Fig. 5 (ii) are as follows: result after treatment with 0.1% DMSO: 75 μm; result after treatment with 5 mM NAM: 67 μm; result after treatment with 5 μM osthole: 84 μm; and result after treatment with 25 μg / mL Cnidium monnieri plant extract: 81 μm. Thus, Fig. 5 (ii) shows that the epidermis thickness in this case was measured highest in the presence of 5 μM osthole, and lowest in the presence of 5 mM NAM. The epidermis thickness was also increased in the presence of 25 μg / mL Cnidium monnieri extract compared to 5 mM NAM or 0.1% DMSO. Fig. 6 shows graphs of the integrated density (normalized to 4′,6-diamidino-2-phenylindole (DAPI)) of: (i) LMNB1 expression; (ii) LMNB1 expression in K10 positive cells; and (iii) LMNB1 expression in K10 negative cells. DAPI is a fluorescent stain that binds strongly to DNA in cell nuclei, used to visualise cells for counting in the present assay. LMNB1 is a gene component of the nucleus of the cells. From left to right in each of (i) to (iii), the bars show: results after treatment with 0.1% DMSO; results after treatment with 5 mM NAM; results after treatment with 5 μM osthole; and results after treatment with 25 μg / mL Cnidium monnieri plant extract. Error bars are indicated. The asterisks indicate the P values, as follows: * < 0.05 ** < 0.01 *** < 0.001 **** < 0.0001 LMNB1 is a cell senescence marker. Its decrease indicates the cells entering senescence. It can be seen from Fig. 6 (i)-(iii) that in each case the highest LMNB1 density was found after treatment with 25 μg / mL Cnidium monnieri plant extract. The LMNB1 density after treatment with 5 μM osthole was slightly affected by the nature of the cells (slightly lower with K10 positive cells, and slightly higher with K10 negative cells, in the reverse trend of the 5 mM NAM treatment). The decrease of LMNB1 is considered indicative of cells becoming senescent. During skin aging, LMNB1 levels are thought to reduce and thus the reduction in decline is considered to be indicative of prevention, reduction or minimising of cell senescence. Accordingly, it was concluded can be seen that the presence of osthole or Cnidium monnieri extract containing osthole each promotes thickening of the epidermal layer. (c) Y27632 withdrawal model (i) Methods Primary keratinocytes were cultured to 80% confluency in Complete Culture Medium with Y27632 (CCMY) consisting of 3:1 DMEM (Gibco®, 11995-065) : F12 (Gibco®, 31765- 035), supplemented with 10% fetal bovine serum (Gibco®, 10091148), 1x Penstrep (Gibco®, 15140-122), 0.2 μg / mL Epidermal Growth Factor (PeproTech®, AF-100-15- 1MG), 1 μg / mL Hydrocortisone (Sigma-Aldrich®, H0888), 10-9M cholera toxin (Sigma- Aldrich®, C8052-2MG) and 10 μM Y27632 (Tocris®, 1254 / 10) at 37°C with 5% CO2. The cells were washed with PBS buffer [5 mL for a 10 cm culture plate] and then incubated at 37°C with 0.125% Trypsin-EDTA (Gibco®, 15400054) [2 mL of Trypsin for a 10 cm culture plate] for 5-10 minutes. When all the cells had detached, neutralisation media consisting of DMEM with 10% FBS and 1x Penstrep (2 mL of neutralisation media for a 10 cm culture plate) was added, and the cells were transferred to a 15 mL conical tube and centrifuged at 1,000 rpm for 5 minutes. After centrifugation, a cell pellet was formed, the supernatant was discarded, and the cells were resuspended in culture medium and counted using Countess 3 FL (Life Technologies®). The cells were cultured in a CelCulture CO2Incubator 170L (Esco Lifesciences). The Rho kinase inhibitor, Y27632 is documented in the literature (see e.g. J. Clin. Invest.; 2010; 120(7); 2619-2626; Human keratinocytes are efficiently immortalized by a Rho kinase inhibitor; Chapman S., et al.) to extend the lifespan of primary keratinocytes in vitro by preventing cellular senescence and promoting proliferation. Primary keratinocytes can be cultured almost indefinitely using media containing Y27632. Conversely, removing Y27632 from the culture media results in the cessation of keratinocyte proliferation and the onset of keratinocyte senescence. Accordingly, in this assay, Y27632 was removed from the culture media to screen for compounds that can mitigate the loss of cell viability and / or the induction of cellular senescence. Cell viability was assessed using Alamar® blue, which contained resazurin: a cell- permeable, non-toxic dye, that can be reduced by metabolically active cells to a highly fluorescent form. Fluorescence intensity was measured and used as a quantitative readout for viable cells. Nuclei counting was determined by staining the cells with a nuclear dye, Hoechst®, then imaged and quantified using an Operetta® high content analysis system as a direct method to quantify cell number. Immunofluorescence for the proliferation marker Ki67 (Abcam®, ab16667, 1:100), was also performed to determine the extent of the loss of proliferation after osthole or Cnidium monnieri extract treatment in the absence of Y27632. The metabolic regulatory effects of osthole or Cnidium monnieri extract treatment in the keratinocytes were determined using the Seahorse XF Analyser. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) was carried out as follows. Primary keratinocytes were seeded at 1.5 x 104cells and test compositions were added to the well of a XFe96-well plate to achieve a final concentration of 50 M for osthole (1 μL of 5M stock solution made up in DMSO into 99 μL of culture media) or 500 / mL for Cnidium monnieri extract (1 l of 50000 g / mL stock solution made up in DMSO into 99 L of culture media) in culture media without Y- 27632 and allowed to sit at room temperature for 1 hour (to ensure consistent seeding density) before being transferred and incubated for 3 days at 37°C with 5% CO2. One day prior to analysis, the utility plate was filled with 200 μL of sterile water to allow hydration of the sensor cartridge in a non-CO2, 37°C incubator overnight. The XFe96 analyser was also turned on and allowed to equilibrate overnight. The next day, water in the utility plate was replaced with 200 μL of pre-warmed (at 37°C) XF calibrant solution (Agilent, 100840-000) to calibrate the sensor cartridge in a non-CO2, 37°C incubator for 1 hour. After which the cells were washed once with 200 μL of pre-warmed (at 37°C) XF assay medium (Agilent, 103575-100) and placed into the pre-warmed (at 37°C) Cytation instrument for brightfield imaging. The plate was incubated for an additional 40 minutes in the Cytation instrument set at 37°C. Mitochondria perturbing agents, Oligomycin (15 μM) and Rotenone+Antimycin (5 μM) were added into the sensor cartridge before being loaded into the Seahorse XFe96 Analyser for calibration. The plate containing cells was washed once with 160 μL of pre-warmed (at 37°C) XF assay medium and loaded into the Seahorse XFe96 Analyser for assessment of energy metabolism. A working solution of NucBlue Live Cell ReadyProbes (Invitrogen, R37605) was prepared by adding 2 drops of NucBlue Live Cell ReadyProbes per 1 mL XF assay medium. 28 μL of working NucBlue Live Cell ReadyProbes solution was added to each well and incubated in non-CO2, 37°C for 25 minutes before quantification of cell numbers with the Cytation Imager. Oligomycin is an ATP synthase inhibitor and was used to block mitochondrial ATP production and therefore cause a decrease in OCR and an increase in ECAR indicating a switch from mitochondrial respiration to glycolysis. Rotenone and antimycin are mitochondrial ETC complex I and III inhibitors, respectively. (ii) Results The results are shown in Figs. 7 to 11. Fig. 7 shows graphs of (i) alamar® blue signal intensity and (ii) nuclei count after incubation with (from left to right) no Y27632 and no osthole; Y27632 and no osthole; 5 mM NAM, no osthole, and no Y27632; and no NAM, 50 μM osthole and no Y27632. Error bars are indicated. The asterisks indicate the P values, as follows: * < 0.05 ** < 0.01 *** < 0.001 **** < 0.0001 It can be seen that the osthole produced a higher signal intensity and nuclei count than the results after incubation with NAM, and without Y27632. Fig. 8 shows a graph of nuclei count after incubation with osthole or Cnidium monnieri extract. From left to right, the bars represent incubation with: no Y27632 and no osthole or Cnidium monnieri extract; Y27632 and no osthole or Cnidium monnieri extract; 50 μM osthole and after removal of Y27632; 500 μg / mL Cnidium monnieri plant extract and after removal of Y27632; 250 μg / mL Cnidium monnieri plant extract and after removal of Y27632; 125 μg / mL Cnidium monnieri plant extract and after removal of Y27632; 62.5 μg / mL Cnidium monnieri plant extract and after removal of Y27632; 31.25 μg / mL Cnidium monnieri plant extract and after removal of Y27632; and 15.625 μg / mL Cnidium monnieri plant extract and after removal of Y27632. The dashed line shows the result for no Y27632 and no osthole or Cnidium monnieri plant extract. It can be seen that each of the incubations with osthole and Cnidium monnieri plant extract produced higher nuclei counts than the osthole-free, Cnidium monnieri-free, and Y27632- free incubation. Fig. 9 (i) shows representative immunofluorescence images following full thickness skin culture. From left to right, the images show results of: incubation without Y27632; incubation with Y27632; incubation with 5mM NAM; incubation with 50 μM osthole; and incubation with 500 μg / mL Cnidium monnieri extract. The black is background; dark grey spots indicate the presence of DAPI; light grey / white spots indicate the presence of Ki67 proliferative cell biomarker. These images indicate that compositions comprising osthole and osthole-containing plant extract lead to increased presence of the proliferative cell biomarker compared to the control (without Y27632). Fig. 9 (ii) shows the percentage of cells containing proliferation marker Ki67. From left to right, the bars indicate: incubation without Y27632; incubation with Y27632; incubation with 5mM NAM; incubation with 50 μM osthole; and incubation with 500 μg / mL Cnidium monnieri extract. For the incubation with 5 mM NAM, p = 0.06. The error bars are indicated. The asterisks indicate the P values, as follows: * < 0.05 ** < 0.01 *** < 0.001 **** < 0.0001 It can be seen that the incubations with 50 μM osthole and 500 μg / mL Cnidium monnieri extract gave higher percentage of Ki67 positive cells than the incubations with no Y27632 and with 5 mM NAM. It was concluded that keratinocytes treated with osthole or Cnidium monnieri extract prevented the loss of Alamar® blue fluorescence signal and cell number due to Y27632 removal, suggesting improved cell viability. Fig. 10 shows graphs of oxygen consumption rate (OCR) (pmol / min, normalized) vs time. Fig. 10 (i) shows results for incubations with: no Y27632 (closed circles); Y27632 (closed squares); 5 mM NAM (closed triangles); 10 μM osthole (open circles); and 50 μM osthole (open squares). Fig. 10 (ii) shows results for incubations with: no Y27632 (closed circles); Y27632 (closed squares); 5 mM NAM (closed triangles); 500 μg / mL Cnidium monnieri plant extract (open triangle with single point upward); and 250 μM μg / mL Cnidium monnieri plant extract (open triangle with single point downward). The incubations with NAM and osthole were carried out without Y27632. Oligomycin (15 μM) or rotenone and antimycin A (5 μM) were added at the time points indicated by the dashed lines. The expected decrease in OCR and increase in ECAR were observed when oligomycin was added, and a further decrease in OCR was observed after addition of the rotenone and antimycin. Fig. 11 shows graphs of ECAR (mpH / min, normalized) vs time. Fig. 11 (i) shows results for incubations with: no Y27632 (closed circles); Y27632 (closed squares); 5 mM NAM (closed triangles); 10 μM osthole (open circles); and 50 μM osthole (open squares). Fig. 11 (ii) shows results for incubations with: no Y27632 (closed circles); Y27632 (closed squares); 5 mM NAM (closed triangles); 500 μg / mL Cnidium monnieri plant extract (open triangle with single point upward); and 250 μM μg / mL Cnidium monnieri plant extract (open triangle with single point downward). The incubations with NAM and osthole were carried out without Y27632. Oligomycin (15 μM) or rotenone and antimycin A (5 μM) were added at the time points indicated by the dashed lines. The expected decrease in OCR and increase in ECAR were observed when oligomycin was added, and a further decrease in OCR was observed after addition of the rotenone and antimycin.

Claims

CLAIMS 1. A composition for use in a method of treating a disease or disorder associated with cell senescence, the composition comprising: (a) a derivative of coumarin or coumarin, and / or (b) a plant extract comprising a derivative of coumarin or coumarin.

2. The composition for use according to claim 1, wherein: (a) the derivative of coumarin or coumarin is osthole, or a salt, protected form, or solvate thereof, and / or (b) the derivative of coumarin or coumarin comprised in the plant extract is osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae.

3. A composition for use according to any one of the preceding claims, wherein (i) the cell is a skin cell, optionally wherein the skin cell is a facial skin cell; and / or (ii) the cell is an epidermal skin cell.

4. A composition for use according to any one of the preceding claims, wherein the composition is administered topically.

5. A composition for use according to any one of the preceding claims, wherein the disease or disorder is selected from a disease or disorder associated with thinning of a skin epidermal layer.

6. A composition for use according to any one of the preceding claims, wherein the derivative of coumarin or coumarin is present in an amount of at least 0.0001 wt%, based on the total weight of the composition, and / or wherein the derivative of coumarin or coumarin is present in an amount of at most 5.0 wt%, and / or wherein the plant extract is present in an amount of at least 0.005 wt%, based on the total weight of the composition, and / or wherein the plant extract is present in an amount of at most 10 wt%, based on the total weight of the composition.

7. A composition for use according to any one of the preceding claims, wherein the plant extract is an Umbelliferae extract.

8. A composition for use according to claim 7, wherein the plant extract is selected from an Angelica extract, such as Angelica japonica, and a Cnidium extract, such as Cnidium monnieri, optionally, wherein the plant extract is a Cnidium monnieri extract.

9. A composition for use according to any one of the preceding claims, wherein the plant extract comprises an extract from a fruit of the plant.

10. A composition for use according to any one of the preceding claims, wherein the plant extract comprises one or more compounds selected from xanthotoxin, bergapten, isopimpinellin and imperatorin.

11. A cosmetic method for preventing, minimising, or reducing cell senescence, the method comprising contacting the skin with a composition comprising: (a) a derivative of coumarin or coumarin, and / or (b) a plant extract comprising a derivative of coumarin or coumarin, wherein the method is not a method of treatment.

12. A cosmetic method according to claim 11, wherein: (a) the derivative of coumarin or coumarin is osthole, or a salt, protected form, or solvate thereof; and / or (b) the derivative of coumarin or coumarin comprised in the plant extract is osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae.

13. A cosmetic method according to claim 11 or claim 12, wherein the method: (i) increases or promotes senescent cell proliferative capacity and / or epidermal growth, and / or (ii) prevents, minimises, or reduces skin epidermal aging, and / or preserves, maintains or improves skin epidermal thickness, function and / or quality.

14. A cosmetic method according to any one of claims 11 to 13, wherein the skin is facial skin.

15. A cosmetic method according to any one of claims 11 to 14, wherein the derivative of coumarin or coumarin is present in an amount of at least 0.0001 wt%, based on the total weight of the composition, and / or wherein the derivative of coumarin or coumarin is present in an amount of at most 5.0 wt%, and / or wherein the plant extract is present in an amount of at least 0.005 wt%, based on the total weight of the composition, and / or wherein the plant extract is present in an amount of at most 10 wt%, based on the total weight of the composition.

16. A cosmetic method according to any one of claims 11 to 15, wherein the plant extract is an Umbelliferae extract.

17. A cosmetic method according to claim 16, wherein the plant extract is selected from an Angelica extract, such as Angelica japonica, and a Cnidium extract, such as Cnidium monnieri, optionally, wherein the plant extract is a Cnidium monnieri extract.

18. A cosmetic method according to any one of claims 11 to 17, wherein: (i) the plant extract comprises an extract from a fruit of the plant, and / or (ii) the plant extract comprises one or more compounds selected from xanthotoxin, bergapten, isopimpinellin and imperatorin.

19. Use of a composition comprising: (a) a derivative of coumarin or coumarin, and / or (b) a plant extract comprising a derivative of coumarin, or coumarin, for preventing, minimising, or reducing cell senescence.

20. Use according to claim 19, wherein: (a) the derivative of coumarin or coumarin is osthole, or a salt, protected form, or solvate thereof; and / or (b) the derivative of coumarin or coumarin comprised in the plant extract is osthole, or a salt, protected form, or solvate thereof, wherein the plant extract is an extract of a plant belonging to a family selected from Umbelliferae, Asteraceae, Rutaceae, Fabaceae, Compositae, Euphorbiaceae, Apiaceae and Leguminosae.

21. Use according to claim 19, for: (i) increasing or promoting senescent cell proliferative capacity and / or epidermal growth, and / or (ii) preventing, minimising or reducing skin epidermal aging, and / or preserving, maintaining or improving skin epidermal thickness, function and / or quality; and optionally in (i) or (ii) wherein the skin is facial skin.

22. Use according to any one of claims 19 to 21, wherein the derivative of coumarin or coumarin is present in an amount of at least 0.0001 wt%, based on the total weight of the composition, and / or wherein the derivative of coumarin or coumarin is present in an amount of at most 5.0 wt%, and / or wherein the plant extract is present in an amount of at least 0.005 wt%, based on the total weight of the composition, and / or wherein the plant extract is present in an amount of at most 10 wt%, based on the total weight of the composition.

23. Use according to any one of claims 19 to 22, wherein the plant extract is an Umbelliferae extract, and optionally, wherein the plant extract is selected from an Angelica extract, such as Angelica japonica, and a Cnidium extract, such as Cnidium monnieri, further optionally, wherein the plant extract is a Cnidium monnieri extract.

24. Use according to any one of claims 19 to 23, wherein: (i) the plant extract comprises an extract from a fruit of the plant; and / or (ii) the plant extract comprises one or more compounds selected from xanthotoxin, bergapten, isopimpinellin and imperatorin.

25. The composition for use according to any one of claims 1-10, or the cosmetic method according to any one of claims 11-18, or the use according to any one of claims 19-24, wherein the composition is provided as a skin care product selected from skin / hand lotion, skin / hand cream, skin / hand gel, skin / hand ointment, skin / hand paste, skin toner, shaving gel, shaving cream, sunscreen, deodorant, antiperspirant, suntan lotion, after sun, aftershave, body oil, bath oil, bubble bath, and skin cleanser.

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