Orchid composite extract, and its use for producing composition with antidepressant effect

Abstract

To provide an orchid composite extract containing volatile aroma compounds, including a plurality of dimethyl octane compounds along with other inseparable components.SOLUTION: This orchid composite extract is continuously administered to a subject in need for a predetermined duration to enhance the subject's brain connectivity and autonomic nervous function and further to modulate subjective emotions. Therefore, it is suitable for production of a composition with an antidepressant effect, as an active ingredient therein.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an orchid extract and its use, in particular to an orchid complex extract containing multiple volatile dimethyloctane compounds, and its use for producing a composition having antidepressant effects. [Background technology]

[0002] Aromatherapy is the use of aromatic plant oils and plant materials containing essential oils and other aromatic compounds to improve mental or physical health. Aromatherapy can be used as a complementary therapy or as a form of alternative medicine. Complementary therapies can be used in conjunction with standard treatments, and there is growing evidence that aromatherapy may have a clinical impact on various aspects of mental and physical illness.

[0003] However, there are few studies that allow the quantification or purification of fragrances themselves. In addition, most fragrances are compounds with complex components. Therefore, there is an urgent need to develop complex extracts of natural plants and their new uses. Summary of the Invention

[0004] Therefore, in one aspect of the present invention, there is provided an orchid complex extract containing volatile aroma compounds, including a plurality of dimethyloctane-based compounds, as active ingredients.

[0005] In another aspect of the present invention, there is provided use of an orchid complex extract for producing a composition having an antidepressant effect, which improves the brain connectivity and autonomic nervous system (ANS) of a subject and adjusts subjective feeling by administering to the subject a solid, liquid or gaseous dosage form containing volatile aroma compounds including multiple dimethyloctane compounds and other inseparable components as an active ingredient of the composition.

[0006] According to the above aspect of the present invention, there is provided an orchid complex extract, which in one embodiment may contain at least 70% by weight (wt.%) of volatile aroma compounds as active ingredients, such as dimethyloctane-based compounds and other inseparable components.

[0007] In the above embodiment, the dimethyl octane-based compound may include, for example, dimethyl octenol. In some examples, the dimethyl octenol may be selected from the group consisting of, for example, 3,7-dimethyl-1,6-octadien-3-ol, 2,6-dimethyl-3,7-octadiene-2,6-diol, 2,6-dimethyl-1,7-octadiene-3,6-diol, 3,7-dimethylocta-2,6-dien-1-ol, and 2,6-dimethyl-2,6-octadiene-1,8-diol.

[0008] In the embodiment, the orchid complex extract may contain 30% to 45% by weight of 3,7-dimethyl-1,6-octadien-3-ol and 40% to 50% by weight of 3,7-dimethyl-2,6-octadien-1-ol, and the content of 3,7-dimethyl-2,6-octadien-1-ol is greater than the content of 3,7-dimethyl-1,6-octadien-3-ol. In some examples, the orchid complex extract may contain, for example, 55% to 95% by weight of 3,7-dimethyl-1,6-octadien-3-ol and 3,7-dimethyl-2,6-octadien-1-ol, and the content of 3,7-dimethyl-2,6-octadien-1-ol may be greater than the content of 3,7-dimethyl-1,6-octadien-3-ol.

[0009] In the above embodiment, the orchid complex extract may contain, for example, 60% to 71% by weight of 3,7-dimethyl-1,6-octadien-3-ol, 3,7-dimethyl-2,6-octadien-1-ol, 2,6-dimethyl-1,7-octadien-3,6-diol, 2,6-dimethyl-2,6-octadien-1,8-diol, and 2,6-dimethyl-3,7-octadien-2,6-diol.

[0010] In the above embodiment, the 3,7-dimethyl-2,6-octadien-1-ol may include one or more isomers, and the isomers may include, for example, cis-3,7-dimethyl-2,6-octadien-1-ol [(2Z)-3,7-dimethylocta-2,6-dien-1-ol] and trans-3,7-dimethyl-2,6-octadien-1-ol [(2E)-3,7-dimethylocta-2,6-dien-1-ol].

[0011] In the above embodiment, the dimethyloctane-based compound may further selectively include dimethyl octanol oxide and / or dimethyl octadienoic acid. In some examples, the dimethyl octanol oxide may include, for example, 1,2-epoxy-3,7-dimethyl-6-octen-3-ol. In other examples, the dimethyl octadienoic acid may include, for example, 3,7-dimethyl-2,6-octadienoic acid [(2E)-3,7-dimethylocta-2,6-dienoic acid].

[0012] In the example, the orchid complex extract is from Phalaenopsis bellina.

[0013] According to another aspect of the present invention, the use of an orchid complex extract for preparing a composition having an antidepressant effect is provided, which comprises administering to a subject a pharmaceutical composition containing an effective amount of an orchid complex extract for at least 28 consecutive days, wherein the orchid complex extract contains at least 70% by weight of volatile aroma compounds, including dimethyloctane compounds containing dimethyloctenol selected from the group consisting of 3,7-dimethyl-1,6-octadien-3-ol, 2,6-dimethyl-3,7-octadien-2,6-diol, 2,6-dimethyl-1,7-octadien-3,6-diol, 3,7-dimethyl-2,6-octadien-1-ol, and 2,6-dimethyl-2,6-octadien-1,8-diol, and the pharmaceutical composition may be in the form of, for example, a solid, liquid, or gas.

[0014] In the above embodiment, the dimethyloctane-based compound further includes dimethyloctanol oxide and / or dimethyloctadienoic acid, where the dimethyloctanol oxide may include, for example, 1,2-epoxy-3,7-dimethyl-6-octen-3-ol, and the dimethyloctadienoic acid may include, for example, 3,7-dimethyl-2,6-octadienoic acid.

[0015] In such embodiments, the antidepressant effect includes improving the subject's brain connectivity and autonomic nervous system, and modulating the subject's subjective emotions.

[0016] In the present invention, the orchid complex extract and its use for preparing a composition having antidepressant effects contain volatile aroma compounds including dimethyloctane compounds and other inseparable components, and are used as active ingredients in the preparation of a composition having antidepressant effects when continuously administered to a subject in need for a certain period of time to improve the brain connectivity and autonomic nervous system of the subject and adjust subjective emotions.

[0017] It is to be understood that both the foregoing general description and the following detailed description are merely exemplary and are intended to provide further explanation of the invention for which protection is sought. [Brief description of the drawings]

[0018] To make the above and other objects, features, advantages and embodiments of the present invention more clear and understandable, detailed description of the accompanying drawings is as follows. [Figure 1] 1 is a gas chromatography-mass spectrometry chromatogram of an orchid complex extract according to an embodiment of the present invention. [Figure 2A] 2A, 2B, and 2C are magnetic resonance imaging images of the sagittal (FIG. 2A), coronal (FIG. 2B), and axial (FIG. 2C) sections of the brain of a subject administered with an orchid complex extract according to one embodiment of the present invention. [Figure 2B]2A, 2B, and 2C are magnetic resonance imaging images of the sagittal (FIG. 2A), coronal (FIG. 2B), and axial (FIG. 2C) sections of the brain of a subject administered with an orchid complex extract according to one embodiment of the present invention. [Figure 2C] 2A, 2B, and 2C are magnetic resonance imaging images of the sagittal (FIG. 2A), coronal (FIG. 2B), and axial (FIG. 2C) sections of the brain of a subject administered with an orchid complex extract according to one embodiment of the present invention. [Diagram 3] 1 is a bar graph showing heart rate variability before and after administration of orchid complex extract and lavender essential oil (control group, containing only aromatic alcohol) to subjects in one embodiment of the present invention. [Figure 4] 1 is a bar graph showing serum C-peptide concentrations before and after administration of orchid complex extract and aromatic alcohol (control group) to subjects in one embodiment of the present invention. [Diagram 5] FIG. 2 is a diagram showing a possible mechanism of action of an orchid complex extract according to an embodiment of the present invention on the brain of a subject. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] To the extent that a definition or use of a term in a reference is inconsistent with or contradicts a definition of that term herein, the definition of that term herein shall control and the definition of that term in the reference shall not apply, and unless the context requires otherwise, singular terms shall include the plural and plural terms shall include the singular.

[0020] As described above, the present invention provides an orchid complex extract having antidepressant effect, which contains volatile aroma compounds including dimethyloctane compounds and other inseparable components as active ingredients, and can improve the brain connectivity and autonomic nervous system (ANS) of a subject in need thereof and adjust subjective feelings by continuous administration for a predetermined period of time, and a use thereof for producing a composition having antidepressant effect.

[0021] In one embodiment, the terms "orchid complex extract" and "orchid essential oil" may be used interchangeably herein and refer to a complex extract containing at least 70% by weight (wt.%) of volatile aroma compounds as active ingredients. In one embodiment, the orchid complex extract may be derived from, for example, Phalaenopsis bellina flowers, without being limited thereto. The volatile aroma compounds are natural (non-synthetic) compounds, and the vapor pressure at 25°C is preferably, but not limited to, 0.2 mmHg or less, for example, 0.0002 mmHg to 0.2 mmHg.

[0022] In one embodiment, the volatile aroma compounds may be, for example, monoterpenes, including, for example, dimethyloctane-based compounds and other inseparable components. In some examples, the dimethyloctane-based compounds may include, for example, dimethyl octenol.

[0023] In some examples, specific examples of the dimethyloctenol include 3,7-dimethyl-1,6-octadien-3-ol (also called linalool, and represented by the following formula (I)), 2,6-dimethyl-3,7-octadiene-2,6-diol, 2,6-dimethyl-1,7-octadiene-2,6-diol, and the like. The diols may include, but are not limited to, the group consisting of 2,6-dimethyl-1,7-octadiene-3,6-diol, 3,7-dimethyl-2,6-octadien-1-ol, and 2,6-dimethyl-2,6-octadiene-1,8-diol. In the above example, 3,7-dimethyl-2,6-octadien-1-ol may include isomers including cis-3,7-dimethyl-2,6-octadien-1-ol [(2Z)-3,7-dimethylocta-2,6-dien-1-ol, also called nerol] and trans-3,7-dimethyl-2,6-octadien-1-ol [(2E)-3,7-dimethylocta-2,6-dien-1-ol, also called geraniol, and represented by the following formula (II)]. TIFF2025027623000001.tif43170

[0024] In another embodiment, the dimethyloctane-based compound may selectively include dimethyl octanol oxide and / or dimethyl octadienoic acid.

[0025] In some examples, specific examples of the dimethyl octanol oxide may include, but are not limited to, 1,2-epoxy-3,7-dimethyl-6-octen-3-ol (also called linalool oxide or 1,2-epoxylinalool).

[0026] In another example, a specific example of the dimethyloctadienoic acid may include, but is not limited to, 3,7-dimethyl-2,6-octadienoic acid (also called geranic acid).

[0027] The orchid complex extract can be prepared by conventional methods, for example, the method disclosed in BMC Plant Biology (Vol. 6, 2006, Paper No. 14 (total 14 pages)) and the collection device for volatile aromatic compounds disclosed in Chinese Patent Publication No. CN211374645U, which are incorporated herein by reference.

[0028] In other words, Phalaenopsis bellina was grown at a temperature of 30°C / 25°C (day / night), a relative humidity of 84%, and a photosynthetic photon flux density (PPFD) of 90 μmol m -2 s -1At the third stage of flowering (i.e., 5-10 days after flowering), the whole Phalaenopsis bellina is placed inside a conventional volatile aroma compound collection device, and the flowers are extracted for 28-42 hours (7 hours per day for 4-6 days) by headspace sorptive extraction (HSSE), using an activated carbon trap (1.5 mg) to draw air from the inside of the device at a rate of 400 ml / min, and the volatile aroma compounds are then collected by removing the solvent using a conventional vacuum concentration method. The volatile aroma compounds are subjected to conventional redissolving, fixing and aging processes to obtain an orchid complex extract. In the aging process, a homogenate of fresh flowers (containing natural catalytic enzymes) is added to the volatile aroma compound solution after redissolving and fixing, and the solution is treated at 30°C to 40°C for 1-3 months to fully react the essential oil and obtain an aged essential oil. In addition, in order to obtain the orchid complex extract containing the volatile aromatic compounds, and thereby improve the brain connectivity and ANS of the subject, and adjust the subjective emotion, the present invention requires the selection of a specific variety of orchid. If the orchid is not selected from the specific variety, it is not expected to obtain the specific components and the specific content of the volatile aromatic compounds, and the effects of improving the brain connectivity and ANS of the subject and adjusting the subjective emotion cannot be expected.

[0029] In one example, the orchid complex extract is rich in volatile aroma compounds, for example, 30% to 45% by weight of 3,7-dimethyl-1,6-octadien-3-ol and 40% to 50% by weight of 3,7-dimethyl-2,6-octadien-1-ol, and the content of 3,7-dimethyl-2,6-octadien-1-ol may be greater than that of 3,7-dimethyl-1,6-octadien-3-ol. In another example, the orchid complex extract may contain 55% by weight (wt.%) to 95% by weight of 3,7-dimethyl-1,6-octadien-3-ol and 3,7-dimethyl-2,6-octadien-1-ol, and the content of 3,7-dimethyl-2,6-octadien-1-ol may be greater than that of 3,7-dimethyl-1,6-octadien-3-ol. In another example, the orchid complex extract rich in volatile aroma compounds may contain, for example, 60% to 71% by weight of 3,7-dimethyl-1,6-octadien-3-ol, 3,7-dimethyl-2,6-octadien-1-ol, 2,6-dimethyl-1,7-octadien-3,6-diol, 2,6-dimethyl-2,6-octadien-1,8-diol, and 2,6-dimethyl-3,7-octadien-2,6-diol.

[0030] The term "other inseparable components" refers to volatile components that cannot be separated or are difficult to separate by conventional pretreatment, extraction, or post-treatment processes. In one example, the orchid complex extract may contain other inseparable components in an amount of, for example, 45% by weight or less, preferably 45% by weight or less, more preferably 30-36% by weight or less.

[0031] When used, the orchid complex extract can improve the brain connectivity and autonomic nervous system (ANS) of a subject in need thereof and adjust subjective feelings by continuously administering the extract for a predetermined period of time, and therefore can be used as an active ingredient in the manufacture of compositions (e.g., pharmaceutical compositions, cosmetic compositions, etc.) having antidepressant effects.

[0032] In one embodiment, the method of administering the orchid complex extract to a subject may be, for example, aromatherapy. In this embodiment, the form of the orchid complex extract may include, but is not limited to, solid, liquid or gas. The term "aromatherapy" as used herein refers to a non-traditional complementary medicine or treatment, and generally refers to administering an orchid complex extract rich in volatile aromatic compounds to a subject by means of incense burning, atomization, direct inhalation, transdermal absorption, etc., to evaluate the antidepressant effect.

[0033] In some examples, the period of administration of the orchid complex extract to a subject is not particularly limited, and may be administered continuously for at least one month, one to three months, two months, or for a period longer or shorter than the aforementioned periods.

[0034] In some other examples, the amount of the orchid complex extract administered to the subject is not particularly limited. In an example where the orchid complex extract is atomized using a commercially available essential oil diffuser, the orchid complex extract is added, for example, 1 to 10 drops per 10 ml to a commercially available electronic essential oil diffuser, and the subject inhales the orchid complex extract for 10 to 30 minutes per day. The space in which the orchid complex extract is atomized and administered to the subject is not particularly limited, and may be any of open, semi-open, or closed spaces, but is preferably about 40 m 3 ~about 60m 3 In order to increase the dosage of the orchid complex extract, the subject may optionally combine inhalation with transdermal absorption when inhaling the orchid complex extract.

[0035] The term "antidepressant effect" as used herein refers to the evaluation of the antidepressant effect of the orchid complex extract on the subject based on objective neurophysiological indices and subjective emotion scales. In one embodiment, the objective neurophysiological indices may include, but are not limited to, brain connectivity and autonomic nervous system (ANS) evaluation indices. In some examples, the brain connectivity evaluation indices may include, but are not limited to, the rate of change of functional connectivity (FC), and the ANS evaluation indices may include, but are not limited to, heart rate variability (HRV), sympathetic nerve activity, and parasympathetic nerve activity. In another embodiment, the subjective emotion scale may include, but is not limited to, a visual analogue scale (VAS) to evaluate subjective emotions such as talking too much, joy, sadness, sleepiness, anxiety, tension, full of energy, calm, fear, depression, anger, excitement, and comfort. In another embodiment, other physiological activities related to brain connectivity and ANS, such as serum c-peptide concentration (related to the reduction of insulin resistance), may also be selected as evaluation indices. If, after administering the orchid complex extract to a subject for a specified period of time, at least one of the following symptoms is observed: a decrease in the rate of change in FC, stabilization of HRV, a decrease in sympathetic nervous activity, an increase in parasympathetic nervous activity, a decrease in c-peptide concentration, a feeling of fullness, calmness, or comfort, the orchid complex extract is determined to have an antidepressant effect.

[0036] It should be understood that the following specific orchid varieties, specific manufacturing processes, specific compositions, specific dosages, specific testing methods, viewpoints, examples and embodiments are merely illustrative and do not limit the present invention. The main features of the present invention can be applied to various embodiments without departing from the spirit and scope of the present invention. Therefore, those skilled in the art can easily determine the necessary technical features of the present technical solution and make various changes and modifications to the present invention to apply it to different uses and conditions without departing from the spirit and scope of the present invention.

[0037] EXAMPLES

[0038] 1.1 Preparation of orchid complex extract

[0039] Orchid complex extract (also called orchid essential oil) and lavender essential oil (control) were prepared according to the method disclosed in BMC Plant Biology (Vol. 6, 2006, Paper No. 14 (total 14 pages)) and the apparatus disclosed in China Patent Publication No. CN211374645U.

[0040] First, Phalaenopsis bellina (P. bellina) was grown at a temperature of 30°C / 25°C (day / night), relative humidity of 84%, and PPFD of 90 μmol m -2 s -1 At the third stage of flowering (i.e., 5-10 days after flowering), the whole Phalaenopsis bellina was placed inside a volatile aroma compound collection device, and the flowers were extracted for 35 hours (7 hours per day for 5 days) by headspace sorptive extraction (HSSE), using an activated carbon trap (1.5 mg) to draw air from the inside of the device at a rate of 400 ml / min, and the flowers were then extracted for 35 hours (7 hours per day for 5 days) by conventional vacuum concentration to remove the solvent and collect the volatile aroma compounds. The volatile aroma compounds were subjected to conventional re-dissolution, retention and aging processes to obtain an orchid complex extract. In the aging process, a homogenate of fresh flowers (containing natural catalytic enzymes) was added to the volatile aroma compound solution after re-dissolution and retention, and the solution was treated at 30°C to 40°C for 2 months to fully react the essential oil and obtain a aged essential oil.

[0041] Analysis by a commercial gas chromatography mass spectrometry (GC-MS) instrument revealed that the volatile aroma compounds in the orchid complex extract included dimethyloctane-based compounds and other inseparable components.

[0042] The dimethyl octane-based compounds include dimethyl octenol, which is a derivative of 3,7-dimethyl-1,6-octadien-3-ol (also called linalool), 2,6-dimethyl-3,7-octadiene-2,6-diol, and 2,6-dimethyl-1,7-octadiene-3,6-diol. , 3,7-dimethylocta-2,6-dien-1-ol [wherein the cis isomer of 3,7-dimethyl-2,6-octadien-1-ol is also called nerol and the trans isomer is also called trans-geraniol], and 2,6-dimethyl-2,6-octadiene-1,8-diol.

[0043] The dimethyloctane-based compound further includes dimethyl octanol oxide and / or dimethyl octadienoic acid. Dimethyl octanol oxide includes 1,2-epoxy-3,7-dimethyl-6-octen-3-ol (also called linalool oxide or 1,2-epoxylinalool). Dimethyl octadienoic acid includes 3,7-dimethyl-2,6-octadienoic acid (also called 3,7-dimethyl-2,6-octadienoic acid, geranic acid).

[0044] Please refer to Figure 1 and Table 1. Figure 1 and Table 1 show the gas chromatography mass spectrometry chromatogram (Figure 1) and the content of each component (Table 1) of the orchid complex extract according to one embodiment of the present invention. As can be seen from the results of Figure 1 and Table 1, the volatile aroma compounds contained in the orchid complex extract of Example 1 are all natural compounds, mainly dimethyloctane compounds such as 3,7-dimethyl-1,6-octadien-3-ol [represented by formula (I) in Figure 1] and trans-3,7-dimethyl-2,6-octadien-1-ol [represented by formula (II) in Figure 1].

[0045] Furthermore, each peak in Figure 1 represents a different compound, and in addition to the major compounds 3,7-dimethyl-1,6-octadien-3-ol and trans-3,7-dimethyl-2,6-octadien-1-ol, there are many other inseparable components that cannot be easily mimicked by standards spiked with said compounds.

[0046] Table 1 TIFF2025027623000002.tif134170

[0047] 1.2 Subjects

[0048] This example is a two-group, randomized, double-blind study. Thirty-nine subjects were recruited and randomly divided into an aromatherapy group (including 19 subjects in the orchid group and 20 subjects in the lavender group) and a non-aromatherapy group (including 18 subjects in the non-aromatherapy group). The subjects' ages ranged from 18 to 65 years old. A physician assessed the subjects for other mental, medical or neurological disorders based on the Chinese version of the Mini International Neuropsychiatric Interview (MINI), and excluded subjects with potential psychiatric disorders. Exclusions included: (i) patients with medical or mental illnesses at the time of the examination / interview, (ii) pregnant women, women who may be pregnant, and women who were breastfeeding, (iii) patients with a history of drug or alcohol dependence or abuse within the past 6 months, (iv) subjects with allergies to orchids and lavender, and (v) subjects with a gardening hobby or frequent contact with the plants. After sufficient explanation, all informed subjects gave their consent. This example was reviewed and approved by the Human Research Ethics Committee of Cheng Kung University Hospital.

[0049] 1.3 Aromatherapy

[0050] The orchid complex extract or lavender essential oil (control) of the same concentration was added to a commercially available electronic essential oil diffuser at 4 drops per 10 ml and aerosolized in the test space (approximately 40 m 3 ~about 60m 3 The experiment used a 10-cm x 10-cm lid (size 100 mm x 100 mm) filled with volatile aroma compounds to effectively provide aromatherapy to the subjects.

[0051] The subjects received aromatherapy once a day for two months. Each aromatherapy session was divided into two phases, each lasting 15 minutes, with a 10-minute break between the two phases.

[0052] Example 2: Evaluation method

[0053] 2.1 Physiological indicators

[0054] 2.1.1 Magnetic resonance imaging of brain function

[0055] (1) Image acquisition

[0056] Before and after aromatherapy, the subjects' brain functions were analyzed using a magnetic resonance imaging scanner. First, the subjects were fitted with an 8-channel head coil, and resting-state functional MRI (fMRI) images were taken using a 3.0 Tesla magnetic resonance imaging (MRI) scanner (MR750, GE Medical Systems, Milwaukee, WI, USA) at the National Cheng Kung University Psychological Research and Imaging Center. High-resolution T1-weighted 3D structural images ([TR] / [TE]=7.7ms / 2.9ms, flip angle=12°, field of view=224mm) were obtained. 2 , in-plane matrix size = 256 × 256, slice thickness = 1 mm, number of slices = 166) and T2 * A weighted echo-planar imaging sequence ([TR] / [TE] = 2000 ms / 33 ms, flip angle = 90°, field of view = 240 mm 2 High-resolution anatomical T1 and fMRI images were obtained using a 3D scanning system (within 10 min, in-plane matrix size = 64 × 64, slice thickness = 3 mm, number of slices = 40, acquired within 5 min 10 s). The first 5 functional images of the resting-state fMRI series were excluded to ensure signal saturation and magnetic field stability. Subjects were required to maintain an awake state (eyes closed, head motionless, relaxed, thinking of nothing) during the scan. A head cushion and earplugs were provided to reduce head movement and noise.

[0057] (2) Image preprocessing

[0058] Preprocessing was performed using the Data Processing Assistant for Resting-State fMRI (DPARSF) toolbox (State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China) and Statistical Parametric Mapping 12 (SPM12, Wellcome Trust Center for Neuroimaging, London, http: / / www.fil.ion.ucl.ac.uk / spm). All functional images were subjected to slice timing correction, head motion realignment, coregistration to individual anatomical images, and standardization using the International Consortium for Brain Mapping (ICBM) spatial template for East Asian brains using MATLAB 2016a software (MathWorks Inc., Natick, MA, USA). Images from subjects with head motions of more than 2 mm or 2° were excluded. In the standardization step, images were aligned 2 mm apart. 3 After being resampled to an isotropic voxel size of 100 nm, the images were spatially smoothed with a 3D Gaussian kernel with a full width at half maximum of 6 mm. The time series were then temporally band-pass filtered (0.01–0.1 Hz) to remove linear trends, regress head movement parameters from the resulting time series, and extract low-frequency oscillations associated with spontaneous neuronal activity.

[0059] (3) Definition of thalamus seeds

[0060] Based on the definition in "The human brain representation of odor identification" published by Kjelvik G. et al. in July 2012, J. Neurophysiol., Vol. 108, No. 2, pp. 645-57, we examined whole-brain resting-state connectivity using 3 mm radius spheres centered on thalamic regions of interest (ROIs) as seeds [Montreal Neurological Institute (MNI) coordinates: left: -7, -10, 8; right: 7, -24, -2]. We calculated voxel-wise whole-brain (VVWB) comparisons between groups. We extracted the mean time series activity of the seed regions for each subject and generated functional connectivity (FC) maps of the thalamic seeds. The resulting individual FC maps were then converted to z maps using Fisher's r-to-z transformation method for secondary group analysis.

[0061] 2.1.2 HRV measurement

[0062] The subject's ANS activity and HRV may be measured before and after aromatherapy.

[0063] (1)ANS activities

[0064] Prior to the cardiovascular measurements starting at 10:00 a.m., subjects underwent 20 min of adaptation training in the supine position in a quiet room maintained at a comfortable temperature (25–27°C). To avoid hyperventilation, subjects were instructed to relax and breathe normally. Cardiac autonomic function was calculated by a geometric method based on short-term measurements of the interbeat interval (IBI). k+1 and IBI k By plotting the sequence of IBIs (IBI1, IBI2, IBI n) was transformed into a two-dimensional plane. The length of the horizontal axis (T) is affected by sympathetic and parasympathetic blockade, while the length of the vertical axis (L) is only affected by parasympathetic blockade. log10(L×T) is the cardiac vagal index, and the L / T ratio is the cardiac sympathetic index. These two indexes have been proven to be more reliable than traditional measurement methods (including spectral analysis). This geometric method is a reliable measurement method, and its advantages are that (i) no control of breathing or other movements is required, and (ii) only 100 IBI values ​​are sufficient for evaluation.

[0065] (2) HRV measurement

[0066] Power spectral density (PSD) analysis of HRV may be performed by fast Fourier transformation (FFT). Relevant spectral components were defined as low frequency (LF) (0.04-0.15 Hz), HF (0.15-0.40 Hz) and total power (≦0.4 Hz). Very low frequency (VLF) values ​​were excluded. Total power represents all spontaneous activity. HF power of HRV represents an index of cardiac parasympathetic (vagus) activity, while LF power represents an index of vasomotor sympathetic activity or sympathetic and vagus activity. The LF / HF ratio is an index of the relative balance of sympathetic and vagus influences on the heart, with a higher LF / HF ratio representing increased sympathetic activity or decreased parasympathetic regulation. These indices were transformed to natural logarithms to correct for skewness.

[0067] 2.1.3 Blood tests

[0068] In this embodiment, the C-peptide concentration in the subject's blood before and after aromatherapy was measured by a conventional blood test method, and since the relevant measurement method is publicly known, a description thereof will be omitted here.

[0069] 2.2 Visual Analogue Scale (VAS)

[0070] Visual analog scales (VAS) are psychometric scales based on questionnaires. VAS is a tool for measuring subjective characteristics or attitudes that cannot be measured directly. When answering each individual item, the respondent indicates the degree of agreement with the statement by the position of the pointer along a solid line between the two end points. In some studies, these scales represent the subjects' emotional reactions before and after the intervention. This scale was used only in the aromatherapy group.

[0071] 2.3 Data Statistics

[0072] The values ​​described herein were verified by analysis of variance (ANOVA) before and after subjects were administered orchid complex extract (experimental group) and lavender essential oil (control group), and the data before and after the administration of essential oil in the control group were the same. The change rates of several physiological parameters before and after aromatherapy use [(value after use-value before use) / value before use)] were calculated, and the correlation between the change rate of FC connectivity in the experimental and control groups and other variables was analyzed. Other analyses were performed with the commercially available software SPSS Statistics 20.0 (SPSS Inc., Chicago, IL), and statistical significance was determined at p<0.05. An asterisk * represents p<0.05.

[0073] Example 3: Evaluation of the antidepressant effect of orchid complex extract

[0074] 3.1 Evaluation of Magnetic Resonance Imaging (MRI) Results

[0075] Please refer to Figures 2A to 2C, which show MRI images of the sagittal (Figure 2A), coronal (Figure 2B) and axial (Figure 2C) sections of the brain of a subject administered with an orchid complex extract according to one embodiment of the present invention.

[0076] As shown in Figures 2A to 2C, when the subjects were administered the orchid complex extract for two consecutive months, the connection between the left thalamus and the right inferior temporal gyrus of the subjects was reduced, indicating that the orchid complex extract has an antidepressant effect.

[0077] 3.2 Assessment of Heart Rate Variability (HRV)

[0078] Please refer to Figure 3, which is a bar graph showing heart rate variability (HRV) before and after administering orchid complex extract and lavender essential oil (control group, containing only aromatic alcohol) to subjects in one embodiment of the present invention.

[0079] As shown in Figure 3, there was no significant difference in HRV before and after the subjects were administered orchid complex extract or lavender essential oil (control group, containing only aromatic alcohol), but a tendency toward a decrease was observed, and the tendency toward a decrease in HRV after administration of orchid complex extract (mean decrease of 1.69 beats / min) was greater than that after administration of lavender essential oil (mean decrease of 0.29 beats / min).

[0080] 3.3 Assessment of serum C-peptide concentrations

[0081] Please refer to Figure 4, which is a bar graph showing serum C-peptide concentrations before and after administering orchid complex extract and lavender essential oil (control group, containing only aromatic alcohol) to subjects in one embodiment of the present invention, where the asterisk * indicates p<0.05.

[0082] As shown in Figure 4, serum C-peptide concentrations were indeed reduced when subjects were administered the orchid complex extract compared to the control group administered lavender essential oil (containing only aromatic alcohols), and this difference was statistically significant.

[0083] 3.4 Evaluation of change rate of FC (functional connectivity) and subjective emotions

[0084] Please refer to Tables 2 and 3. Table 2 shows the results of HRV and visual analog scale of emotion before and after administering orchid complex extract and lavender essential oil (control group, containing only aromatic alcohol) to a subject in one embodiment of the present invention, and Table 3 shows the correlation results of the change rate of FC (functional connectivity) and visual analog scale of emotion before and after administering orchid complex extract and lavender essential oil (control group, containing only aromatic alcohol) to a subject in one embodiment of the present invention.

[0085] As shown in Tables 2 and 3, when the subjects were administered the orchid complex extract for two consecutive months, the rate of change in FC decreased and subjective feelings such as full of energy, calmness, and comfort improved, indicating that the orchid complex extract has an antidepressant effect.

[0086] Autonomic nerves are divided into sympathetic nerves and parasympathetic nerves. When dealing with stress, the sympathetic nerves usually put the body's organs into a fighting state, causing physiological arousal such as an increase in blood pressure, an increase in heart rate, and muscle contraction. When stress is eliminated, the parasympathetic nerves put the organs to rest, and the physiological arousal caused by stress is reduced. In addition, the sympathetic nerves and parasympathetic nerves are also closely related to emotion regulation (especially calmness or fear, etc.). As can be seen from Figure 3, Tables 2 and 3, from various subjective emotions closely related to autonomic nerve function (e.g., the emotional indexes of full of energy, calmness, and comfort are significantly improved, and the emotional index of fear is significantly reduced), it can be reasonably inferred that the orchid complex extract has the effect of reducing sympathetic nerve activity and increasing parasympathetic nerve activity, and therefore it was determined that the orchid complex extract has an antidepressant effect.

[0087] Please refer to Figure 5. Figure 5 shows one of the possible mechanisms of interaction between the prefrontal cortex (PFC)-serotonin transporter (SERT)-autonomic nervous system (ANS) in the anterior 501 of the brain. Currently, it is known that brain-derived neurotrophic factor (BDNF) is thought to be related to the pathological mechanism of depression, and stress and depression can cause a decrease in BDNF in the hippocampus. Dysfunction of the ANS is also thought to be one of the neurophysiological indicators of the occurrence of depression. Dysfunction of top-down control (e.g., BDNF, PFC, etc.) can be compensated for by interactions of downstream neural networks (e.g., ANS, nucleus tractus solitaries (NTS)). The interaction between serotonin and the ANS may be adjusted by the decrease in BDNF levels and the decrease in PFC function to maintain the physiological and psychological homeostasis of the brain. However, in the above example, after aromatherapy with the orchid complex extract, the orchid complex extract exerts an antidepressant effect by affecting the PFC and then the ANS.

[0088] In summary, the specific orchid variety, the specific manufacturing process, the specific composition, the specific dosage, the specific testing method, or the specific evaluation method in the present invention are merely for illustrating and explaining the orchid complex extract of the present invention and its use for manufacturing a composition having antidepressant effect. However, those skilled in the art will understand that the orchid complex extract can be selectively combined with other known plant extracts (e.g., essential oils, aromatic distilled water, etc.), and other compositions, other dosages, other testing methods, or other evaluation methods can also be used to manufacture a composition having antidepressant effect without departing from the spirit and scope of the present invention, and are not limited to the above. For example, the orchid complex extract may be a pharmaceutical composition, a cosmetic composition, or a food composition, and may selectively contain a carrier, excipient, and / or additive acceptable for pharmaceuticals, cosmetics, or foods, and may be manufactured into a dosage form such as a powder, tablet, granule, microcapsule, ampoule, spray, solution, oil, O / W emulsion, W / O emulsion, W / O / W emulsion, O / W / O emulsion, etc.

[0089] According to the above embodiment, the advantage of the orchid complex extract of the present invention is that it contains volatile aroma compounds, including multiple dimethyloctane compounds and other inseparable components.This orchid complex extract can be continuously administered to a subject in need for a certain period of time to improve the brain connectivity and ANS of the subject, and further adjust subjective emotion, so that it can be used as an active ingredient in the preparation of a composition with antidepressant effect.

[0090] Although the invention has been disclosed in terms of several specific embodiments, other embodiments are possible, and therefore, the spirit and scope of the claims appended hereto should not be limited to the description of the embodiments contained herein.

[0091] Table 2 TIFF2025027623000003.tif212170TIFF2025027623000004.tif225170BMI: Body mass index HRV: Heart rate variability HF: high frequency LF: low frequency VLF: very low frequency Total Power: Total power RMSSD: Root mean square of the successive differences PNN: Probabilistic neural network

[0092] Table 3 TIFF2025027623000005.tif237170TIFF2025027623000006.tif65170FC ratio: Correlation ratio of functional connectivity FC change rate: [(rear-front) / front] r:RMSSD p:PNN Bold italic numbers: statistically significant [Explanation of symbols]

[0093] 201, 501: Front 203, 503: Rear side 205: Right side 207: Left side

Claims

1. An orchid complex extract containing at least 70% by weight of volatile aroma compounds including dimethyloctane-based compounds and other inseparable components as active ingredients.

2. The dimethyloctane compound is 3,7-dimethyl-1,6-octadien-3-ol, 2,6-dimethyl-3,7-octadiene-2,6-diol, 2,6-dimethyl-1,7-octadiene-3,6-diol, The orchid complex extract according to claim 1, further comprising dimethyl octenol selected from the group consisting of 3,7-dimethyl-2,6-octadiene-1-ol, 3,7-dimethyl-2,6-octadiene-1-ol and 2,6-dimethyl-2,6-octadiene-1,8-diol.

3. The orchid complex extract according to claim 2, comprising 30% by weight to 45% by weight of said 3,7-dimethyl-1,6-octadien-3-ol and 40% by weight to 50% by weight of said 3,7-dimethyl-2,6-octadien-1-ol, wherein the content of said 3,7-dimethyl-2,6-octadien-1-ol is greater than the content of said 3,7-dimethyl-1,6-octadien-3-ol.

4. The orchid complex extract according to claim 2, comprising 55% by weight to 95% by weight of said 3,7-dimethyl-1,6-octadien-3-ol and said 3,7-dimethyl-2,6-octadien-1-ol, and the content of said 3,7-dimethyl-2,6-octadien-1-ol is greater than the content of said 3,7-dimethyl-1,6-octadien-3-ol.

5. The orchid complex extract according to claim 2, comprising 60% by weight to 90% by weight of said 3,7-dimethyl-1,6-octadien-3-ol, said 3,7-dimethyl-2,6-octadien-1-ol, said 2,6-dimethyl-1,7-octadien-3,6-diol, said 2,6-dimethyl-2,6-octadien-1,8-diol, and said 2,6-dimethyl-3,7-octadien-2,6-diol.

6. The orchid complex extract according to claim 2, wherein the 3,7-dimethyl-2,6-octadien-1-ol contains isomers including cis-3,7-dimethyl-2,6-octadien-1-ol [(2Z)-3,7-dimethylocta-2,6-dien-1-ol] and trans-3,7-dimethyl-2,6-octadien-1-ol [(2E)-3,7-dimethylocta-2,6-dien-1-ol].

7. The orchid complex extract according to claim 1, wherein the dimethyloctane compound further comprises dimethyloctanol oxide and / or dimethyloctadienoic acid.

8. The orchid complex extract according to claim 7, wherein the dimethyloctanol oxide comprises 1,2-epoxy-3,7-dimethyl-6-octen-3-ol.

9. The orchid complex extract according to claim 7, wherein the dimethyloctadienoic acid comprises 3,7-dimethyl-2,6-octadienoic acid.

10. 2. The orchid complex extract according to claim 1, which is derived from Phalaenopsis bellina.

11. Use of an orchid complex extract for producing a composition having an antidepressant effect, comprising continuously administering to a subject in need thereof an effective amount of a composition comprising an orchid complex extract for at least one month, wherein the orchid complex extract contains at least 70% by weight of volatile aroma compounds including dimethyloctane compounds including dimethyloctenol selected from the group consisting of 3,7-dimethyl-1,6-octadien-3-ol, 2,6-dimethyl-3,7-octadien-2,6-diol, 2,6-dimethyl-1,7-octadien-3,6-diol, 3,7-dimethyl-2,6-octadien-1-ol, and 2,6-dimethyl-2,6-octadien-1,8-diol, and other inseparable components, and the composition has a dosage form comprising a solid, liquid, or gas.

12. The use of an orchid complex extract for producing a composition having an antidepressant effect according to claim 11, wherein the dimethyloctane compound further comprises dimethyloctanol oxide and / or dimethyloctadienoic acid, the dimethyloctanol oxide comprises 1,2-epoxy-3,7-dimethyl-6-octen-3-ol, and the dimethyloctadienoic acid comprises 3,7-dimethyl-2,6-octadienoic acid.

13. The use of an orchid complex extract for producing a composition having an antidepressant effect as described in claim 11, wherein the antidepressant effect includes improving the subject's brain connectivity and autonomic nervous system, and regulating the subject's subjective emotions.

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