Application of premna microphylla leaves in preparation of medicine and food for preventing and treating radioactive injury

Abstract

The invention discloses application of premna microphylla leaves in preparation of drugs and food for preventing and treating radioactive injury. The medicine has prevention and treatment effects on inappetence, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radioactive therapy, and has a good development prospect. The traditional Chinese medicine composition can be used for improving a series of side effects generated during radiotherapy of pelvic and abdominal cavities such as cervical cancer, so that the total treatment time is prolonged, and the treatment effect is improved.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and particularly relates to the use of Premna microphylla Turcz. leaves in the preparation of drugs and foods for preventing and treating radiation injuries. Background Art

[0002] Radiotherapy is one of the most important treatment means for cervical cancer. Radiotherapy releases multiple beams of high-energy rays to the planned target area to damage the DNA of tumor cells and achieve the anti-tumor effect. However, during the implementation of radiotherapy, some challenges are also faced. Due to the special anatomical positions of the uterus and cervical cancer tumor lesions, many important organs are closely surrounded, such as the bladder and colorectum. Radiation-induced intestinal injury is one of the most common adverse reactions of pelvic and abdominal radiotherapy. Mild cases show symptoms such as abdominal pain, diarrhea, tenesmus, and bloody stools, and severe cases can present intestinal obstruction, intestinal necrosis, or even intestinal fistula, thus endangering life. Although radiotherapy techniques and radiotherapy machines have been updated, and the distribution of target area doses is more precise, such as external radiotherapy combined with MRI-guided adaptive brachytherapy, the cumulative 3-5 grade gastrointestinal toxicity at 5 years still reaches 8.5%. The liver and kidneys are crucial organs of the digestive and urinary systems. Radiation-induced liver injury and kidney injury are complications that may be caused by radiotherapy, and their harm to the body is multi-faceted, including digestive system symptoms, abnormal liver function, systemic symptoms, urinary system symptoms, abnormal kidney function, edema, hypertension, as well as anemia and electrolyte disorders. Severe radiation injuries usually lead to the suspension of radiotherapy, an extended total treatment time, and affect the treatment effect.

[0003] However, there is currently no effective treatment for radiation-induced intestinal, liver, and kidney injuries, and only symptomatic supportive treatment can be carried out. Therefore, finding effective and safe drugs has become an urgent task in contemporary medical treatment.

[0004] Premna microphylla Turcz. leaves are the dried leaves of Premna microphylla Turcz. (PMT) of the Verbenaceae family, and have functions such as antioxidant, antibacterial, enhancing intestinal inflammation defense, and protecting the skin from ultraviolet B-induced aging. Their role in preventing and treating radiation injuries has not been studied. Summary of the Invention

[0005] The present invention discloses the use of Premna microphylla Turcz. leaves in the preparation of drugs for preventing, improving, and treating radiation injuries.

[0006] The present invention is realized by the following technical solutions:

[0007] In the first aspect, the present invention provides a use of Premna microphylla Turcz. leaves in the preparation of drugs for preventing, improving, or treating radiation injuries.

[0008] Preferably, as the first aspect described above, the radiation injury is selected from one or more of anorexia, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy.

[0009] Second aspect, the present invention provides a drug for preparing a drug for preventing, improving or treating radiation injury, which contains premna microphylla turcz leaves as an active ingredient.

[0010] Preferably, as the second aspect described above, the drug is a composition composed of premna microphylla turcz leaf powder and one or more pharmaceutically acceptable carriers.

[0011] Preferably, as the second aspect described above, the drug is a polyethylene glycol suspension of premna microphylla turcz leaf powder.

[0012] Preferably, as the second aspect described above, the radiation injury is selected from one or more of anorexia, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy.

[0013] Third aspect, the present invention provides the use of premna microphylla turcz leaves in the preparation of a food for preventing, improving or treating radiation injury.

[0014] Preferably, as the third aspect described above, the radiation injury is selected from one or more of anorexia, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy.

[0015] Fourth aspect, the present invention provides a food composition for preventing or improving radiation injury, and the food composition contains premna microphylla turcz leaves as an active ingredient.

[0016] Preferably, as the fourth aspect described above, the radiation injury is selected from one or more of anorexia, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] The present invention discovers that using premna microphylla turcz leaves as an active ingredient can prevent, improve and treat anorexia, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy. The present invention can be used to improve a series of side effects generated during pelvic and abdominal radiotherapy such as cervical cancer, thereby prolonging the total treatment time and improving the treatment effect. Description of the Drawings

[0019] Figure 1 It is a graph of the change in the body weight (Weight) of mice in the examples of the present invention.

[0020] Figure 2Statistical chart of the colon length of mice in the embodiments of the present invention.

[0021] Figure 3 Statistical chart of the qualitative of fecal occult blood of mice in the embodiments of the present invention.

[0022] Figure 4 H&E staining map of colon tissue in the embodiments of the present invention.

[0023] Figure 5 Statistical chart of the liver index in the embodiments of the present invention.

[0024] Figure 6 H&E staining map of liver tissue in the embodiments of the present invention.

[0025] Figure 7 Statistical chart of the kidney index in the embodiments of the present invention.

[0026] Figure 8 Statistical chart of the content of Serum Cr in the embodiments of the present invention.

[0027] In the figure: Normal is the normal group, Control is the control group, IR is the radiotherapy group, PMT(L) is the radiotherapy + low-dose Premna microphylla Turcz. group, PMT(M) is the radiotherapy + medium-dose Premna microphylla Turcz. group, and PMT(H) is the radiotherapy + high-dose Premna microphylla Turcz. group. ; a represents P < 0.05 compared with the Normal group, b represents P < 0.05 compared with the Control group, c represents P < 0.05 compared with the IR group, and d represents P < 0.05 compared with the PMT(L) group. Detailed implementation manners

[0028] To make the above objects, features, and advantages of the present invention more obvious and understandable, the following will describe the detailed implementation manners of the present invention with reference to the accompanying drawings. Many specific details are set forth in the following description to fully understand the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below. The technical features in each embodiment of the present invention can be combined correspondingly without conflict.

[0029] The present invention provides the use of Premna microphylla Turcz. leaves in the preparation of drugs and foods for preventing and treating radiation injuries. It should be noted that the "prevention and treatment" in the present invention can be one or more of prevention, improvement, or treatment.

[0030] It should be noted that the "radiation injury" in the present invention can be selected from one or more of anorexia, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy.

[0031] Based on the above uses, a drug for preparing a preventive, ameliorative or therapeutic agent for radiation injury, or a food composition for preparing a preventive, ameliorative or therapeutic agent for radiation injury can also be provided. The active ingredient in these drugs or food compositions is Premna microphylla Turcz. leaves.

[0032] For the above-mentioned drugs in the present invention, Premna microphylla Turcz. leaves can be compounded with one or more pharmaceutically acceptable carriers to form a pharmaceutical preparation in the form of a composition. The specific pharmaceutically acceptable carriers can be selected according to the final form of the drug. In the examples of the present invention, an optional form of the drug is a polyethylene glycol suspension of Premna microphylla Turcz. leaf powder. Such a suspension-form drug can be used by oral administration or gavage.

[0033] In addition, it should be noted that the form of Premna microphylla Turcz. leaves in the above various uses is preferably powder, which can be prepared according to conventional methods known in the art, such as pulverizing into fine powder, micropowder or nanopowder. At the same time, the active ingredient can also be extracted by using an extraction solvent at an appropriate temperature and pressure. The solvent can be selected from distilled water, C1-C4 lower alcohols, hexane, ethyl acetate, chloroform, diethyl ether, dichloromethane, acetone, and mixtures thereof.

[0034] To make the above objects, features and advantages of the present invention more obvious and understandable, the technical solutions of the present invention will be further described below in conjunction with examples. However, the present invention is not limited to the listed examples, and should also include any other known changes within the scope of the rights required by the present invention.

[0035] Example 1. Preparation of Premna microphylla Turcz. leaf powder

[0036] Take 5000 grams of Premna microphylla Turcz. leaves, dry them at 60 °C and then pulverize them, pass through a 60-mesh sieve, and pack them into bags of 10 grams each to obtain Premna microphylla Turcz. leaf powder.

[0037] Example 2. Pharmacodynamic experiment

[0038] The mice used in the experiments in this example were SPF-grade C57BL / 6 mice (female, 8 weeks old), purchased from Zhejiang Laboratory Animal Center.

[0039] Preparation of tofu shiitake leaf suspension: Take 10mL of polyethylene glycol PEG400, mix it with 26g of tofu shiitake leaf powder, add an equal volume of deionized water, and shake thoroughly to obtain a 13g / mL tofu shiitake solution. Take 20mL PEG400 and 20mL deionized water to make a 50% PEG400 solution, then take 5mL of 13g / mL tofu shiitake solution and mix it with 5mL 50% PEG400 solution to obtain a 6.5g / mL tofu shiitake solution. Take 2.5mL13g / mL tofu shiitake solution and mix it with 7.5mL 50% PEG400 solution to obtain a 3.25g / mL tofu shiitake solution. The above three types of tofu shiitake solutions with concentrations of 13g / mL, 6.5g / mL, and 3.25g / mL are used for oral administration in subsequent experiments, so as to accurately control the dose given per unit body weight of mice.

[0040] Animal grouping and administration: 36 female C57BL / 6 mice were randomly divided into 6 groups after adaptive feeding, namely Normal group, Control group, IR group, PMT(L) group, PMT(M) group, and PMT(H) group, with 6 mice in each group. The treatments of the 6 groups were as follows: the Normal group was given free diet; the Control group was given 200ul of PEG400 aqueous solution by gavage every day; the IR group was given 200ul of PEG400 aqueous solution by gavage every day; the PMT(L) group was given 0.325g / kg of tofu bupleurum leaf by gavage every day; the PMT(M) group was given 0.65g / kg of tofu bupleurum leaf by gavage every day; and the PMT(H) group was given 1.3g / kg of tofu bupleurum leaf by gavage every day. The IR group, PMT(L) group, PMT(M) group, and PMT(H) group were given 8Gy abdominal radiation treatment on the 4th day after gavage, and then bled to death after gavage for 7 days. Blood was collected to measure the levels of ALT, AST, and Cr in serum. The colon, liver, and kidney were collected after autopsy for morphological observation and pathological examination. The weight, food intake, and water intake of mice were recorded daily after radiation treatment. Feces were collected to evaluate fecal occult blood.

[0041] The above experimental results of this embodiment are as follows:

[0042] 1. General observation:

[0043] The diet, water intake, activity, and defecation of the mice in the Normal group and the Control group were all normal, and their mental state was good. After radiation treatment, the food intake and water intake of the mice in the IR group decreased, their mental state was listless, their feces became thinner, and their body weight decreased significantly (P < 0.05 for all). The reduction in food intake and water intake in the PMT(L) group, PMT(M) group, and PMT(H) group was less than that in the IR group, and their mental state improved, showing an obvious dose-effect relationship. The reduction in body weight of the group given Premna microphylla leaves was significantly lower than that in the IR group (P < 0.05 for all), and there was no difference between the PMT(M) group and the Normal group. The body weight changes of the mice in each group are shown in Figure 1 。

[0044] 2. Protective effect on colon injury:

[0045] The colon length of the IR group was significantly shorter than that of the Normal group and the Control group (P < 0.05 for all). The colon length of the group given Premna microphylla leaves was longer than that of the IR group. The colon lengths of the PMT(M) group and the PMT(H) group were statistically significant compared with the IR group (P < 0.05 for all), and there was no significant difference between the PMT(H) group and the Normal group. The results of the colon lengths of the mice in each group are shown in Figure 2 。

[0046] After radiation treatment, the content of hemoglobin in the feces of the IR group increased significantly. The hemoglobin content in the feces of the group given Premna microphylla leaves by gavage was lower than that in the IR group. The statistical results of fecal occult blood of the mice in each group are shown in Figure 3 。

[0047] Local colonic tissue necrosis occurred in 4 mice (4 / 6) in the IR group. Under high magnification, a large number of necrotic cells could be seen, with epithelial cell necrosis and shedding, intestinal wall structure disorder, disappearance of intestinal crypts, necrosis and atrophy of the muscular layer, and significant separation from the submucosa. Feeding Premna microphylla leaves could significantly reduce radiation-induced intestinal necrosis. Only 1 mouse (1 / 6) in the PMT(L) group showed tissue necrosis as indicated by H&E staining of the colon, while there was no manifestation of colonic necrosis in the medium- and high-dose groups. The H&E staining results of the colonic tissues of the mice in each group are shown in Figure 4 。

[0048] The above results indicate that Premna microphylla leaves have obvious preventive and therapeutic effects on radiation-induced intestinal injury.

[0049] 3. Protective effect on the liver:

[0050] In the IR group, the livers of mice showed edema and increased volume, and the liver index was significantly higher than that in the Normal group and the Control group (P < 0.05 for both). The liver indices in the PMT(M) group and the PMT(H) group were significantly lower than that in the IR group (P < 0.05), and there were no significant differences compared with the Normal group and the Control group. Histopathological sections showed that the liver interstitium in the IR group of mice was loose and edematous, and there was a large infiltration of inflammatory cells in the local liver, indicating that radiation caused acute liver injury. The Premna microphylla Turcz. leaf group had less liver edema and had a significant protective effect on acute liver injury. The liver indices of mice in each group and the results of H&E staining of liver tissues are shown respectively as Figure 5 and Figure 6 shown.

[0051] 4. Protective effect on the kidney

[0052] The kidney index of mice in the IR group was significantly higher than that in the Normal group and the Control group, and the Cr content in the serum of mice was significantly increased compared with the Normal group. The kidney indices of mice in the Premna microphylla Turcz. leaf gavage group were not significantly different from those in the Normal group and the Control group, and there were no significant changes in the Cr levels of mice in the low-, medium-, and high-dose Premna microphylla Turcz. leaf gavage groups. This indicates that Premna microphylla Turcz. leaves have a protective effect on kidney injury. The Figure 7 for the kidney indices and serum Cr contents of mice in each group are shown respectively as Figure 7 and Figure 8 shown.

[0053] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not restrictive. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered within the scope of the claims of the present invention.

Claims

1. Use of Premna microphylla Turcz. leaves in the preparation of a drug for preventing, improving or treating radiation injury.

2. The use according to claim 1, characterized in that, The radiation injury is selected from one or more of loss of appetite, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy.

3. A drug for preparing a medicament for preventing, improving or treating radiation injury, characterized in that, Comprising Premna microphylla Turcz. leaves as an active ingredient.

4. The drug according to claim 3, characterized in that, The drug is a composition compounded by Premna microphylla Turcz. leaf powder and one or more pharmaceutically acceptable carriers.

5. The medicament according to claim 3, characterized in that, The drug is a polyethylene glycol suspension of Premna microphylla Turcz. leaf powder.

6. The drug according to claim 3, characterized in that, The radiation injury is selected from one or more of loss of appetite, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy.

7. Use of Premna microphylla Turcz. leaves in the preparation of a food for preventing, improving or treating radiation injury.

8. The use according to claim 7, characterized in that, The radiation injury is selected from one or more of loss of appetite, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy.

9. A food composition for preventing or improving radiation damage, characterized in that, The food composition comprises Premna microphylla Turcz. leaves as an active ingredient.

10. The food composition according to claim 8, characterized in that, The radiation injury is selected from one or more of loss of appetite, diarrhea, weight loss, intestinal injury, kidney injury or liver injury caused by radiotherapy.

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