Research progress of natural products in treating polycystic ovary syndrome

JI Min, WANG Wen‑ting, WU Ying, HUANG Zi‑bao, DONG Lin, ZHANG Xiao‑po,MA Ning, LU Wei‑ying

1.Department of Pharmacy, Hainan Medical University, Haikou 571199, China

2.Reproductive Medical Center, Hainan Women and Children’s Medical Center, Haikou 570206, China

Keywords:

ABSTRACT Polycystic ovary syndrome (PCOS) is a common metabolic disorder reproductive endocrine disease in puberty and women of childbearing age.At present, metformin is mainly used in clinical to treat PCOS.From recent researches, many natural products, such as flavonoids,alkaloids, cumarins, etc, showed curing effects on PCOS.These have been attracting more and more attention.By searching the researches from database of CNKI, PubMed etc, this paper aims at providing a reference for PCOS drug research and development.

1.Introduction

Polycystic ovary syndrome (PCOS) is a complex metabolic disorder characterized by complex manifestations in the majority of women at the stage of growth.In clinic, it is mainly ovulation dysfunction and high level of androgen secretion in women.The incidence rate of 4%‑18%[1] is about 4%‑18%[1] in women of childbearing age.In addition, PCOS also has symptoms such as infertility, menstrual cycle disorder, skin acne and so on.It is easy to increase pregnancy complications and[2] risk of cardiovascular disease, diabetes and endometrial cancer in female climacteric.At present, there are many clinical measures and types of Western medicine for the treatment of PCOS patients.The commonly used western medicine drugs include glucocorticoid, oral contraceptive,spironolactone, gonadotropin, fluorinated amide, clomiphene,insulin sensitizer, letrozole, etc.Although western medicine is convenient to take and increases the ovulation rate, the pregnancy rate is still low and the abortion rate is high, which can not improve the female reproductive endocrine function as a whole, and may cause multiple pregnancy, ovarian hyperstimulation syndrome and other adverse reactions[3].At present, many natural products have made more progress in the treatment of polycystic ovary syndrome.For example, nearly 30 natural products such as alkaloids and flavonoids have significant effects in the treatment and improvement of polycystic ovary syndrome, and the toxic and side effects brought by natural products are more promising than the existing western drugs.Natural products are of great significance in the treatment of polycystic ovary syndrome.This paper reviews the effects of natural products on the treatment of polycystic ovary syndrome.

2.Flavonoids

2.1 Glycyrrhizin

Glycyrrhizin is one of the components of licorice, is a dihydroflavonoid compound, is a plant estrogen, and has a certain antioxidant effect[4].Jiang Lu et al.[4] found that after giving 300 mg/kg Glycyrrhizin to PCOS rats, the ovarian morphology of rats in the administration group was significantly lower than that of rats without administration, and the number of cystic expanded follicles and corpus luteum in the administration group were significantly increased.Compared with the model group, the content of estradiol in peripheral blood of rats increased, the content of testosterone decreased, and the expression of P450 aromatase (P450arom) in ovarian tissue decreased, indicating that glycyrrhizin can reduce the content of P450arom, significantly improve the activity of P450arom and promote the transformation of androgen to estrogen[4].The results showed that glycyrrhizin could reduce the increased ovarian mass of rats with polycystic ovary syndrome, make the morphology of ovarian tissue tend to be normal, reduce the level of luteinizing hormone in serum, increase the level of estradiol, reduce the level of testosterone, and reduce the content of CYP19 mRNA in ovarian tissue, the expression of P450arom decreased, which eventually caused the transformation of androgen in ovary to estrogen, and played a role in improving the pathological characteristics of polycystic ovary syndrome.

2.2 Soybean isoflavones

Soybean isoflavones are flavonoids and secondary metabolites of soybean growth process.Their structure is similar to estrogen.They can affect hormone secretion and protein synthesis.They are natural cancer chemopreventive agents[4].Takafumi Kohama[5] found in the study that the ovulation of patients with secondary amenorrhea was significantly improved after taking soybean isoflavones, resulting in the increase of estradiol.The results showed that the body weight and blood glucose of PCOS patients were reduced by giving soybean isoflavones, and the effect was almost no different from that of metformin, suggesting that soybean isoflavones have the effect of improving insulin resistance similar to metformin.Its mechanism is mainly through inducing islet B cell proliferation, activating cyclic adenosine monophosphate / cyclic adenosine monophosphate dependent protein kinase (cAMP / PKA) signal pathway, increasing insulin secretion and regulating blood glucose level[5].

2.3 Genistein

Genistein, also known as genistein, has the highest activity among isoflavones.It exists in the seeds, stems and leaves of leguminous plants such as soybean, Sophora japonica, alfalfa and so on.It is used for anti‑tumor, bacteriostasis, lipid‑lowering and estrogen like effects.Behnaz khani et al.[6] found that genistein may be selected as an alternative treatment for women with PCOS and may provide favorable advantages and reduce related complications.Sanaz alivandi farkhad et al.[7] found that genistein extracted from soybean isoflavone aglycon can reduce tissue inflammation and oxidative stress and increase TAC (total antioxidant capacity) in PCOS rats.These biochemical and histological findings can support the view that genistein plays a beneficial role in the animal model of polycystic ovary syndrome.

2.4 Puerarin

Puerarin, also known as puerarin flavonoids, is extracted and isolated from the root of Pueraria lobata, a traditional Chinese medicine.It is an isoflavone compound[8].Puerarin has sedative,antipyretic and protective effects on acute myocardial hemorrhage caused by pituitrin[8].Li Wenjing[8] concluded that puerarin can improve PCOS symptoms by resisting hyperandrogen, abnormal lipid metabolism and insulin resistance, and the effect is more obvious for obese people; The changes in antioxidant capacity are more obvious in the cases of thin people.Zhang Linjing et al.[9]showed in the research results that puerarin can effectively reduce the insulin level and blood glucose level of PCOS rats and improve insulin resistance.Comprehensively considered, puerarin has a certain effect on improving PCOS symptoms.

2.5 Procyanidins

Procyanidins, also known as grape polyphenols, are ubiquitous in plants and are flavonoids[10].It can resist oxidation, eliminate free radicals, eliminate superoxide anion free radicals and hydroxyl free radicals, participate in the metabolism of arachidonic acid and phosphate and protein phosphorylation, protect lipids and prevent peroxidation[10].LAN Huan et al.[10] found that compared with the model group (perfused with letrozole carboxymethyl cellulose suspension), low dose (taking procyanidins) and high dose The phosphorylation of Smad2 and Smad3 protein decreased, the expression of Smad4 protein decreased, and the expression of Smad7 protein increased in the ovaries of rats in the (procyanidin) group,and the improvement effect was more significant in the high‑dose procyanidin group The levels of serum T and E2 were also decreased in the high‑dose procyanidin group.

2.6 Quercetin

Quercetin, also known as quercetin and quercetin, exists in many plant stems, leaves, flowers, buds, fruits and seeds, mostly in the form of glycosides.Quercetin is a flavonol compound, which has the effects of resisting free radicals, preventing lipid peroxidation,inhibiting tumor and anticancer.Yang Kailin et al.[11] found that quercetin directly inhibits toll like receptor / NF‑ κ B signaling pathway to improve the microenvironment of ovarian inflammation(interleukin [IL] 1 β, IL‑6 and tumor necrosis factor [TNF]‑α),it can also inhibit the inhibition of phosphatidylinositol 3‑kinase(PI3K) and reduce the expression of CYP17A1 gene.At the same time, it may affect insulin related signal pathways and biological processes, such as (hsa04910) insulin signal pathway, (hsa04931)insulin resistance, from (go: 0032869) Cell response stimulated by insulin.Quercetin can improve ovarian inflammation and oxidative stress in PCOS.In terms of regulating hormones, quercetin can reduce the levels of resistin, testosterone and LH in PCOS patients.It is found that quercetin can alleviate the symptoms of hormone and metabolic disorders in PCOS animals by reducing the levels of testosterone, estradiol and progesterone in animal models.ASMA neisy et al.[12] It was found that quercetin significantly improved the insulin resistance of PCOS rats.PCOS resulted in the decrease of hepatic hexokinase (GK) and the increase of hepatic glucokinase(HK) specific activity, while quercetin increased hepatic HK and GK activities.The data also showed that uterine estrogen receptor in PCOS group α (ERα) The expression of glucose transporter 4(GLUT4) was significantly decreased and increased by quercetin.One of the significant effects of quercetin was to significantly reduce PCOS infrared spectrum and significantly induce uterine glucose transporter 4 and ER α Therefore, it may be an effective method for the treatment of PCOS and its complications, insulin resistance and infertility.

2.7 Baicalin

Baicalin, also known as bejialing, is extracted from the dried roots of the plant Scutellaria baicalensis.It is a flavonoid.Baicalin has diuretic, cholesterol lowering, anti‑inflammatory and regulating some diseases.Wang Wei et al.[13] In the study, it was found that baicalin significantly reduced the levels of free testosterone, follicle stimulating hormone, testosterone, progesterone, luteinizing hormone and estradiol in the serum of PCOS rats.Baicalin significantly inhibited the level of serum insulin and the increase of insulin resistance.In addition, baicalin reduced the body weight of rats,increased the number of rats with regular estrous cycle, and could effectively improve the ovarian histological changes and follicular development of PCOS rats treated with dehydroepiandrosterone.Baicalin can inhibit the pro‑inflammatory cytokine (interleukin‑1) in PCOS rats β, tumor necrosis factor α, The increase of interleukin-18) and the decrease of anti‑inflammatory cytokines (interleukin‑10) in rats.Baicalin induces steroidogenic enzymes (including 3)in ovarian tissue of PCOS rats β‑ The gene expression of HSD,CYP1A 1, CYP1A 1 and star) decreased significantly.Baicalin also inhibited the decrease of adenylate activated protein kinase protein level and phosphorylation level, Akt phosphorylation level and 5 α- Increased expression of reductase 1.Jin Yu et al.[14] It was found that baicalin could reduce the concentration of testosterone in NCI H295R cells by inhibiting the expression of HSD3B2 gene in a dose‑dependent and time‑dependent manner.The hyperandrogen PCOS model rats treated with baicalin significantly reversed the increase of serum androgen level and abnormal ovarian state, and restored the estrous cycle of rats.Baicalin inhibited the transcriptional stimulation of HSD3B2 promoter through GATA1 In conclusion,baicalin has a certain effect on polycystic ovary syndrome.

2.8 Apigenin

Apigenin, also known as apigenin, exists in most fruits, vegetables,beans and other plants.It is a flavonoid compound and can be used to treat diseases caused by HIV or virus.Akingbolabo Daniel ogunnlakin et al.[15] It is found that apigenin inhibits the proliferation of HeLa and CHO cell lines, improves the estrous cycle by increasing the occurrence of estrous cycle and reducing the duration of estrous cycle.In addition, apigenin has antioxidant ability, reduces the level of estradiol, luteinizing hormone, estradiol and follicle stimulating hormone, restores follicular formation to normal, and may restore fertility.In summary, Apigenin can improve the therapeutic effect of polycystic ovary syndrome.

2.9 Amanto biflavones

Amantol biflavone is a flavonoid compound, which has the functions of anti‑oxidation, anti‑tumor, antibacterial, anti‑virus,anti‑aging, treatment of central nervous system and cardiovascular system[16].Zhang Peng[16] In the study, it was found that amantol biflavone could significantly reduce the proportion of estrous cycle disorder in rats, and the time of estrous cycle disorder was later.After amantol biflavone treatment, the average daily weight increase and ovarian weight of rats were significantly lower than those in epilepsy model group.Compared with epilepsy group, the color of ovaries of rats treated with amantol biflavone was more red In addition, the ovarian volume was small, the ratio of serum LH / FSH (luteinizing hormone / follicle stimulating hormone) was lower, LH (luteinizing hormone) was lower, and FSH (follicle stimulating hormone) was lower In conclusion, it can be considered that amanto biflavone can play a protective role in polycystic ovary in epileptic rats, and its mechanism may be to reduce the occurrence of polycystic ovary induced by epilepsy by changing the level of serum hormone in rats.

3.Alkaloids

3.1 Berberine

Berberine, also known as berberine, is a quaternary ammonium alkaloid obtained from the plant Coptis chinensis.It has antibacterial effect and can regulate blood lipid and blood glucose.Francesco Orio et al.[17] Human studies have found that after berberine treatment, the insulin resistance index, triglyceride and total cholesterol of PCOS women are significantly reduced.The use of berberine treatment can make the low‑density lipoprotein have a downward trend, the high‑density lipoprotein has an upward trend, and the menstrual frequency is significantly increased, which also improves the menstrual cycle,and the significant menstrual frequency can be observed in patients Lu Caixia et al.[18] The study found that after using berberine for 3 months, the levels of serum androgen, LH, insulin and fasting blood glucose decreased, the sensitivity to insulin increased, the patient’s IR improved, the level of serum low-density lipoprotein decreased, and the level of serum total cholesterol decreased;berberine improved the patient’s body mass and BMI by regulating the patient’s blood lipid metabolism, and improved the symptoms of PCOS Good therapeutic effect.

3.2 Evodiamine

Evodiamine (Evo), also known as cornelamine, is an alkaloid extracted from the dried and nearly mature fruit of Evodia rutaecarpa.Evodiamine has pharmacological effects such as reducing blood glucose, reducing body weight, improving insulin resistance, anti‑inflammatory and regulating body temperature[19].Du Fang et al.[19]gave PCOS rats high and low doses of Evo respectively.After 22 days, it was found that 80% and 60% of the animals in Evo high dose group and Evo low dose group maintained a regular estrous cycle,and the weight of rats decreased significantly.The ovarian weight,mop (average ovarian area) and V (ovarian volume) decreased,and the levels of INS (insulin) and t decreased significantly, The serum E2 level of rats increased significantly.Evodiamine can play a positive role in the clinical symptoms of PCOS, such as obesity,hyperandrogenemia and insulin resistance[19].

3.3 Polydatin

Polydatin, also known as resveratrol glycoside, is extracted from Polygonum cuspidatum.It has pharmacological effects such as regulating blood lipid, reducing cholesterol, anti‑oxidation and anti‑tumor.Kailin Yang et al.[20] observed that after administration of resveratrol to PCOS rats, androgens in ovaries and adrenal glands of rats were significantly reduced, and their sensitivity to insulin was also improved.TNF in visceral subcutaneous adipose tissue of PCOS rats‑αAnd IL‑6 mRNA expression was also inhibited,thereby inhibiting the inflammatory response.Resveratrol can promote cell apoptosis, reduce the growth of rat membrane stromal cells in vitro, inhibit insulin induced rat membrane stromal cells and reduce the expression of vascular endothelial growth factor (VEGF).In addition, resveratrol can inhibit lipid peroxidation and insulin resistance by interfering with serum malondialdehyde (MDA) and homa‑ir55, and improve PCOS and its complications.Apoptosis or inhibition of stromal cells may be a potential method for the treatment of polycystic ovary syndrome.

4.Other categories

4.1Auraptehe

Auraptehe, also known as hesperidin and glucolactone, is a coumarin derivative, which mainly exists in citrus fruits[21].Ovarian TNF was detected in PCOS animals intervened by auraptehe and metformin α The concentration of TNF was found in auraptehe group and metformin group α The level was similar to that of normal mice.The abnormal rate, germinal vesicle rate and Mi phase percentage of oocytes in model animals were significantly lower than those in other experimental groups.The percentage and expansion rate of MII were significantly higher than those of other experimental groups.Studies have shown that auraptehe can improve the maturation and in vitro fertilization potential of PCOS oocytes by anti‑inflammatory properties, increasing intracellular GSH (glutathione) level and protecting reactive oxygen species (ROS) activity.Auraptehe and metformin significantly reduced ovarian TNF in PCOS mice α The level of Caspase‑3 in cumulus cells of mice in auraptehe and metformin group decreased significantly, indicating that the apoptosis rate decreased.Okuyama et al.[21] researchers found that auraptehe could inhibit inflammatory response, and auraptehe and metformin significantly increased the sperm receiving rate, 2‑cell rate and blastocyst formation rate of oocytes in PCOS animals.The results of oocyte maturation (OM) and in vitro fertilization experiments are consistent with other relevant studies.It shows that veratrol has a positive effect on oocyte maturation of PCOS by increasing intracellular GSH level and reducing ROS activity.Auraptehe can reduce inflammation and apoptosis, and then improve the fertilization rate of mice and the development ability of mouse oocytes.

4.2 Silymarin

Silymarin can be isolated and extracted from milk thistle.It can promote hepatocyte regeneration by inhibiting oxidative stress and antioxidant activity, reduce inflammatory reaction, inhibit the formation of fibrosis, anti lipid peroxidation and immune regulation[22].Shao Fei et al.[22] found that the increasing trend of rat body mass in each administration group (metformin group,silymarin group and metformin + silymarin group) was slower than that in the model group (PCOS).The fasting insulin level,insulin resistance index, 2‑hour postprandial blood glucose, 2‑hour postprandial insulin, testosterone level and luteinizing hormone in the administration group were significantly lower than those in the model group; The levels of serum follicle stimulating hormone and sex hormone binding globulin in the administration group were higher than those in the model group; After the combined use of silymarin and metformin, it was found that all indexes of rats were better than those of single use.The comprehensive data showed that silymarin and metformin had synergistic effects on glucose metabolism and sex hormone levels in PCOS rats.Silymarin can reduce the levels of inflammatory factors and fibrosis indexes in PCOS rats, improve insulin resistance in rats, prevent or even reverse ovarian fibrosis, regulate the level of sex hormones in rats, and promote the development of follicles.It can be considered that the effect of silymarin combined with metformin is better[22].

4.3 Cryptotanshinone

Cryptotanshinone, extracted from Salvia miltiorrhiza, has the effect of promoting blood circulation and dredging menstruation and estrogen like effect[23].Because of its mild estrogen activity, it will be used to treat climacteric syndrome[24].Yang Xinming et al.[23]believe that cryptotanshinone can reduce the functional abnormalities caused by insulin resistance of follicular membrane cells and help to improve reproductive function.Xiong Shukang et al.[24] found that cryptotanshinone can reduce the androgen level of male offspring of PNA rats and AKT2 gene deletion mice, and improve the insulin sensitivity of female offspring of PNA rats and insulin resistance cell model.Cryptotanshinone may directly inhibit the proliferation and lipid synthesis of sebaceous gland cells or indirectly down regulate the expression of androgen receptor in sebaceous gland cells.It can also activate AMPK pathway to affect the activity of PI3K pathway,and then regulate the metabolism of sugar and lipid in PCOS,indicating that cryptotanshinone may directly regulate the synthesis of steroids.In conclusion, cryptotanshinone can reduce the insulin resistance of theca cells and reduce the synthesis of steroids in theca cells.It is considered that cryptotanshinone can be used to alleviate hyperandrogenism caused by PCOS.

4.4 α‑ thujone

α‑ Thujone, an active component of Thuja occidentalis, a cypress plant, belongs to volatile oil.It is used in folk medicine to treat rheumatism, amenorrhea, cystitis and uterine cancer.It is also used as abortion medicine and contraceptive.It has antibacterial,anticancer, anti‑oxidation, anti‑virus, anti‑diabetes, insecticidal,liver protection and radioprotective effects of[25].ESRA K ü Peli akkol et al.[25] showed that after 1 α‑ After thujone treatment,the levels of estradiol and progesterone in PCOS rats increased significantly, the levels of testosterone and luteinizing hormone decreased significantly, and the concentrations of leptin, plasma low density lipoprotein cholesterol (LDL‑C) and glucose also decreased significantly.It can also improve the estrous cycle, make it regular,and regulate hormones by promoting the release of progesterone and estrogen.infer α‑ Thujone can be used to treat PCOS without causing osteoporosis.

4.5 Spearmint oil

Spearmint oil, also known as peppermint oil, is a volatile oil that has anti androgen properties and can significantly reduce the T (Gao Tong) level and hairy symptoms of PCOS women, and has anti‑cancer, antioxidant, anti‑inflammatory and anti diabetic properties.Mahmood Sadeghi ataabadi et al.[26] found that after administration of spearmint oil to PCOS rats, the level of corpus luteum decreased,the weight of rats decreased, the number of ovarian cysts in rats was significantly lower than that in PCOS induced group, and the production of androgen in rats decreased significantly.At the same time, spearmint oil can also significantly reduce the level of testosterone and the number of atretic follicles in PCOS rats, which is related to the antioxidant and anti androgen effects of spearmint oil.In general, spearmint oil can make rats have a higher ovulation rate, and has a certain therapeutic potential for PCOS by inhibiting testosterone and restoring ovarian follicle development.

4.6 Glycyrrhetinic acid

Glycyrrhetinic acid mainly exists in licorice and belongs to saponins.It has the effects of anti immunity, anti inflammation,antitussive and expectorant, antidiuretic and so on.Decio armanini et al.[27] found that glycyrrhetinic acid has antioxidant, antiviral and estrogen like functions and can reduce serum testosterone level.The mechanism may be related to the inhibition of 17 hydroxysteroid dehydrogenase and 17‑20 lyase.Glycyrrhetinic acid can be used as an adjuvant treatment for polycystic ovary syndrome and hirsutism.Zhao Haiyan and other[28] observed that after giving glycyrrhetinic acid to diabetic rats, fasting blood glucose, triglyceride, low density lipoprotein cholesterol, total cholesterol and HOMA‑IR were all decreased.Li Wei et al.[29] treated insulin resistant ovarian granulosa cells with glycyrrhetinic acid.After 48 hours, the level of testosterone in cell culture medium decreased, the level of estradiol (E2) increased slightly, and the level of progesterone (P)was not affected.Lanhuan et al.[30] found that glycyrrhetinic acid can regulate sex hormone level, improve ovulation rate and increase insulin sensitivity.These effects are of great reference significance for the treatment and improvement of PCOS symptoms.Overall,glycyrrhetinic acid has the ability to deal with the common clinical symptoms of PCOS and plays a positive role in the treatment and improvement of PCOS.

4.7 Ginsenosides

Ginsenoside has the functions of anti‑aging, whitening and hair care.Zeng Jie et al.[31] found that the weight of rats taking ginsenoside decreased significantly, the quality of ovaries decreased significantly, the morphology of ovaries was similar to that of normal ovaries, the corpus luteum was large, the follicle was small,contained cumulus and egg cells, the layers of granulosa cells were arranged orderly, the estrous cycle of rats changed periodically,and 23.3% of rats could completely return to the normal estrous cycle; The levels of FT, LH / FSH and the expression of NGF in ovary decreased significantly; Total saponins of red ginseng is the main component of red ginseng rhizome.Oral administration can nourish and slow down aging.Sok Cheon Pak, Ph.D.et al.[32] found that intraperitoneal injection of total saponins of red ginseng can significantly reduce the expression level of NGF in the ovary of PCOS rats.The brain regions of pituitary and hippocampus were not affected by total saponins of red ginseng.This also suggests that the action site of red ginseng saponins regulating NGF expression may be in the periphery of the brain rather than in the center of the brain.

4.8 Astragaloside IV

Astragaloside IV can enhance the body’s immunity, anti‑virus,improve patients’ cardiopulmonary function and anti stress.Li Yanqing et al.[33] observed that after giving astragaloside IV to PCOS rats, the estrous cycle of rats recovered, the ovarian index decreased,the ovarian volume decreased significantly, the ovarian polycystic appearance decreased significantly, the contents of T, LH and MDA in serum decreased significantly, the contents of E2 and FSH and the activities of glutathione peroxidase (GSH PX) and superoxide dismutase (SOD) increased significantly, The content of MDA and the levels of star, cleaved caspase‑3 and Bax protein in ovarian tissue decreased significantly, while the activities of GSH PX and SOD and the level of Bcl‑2 protein increased.Astragaloside IV can effectively balance the level of sex hormones in PCOS rats and alleviate oxidative stress injury.Its mechanism may be related to inhibiting the expression of star.It can be considered that astragaloside IV is beneficial to improve the level of sex hormones in PCOS.

4.9 Geniposide

Geniposide is a iridoid glycoside, which can treat soft tissue injury and has curative effect on diseases of digestive system,cardiovascular system and central nervous system.Wu Chunfeng[34]found that after giving geniposide to PCOS rats, the weight of rats decreased compared with the control group of PCOS rats; T value and LH value decreased compared with the control group.Through visual comparison, the ovaries of rats taking geniposide were red,without cystic expanded follicles, with a large number of corpus luteum, arranged in gyrus, large and round cells and rich cytoplasm.The body weight and ovarian index of rats were significantly lower than those in PCOS group, and the level of sex hormone was also improved.In general, geniposide can improve the clinical symptoms of PCOS, such as hyperandrogenemia, and has a certain reference effect on the improvement of PCOS treatment.

4.10 Tripterygium wilfordii polyglycoside

Tripterygium glycosides have anti‑inflammatory and immune effects and are used to treat primary glomerular nephropathy, lupus erythematosus, rheumatoid arthritis, subacute and chronic severe hepatitis.Tian Fuying et al.[35] found that after three cycles of Tripterygium glycoside treatment of PCOS patients, the volume of ovary and the number of sinus follicles decreased.It also confirmed that Tripterygium glycoside can directly act on ovary and cause partial apoptosis of ovary.The reduction of T level to normal, acne,hairiness and weight is related to the dual role of Tripterygium Wilfordii in ovary.From the above results, it can be considered that Tripterygium wilfordii polyglycoside has a certain effect on improving the clinical symptoms of PCOS and has a certain therapeutic effect on PCOS.

4.11 Poria acid

Poria acid is a triterpene compound, which can competitively inhibit the biological activity of phospholipase A2 (PLA2) and reduce the cell damage mediated by PLA2.It has anti‑inflammatory,anti‑tumor, hypoglycemic, antioxidant, sedative and hypnotic effects[36].Fu Xianpei[37] found that after giving Poria acid to PCOS mice, it can significantly improve the weight gain of PCOS mice, and also improve the abnormal glucose tolerance of mice.Moreover, Poria acid can improve the hormone disorder, chronic inflammation and hyperlipidemia caused by PCOS, and reduce the total cholesterol, triglyceride and triglyceride of mice Low density lipoprotein decreased and high density lipoprotein increased in mice.At the same time, the number of ovarian germinal vesicle (GV)oocytes in PCOS mice increased and the development potential was improved.The mortality of GV oocytes in mice treated with Poria acid was lower than that in PCOS mice, which also showed that Poria acid improved the quality of GV oocytes in PCOS mice by inhibiting the apoptosis of GV oocytes[37].In addition, Poria acid can also reduce the number of oocytes in the second stage of abnormal meiosis (m‑2) of PCOS mice.The number of abnormal oocytes in Poria acid treated mice is less than that in PCOS mice,and the number of oocytes with serious chromosome defects is also significantly lower than that in PCOS mice.Poria acid also played a positive role in the development of follicles.It was observed that the ovaries of PCOS mice had cystic follicles and abnormal appearance of interstitial tissue.Compared with the mice treated with Poria acid, the number of granulosa cells in the ovaries was significantly more normal and more.Poria acid can also significantly inhibit the apoptosis of growing follicular granulosa cells in PCOS mice,and can improve the damage of mitochondria and other organelles in various cells.Poria acid has a wide range and obvious effect in improving the treatment of PCOS.

4.12 Curcumin

Curcumin is extracted from the rhizomes of Zingiberaceae plants.It has the effects of reducing blood lipid, anti‑tumor, antioxidant and anti‑inflammatory.Wu Jinlin et al.[38] found that curcumin has a certain therapeutic effect on PCOS patients during the three‑month treatment.Under the action of curcumin, waist hip ratio, body mass index, triglyceride, total cholesterol, low density lipoprotein cholesterol, (FAI), fasting blood glucose (glu0), blood glucose 2 hours after oral glucose tolerance (glu120), fasting insulin (ins0),insulin 2 hours after oral glucose tolerance (ins120), glycosylated hemoglobin (HbA1c) of PCOS patients decreased significantly,and high density lipoprotein cholesterol (HDL‑C) rise.also β There were also significant changes in cell function indexes,mainly in HOMA patients treated with curcumin and metformin hydrochloride‑β, AUCIns / Glu decreased and DI0, di30 and di120 increased.Compared with metformin hydrochloride alone, HOMA was better in patients treated with curcumin‑ β The decrease is more obvious.After metformin hydrochloride and curcumin combined treatment and metformin hydrochloride alone, the Matsuda index and m value increased, while HOMA‑IR decreased, and HOMA‑IR decreased in patients with curcumin, and the Matsuda index and m value increased more significantly.Qi Yuedong et al.[39] found that curcumin can reduce the ovarian mass of PCOS rats, and may be related to reducing the body weight of rats.In conclusion, curcumin can improve the treatment of PCOS.

4.13 Labisia pumilavar.Alata

Labisia pumilavar.alata (LPVA) is an active ingredient of Golden Lotus in Malaysia, which can promote and induce labor and treat irregular menstruation[40].L.manner š s[40] found that oral LPVA can increase the sensitivity of rats to insulin, increase the level of circulating resistin, reduce the levels of triglyceride and total cholesterol, and reduce the expression of leptin mRNA in mesenteric adipose tissue.Since LPVA did not affect weight change or body composition, but increased uterine weight, it showed that lpva had estrogen effect, which showed that LPVA had the potential to improve PCOS.

5.Summary

Clinically, there is a lack of drugs for the treatment of PCOS caused by insulin resistance, and only metformin is used in clinic.However, long‑term use will produce gastrointestinal side effects,drug resistance and so on.New drugs for the treatment of PCOS need to be developed.According to previous studies, natural drugs often have the characteristics of mild action and multi‑target, so they are favored by people.Many components of natural drugs have the effect of improving PCOS, including alkaloids, flavonoids and lignans, especially berberine, astragaloside IV and curcumin.Systematic research has been carried out, which provides a solid scientific foundation for the discovery of new drugs.However,there are still many natural products that need clinical research,especially the safety evaluation research, which determines whether they can be made into drugs.The natural product has rich structure and significant activity, which provides a choice for the treatment of PCOS and will be an important source of drug research and development for the treatment of PCOS.