Effect of Turmeric Herbal on Polycystic Ovary Syndrome: A Systematic Review

: Polycystic Ovary Syndrome (PCOS) is an endocrine disorder that is increasingly affecting women in the reproductive age group. Women commonly experience menstrual irregularities, hirsutism, weight gain, and acne, as well as the development of a complex endocrine disorder that presents with oligomenorrhea, hyperandrogenism, and polycystic ovaries. Herbal medicine is a complex intervention with the potential for synergistic and antagonistic interactions between compounds. These drugs are essential for the treatment of PCOS and have fewer side effects compared to allopathic drugs. One of the herbal medicines to treat PCOS is turmeric or curcumin, curcumin has various biological activities including antioxidant, anti-inflammatory, anti-microbial, anti-tumor, cardioprotective and neuroprotective effects involving various mechanisms. Curcumin can stimulate insulin-mediated glucose uptake via the phosphatidylinositol 3-kinsase (PI3K)/Akt pathway, which, in turn, upregulates glucose transporter 4 (GLUT4) in adipocytes and skeletal muscle, leading to increased glucose levels. Curcumin supplementation improves glycemic control and lipid metabolism, and reduces oxygen radical species in PCOS patients. Curcumin is a diarylheptanoid derived from the rhizome of the Curcuma longa plant, which functions as an anti-inflammatory and antioxidant which is very important in the treatment of PCOS. In addition, nearly half of patients with PCOS develop metabolic syndrome and insulin resistance, and are associated with a much higher risk of type 2 diabetes mellitus.

pharmacological effects.Significant research has shown that curcumin has strong biochemical and biological activities.In addition, curcumin has low toxicity and almost no adverse reactions.Several in vivo and in vitro studies have confirmed that curcumin or turmeric can improve glucose metabolism in diabetes [12].About 70% of people worldwide are interested in the prevention and treatment of disease with complementary and alternative medicine (CAM) although there is not enough scientific assessment evidence to prove its safety and effectiveness [13].Complementary and alternative medicine (CAM), an alternative therapy independent of Western medicine, is widely used in healthcare systems worldwide [14].
Herbal medicine is a complex intervention with the potential for synergistic and antagonistic interactions between compounds.These drugs are essential for the treatment of PCOS and have fewer side effects compared to allopathic drugs.Regular use of herbs is safer and more efficacious in treating PCOS and suppressing the events that contribute to the development of cysts in PCOS.Today, herbal medicine plays an important role in treating various chronic disorders, including PCOS.Using herbal medicines and dietary modifications can help treat PCOS more effectively [15].
Curcumin is a natural medicine containing phenol and quinone groups extracted from turmeric in the ginger family.It is known as a safe dietary supplement worldwide.In several randomized, double-blind clinical trials, patients with PCOS received curcumin (in a dose of 500-1500 mg 3 times daily for 1-3 months) or placebo.It is suggested that curcumin can effectively improve blood glucose, insulin resistance, and hyperandrogenemia in PCOS.In addition, curcumin is reported to exert many beneficial biologic effects through a multitargeting mechanism [16].Consumption of foods containing curcumin also has a protective effect on most of the body's organs.Curcumin is used to prevent various diseases including colon, breast and pancreatic cancer [17].
One of the main features of PCOS is increased androgen levels.Curcumin has been shown to reduce high androgen levels in PCOS in three studies.A randomized controlled clinical trial involving 67 women with PCOS who were treated with 500 mg of powdered curcumin for 12 weeks three times daily showed that dehydroepiandrosterone levels decreased compared to the placebo group.Apart from disrupting androgen levels, PCOS also affects the balance of a woman's LH/FSH ratio.However, a randomized controlled clinical trial showed that curcumin had no effect on LH, FSH and estrogen levels in PCOS women [18].
Curcumin is also known to reduce plasma cholesterol and triglycerides by increasing lipoprotein lipase activity and through mechanisms that alter lipid and cholesterol gene expression.Additionally, the anti-inflammatory effects of curcumin have been shown to reduce oxidative stress in patients with PCOS.Previous literature revealed that curcumin significantly increased fasting blood glucose and triglycerides in patients with metabolic syndrome.Further in vivo studies demonstrated the same effect in PCOS models [19].

RESEARCH METHODS
A systematic review using studies related to herbal ingredients related to curing cervical cancer identified by conducting a literature search.For this systematic review, we conducted an online search strategy involving several databases namely: PubMed, Wiley Online Library, SpringerLink, ProQuest, Science Direct and Google Scholar for articles published in English from 2016 to February 2023.The following keywords were used during the strategy search: "Herbal AND PCOS" OR "Curcumin AND PCOS" OR "Turmeric AND PCOS".

Quality Appraising
For quality purposes, PRISMA was used to ensure the complete results of this study which are shown in Figure 1.

RESULTS
Based on 10 articles discussing the benefits of herbal ingredients that have an effect on curing cervical cancer, they come from various countries, such as Iran, Turkey, Egypt, India.The results of this analysis reported in 10 articles that herbal therapy has a positive effect on healing PCOS as an anti-inflammatory.Journals were obtained from pubmed, science direct, proquest databases (635) and Google Scholar (1710).Article removed due to duplicates (1000).Literature screening by title and abstract (720).Literature excluded for abstract (534).Eligible full text articles (330), published full text literature (95).Article removed for reasons (93).Quantitatively suitable articles (10).Articles that are appropriate and meet the criteria (10).

DISCUSSION
The results obtained from these findings are used to reduce the effect of pharmacological therapy in patients with PCOS.After screening 2345 articles using the PRISMA flowchart, 1000 articles were excluded based on duplication and were omitted because of the journal criteria used, so 10 articles were selected to be included in this systematic review.Many Indonesian plants can be used as herbal medicine, one of which is turmeric 1,11,12,15,16,18-20,22-24,26, Herbal medicine is a type of complementary and alternative medicine and its use by women has increased significantly in the last decades.Curcumin has various biological activities including antioxidant, anti-inflammatory, anti-microbial, anti-tumor, cardioprotective and neuroprotective effects involving various mechanisms.[29].Curcumin can stimulate insulin-mediated glucose uptake via the phosphatidylinositol 3-kinsase (PI3K)/Akt pathway, which, in turn, upregulates glucose transporter 4 (GLUT4) in adipocytes and skeletal muscle, leading to increased glucose levels.In addition, curcumin can also increase GLUT4 and glucose uptake in adipocytes.Curcumin has been shown to inhibit hepatic gluconeogenesis through modulation of 5'AM Pactivated protein kinase (AMPK), thereby reducing blood glucose levels [30].Among the natural phenols, the therapeutic properties of curcumin have been further investigated.Curcumin (diferuloylmethane) is a lipophilic yellow pigment extracted from turmeric (Curcuma longa L.) rhizome.Curcumin supplementation improves glycemic control and lipid metabolism, and reduces oxygen radical species in PCOS patients [31].
Curcumin is a diarylheptanoid derived from the rhizome of the Curcuma longa plant.It is reported to have anti-inflammatory and antioxidant activity which is very important in the treatment of PCOS.Numerous reports are available on the effects of curcumin on various aspects of PCOS in animal models [32].Curcumin or diferuloylmethane is a lipophilic polyphenol in the form of yellow crystals.This is the active ingredient of turmeric with anti-oxidant and anti-inflammatory properties.Several studies have shown curcumin to have an acceptable safety profile with minimal side effects [33].C. longa is rich in polyphenolic curcuminoids, namely curcumin (80%), demethoxycurcumin (12%), bisdemethoxycurcumin (8%), and essential oils (5.8%).The essential oils contained in the rhizomes include α-phellandrene (1%), sabinene (0.6%), cineol (1%), borneol (0.5%), zingiberene (25%), and sesquiterpenes (53%) .These phytochemicals can exhibit important pharmacological activities, including anti-inflammatory, anti-microbial, antioxidant [34].Curcumin also works by inhibiting the activity of pro-inflammatory proteins such as activated protein-1, peroxisome proliferator activated receptor gamma, signal translator, and transcription activator, as well as the expression of bcatenin, cyclooxygenase 2, 5-lipoxygenase, and nitric oxide which can be induced synthase isoform, which plays a key role in inflammation.In addition, it acts by blocking the binding between TNF-α and its receptors, preventing the continuation of cytokineinduced inflammation [35].

CONCLUSION
PCOS is a reproductive endocrine disease characterized by menstrual disorders, infertility, and obesity, usually accompanied by insulin resistance and metabolic disorders.The most common signs of PCOS are ovulatory dysfunction, hyperandrogenism, and polycystic ovaries.In addition, nearly half of patients with PCOS develop metabolic syndrome and insulin resistance, and are associated with a much higher risk of type 2 diabetes mellitus, cardiovascular disease, and even cancer.Women commonly experience menstrual irregularities, hirsutism, weight gain, and acne, as well as the development of a complex endocrine disorder that presents with oligomenorrhea, hyperandrogenism, and polycystic ovaries.Women with PCOS are more likely to be obese/overweight than age-matched controls, and being overweight exacerbates PCOS features.Curcumin can stimulate insulinmediated glucose uptake via the phosphatidylinositol 3-kinsase (PI3K)/Akt pathway, which, in turn, upregulates glucose transporter 4 (GLUT4) in adipocytes and skeletal muscle, leading to increased glucose levels.Curcumin also works by inhibiting the activity of pro-inflammatory proteins such as activated protein-1, peroxisome proliferator activated receptor gamma, signal translator, and transcription activator, as well as the expression of b-catenin, cyclooxygenase 2, 5-lipoxygenase, and nitric oxide which can be induced synthase isoform, which plays a key role in inflammation.Suggestions for future researchers can conduct more research regarding the level of effectiveness of herbal turmeric in healing PCOS, as well as suggestions for health workers to recommend herbal turmeric therapy as an alternative treatment apart from medical treatment.