HERBAL DRUGS FOR THE TREATMENT OF POLYCYSTIC OVARY ... · chosen botanical treatment.[17] 7....

Pharmaceutical Resonance 2019 Vol.2 - Issue 1

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HERBAL DRUGS FOR THE TREATMENT OF POLYCYSTIC OVARY SYNDROME (PCOS) AND ITS COMPLICATIONS

Shantaram Gajanan Khanage1*, Tarkasband Yogita Subhash2 and Inamdar Rahat Bhaiyyasaheb3 1Department of Pharmaceutical Chemistry, Dr. N. J. Paulbudhe college of Pharmacy, Ahmednagar, Dist.-Ahmednagar, Maharashtra, India-414003. 2Department of Pharmacognosy, N. M. S. M.’ S Abasaheb Kakade College of B. Pharmacy, Bodhegaon, Tal-Shevgaon, Dist.-Ahmednagar, Maharashtra, India-414503. 3Department of QAT,N. M. S. M.’ S Abasaheb Kakade College of B. Pharmacy, Bodhegaon, Tq-Shevgaon, Dist.-Ahmednagar, Maharashtra, India-414503.

Dr. Shantaram Gajanan Khanage Principal, Dr. N. J. Paulbudhe College of Pharmacy, Ahmednagar, Maharashtra, India - 414 003 Email : [email protected] Contact : +91 9822652921, 9405476268

ABSTRACT:

The polycystic ovary syndrome (PCOS) is a hyperandrogenic disorder associated with chronic oligo-anovulation. Asians are less influenced by PCOS also to develop hirsutism. The ages of 18 and 44 influenced approximately 5% to 10% of this age group. Infertility, failure to conceive over 1year period of continuous exposure to normal unprotected coitus regularly during the appropriate period of menstrual cycle, is the common global problem. Female infertility accounts to 35%-40% of the overall infertility in humans. So there is more need for study as well as awareness of PCOS. On the basis of above factors there is need to develop polyhedral formulation to reduce the cost, duration, and side effects of existed treatment. Now a day’s herbal drugs are used to overcome polycystic ovary syndrome and its complications, associated sign and symptoms like obesity, irregulation of menstrual cycles, excessive hair growth etc.

Keywords: Polycystic ovary syndrome, hyperandrogenic, infertility, polyhedral formulation.

Introduction

1. Polycystic ovarian syndrome (PCOS):

Polycystic ovarian syndrome, first described in 1935 by Stein and Leventhal, is allied with chronic oligo-anovulation and polycystic ovarian morphology also with psychological impairments, metabolic derangements mainly insulin resistance and compensatory hyperinsulinemia, which may be responsible for altered androgen production and metabolism reproductive age. The lack of well-defined diagnostic criteria confuses the identification of this common disease to many clinicians [1]. Women with PCOS are at increased risk of reproductive abnormalities [2]. This is a major cause of infertility in women, also known as stein-

Leventhal syndrome. With no definite cause known various theories describes the imbalance of hormones. It is characterized by hyperandrogenism, polycystic ovaries, and multiple metabolic aberrations (such as insulin resistance and hyperinsulinaemia) [3]. Currently, the standard care treatment for women with PCOS ranges from lifestyle modification to pharmacological interventions. Lifestyle modifications are associated with diet, weight loss, and exercise. Pharmacological interventions include antiandrogens (spironolactone, flutamide), hypoglycemic agents (metformin and thiazolidinediones), and estrogen - progestin combination (oral contraceptives). Though effective, such treatment is associated with substantial cost and may cause various side effects, such as irregular menstruation, gastrointestinal symptoms, weight gain, and increased insulin resistance [7]. There has been a special attention to medicinal plants since ancient times and today, with numerous studies performed, worthwhile and beneficial medicinal plants are discovered [8]. As the side effects of these medicines and their identification have significant importance, so many studies including randomized controlled trials, case studies, and animal experiments

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are investigated for herbal drugs. Women with PCOS show about twice the level of testosterone as other women, and they are often insulin-resistant. [4] Since then newer rat PCOS models have been developed and validated. These studies provide unique concepts in understanding the nature of chronic anovulation and polycystic ovary. Animal models are central to making the transition from scientific concepts to understanding the reality of a human disease. Validated animal models can be used for therapeutic screens, in preclinical trials, and for basic research in reproductive biology.[9] However, animal models of chronic anovulation and PCOS may not fully reproduce the reproductive events seen in the human syndrome.

2. Symptoms:

Symptoms such as the start of the first period or maybe health issues started later on in your twenties or thirties. These symptoms differ from woman to woman but to be diagnosed with polycystic ovarian syndrome one need to have at least two of the following issues:

Absent periods

Acne not associated with puberty

Darkening of the skin

Excessive hair growth

Fatigue

Fluid retention

Heavy or prolonged periods

Infertility

Irregular periods

Male pattern baldness

Menstrual pain

Mood swings

Ovarian cysts

Weight gain

Female infertility accounts to 35–40% of the overall infertility.[10-12] Polycystic ovarian syndrome (PCOS) is one of the most common female endocrine disorders affecting circa 5–10% of women of reproductive age, and it is thought to be one of the leading causes of female subfertility.

3. Causes of PCOS:

Genetic predisposition

Strong stimulation in adrenals in childhood

Raised insulin levels

Contraceptive pills

Hormonal imbalance

Stress [11]

4. Organs involved in PCOS:

OVARY- The female gonad organ present at either side of uterus.

ADRENAL GLAND- The gland which are placed just above the both the kidneys

PANCREAS- Gland that produces insulin in our body.

PITUTARY GLAND- The gland just below the brain, which is responsible for all the hormonal control.

There is increased production of ANDROGEN by the ovaries which suppresses the maturation of ovarian follicles. So, ovum does not form properly and not released, leading to anovulation. Ovum meets with sperm during intercourse leading to conception. So, in case of PCOS, the woman will encounter conception problem due to unavailability of ovum. There are various anatomical abnormalities associated with PCOS. The ovaries are enlarged two to five times the normal size (PCOS - Ovarian cysts). Stroma is increased. The capsule is thickened and pearly white in color. Ovary which is normally oval in shape will have many cysts within it.[13] A survey concludes that the biggest lifestyle contributor to PCOS is poor diet. Young and stressful women with PCOS tend to eat far too much fat, sugar or carbonized drinks, and highly refined carbohydrates, which causes unhealthy raise in insulin levels. Insulin stimulates androgen receptors outside of ovary, causing typical PCOS symptoms which also play a role in blocking release of ovum from follicle. This type of diet will cause obesity and thus aggravates PCOS[12], and also leads to development of obesity- linked PCOS. The modern stressful lifestyle and food- habits are linked and contribute or accelerate many diseases, PCOS being one among them.

5. Histological Features of PCOS:

Histological features of PCOS include:

Whole ovarian hypertrophy

Thickened capsule (>100 μ)

Increased number of sub capsular follicle cysts

Scarcity of corporea lutea or albicantia

Hyperplasia and fibrosis of the ovarian stroma

Premature luteinization of theca cells. [14]

6. Necessity to Study PCOS:

Two in every 10 women in India has PCOS, according to a study by PCOS Society. Out of every 10 women diagnosed with PCOS, six are teenaged. A



Figure 1: Polycyst Ovary and Histological Features of PCOS.

Figure 2: Hypotylamic-Pitutary-Ovarian Dystruction In PCOS.

study carried by the department of endocrinology and metabolism, AIIMS, shows that about 20-25% of childbearing aged women are suffering from PCOS. While 60% of women with PCOS are obese, 35-50% has a fatty liver. About 70% have insulin resistance, 60-70 has high level of androgen and 40-60 has glucose intolerance. Though the pathophysiology of PCOS is not clear, some women with PCOS have higher than normal insulin levels. Too-high levels of insulin can cause the ovaries to produce more androgens, such as testosterone. Insulin resistance can make it harder to lose weight, which is why women with PCOS often struggle with obesity issue.[15] The reason it is dangerous is that if this condition is left unchecked or undiagnosed, it can lead to infertility among other long-term health concerns. Girls and women suffering from PCOS exhibit a range of symptoms such as weight gain, fatigue, unsolicited hair growth, thinning of hair, infertility, acne, pelvic pain, headaches, sleep problems, and mood changes. Whereas, if caused in ageing individuals it causes diabetes mellitus, high blood pressure, and abnormal blood lipid. In comparative studies of Allopathy, Ayurveda, and Homeopathy, the Allopathy does not cure PCOS, but helps in managing and controlling effects and requires more money and duration while Ayurveda and homeopathy can be considered as best cure and promising treatment with no side effects. So there is more need for study as well as awareness of PCOS. On the basis of above factors there is need to develop polyhedral formulation to reduce the cost, duration, and side effects of existing treatment.

Herbs can be defined generally in commerce as a plant, plant part, or extract there of used for flavor, fragrance, or medicinal purposes. Traditional herbal medicines are naturally occurring substances with minimal or no industrial processing that have been used to treat various illnesses. Traditional herbal medicines are getting significant attention in global health debates. Traditional medicine has established preventive, curative, and rehabilitative role.[1] Herbal therapies can be a very effective treatment option for PCOS because they are usually quite tender on the body and have fewer side effects than medication.[20] Herbal therapy has reached a whirling point. It is fighting to be renowned as a science-a particular field with its own uniqueness. It has become necessary to show that herbal rehabilitation can match other fields of medicine in the thoroughness of its scientific work and its practical use. Benefit of herbal therapy compared to conventional therapy is that herbal therapy is safe with lesser side effects and presence of multiple active compounds in medicinal herbs altogether provides a potentiating effect. [16]

One can use herbs for a longer duration with fewer



side effects which is imperative since PCOS requires a long-term management. They can prove to be efficacious in treating the contributing factors of PCOS, providing relief for symptoms, and healing the body by boosting your immune system. We can combine the herbal remedies with PCOS friendly diet and exercise plan to boost the effectiveness of the chosen botanical treatment.[17]

7. Ayurvedic herbal remedy for PCOS:

Ayurvedic treatment is by applying a multi-pronged approach towards -

Correcting the hormonal imbalance, Treatment to obesity and avoiding high

cholesterol levels, Treatment to insulin resistance.

7.1 Liquorice:

Botanical Name: Glycyrrhiza glabra, Family: Leguminosae. The effect of liquorice was explored on androgen metabolism in nine healthy women 22–26 years old, in the luteal phase of the cycle. They were given 3.5 g of a commercial preparation of licorice (containing 7.6% W/W of glycyrrhizic acid) daily for two cycles. [18] They were not on any other treatment. Plasma renin activity, serum adrenal and gonadal androgens, aldosterone, and cortisol were measured by radioimmunoassay. Total serum testosterone decreased gradually within two months. It returned to pretreatment levels after discontinuation. Licorice can reduce serum testosterone probably due to the block of 17- hydroxysteroid dehydrogenase and 17-20 lyase. Licorice could be considered an adjuvant therapy of hirsutism and polycystic ovary syndrome.

7.2 Aloe-vera:

Botanical Name: Aloe barbadensis, Family: Liliaceae. In a study, the efficacy of Aloe vera gel formulation in a PCOS rat model was checked. Five month old Charles Foster female rats were orally fed with letrozole, a non-steroidal aromatase inhibitor, to induce PCOS. The rats were then treated orally with the Aloe vera gel formulation (1 ml dose daily for 45 days). This restored their estrus cyclicity, glucose

Figure 3: Liquor ice

sensitivity, and steroidogenic activity. [19] Co-treatment of the inductive agent (letrozole) with the Aloe vera gel prevented the development of the PCOS phenotype. Aloe vera gel formulation exerts a protective effect in against the PCOS phenotype by restoring the ovarian steroid status, and altering key steroidogenic activity. This can be attributed to phyto-components present in the extract.

7.3 Flax Seed:

Figure 4: Aloe-Vera

Botanical Name: Linum usitatissimum, Family: Linaceae. A study observed the impact of flaxseed supplementation (30 g/day) on hormonal levels in a 31-year old woman with PCOS. During a four months period, the patient consumed 83% of the flaxseed dose. Height-weight measurement and fasting blood samples taken at baseline and at 4-months follow-up indicated significant decrease in Body Mass Index (BMI), insulin, total serum testosterone, and free serum testosterone levels. The patient also reported a decrease in hirsutism at the completion of the study period. The clinically-significant decrease in androgen levels with a concomitant reduction in hirsutism reported in this case study. [20]

7.4 Gymnema sylvestre (Gymnema):

Gymnema is a traditional Ayurvedic herb used as an antidiabetic, hypogylcemic, lipid lowering agent and to support weight reduction. Gymnema possibly has a trophorestorative action of the beta cells of the

Figure 5: Flax Seed



pancreas. The plant part used as medicine is the leaf. Gymnema is well indicated for PCOS, due to its insulin modulating activity and the added benefits of reducing the elevated triglycerides associated with PCOS. [21-23] Key constituents of Gymnema include saponins, especially the gymnemic acids. Gymnemic acid suppresses the sweet taste on the taste buds, so if taken before food masks the sweet sensation.

Gymnema has demonstrated hypoglycemic activity in experimental models of diabetes and regulatedblood sugar in hyperglycemia. The mechanism of action also includes the inhibition of glucose absorption in the intestine. The daily dose of Gymnema is 3.5 to 11 mL of 1:1 liquid extract. Since conventional medical models are focussing on pharmaceutical agents such as metformin to control PCOS, Gymnema may prove to be one of the most significant herbs in the treatment of the underlying factor of insulin resistance.

7.5 Fennel Seeds:

Fennel seeds are said to help in treating PCOS as they have anti hirsutism properties and help decrease androgen (male hormones) levels. [24]

Figure 6: Gymnema sylvestre (Gymnema)

Figure 6: Fennel Seeds

7.6 Cinnamon

Botanical Name: Cinnamomum zeylanicum, Family: Lauraceae. Cinnamon extract has been shown to reduce insulinresistance in in vitro and in vivo studies by increasing phosphatidylinositol 3-kinase activity

in the insulin signaling pathway and thus potentiating insulin action. Fifteen women with polycystic ovary syndrome (PCOS) were randomized to daily oral cinnamon and placebo for 8 weeks. [25] Comparisons of post-treatment to baseline insulin sensitivity indices using fasting and 2-hour oral glucose tolerance tests showed significant reductions in insulin resistance in the cinnamon group but not in the placebo group.

7.7 Chaste berry:

Figure 8: Cinnamon

This herb has been used for centuries for hormone imbalances and is considered an adaptogen. Chaste berry is one of the most common herbs used to treat PCOSbecause it helps to stimulate and stabilize the function of the pituitary gland. The pituitary gland is responsible for the release of luteinising hormone which can reduce the level of estrogen and androgen levels while raising progesterone levels.

Side effects: This herb is not associated with major side effects but it can cause dizziness, rash and stomach issues. Since it affects the hormones women who are pregnant or taking birth control pills should avoid this herb. People taking dopamine related drugs such as Parkinson’s medications or antipsychotics should also not take chaste berry.

7.8 Stinging Nettle (Urtica Dioica):

The root of this plant increases the production of SHBG (sex hormone-binding globulin) which

Figure 9: Chaste berry (Vitex agnus-castus)



reduces the level of free testosterone in the blood helping to normalize hormone levels. SHBG is often low in women with polycystic ovarian syndrome.

Figure 10: Stinging Nettle (Urtica Dioica)

Side effects: Nettle root should not be taken long-term. It can lower blood pressure so do not take this herb if you are taking medication that lowers blood pressure as well or diuretics.

7.9 Red Clover (Trifolium pretense)

This herb has isoflavones which change to phytoestrogens when in the body. [26] This means red clover acts like estrogen. Red clover is used to purify the blood and treat the acne associated with conditions like polycystic ovarian syndrome

Figure 11: Red Clover (Trifolium pretense)

Side effects: Red clover has been associated with headaches, nausea, vaginal bleeding, muscle ache and rash. Do not take this herb if you have conditions that are worsened by estrogen exposure such as endometriosis, breast cancer, ovarian cancer or if you are pregnant or breastfeeding. Red clover might also increase the chance of bleeding so avoid this herb if you have any kind of bleeding disorder.

7.10 Black Cohosh Root (Cimicifuga racemosa):

This herb has a very strong effect on the endocrine system because it contains phytochemicals that can suppress luteinising hormone secretion. Black cohosh is very effective for PMS, excessive menstrual cramps and hormone related symptoms. [27]

Side effects: This herb can cause several side effects including muscle pain, gastrointestinal issues, weight gain, headache, dizziness and vaginal spotting. Black Cohosh has also been associated with liver disease so be watchful for symptoms like dark urine, loss of appetite, yellowing of the skin or eyes and nausea which can be signs of liver complications.

7.11 Green Tea:

Figure 12: Black Cohosh Root (Cimicifuga racemosa)

The potent antioxidants present in green tea, namely catechins, are responsible for bringing down the levels of the hormones that are causing ovarian cysts and related symptoms. Insulin levels are also brought under control by the green tea antioxidants. Drinking green tea every day also impacts the weight gain that is commonly seen in PCOS and helps you to shed this excessive weight.

7.12 Amla:

Amla is a wonderful detoxifying and cholesterol reducing agent. Its free radical scavenging and anti-inflammatory effects can help to restore the hormonal balance in the body.

7.13 Sesame Seeds:

Sesame seeds contain nutrients beneficial for PCOS patients. Its healthy fats help to regulate blood glucose levels. It also contains minerals like calcium,

Figure 13: Green Tea



magnesium, and zinc.

7.14 Pumpkin Seeds:

Pumpkin seeds also contain the healthy omega-3 fatty acids that can help manage the high cholesterol and high insulin levels seen in PCOS. They also contain beta-sitosterol that can remove excess androgens and treat the hirsutism, acne and weight gain symptoms of PCOS. [28]

Figure 14: Amla

Figure 15: Sesame Seeds

7.15nTulsi:

The androgens are not utilized because the ovulation process does not take place. Also, the SHBG protein produced by liver is also pretty low. This is why

Figure 16: Pumpkin Seeds

Figure 17: Tulsi

women have excessive facial hair growth and acne, and trouble conceiving. Tulsi can control androgens and moderate insulin levels. It's also an excellent antioxidant. Chew at least 10 leaves early in the morning on an empty stomach. Consume boiled tulsi water on a regular basis.

7.16 Curcumin:

Curcumin showed beneficial effects in Letrozole induced PCOS in female Wistar rats. Its effect was comparable to that of Clomiphene citrate, most widely used treatment for ovulation induction in PCOS condition

Figure 18: Curcumin

8. Conclusion:

An ovarian cyst is a health condition becoming very common now a days. Nature has given us so many herbal remedies for ovarian cysts which can be used in both benign and malignant cases along with the other remedies you are taking. These herbs help other treatments to work better and sometimes these herbs are so effective that they alone are good enough to care ovarian cysts naturally.

Acknowledgements:

Authors are heartily thankful to the management and the Principal Dr. N. J. Paulbudhe college of



Pharmacy, Ahmednagar and N. M. S. M.’ S Abasaheb Kakade College of B. Pharmacy, Bodhegaon, Shevgaon for encouragement to carry out this review work.

Yoneto K, Li SK, Higuchi WI, Jiskoot W, Herron JN. Fluorescent probe studies of the interactions of 1-alkyl-2-pyrrolidones with stratum corneum lipid liposomes. J Pharm Sci 1996;85(5):511-517.

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HERBAL DRUGS FOR THE TREATMENT OF POLYCYSTIC OVARY ... · chosen botanical treatment.[17] 7....

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