Gynecology & Obstetrics

Gynecology & Obstetrics
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ISSN: 2161-0932

Review Article - (2014) Volume 4, Issue 1

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A Novel Molecular Mechanistic Hypothesis to Validate the Therapeutic Effects of Tribulus terrestris (Gokshur) to Ameliorate Pathophysiology and Improve Pregnancy and Fetal Outcome in Preeclampsia

Anitha Kilari1*, Manasi Deshpande2 and Sadhana Joshi1
1Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, India
2Department of Dravyagun Vignan, College of Ayurveda, Bharati Vidyapeeth University, Pune, India
*Corresponding Author: Anitha Kilari, Scientist ‘B’, Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune 411043, India, Tel: (020) 24366929, (020) 24366931, Fax: (020) 24366929 Email:

Abstract

Preeclampsia is a pregnancy hypertensive disorder which leads to both maternal and fetal morbidity and mortality. Evidences suggest that factors such as maternal micronutrients and oxidative stress are involved in the pathology of preeclampsia. Studies on preeclampsia and preterm have shown altered maternal micronutrients (folic acid, vitamin B12) and their probable epigenetic mechanisms leading to metabolic and neurobehavioral disorders in the offspring in later life. Our earlier study has also shown increased oxidative stress and reduced birth outcome in preeclampsia. Reports also suggest that micronutrients deficiency is prevalent in Indian women leading to oxidative stress and adverse pregnancy outcomes. However, studies on supplementation with micronutrients/synthetic antioxidants have shown controversial results in preeclampsia. Further, there are no reports on supplementation with natural antioxidant rich Ayurved herbal agents in preeclampsia. Tribulus terrestris (TT) is aprostate herb, used extensively in traditional Indian medicine (Ayurved) to treat inflammatory (Shotha), cardiovascular (Hridroga) and renal disorders. TT has been advised during sixth month of pregnancy in Ayurveda to maintain pregnancy. Further, several clinical and experimental studies have validated the effects of TT in cardiovascular, hepatic and reproductive disorders due to its antioxidant and antihypertensive activities. However, no studies have examined the effect of TT in the prevention/treatment of preeclampsia and fetal programming. Hence, future studies should investigate the efficacy of TT along with micronutrients like folate and vitamin B12 in the treatment of preeclampsia using well defined molecular mechanisms.

Keywords: Tribulus terrestris, Gokshur, Pregnancy, Preeclampsia, Ayurved

Abbreviations

ACE: Angiotensin-Converting Enzyme; DHA: Docosahexaenoic Acid; DNA: Deoxyribonucleic Acid; IUGR: Intrauterine Growth Restriction; IQ: Intelligent Quotient; LCPUFA: Long Chain Polyunsaturated Fatty Acids; PE: Preeclampsia; RDA: Recommended Dietary Allowance; RNA: Ribonucleic Acid; TT: Tribulus terrestris

Introduction

Preeclampsia (PE), a pregnancy-specific syndrome remains a leading cause of maternal and neonatal morbidity and mortality [1]. PE incidence ranges from 3 to 10% of all pregnancies worldwide [2]. Reports indicate that the occurrence of PE is higher in developing countries than in developed countries [3]. Delivery of the baby is the only current cure in PE that inflicts severe prematurity on the baby [4]. PE increases the risk for long-term cardiovascular diseases in mothers and in the offspring [5-8]. It is also evident that children born to mothers with preeclampsia had an increased risk for endocrine, nutritional, metabolic disorders [9]. Growth restricted babies especially born to mothers with preeclampsia are reported to have a lower IQ and reduced adult cognitive performance leading to neurodevelopmental impairment in later life [10-12].

Despite of extensive research on PE worldwide, unfortunately, since the pathogenesisis complex, the precise underlying cellular and molecular mechanisms of PE are unclear [13,14]. Although the precise origins of the disease remain enigmatic, the placenta plays a key role since delivery inevitably leads to rapid recovery suggesting that a hypoxic or ischemic placenta is the trigger of pathophysiology of PE [15,16]. Reports suggest that defective spiral artery remodeling may be the key initiating factor of PE which leads to improper placental perfusion, endothelial dysfunction and fetal growth restriction [17,18]. The hypoxia at the fetal-maternal interface can result in the generation of free radicals leading to increased oxidative stress which will further trigger a wide range of pathophysiological changes in blood and tissues of women with preeclampsia [8,19]. Human studies in our laboratory have shown reduced antioxidants, increased oxidative stress, altered levels of micronutrients (folic acid and vitamin B12) and omega 3 Long Chain Polyunsaturated Fatty Acids (LCPUFA) which were associated with adverse birth outcome in pregnancy complications like PE and preterm deliveries [20-24]. Further, animal studies have shown maternal micronutrient imbalance alters fatty acid desaturasesin dams and increases oxidative stress in the offspring [25-27].

Even though oxidative stress is well established in preeclampsia, supplementation studies with antioxidants like vitamin C and E in preeclampsia are inconclusive [28-30]. A study reveals that antioxidant supplementation to pregnant women with low antioxidant status was associated with better maternal and perinatal outcome [31]. In contrast, a recent review does not support the use of synthetic antioxidants during pregnancy for the prevention of preeclampsia [32]. Further, antioxidant/ phytonutrient (vegetable and fruit juice powder) supplementation in early pregnancy did not decrease rates of preeclampsia [33]. There are number of reviews which have evaluated interventions for prevention of preeclampsia which includes antenatal surveillance, modification of lifestyle, nutritional supplementation and pharmacological therapy [34,35]. Despite the variety of possible prophylactic interventions described, studies have produced disappointing results [36]. Interventions such as rest, exercise, reduced salt intake, garlic, marine oil, antioxidants, progesterone, diuretics, and nitric oxide showed insufficient evidence to be recommended as preventive measurements for PE [35]. On the other hand, reports suggest that many traditional herbal compounds possess rich antioxidant properties [37]. However, no reports or reviews have evaluated the effect of traditional herbal interventions in preeclampsia. Thus, at present, there are no well standardized therapeutic means in both modern medicine as well as traditional medicine to ameliorate the pathophysiology of PE and improve pregnancy and fetal outcome. In order to have effective therapeutic strategy for PE, it is essential that use of traditional herbal compounds should be combined with proper micronutrient dietary balance.

Balanced Traditional Herbal Medicines and Dietary Micronutrients

Dietary regimen advised in ayurved during pregnancy

The traditional knowledge of Indian medicinal plants which is inherited from ancestors is very effective, valuable, useful and with fewer side effects than the synthetic pharmacological agents. Ancient Indian traditional medicine known as ‘Ayurved’ dates back to 3000 B.C and is a holistic system of medicine which encourages the appropriate changes in diet and lifestyle to maintain an individual’s health. Ayurved advises the month wise dietary regimen during pregnancy to nourish the mother, to help the growth and development of the fetus, to ensure smooth child birth and to help the secretion of breast milk [38]. This regimen includes food and herbal preparations and are predominantly sweet in taste, easy to digest, cooling to the body and liquid in consistency. During sixth month of pregnancy, Gokshur (Tribulus terristris), processed in clarified butter (Ghee), added to gruel (Kanji) and Ghee processed with sweet herbs were advised. Since preeclampsia develops after 20 weeks of gestation (6th month of pregnancy) and Gokshur was also advised during 6th month of pregnancy, it is interesting to explore the efficacy of Gokshur in ameliorating the pathophysiology of preeclampsia.

Tribulus terrestris in ayurved: Tribulus terrestris (TT) is known as ‘Gokshur’ in Ayurved, ‘caltrop’ in English, ‘Gokharu’ in Hindi (national language of India). Gokshur has been referred in many contexts in Ayurved classics like Charaksamhita and Sushrutsamhita. TT is aprostate herb, annual/perennial with many slender, spreading branches in all directions and belongs to Zygophyllaceae family. TT is a common weed, springing in waste lands, road sides and in fields soon afterfirst shower. In Ayurved, Gokshur has been indicated in many disease conditions such as cardiovascular (Hridroga), inflammation (Shotha) and to maintain pregnancy (Garbhasthapana) etc. [39]. Clinical studies on Gokshur and its formulations have shown improved sperm count and motility, effective in the treatment of urolithiasis, reduced symptoms scores in benign prostate hyperplasia and improved lipid profile [40-43]. Diuretic action of Gokshur has been studied using rats [44].

Saponins of Tribulus terrestris: Several studies have isolated, identified and reported the saponins from the TT. Tribulus species are rich source of steroidal saponins and steroidal glycosides [45,46]. Feruloyl amide derivative (tribulusamide C) and Furostanol saponins were isolated from the fruits of Tribulus terrestris while steroidal saponins such as protodioscin, tribulosaponin B, metilprotodiostsin, terrestrozin H, prototribestin, gracillin were found from Tribulus terrestris [47-49].

Therapeutic activities of TT on various biological systems: There were several reported clinical and experimental studies on different therapeutic actions of TT on various physiological systems which have been systematically reviewed in this paper and compiled according to the biological systems.

Renal system: A very common clinical condition known as urolithiasis (kidney stones) which is due to adhesion of calcium oxalate crystals to kidney cells is associated with severe pain and discomfort in the abdomen. Purified protein biomolecule from TT can be used in kidney stones [50]. TT extract protects kidney against cadmium induced toxicity [51]. Glycolate oxidase (GOX) is one of the key enzymes involved in the pathway of oxalate synthesis and the anti- GOX leads from TT have been reported [52]. Aqueous extract of TT restores kidney tissue in oxidative stress induced rats [53]. A capsule containing TT showed beneficial effect in treating the urolithiasis [54]. In contrast, use of TT to prevent renal calculi induced hepatotoxicity, nephrotoxicity and neurotoxicity in an Iranian male patient [55]. Methanolic extract of TT has shown protective effect on kidney by regulating oxidative parameters [56]. Saponins from TT have inhibited the growth of the renal carcinoma cells [57]. TT has shown diuretic and contractile effects in propelling urinary stones [58].

Reproductive system: TT has long been used as a traditional medicine to treat impotency and improve sexual functions in humans and also treatment with TT has decreased ovarian cysts in polycystic ovary induced rats [59]. Histological study revealed that the testes of fish treated with TT extract contained all stages of spermatogenesis and sperm quality [60,61]. A review on the potential role of plant based antioxidants includes TT to control the oxidative stress induced sperm production and quality in livestock [62]. TT has significantly lowered IPSS scores in the initial treatment of symptomatic benign prostatic hyperplasia [63]. A recent review on scientific validation of traditionally used herbal plants including TT as aphrodisiac herbs for the management of sexual disorder erectile dysfunction [64-66], little evidence in improving female sexual dysfunction and increase in reproduction rate up to two generations [64-68]. A study showed a protective effect of TT against cadmium induced testicular damage and improved the serum testosterone in rats [69,70]. TT has improved sperm production in rats without altering circulating androgens but not able to stimulate endocrine sensitive tissues such as the prostate, seminal vesicle, uterus and vagina in Wistar rats [71].

Hepatic system: TT fruit extract has provided protection against induced hepatic damage in the mice [72]. Ethanolic extract of TT reversed the cadmium induced oxidative stress and changes in hepatic functional markers [73]. TT is protective against cytotoxicity in HepG2 cells and liver cancer cell line [74,75]. TT also showed inhibitory effect on human pancreatic amylase and hypoglycemic effect in mice by inhibiting oxidative stress. TT has also shown antimicrobial and antifungal activity 79 [76-79].

Nervous system: A study supports the protective role of TT in cerebral architecture in dietary induced hyperlipidemia [80]. In vitro studies have shown that TT saponin decreases the apoptosis of rat cortical neurons [81]. A formulation containing TT showed both antidepressant and antianxiolytic activity in rats [82]. Baisong tablet containing TT has the antidepressant effect by downregulating CRH mRNA expression in brain [83].

Anticancer activity: Aqueous extract of TT proliferates and induces apoptosis in human liver cancer cells through the inhibition of NF-κB signaling and regulating polyamines’ homeostasis [84,85]. TT has shown protective effect against UVB-induced carcinogenesis [86].

Cardiovascular system: Tribulosin, a component of TT has protective effects on cardiac myocytes via ERK1/2 pathway [87]. Saponins of TT can protect cardiocytes with its effect of resisting oxygen free radical in rats [88]. Saponin of TT has shown preventive effect against myocardial apoptosis [89]. Dietary intake of TT has lowered serum lipid profiles and may partially repair the endothelial dysfunction resulting from hyperlipidemia in rabbits and mice [90,91]. Triterpenesaponin of TT protects cardiocytes during chemical hypoxiaischaemia in vitro [92]. Saponins from TT can relieve the damage of cardiac muscle cell and attenuate the ventricular remodeling after myocardial infarction [93].

Antihypertensive effect: A clinical study has showed antihypertensive effect of TT without any side effects suggesting that TT can be safely recommended for a longer period to the patients of mild to moderate hypertension mainly associated with fluid retention [94]. Antihypertensive effect of TT and a negative association between TT consumption and ACE activity have been reported in rats [95,96].

Antioxidant activity: Aqueous extract of TT has attenuated neuropathic pain by regulating oxidative stress markers in diabetic neuropathic pain model [97]. TT extract has shown considerable anti-oxidant potential [98]. Crude extract of TT showed antioxidant and antimicrobial properties in vitro [99]. Aqueous extract of TT has reduced tumor incidence and number of papillomas in mice by decreased lipid peroxidation levels and increased glutathione levels in the liver [100]. TT saponin, ingredient of Xinnao Shutong capsule, revealed the protective effect against cerebral ischemic injury by reducing malondialdehyde levels [101]. TT showed potent inhibition of COX-2 activity [102].

Rationale of Gokshur in the treatment of preeclampsia: Extensive literature review on TT suggests that TT is effective in treating many disease conditions through its rich antioxidant activity [88,97]. It is evident that TT have antihypertensive and antioxidant effect and preeclampsia is known to be associated with broad range of pathophysiologies particularly hypertension and oxidative stress. This makes TT a preferred herbal agent for treatment of PE. However, there are no studies on TT interventions during pregnancy in reducing the risk of preeclampsia. Therefore, there is a need to explore the effect of TT in ameliorating the preeclampsia symptoms using animal models followed by clinical trials. Furthermore, it is important to have a molecular mechanistic hypothesis to validate its efficacy.

Micronutrients in one-carbon metabolism–risk for adult disorders in the offspring

Maternal micronutrients like folate and vitamin B12 play key role in one-carbon metabolism. Folate (B9) is a water soluble vitamin and involved in DNA synthesis during embryonic and fetal development [103], maintains adequate cellular levels of S-Adenosylmethionine (SAM) known as a methyl donor required for biological methylation [104]. Disruption of folate-mediated one-carbon metabolism is associated with many pathologies and developmental anomalies [105]. Vitamin B12 (cobalamin) is required for cellular metabolism and is essential during pregnancy because of its role in DNA and methionine synthesis. Cobalamine deficiency leads to hematological (megaloblasticanaemia), neurological (tingling and numbness of the extremities) and cognitive disturbances (gait abnormalities, visual disturbances, memory loss and dementia) [106]. Recent review has mentioned that low maternal vitamin B12 status is associated with increased risk of neural tube defects and poor offspring cognitive functions [107]. Hence, both folate and vitamin B12 are necessary for fetal development and the deficiency of these micronutrients is associated with multiple disorders. The deficiency of folate and vitamin B12 raise the concern for the community at large, more specifically neonatal and child health [108].

Indian studies have reported lower dietary intakes of micronutrients such as calcium, Iron and folate well below the Indian RDA and also lower micronutrients (vitamin B12) status in Indian pregnant women [109,110]. Further, both maternal and fetal vitamin B12 levels in Indians were lower than that reported in western subjects [111,112]. In developing countries, diets are generally low in animal products and consequently in vitamin B12 content which may cause reduced fetal growth [113]. Further, most of the Indians are being vegetarians; a high prevalence of vitamin B12 deficiency in early pregnancy among urban South Indian women was reported [114]. Children born to mothers with a lower vitamin B12 status have shown a reduced cardiac sympathetic activity [115]. Another Indian study has revealed that the two thirds of the mothers had low vitamin B12 concentrations and high circulating concentrations of homocysteine in IUGR [110]. Vitamin B12 is essential in homocysteine metabolism and hyperhomocysteinemia is associated with preeclampsia. Evidences clearly suggest that the prevalence of vitamin B12 and folate deficiency is high in the Indian population [116]. Although a National program of prenatal Iron folic acid supplementation is in operation for over 30 years in India, micronutrient status did not improve in Indian pregnant women due to inadequate antenatal care [117]. Further, large dose (3-5 mg) of folic acid per day was given118 as compared to folate RDA (400- 500 μg/day) for pregnant women [118,119]. High folate in the presence of lower vitamin B12 may affect the one–carbon metabolism leading to epigenetic changes and increase the risk for adult diseases.

Several studies in our laboratory on both human and animals regarding the role of maternal micronutrients and DHA in onecarbon metabolism and their association with adverse birth outcome in pregnancy complications have been reported. For instance, the associations of folic acid, vitamin B12, homocysteine with DHA and baby weight during pregnancy in humans [24]. Further, animal experiments have shown the effects of maternal micronutrients imbalance during pregnancy on maternal fatty acid desaturases & transport proteins; and offspring brain oxidative stress and antioxidant enzymes [25-27]. A hypothesis has been proposed that altered maternal micronutrients will increase homocysteine and oxidative stress leading to pregnancy complications and adverse birth outcomes and result in epigenetic programming of adult diseases in later life [22,23]. Epigenetics is defined as changes in gene expression which are not caused by changes in DNA sequence1 [120]. This epigenetic regulation is examined by 4 main modes i.e. DNA methylation, imprinting, histone modification, and small RNA-mediated control, specifically miRNAs [121]. A recent study has shown altered DNA methylation in placental angiogenesis in preeclampsia [122]. The above evidences clearly indicates that factors like altered maternal micronutrients, omega 3 fatty acids, increased homocysteine and oxidative stress are involved in the pathology, epigenetic changes and fetal programming in preeclampsia. Despite essential role of maternal micronutrients (folate and vitamin B12) in pregnancy, studies on supplementation with micronutrients during pregnancy are controversial. Studies with daily consumption of either 400 μg or high doses of folic acid during early pregnancy could not prevent the occurrence of gestational hypertension and preeclampsia [123,124]. In contrast, supplementation of multivitamins containing folic acid in the second trimester has shown the association with reduced risk of preeclampsia [125]. A recent report has been demonstrated the association between folic acid supplementation and oxidized lowdensity lipoprotein which effects oxygen free radicals during pregnancy and are a risk factor for preeclampsia [126]. Maternal RBC folate concentration in early pregnancy is associated with small for gestation age and preterm births, but not with preeclampsia [127]. Furthermore, Indian cohort has shown reduced micronutrients and antioxidant enzymes which were associated with oxidative stress in preeclampsia [128]. A recent review explains that maternal macronutrients deficiency plays an important role in fetal programming in developing countries leading to insulin resistance, glucose intolerance, hypertension and adiposity in adulthood [129]. Research on epigenetics started focusing on prenatal supplementation and their epigenetic changes during embryonic development [130]. However, there are no studies on prenatal herbal (antioxidant rich) supplementation and epigenetic regulation of antioxidant genes which are major contributor in pathology of preeclampsia. Therefore, it is important to explore the efficacy of herbal agents (natural antioxidants) along with micronutrients during pregnancy in ameliorating preeclampsia and reduce the risk of adult disorders in the offspring.

Hypothesis

We hypothesize that the well standardized use of TT or formulations of TT with micronutrients in preeclampsia may ameliorate the symptoms of preeclampsia primarily due to its high antioxidant potential, improve the birth outcome, control the epigenetic changes and reduce the risk of adult metabolic and behavioral disorders in the offspring.

Conclusion

In summary, micronutrients deficiency, hyperhomocysteinemia leading to oxidative stress are implicated in the pathology of preeclampsia and fetal programming of adult diseases. However, supplementation with micronutrients/synthetic antioxidants during pregnancy showed controversial results. Further, there are no reported studies on supplementation with antioxidant rich Ayurved herbal agents in preeclampsia. Ayurved has mentioned multiple therapeutic effects such as cardioprotective, anticancer, neuroprotective, hepatoprotective, renal and aphrodisiac etc. of TT and several clinical and experimental studies have well established and validated the beneficial effects of TT including its antioxidant and antihypertensive activities. However, no study has examined the effect of TT in the prevention/treatment of preeclampsia. Therefore, there is a need to explore the efficacy of TT along with micronutrients in the treatment of preeclampsia and regulation of epigenetic changes in preeclampsia. Hence, future studies should investigate the efficacy of TT along with micronutrients in the treatment of preeclampsia using well defined molecular mechanisms.

References

  1. Facca TA, Kirsztajn GM, Pereira AR, Moreira SR, Teixeira VP, et al. (2012) Renal evaluation in women with preeclampsia. Nephron Extra 2: 125-132.
  2. WHO (2005) The World Health Report 2005 - make every mother and child count, World Health Organization, Geneva, Switzerland.
  3. Kaitu'u-Lino TJ, Palmer K, Tuohey L, Ye L, Tong S (2012) MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin. PLoS One 7: e39864.
  4. Sibai B, Dekker G, Kupferminc M (2005) Pre-eclampsia. Lancet 365: 785-799.
  5. Duley L (2009) The global impact of pre-eclampsia and eclampsia. Semin Perinatol 33: 130-137.
  6. Silasi M, Cohen B, Karumanchi SA, Rana S (2010) Abnormal placentation, angiogenic factors, and the pathogenesis of preeclampsia. Obstet Gynecol Clin North Am 37: 239-253.
  7. Roberts JM, Pearson G, Cutler J, Lindheimer M; NHLBI Working Group on Research on Hypertension During Pregnancy (2003) Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy. Hypertension 41: 437-445.
  8. Wu CS, Nohr EA, Bech BH, Vestergaard M, Catov JM, et al. (2009) Health of children born to mothers who had preeclampsia: a population-based cohort study. Am J Obstet Gynecol 201: 269.
  9. Many A, Fattal A, Leitner Y, Kupferminc MJ, Harel S, et al. (2003) Neurodevelopmental and cognitive assessment of children born growth restricted to mothers with and without preeclampsia. Hypertens Pregnancy 22: 25-29.
  10. Ehrenstein V, Rothman KJ, Pedersen L, Hatch EE, Sørensen HT (2009) Pregnancy-associated hypertensive disorders and adult cognitive function among Danish conscripts. Am J Epidemiol 170: 1025-1031.
  11. Streimish IG, Ehrenkranz RA, Allred EN, O'Shea TM, Kuban KC, et al. (2012) Birth weight- and fetal weight-growth restriction: impact on neurodevelopment. Early Hum Dev 88: 765-771.
  12. Maynard SE, Min JY, Merchan J, Lim KH, Li J, et al. (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111: 649-658.
  13. Granger JP, Alexander BT, Bennett WA, Khalil RA (2001) Pathophysiology of pregnancy-induced hypertension. Am J Hypertens 14: 178S-185S.
  14. Poston L (2006) Endothelial dysfunction in pre-eclampsia. Pharmacol Rep 58 Suppl: 69-74.
  15. Myatt L, Webster RP (2009) Vascular biology of preeclampsia. J Thromb Haemost 7: 375-384.
  16. George EM, Granger JP (2010) Recent insights into the pathophysiology of preeclampsia. Expert Rev Obstet Gynecol 5: 557-566.
  17. Roberts JM, Gammill HS (2005) Preeclampsia: recent insights. Hypertension 46: 1243-1249.
  18. Hubel C, Roberts J (1999) Lipid metabolism and oxidative stress. In: Lindheimer M, Roberts J, Cunningham F (Eds.) Chesley’s Hypertensive Disorders in Pregnancy. (3rd Edn.), Academic press, USA, P: 453-486.
  19. Mehendale S, Kilari A, Dangat K, Taralekar V, Mahadik S, et al. (2008) Fatty acids, antioxidants, and oxidative stress in pre-eclampsia. Int J Gynaecol Obstet 100: 234-238.
  20. Dangat KD, Mehendale SS, Yadav HR, Kilari AS, Kulkarni AV, et al. (2010) Long-chain polyunsaturated fatty acid composition of breast milk in pre-eclamptic mothers. Neonatology 97: 190-194.
  21. Dhobale M, Joshi S (2012) Altered maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids through oxidative stress may reduce neurotrophic factors in preterm pregnancy. J Matern Fetal Neonatal Med 25: 317-323.
  22. Sundrani DP, Chavan Gautam PM, Mehendale SS, Joshi SR. (2011) Altered metabolism of maternal micronutrients and omega 3 fatty acids epigenetically regulate matrix metalloproteinases in preterm pregnancy: a novel hypothesis. Med Hypotheses 77: 878-883.
  23. Wadhwani NS, Pisal HR, Mehendale SS, Joshi SR (2013) A prospective study of maternal fatty acids, micronutrients and homocysteine and their association with birth outcome. Matern Child Nutr .
  24. Wadhwani NS, Dangat KD, Joshi AA, Joshi SR (2013) Maternal micronutrients and omega 3 fatty acids affect placental fatty acid desaturases and transport proteins in Wistar rats. Prostaglandins Leukot Essent Fatty Acids 88: 235-242.
  25. Wadhwani NS, Manglekar RR, Dangat KD, Kulkarni AV, Joshi SR (2012) Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats. Prostaglandins Prostaglandins Leukot Essent Fatty Acids 86:21-27.
  26. Roy S, Sable P, Khaire A, Randhir K, Kale A, et al. (2013) Effect of maternal micronutrients (folic acid and vitamin B12) and omega 3 fatty acids on indices of brain oxidative stress in the offspring. Brain Dev.
  27. Conde-Agudelo A, Romero R, Kusanovic JP, Hassan SS (2011) Supplementation with vitamins C and E during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes: a systematic review and metaanalysis. Am J Obstet Gynecol 204: 503e1-12.
  28. McCance DR, Holmes VA, Maresh MJ, Patterson CC, Walker JD, et al. (2010) Diabetes and Pre-eclampsia Intervention Trial (DAPIT) Study Group. Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial. Lancet 376: 259-266.
  29. Rumbold A, Middleton P, Pan N, Crowther CA (2005) Antioxidants for preventing pre-eclampsia. Cochrane Database Syst Rev.
  30. Rumiris D, Purwosunu Y, Wibowo N, Farina A, Sekizawa A (2006) Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status. Hypertens Pregnancy 25: 241-253.
  31. Salles AM, Galvao TF, Silva MT, Motta LC, Pereira MG (2012) Antioxidants for preventing preeclampsia: a systematic review. ScientificWorldJournal 2012: 243476.
  32. Parrish MR, Martin JN Jr, Lamarca BB, Ellis B, Parrish SA, et al. (2013) Randomized, placebo controlled, double blind trial evaluating early pregnancy phytonutrient supplementation in the prevention of preeclampsia. J Perinatol 33: 593-599.
  33. Meher S, Duley L (2005) Interventions for preventing preeclampsia and its consequences: generic protocol. Cochrane Database Syst Rev.
  34. Bezerra Maia E Holanda, Moura S, Marques Lopes L, Murthi P, da Silva Costa F (2012) Prevention of preeclampsia. J Pregnancy 2012: 435090.
  35. Leslie K, Thilaganathan B, Papageorghiou A (2011) Early prediction and prevention of pre-eclampsia. Best Pract Res ClinObstetGynaecol 25: 343-354.
  36. Wachtel-Galor S, Benzie IFF (2011) Herbal Medicine: An Introduction to Its History, Usage, Regulation, Current Trends, and Research Needs. In: Benzie IFF, Wachtel-Galor S (Eds.), Herbal Medicine: Biomolecular and Clinical Aspects. (2ndedn): CRC Press, Boca Raton (FL), Chapter 1.
  37. Girija PL (2008) Diet and regimen during pregnancy. Anc Sci Life 28: 40-43.
  38. Sharma PC, Yelne MB, Dennis TJ, Aruna Joshi (2004) Database on medicinal plants used in Ayurveda, Central Council for Research in Ayurveda and Siddha, New Delhi.
  39. Sudev C, Suresh RD (2012) A clinical study on gokshuradichurna in the Management of oligospermia. GJRMI 1: 22-31.
  40. Arawatti S, Yadav P, Murthy S, Basalingappa, Verma JP (2012) Clinical Study on Gokshuradi Kashaya in the Management of Urolithiasis (Mutrashmari). Int J of Ayurvedic and Herbal Medicine 5: 520-529.
  41. Vasava YR, Bhuyan C, Rajagopala M, Gupta SK, Dudhamal TS (2010) Effect of Mahayavanala Roma Kshara and DhanyakaGokshuraGhrita in benign prostatic hyperplasia. Ayu 31: 332-337.
  42. Nadkarni MA, Vyas SN, Baghel MS, Ravishankar B (2010) Randomized placebo-controlled trial of MustadiGhanavati in hyperlipidemia. Ayu 31: 287-293.
  43. Singh RG, Singh RP, Usha KP, Singh P (1991) Experimental Evaluation of Diuretic Action of Herbal Drug (Tribulusterrestris) on Albino Rats. Journal of Research and Education in Indian Medicine 10: 19-21.
  44. Hamed AI, Janda B, Mahalel UA, Stochmal A, Oleszek W (2012) Profiles of steroidal saponins from the aerial parts of Tribuluspentandrus, T. megistopterus subsp. pterocarpus and T. parvispinus by LC-ESI-MS/MS. Phytochem Anal 23: 613-621.
  45. Chen G, Liu T, Lu X, Wang HF, Hua HM, et al. (2012) New steroidal glycosides from Tribulusterrestris L. J Asian Nat Prod Res 14: 780-784.
  46. Xu Y, Liu Y, Xu T, Xie S, Si Y, et al. (2010) A new furostanol glycoside from Tribulusterrestris. Molecules 15: 613-618.
  47. Zhang X, Wei N, Huang J, Tan Y, Jin D (2012) A new feruloyl amide derivative from the fruits of Tribulusterrestris. Nat Prod Res 26: 1922-1925.
  48. Kozlova OI, Perederiaev OI, Ramenskaia GV (2011) [Determination by high performance chromatography, steroid saponins in a biologically active food supplements containing the extract of Tribulusterrestris]. Vopr Pitan 80: 67-71.
  49. Aggarwal A, Tandon S, Singla SK, Tandon C (2012) A novel antilithiatic protein from Tribulusterrestris having cytoprotective potency. Protein Pept Lett 19: 812-819.
  50. Lakshmi GD, Kumar PR, Bharavi K, Annapurna P, Rajendar B, et al. (2012) Protective effect of Tribulusterrestrislinn on liver and kidney in cadmium intoxicated rats. Indian J Exp Biol 50: 141-146.
  51. Shirfule AL, Sangamwar AT, Khobragade CN (2011) Exploring glycolate oxidase (GOX) as an antiurolithic drug target: molecular modeling and in vitro inhibitor study. Int J Biol Macromol 49: 62-70.
  52. Kamboj P, Aggarwal M, Puri S, Singla SK (2011) Effect of aqueous extract of Tribulusterrestris on oxalate-induced oxidative stress in rats. Indian J Nephrol 21: 154-159.
  53. Jarald EE, Kushwah P, Edwin S, Asghar S, Patni SA (2011) Effect of Unex on ethylene glycol-induced urolithiasis in rats. Indian J Pharmacol 43: 466-468.
  54. Talasaz AH, Abbasi MR, Abkhiz S, Dashti-Khavidaki S (2010) Tribulusterrestris-induced severe nephrotoxicity in a young healthy male. Nephrol Dial Transplant 25: 3792-3793.
  55. Kavitha AV, Jagadeesan G (2006) Role of Tribulusterrestris (Linn.) (Zygophyllacea) against mercuric chloride induced nephrotoxicity in mice, Musmusculus (Linn.). J Environ Biol 27: 397-400.
  56. Yang HJ, Qu WJ, Sun B (2005) [Experimental study of saponins from Tribulusterrestris on renal carcinoma cell line]. Zhongguo Zhong Yao Za Zhi 30: 1271-1274.
  57. Al-Ali M, Wahbi S, Twaij H, Al-Badr A (2003) Tribulusterrestris: preliminary study of its diuretic and contractile effects and comparison with Zea mays. J Ethnopharmacol 85: 257-260.
  58. Dehghan A, Esfandiari A, Bigdeli SM (2012) Alternative treatment of ovarian cysts with Tribulusterrestris extract: a rat model. Reprod Domest Anim 47: e12-15.
  59. Kavitha P, Ramesh R, Subramanian P (2012) Histopathological changes in Poecilialatipinna male gonad due to Tribulusterrestris administration. In Vitro Cell Dev Biol Anim 48: 306-312.
  60. Frydrychová S, Opletal L, Macáková K, Lustyková A, Rozkot M, et al. (2011) Effects of herbal preparation on libido and semen quality in boars. Reprod Domest Anim 46: 573-578.
  61. Clément C, Witschi U, Kreuzer M (2012) The potential influence of plant-based feed supplements on sperm quantity and quality in livestock: a review. Anim Reprod Sci 132: 1-10.
  62. Sengupta G, Hazra A, Kundu A, Ghosh A (2011) Comparison of Murraya koenigii- and Tribulusterrestris-Based Oral Formulation Versus Tamsulosin in the Treatment of Benign Prostatic Hyperplasia in Men Aged >50 Years: A Double-Blind, Double-Dummy, Randomized Controlled Trial. Clin Ther 33: 1943-1952.
  63. Malviya N, Jain S, Gupta VB, Vyas S (2011) Recent studies on aphrodisiac herbs for the management of male sexual dysfunction--a review. Acta Pol Pharm 68: 3-8.
  64. Gauthaman K, Ganesan AP (2008) The hormonal effects of Tribulusterrestris and its role in the management of male erectile dysfunction--an evaluation using primates, rabbit and rat. Phytomedicine 15: 44-54.
  65. McKay D (2004) Nutrients and botanicals for erectile dysfunction: examining the evidence. Altern Med Rev 9: 4-16.
  66. Mazaro-Costa R, Andersen ML, Hachul H, Tufik S (2010) Medicinal plants as alternative treatments for female sexual dysfunction: utopian vision or possible treatment in climacteric women? J Sex Med 7: 3695-3714.
  67. Riaz A, Khan RA, Ahmed S, Afroz S (2010) Assessment of acute toxicity and reproductive capability of a herbal combination. Pak J Pharm Sci 23: 291-294.
  68. Rajendar B, Bharavi K, Rao GS, Kishore PV, Kumar PR, et al. (2011) Protective effect of an aphrodisiac herb Tribulusterrestris Linn on cadmium-induced testicular damage. Indian J Pharmacol 43: 568-573.
  69. Singh S, Nair V, Gupta YK (2012) Evaluation of the aphrodisiac activity of Tribulusterrestris Linn. in sexually sluggish male albino rats. J Pharmacol Pharmacother 3: 43-47.
  70. Martino-Andrade AJ, Morais RN, Spercoski KM, Rossi SC, Vechi MF, et al. (2010) Effects of Tribulusterrestris on endocrine sensitive organs in male and female Wistar rats. J Ethnopharmacol 127: 165-170.
  71. Jagadeesan G, Kavitha AV (2006) Recovery of phosphatase and transaminase activity of mercury intoxicated Musmusculus (Linn.) liver tissue by Tribulusterrestris (Linn.) (Zygophyllaceae) extract. Trop Biomed 23: 45-51.
  72. Lakshmi GD, Kumar PR, Bharavi K, Annapurna P, Rajendar B, et al. (2012) Protective effect of Tribulusterrestrislinn on liver and kidney in cadmium intoxicated rats. Indian J Exp Biol 50: 141-146.
  73. Byun E, Jeong GS, An RB, Min TS, Kim YC (2010) Tribulifructus constituents protect against tacrine-induced cytotoxicity in HepG2 cells. Arch Pharm Res 33: 67-70.
  74. Sun B, Qu WJ, Zhang XL, Yang HJ, Zhuang XY, et al. (2004) [Investigation on inhibitory and apoptosis-inducing effects of saponins from Tribulusterrestris on hepatoma cell line BEL-7402]. Zhongguo Zhong Yao ZaZhi 29: 681-684.
  75.  Ponnusamy S, Ravindran R, Zinjarde S, Bhargava S, Ravi Kumar A (2011) Evaluation of Traditional Indian Antidiabetic Medicinal Plants for Human Pancreatic Amylase Inhibitory Effect In Vitro. Evidence-Based Complementary and Alternative Medicine.
  76. Li M, Qu W, Wang Y, Wan H, Tian C (2002) [Hypoglycemic effect of saponin from Tribulusterrestris]. Zhong Yao Cai 25: 420-422.
  77. Amin A, Lotfy M, Shafiullah M, Adeghate E (2006) The protective effect of Tribulusterrestris in diabetes. Ann N Y Acad Sci 1084: 391-401.
  78. Al-Bayati FA, Al-Mola HF (2008) Antibacterial and antifungal activities of different parts of Tribulusterrestris L. growing in Iraq. J Zhejiang Univ Sci B 9: 154-159.
  79. Berkman Z, Tanriover G, Acar G, Sati L, Altug T, et al. (2009) Changes in the brain cortex of rabbits on a cholesterol-rich diet following supplementation with a herbal extract of Tribulusterrestris. HistolHistopathol 24: 683-692.
  80. Liu XM, Huang QF, Zhang YL, Lou JL, Liu HS, et al. (2008) [Effects of Tribulusterrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats]. Zhong Xi Yi Jie He Xue Bao 6: 45-50.
  81. Deole YS, Chavan SS, Ashok BK, Ravishankar B, Thakar AB, et al. (2011) Evaluation of anti-depressant and anxiolytic activity of Rasayana Ghana Tablet (A compound Ayurvedic formulation) in albino mice. Ayu 32: 375-379.
  82. Cao MQ, Hu SY, Zhang CH, Wang YH (2005) [The effects of Baisong tablet on the behaviors and CRHmRNA expression in the brain of rats following chronic stress]. Zhongguo Zhong Yao ZaZhi 30: 219-222.
  83. Kim HJ, Kim JC, Min JS, Kim MJ, Kim JA, et al. (2011) Aqueous extract of Tribulusterrestris Linn induces cell growth arrest and apoptosis by down-regulating NF-κB signaling in liver cancer cells. J Ethnopharmacol 136: 197-203.
  84. Neychev VK, Nikolova E, Zhelev N, Mitev VI (2007) Saponins from Tribulusterrestris L are less toxic for normal human fibroblasts than for many cancer lines: influence on apoptosis and proliferation. ExpBiol Med (Maywood) 232: 126-133.
  85. Sisto M, Lisi S, D'Amore M, De Lucro R, Carati D, et al. (2012) Saponins from Tribulusterrestris L. protect human keratinocytes from UVB-induced damage. J Photochem Photobiol B 117: 193-201.
  86. Zhang S, Li H, Yang S (2011) Tribulosin suppresses apoptosis via PKC epsilon and ERK1/2 signaling pathway during hypoxia/reoxygenation in neonatal rat ventricular cardiac myocytes. Journal of Asian Natural Products Research 13: 1135-1145.
  87. Zhang S, Li H, Yang SJ (2010) Tribulosin protects rat hearts from ischemia/reperfusion injury. Acta Pharmacol Sin 31: 671-678.
  88. Wang SS, Ji YS, Li H, Yang SJ (2009) [Mechanisms of gross saponins of Tribulusterrestris via activating PKCepsilon against myocardial apoptosis induced by oxidative stress]. Yao Xue Xue Bao 44: 134-139.
  89. Tuncer MA, Yaymaci B, Sati L, Cayli S, Acar G, et al. (2009) Influence of Tribulusterrestris extract on lipid profile and endothelial structure in developing atherosclerotic lesions in the aorta of rabbits on a high-cholesterol diet. Acta Histochem 111: 488-500.
  90. Chu S, Qu W, Pang X, Sun B, Huang X (2003) [Effect of saponin from Tribulusterrestris on hyperlipidemia]. Zhong Yao Cai 26: 341-344.
  91. Sun W, Li H, Yang SJ (2008) A triterpenesaponin from Tribulusterrestris attenuates apoptosis in cardiocyte via activating PKC signalling transduction pathway. J Asian Nat Prod Res 10: 39-48.
  92. Guo Y, Yin HJ, Shi DZ (2006) [Effect of xinnaoshutong capsule on cardiac muscle cell apoptosis and protein expressions of Bcl-2 and Bax in hyperlipidemia rats after myocardial infarction]. ZhongguoZhong Xi Yi Jie He ZaZhi 26: 541-544.
  93. Murthy AR, Dubey SD, Tripathi K (2000) Anti-hypertensive effect of Gokshura (Tribulusterrestris Linn.) - A clinical study. AncSci Life 19: 139-145.
  94. Phillips OA, Mathew KT, Oriowo MA (2006) Antihypertensive and vasodilator effects of methanolic and aqueous extracts of Tribulusterrestris in rats. J Ethnopharmacol 104: 351-355.
  95. Sharifi AM, Darabi R, Akbarloo N (2003) Study of antihypertensive mechanism of Tribulusterrestris in 2K1C hypertensive rats: role of tissue ACE activity. Life Sci 73: 2963-2971.
  96. Ranjithkumar R, Balaji SP, Balaji B, Ramesh RV, Ramanathan M (2012) Standardized Aqueous Tribulusterristris (Nerunjil) Extract Attenuates Hyperalgesia in Experimentally Induced Diabetic Neuropathic Pain Model: Role of Oxidative Stress and inflammatory Mediators. Phytother Res 27: 1646-1657.
  97. Gacche RN, Dhole NA (2011) Profile of aldose reductase inhibition, anti-cataract and free radical scavenging activity of selected medicinal plants: an attempt to standardize the botanicals for amelioration of diabetes complications. Food Chem Toxicol 49: 1806-1813.
  98. Sengul M, Yildiz H, Gungor N, Cetin B, Eser Z, et al. (2009) Total phenolic content, antioxidant and antimicrobial activities of some medicinal plants. Pak J Pharm Sci 22: 102-106.
  99. Kumar M, Soni AK, Shukla S, Kumar A (2006) Chemopreventive potential of Tribulusterrestris against 7,12- dimethylbenz (a) anthracene induced skin papillomagenesis in mice. Asian Pac J Cancer Prev 7: 289-294.
  100. Zhang J, Zhang YL, Lou JL, Zheng H, Liu XM, et al. (2006) [Protective effects of XinnaoShutong capsule on acute cerebral ischemic injury of multiple infarcts in rats]. ZhongguoZhong Yao ZaZhi 31: 1979-1982.
  101. Hong CH, Hur SK, Oh OJ, Kim SS, Nam KA, et al. (2002) Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J Ethnopharmacol 83: 153-159.
  102. Tamura T, Picciano MF (2006) Folate and human reproduction. Am J ClinNutr 83: 993-1016.
  103. Pufulete M, Al-Ghnaniem R, Khushal A, Appleby P, Harris N, et al. (2005) Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma. Gut 54: 648-653.
  104. Fox JT, Stover PJ (2008) Folate-mediated one-carbon metabolism. VitamHorm 79: 1-44.
  105. Moreno-Garcia MA, Rosenblatt DS, Jerome-Majewska LA (2013) Vitamin B(12) metabolism during pregnancy and in embryonic mouse models. Nutrients 5: 3531-3550.
  106. Deshmukh U, Katre P, Yajnik CS (2013) Influence of maternal vitamin B12 and folate on growth and insulin resistance in the offspring. Nestle NutrInst Workshop Ser 74: 145-154.
  107. Sukla KK, Tiwari PK, Kumar A, Raman R (2013) Low birthweight (LBW) and neonatal hyperbilirubinemia (NNH) in an Indian cohort: association of homocysteine, its metabolic pathway genes and micronutrients as risk factors. PLoS One 8: e71587.
  108. Samuel TM, Duggan C, Thomas T, Bosch R, Rajendran R, et al. (2013) Vitamin B(12) intake and status in early pregnancy among urban South Indian women. Ann Nutr Metab 62: 113-122.
  109. Yajnik CS, Deshmukh US (2012) Fetal programming: maternal nutrition and role of one-carbon metabolism. Rev Endocr Metab Disord 13: 121-127.
  110. Muthayya S, Dwarkanath P, Mhaskar M, Mhaskar R, Thomas A, et al. (2006) The relationship of neonatal serum vitamin B12 status with birth weight. Asia Pac J ClinNutr 15: 538-543.
  111. Bjørke Monsen AL, Ueland PM, Vollset SE, Guttormsen AB, Markestad T, et al. (2001) Determinants of cobalamin status in newborns. Pediatrics 108: 624-630.
  112. Hovdenak N, Haram K (2012) Influence of mineral and vitamin supplements on pregnancy outcome. Eur J ObstetGynecolReprodBiol 164: 127-132.
  113. Samuel TM, Thomas T, Finkelstein J, Bosch R, Rajendran R, et al. (2013) Correlates of anaemia in pregnant urban South Indian women: a possible role of dietary intake of nutrients that inhibit iron absorption. Public Health Nutr 16: 316-324.
  114. Sucharita S, Dwarkanath P, Thomas T, Srinivasan K, Kurpad AV, et al. (2012) Low maternal vitamin B12 status during pregnancy is associated with reduced heart rate variability indices in young children. Matern Child Nutr .
  115. Refsum H, Yajnik CS, Gadkari M, Schneede J, Vollset SE, et al. (2001) Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians. Am J ClinNutr 74: 233-241.
  116. Thakur N, Saili A, Kumar A, Kumar V (2013) Predictors of mortality of extremely low birthweight babies in a tertiary care centre of a developing country. Postgrad Med J 89: 679-684.
  117. Sarkate P, Patil A, Parulekar S, Rege NN, Samant BD, et al. (2007) Arandomised double-blind study comparing sodium feredetate with ferrous fumarate in anaemia in pregnancy. J Indian Med Assoc 105: 278, 280-281.
  118. Kelly D, O'Dowd T, Reulbach U (2012) Use of folic acid supplements and risk of cleft lip and palate in infants: a population-based cohort study. Br J Gen Pract 62: e466-472.
  119. Maccani MA, Marsit CJ (2009) Epigenetics in the placenta. Am J ReprodImmunol 62: 78-89.
  120. Sundrani DP, Reddy US, Joshi AA, Mehendale SS, Chavan-Gautam PM, et al. (2013) Differential placental methylation and expression of VEGF, FLT-1 and KDR genes in human term and preterm preeclampsia. Clin Epigenetics 5: 6.
  121. Li Z, Ye R, Zhang L, Li H, Liu J, et al. (2013) Folic acid supplementation during early pregnancy and the risk of gestational hypertension and preeclampsia. Hypertension 61: 873-879.
  122. Bánhidy F, Dakhlaoui A, Dudás I, Czeizel AE (2011) Birth outcomes of newborns after folic Acid supplementation in pregnant women with early and late pre-eclampsia: a population-based study. Adv Prev Med 2011: 127369.
  123. Wen SW, Chen XK, Rodger M, White RR, Yang Q, et al. (2008) Folic acid supplementation in early second trimester and the risk of preeclampsia. Am J Obstet Gynecol 198: 45.
  124. Shiraishi M, Haruna M, Matsuzaki M, Ota E, Murayama R, et al. (2013) Association between oxidized LDL and folate during pregnancy. Biol Res Nurs 15: 213-218.
  125. Furness DL, Yasin N, Dekker GA, Thompson SD, Roberts CT (2012) Maternal red blood cell folate concentration at 10-12 weeks gestation and pregnancy outcome. J Matern Fetal Neonatal Med 25: 1423-1427.
  126. Negi R, Pande D, Karki K, Kumar A, Khanna RS, et al. (2012) Trace elements and antioxidant enzymes associated with oxidative stress in the pre-eclamptic/eclampticmothersduring fetal circulation. Clin Nutr. 31: 946-950.
  127. Lakshmy R (2013) Metabolic syndrome: role of maternal undernutrition and fetal programming. Rev Endocr Metab Disord 14: 229-240.
  128. Vasquez K, Kuizon S, Junaid M, Idrissi AE (2013) The effect of folic acid on GABA(A)-B 1 receptor subunit. AdvExp Med Biol 775: 101-109.
Citation: Kilari A, Deshpande M, Joshi S (2014) A Novel Molecular Mechanistic Hypothesis to Validate the Therapeutic Effects of Tribulus terrestris (Gokshur) to Ameliorate Pathophysiology and Improve Pregnancy and Fetal Outcome in Preeclampsia. Gynecol Obstet (Sunnyvale) 4:195.

Copyright: © 2014 Kilari A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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