Ashwagandha Diminishes Hippocampal Apoptosis Induced by Microwave Radiation by Acetylcholinesterase Dependent Neuro-Inflammatory Pathway in Male Coturnix coturnix Japonica.

Microwave radiation (MWR) has been linked to neurodegeneration by inducing oxidative stress in the hippocampus of brain responsible for learning and memory. Ashwagandha (ASW), a medicinal plant is known to prevent neurodegeneration and promote neuronal health. This study investigated the effects of MWR and ASW on oxidative stress and cholinergic imbalance in the hippocampus of adult male Japanese quail. One control group received no treatment, the second group quails were exposed to MWR at 2 h/day for 30 days, third was administered with ASW root extract orally 100 mg/day/kg body weight and the fourth was exposed to MWR and also treated with ASW. The results showed that MWR increased serum corticosterone levels, disrupted cholinergic balance and induced neuro-inflammation. This neuro-inflammation further led to oxidative stress, as evidenced by decreased activity of antioxidant enzymes SOD, CAT and GSH. MWR also caused a significant decline in the nissil substances in the hippocampus region of brain indicating neurodegeneration through oxidative stress mediated hippocampal apoptosis. ASW, on the other hand, was able to effectively enhance the cholinergic balance and subsequently lower inflammation in hippocampus neurons. This suggests that ASW can protect against the neurodegenerative effects of MWR. ASW also reduced excessive ROS production by increasing the activity of ROS-scavenging enzymes. Additionally, ASW prevented neurodegeneration through decreased expression of caspase-3 and caspase-7 in hippocampus, thus promoting neuronal health. In conclusion, this study showed that MWR induces apoptosis and oxidative stress in the brain, while ASW reduces excessive ROS production, prevents neurodegeneration and promotes neuronal health.

Dietary restriction-induced alterations on estrogen receptor alpha expression in regulating fertility in male Coturnix coturnix japonica: Relevance of Withania somnifera in modulation of inflammation and oxidative stress in testis.

PROBLEM: Reproductive performance of animals gets affected by nutritional restrictions which act as potential stressors leading to hormonal imbalance and testicular inflammation, the major causes of infertility. Withania somnifera (WS), well-known traditional medicinal plant, has been used as antistress and infertility treatment. Therefore, the present study looks into the ameliorative effects of WS on the reproductive and immune system of male Coturnix coturnix japonica in stressed conditions like water and food restriction focussing on the modulation in estrogen receptor alpha (ERα). METHOD OF STUDY: Biochemical estimations for oxidative stress, histological alterations, immuno-fluorescent localization of ERα, interleukin (IL)-1ß, IL-4, and interferon gamma (IFN-γ) in testicular cells were performed. RESULTS: Nutritional restriction declines endogenous estradiol, ERα in testicular cells while it elevates corticosterone leading to oxidative stress in testis thereby reducing fertility by decrease in sperm. Results indicate significant reversal in all the parameters after the administration of WS by improving testicular cell morphology, increased superoxide and catalase activity thus reducing oxidative stress. WS increases spermatogenesis and enhances expression of ERα in testicular cells in quail. Further, WS increases IL-4, decreases IL-1ß and IFN-γ expression in testis, thereby improving immune profile contrary to stressed conditions. CONCLUSION: WS stimulates HPG-axis even after stress resulting in increased endogenous estradiol which stimulates the expression of ERα in testis; increases sperm count and immunity thereby improving the reproductive performance. WS may be the best therapy against nutritional-restriction stress induced reproductive toxicity by reducing oxidative stress mediated inflammatory response via increased testicular expression of ERα in quail.

Withania somnifera inhibits photorefractoriness which triggers neuronal apoptosis in both pre-optic and paraventricular hypothalamic area of Coturnix coturnix japonica: involvement of oxidative stress induced p53 dependent Caspase-3 mediated low immunoreactivity of estrogen receptor alpha.

Light has a very important function in the regulation of the normal physiology including the neuroendocrine system, biological rhythms, cognitive behavior, etc. The variation in photoperiod acts as a stressor due to imbalance in endogenous hormones. Estrogen and its receptors ER alpha and beta play a vital role in the control of stress response in birds. The study investigates the estrogenic effects of a well-known medicinal plant Withania somnifera (WS), mediated by estrogen receptor alpha (ERα) in the hypothalamic pre-optic area (POA) and paraventricular nuclei (PVN). Further the study elucidates its anti-oxidants and anti-apoptotic activities in the brain of Japanese quail. To validate this hypothesis, mature male quails were exposed to long day length for 3 months and then transferred to intermediate day length to become photorefractory (PR) while controls were still continued under long daylength. Supplementation of WS root extract in PR quail increases plasma estrogen and lowers corticosterone. Further, in PR quail the variation in light downregulates immunoreactivity of ERα, oxidative stress and antioxidant enzyme activities i.e. superoxide dismutase and catalase in the brain. Neuronal apoptosis was observed in the POA and PVN of PR quail as indicated by the abundant expression of Caspase-3 and p53 which reduces after the administration of WS root extract. The neuronal population also found to decrease in PR although it increased in WS administered quails. Further, the study concluded that change in photoperiod from 3 months exposure of 16L: 8D to 13.5L: 10.5D directly activates neuronal apoptosis via expression of Caspase3 and p53 expression in the brain and increases neuronal and gonadal oxidative stress while WS root extract reverses them via enhanced estrogen and its receptor ERα expression in the hypothalamic pre-optic and PVN area of Japanese quail.

Photoperiod dependent expression of estrogen receptor alpha in testes of Japanese quail: Involvement of Withania somnifera in apoptosis amelioration.

Light plays important function in the regulation of reproduction in vertebrates including birds. The prolonged long day length exposure causes reproductively inactive state or photorefractoriness in many avian species including Japanese quail. Withania somnifera (WS) is a medicinal plant known to have beneficial effects on stress and infertility. The study investigates the physiological effect of WS on the light-induced stress in quail mediated by estrogen receptor alpha. Quails were exposed to long day length for three months and then transferred into intermediate day length to make them photorefractory (PR) while controls under natural day length. Administration of Withania somnifera root extract (WSRE) in PR quail induces estrogen and decreases corticosterone in male Japanese quail. Immunoreactivity of ERα decreased in testis of PR quail and increased after oral administration of WSRE compared to control. Expression of ir-Caspase-3 and ir-p53 in the testis increased in PR while decreased in PR + WS. Histologically, seminiferous tubules size decreased in PR whereas increased in PR + WS quails. Scanning electron microscopic study reveals sperms in clusters with proper head and tail in control. In PR quails sperms were few and distorted while WSRE improved the sperm morphology. From the study, it is concluded that during photorefractoriness gonadal regression occurs due to testicular apoptosis which causes stress. WSRE helps to overcome stress and improve reproductive performance via increase in expression of ir-ERα during PR condition. Further, the stress ameliorating effect of WSRE in reducing apoptosis mediated by ir-Caspase-3 and ir-p53 in the testes is clearly evident in Japanese quail.

Nutritional interventions in primary mitochondrial disorders: Developing an evidence base.

In December 2014, a workshop entitled "Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base" was convened at the NIH with the goals of exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Sponsors included the NIH, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Dietary supplements have historically been used in the management of PMD due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMD are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Regulatory issues pertaining to the use of dietary supplements as treatment modalities further complicate the research and patient access landscape. As a preface to exploring a research agenda, the workshop included presentations and discussions on what PMD are; how nutritional interventions are used in PMD; challenges and barriers to their use; new technologies and approaches to diagnosis and treatment; research opportunities and resources; and perspectives from patient advocacy, industry, and professional organizations. Seven key areas were identified during the workshop. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. Short- and long-term goals within each of these areas were identified. An example of an overarching goal is the enrollment of all individuals with PMD in a natural history study and a patient registry to enhance research capability. The workshop demonstrates an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community to address research challenges on the use of dietary supplements in PMD.

Expression of arginine vasotocin and estrogen receptor alpha (ERα) in the shell gland altered by the specific phase relations of neural oscillations affects the reproductive physiology of Japanese quail.

In order to study the effect of specific phase relation of neural oscillations on reproductive regulation and the response of AVT (the avian homologue of mammalian AVP) the expression of AVT in the shell gland was monitored in sexually immature quail. In this study 3-week-old female Japanese quail were administered with serotonin precursor, 5-hydroxytryptophan followed by the dopamine precursor, l-dihydroxyphenylalanine at interval of 8h and 12h daily over a period of 13days. At thirty two days post treatment, a significant decrease in gonadal activity was seen in 8h quail although 12h quail exhibited an increase as compared to controls. A significant decrease in plasma estradiol level was noted in 8h quail while 12h exhibited no significant difference compared to controls. To address the relative roles of estrogen mediated action we also investigated estrogen receptor alpha (ER-α) expression and localization in the shell gland by visualizing it through confocal immuno-fluorescence microscopy. Results indicate increased expression of immunoreactive (ir)-AVT (myometrium), ir-ER-α (epithelial cells of endometrial region), along with significant increase in hypothalamic, plasma and shell gland AVT and a rapid increase in egg laying thus maintaining full breeding condition in 12h while low expression of ir-AVT and ir-ER-α was observed in 8h quail along with a significant decrease in hypothalamic, plasma and shell gland AVT with the suppression of gonads thereby stopping the egg-laying behaviour was noted. These findings not only suggest the modulation of gonadal development by changing the specific phase relation of neural oscillations but also demonstrate a parallel relation of AVT and gonadal activity in both conditions. It is concluded that the egg laying performance in response to AVT is regulated by the temporal phase relationship of neurotransmitters, and in part, this effect appears to be estrogen dependent.

Expanding research to provide an evidence base for nutritional interventions for the management of inborn errors of metabolism.

A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions. Further research is needed to demonstrate the impact of nutritional interventions on individual health outcomes and on the psychosocial issues identified by patients and their families. A series of meetings and discussions were convened to explore the current United States' funding and regulatory infrastructure and the challenges to the conduct of research for nutritional interventions for the management of IEM. Although the research and regulatory infrastructure are well-established, a collaborative pathway that includes the professional and advocacy rare disease community and federal regulatory and research agencies will be needed to overcome current barriers.

Female sexual dysfunction in obstetrics and gynecology.

Sexual dysfunction in women is common, with a community prevalence of 30% to 50%. The sexual response cycle in women is complex, with multiple overlapping dimensions, which necessitates a biopsychosocial approach for understanding the basis of dysfunction. Physiological events such as pregnancy, childbirth, menopause, aging as well as gynecological conditions like infertility, prolapse, urinary incontinence, and gynecological cancers, have an impact on sexual well-being. The interaction of these conditions with sexual health needs to be better understood to deal effectively with the problems as a whole. However, the woman concerned should be sufficiently distressed by her problem for the diagnosis of female sexual dysfunction to be made. Overall, gynecological surgery performed to alleviate symptoms which have an organic basis have the potential to improve sexual function, and this does not necessarily correlate with the anatomical outcome of the surgery. Hysterectomy done by any approach does not compromise sexual function. Sexual health enquiry and evaluation in clinical practice can be done with the help of simple screening questions, a comprehensive history followed by an adequate examination. As no single laboratory test is recommended as a marker of sexual dysfunction, investigations are best dictated by clinical judgment. Detailed assessment tools in the form of self-report questionnaires and diagnostic tests for objective measures of sexual dysfunction could be used in special circumstances. Therapy entails understanding the point of break in the sexual response cycle and the underlying pathophysiology. While there are multiple treatment options available, integrated therapy which deals with both the psyche and the soma yield best results. Sexual counseling plays a vital role when therapy becomes necessary.

Phytotoxic and antimicrobial constituents of Bacopa monnieri and Holmskioldia sanguinea.

The phytochemicals betulinic acid (1), wogonin (2) and oroxindin (3) isolated from the aerial parts of Bacopa monnieri and Holmskioldia sanguinea showed significant antifungal activity against the two fungi Alternaria alternata and Fusarium fusiformis. Inhibition of root growth germination of wheat seeds was observed for all three compounds which showed 100% inhibition at 10 micro g/mL. Compounds (1) and (2) showed potent inhibition of Alternaria alternata compared with oroxindin at a concentration of 4 micro g/mL, whereas compound (2) was an effective inhibitor of both fungi. The structures of the compounds were established by spectral and chemical studies.