Revalidation of the neuroprotective effects of a United States patented polyherbal formulation on scopolamine induced learning and memory impairment in rats.

OBJECTIVE: Alzheimer's disease (AD) is the most common cause of dementia yet treatment options are extremely limited. The disease is associated with cognitive impairment as well as structural irregularities, accumulation of plaques and neurofibrillary tangles, diminished levels of acetylcholine, oxidative stress, and inflammation in the brain. We have previously reported on the positive effects of a united states patented (US 7,273,626 B2) poly herbal test formulation, consisting of Bacopa monnieri, Hippophae rhamnoides and Dioscorea bulbifera extracts, on cognitive deficits in AD patients. The present study was conducted to investigate the mechanism(s) of action of the formulation using scopolamine treated rats as an AD model. METHOD: The formulation was administered daily along with scopolamine for a period of 14days following which the elevated plus maze, passive avoidance, and Morris water maze tests were performed to assess learning and memory. Rats treated with scopolamine or vehicle only were also included in the experiment. Acetylcholine levels and activities of acetylcholinesterase (AChE) and anti-oxidant enzymes in the brain were also measured at the end of the treatment period. RESULTS: The study demonstrate that scopolamine treatment resulted in learning and memory deficits which were partially and significantly ameliorated by the formulation. The formulation also counteracted scopolamine-induced decreases in acetylcholine levels, increases in AChE activity, and decreases in activities of the antioxidant enzymes. CONCLUSION: The study demonstrates the ability of the test formulation to reverse scopolamine-induced learning and memory deficits in rats which may at least partially be explained by the reversal of scopolamine-induced reductions in brain acetylcholine levels and antioxidant activities by the test formulation.

Metaflammatory responses during obesity: Pathomechanism and treatment.

Obesity induced inflammation acts as a reflex produced due to altered metabolic homeostasis in accordance to the nutrient overload on the metabolic cells. It involves up-regulation of the genes encoding for cytokines, chemokines and other inflammatory mediators through activated transcription factors - nuclear factor-kB, activator protein-1, nuclear factor of activated T cells and signal transducer and activator of transcription 3. These execute macromolecular innate immune cell sensor - inflammasome to activate caspase-1 pathway resulting in proteolytic maturation. Secretion of pro-inflammatory cytokines including TNF-α, IL-6, CRP, IL-1ß, etc. from the M1 macrophages of white adipose tissue is increased, whereas there occurs a steep decline in the production of anti-inflammatory cytokines like IL-10, IL-Ra, adiponectin. Not only the adipose tissue, but also the immune cells, liver, brain, muscles and pancreas suffers from the inflammatory insult during obese condition and are exaggeratedly affected. The inflammatory kinases like JNK and IKK apart from inhibiting insulin action and glucose uptake, down-regulate transcriptional process resulting in increased expression of pro-inflammatory cytokines. Macrophage-like Kupffer cells initiate the inflammatory process in the liver preceding the inflammatory signals produced by the white adipose tissue which may further lead to hepatic-necro-inflammation. The muscle-fibre is affected by the cytokines and therefore results in decreased glycogen synthesis. The triggered hypothalamic-pituitary-adrenal axis further affects the expression of inflammatory cytokines thus altering insulin homeostasis and initiating glucose intolerance. Anti-inflammatory treatment so as to curb the severity of inflammatory responses includes administration of synthetic drugs to target the actual inflammatory molecules and various therapeutic interventions.

Antidiabetic and antihyperlipidemic activities of a novel polyherbal formulation in high fat diet/streptozotocin induced diabetic rat model.

OBJECTIVE: To investigate the antidiabetic and antihyperlipidemic activities of polyherbal formulation (PHF) containing hydroalcoholic extracts of four plants namely Salacia oblonga, Salacia roxbhurgii, Garcinia indica and Lagerstroemia parviflora in streptozotocin (STZ)-induced diabetic rats by administering oral doses (200 and 400 mg/kg body weight). MATERIALS AND METHODS: Animals were divided into diabetic and nondiabetic groups. Rats were fed with a high-fat diet (HFD) and induced with a single low dose of STZ (35 mg/kg) i.p. Diabetic rats were treated with formulation (200 and 400 mg/kg) and metformin 250 mg/kg. Blood glucose levels were measured using blood glucose test strips with ACCU CHEK glucometer. Lipid profile and gluconeogenic enzymes were determined in normal and STZ-induced diabetic rats after oral administration of the PHF for 28 days. Histopathological changes in diabetic rat organs (pancreas, liver, and kidney) were also observed after PHF treatment. RESULTS: Treatment of diabetic rats with PHF and metformin decreased plasma glucose and lipid profile levels. Blood glucose level showed significant reduction after 28 days of treatment with formulation at 200 and 400 mg/kg and in metformin. Formulation treated rats showed significant (P < 0.001) decrease in the activities of gluconeogenic enzymes. Histological examination of various organ tissues of normal control, diabetic control, and drug-treated rats revealed significant results. Treatment with PHF reverses the most blood and tissue changes toward the normal level. CONCLUSION: These findings suggested the antihyperglycemic and antihyperlipidemic properties of the PHF and thus help in preventing future complications of diabetes.

Comparative inhibitory potential of selected dietary bioactive polyphenols, phytosterols on CYP3A4 and CYP2D6 with fluorometric high-throughput screening.

Cytochrome P450 (CYP450) inhibition by the bioactive molecules of dietary supplements or herbal products leading to greater potential for toxicity of co-administered drugs. The present study was aimed to compare the inhibitory potential of selected common dietary bioactive molecules (Gallic acid, Ellagic acid, ß-Sitosterol, Stigmasterol, Quercetin and Rutin) on CYP3A4 and CYP2D6 to assess safety through its inhibitory potency and to predict interaction potential with co-administered drugs. CYP450-CO complex assay was carried out for all the selected dietary bioactive molecules in isolated rat microsomes. CYP450 concentration of the rat liver microsome was found to be 0.474 nmol/mg protein, quercetin in DMSO has shown maximum inhibition on CYP450 (51.02 ± 1.24 %) but less when compared with positive control (79.02 ± 1.61 %). In high throughput fluorometric assay, IC50 value of quercetin (49.08 ± 1.02-54.36 ± 0.85 µg/ml) and gallic acid (78.46 ± 1.32-83.84 ± 1.06 µg/ml) was lower than other bioactive compounds on CYP3A4 and CYP2D6 respectively but it was higher than positive controls (06.28 ± 1.76-07.74 ± 1.32 µg/ml). In comparison of in vitro inhibitory potential on CYP3A4 and CYP2D6, consumption of food or herbal or dietary supplements containing quercetin and gallic acid without any limitation should be carefully considered when narrow therapeutic drugs are administered together.

Quantitative analysis of heavy metals in medicinal plants collected from environmentally diverse locations in India for use in a novel phytopharmaceutical product.

It is important to monitor the quality of the phytopharmaceutical product as its therapeutic potential depends on standardized delivery of active ingredients present in the botanical source. Minimal presence of toxic impurities like heavy metals (HMs) is warranted to ensure product safety and prevent hazardous health impacts. In the present study, conducted as part of the development of a novel phytopharmaceutical product, the chemical profile of 13 heavy metals (Fe, Cu, Mn, Zn, Ni, Co, Mo, V, Cr, As, Pb, Hg, and Cd) was studied in the whole plant, fruit, and rhizome of Bacopa monnieri, Hippophae rhamnoides, and Dioscorea bulbifera, respectively, from environmentally diverse regions in India. Most samples had HM profiles within permissible limits as established by regulatory authorities, with the exception of Cd and Hg in low-altitude regions. This study indicates geographical regions in India suitable for procuring raw materials to develop and manufacture phytopharmaceutical products.

Evaluation of plant based formulation on adolescent obesity and its associated bio-markers: a randomized, double blind, placebo controlled study.

OBJECTIVE: Obesity and overweight are the fifth most fatal diseases leading to an increased rate of morbidity and mortality in global population, with its incidence increasing drastically. Taking this into consideration we have conducted the present study in order to explore the efficacy of plant based formulation in the management of adolescent obesity and its associated biomarkers. DESIGN: Randomized, double blind, placebo controlled trial was conducted in 130 obese adolescent of both sexes, with BMI above 25kg/m(2). The subjects were randomly assigned into test formulation group (TFG) and placebo group (PG). TFG received two 500mg capsule containing test formulation whereas, the PG received two 500mg of cellulose powder containing capsule daily for 3 months. The parameters such as blood pressure, inflammatory cytokines, adipokines and lipid profile were assessed in all subjects pre and post treatment. RESULTS: There was a considerable improvement in the levels of lipid profile, inflammatory cytokines, adipokines and blood pressure after treatment in TFG compared to PG. The statistical difference obtained between the groups after three months of treatment for the various biomarkers are given as mean with 95% CI for BMI (-1.4±0.6 (-2.5 to -0.7)), total cholesterol mg/dl (-20.9±5.0 (-30.8 to -11.0)), triglyceride mg/dl (-12.9±5.7 (-23.9 to -1.2)), HDL-c mg/dl (7.2±0.8 (5.6-8.8)), IL-6 (-0.7±0.1 (-0.9 to -0.6)), hs C-reactive protein (CRP) mg/l(-1.0±0.01 (-1.2 to -0.8)), adiponectin µg/ml(4.9±0.4 (4.2-5.7)), leptin ng/ml (-8.0±1.4 (-10.7 to -5.3)), diastolic blood pressure (DBP) mmHg (-10.4±0.8 (-12.0 to -8.7)) and systolic blood pressure (SBP) mmHg (-6.7±0.7 (-8.1 to -5.3)). Also, there was a statistical significance within group TFG. CONCLUSION: The study concludes that the test formulation may prevent the future cardio vascular risk incidence in obese adolescents by reducing inflammation, overweight, lipid profile and by regulating adipokines. Thus it may help to improve the health pattern in obese patients with least side effects.

Age dependent levels of plasma homocysteine and cognitive performance.

Elevated plasma homocysteine (hcy) levels, also known as hyperhomocysteinemia (hhcy), have been associated with cognitive impairment and neurodegenerative disorders. Hhcy has been attributed to deficiency of B vitamins which can adversely affect the brain and result in memory loss and poor attention power. Monitoring hcy levels and the use of vitamin supplementation to treat hhcy may therefore prove advantageous for the prevention and management of cognitive impairment. With this in consideration, we measured plasma hcy, folate and vitamin B12 levels in 639 subjects from different age groups in two sub-regions of India. Cognitive function was also measured using attention span and immediate and delayed memory recall tests. Depression scores were obtained using the Beck Depression Inventory-II and functional impairment was assessed using the functional activities questionnaire (FAQ) score. As hhcy has also been linked to inflammation, plasma levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were also measured. The results demonstrated significant negative correlations between hcy levels and folic acid levels, vitamin B12 levels and cognitive performance (attention span and delayed but not immediate memory recall) along with significant positive correlations between hcy levels and depression scores and hsCRP (but not IL-6) levels. A positive correlation was also observed between hcy levels and FAQ scores, however this was not found to be significant. Based on these results, folic acid and vitamin B12 intervention in people with elevated hcy levels in India could prove to be effective in lowering hcy levels and help maintain or improve cognitive function.

Effects of Salacia oblonga on cardiovascular risk factors in chronic kidney disease patients: a prospective study.

The present study is aimed to evaluate the effect of the herbal drug Salacia oblonga on reduction of cardiovascular risk factors in patients with chronic kidney disease (CKD). Sixty patients were randomized in four groups; group A1 = non-diabetic CKD given trial drug Salacia oblonga for six months, group A 2 = non-diabetic CKD intended to receive placebo, group B1 = diabetic CKD treated with Salacia oblonga for six months and group B 2 = diabetic CKD patients intended to receive placebo. Estimation of renal function tests including blood urea, serum creatinine and creatinine clearance was performed at baseline and after that at monthly intervals. Lipid profile, interleukin-6 (IL-6) and C-reactive protein (CRP) were measured at baseline and were repeated at three months and six months. After six months of treatment, Salacia oblonga could reduce the triglyceride levels by 23.66% (P = 0.008) in non-diabetic and by 17.45% (P = 0.01) in diabetic CKD patients. In comparison with placebo, both non-diabetic and diabetic CKD patients treated with Salacia oblonga showed significant reduction in CRP levels (P = 0.002 and 0.03, respectively), while significant reduction in IL-6 (P-value = 0.0003) and serum cholesterol levels (P-value = 0.0001) was seen only in diabetic CKD patients treated with Salacia oblonga. Stabilization of creatinine clearance with Salacia oblonga was observed in both non-diabetic (P = 0.05) and diabetic CKD (P = 0.04) patients in comparison with placebo. Salacia oblonga has significant beneficial effects on lipid profile and markers of inflammation and endothelial dysfunction in CKD patients. Salacia oblonga also seems to have a reno-protective effect, as reflected by stabilization of creatinine clearance at six months in this study.

Comparative pharmacokinetic interactions of Quercetin and Rutin in rats after oral administration of European patented formulation containing Hipphophae rhamnoides and Co-administration of Quercetin and Rutin.

Quercetin and Rutin are most common flavone constituents of some herb extracts such as Hippophae rhamnoides L. Inter and intra herb pharmacokinetics interactions of Quercetin and Rutin were investigated in the present study. Pharmacokinetic study was investigated in the two groups of rats (n = 6) for pharmacokinetic interactions between the Quercetin and Rutin (2.5 mg/kg) mixture treated alone with European patented polyherbal formulation containing equivalent weight of the above. The total plasma concentrations of Quercetin and Rutin were determined by liquid chromatography mass spectrometry (LC-MS). A method was developed and validated according to the ICH guidelines. The results of the present study shows that there are great differences in the pharmacokinetics of Quercetin and Rutin when they are administered together and from the polyherbal formulation which will be interacted by many other constituents. The bioavailability of Quercetin was lowered from the polyherbal formulation when compared with the co-administration, whereas the Rutin bioavailability has increased from the polyherbal formulation when compared with the co-administration. The maximum plasma concentration of Quercetin from coadministration and polyherbal formulation was 165.3 ± 31.9 and 90.8 ± 21.4 ng/mL, respectively, whereas in the case of Rutin it was 61.1 ± 29.3 and 121.7 ± 19.2 ng/mL. After polyherbal formulation administration to rats the AUC0-24, AUC0-∞ and AUMC0-∞ of both Quercetin and Rutin significantly increased when compared to co-administration. The above results proved that inter and intra herb pharmacokinetic interactions between Quercetin and Rutin. Possible interactions of the other constituents with hydrolyzing enzymes in the formulation enhances the oral bioavailability of Rutin. Accordingly besides the drug herb interactions, inter and intra herb interaction might be brought into view with the wide use of herbal remedies.

Comparative pharmacokinetic study of mangiferin after oral administration of pure mangiferin and US patented polyherbal formulation to rats.

The US patented polyherbal formulation for the prevention and management of type II diabetes and its vascular complications was used for the present study. The xanthone glycoside mangiferin is one of the major effector constituents in the Salacia species with potential anti-diabetic activity. The pharmacokinetic differences of mangiferin following oral administration of pure mangiferin and polyherbal formulation containing Salacia species were studied with approximately the same dose 30 mg/kg mangiferin and its distribution among the major tissue in Wistar rats. Plasma samples were collected at different time points (15, 30, 60, 120, 180, 240, 360, 480, 600, 1,440, 2,160, and 2880 min) and subsequently analyzed using a validated simple and rapid LC-MS method. Plasma concentration versus time profiles were explored by non-compartmental analysis. Mangiferin plasma exposure was significantly increased when administered from formulation compared to the standard mangiferin. Mangiferin resided significantly longer in the body (last mean residence time (MRTlast)) when given in the form of the formulation (3.65 h). Cmax values of formulation (44.16 µg/mL) administration were elevated when compared to equivalent dose of the pure mangiferin (15.23 µg/mL). Tissue distribution study of mangiferin from polyherbal formulation was also studied. In conclusion, the exposure of mangiferin is enhanced after formulation and administration and could result in superior efficacy of polyherbal formulation when compared to an equivalent dose of mangiferin. The results indicate that the reason which delays the elimination of mangiferin and enhances its bioavailability might the interactions of the some other constituents present in the polyherbal formulation. Distribution study results indicate that mangiferin was extensively bound to the various tissues like the small intestine, heart, kidney, spleen, and liver except brain tissue.

Management of cognitive determinants in senile dementia of Alzheimer's type: therapeutic potential of a novel polyherbal drug product.

BACKGROUND AND OBJECTIVE: The enigmatic etiology of neurodegenerative diseases poses a challenge for the development of novel and efficient drugs. The objective of the present study was to evaluate the efficacy of a polyherbal (test) formulation on cognitive functions, inflammatory markers and oxidative stress in healthy elderly as well as senile dementia of Alzheimer's type (SDAT) patients. METHOD: A randomized double-blind placebo- and active-controlled clinical trial was performed in healthy elderly subjects and SDAT patients with an age range of 60-75 years. The polyherbal test formulation along with a placebo was given to healthy elderly subjects while the SDAT patients received either the test formulation containing extracts of Bacopa monnieri (whole plant), Hippophae rhamnoides (leaves and fruits) and Dioscorea bulbifera (bulbils) at a dose of 500 mg or donepezil drug (Aricept) at a dose of 10 mg, twice daily, for a period of 12 months. After every three months, cognitive functions were assessed by determining the mini mental state examination (MMSE) score, digital symbol substitution (DSS; subtest of the Wechsler Adult Intelligence Scale-Revised), immediate and delayed word recall (digital memory apparatus-Medicaid systems, Chandigarh, India), attention span (Attention Span Apparatus-Medicaid systems, Chandigarh, India), functional activity questionnaire (FAQ) and depression (geriatric depression scale) scores. Further inflammatory markers and level of oxidative stress were analyzed using standard biochemical tests. RESULTS: The trial was performed in 109 healthy subjects and 123 SDAT patients of whom 97 healthy subjects and 104 SDAT patients completed the study. Administration of the test formulation for a period of 12 months was effective in improving cognitive functions in the SDAT patients, when compared to the donepezil-treated group, as determined by the DSS (38.984 ± 3.016 vs 35.852 ± 4.906, P = 0.0001), word recall immediate (3.594 ± 1.003 vs 2.794 ± 0.593, P < 0.0001) and attention span (4.918 ± 1.239 vs 4.396 ± 0.913, P = 0.0208) scores. A significant improvement in the FAQ (11.873 ± 2.751 vs 9.801 ± 1.458, P < 0.0001) and depression (16.387 ± 2.116 vs 21.006 ± 2.778, P < 0.0001) scores was also observed, whereas no significant differences were observed in the MMSE and word recall delayed scores. The level of inflammation and oxidative stress was markedly reduced in the SDAT patients treated with the test formulation when compared to the donepezil-treated group indicating a likely mechanism of action of the test formulation (homocysteine 30.22 ± 3.87 vs 44.73 ± 7.11 nmol/L, P < 0.0001; C-reactive protein [CRP] 4.751 ± 1.149 vs 5.887 ± 1.049 mg/L, P < 0.0001; tumour necrosis factor alpha [TNF-α] 1139.45 ± 198.87 vs 1598.77 ± 298.52 pg/ml, P < 0.0001; superoxide dismutase [SOD] 1145.92 ± 228.75 vs 1296 ± 225.72 U/g Hb, P = 0.0013; glutathione peroxidase [GPx] 20.78 ± 3.14 vs 25.99 ± 4.11 U/g Hb, P < 0.0001; glutathione [GSH] 9.358 ± 2.139 vs 6.831 ± 1.139 U/g Hb, P < 0.0001; thiobarbituric acid reactive substances [TBARS] 131.62 ± 29.68 vs 176.40 ± 68.11 nmol/g Hb, P < 0.0001). Similarly, when healthy elderly subjects treated with the test formulation for 12 months were compared to the placebo group, a significant (P < 0.001) improvement in cognitive measures (MMSE, DSS, word recall delayed but not immediate, attention span, FAQ and depression scores) and a reduction in inflammation (reduction in homocysteine, CRP, IL-6 and TNF-α levels) and oxidative stress levels (reduction in SOD, GPx and TBARS and increase in GSH) was observed. This indicated a protective effect of the test formulation in managing cognitive decline associated with the ageing process. CONCLUSION: The results of this study demonstrate the therapeutic potential of this novel polyherbal formulation for the management and treatment of SDAT.

Anticancer activity of Moringa oleifera mediated silver nanoparticles on human cervical carcinoma cells by apoptosis induction.

Silver nanomaterial plays a crucial role in the growing field of nanotechnology as there is an increasing commercial demand for silver nanoparticles (AgNPs) owing to their wide biological applications. The present investigation aims at developing anti-cancerous colloidal silver using Moringa olifera stem bark extract. Electron and atomic force microscopic images were taken to analyze the surface morphology of the synthesized AgNPs. The effects of synthesized AgNPs were tested against human cervical carcinoma cells (HeLa) and cell morphology was further evaluated using 4,6-diamidino-2-phenylindole (DAPI) staining. The efficiency of green synthesized AgNPs was studied with the help of fluorescence activated cell sorting (FACS) and was shown to induce apoptosis through reactive oxygen species (ROS) generation in HeLa cells.

Protective effect of curcuminoids on age-related mitochondrial impairment in female Wistar rat brain.

The present study demonstrated the neuroprotective effect of curcuminoids, the active polyphenols of Curcuma longa (L.) rhizomes on mitochondrial dysfunctioning in middle aged and aged female Wistar rat brain. Rats were orally treated with curcuminoids (100 mg/kg) for 3 months and their brain was collected for evaluation of mitochondrial enzymes and complexes activity, ultra structural changes in mitochondria, neuronal nitric oxide synthase (nNOS) protein expression, adenosine triphosphate (ATP) and lipofuscin content. Significant alterations were observed in all the tested parameters in highly aged rat brain when compared with young control. Long term curcuminoids administration prevented this age associated loss of mitochondrial enzymes and complexes activity in middle aged rat brain except for malate dehydrogenase, Complex II and IV activity when compared with young control. Among aged rats, curcuminoids treatment specifically elevated isocitrate and NADH dehydrogenase, cytochrome c oxidase, Complex I and total ATP content. A significant down-regulation of nNOS protein expression along with reduced lipofuscin content was also observed in curucminoids treated middle aged and aged rats. Thus, it was suggested that curcuminoids may act as a putative drug candidate for the prevention of deleterious effects of ageing and age associated neurodegenerative disorders through amelioration of aberrant mitochondrial functioning.

Androgenetic alopecia and risk of coronary artery disease.

BACKGROUND: Androgenetic alopecia (AGA) or male pattern baldness (MPB) has been found to be associated with the risk of coronary artery disease (CAD). The well-known risk factors are family history of CAD, hypertension, increased body mass index (BMI), central obesity, hyperglycemia, and dyslipidemia. The newer risk factors are serum lipoprotein-a (SL-a), serum homocysteine (SH), and serum adiponectin (SA). AIM: Identifying individuals at risk of CAD at an early age might help in preventing CAD and save life. Hence, a comparative study of CAD risk factors was planned in 100 males of AGA between the age of 25 and 40 years with equal number of age- and sex-matched controls. MATERIALS AND METHODS: Patients of AGA grade II or more of Hamilton and Norwood (HN) Scale and controls were examined clinically and advised blood test. The reports were available for fasting blood sugar (FBS), serum total serum cholesterol (SC) in 64 cases, 64 controls; lipoproteins (high, low, very low density, HDL, LDL, VLDL), serum triglycerides (ST) in 63 cases, 63 controls; SL-a in 63 cases, 74 controls; SH in 56 cases, 74 controls; and SA in 62 cases, 74 controls. RESULTS: In these cases family history (FH) of AGA and CAD was significantly high. The blood pressure (BP) was also found to be significantly high in the cases. The difference of mean serum HDL, LDL, VLDL, ST, SH, and SL-a in cases and controls were statistically significant and with increasing grade of AGA, the risk factors also increased. CONCLUSION: Patients with AGA appear to be at an increased risk of developing CAD, therefore, clinical evaluation of cases with AGA of grade II and above may be of help in preventing CAD in future.

Assessment of serum leptin and resistin levels in association with the metabolic risk factors of pre- and post-menopausal rural women in South India.

OBJECTIVES: Menopausal status is related with weight gain, abnormal lipid and glucose metabolism leading to metabolic syndrome susceptibility. The aim of this study is to determine circulating serum leptin and resistin levels and to correlate these levels in relationship with the metabolic factors in pre- and post-menopausal women. METHODS: A cross-sectional study has been carried out for 34 subjects who were in post-menopause and 31 subjects who had regular menstruation in south Indian rural women. Anthropometric indices, blood pressure, fasting blood sugar (FBS), fasting lipid profile, fasting leptin and resistin levels were measured. RESULTS: In a total of 65 subjects, the mean age of pre-menopausal group was 38.65±6.21 and that of post-menopausal group was 55.32±6.32. Fasting serum leptin level was increased considerably in post-menopausal women when compared to pre-menopausal women (P=0.018). Resistin has no significant relationship with metabolic factors except Body Mass Index (BMI) in both the groups. Triglycerides and FBS were lower in pre-menopausal group when compared to post-menopausal group (P<0.001). Leptin was well correlated with BMI in pre-menopausal women (r(2)=0.7120, P<0.0001) as well as post-menopausal women (r(2)=0.2470, P=0.0028). Leptin also had significant correlation with FBS in both pre (r(2)=0.1373, P=0.0402) and post-menopausal women (r(2)=0.2141, P=0.0401). Systolic blood pressure was positively associated with the leptin levels in post-menopausal women (P<0.001). CONCLUSION: Leptin was found to have significant association with metabolic factors when compared to resistin in pre- and post-menopausal women and there is no doubt that association of BMI and FBS elevates the level of leptin in both the category.

Immunomodulating and antiproteinuric effect of Hippophae rhamnoides (Badriphal) in idiopathic nephrotic syndrome.

OBJECTIVE: The treatment of idiopathic nephrotic syndrome is still not well settled and at times is very frustrating. Number of protocols have been reported with variable results outcome in various conditions. The main pillar of treatment of idiopathic nephrotic syndrome is use of immunomodulating and suppressive drugs in various combinations. The herbal preparations have also been reported to have immunomodulating property. The study has been planned to record Immunomodulating and antiproteinuric effect of Hippophae rhamnoides. MATERIAL AND METHODS: In the present study had 2 groups having 28 patients of idiopathic nephrotic syndrome in each group have been included. The patients were subjected to haematological, biochemical, immunological investigation at 0, 1, 2 and 3 months interval with dietic advise. Group A have been put on standard treatment, whereas group B on Badriphal in the well worked up doses. The hydroalcoholic extract of 350 mg twice daily of Badriphal was given to group B as add on treatment. Patients were followed up with definite protocol at monthly interval for 3 months. RESULTS: At the end of 3 month patients showed improvement in the symptoms of oedema, anorexia, oliguria in the herbal group. The urinary estimation of protein showed significant decrease in Group B with elevation of S. albumin levels. The inflammatory cytokines has showed significant decrease at the end of 3 month. CONCLUSION: Thus the pilot study showed beneficial effect of the herbal preparation Hippophae rhamnoides as add on treatment. A large perspective study is recommended to establish these findings.

Neuroprotective effect of curcuminoids against inflammation-mediated dopaminergic neurodegeneration in the MPTP model of Parkinson's disease.

The present study investigated the neuroprotective effect of curcuminoids, the active polyphenols of Curcuma longa (L.) rhizomes against inflammation-mediated dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Male C57BL/6 mice were pre-treated with curcuminoids (150 mg/kg/day) for 1 week, followed by four intra-peritoneal (i.p.) injections of MPTP (20 mg/kg) at 2 h intervals with further administration of curcuminoids or deprenyl (3 mg/kg/day) for 2 weeks. Our results show that oral administration of curcuminoids significantly prevented MPTP-mediated depletion of dopamine and tyrosine hydroxylase (TH) immunoreactivity. In-addition, pre-treatment with curcuminoids reversed glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS) protein expression, as well as, reduced pro-inflammatory cytokine and total nitrite generation in the striatum of MPTP-intoxicated mice. Significant improvement in motor performance and gross behavioural activity, as determined by rota-rod and open field tests were also observed. Taken together, our findings suggest that curcuminoids exert a neuroprotective effect against MPTP-induced dopaminergic neurodegeneration through its anti-inflammatory action and thus holds immense potential as a therapeutic candidate for the prevention and management of PD.

Amelioration of age associated neuroinflammation on long term bacosides treatment.

Bacopa monnieri (L.) is a revered medicinal plant of traditional Indian system of medicine effective against cognitive impairment in ageing and SDAT. In our previous study, long term administration of bacosides was found to exhibit remarkable anti ageing effect, ameliorate age associated neurochemical and neurobehavioral deficits and prevent hippocampal neuronal degeneration in middle aged and aged rat brain cortex. In continuation to the previous study, the present study aims to investigate the neuroprotective effect of bacosides against age related chronic neuroinflammation in Wistar rat brain on 3 months treatment. Recently, neuroinflammation has gained considerable interest in age associated neurodegeneration and pathologies like SDAT due to its slow onset and chronic nature. The results of the present study demonstrated the significant attenuation of age dependant elevation of pro inflammatory cytokines, iNOS protein expression, total nitrite and lipofuscin content in middle aged and aged rat brain cortex on long term oral administration of bacosides. Thus, the present results suggest that bacosides possess immense potential to act as a neuroprotective agent due to its pleiotropic action for the prevention of ageing complications and SDAT progression.

Prevention of age-associated neurodegeneration and promotion of healthy brain ageing in female Wistar rats by long term use of bacosides.

Bacopa monnieri (L.), popularly known as Brahmi, is a revered Ayurvedic medicinal plant used as nerve tonic since time immemorial. The present study aims to investigate the neuroprotective effect of bacosides, the active saponins of Bacopa monnieri (L.) against age associated neurodegeneration and its impact over the prevention of Senile Dementia of Alzheimer's Type (SDAT). The optimum dose of bacosides with no adverse effect was selected by screening its dose dependant activity on ageing biomarker lipofuscin and SDAT biomarker neurotransmitter acetylcholine in the aged female Wistar rat brain. The selected therapeutic dose of bacosides (200 mg/kg) was orally administered for 3 months in middle aged and aged rats and further investigated for its protective action against age associated alterations in neurotransmission system, behavioral paradigms, hippocampal neuronal loss and oxidative stress markers. The results of the present study suggest that bacosides may act as a potential therapeutic intervention in forestalling the deleterious effects of ageing and preventing the age associated pathologies like SDAT.