Association of taurine with ovarian follicular steroids and postpartum anestrus condition in Murrah buffaloes.

Taurine is an abundant intracellular beta-amino acid majorly synthesized in the liver and transported through plasma. In mammals, taurine was reported to be involved in various physiological functions, including the enhancement of testosterone levels, the major estradiol precursor. Therefore, we hypothesize that taurine levels are associated with ovarian follicular steroids as well as with a reproductive problem called postpartum anestrus (PPA) in dairy buffaloes. To understand the taurine levels and its possible role in buffalo ovarian follicles, a correlation was established among taurine, estradiol, and testosterone levels in the ovarian follicular fluid. For this purpose, buffalo ovaries were obtained from the slaughterhouse, and follicular fluid samples were collected from small (<4 mm), medium (4-8 mm) and large (>8 mm) follicles. Taurine and steroid levels in the follicular fluid were analyzed by TLC and ELISA, respectively. Taurine and testosterone levels were significantly (P < 0.05) higher in the follicular fluid of small and medium follicles than large follicles, whereas the estradiol levels were significantly (P < 0.001) higher in the large follicles. Thus, taurine showed a positive correlation (r = 0.75) with testosterone and a negative correlation (r = -0.77) with estradiol in buffalo follicular fluid, indicating its possible role in testosterone function during follicular development. Interestingly, significantly (P < 0.001) lower plasma taurine levels in PPA (n = 50) than normal cyclic (n = 50) buffaloes represented its association with PPA. Therefore, our present study recommends the need for future nutrition studies on taurine supplementation to PPA buffaloes.

Rooting behaviour and soil properties in different bamboo species of Western Himalayan Foothills, India.

Due to extensive root system, connected rhizome bamboos are considered suitable for improving soil properties within a short period, though most of the claims are anecdotal and need to be supported with quantified data. The study evaluates seven bamboo species viz., Bambusa balcooa, Bambusa bambos, Bambusa vulgaris, Bambusa nutans, Dendrocalamus hamiltonii, Dendrocalamus stocksii and Dendrocalamus strictus for their rooting pattern and impact on soil health properties. Coarse and fine root intensity was maximum in B. vulgaris. Coarse root biomass ranged from 0.6 kg m-3 in B. nutans to 2.0 kg m-3 in B. vulgaris and B. bambos. Fine root biomass ranged from 1.1 kg m-3 in B. nutans to 4.5 kg m-3 in D. hamiltonii. Contribution of fine roots in terms of intensity and biomass was much higher than coarse roots. Fine root biomass showed declining trend with increase in soil depth in all the species. During sixth year, the litter fall ranged from 8.1 Mg ha-1 in D. stocksii to 12.4 Mg ha-1 in D. hamiltonii. Among soil physical properties significant improvement were recorded in hydraulic conductivity, water stable aggregates and mean weight diameter. Soil pH, organic carbon and available phosphorus under different species did not reveal any significant changes, while significant reduction was observed in total nitrogen and potassium. Significant positive correlation was observed between WSA and iron content. Soil microbial population and enzyme activities were higher in control plot. Considering root distribution, biomass, soil hydraulic conductivity and water stable aggregates, B. bambos, B. vulgaris and D. hamiltonii are recommended for rehabilitation of degraded lands prone to soil erosion.

HPLC characterization of molluscicidal component of Tamarindus indica and its mode of action on nervous tissue of Lymnaea acuminata.

BACKGROUND: Fasciolosis is a water-borne disease with gastropods snail (Lymnaea acuminata) act as key-link is still burden for mankind especially in developing countries. Snail control is one of the important tools to trim down the frequency of fasciolosis. OBJECTIVE: To evaluate the toxic effect and inhibitory potential of plant Tamarindus indica and their active constituent on the key enzyme of nervous tissue of snail L. acuminata. METHOD: The present study deals with the chromatographic isolation and identification of molluscicidal component from Tamarindus indica bark and its effects on enzymes activities of vector snail L. acuminata. RESULT: The toxicity study reveals that among all organic extract ethanol extract of T. indica bark (96 h LC50:127.4 mgL-1) was more effective than other organic extracts. The 96 h LC50 of column purified fraction of T. indica bark was 13.78 mgL-1 respectively. Saponin was isolated, characterized and identified as active molluscicidal component in the bark of T. indica by column chromatography, TLC and HPLC chromatographic methods. The in vivo and in vitro treatment of column purified fraction and saponin has significant inhibition in enzyme AChE, ACP and ALP activities. The study of inhibition kinetics indicates that inhibition of AChE and ALP is competitive, while ACP is uncompetitive in both the treatments. CONCLUSION: Thus inhibition of these enzyme activities by T. indica bark column purified fraction and saponin in the snail L. acuminata may be the cause of its molluscicidal activity which leads snail death.

Associations Between Religious/Spiritual Practices and Well-Being in Indian Elderly Rural Women.

Religion and spirituality (R/S) are embedded in all aspects of life in India, a predominantly rural economy. The aim of this mixed methods study was to assess the associations between a culturally tailored intervention and preexisting religious/spiritual (R/S) practices with indicators of well-being and factors which contribute to happiness among elderly rural women from Haryana state, India. The study consisted of three groups: field experimental group (FEG; n = 24); practitioners of preexisting R/S practices for at least 6 weeks Satsang (SG, n = 54), Brahma Kumaris (BKG, n = 54), and Radha Soami (RSG, n = 30), and non-practitioners of R/S practices (n = 64). All groups completed self-report measures of overall happiness and life satisfaction, global health, quality of life, and health status and physical health. Results revealed that FEG participants improved significantly on physical health, body balancing, and self-care; no changes were observed on the other well-being measures following the intervention. Practitioners of preexisting R/S practices were found significantly different from the non-practitioners on some indicators of health, quality of life, and well-being. Qualitative measures pointed to the importance of R/S and family and interpersonal relationships among elderly rural women.

Comparison of pharmacological properties and phytochemical constituents of in vitro propagated and naturally occurring liverwort Lunularia cruciata.

BACKGROUND: Study of phytochemicals and pharmacological properties of bryophytes has been neglected for a long time because of the three main reasons i.e. (i) difficulty in collection in large amount for analysis; (ii) their availablility only in particular season and (iii) their restricted geographic distribution. So, the aim of this work was to propagate Lunularia cruciata under in vitro condition for comparing its pharmacological properties and phytocmecial constituents with naturally grown counterparts. METHOD: Axenic culture of L. cruciata was established by propagating gemmae under in vitro condition. Appropriate culture conditions, media, and the effect of hormones on growth and development were studied. The phytochemical composition was determined by GC-MS analysis and pharmacological activity was evaluated by assessing the antioxidant and anti-diabetic activities. For the antioxidant activity ABTS+ [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)], DPPH• (2,2-diphenyl-1-picrylhydrazyl) and metal chelating assays were done and for evaluation of the in vitro anti-diabetic activity α-glucosidase and α-amylase inhibitory activities were done. RESULT: Growth of L. cruciata was recorded in half strength MS media. Benzylaminopurine (BAP: 2 mg/L) and 1-Naphtheleneacetic acid (NAA: 0.5 mg/L) were the successful hormonal combination. GC-MS analysis revealed the existence of nine key compounds in both in vitro and naturally grown L. cruciata. Result of antioxidant and anti-diabetic activity showed that in vitro grown L. cruciata has a more or less similar antioxidant and anti-diabetic activities as naturally grown ones. This result confirms the possibility of using in vitro grown plants in place of naturally grown plants for research and clinical purposes.

Intranasal curcumin regulates chronic asthma in mice by modulating NF-ĸB activation and MAPK signaling.

BACKGROUND: Curcumin, a natural product found in the plant Curcuma longa, has been reported to have diverse range of molecular targets that influence numerous biochemical and molecular cascades including anti-inflammatory and antioxidant properties. PURPOSE: The aim of the study was to investigate the therapeutic potential of intranasal curcumin on ovalbumin (OVA)-induced chronic asthma and to elucidate underlying molecular mechanisms. STUDY DESIGN/METHOD: Mice were sensitized and exposed to 2% OVA aerosol for 2 times in a week for five consecutive weeks to study effect of intranasal curcumin on various MAPK pathway enzymes involved in chronic asthma and its effect on the activation of nuclear factor kB (NF-kB). RESULTS: Curcumin treatment decreased the ROS level in BALF and nitrite level in blood serum of chronic asthmatic mice. Curcumin treatment had significantly decreased the phosphorylation of JNK, ERK1/2, and p38 and COX-2 expression thereby nuclear factor κB (NF-κB) activation and expression in lung tissues. CONCLUSION: These results suggest that intranasal curcumin protects against asthma via action on mitogen-activated protein kinase (MAPK)/NF-κB signaling pathways.

Lactobacillus plantarum MTCC 9510 supplementation protects from chronic unpredictable and sleep deprivation-induced behaviour, biochemical and selected gut microbial aberrations in mice.

AIM: Here, we evaluated any beneficial effects of a potential probiotic bacterial strain (Lactobacillus plantarum MTCC 9510) in two different stress paradigms in mice. METHODS AND RESULTS: Lactobacillus plantarum MTCC 9510 (2 × 1010 CFU per mice) was supplemented to male Swiss albino mice either subjected to chronic unpredictable mild stress or sleep deprivation (SD) stress. Various behavioural and biochemical tests along with selected gut bacterial abundances were determined. Lactobacillus plantarum MTCC 9510 supplementation prevented stress-induced behavioural despair (depression, anxiety, learning and memory, stereotypic behaviour), oxidative stress markers and inflammatory cytokines in brain and serum. Its supplementation also improved gut and blood brain barrier integrity. It also affected caecal short-chain fatty acids along with the promotion of Lactobacillus sp. and reduction in Enterobacteriaceae abundances. We also observed that two different stresses variably affected various behavioural and biochemical changes but L. plantarum MTCC 9510 supplementation most effectively prevented all these changes. CONCLUSION: We provide evidence that positive modulation of the selected beneficial gut microbial population could serve as a viable strategy to neutralize day-to-day and SD stress-induced pathological alterations. SIGNIFICANCE AND IMPACT OF THE STUDY: Therapeutic potential of this/other probiotic strains in tackling the deleterious neurobiological effects on exposure to various stress-related conditions can be explored.

Adjuvant activity of ethanol extract of Hippophae rhamnoides leaves with inactivated rabies virus antigen.

CONTEXT: Hippophae rhamnoides L. (Elaeagnaceae), commonly known as seabuckthorn (SBT), is known for its medicinal and nutritional properties. OBJECTIVE: Evaluation of in vivo adjuvant activity of SBT leaf extract (SBTE) with inactivated rabies virus antigen (Rb). MATERIALS AND METHODS: Swiss albino mice were immunized with aqueous-alcoholic SBTE (100 mg/kg body weight) or algel (aluminium hydroxide gel) with or without Rb (5% v/v). After priming, booster was administered on day 14. Rabies virus neutralizing antibody (RVNA) titers were estimated by rapid fluorescent focus inhibition test in sera samples collected on days 7, 14, 21, 28 and 35. Effect of adjuvant administration on cytotoxic T lymphocytes (CTLs), memory T cells, plasma and CD11c+ cells was studied by flow cytometry. In vitro hemolysis was assayed in human RBC. RESULTS: RVNA titers were significantly enhanced (p < 0.05) after booster administration in mice immunized with SBTE + Rb as compared to the controls. In combination, SBTE, algel and Rb, enhanced the RVNA titers. CTLs significantly increased (p < 0.05) in SBTE + Rb immunized mice. Memory T cells and plasma cells were 27.9 and 15.9%, respectively, in SBTE + Rb immunized mice as compared to that of 20.3 and 11.3%, respectively, in Rb immunized group. SBTE + Rb enhanced peritoneal CD11c+ cells (25.8%) as compared to 9.4% cells in Rb immunized mice, showed 3.2-fold increment in LPS induced IL-1ß. No RBC hemolysis was observed with SBTE. CONCLUSIONS: This study demonstrates the potential adjuvant activity of SBTE with Rb by increasing RVNA titers and CTL response.

Regulation of oxidative stress and mineral nutrient status by selenium in arsenic treated crop plant Oryza sativa.

The present study was conducted to examine the impact of selenium (Se) on mineral nutrient status and oxidative stress in crop plant Oryza sativa treated with arsenic (As). Scanning electron microscopy (SEM) coupled with Energy dispersive x-ray spectroscopy (EDS) study revealed the morphological deformities in leaf veins along with granular deposition on the leaf surface. The EDS analysis exhibited loss of elements (S, Si, Cl, K, Ca, Fe and Cu) in As(III) treatment in rice roots as compared to untreated root. In the case of As(III) treated shoot, changes in elements content in term of percent atomic weight was K (1.17-0.90%), Cl (1.04-24.75%), Na (0.65-3.52%) and S (0.49-2.52%) when compared with untreated shoot. The result of EDS analysis showed that As limits the concentration of important mineral elements present in the rice root and shoot. Rice plant treated with Se (10µM) and sub lethal dose of As(III) (60µM) showed better growth responses in term of root, shoot length (11.4% and 10.71%, respectively), biomass (11.7%), reduced malonyldialdehyde content (35.14%) and stimulated antioxidant level indicating better As tolerance potential against As. Further, a selenium dependent significant reduction in As accumulation was also observed in root (14.24%) and shoot (23.78%) of rice plant when compared with plant treated with As alone. This study highlights the potential of Se to ameliorate the ecotoxicological risks associated with the As buildup in agricultural land.

Seasonal alterations in the daily rhythms in hypothalamic expression of genes involved in the photoperiodic transduction and neurosteroid-dependent processes in migratory blackheaded buntings.

The present study investigated seasonal alterations in the daily rhythms of hypothalamic expression of genes involved in the photoperiodic regulation of annual cycles in birds. We measured the 4-hourly mRNA expression of genes involved in the photoperiodic transduction (OPN5, EYA3, CGA, TSHß, DIO2, DIO3) and neurosteroid-dependent processes (AR, CYP19, ERα, ERß) in the hypothalamus of migratory blackheaded buntings photoinduced with photosensitive, photostimulated (early and late stimulated) and photorefractory seasonal states. There were significant differences in daily mRNA profiles between the photoperiodic states. Particularly, increased CGA, TSHß and DIO2 and decreased DIO3 mRNA levels in the early photostimulated state, compared to the photosensitive state, suggest that thyroid hormones have a role in photostimulation in buntings. Similar differences in the expression of genes coding for the aromatase enzyme (CYP19) and receptors for oestrogen (ERα, ERß) (but not androgen; AR) indicate that there is seasonal alteration in the neuro-oestrogen-mediated functions. Furthermore, peak expression times of CGA, TSHß and DIO2 genes at hours 14-15 of the day in the early stimulated state indicated molecular regulation of the daily rhythm of photoinducibility in buntings. Most significantly, however, we found an attenuated daily rhythm in thyroid hormone modulatory genes and a switch of peak expression time from day to night in CYP19 mRNA rhythm in the subsequent late photostimulated state, although testicular maturation still persisted. These alterations in daily rhythms may have signalled the initiation of processes underlying other seasonal phenologies in parallel with the gonadal response, such as a manifestation of the night-time flight in buntings. These results show alterations in daily rhythms underlying the transcriptional regulation of the photoperiod-induced seasonal states in migratory blackheaded buntings.

Functional block of IL-17 cytokine promotes bone healing by augmenting FOXO1 and ATF4 activity in cortical bone defect model.

We determine the effect of interleukin (IL)-17 neutralizing antibody on new bone regeneration. Anti-IL-17 antibody promoted new bone regeneration in cortical bone defect model by augmenting FOXO1 and ATF4 activity thereby decreasing oxidative stress. Our study demonstrates the bone healing and regeneration potential of neutralizing IL-17antibody in osteoporotic fractures. INTRODUCTION: The immune system plays important role in the fracture healing process. However, fracture healing is prolonged in disorders associated with systemic inflammation. Fracture healing is decelerated in osteoporosis, condition linked with systemic inflammation. Bone regeneration therapies like recombinant human BMP2 are associated with serious side effects. Studies have been carried out where agents like denosumab and infliximab enhance bone regeneration in osteoporotic conditions. Our previous studies show the osteoprotective and immunoprotective effects of neutralizing IL-17 antibody. Here, we determine the effect of IL-17 neutralizing antibody on new bone regeneration and compare its efficacy with known osteoporotic therapies. METHODS: For the study, female BALB/c mice were ovariectomized or sham operated and left for a month followed by a 0.6-mm drill-hole injury in femur mid-diaphysis. The treatment was commenced next day onwards with anti-IL-17, anti-RANKL (Receptor activator of nuclear factor kappa-B ligand), parathyroid hormone (PTH), or alendronate for a period of 3, 10, or 21 days. Animals were then autopsied, and femur bones were dissected out for micro-CT scanning, confocal microscopy, and gene and protein expression studies. RESULTS: Micro-CT analysis showed that anti-IL-17 antibody promoted bone healing at days 10 and 21, and the healing effect observed was significantly better than Ovx, anti-RANKL antibody, and ALN, and equal to PTH. Anti-IL-17 also enhanced new bone regeneration as assessed by calcein-labeling studies. Additionally, anti-IL-17 therapy enhanced expression of osteogenic markers and decreased oxidative stress at the injury site. CONCLUSION: Overall, our study demonstrates bone healing and regeneration potential of neutralizing IL-17 antibody in osteoporotic fractures.

Phytotherapy of chlorophyllin exposed Lymnaea acuminata: A new biotechnological tool for fasciolosis control.

Phytotherapy of chlorophyllin formulations against Fasciola gigantica infected Lymnaea acuminata under sunlight exposure was highly toxic against redia and cercaria larvae. Binary combinations (1:1 ratio) of chlorophyllin (CHL) + freeze dried cow urine (FCU) were more toxic against cercariae (8 h LC50: 9.6 mg L- 1) than single treatment with chlorophyllin (8 h LC50: 12.6 mg L- 1) in sunlight. The larvicidal activity of sunlight exposed CHL against rediae (8 h LC50: 13.5 mg L- 1) and cercariae (8 h LC50: 12.6 mg L- 1) was more pronounced than laboratory conditions CHL treatment (rediae- 8 h LC50: 305.9 mg L- 1; cercariae- 8 h LC50: 765.4 mg L- 1). Larvicidal activity of FCU was less than CHL and CHL + FCU against both redia and cercaria. Chlorophyllin and its formulations were more toxic against redia and cercaria larvae in sunlight than laboratory conditions. CHL and its different formulations may be used as potent larvicides against Fasciola gigantica larvae. Chlorophyllin formulations will be economical, ecologically sounder and their use in aquatic environment will be safe.

A novel cobiotic-based preventive approach against high-fat diet-induced adiposity, nonalcoholic fatty liver and gut derangement in mice.

BACKGROUND: High-fat diets (HFDs) induce systemic inflammation, gut microbial derangements and disturb metabolic homeostasis, resulting in weight gain, insulin resistance and nonalcoholic fatty liver (NAFL). Numerous antioxidants and prebiotic/probiotics per se may prevent HFD-associated comorbidities, but there are no reports related to their combination. OBJECTIVE: In the present study, we aim to evaluate a cobiotic combination of lycopene (antioxidant) and isomalto-oligosaccharides (IMOs, a prebiotic) for prevention of HFD-induced alterations. DESIGN: Male Swiss albino mice were fed either normal pellet diet (NPD) or HFD and lycopene (5 and 10 mg kg(-1)), IMOs (0.5 and 1 g kg(-1)) or their combination for 12 weeks. Systemic adiposity, glucose tolerance, insulin sensitivity, feeding regulators in hypothalamus, hepatosteatosis and liver inflammation, cecal short chain fatty acids (SCFAs), serum inflammatory cytokines, gut morphology and alterations in selected gut microbes were studied. RESULTS: Lycopene, IMOs and their combination prevented weight gain, adiposity, improved adipose tissue fat mobilization and reduced insulin resistance. Hypothalamic orexigenic and anorectic genes have also been modulated by these treatments. Dietary interventions prevented NAFL-like symptoms and improved glucose homeostasis. Improvement in selected gut microbial abundance and SCFA concentration along with reduced systemic inflammation, metabolic endotoxemia and improved ileal and colonic health were observed in mice supplemented with lycopene, IMOs and their combination. Interestingly, cobiotic combination synergistically improved many of the HFD-induced alterations. CONCLUSION: The present work provide evidence that new approach based on cobiotic combination (antioxidant plus prebiotic) can be employed to develop novel class of functional foods for their application against HFD-associated pathological complications.

Nutrition and Frailty: A Review of Clinical Intervention Studies.

Frailty is one of the major health concerns in aging. It is considered a geriatric syndrome characterized by muscle weakness, sarcopenia and fatigue. It is also associated with several adverse health outcomes, including disability. Literature shows that there are a number of studies conducted to define the relationship between frailty and nutrition. The majority is from cross sectional, longitudinal, and cohort studies. Few intervention studies using micronutrients, macronutrients, nutritional supplement, or food regimens have been found. This review examines the nutrition intervention studies targeted towards older adults with frailty, and evaluates the effectiveness of nutrition interventions on frailty indicators. Twenty-four intervention studies from six electronic databases met the inclusion criteria. Sixteen were randomized controlled clinical trials; one was a quasi-experimental design, whilst the rest were controlled trials. Participants included in the studies differed in terms of age and frailty status. The studies were inconsistent in intervention type, duration, and targeted outcomes. Most of the studies indicated that modification of nutrition quality, either by giving supplements or by improving diet intake, could improve strength, walking speed, and nutritional status in majority of frail or pre-frail older adults. However, there was limited evidence on the effectiveness of intervention on inflammatory status and other biomarkers related to frailty due to limited number of studies targeting frailty biomarkers as a major outcome.

Effect of salt-tolerant plant growth-promoting rhizobacteria on wheat plants and soil health in a saline environment.

Salt-tolerant plant growth-promoting rhizobacteria (ST-PGPR) significantly influence the growth and yield of wheat crops in saline soil. Wheat growth improved in pots with inoculation of all nine ST-PGPR (ECe = 4.3 dS·m(-1) ; greenhouse experiment), while maximum growth and dry biomass was observed in isolate SU18 Arthrobacter sp.; simultaneously, all ST-PGPR improved soil health in treated pot soil over controls. In the field experiment, maximum wheat root dry weight and shoot biomass was observed after inoculation with SU44 B. aquimaris, and SU8 B. aquimaris, respectively, after 60 and 90 days. Isolate SU8 B. aquimaris, induced significantly higher proline and total soluble sugar accumulation in wheat, while isolate SU44 B. aquimaris, resulted in higher accumulation of reducing sugars after 60 days. Percentage nitrogen (N), potassium (K) and phosphorus (P) in leaves of wheat increased significantly after inoculation with ST-PGPR, as compared to un-inoculated plants. Isolate SU47 B. subtilis showed maximum reduction of sodium (Na) content in wheat leaves of about 23% at both 60 and 90 days after sowing, and produced the best yield of around 17.8% more than the control.

A novel therapeutic approach with Caviunin-based isoflavonoid that en routes bone marrow cells to bone formation via BMP2/Wnt-ß-catenin signaling.

Recently, we reported that extract of Dalbergia sissoo made from leaves and pods have antiresorptive and bone-forming effects. The positive skeletal effect attributed because of active molecules present in the extract of Dalbergia sissoo. Caviunin 7-O-[ß-D-apiofuranosyl-(1-6)-ß-D-glucopyranoside] (CAFG), a novel isoflavonoid show higher percentage present in the extract. Here, we show the osteogenic potential of CAFG as an alternative for anabolic therapy for the treatment of osteoporosis by stimulating bone morphogenetic protein 2 (BMP2) and Wnt/ß-catenin mechanism. CAFG supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur and decreased bone turnover markers better than genistein. Oral administration of CAFG to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased the expression of osteogenic genes in femur and show new bone formation without uterine hyperplasia. CAFG increased mRNA expression of osteoprotegerin in bone and inhibited osteoclast activation by inhibiting the expression of skeletal osteoclastogenic genes. CAFG is also an effective accelerant for chondrogenesis and has stimulatory effect on the repair of cortical bone after drill-hole injury at the tissue, cell and gene level in mouse femur. At cellular levels, CAFG stimulated osteoblast proliferation, survival and differentiation. Signal transduction inhibitors in osteoblast demonstrated involvement of p-38 mitogen-activated protein kinase pathway stimulated by BMP2 to initiate Wnt/ß-catenin signaling to reduce phosphorylation of GSK3-ß and subsequent nuclear accumulation of ß-catenin. Osteogenic effects were abrogated by Dkk1, Wnt-receptor blocker and FH535, inhibitor of TCF-complex by reduction in ß-catenin levels. CAFG modulated MSC responsiveness to BMP2, which promoted osteoblast differentiation via Wnt/ß-catenin mechanism. CAFG at 1 mg/kg(/)day dose in ovariectomy mice (human dose ∼0.081 mg/kg) led to enhanced bone formation, reduced bone resorption and bone turnover better than well-known phytoestrogen genistein. Owing to CAFG's inherent properties for bone, it could be positioned as a potential drug, food supplement, for postmenopausal osteoporosis and fracture repair.

Evaluation of antihyperlipidemic potency of a polyherbomineral formulation (AF-LIP) in experimental animal models.

There is a growing interest in the screening of antihyperlipidemic activity and the present study deals with the screening of a polyherbomineral formulation (AF-LIP) which possess many important ingredients reported to have antihyperlipidemic potency. Acute antihyperlipidemic activity was evaluated by using Triton WR-1339 (100 mg kg(-1)) and chronic, induced by high fat diet. Total Cholesterol (TC), triglycerides (TG), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) and Very Low Density Lipoproteins (VLDL) were examined in addition to HMG-CoA reductase enzyme activity and fecal cholesterol excretion. In Triton WR-1339 (acute model) at the dose of 400 mg kg(-1), AF-LIP significantly lowered TC, TG, very Low Density Lipoproteins Cholesterol (VLDL-C), Low Density Lipoproteins Cholesterol (LDL-C) levels with simultaneous increase in High Density Lipoproteins Cholesterol (HDL-C) levels (p < 0.01) at 6 and 24 h. Also there was significant reduction in TC and LDL-C levels at 48 h at the dose of 400 mg kg(-1). In chronic model also at the dose of 100, 200 and 400 mg kg(-1), AF-LIP significantly reduced (p < 0.001) TC and LDL-C levels with increase in HDL-C levels. TG and VLDL-C levels were also not much affected. HMG-CoA reductase enzyme activity when estimated was not much decreased. Also AF-LIP showed significant reduction in atherogenic index (p < 0.01) with significant increase in HDL/TC ratio (p < 0.01). Fecal cholesterol excretion was significantly enhanced (p < 0.01) in all the test doses of AF-LIP. AF-LIP may be beneficial for the treatment of atherosclerosis, since atherosclerosis is one of the secondary complications of hyperlipidemia.

miR-542-3p suppresses osteoblast cell proliferation and differentiation, targets BMP-7 signaling and inhibits bone formation.

MicroRNAs (miRNAs) are short non-coding RNAs that interfere with translation of specific target mRNAs and thereby regulate diverse biological processes. Recent studies have suggested that miRNAs might have a role in osteoblast differentiation and bone formation. Here, we show that miR-542-3p, a well-characterized tumor suppressor whose downregulation is tightly associated with tumor progression via C-src-related oncogenic pathways, inhibits osteoblast proliferation and differentiation. miRNA array profiling in Medicarpin (a pterocarpan with proven bone-forming effects) induced mice calvarial osteoblast cells and further validation by quantitative real-time PCR revealed that miR-542-3p was downregulated during osteoblast differentiation. Over-expression of miR-542-3p inhibited osteoblast differentiation, whereas inhibition of miR-542-3p function by anti-miR-542-3p promoted expression of osteoblast-specific genes, alkaline phosphatase activity and matrix mineralization. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay identified BMP-7 (bone morphogenetic protein 7) as a direct target of miR-542-3p. It was seen that over-expression of miR-542-3p leads to repression of BMP-7 and inhibition of BMP-7/PI3K- survivin signaling. This strongly suggests that miR-542-3p suppresses osteogenic differentiation and promotes osteoblast apoptosis by repressing BMP-7 and its downstream signaling. Furthermore, silencing of miR-542-3p led to increased bone formation, bone strength and improved trabecular microarchitecture in sham and ovariectomized (Ovx) mice. Although miR-542-3p is known to be a tumor repressor, we have identified second complementary function of miR-542-3p where it inhibits BMP-7-mediated osteogenesis. Our findings suggest that pharmacological inhibition of miR-542-3p by anti-miR-542-3p could represent a therapeutic strategy for enhancing bone formation in vivo.

Withaferin A: a proteasomal inhibitor promotes healing after injury and exerts anabolic effect on osteoporotic bone.

Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic ß subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation. WFA increased expression of osteoblast-specific transcription factor and mineralizing genes, promoted osteoblast survival and suppressed inflammatory cytokines. In osteoclast, WFA treatment decreased osteoclast number directly by decreasing expression of tartarate-resistant acid phosphatase and receptor activator of nuclear factor kappa-B (RANK) and indirectly by decreasing osteoprotegrin/RANK ligand ratio. Our data show that in vitro treatment of WFA to calvarial osteoblast cells decreased expression of E3 ubiquitin ligase, Smad ubiquitin regulatory factor 2 (Smurf2), preventing degradation of Runt-related transcription factor 2 (RunX2) and relevant Smad proteins, which are phosphorylated by bone morphogenetic protein 2. Increased Smurf2 expression due to exogenous treatment of tumor necrosis factor α (TNFα) to primary osteoblast cells was decreased by WFA treatment. This was corroborated by using small interfering RNA against Smurf2. Further, WFA also blocked nuclear factor kappa-B (NF-kB) signaling as assessed by tumor necrosis factor stimulated nuclear translocation of p65-subunit of NF-kB. Overall data show that in vitro proteasome inhibition by WFA simultaneously promoted osteoblastogenesis by stabilizing RunX2 and suppressed osteoclast differentiation, by inhibiting osteoclastogenesis. Oral administration of WFA to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased expression of osteogenic genes. WFA supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur, decreased bone turnover markers (osteocalcin and TNFα) and expression of skeletal osteoclastogenic genes. It also increased new bone formation and expression of osteogenic genes in the femur bone as compared with vehicle groups (Sham) and ovariectomy (OVx), Bortezomib (known PI), injectible parathyroid hormone and alendronate (FDA approved drugs). WFA promoted the process of cortical bone regeneration at drill-holes site in the femur mid-diaphysis region and cortical gap was bridged with woven bone within 11 days of both estrogen sufficient and deficient (ovariectomized, Ovx) mice. Together our data suggest that WFA stimulates bone formation by abrogating proteasomal machinery and provides knowledge base for its clinical evaluation as a bone anabolic agent.

Enhanced antilipopolysaccharide (LPS) induced changes in macrophage functions by Rubia cordifolia (RC) embedded with Au nanoparticles.

In this paper, we have shown that gold nanoparticles (Au (NPs)) embedded in Rubia cordifolia (RC) matrix (RC-Au (NPs)) exhibit a high therapeutic value relating to its anti-inflammatory characteristics. It was prepared by utilizing the reducing properties of RC to convert HAuCl4 into Au (NPs). In order to compare its effectiveness, with respect to Au (NPs), the latter was synthesized separately by reducing HAuCl4 with lemon extract. These Au (NPs) along with RC-Au (NPs) were characterized by X-ray diffractometry (XRD), transmission electron microscopy (TEM), and UV-visible spectroscopy. The enhancement in anti-inflammatory characteristics was assessed as its inhibitory potential for lipopolysaccharide (LPS)-induced nitric oxide (NO) release, by rat peritoneal macrophages. The RC-Au (NPs) significantly enhanced its potential to inhibit NO release, which was reported in terms of inhibitory concentration for 50% inhibition (IC50=11.98 ng/ml), as compared to either RC extract (IC50=47 × 10(3)ng/ml) or to Au (NPs) (IC50=587.50 ng/ml).