Pragyanshu Khare

Cinnamaldehyde supplementation prevents fasting‐induced hyperphagia, lipid accumulation, and inflammation in high‐fat diet‐fed mice

Cinnamaldehyde, a bioactive component of cinnamon, is increasingly gaining interest for its preventive and therapeutic effects against metabolic complications like type-2 diabetes. This study is an attempt to understand the effect of cinnamaldehyde in high-fat diet (HFD)-associated increase in fasting-induced hyperphagia and related hormone levels, adipose tissue lipolysis and inflammation, and selected cecal microbial count in mice. Cinnamaldehyde, at 40 µM dose, prevented lipid accumulation and altered gene expression toward lipolytic phenotype in 3T3-L1 preadipocyte cell lines. In vivo, cinnamaldehyde coadministration prevented HFD-induced body weight gain, decreased fasting-induced hyperphagia, as well as circulating leptin and leptin/ghrelin ratio. In addition to that, cinnamaldehyde altered serum biochemical parameters related to lipolysis, that is, glycerol and free fatty acid levels. At transcriptional level, cinnamaldehyde increased anorectic gene expression in hypothalamus and lipolytic gene expression in visceral white adipose tissue. Furthermore, cinnamaldehyde also decreased serum IL-1β and inflammatory gene expression in visceral white adipose tissue. However, cinnamaldehyde did not modulate the population of selected gut microbial (Lactobacillus, Bifidibaceria, and Roseburia) count in cecal content. In conclusion, cinnamaldehyde increased adipose tissue lipolysis, decreased fasting-induced hyperphagia, normalized circulating levels of leptin/ghrelin ratio, and reduced inflammation in HFD-fed mice, which augurs well for its antiobesity role.

Protective effects of phyllanthin, a lignan from Phyllanthus amarus, against progression of high fat diet induced metabolic disturbances in mice

Evidence based studies have proved the efficacy of plant derived bioactives against lifestyle oriented disorders as they can be incorporated in to the diet or diet based supplements. Phyllanthin is one such lignan from Phyllanthus amarus as well as different Phyllanthus species. Phyllanthin was evaluated as a chronic intervention (12 weeks) in mice, at a daily dose of 2 and 4 mg kg−1 of body weight along with a lard based high fat diet (HFD). Phyllanthin protected against HFD induced weight gain and adiposity. Phyllanthin supplementation reduced mRNA expression of adipogenic genes and increased expression of lipolytic genes in white adipose tissue. Treatment also showed reduction in liver triglyceride accumulation. HFD induced serum lipid disturbances were found to be restored by phyllanthin. Treatment reduced serum triglycerides and free fatty acids in HFD fed mice. Phyllanthin counteracted coexisting low grade inflammation and oxidative stress in adipose tissue and liver. Along with serum proinflammatory cytokines, expression of NF-κB and F4/80 was decreased by phyllanthin. Supplementation of phyllanthin accelerated glucose clearance along with alleviation of insulin resistance in terms of HOMA-IR. Furthermore, mRNA expression of the insulin receptor and insulin receptor substrate-1 was elevated by phyllanthin in liver and adipose tissue. The present study confirmed the protective effects of phyllanthin against HFD induced metabolic changes. Daily consumption of phyllanthin in the diet as a nutraceutical can ameliorate the development of metabolic disorders.

Dihydrocapsiate supplementation prevented high fat diet induced adiposity, hepatic steatosis, glucose intolerance and gut morphological alterations in mice

Despite the lipolytic and thermogenic properties of capsaicin, its putative use as a weight-lowering dietary supplement has been limited because of the burning sensation caused by capsaicin when it comes in contact with mucous membranes. A potential alternative to capsaicin are the capsinoids, nonpungent capsaicin analogs that exhibit effects similar to capsaicin. Whereas the antiobesity properties of capsinoids have been reported, the effectiveness of FDA-approved synthetic dihydrocapsiate has not yet been investigated. In the present study, we hypothesized that dihydrocapsiate might ameliorate high-fat diet (HFD)-induced metabolic disorders in a manner similar to capsaicin and therefore can be its nonpungent alternative. To test this hypothesis, HFD-fed mice were orally administered dihydrocapsiate (2 and 10mg/kg body weight) for 12weeks. Dihydrocapsiate modestly reduced the HFD-induced weight gain and significantly prevented the associated hyperglyceridemia and hyperinsulinemia while improving glucose tolerance. Histological and gene expression analysis showed that dihydrocapsiate significantly prevented the lipid accumulation in white adipose tissue and brown adipose tissue via targeting genes involved in energy expenditure and mitochondrial biogenesis, respectively. Dihydrocapsiate corrected hepatic triglyceride concentrations and normalized expression of genes regulating hepatic lipid and glucose metabolism. Moreover, dihydrocapsiate administration significantly improved gut morphology and altered gut microbial composition, resulting in reduced host energy availability. Collectively, these results indicate that dihydrocapsiate administration improved glucose tolerance, prevented adiposity and hepatic steatosis, as well as improved HFD-induced gut alterations, positing dihydrocapsiate as a potential food ingredient for the dietary management of HFD-induced metabolic alterations.

Managing colonic inflammation associated gut derangements by systematically optimised and targeted ginger extract-Lactobacillus acidophilus loaded pharmacobiotic alginate beads

Presently, we explore a cobiotic-ginger extract (GE; antioxidant-antiinflammatory) and Lactobacillus acidophilus (LAB, probiotic), for control of oxidative-stress, inflammation and dysbiosis mediated gut ailments. Since orally administered LAB looses viability while GE is a gastric irritant with poor ADME, we encapsulated them into calcium-alginate beads. Water-loving, viscolysing, and osmotic-building effects of polyethylene glycol were used to address poor probiotic encapsulation (≤10%) by effective sealing of numerous fine voids formed in the alginate gel. Beads were systematically optimized for maximum entrapment (92±2.3% for GE, and 30±1.2% for LAB) and sustained release, and were coated with eudragit-S100 for colonic-targetability, as established by in-vitro release. In-vivo evaluation in DMH-DSS induced colitis and precancerous lesions, in rats, indicated attenuation of oxidative stress (catalase, SOD, LPO) and inflammatory burden (IL-6 and TNF-α), and downregulation of COX-2, iNOS, and c-Myc by both GE and LAB; restoration of colonic permeability by GE; and modulation of gut bacteria and SCFAs by LAB as the mechanisms of action. Complementing activities of GE and LAB in cobiotic beads lead to better reversals. Histology (H&E and toluidine blue) confirmed healing of precancerous lesions.

Effect of mahanimbine, an alkaloid from curry leaves, on high-fat diet-induced adiposity, insulin resistance, and inflammatory alterations.

Spices and condiments, small but an integral part of the daily diet, are known to affect physiological functions. This study evaluated the effects of mahanimbine, a major carbazole alkaloid from Murraya koenigii (curry leaves), against progression of high-fat diet (HFD)-induced metabolic complications in mice (male and female). Mahanimbine at 2 mg/kg (HFD + LD) and 4 mg/kg (HFD + HD) of body weight was administered daily along with HFD feeding for 12 weeks. At the end of the study, male HFD + LD and HFD + HD groups showed 51.70 ± 3.59% and 47.37 ± 3.73% weight gain, respectively, as compared with 71.02 ± 6.04% in HFD fed mice whereas female HFD + LD and HFD + HD groups showed 24.31 ± 1.68% and 25.10 ± 2.61% weight gain as compared with HFD group with 36.69 ± 3.60% of weight gain. Mahanimbine prevented HFD-induced hyperlipidemia and fat accumulation in adipose tissue and liver along with the restricted progression of systemic inflammation and oxidative stress. Moreover, mahanimbine treatment improved glucose clearance and upregulated the expression of insulin responsive genes in liver and adipose tissue. Male and female mice showed different traits in development of HFD-induced metabolic disturbances; however, mahanimbine treatment exerted similar effects in both the sexes. In addition, mahanimbine lowered the absorption of dietary fat resulting in dietary fat excretion. In conclusion, daily consumption of mahanimbine and thereby curry leaves may alleviate development of HFD-induced metabolic alterations.

Coadministration of ginger extract-Lactobacillus acidophilus (cobiotic) reduces gut inflammation and oxidative stress via downregulation of COX-2, i-NOS, and c-Myc : Novel cobiotic for DMH-DSS associated gut derangements

Aim of the study was to evaluate a combination of ginger extract (GE; antioxidant, anti‐inflammatory) and Lactobacillus acidophilus (LAB; probiotic), in DMH‐DSS‐induced inflammation‐driven colon cancer, in Wistar rats. Effect of varying GE concentration on growth of LAB was assessed in vitro. Colonic histology and permeability, oxidative stress, serum proinflammatory cytokines, expression of selected genes, gut bacteria, and SCFA determination of gut content was monitored after treatment with agents alone or in combination, postdisease induction. Significant increase in LAB CFU was observed following 48 and 96 hr of incubation with GE; 0.4% w/v GE showed the best results and was used in the cobiotic. Cobiotic administration significantly reversed the DMH‐DSS‐induced colonic histological alterations. Significant (p < .05) reduction in lipid peroxidation and increase in antioxidant levels (catalase and SOD) was observed in cobiotic group, whereas individual agents did not show any effect. Restoration of colonic permeability, decrease in serum inflammatory burden, and downregulation of COX‐2, iNOS, and c‐Myc expression on treatment with cobiotic was significantly (p < .05) better than individual agents. Neither LAB nor cobiotic administration produced any change in gut bacteria nor SCFA levels, probably due to loss of LAB viability under adverse gut conditions. Study concludes that presented cobiotic has a promising therapeutic potential, which can be improved by a smartly designed formulation.

Anthocyanin bio-fortified colored wheat: Nutritional and functional characterization

Colored wheat, rich in anthocyanins, has created interest among the breeders and baking industry. This study was aimed at understanding the nutritional and product making potential of our advanced, high yielding and regionally adapted colored wheat lines. Our results indicated that our advanced colored wheat lines exhibited higher anthocyanin content and antioxidant activity than donor wheat lines and it varied in the order of white<purple<blue<black wheat. UPLC chromatogram revealed that anthocyanin composition and peak pattern is not only dependent on donor genotype but also background of recipient genotype. Interestingly, the purple wheat extract showed highest anti-inflammatory effect and followed the trend of white<blue<black<purple. Nutritional (carbohydrates, sugar, protein, ash, dietary fibre and vitamins) and processing parameters in relation to end-use quality (SDS sedimentation, gluten content, alveograph) of advanced colored lines were similar to high yielding white wheat cultivar. Colored wheat lines showed high iron and zinc content compared to white wheat indicating double bio-fortification. Therefore, our advanced colored wheat lines with high anthocyanin, iron and zinc contents showed antioxidant and anti-inflammatory activity and possessed desirable features for product making and commercial utilization.

Finger millet arabinoxylan protects mice from high-fat diet induced lipid derangements, inflammation, endotoxemia and gut bacterial dysbiosis

Arabinoxylan (AX), a non-starch polysaccharide extracted from cereals such as wheat, rice and millets, is known to impart various health promoting effects. Our earlier study suggested that finger millet (FM) could ameliorate high fat diet (HFD)-induced metabolic derangements. The present study is aimed to evaluate the effect of FM-AX supplementation, a key bioactive from finger millet, on HFD-induced metabolic and gut bacterial derangements. Male Swiss albino mice were fed with normal chow diet (NPD) or HFD (60%kcal from fat) for 10 weeks. FM-AX was orally supplemented at doses of 0.5 and 1.0g/kg bodyweight on every alternate day for 10 weeks. Glucose tolerance, serum hormones, hepatic lipid accumulation and inflammation, white adipose tissue marker gene expression, adipocyte size and inflammation; metagenomic alterations in cecal bacteria; cecal short chain fatty acids and colonic tight junction gene expressions were studied. FM-AX supplementation prevented HFD-induced weight gain, alerted glucose tolerance and serum lipid profile, hepatic lipid accumulation and inflammation. Hepatic and white adipose tissue gene expressions were beneficially modulated. Further, AX supplementation prevented metagenomic alterations in cecum; improved ileal and colonic health and overall prevented metabolic endotoxemia. Present work suggests that AX from finger millet can be developed as a nutraceutical for the management of HFD- induced obesity.

The Role of TRPV1 in Acquired Diseases: Therapeutic Potential of TRPV1 Modulators

Abstract The transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel with high calcium permeability that has been studied extensively since its identification and characterization in 1997. Its involvement in different modalities of pain has been well documented, which has resulted in the development of novel strategies for the treatment of pain. However, TRPV1 is also involved in a plethora of other physiological and pathophysiological functions related to urinary, cardiovascular, gastrointestinal, respiratory, and central nervous systems. Here, we summarize the recent developments of the role of TRPV1 in acquired diseases and review the current perspective of TRPV1 agonist and antagonist as potential drugs for therapeutic intervention.