Supplementation of pyrroloquinoline quinone with atorvastatin augments mitochondrial biogenesis and attenuates low grade inflammation in obese rats.

Mitochondrial dysfunction and Inflammation play a significant role in the manifestation of the co-morbidities of obesity. The study deciphered the impact of Pyrroloquinoline quinone (PQQ) per se and with Atorvastatin (ATS) on high fat, 10% fructose diet (HFFD) induced obese rats expressing low-grade inflammation, dyslipidemia, and mitochondrial dysfunction. HFFD was fed for 10 weeks followed by treatment for 5 weeks with ATS 10 or 20 mg/kg, PQQ 10 or 20 mg/kg, p.o. per se or their combinations. The impact on blood glucose, lipid profile and serum insulin, TNF-α, IL-1ß, IL-18, IL-6 was estimated. Gene and protein expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC 1α), Sirtuin 1 (SIRT1), Mitochondrial transcriptional factor A (TFAM) and augmented mitochondrial DNA (mtDNA), NOD like receptor protein 3 (NLRP3) and Caspase 1 was assessed. Rats receiving PQQ and ATS revealed significant decrease in body weights, anthropometric parameter, and adipose tissue vis-à-vis positive control. PQQ alone and with ATS improved glucose tolerance, lipid profile, insulin indices and lowered serum levels of inflammatory cytokines IL-18, IL-1ß, TNF-α and IL-6 along with a rise in adiponectin. PQQ supplementation with ATS upregulated the mRNA expression of PGC 1α, SIRT1, TFAM and augmented mtDNA while downregulating inflammatory markers NLRP3 and Caspase 1. PQQ supplementation with atorvastatin holds therapeutic promise to effectively combat mitochondrial dysfunction and chronic low-grade inflammation in obesity.

Therapeutic interventions using a combination of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction in rats: modulation through ATP-sensitive K+ channels and eNOS.

BACKGROUND: Effective diet/drug combinations may show additive or synergistic effects in reducing endothelial risk factors vis-à-vis monotherapies. The study evaluated the effect of combined therapy of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. METHODS: Forty-eight male Wistar rats (180-220 g) were randomized into eight groups; control, sodium arsenite (1.5 mg/kg/day) exposed, sodium arsenite exposure followed by treatment with Telmisartan, omega 3-fatty acids, the combination and/or endothelial modulators for 2 weeks depending on the allocated group. VED was assessed by estimating vascular reactivity. Serum thiobarbituric acid-reactive substances (TBARS), nitrite/nitrate levels, reduced glutathione (GSH) levels, superoxide dismutase (SOD) activity, serum cholesterol and triglyceride levels were also determined. RESULTS: Sodium arsenite produced VED by attenuating acetylcholine-induced endothelial relaxation (% Rmax= 45.36), decreasing levels of serum nitrite/nitrate (9.28 µM/mg protein), GSH (16.06 µg/mg of protein), SOD activity (30.69 units/mg protein) and increasing TBARS (0.19 µM/mg protein) compared with control group. The combined therapy with Telmisartan (10 mg/kg/day) and omega 3-fatty acids (180 mg/kg/day) (% Rmax = 80.93, 13.09 µM/mg protein, 25.93 µg/mg of protein, 57.84 units/mg protein and 0.08 µM/mg protein, respectively) significantly abolished the respective derangements induced by sodium arsenite. Further, this combination significantly prevented rise in serum cholesterol and triglyceride levels that was induced by sodium arsenite. However, the ameliorative effects of this combination were abated by N-omega-nitro-L-arginine methyl ester (L-NAME) and glibenclamide. CONCLUSIONS: Combined therapy of Telmisartan and omega 3-fatty acids attenuated VED, by activating enzyme nitric oxide synthase (eNOS) through opening of ATP-sensitive K(+) channels.

Phytochemicals and their potential usefulness in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with unclear etiology, namely ulcerative colitis and Crohn's disease. Various drug therapies including aminosalicylates and immunomodulators have been approved for use; they have shown to produce diverse side effects. To overcome these limitations of the current therapeutics for IBD, extensive research is underway to identify drugs that are effective and free of undesirable side effects. Recently, various naturally occurring phytochemicals that cover a wide range of chemical entities such as polyphenols, terpeniods, flavonoids, and alkaloids have received attention as alternative candidates for IBD therapy. These phytochemicals act by modulating the immune response, various transcription factors, or reduce cytokine secretion. This review summarizes the findings of recent studies on phytochemicals as therapeutic agents in the management of IBD.

Detoxification of Abrus precatorius L. seeds by Ayurvedic Shodhana process and anti-inflammatory potential of the detoxified extract.

BACKGROUND: Abrus precatorius seeds traditionally used for the treatment of sciatica and alopecia contains the toxic protein, abrin, a Type II Ribosome Inactivating Protein. Ayurveda recommends the use of Abrus seeds after the Shodhana process (detoxification). OBJECTIVE: The current study was aimed at performing the Shodhana process, swedana (boiling) of Abrus precatorius seeds using water as a medium and to evaluate the anti-inflammatory potential of seed extract post detoxification. MATERIALS AND METHODS: Non-detoxified and detoxified extracts were prepared and subsequently subjected to various in vitro and in vivo assays. In hemagglutination assay, the non-detoxified extract shows higher agglutination of RBCs than detoxified extract indicating riddance of toxic hemagglutinating proteins by Shodhana. This was confirmed by the SDSPAGE analysis of detoxified extract revealing the absence of abrin band in detoxified extract when compared to non-detoxified extract. RESULTS: The cytotoxicity assay in HeLa cell line expresses a higher reduction in growth percentage of the cells with non-detoxified extract as compared to detoxified extract indicating successful detoxification. Brine shrimp lethality test indicated the reduction in toxicity index of detoxified extract as compared to non-detoxified extract. Further, the whole body apoptosis assay in zebrafish revealed that percentage of viable cells were greater for detoxified extract than non-detoxified extract. The anti-inflammatory studies using carrageenan induced paw edema model in rats was carried out on the extracts with doses of 100 mg/kg and 200 mg/kg, per oral, where the detoxified extract exhibited significant inhibition of rat paw edema at both the doses comparable to that of Diclofenac sodium. CONCLUSION: Absence of toxicity and the retention of the anti-inflammatory activity of detoxified Abrus seed extract confirmed that the Swedana process is effective in carrying out the detoxification without affecting its therapeutic potential.

Coenzyme q10 abrogated the 28 days aluminium chloride induced oxidative changes in rat cerebral cortex.

OBJECTIVE: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. MATERIALS AND METHODS: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. RESULTS: Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. CONCLUSION: Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3.

Hepatoprotective activity of polyherbal formulation (Normeta) in oxidative stress induced by alcohol, polyunsaturated fatty acids and iron in rats.

In recent years, oxidative stress has been implicated in the pathophysiology of a large number of diseases or disorders which are initiated and/or exacerbated by pro-oxidants such as various drugs including alcohol and food additives. The present study was carried out to evaluate the effects of oral treatment with polyherbal formulation Normeta (2 ml and 4 ml/kg) on hepatic damage induced by alcohol 10-30% (blood alcohol was maintained at levels between 150 and 350 mg/dl), thermally oxidized oil (polyunsaturated fatty acids) (15% of diet) and carbonyl iron (1.5-2% of diet) for 30 days in rats. In vitro studies with 1, 1-Diphenyl, 2-Picrylhydrazyl (DPPH), Nitric oxide and Ferric chloride (Fe(+3) ions) showed that Normeta possesses antioxidant and metal chelating activity. Alcohol, polyunsaturated fatty acids and iron feeding produced an increase in serum levels of iron, serum glutamate pyruvate transaminase and decrease in serum proteins. It was also associated with elevated lipid peroxidation (thiobarbituric acid reactive substances) and disruption of antioxidant defence mechanism in liver, decreased body weight and increased liver to body weight ratio. Oral administration of Normeta along with alcohol, polyunsaturated fatty acids and iron decreased the serum iron, serum glutamate pyruvate transaminase levels and increased serum protein levels. The levels of liver thiobarbituric acid reactive substances were decreased and the activities of antioxidant enzymes superoxide dismutase and catalase were increased. Improvement in body weight and liver to body weight ratio was also observed. The effects of Normeta on physico-metabolic parameters were comparable with silymarin. This indicates that Normeta has favourable effect in bringing down the severity of hepatotoxicity.