In vitro and in vivo evaluation of pterostilbene for the management of diabetic complications.

BACKGROUND: Aldose reductase (AR) and Advanced glycation end product (AGE) are known to play important roles in the development of diabetic complications. The inhibitors of AR and AGE would be potential agents for the prevention of diabetic complications. OBJECTIVE: The present study was aimed to evaluate the aldose reductase (AR) and advanced glycation end product (AGE) inhibitory potential of pterostilbene for its possible role in the treatment of diabetic complications such as cataract. MATERIALS AND METHODS: The compound was studied for its inhibitory activity against rat lens AR (RLAR) and rat kidney AR (RKAR) in vitro along with its ability to inhibit the formation of AGEs. Anticataract activity of pterostilbene was demonstrated using sugar induced lens opacity model in isolated cattle lens. Further, the involvement of pterostilbene in galactosemia in rats was investigated by assessing the key markers in the polyol pathway and the results were compared with that of a potent AR inhibitor, fidarestat. RESULTS: Pterostilbene exhibited inhibitory activity against RLAR and RKAR with IC50 values of 5.49 mg/ml (21.4 mM) and 6.40 mg/ml (25.02 mM), respectively. In sugar-induced lens opacity model, pterostilbene displayed a significant protective effect by preventing opacification and formation of polyols in cattle lens. Besides, the compound exhibited in vivo inhibition of galactitol accumulation in lens and sciatic nerves of galactose fed rats. CONCLUSION: The results obtained in the study underline the potential of pterostilbene as possible therapeutic agent against long-term diabetic complications.

Simultaneous determination of linagliptin and metformin by reverse phase-high performance liquid chromatography method: An application in quantitative analysis of pharmaceutical dosage forms.

To enhance patient compliance toward treatment in diseases like diabetes, usually a combination of drugs is prescribed. Therefore, an anti-diabetic fixed-dose combination of 2.5 mg of linagliptin 500 mg of metformin was taken for simultaneous estimation of both the drugs by reverse phase-high performance liquid chromatography (RP-HPLC) method. The present study aimed to develop a simple and sensitive RP-HPLC method for the simultaneous determination of linagliptin and metformin in pharmaceutical dosage forms. The chromatographic separation was designed and evaluated by using linagliptin and metformin working standard and sample solutions in the linearity range. Chromatographic separation was performed on a C18 column using a mobile phase of 70:30 (v/v) mixture of methanol and 0.05 M potassium dihydrogen orthophosphate (pH adjusted to 4.6 with orthophosphoric acid) delivered at a flow rate of 0.6 mL/min and UV detection at 267 nm. Linagliptin and metformin shown linearity in the range of 2-12 µg/mL and 400-2400 µg/mL respectively with correlation co-efficient of 0.9996 and 0.9989. The resultant findings analyzed for standard deviation (SD) and relative standard deviation to validate the developed method. The retention time of linagliptin and metformin was found to be 6.3 and 4.6 min and separation was complete in <10 min. The method was validated for linearity, accuracy and precision were found to be acceptable over the linearity range of the linagliptin and metformin. The method was found suitable for the routine quantitative analysis of linagliptin and metformin in pharmaceutical dosage forms.

Therapeutic potential of resveratrol in diabetic complications: In vitro and in vivo studies.

BACKGROUND: Various mechanisms with a complex integrating paradigm have been implicated in diabetic complications. The present study was aimed to evaluate the aldose reductase (AR) and advanced glycation end products (AGEs) inhibitory activity of resveratrol (RSV) and its potential in the treatment of diabetic complications such as cataract and nephropathy. METHODS: RSV was studied for its inhibitory activity against rat lens AR (RLAR) and rat kidney AR (RKAR) in vitro along with its ability to inhibit formation of AGEs. Anticataract activity of RSV was demonstrated using sugar induced lens opacity model in isolated cattle lens. Furthermore the involvement of RSV in streptozotocin-induced diabetic nephropathy was investigated by assessing the key markers of kidney function along with the formation of AGEs. The potent AR inhibitor, fidarestat was as a standard. RESULTS: RSV exhibited inhibitory activity against RLAR and RKAR with IC50 values of 4.99 µg/ml (21.9 µM) and 5.49 µg/ml (24.5 µM), respectively. It also showed a significant inhibition of AGEs formation in vitro. In sugar-induced lens opacity model, RSV displayed a significant protective effect preventing opacification and formation of polyols in cattle lens. RSV significantly improved glycaemic status and renal function in diabetic rats with a significant decrease in the formation of AGEs in the kidneys. CONCLUSIONS: The results obtained in this study underline the potential of RSV as a possible therapeutic agent against long-term diabetic complications.

Targeting oxidative stress attenuates trinitrobenzene sulphonic acid induced inflammatory bowel disease like symptoms in rats: role of quercetin.

OBJECTIVE: This study was aimed to investigate the beneficial effects of quercetin (QCT) against trinitrobenzene sulfonic acid (TNBS) induced clinical, morphological, and biochemical alterations in rats. MATERIALS AND METHODS: Colitis in rats was induced by administration of TNBS (25 mg dissolved in 0.25 ml of 30% ethanol) 8 cm into the rectum of the rat using a catheter. The animals were divided into six experimental groups (n = 6); naive (saline only without TNBS administration), control (saline + TNBS), standard (sulfasalazine 25 mg/kg + TNBS), QCT (25) (QCT 25 mg/kg + TNBS), QCT (50) (QCT 50 mg/kg + TNBS), QCT (100) (QCT 100 mg/kg + TNBS). Sulfasalazine (25 mg/kg) and QCT (25, 50 and 100 mg/kg) were administered per oral for 11 days and the colonic damage was evaluated in terms of macroscopical (body weight, stool consistency, rectal bleeding, and ulcer index) and biochemical parameters (myeloperoxidase activity, lipid peroxidation, nitrite, and glutathione). RESULTS: Treatment with QCT (50, 100 mg/kg) for 10 days following TNBS administration significantly attenuated the clinical, morphological, and biochemical alterations induced by TNBS, whereas it was found to be not effective at its lower dose (25 mg/kg) throughout the experimental protocol. CONCLUSION: QCT attenuates the clinical, morphological and biochemical alterations induced by TNBS possibly via its antioxidant mechanism.

Protective effect of quercetin against acetic acid induced inflammatory bowel disease (IBD) like symptoms in rats: possible morphological and biochemical alterations.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by most common symptoms such as rectal bleeding. Lack of specific, curative treatments tempted us to evaluate the therapeutic efficacy of quercetin against acetic acid induced IBD like symptoms. METHODS: Animals were randomly divided into five groups (n = 6): naive, control, sulphasalazine and quercetin, and were pretreated for three days. Colitis was induced by intra-rectal administration of 3% acetic acid. RESULTS: Pretreatment with sulphasalazine or quercetin significantly attenuated the biochemical and morphological alterations in the colon induced by acetic acid in rats. CONCLUSIONS: The findings of the study suggest the possible role of quercetin as therapeutics in IBD.