Mechanism of immunoprotective effects of curcumin in DLM-induced thymic apoptosis and altered immune function: an in silico and in vitro study.

Curcumin, a main component of Curcuma Longa Linn, is a plant polyphenol used as an immune-enhancer in the Indian system of traditional medicine. However, its underlying mechanism of immune-protection remains unknown. The present study is designed to delineate the role of curcumin in deltamethrin (DLM)-induced thymocyte apoptosis and altered immune functions. In silico studies revealed that curcumin has a strong binding affinity toward CD4 and CD8 receptors. DLM (25 µM) induces thymocytes apoptosis through oxidative stress and caspase-dependent pathways. Various concentrations of curcumin (1, 10 and 50 µg/ml), when added along with DLM, caused a concentration- and time-related amelioration in apoptogenic signaling pathways induced by DLM. Inhibition of DLM-induced reactive oxygen species production, replenishment of glutathione and suppression of caspase activities by curcumin may thus be responsible for the suppression of downstream cascade of events, i.e. apoptosis, phenotypic changes and altered cytokine release. Thus, this study clearly demonstrates that the mechanism of immunoprotection of curcumin in DLM-induced thymic apoptosis includes inhibition of oxidative stress and caspase-dependent pathways underlying apoptosis.

Antidiabetic activity of Pterospermum acerifolium flowers and glucose uptake potential of bioactive fraction in L6 muscle cell lines with its HPLC fingerprint.

The present study was designed to estimate the detailed antidiabetic activity of Pterospermum acerifolium (L.) Willd flowers. In vitro alpha amylase inhibition study was carried out on 50% ethanol extract of flowers (PAFEE) and its various fractions. The active ethyl acetate fraction (PAFEF) was subfractionated into three subfractions (PAFE1, PAFE2, and PAFE3) and subjected to acute toxicity studies followed by antidiabetic screening in vivo by streptozotocin-nicotinamide induced type II diabetes. Diabetic animals treated with PAFE2 (30 mg/kg) reduced the levels of fasting blood glucose, significantly (P<0.001) compared to that of diabetic control animals. Histological studies on drug treated groups did not show remarkable positive changes in ß-cells. PAFE2 showed 32.6±1.93% glucose uptake over control and, in the presence of PI3K inhibitor wortmannin, declined to 13.7±2.51%. HPLC analysis of PAFE2 reveals the presence of quercetin and apigenin as major constituents and both are inhibiting the glycogen phosphorylase enzyme in molecular modelling studies. The study evidenced strongly that the probable glucose lowering mechanism of action of active subfraction PAFE2 is by increasing the glucose uptake in peripheral tissues and by inhibition of gluconeogenesis.

Evaluation of in silico, in vitro α-amylase inhibition potential and antidiabetic activity of Pterospermum acerifolium bark.

CONTEXT: Pterospermum acerifolium (L.) Willd (Sterculiaceae) has been traditionally used in the treatment of diabetes mellitus but no scientific data has been published supporting the claimed ethnomedical use. OBJECTIVE: The present study was designed to estimate the in silico, in vitro α-amylase inhibition potential and anti-diabetic activity of Pterospermum acerifolium bark. MATERIALS AND METHODS: In silico studies were performed between human pancreatic α-amylase (HPA) and ß-sitosterol by using autodock 4.2 software. In vitro α-amylase inhibition study was carried out with 50% ethanol extract of the bark (PABEE) and its various fractions. The active ethyl acetate fraction (PABEF) was sub-fractionated into three fractions (PABE1, PABE2 and PABE3). Two doses (15 and 30 mg/kg) based on acute toxicity studies, of the above fractions were subjected to antidiabetic screening in vivo by STZ-nicotinamide induced type II diabetic rats. RESULTS: In silico studies showed the potent inhibition of ß-sitosterol on human pancreatic amylase (HPA) with an estimated inhibition constant (Ki) of 269.35 nmol and two hydrogen bond interactions. PABEF showed marked α-amylase inhibition (69.94%) compared to other fractions. Diabetic rats treated with PABE3 (30 mg/kg) reduced the levels of fasting blood glucose, HbA1c, ALT, AST, ALP, triglycerides, total cholesterol, TBARS significantly (p < 0.01) and increased the levels of HDL-C, catalase, GSH, SOD significantly (p < 0.01) as compared to that of diabetic control animals. Histological studies on PABE3 treated group showed remarkable positive changes in ß-cells. CONCLUSION: The present study confirmed the antihyperglycemic activity along with its status on hepatic biomarkers, antihyperlipidemic and antioxidant properties of Pterospermum acerifolium bark.

Evaluation of antiarthritic and immunomodulatory activity of Barleria lupulina

Objective: Barleria lupulina Lindl (Acanthaceae) (B. lupulina) has been traditionally used in the treatment of rheumatoid arthritis but, no scientific data has been published supporting the claimed ethnomedical use. This study was designed to investigate the anti-arthritic potential of B. lupulina leaves and its role in immunomodulation. Methods: Methanol extract of B. lupulina (MEBL) leaves (300 and 600 mg/kg BW) was tested for its antiarthritic activity by various models namely, formalin-induced arthritis, adjuvant induced arthritis, collagen type II-induced arthritis and monosodium iodoacetate induced osteoarthritis. Immunomodulatory activity of the same was tested by measuring WBC Count, Spleen Weight, Spleen WBC Count and Delayed Type Hypersensitivity (DTH) Reaction.Results:MEBL extracts 300 mg/kg and 600 mg/ kg showed statistically significant inhibition (P<0.05 and P<0.001) of the edema formation and Myeloperoxidase (MPO) during experimental period and activities of antioxidants were restored significantly. MEBL extracts 300 mg/kg and 600 mg/kg significantly increased the Hemoglobin (Hb) level, serum albumin, total protein, calcium and phosphorus levels and reverted back the levels of WBC count and Erythrocyte Sedimentation Rate (ESR) (P<0.05 and P<0.01). Histopathological studies of ankle joints also supported this finding. Immunomodulatory study revealed an increase in the blood leukocytes count, weight of spleen, spleenic leukocytes count and increase in paw volume on delayed type hypersensitivity footpad thickness suggesting an uplift of immune status. Conclusions: The present study concluded that, MEBL holds antiarthritic and Immunomodulatory activity. Although subsequent study is required to evaluate the active constituents responsible for the activity.

Aqueous extract of Boerhaavia diffusa root ameliorates ethylene glycol-induced hyperoxaluric oxidative stress and renal injury in rat kidney.

INTRODUCTION: Boerhaavia diffusa Linn. (Nyctaginaceae) is widely used in traditional Indian medicines against renal afflictions including calcium oxalate (CaOx) urolithiasis and is known for antioxidant activity. OBJECTIVE: The present study was designed to investigate the ameliorating effect of aqueous extract of B. diffusa roots (BDE) in hyperoxaluric oxidative stress and renal cell injury. MATERIAL AND METHODS: In vitro antioxidant activity of BDE was estimated in terms of total phenolic content and 1,1-diphenyl-2-picryl hydrazyl free radical scavenging activity. Wistar albino rats were given 0.75% v/v ethylene glycol in drinking water to induce chronic hyperoxaluria and simultaneously BDE was given to nephrolithiasic treated rats at the dose of 100 and 200 mg/kg b.w. orally for 28 days. Urinary volume, oxalate, serum creatinine, blood urea nitrogen (BUN), malondialdehyde (MDA) and antioxidant enzyme (SOD, CAT, GST, GPx) were evaluated. RESULTS AND DISCUSSION: BDE extract was found to posses a high total phenolic content and exhibited significant free radicals scavenging activity. Oxalate excretion significantly increased in hyperoxaluric animals as compared to control which was protected in BDE-treated animals. BDE treatment significantly reduced level of MDA and improved the activity of antioxidant enzymes followed by reduction in BUN and serum creatinine. In addition, BDE reduced the number of CaOx monohydrate crystals in the urine. Histological analysis depicted that BDE treatment inhibited deposition of CaOx crystal and renal cell damage. CONCLUSION: The present study reveals that antioxidant activity of BDE significantly protects against hyperoxaluric oxidative stress and renal cell injury in urolithiasis.

Anti-inflammatory and antinociceptive activity of arbortristoside-A.

Nyctanthes arbortristis Linn is a well-documented plant. It is evident from literature and previous investigations that Nyctanthes arbortristis possesses anti-inflammatory and analgesic activity. In the present study arbortristoside-A has been isolated from the ethanolic extract of its seeds. The structure of the isolated compound was determined by chemical reactions and spectroscopic methods. Arbortristoside-A was found to possess significant and dose-dependent anti-inflammatory and antinociceptive activity. It seems arbortristoside-A inhibited the histamine, serotonin and carrageenan-induced edema suggesting its inhibiting effect on carrageenan, arachidonic acid, histamine and serotonin-induced edema suggesting its anti-inflammatory activity may be due to the inhibiting effect of prostaglandin, histamine and serotonin. The analgesic activity of arbortristoside-A may be due to the inhibition of the action of prostaglandin.