Pinaki Ghosh

Therapeutic role of curcumin in prevention of biochemical and behavioral aberration induced by alcoholic neuropathy in laboratory animals

Painful peripheral neuropathy induced by chronic ethanol consumption is a major medico-socioeconomical problem. The objective of present investigation was to study the effect of curcumin (20, 40 and 80mg/kg; p.o.) in alcohol-induced neuropathy in rats. Ethanol (35% v/v, 10g/kg; p.o.) was administered for 10 weeks which showed a significant decrease in thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia and nerve conduction velocity. It caused enhanced malondialdehyde, oxidative-nitrosative stress, total calcium levels, inflammatory mediators (TNF-α and IL-1β levels) along with DNA damage. Co-administration of curcumin and α-tocopherol for 10 weeks significantly and dose-dependently improved nerve functions, biochemical as well as molecular parameters and DNA damage in sciatic nerve of ethanol treated rats. Hence, it was concluded that curcumin is of potent therapeutic value in the amelioration of alcoholic neuropathy in rats and acts by inhibition of pro-inflammatory mediators like TNF-α and IL-1β.

Effect of hydroalcoholic extract of Hibiscus rosa sinensis Linn. leaves in experimental colitis in rats.

OBJECTIVE To elucidate the ameliorative effect of hydroalcoholic extract of leaves of Hibiscus rosa sinensis (HRS) in acetic acid induced experimental colitis in male wistar rats. METHODS The animals were administered with 2 mL acetic acid (4%) via intra rectal. The animals were divided into various treatment groups (n=6). Prednisolone was used as standard drug and HRS was administered at a dose of 50, 100 and 200 mg/kg p.o. The control group of animals received 1 mL of vehicle (distilled water). Ulcer area, ulcer index, spleen weight, colon weight to length ratio, macroscopic score, haematological parameters, colonic superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and histological changes were recorded after the treatment regimen of 11 days. RESULTS Intrarectal instillation of acetic acid caused enhanced ulcer area, ulcer index, spleen weight, colon weight to length ratio, colonic MPO, MDA, NO and TNF-α It caused significant decreased level of SOD and GSH. Pretreatment with HRS for 7 days exhibited significant effect in lowering of oxidative stress, colonic NO, TNF-α and elevation of SOD and GSH at a dose of 100 and 200 mg/kg in acetic acid induced colitis. CONCLUSIONS The present investigation demonstrates HRS is of potent therapeutic value in the amelioration of experimental colitis in laboratory animals by inhibiting the proinflammatory mediator like NO and TNF-α.

Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats

Chronic, unhealed diabetic foot ulcer (DFU) is one of the most severe complications of diabetes mellitus (DM). Naringin, a flavanone glycoside antioxidant, was reported to have antidiabetic and anti-apoptotic properties. In the present study DM was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.). In surgically introduced wounds on the dorsal surface of the hind paw of rats, the healing potential of naringin was investigated. Rats were treated with naringin (20, 40 and 80 mg/kg, p.o.), insulin (10 IU/kg, s.c.) and tetrachlorodecaoxide (TCDO) (1 drop, twice a day, topically) for 16 days. The wound area was measured every second day, and on day 17 various biochemical parameters were determined in serum, wound tissue, and histopathological examination of the wound was performed. Naringin (40 and 80 mg/kg) significantly (P<0.05) improved wound area, serum glucose level, glycated Hb and serum insulin. Naringin treatment at 40 and 80 mg/kg resulted in significant (P<0.05) up-regulation of mRNA expression of growth factor (IFG-1, TGF-β and VEGF-c), Ang-1 and collagen-1 whereas mRNA expression of inflammatory mediators (TNF-α, IL-1β and IL-6) was down-regulated. Furthermore, naringin significantly (P<0.05) attenuated STZ-induced apoptosis and stimulated angiogenesis in the wound tissue. Further results suggest that angiogenesis was improved via naringin-mediated inhibition of hyperglycemia, oxidative stress, down-regulation of inflammatory mediator expression and up-regulation of growth factor expression, leading to improved wound healing of DFU.

Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions

Abstract Aim: Diabetic neuropathy (DN) is one of the most common long-term complications of diabetes mellitus and clinically can be characterized by an elevated nociceptive response with electrophysiological conduction abnormalities. The present investigation was designed to evaluate the neuroprotective effect of hesperidin against STZ induced diabetic neuropathic pain in laboratory rats. Materials and methods: DN was induced in Sprague–Dawley rats (150–200 g) by intraperitoneal administration of streptozotocin (STZ) (55 mg/kg, p.o.). Rats were divided into various groups, namely, STZ control (vehicle), hesperidin (25, 50, and 100 mg/kg, p.o.), insulin (10 IU/kg, s.c.), and combination of hesperidin (100 mg/kg, p.o.) with insulin (10 IU/kg, s.c.) for 4 weeks. Various behavioral (allodynia and hyperalgesia), biochemical parameters [oxido-nitosative stress, Na–K–ATPase, aldose reductase (AR)], and molecular changes (TNF-α and IL-1β) along with hemodynamic changes were determined. Results: Rats treated with hesperidin (50 and 100 mg/kg, p.o., 4 weeks) significantly reduced (p < 0.05) hyperglycemia and its metabolic abnormalities induced by intraperitoneal administration of STZ. The decreased nociceptive threshold, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV), serum insulin as well as Na–K–ATPase activity were significantly increase (p < 0.05) by hesperidin (50 and 100 mg/kg, p.o.) treatment. It significantly attenuated (p < 0.05) elevated glycated hemoglobin, AR activity, oxido-nitrosative stress, neural calcium, and pro-inflammatory cytokines (TNF-α and IL-1β) levels. Histological aberration induced after STZ administration was restored by administration of hesperidin (50 and 100 mg/kg, p.o.) Conclusion: In combination with insulin, hesperidin not only attenuated the diabetic condition but also reversed neuropathic pain via control over hyperglycemia as well as hyperlipidemia to down-regulate generation of free radical, release of pro-inflammatory cytokines as well as elevation in membrane bound enzyme.

Elucidation of molecular mechanism involved in neuroprotective effect of Coenzyme Q10 in alcohol-induced neuropathic pain

The aim of the present investigation was to evaluate the effect of Coenzyme Q10 and its combination with vitamin E in alcohol‐induced chronic neuropathic pain. Male Wistar rats were orally treated with alcohol (10 g/kg, 35% v/v, b.i.d.) for 10 weeks. Coenzyme Q10 (25, 50, and 100 mg/kg) and vitamin E (100 mg/kg) were coadministered orally for 1 h after ethanol administration for 10 weeks. Various nerve functions, biochemical, and molecular parameters were assessed. Chronic administration of ethanol for 10 weeks resulted significant development of neuropathic pain. Treatment with Coenzyme Q10 (50 and 100 mg/kg) for 10 weeks showed significant and dose dependently increased in level of nociceptive threshold, endogenous antioxidant, and Na,K‐ATPase enzyme. Coenzyme Q10 (50 and 100 mg/kg) significantly restored the levels of motor nerve conduction velocity and sensory nerve conduction velocity. It also showed significant decrease in levels of endogenous calcium, oxidative–nitrosative stress, TNF‐α, IL‐1β, and IL‐4 level. Alteration in protein expression of polymerase gamma (pol γ) was significantly restored the Coenzyme Q10 treatment. The important finding of the study is that, Coenzyme Q10 (100 mg/kg) and α‐tocopherol (100 mg/kg) combination‐treated rats showed more significant prevention of behavioral, biochemical, and molecular neurotoxic effect of alcohol administration than Coenzyme Q10 or α‐tocopherol alone treated group. It is evident from the finding of present investigation that plethora of mechanism including inhibition of oxido‐nitrosative stress, release of pro‐inflammatory cytokine, modulation of endogenous biomarker, and protection of pol γ protein expression simultaneously orchestrate to exhibits neuroprotective effect of Coenzyme Q10, vitamin E and their combination.

Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats.

The aim of this study was to evaluate the effect of naringin on experimentally induced inflammatory bowel disease in rats. Naringin (20, 40 and 80 mg/kg) was given orally for 7 days to Wistar rats before induction of colitis by intrarectal instillation of 2 mL of 4% (v/v) acetic acid solution. The degree of colonic mucosal damage was analyzed by examining mucosal damage, ulcer area, ulcer index and stool consistency. Intrarectal administration of 4% acetic acid resulted in significant modulation of serum alkaline phosphatase, lactate dehydrogenase, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) content along with colonic nitric oxide (NO), xanthine oxidase (XO) level and protein carbonyl content in the colonic tissue as well as in blood. Naringin (40 and 80 mg/kg) exerted a dose dependent (P < 0.05) ameliorative effect, as it significantly increased hematological parameter as well as colonic SOD and GSH. There was a significant (P < 0.05) and dose dependant inhibition of macroscopical score, ulcer area along with colonic MDA, MPO activity by the 7 days of pretreatment of naringin (40 and 80 mg/kg). Biochemical studies revealed a significant (P < 0.05) dose dependant inhibition in serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels by pretreatment of naringin. Increased levels of colonic NO, XO, protein carbonyl content and DNA damage were also significantly decreased by naringin pretreatment. The findings of the present investigation propose that naringin has an anti-inflammatory, anti-oxidant and anti-apoptotic potential effect at colorectal sites as it modulates the production and expression of oxidative mediators such as MDA, MPO, NO and XO, thus reducing DNA damage.

Endothelin receptor blocker bosentan inhibits hypertensive cardiac fibrosis in pressure overload-induced cardiac hypertrophy in rats

AimThe aim of this study was to investigate the effect of bosentan (25, 50, 100 mg/kg) on left ventricular contractile function, cardiac fibrosis, and oxidative stress in pressure overload-induced cardiac hypertrophy in rats. MethodsMale rats (200–250 g) were assigned into various groups, namely, sham, aortic constriction, aortic constriction+bosentan (25, 50, and 100 mg/kg), and sham+bosentan (100 mg/kg). Myocardial hypertrophy was produced by constriction of the abdominal aorta. Four weeks after treatment with bosentan (25, 50, and 100 mg/kg perorally), the left ventricular contractile function was measured using a Millar catheter and ECG was carried out. ResultsTreatment with bosentan (50 and 100 mg/kg perorally) significantly and dose-dependently (P<0.01 and <0.001) restored hemodynamic parameters including ECG, blood pressure, and left ventricular function. It also significantly elevated the levels of biochemical markers (P<0.001), that is, superoxide dismutase, reduced glutathione, and membrane-bound inorganic phosphate enzymes like Na+–K+-ATPase and Ca2+-ATPase. The elevated levels of creatine kinase-MB and lactate dehydrogenase enzymes, as well as the activities of malondialdehyde and tumor necrosis factor-&agr;, were significantly attenuated (P<0.05 and <0.001) by bosentan (50 and 100 mg/kg perorally) treatment. An upregulation in the mRNA expression of endothelin-1 was significantly (P<0.05 and <0.001) attenuated by bosentan (50 and 100 mg/kg perorally) treatment. Histological aberration induced after pressure overload was restored by bosentan treatment. ConclusionBosentan attenuates the development of cardiac hypertrophy by blocking the endothelin-1 receptor and improving left ventricular function; it also ameliorates endogenous biomarkers in pressure overload-induced cardiac hypertrophy in rats.

Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction

Abstract Background: Gentamicin (GM) is the commonly used antibiotics against Gram-negative infection, but the nephrotoxic potential of drug limit its clinical interest. The aim of this study was to investigate the protective effect of berberine (BER) against GM-induced nephrotoxicity and possible underlying mechanisms. Material and methods: The rats were divided into various group, namely normal, GM-control, GM + BER (10, 20, and 40 mg/kg). Nephrotoxicity was induced by intraperitoneal administration of GM (120 mg/kg) for 7 consecutive days. BER (10, 20, and 40 mg/kg; p.o.) was also administered for the 7 days. Various biochemical, molecular, and histological parameters were assessed in serum and kidney. Results: GM-administration significantly increased (p < 0.001) the serum creatinine and blood urea nitrogen (BUN) as well as renal malonaldehyde (MDA), nitric oxide (NO) along with Kidney Injury Molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor-kappa B (NF-KB) renal mRNA expressions. In addition, GM also significantly decreased (p < 0.001) the renal superoxide dismutase (SOD), reduced glutathione (GSH), B-cell lymphoma 2 (Bcl-2) mRNA expression, and mitochondrial enzymes (NADH dehydrogenase and cytochrome c oxidase) activities. Rats treated with BER (20 and 40 mg/kg; p.o.) significantly and dose-dependently (p < 0.05 and p < 0.01) restore the altered levels of antioxidant, inflammatory, apoptosis, AKI markers as well as depleted mitochondrial enzymes. Histopathological abbreviations were also ameliorated by BER administration. Conclusion: Berberine exerts renoprotective effects through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

Therapeutic effect of H. pylori nosode, a homeopathic preparation in healing of chronic H. pylori infected ulcers in laboratory animals

Abstract Objective H. pylori is classified as class I carcinogen by World Health Organization and is a global as it is the primary cause of gastric carcinoma. The objective of present investigation was made to investigate the protective effect of homeopathically potentized H. pylori nosode in rats infected with H. pylori . Methods The infection was induced in the rats using a bacterial suspension of 5 × 10 8 CFU per ml. The various animals were treated with three potencies of H. pylori nosode (3X, 6X and 12X) and standard (Clarithromycin 25mg/kg + amoxicillin 50 mg/kg + omeprazole 20 mg/kg). A period of ten weeks followed and then the rats were sacrificed. Results H. pylori nosode was able to stop the initiation of infection in the pretreatment group of animals. This defines and provides us with the data regarding its sphere of action. A plethora of parameters such as ulcer area, infection status, biomarkers of oxidative stress, total intracellular ROS, degree of apoptosis, TNF level and load of bacteria in the gastric tissue served as the hallmarks to prove the preventive role of H. pylori nosode in the amelioration of the infection. It is evident that homeopathic drug H. pylori nosode was able to transform the susceptibility of the animals to the induction of infection. It provides a novel avenue in the field of research in homeopathy as the results suggest that H. pylori nosode was able to initiate the infection resistive forces in the animals before being subjected to the infection of H. pylori . Conclusion H. pylori nosode possesses potent prophylactic anti H. pylori activity in vivo .

Determination of efficacy, adverse drug reactions and cost effectiveness of three triple drug regimens for the treatment of Helicobacter pylori infected acid peptic disease patients

Objective To evaluate the clinical outcome and Helicobacter pylori (H. pylori) infection status by GLQI and PCR, before and after the triple (CMO, CAO or LTC) treatment regimen.