Therapeutic Versus Preventative Use of Ginkgo biloba Extract (EGb 761) against Indomethacin-Induced Gastric Ulcer in Mice.

The main bioactive constituents in the standardized Ginkgo biloba leaf extract (EGb 761) are the terpene lactones and flavonoid glycosides. EGb 761's antioxidant and anti-inflammatory properties have previously been demonstrated. Indomethacin-induced gastric ulcers have a multifactorial etiology and represent a major restriction to its therapeutic utility. The underlying ulcerogenic process involves oxidative and inflammatory biomolecular insults. This study was performed to explore the curative and preventative benefits of EGb 761 in experimentally-induced ulcers. To develop gastric ulcers in mice, indomethacin (40 mg/kg) was administered orally. EGb 761 (200 mg/kg) was given by gavage for 7 days before (preventative) and after (therapeutic) indomethacin administration. The histological alterations and macroscopic mucosal lesions were assessed. In gastric tissue homogenates, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and inflammatory cytokines were measured. The expressions of cyclooxygenase-2 (COX-2), cytokines, and proliferating cell nuclear antigen (PCNA) in the stomach mucosa were also investigated. The ulcer index, histological alterations, gastric oxidants, and inflammatory biomarkers were all significantly increased by indomethacin. In stomach specimens, it increased COX-2 and PCNA expression. EGb 761 treatments, both prophylactic and therapeutic, resulted in significant reductions in ulcer lesions, nitrosative and oxidative damage, and inflammatory markers, along with the lowering of COX-2 and PCNA expressions. Furthermore, in the fight against stomach ulcers, EGb 761 treatment was found to be more efficient than prevention.

Effect of l-carnitine supplementation on lead acetate-induced liver cell apoptosis and inflammation: role of caspase-3 and glycogen synthase kinase-3ß enzymes.

AIM: The study aimed at studying the hepatoprotective effect of l-carnitine against lead (Pb) acetate-induced hepatocellular injury, emphasizing the role of caspase-3 and glycogen synthase kinase-3ß in hepatocellular apoptosis and inflammation. MATERIALS AND METHODS: Male Wistar rats were used. The experimental approach involved estimation of the liver enzymes' serum levels. Oxidative and inflammatory biomarkers were measured in hepatic tissue homogenates. Paraffin-embedded hepatic sections were prepared for histopathology and immunohistochemistry. Quantitative determination of the phosphorylated glycogen synthase kinase-3 beta was performed. KEY FINDINGS: The serum showed a significant elevation in ALT, AST, and LDH; tissue homogenates showed significant elevation in lipid peroxide and inflammatory biomarkers with significant reduction in reduced glutathione in the Pb acetate-treated group. Co-administration of l-carnitine with Pb acetate produced significant reduction in liver enzymes with significant improvement in oxidant, antioxidant and inflammatory markers. Lead acetate treatment significantly reduced the phosphorylated glycogen synthase kinase-3 beta, while l-carnitine enhanced its phosphorylation. Histopathological examination showed inflammatory reaction around blood vessels with fatty degeneration in hepatocytes of the Pb acetate intoxicated group. l-Carnitine caused a decrease in hepatic damage with minimal vascular alterations in central vein. Caspase-3 expression in hepatocytes was decreased in Pb-treated group supplemented with l-carnitine. SIGNIFICANCE: Our study reveals that oxidative stress and inflammation participate in Pb acetate-induced hepatocellular injury. Glycogen synthase kinase-3ß and caspase-3 play role in Pb acetate-induced hepatic damage. l-Carnitine shows significant protective effects against hepatocellular apoptosis and inflammation induced by Pb acetate through antioxidant, anti-inflammatory and anti-apoptotic pathways in part mediated by GSK-3ß inhibition.

Systemic and topical Ginkgo biloba leaf extract (Egb-761) ameliorated rat paw inflammation in comparison to dexamethasone.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo Biloba leaf extract (Egb-761) is used for treating various inflammatory disease conditions therefore this study was performed. AIM OF THE STUDY: The present study aimed at comparing the ameliorative effects of both systemic and topical Egb-761 versus dexamethasone on carrageenan-induced hind paw inflammation in rats. MATERIAL AND METHODS: Wistar albino rats were injected with carrageenan solution in the sub-planter region of the right hind paw. Egb-761 and dexamethasone were administered systemically to two groups while Egb-761 ointment 2% and dexamethasone sodium phosphate ointment were applied topically for another two groups. Vernier Caliper was used to assess rat paw thickness. Tissue malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor-α (TNF-α) levels have been estimated. RESULTS: Carrageenan induced a significant rat paw edema and inflammation noticed 1 h post-injection as well as an increase of MDA, NO, and TNF-α in the inflamed skin tissues compared to the control group. Systemic and topical administration of Egb-761 and dexamethasone resulted in a significant reduction in carrageenan-induced rat paw edema. They reduced the tissue levels of MDA, NO, and TNF-α. Dexamethasone showed a little bit superior anti-inflammatory and antioxidant efficacy over Egb-761. CONCLUSION: Our findings indicate the possibility of the therapeutic value of Egb-761 for alleviation of local inflammation by attenuating the increased MDA, NO and TNF-α levels.

Ameliorative effect of L-carnitine on chronic lead-induced reproductive toxicity in male rats.

Lead toxicity is one of the causative agents of male infertility that raised concern from environmental contamination worldwide. L-carnitine, a biologically active amino acid, present in high concentration in the reproductive organs such as the epididymis, is involved in sperm maturation. The possible protective effect of L-carnitine in experimentally lead-induced male reproductive toxicity in rats was evaluated in this study. Thirty adult male Wistar rats were divided into three groups. Group 1: the negative control group was treated with normal saline; Group 2: exposed to 50 mg/kg lead acetate (2% solution in saline); and Group 3: treated with lead acetate 50 mg/kg (2% solution in saline) + L-carnitine 100 mg/kg. At the end of the experimental period, body and testicular weights were determined, blood samples were withdrawn for hormonal assays of FSH, LH and testosterone. Sperm parameters as sperm count, morphology, viability and motility were measured. Testicular tissue homogenates were prepared for enzymatic assays and for measuring oxidative stress parameters. Lead significantly increased both oxidative stress and the concentration of lactate dehydrogenase-C in the testicular tissues with a decrease in sperm count, motility and viability. Lead acetate treatment, induced alteration in sperms with normal morphology together with reductions in the serum FSH, LH, testosterone, body and testicular weights. The concentration of 17ß-hydroxysteroid dehydrogenase was significantly reduced. Co-administration of L-carnitine significantly reduced testicular oxidative stress, improved sperm parameters, elevated serum FSH, LH and testosterone with an insignificant reduction in the testicular weight. The concentrations of 17ß-hydroxysteroid dehydrogenase and lactate dehydrogenase-C were significantly improved by L-carnitine. The overall results indicate that L-carnitine is expected to improve the lead acetate-induced male reproductive toxicity.