Esculetin Mitigates Ethanol and Lipopolysaccharide-Induced Hepatotoxicity in Male Wistar Rats: Anti-apoptotic and Anti-inflammatory Mechanisms

Ethanol-induced liver disease is a major global health concern. This study investigated the protective effects of esculetin against hepatotoxicity induced by ethanol and ethanol combined with lipopolysaccharide (LPS) in rats, with a focus on its anti-apoptotic and anti-inflammatory mechanisms. In this experiment, thirty adult male Wistar rats were randomly assigned to five groups (six rats per group). The rats received ethanol (5 mL/kg b.w) for 10 days, followed by a single intraperitoneal dose of LPS (5 mL/kg b.w) on the 11th day. Esculetin was administered orally at 50 mg/kg b.w for the same 11-day period, one hour before ethanol or LPS administration. At the end of the study, hepatotoxicity was assessed through biochemical, histopathological, immunohistochemical, and mRNA expression analyses. Biochemical evaluation revealed significant increases in bilirubin, creatinine, and phase II detoxification enzymes, along with reductions in phase I detoxification enzymes in the ethanol and ethanol+LPS groups. Additionally, ethanol and ethanol+LPS exposure upregulated the expression of Bax, caspase-3, TNF-α, NF-κB, and COX-2, while downregulating Bcl-2 expression. However, esculetin treatment mitigated these biochemical and molecular alterations, restoring them closer to normal levels compared to the ethanol and ethanol+LPS groups. These findings suggest that esculetin may serve as a potential therapeutic agent for ethanol-induced liver injury by exerting anti-apoptotic and anti-inflammatory effects. Further research using this model could provide valuable insights into the mechanisms underlying alcoholic liver disease in humans

Hepatoprotective Effect of Quinic Acid Against Ethanol-Induced Liver Toxicity in Rats: Biochemical, Physiological, and Histological Insights

Alcohol consumption is associated with several health issues, including Alcoholic Liver Disease (ALD). Quinic acid, a cyclic polyol compound, is known for its antioxidant, anticancer, anti-inflammatory, and hepatoprotective properties. This study aims to elucidate the protective mechanisms of quinic acid against ethanol-induced liver toxicity in rats. Male rats (n=32) were divided into four groups (n=8 per group) and treated over 60 days. Group 1 received a standard diet with isocaloric glucose; Group 2 was treated with 30% ethanol daily; Group 3 received 30% ethanol and quinic acid (50 mg/kg) from day 31; Group 4 was given glucose and quinic acid from day 31. Biochemical, physiological, and histological evaluations were performed post-treatment. Ethanol-treated rats exhibited significant decreases in body weight, abnormal liver morphology, increased liver enzyme levels (AST, ALT, ALP, and GGT), disrupted lipid and renal profiles, and altered phase I and II enzyme activities. Quinic acid supplementation in ethanol-treated rats significantly reversed these changes by improving body weight, restoring liver morphology, normalizing liver enzyme activities, and maintaining lipid-lipoprotein balance and enzyme levels. Histopathological analysis demonstrated reduced liver damage in quinic acid-treated groups. Quinic acid exhibits hepatoprotective effects against ethanol-induced toxicity by reducing oxidative stress, normalizing liver functions, and preserving liver structure. These findings highlight its potential as a therapeutic agent for managing ALD

Biochemical Alterations in the Haemolymph of Silkworm [Bombyx mori (L).(Lepidoptera: Bombycidae)] Fed with Mulberry Leaves Enriched with Indian Bean (Dolichos lablab)

A study was carried out to evaluate the effect of Indian bean (Dolichos lablab) supplementation on silkworm. Finely powdered Dolichos lablab was dissolved in distilled water and diluted to 2.5 %, 5 %, 7.5 % and 10 % concentrations. Fresh mulberry leaves (Morus alba L.) were sprayed by each concentration and were fed to silkworms, from 3rd to 5th instar, five feedings/day. Group 1 larvae received mulberry leaves sprayed with distilled water and served as control, group 2  larvae received 2.5% Dolichos lablab sprayed mulberry leaves, group 3 larvae received 5 % Dolichos lablab sprayed mulberry leaves, group 4 larvae received 7.5 % Dolichos lablab sprayed mulberry leaves and group 5 larvae received 10 % Dolichos lablab sprayed mulberry leaves. Silkworm larvae fed on Morus alba. L. (mulberry) leaves enriched with 7.5 % concentrations of Dolichos lablab, significantly gained more Cocoon weight, Shell weight and Shell/cocoon ratio as compared to those fed on normal MR2 mulberry leaves. Hence, 7.5% dose was fixed as an effective dose. Further, same study was conducted to find out the biochemical changes in the haemolymph occurred in the first day of Vth instar larvae. There was a significant increase in the haemolymph glucose, cholesterol, urea, total protein, aspartate transaminase, alanine transaminase and alkaline phosphatase. But haemolymph uric acid was significantly decreased. The results suggest that coadministration of   Dolichos lablab with mulberry leaves at a concentration of 7.5% has enhanced the biochemical reaction involved in the silk production in the silkworm.  ÂÂ

INSIGHTS INTO THE MOLECULAR AND BIOCHEMICAL ROLE OF QUINIC ACID IN ALLEVIATING ETHANOL-INDUCED LIVER TOXICITY IN A RAT MODEL: EXPLORING OXIDATIVE STRESS, INFLAMMATION, AND APOPTOSIS SIGNALING PATHWAYS

Objective: The study aimed to evaluate the effects of quinic acid, a natural bioactive compound, on tissue and circulatory antioxidant status, lipid peroxidation, and its anti-apoptotic and anti-inflammatory mechanisms in ethanol-induced hepatotoxicity in rats. Methods: The rats were divided into four groups. Groups 1 and 4 were administered isocaloric glucose. Groups 2 and 3 received 30% ethanol at a dose of 5 g/kg body weight daily. In addition, Groups 3 and 4 were treated with quinic acid (50 mg/kg body weight) dissolved in 2% dimethyl sulfoxide. Results: The results demonstrated significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and lipid hydroperoxides (LOOH), along with significantly reduced enzymatic and non-enzymatic antioxidant activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione-related enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST), as well as reduced levels of glutathione (GSH), Vitamin C, and Vitamin E in ethanol-treated rats compared to the control group. Administration of quinic acid to rats with ethanol-induced liver injury significantly reduced the levels of TBARS, LOOH, and CD while markedly increasing the activity of SOD, CAT, GPx, GR, GST, and levels of GSH, Vitamin C, and Vitamin E in liver tissues compared to untreated ethanol-exposed rats. In addition, ethanol-treated rats showed increased mast cell accumulation, which was reduced by quinic acid treatment, along with elevated expressions of inflammatory and apoptotic markers, including Bax, Caspase-9, tumor necrosis factor-alpha, Nuclear factor kappa B, and interleukin-6, and a decreased expression of Bcl2 in the liver. Quinic acid supplementation in ethanol-fed rats reversed these ethanol-induced changes. Immunohistochemical studies further supported these findings. Conclusion: Quinic acid, with its antioxidant, anti-inflammatory, and anti-apoptotic properties, may offer a therapeutic option for protecting against ethanol-induced hepatotoxicit

Effect of aqueous extracts of <em>Enicostema axillare</em> and <em>Toddalia asiatica</em> on complement system alternative pathway activity

628-633Complement system, precisely, the Alternative complement pathway (AP) is the first line of defence against microbial infection. Herbal extracts are known to suppress as well as boost these pathways and have applications accordingly. Here, we explored the effect of aqueous extracts of two commonly used medicinal plants Enicostema axillare (Poir. ex Lam.) A.Raynal (AEEA) and Toddalia asiatica (L.) Lam. (AETA), on in vitro and in vivo AP activity and also compared factor B activity with that of the known immunostimulant levamisole. The in vitro results revealed a concentration dependent increase in the AP for levamisole, AEEA and AETA. The in vivo AP and factor B were studied using rat animal model. The studies were carried out independently using Veronal Buffer Saline (VBS)-AP buffer and Triethanolamine (TEA)-AP buffer to compare the suitability of TEA buffer. The AP activity in terms of concentration of the sample required to cause 50 % hemolysis (APC50) and factor B activity of AEEA and AETA treated animals were significantly (P P P P < 0.05). The results sugggest VBS buffer to be more sensitive than TEA buffer