Boldine protects against carbon tetrachloride-induced chronic liver injury by regulating NF-κB signaling pathway.

Sustained liver injuries predominantly promote oxidative stress and inflammation that lead to the progression of chronic liver disease (CLD), including fibrosis, cirrhosis, and hepatocellular carcinoma. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects. Currently, there is no definitive treatment option available for CLD. Therefore, we investigated the hepatoprotective effect of boldine against carbon tetrachloride (CCl4 )-induced chronic liver injury in rats. CCl4 (2 mL/kg., b.w., i.p.) was administered twice weekly for 5 weeks to induce chronic liver injury in rats. Separate groups of rats were given boldine (20 mg/kg b.w., and 40 mg/kg b.w.) and silymarin (100 mg/kg b.w.) orally, daily. Serum transaminases, lipid peroxidation, and antioxidant levels were measured, and nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (cox-2), interleukin-1 ß (IL-1ß), and α-smooth muscle actin (α-SMA) gene and protein expressions were evaluated. CCl4 administration increased liver marker enzymes of hepatotoxicity in serum and oxidative stress markers, inflammatory genes and α-smooth muscle actin expression in liver tissue. Boldine concurrent treatment suppressed CCl4 -induced elevation of transaminase levels in serum, restored enzymic and non-enzymic antioxidants, and downregulated NF-κB, TNF-α, Cox-2 and IL-1ß expressions, thereby suppressing hepatic inflammation. Boldine administration also repressed α-SMA expression. The results of this study demonstrate the antioxidant, anti-inflammatory, and antifibrotic properties of boldine, and it can be a potential therapeutic candidate in the treatment of CLD.

Lagerstroemia speciosa Pers. (Lythraceae) Ethanolic Extract Attenuates Isoniazid-Induced Oxidative Stress and Hepatic Inflammation in Rats.

Background Drug-induced liver injury is a common cause of acute liver failure. Isoniazid (INH) is used as a first-line treatment for tuberculosis. Clinical and experimental studies have reported abnormal liver function after INH therapy. Lagerstroemia speciosa Pers., commonly known as banaba, has been traditionally used to treat various ailments including diabetes and obesity due to its antioxidant and anti-inflammatory properties. Aim To investigate the hepatoprotective effect of ethanolic banaba leaf extract (EBLE) against INH-induced hepatotoxicity in rats. Materials and methods A total of 30 male Wistar albino rats (150 - 200 g) were divided into five groups (n = 6). Group I rats were served as a control and were administered dimethyl sulfoxide for the first 30 days and water for the next 30 consecutive days. Group II rats were administered INH (50 mg/kg, p.o.) once in the first 30 consecutive days and sacrificed at Day 30. Group III rats were administered INH for 30 consecutive days and left without treatment for the next 30 days. In Groups IV and V, rats were post-treated orally with EBLE 250 and 500 mg/kg, p.o. (0.3 ml/rat) for 30 days after INH administration. At the end of Day 60, the remaining group of animals were sacrificed. The blood and liver tissues were collected. The marker enzymes of hepatotoxicity, oxidative stress markers, inflammatory markers, and histopathology were analyzed. Results INH administration induced significant elevation of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transpeptidase) of hepatotoxicity in the serum. This treatment also increased lipid peroxidation and proinflammatory marker expression (tumor necrosis factor-alpha, transforming growth factor-beta, and nuclear factor kappa B (NF-κB) except inhibitor of NF-κB) and decreased antioxidants such superoxide dismutase, catalase, and glutathione in the liver tissue. All these abnormalities were significantly mitigated after treatment with EBLE. Conclusion The results of this study suggest that EBLE can be used for INH-induced hepatotoxicity.

Ethyl gallate concurrent administration protects against acetaminophen-induced acute liver injury in mice: An in vivo and in silico approach.

Acetaminophen (APAP) in high doses causes acute liver injury and acute liver failure. Ethyl gallate (EG) is a natural polyphenol, possessing antioxidant, anti-inflammatory, and anti-microbial properties. Therefore, in this study, we evaluated the protective role of EG against APAP-induced acute liver injury in mice. Acute liver injury was induced by a single dose of APAP (400 mg/kg., i.p.). In separate groups, EG (10 mg/kg), EG (20 mg/kg), and N-acetylcysteine (NAC; 1200 mg/kg., i.p.) were administered concurrently with APAP. The mice were sacrificed after 24 h of treatment. Liver marker enzymes of hepatotoxicity, antioxidant markers, inflammatory markers, and histopathological studies were done. APAP administration caused a significant elevation of marker enzymes of hepatotoxicity and lipid peroxidation. APAP administration also decreased enzymic and nonenzymic antioxidants. Acute APAP intoxication induced nuclear factor κ B, tumor necrosis factor-α, interleukin-1, p65, and p52 and downregulated IκB gene expressions. Our histopathological studies have confirmed the presence of centrilobular necrosis, 24 h after APAP intoxication. All the above abnormalities were significantly inhibited in groups of mice that were concurrently administered with APAP + EG and APAP + NAC. Our in silico analysis further confirms that hydroxyl groups of EG interact with the above inflammatory proteins at the 3,4,5-trihydroxybenzoic acid region. These effects of EG against APAP-induced acute liver injury could be attributed to its antioxidative, free radical scavenging, and anti-inflammatory potentials. Therefore, this study suggests that EG can be an efficient therapeutic approach to protect the liver from APAP intoxication.

Coleus vettiveroides ethanolic root extract protects against thioacetamide-induced acute liver injury in rats.

Acute liver injury is caused by various factors, including oxidative stress and inflammation. Coleus vettiveroides, an ayurvedic medicinal plant, is known to possess antioxidant, antibacterial, and antidiabetic properties. In this current study, we investigated the protective effect of C. vettiveroides ethanolic root extract (CVERE) against thioacetamide (TAA)-induced acute liver injury in rats. A single dose of TAA (300 mg/kg, b.w., i.p.) was administered to induce acute liver injury. The treatment groups of rats were concurrently treated with CVERE (125 and 250 mg/kg, b.w., p.o.) and silymarin (100 mg/kg, b.w., p.o.), respectively. After 24 h of the experimental period, TAA-induced liver injury was confirmed by increased activity of serum transaminases and malondialdehyde levels in liver tissue, decreased levels of antioxidants, upregulated expression of the inflammatory marker gene, and altered liver morphology. Whereas CVERE simultaneous treatment inhibited hepatic injury and prevented the elevation of serum aspartate and alanine transaminases, alkaline phosphatase, and lactate dehydrogenase activities. CVERE attenuated TAA-induced oxidative stress by suppressing lipid peroxidation and restoring antioxidants such as superoxide dismutase, catalase, and reduced glutathione. Further, CVERE treatment was found to inhibit nuclear factor κB-mediated inflammatory signaling, as indicated by downregulated pro-inflammatory cytokines including tumor necrosis factor-α and interleukin-1ß. Our findings suggest that CVERE prevents TAA-induced acute liver injury by targeting oxidative stress and inflammation.