New IMB16-4 Nanoparticles Improved Oral Bioavailability and Enhanced Anti-Hepatic Fibrosis on Rats

Liver fibrosis is challenging to treat because of the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamido) benzamide referred to as IMB16-4. However, its poor aqueous solubility and poor oral bioavailability obstruct the drug discovery programs. To increase the dissolution, improve the oral bioavailability and enhance the antifibrotic activity of IMB16-4, PVPK30 was selected to establish the IMB16-4 nanoparticles. Drug release behavior, oral bioavailability, and anti-hepatic fibrosis effects of IMB16-4 nanoparticles were evaluated. The results showed that IMB16-4 nanoparticles greatly increased the dissolution rate of IMB16-4. The oral bioavailability of IMB16-4 nanoparticles was improved 26-fold compared with that of pure IMB16-4. In bile duct ligation rats, IMB16-4 nanoparticles significantly repressed hepatic fibrogenesis and improved the liver function. These findings indicate that IMB16-4 nanoparticles will provide information to expand a novel anti-hepatic fibrosis agent.

Liposome Extract of Stachys pilifera Benth Effectively Improved Liver Damage due to Bile Duct Ligation Rats

Herbal medicines harbor essential therapeutic agents for the treatment of cholestasis. In this study, we have assessed the anticholestatic potential of Stachys pilifera Benth’s (SPB’s) hydroalcoholic extract encapsulated into liposomes using bile duct ligation- (BDL-) induced hepatic cholestasis in rats. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), total thiol (T-SH) content, protein carbonyl (PCO), total bilirubin (TBIL), albumin (ALB), and nitric oxide (NO) metabolite levels were measured in either liver tissue or plasma to assess liver damage. Moreover, expression of proinflammatory cytokines (IL-1β and TNF-α) and liver fibrosis markers (TGF-β and SM-α) which are driving forces of many liver disorders was also determined. The activity of AST, ALT, and ALP was significantly enhanced in the BDL group in comparison to the control group; however, treatment with liposomal (SPB) hydroalcoholic extract significantly reduced AST and ALT’s activity. Increases in MDA, TBIL, and NO levels and T-SH content due to BDL were restored to control levels by liposomal (SPB) hydroalcoholic extract treatment. Similarly, hepatic and plasma oxidative marker MDA levels, significantly enhanced by BDL, were significantly decreased by liposomal (SPB) hydroalcoholic extract treatment. Moreover, histopathological findings further demonstrated a significant decrease in hepatic damage in the liposomal (SPB) hydroalcoholic extract-treated BDL group. In addition, liposomal (SPB) hydroalcoholic extract treatment decreased the liver expression of inflammatory cytokines (IL-1β, TNF-α) and liver fibrosis markers (TGF-β and SM-α). Since liposomal (SPB) hydroalcoholic extract treatment alleviated the BDL-induced injury of the liver and improved the hepatic structure and function more efficiently in comparison to free SPB hydroalcoholic extract, probable liposomal (SPB) hydroalcoholic extract exhibits required potential therapeutic value in protecting the liver against BDL-caused oxidative injury.

Effects of melatonin on liver and lung tissues of animals with bile duct ligation-induced hepatopulmonary syndrome

The objective was to assess the antioxidant effect of melatonin (MLT) on liver and lung tissues of animals with bile duct ligation (BDL)-induced hepato-pulmonary syndrome (HPS). A model of BDL-induced biliary cirrhosis was used in male Wistar rats. Results suggest that MLT has an antioxidant effect on liver and lung tissues in animals with BDL-induced HPS by higher activity of antioxidant enzymes in the group HPS treated with MLT and the histological analysis of lung parenchyma showing decreased damage in this same group, including other analysis described below.