Effects of andrographolide on intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats.

Cholestasis is a cardinal manifestation of liver diseases but effective therapeutic approaches are limited. Therefore, alternative therapy for treating and preventing cholestatic liver diseases is necessary. Andrographolide, a promising anticancer drug derived from the medicinal plant Andrographis paniculata, has diverse pharmacological properties and multi-spectrum therapeutic applications. However, it is unknown whether andrographolide has a hepatoprotective effect on intrahepatic cholestasis. The aims of this study were to investigate the protective effect and possible mechanisms of andrographolide in a rat model of acute intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT). Andrographolide was administered intragastrically for four consecutive days, with a single intraperitoneal injection of ANIT on the second day. Liver injury was evaluated biochemically and histologically together with hepatic gene and protein expression analysis. Rats pretreated with andrographolide prior to ANIT injection demonstrated lower levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, as well as bilirubin and bile acids as compared to rats treated with ANIT alone. Andrographolide also decreased the incidence and extent of periductular fibrosis and bile duct proliferation. Analysis of protein expression in livers from andrographolide-treated cholestatic rats revealed markedly decreased expression of alpha-smooth muscle actin and nuclear factor kappa-B (NF-κB). In conclusion, andrographolide has a potent protective property against ANIT-induced cholestatic liver injury. The mechanisms that underlie this protective effect are mediated through down-regulation of NF-κB expression and inhibition of hepatic stellate cell activation. These findings suggest that andrographolide could be a promising therapeutic option in prevention and slowing down the progression of cholestatic liver diseases.

Gonadotropin-releasing hormone and adipokinetic hormone/corazonin-related peptide in the female prawn.

Crustacean neuropeptides (NPs) play important roles in the regulation of most physiological activities, including growth, molting and reproduction. In this study, we have performed an in silico analysis of female prawn (Macrobrachium rosenbergii) neural transcriptomes to identify NPs not previously identified. We predict that approximately 1309 proteins are destined for the secretory pathway, many of which are likely post-translationally processed to generate active peptides. Within this neural secretome, we identified a gene transcript that encoded a precursor protein with striking similarity to a gonadotropin-releasing hormone (GnRH). We additionally identified another GnRH NP superfamily member, the adipokinetic hormone/corazonin-related peptide (ACP). M. rosenbergii GnRH and ACP were widespread throughout the nervous tissues, implicating them as potential neuromodulators. Furthermore, GnRH was found in non-neural tissues, including the stomach, gut, heart, testis and ovary, in the latter most prominently within secondary oocytes. The GnRH/corazonin receptor-like gene is specific to the ovary, whereas the receptor-like gene expression is more widespread. Administration of GnRH had no effect on ovarian development and maturation, nor any effect on total hemolymph lipid levels, while ACP administration decreased oocyte proliferation (at high dose) and stimulated a significant increase in total hemolymph lipids. In conclusion, our targeted analysis of the M. rosenbergii neural secretome has revealed the decapod GnRH and ACP genes. We propose that ACP in crustaceans plays a role in the lipid metabolism and the inhibition of oocyte proliferation, while the role of the GnRH remains to be clearly defined, possibly through experiments involving gene silencing.