ABSTRACT
Liver fibrosis progresses to cirrhosis in several settings, for example, severe acute alcoholic hepatitis, and hepatitis C virus [HCV] reinfection after liver transplantation. Cirrhosis produces hepatocellular dysfunction, which is also a risk factor for hepatocellular carcinoma. We studied verapamil as a prophylactic, therapeutic antifibrotic drug alone and in combination with silymarin in experimental rat's liver-induced fibrosis. Liver fibrosis was induced by intra-peritoneal injection of rats with pig serum 0.5 ml twice weekly for 6 weeks, which resulted in score three fibrosis. Prophylactic verapamil alone and silymarin alone and a combination of both were administered at the same time of induction of liver fibrosis and continued for the duration of induction. Therapeutic verapamil was started on the last day of fibrosis induction and continued for 4 weeks. The extent of liver fibrosis was evaluated using Ishak's fibrosis score. Serum alanine aminotransferase [ALT] was measured for follow-up. Compared to fibrotic model rats, prophylactic verapamil, silymarin and combined verapamil plus silymarin significantly resulted in lower serum ALT levels. Prophylactic use of verapamil and silymarin each alone revealed score 2 fibrosis with positive alpha-SMA immunostaining; while prophylactic treatment with combined verapamil plus silymarin revealed no fibrosis supported by negative alpha-SMA immunostaining. Verapamil treated fibrotic rat's liver revealed significant regression in liver fibrosis scores with positive alpha-SMA immunostaining. Verapamil alone has a more significant prophylactic than therapeutic antifibrotic effect against induced liver fibrosis; it was more significant than silymarin. The combination of verapamil and silymarin, showed the best protection through their synergistic antifibrotic effect
ABSTRACT
The two plants under investigation were reported to have some traditional uses, e.g. H. salicornicum is used by the Bedouins in the remedy of coryza and as food in time of famine, while A. Glaucum is used in the remedy of anuria and to increase menstruation. The present study examined in a comparative fashion the pharmacological effects of these plants on isolated rectus abdominis muscle of the toad and rat phrenic nerve diaphragm preparation through their variable extracts. Th materials used in this study were the aqueous solutions of the dried ethanolic extracts of the overground parts, the hydrochloric acid solutions of the dried chloroformic soluble alkaloidal fractions and the aqueous solutions of the dried chloroformic insoluble alkaloidal fractions of the two plants. It was found that the dried ethanolic extract of H. Salicornicum relaxed the rectus and diaphragm muscles while that of A. glaucoma stimulated both preparations. The hydrochloric acid solution of chloroformic-soluble alkaloidal fractions of both plants relaxed the rectus and rat diaphragm muscles, while the aqueous solution of the dried chloroformic insoluble alkaloidal fractions of the two plants possessed anticholinesterase activity on both the rectus and rat diaphragm muscles. These pharmacological actions can explain the reported effects of both plants and their uses in folk medicine