Govaniadine Ameliorates Oxidative Stress, Inflammation, and Kupffer Cell Activation in Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

Liver diseases such as hepatic carcinoma are one of the main health problems worldwide. Herbal drugs are largely used to treat liver injury in the indigenous system of medicine and may provide lead compounds for hepatoprotective drug discovery. The present study is investigated to test the Corydalis govaniana Wall. extract, fraction, and isolate therapeutically active constituents to explore their hepatoprotective, anti-inflammatory, and antioxidant activities. For this purpose, the antioxidant activity of govaniadine, caseadine, caseamine, and protopine was performed by assessing the scavenging events of the stable 2,2-diphenyl-1-picrylhydrazyl. Hepatoprotection of govaniadine was assessed in terms of reduction in serum enzymes (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) caused by CCl4-induced liver injury in rats and by histopathological techniques. All the compounds showed significant antioxidant activity with a percentage inhibition of 92.2, 86.7, 85.3, and 79.7, respectively, compared to propyl gallate 90.3%. Treatment with govaniadine reduced the serum enzyme level down to normal levels in the CCl4-treated group while inhibiting the increase of malondialdehyde, and the induction of superoxide dismutase and the glutathione level was upregulated. Histopathology showed ∼47% damage to the liver cells in the CCl4-treated group; reduction in this damaged area was found to be better upon using govaniadine. Immunohistochemistry results showed that govaniadine as compared to silymarin has exceedingly decreased the inflammation by halting the CCl4-induced activation of hepatic macrophages. In carrageenan-induced paw edema assay, govaniadine significantly alleviated the edema after 1-5 h at a dose of 20 mg/kg (26.00 and 28.5%), 50 mg/kg (22.05 and 27.0%), and 100 mg/kg (20.02 and 25.30%), respectively. The results of our experiments suggest that govaniadine showed antioxidant and hepatoprotective activity in liver injury. The hepatoprotective function of govaniadine may be associated to the scavenging of the free radical and attenuation of oxidative stress as well as inflammatory responses in the liver. Hence, govaniadine may be a lead compound for the hepatoprotective drug discovery process and further research is needed to find out their molecular mechanism of protection.

Steroidal alkaloids efficient aromatase inhibitors with potential for the treatment of postmenopausal breast cancer.

Plant-derived natural products are of great interest due to their diversity in modern drug discovery. Sarcococca saligna has been used for the treatment of different diseases. The present study was aimed at isolating phytochemical constituents including Alkaloid-C (a), Dictyophlebine (b), Sarcovagine-D (c) and Saracodine (d) Holaphylline (e) from Sarcococca saligna to investigate the anticancer effect of these compounds. These compounds were evaluated for inhibition of aromatase enzyme of breast cancer in assistance by molecular docking simulations to understand molecular interaction between the enzyme and ligands. The IC50 values of compound 1 and 5 were found 138.27 ± 0.01 µl and 12.91 ± 0.01 µl, respectively, and both were found active due to their bulky structures in comparison to the active site of aromatase enzyme. The standard drug exemestane showed potent activity in comparison with the test compounds, having IC50 values of 0.052 ± 0.01 µl. Both compounds showed favorable electrostatic interactions with the active site of aromatase enzyme but the shape and steric bulk of the compounds was the limiting factor in their inhibitory effects. New lead compounds could be generated after extensive modifications guided by computational and experimental tools as a possible anticancer agents by targeting aromatase enzyme.