In vivo and In silico Hepatoprotective Activity of Elaeocarpus serratus
Valentina Mendonca, Rajesh Kaverikana Shankara, Chandrashekar Kodangala Subraya, Vasudev Pai, Aravinda PaiIntroduction:
Elaeocarpus serratus, the Ceylon olive, is a tropical flowering plant in the family Elaeocarpaceae. Rudraksha is a common name for the plant in India. Crude extracts of certain plant parts are used to treat various conditions, including skin disease, ascites, worms, inflammation, leprosy, cough, diarrhoea, and chronic rheumatism. Liver toxicity is one of the common problems leading to severe disabilities, extending from severe metabolic imbalance to even mortality. Even with notable progress in modern medicine, efficient drugs that promote liver function, whole organ protection, or repair the hepatocytes are lacking. To develop highly potent and least injurious drugs for the management of hepatic diseases is therefore important to identify newer treatment options.
Methods:
The leaves of Elaeocarpus serratus were subjected to ethanolic extraction using maceration. The animals, after quarantine, were distributed into 6 different groups (with n=6); normal control, Disease control (Acetaminophen, APAP), standard (silymarin), and E. serratus (100, 200, and 400 mg/kg p.o). The animals were treated for 7 days with the plant extract. On the 5th day, APAP was administered to induce hepatotoxicity. On the 7th day, blood was withdrawn and subjected to different liver function tests. The organs were dissected for histopathology. In-silico evaluations were performed to determine the interactions between the leaf’s phytoconstituents with the proteins involved in the hepatic damage pathway. A total of 20 phytoconstituents, in addition to a standard silymarin, were docked against the selected target proteins involved in the process of liver toxicity, which include proteins bearing the PDB IDs 3KRR, 4CIK, 5WUU, 6V7K, 6VL4, and 7XGJ.
Results and Discussion:
Following the administration of Acetaminophen, marked changes in the values of liver enzymes and proteins were observed. The extract of the leaf, at 400 mg/kg, exhibited significant hepatoprotective action, aiding in normalizing the parameters, which was comparable with the action of the standard drug, silymarin. Histopathology study of the tissues also proved the benefits of the plant extract as a hepatoprotective agent. In silico analysis of targets involved in liver toxicity revealed evidence of participation of these constituents in the potential treatment of the damage that could occur, utilizing those protein targets.
Conclusion:
The results of the present work confirm that the ethanolic leaf extract of Elaeocarpus serratus has hepatoprotective action in a dose-dependent fashion. However, there is a need to investigate this further on the possible mechanism of action and other aspects. In-silico studies by carrying out molecular docking of various phytoconstituents of Elaeocarpus serratus leaves against the selected targets involved in liver toxicity revealed evidence of participation of these constituents in the potential treatment of the damage that could occur, utilizing those protein targets.