Hepatoprotective Potential of Pomegranate in Curbing the Incidence of Acute Liver Injury by Alleviating Oxidative Stress and Inflammatory Response

Hamid Ali; Azra Jahan; Samrana Samrana; Abid Ali; Safdar Ali; Nurul Kabir; Amjad Ali; Riaz Ullah; Ramzi A Mothana; Bibi Nazia Murtaza; Muhammad Kalim

doi:10.3389/fphar.2021.694607

Hepatoprotective Potential of Pomegranate in Curbing the Incidence of Acute Liver Injury by Alleviating Oxidative Stress and Inflammatory Response

Front Pharmacol. 2021 Nov 26:12:694607. doi: 10.3389/fphar.2021.694607. eCollection 2021.

Authors

Hamid Ali¹, Azra Jahan², Samrana Samrana³, Abid Ali³, Safdar Ali⁴, Nurul Kabir⁵, Amjad Ali⁶, Riaz Ullah⁷, Ramzi A Mothana⁷, Bibi Nazia Murtaza⁸, Muhammad Kalim⁹

Affiliations

¹ Department of Biosciences, COMSATS University, Islamabad, Pakistan.
² Department of Zoology, Abdul Wali Khan University, Mardan, Pakistan.
³ College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.
⁴ Department of Physics, University of Swabi-Anbar, Mardan, Pakistan.
⁵ Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia.
⁶ Faculty of Biological Sciences, Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
⁷ Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁸ Department of Zoology, Abbottabad University of Science and Technology, Abbottabad, Pakistan.
⁹ Cancer Research Institute, Houston Methodist Hospital, Houston, TX, United States.

Abstract

Hepatitis is an inflammatory disease of the liver and is considered one of the leading causes of death worldwide. Due to its scavenging activity, Punica granatum may be used for the treatment and prevention of liver diseases. The current study investigated the protective mechanism underlying the effects of pomegranate against a rat model of carbon tetrachloride-induced liver injury. Intraperitoneal injection of CCl₄ resulted in liver inflammation, oxidative stress, and accumulation of lipid in hepatocytes. CCl₄ induced a downregulation of superoxide dismutase (SOD), glutathione (GSH), and melonaldehyde (MDA). Pomegranate protection was assessed in terms of biochemical parameters, histopathology, and immunohistochemistry. Promegranate administration decreased inflammation, elevated serum enzymes and ROS production, and countered the debilitating effects caused by CCl₄. In addition, CCl₄-induced histological changes were absent in the crude pomegranate extract group, which also enhanced the scavenging activity of reactive oxygen species by enhancing the antioxidant defense mechanism as confirmed by detecting MDA, SOD, and GSH expressions. The migration of CD68⁺ macrophages was halted at the injured area of the central vein and the number of macrophages was reduced to the normal control by the crude extract compared to the positive control silymarin group. Likewise, protective effects of ethylacetate and the aqueous fraction of the crude extract were also observed. However, the butanol and n-hexane fractions displayed increased levels of ALT, AST, and ALP as compared to silymarin. About 25% damage to hepatocytes was observed in the butanol and n-hexane group by histopathological examination, which is a little better compared to the CCl₄-treated group. The crude extract and its ethyl acetate and aqueous fractions may be accountable for the hepatoprotective potential of Punica granatum, which was further confirmed by in vivo experiments. Together, these findings confirm that pomegranate exerts hepatoprotective activity against CCl₄-induced oxidative stress and liver damage.

Keywords: Kupffer cells; hepatotoxicity; histology; iNOS; oxidative stress; pomegranate.