Beta‐caryophyllene attenuates experimental hepatocellular carcinoma through downregulation of oxidative stress and inflammation

Author:

Ahmad Zaved1,Jain Subodh Kumar1,Mishra Siddhartha Kumar2ORCID

Affiliation:

1. Cancer Biology Laboratory, Department of Zoology, School of Biological Sciences Dr. Harisingh Gour Central University Sagar India

2. Department of Biochemistry University of Lucknow Lucknow India

Abstract

AbstractHepatocellular carcinoma (HCC) is caused by various factors including toxic substances and xenobiotics. Numerous treatment strategies are used to address toxicity to the liver and HCC, yet their adverse effects are drawbacks. This study aimed to assess the effect of DEN/CCl4 on morphological changes in the liver, body weight, tumor incidence, and hematological tumor incidence, hematological parameters, hepatic markers, and histopathological analysis in mice following a preventive measure by using β‐caryophyllene (BCP). Adult Balb/c mice were administered a single dose of DEN 1‐mg/kg body weight and 0.2‐mL CCl4/kg body weight intraperitoneal twice a week (i.p.) for 22 weeks. BCP was treated in one group of mice at 30‐mg/kg body weight, intraperitoneal, for 7 weeks. BCP alone was treated in one group of mice at 300‐mg/kg body weight intraperitoneal for 22 weeks. DEN/CCl4 caused a reduction in mice's body weight, which was significantly attenuated by BCP administration. BCP supplementation attenuated the tumor incidence DEN/CCl4 (100%) to about 25%. DEN/CCl4 caused alterations in the hematological parameters, serum total protein albumin globulin, A/G ratio, liver function markers (AST, ALT, ALP, GGT, ACP, and bilirubin), and lipid profile markers that were significantly reinstated by BCP administration. Oxidative stress markers (MDA, SOD, CAT, NO, LDH, and GST) were reduced by DEN/CCl4, which were significantly increased in BCP‐treated groups. The liver histopathology alterations caused by DEN/CCl4 were amended considerably by BCP treatment. Immunohistochemical studies suggest that AFP, caspase‐3, and COX‐2 were chronically overexpressed in DEN/CCl4‐exposed mice, notably attenuated by BCP administration. BCP suppressed tumor incidence by downregulating inflammation and inducing caspase‐3‐mediated apoptosis. Conclusively, BCP appears to be a potent natural supplement capable of repressing liver inflammation and carcinoma through the mitigation of oxidative stress and inflammation pathways.

Publisher

Wiley

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