Hepatoprotective role of verbenone against cyclophosphamide-induced oxidative stress, inflammation, apoptosis, and fibrosis in Swiss albino mice: insights into the involvement of NF-κB, caspase-3, and TGF-β signaling pathways

Mohd Wasim ¹, Mansoor Ali Syed ², Syed Ehtaishamul Haque ¹

⁰Department of Pharmacology, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi, 110062 India.

3 Biotech +

|

September 8, 2025

View abstract on PubMed

Summary

Verbenone (VRB) effectively protected mice livers against cyclophosphamide (CP)-induced toxicity. This study shows VRB reverses liver damage by reducing oxidative stress, inflammation, and apoptosis, highlighting its hepatoprotective potential.

Area Of Science

Hepatology
Pharmacology
Toxicology

Background

Cyclophosphamide (CP) is an anti-cancer drug known to induce liver toxicity through oxidative stress, inflammation, apoptosis, and fibrosis.
Verbenone (VRB), a natural monoterpene ketone, possesses documented antioxidant, anti-inflammatory, and anti-apoptotic properties.
Investigating VRB's potential to counteract CP-induced hepatotoxicity is crucial for developing protective therapeutic strategies.

Purpose Of The Study

To evaluate the hepatoprotective efficacy of Verbenone (VRB) against Cyclophosphamide (CP)-induced liver injury in a mouse model.
To elucidate the underlying mechanisms of VRB's protective effects, focusing on oxidative stress, inflammation, apoptosis, and fibrosis.

Main Methods

Mice were administered CP (200 mg/kg) to induce hepatotoxicity, with co-administration of VRB (200 and 300 mg/kg) or fenofibrate (FF, 80 mg/kg) daily for 14 days.
Biochemical analyses assessed liver enzymes (AST, ALT, ALP, GGT), oxidative stress markers (malondialdehyde), inflammatory markers (NF-κB, TNF-α, IL-1β, IL-6, IL-10), and apoptotic markers (cleaved caspase-3).
Histopathological and immunohistochemical analyses evaluated liver structure, fibrosis, and antioxidant enzyme levels (SOD, catalase, glutathione).

Main Results

CP treatment significantly elevated liver enzymes, oxidative stress, inflammation, and apoptosis markers while decreasing antioxidant enzyme levels.
VRB administration markedly reduced CP-induced liver damage, improving liver function and restoring normal hepatocyte structure.
VRB treatment normalized antioxidant enzyme levels and significantly decreased inflammatory and apoptotic markers, indicating potent antioxidative, anti-inflammatory, and anti-apoptotic effects.

Conclusions

Verbenone (VRB) demonstrates significant hepatoprotective effects against Cyclophosphamide (CP)-induced liver toxicity.
VRB counteracts CP-induced liver damage through multifaceted mechanisms including antioxidative, anti-inflammatory, anti-apoptotic, and anti-fibrotic actions.
Further studies in animal cancer models are warranted to confirm VRB's therapeutic potential in mitigating chemotherapy-induced liver injury.

Keywords:

Apoptosis Cyclophosphamide Fibrosis Hepato-toxicity Inflammation Verbenone

Related Concept Videos

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...