Protection Against Drug-Induced Liver Injuries Through Nutraceuticals via Amelioration of Nrf-2 Signaling

Abstract

Hepatotoxicity caused by the overdose of various medications is a leading cause of drug-induced liver injury. Overdose of drugs causes hepatocellular necrosis. Nutraceuticals are reported to prevent drug-induced liver failure. The present article aims to review the protection provided by various medicinal plants against hepatotoxic drugs. Ayurveda is considered a conventional restorative arrangement in India. It is consistently used for ages and is still used today to cure drug-induced hepatotoxicity by focusing on antioxidant stress response pathways such as the nuclear factor erythroid-2 (Nrf-2) antioxidant response element signaling pathway. Nrf-2 is a key transcription factor that entangles Kelch-like ECH-associating protein 1, a protein found in the cell cytoplasm. Some antioxidant enzymes, such as gamma glycine cysteine ligase (γ-GCL) and heme oxygenase-1 (HO-1), are expressed in Nrf-2 targeted genes. Their expression, in turn, decreases the stimulation of hepatic macrophages and induces the messenger RNA (mRNA) articulation of proinflammatory factors including tumor necrosis factor α. This review will cover various medicinal plants from a mechanistic view and how they stimulate and interact with Nrf-2, the master regulator of the antioxidant response to counterbalance oxidative stress. Interestingly, therapeutic plants have become popular in the medical sector due to safer yet effective supplementation for the prevention and treatment of new human diseases. The contemporary study is expected to collect information on a variety of therapeutic traditional herbs that have been studied in the context of drug-induced liver toxicity, as nutraceuticals are the most effective treatments for oxidative stress-induced hepatotoxicity. They are less genotoxic, have a lower cost, and are readily available. Together, nutraceuticals exert protective effects against drug-induced hepatotoxicity through the inhibition of oxidative stress, inflammation, and apoptosis. Its mechanism(s) are considered to be associated with the γ-GCL/HO-1 and Nrf-2 signaling pathways.

KEY TEACHING POINTS

• The liver is the most significant vital organ that carries out metabolic activities of the body such as the synthesis of glycogen, the formation of triglycerides and cholesterol, as well as the formation of bile.

• Acute liver failure is caused by the consumption of certain drugs; drug-induced liver injury is the major condition.

• The chemopreventive activity of nutraceuticals may be related to oxidative stress reduction and attenuation of biosynthetic processes involved in hepatic injury via amelioration of the nuclear factor erythroid-2 (Nrf-2) signaling pathway.

• Nrf-2 is a key transcription factor that is found in the cell cytoplasm resulting in the expression of various genes such as gamma glycine cysteine ligase and heme oxygenase-1.

• Nutraceutical-rich phytochemicals possess high antioxidant activity, which helps in the prevention of hepatic injury.

Keywords:

• Liver injuries
• nutraceuticals
• Nrf-2 signaling
• acetaminophen
• γ-GCL
• HO-1
• chemoprevention

Acknowledgments

The authors wish to thank the Lovely Professional University for providing basic facilities. The authors are also grateful to Dr. Bimlesh Kumar, Professor, School of Pharmaceutical Sciences, Lovely Professional University, and Simran (Reseearch Scholar) for assistance in the revision.

Author contributions

MPS conceptualized the idea, edited the manuscript, and supervised the review; SY wrote the first draft; and SS constructed some portion of the manuscript and provided assistance with tables.

Disclosure statement

The authors declare no conflict of interest.