Summary of Natural Products Ameliorate Concanavalin A-Induced Liver Injury: Structures, Sources, Pharmacological Effects, and Mechanisms of Action

Abstract

Liver diseases represent a threat to human health and are a significant cause of mortality and morbidity worldwide. Autoimmune hepatitis (AIH) is a progressive and chronic hepatic inflammatory disease, which may lead to severe complications. Concanavalin A (Con A)-induced hepatic injury is regarded as an appropriate experimental model for investigating the pathology and mechanisms involved in liver injury mediated by immune cells as well as T cell-related liver disease. Despite the advances in modern medicine, the only available strategies to treat AIH, include the use of steroids either solely or with immunosuppressant drugs. Unfortunately, this currently available treatment is associated with significant side-effects. Therefore, there is an urgent need for safe and effective drugs to replace and/or supplement those in current use. Natural products have been utilized for treating liver disorders and have become a promising therapy for various liver disorders. In this review, the natural compounds and herbal formulations as well as extracts and/or fractions with protection against liver injury caused by Con A and the underlying possible mechanism(s) of action are reviewed. A total of 53 compounds from different structural classes are discussed and over 97 references are cited. The goal of this review is to attract the interest of pharmacologists, natural product researchers, and synthetic chemists for discovering novel drug candidates for treating immune-mediated liver injury.

Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis

“…Additionally, TNF-α induces the activation and release of other inflammatory mediators, leading to the augmentation of the inflammatory response and recruitment of other immune cells [ 52 ]. Another apoptotic pathway that happens alongside the TNF-α/JNK axis is the TNF-α-dependent activation of caspase-8 and -3 which results in hepatocyte apoptosis [ 16 ]. Furthermore, Con A injection induces the elevated expression of proapoptotic proteins: Bax and caspase-8.…”

“…Many of the therapeutically used agents in liver diseases are either natural products or their derivatives because of their capacity to act on various biological targets [ 15 ]. Moreover, many natural compounds, extracts, and herbal formulations have been proven to ameliorate Con-A-induced hepatitis [ 16 ]. Garcinia mangostana L. (GM, mangosteen, Queen of fruits, Clusiaceae), amongst the most common tropical fruits, is popular for its juiciness and sweetness, plus its importance in promoting people’s health [ 17 , 18 , 19 , 20 , 21 , 22 ].…”

Molecular mechanism and research progress on pharmacology of ferulic acid in liver diseases

“…Concanavalin A-induced liver injury is an immune liver injury caused by T-cell-mediated cytokine imbalance and can mimic the pathologic characteristics of multiple viral and autoimmune hepatitis ( Ibrahim et al, 2021 ). Concanavalin A-induced liver injury model is a widely used model of immune liver injury.…”

Alpha-Mangostin as a New Therapeutic Candidate for Concanavalin A-Induced Autoimmune Hepatitis: Impact on the SIRT1/Nrf2 and NF-κB Crosstalk

“…The inflammatory cells infiltrating into the hepatic tissue are the substantiating characteristics of AIH in addition to the augmented levels of aminotransferases, IgG, and autoantibodies. The approach to AIH is a clinical challenge as it is a polygenic disease in which the severity and complexity vary among patients, from hepatocellular necrosis to liver cirrhosis, that necessitates a liver transplant [1,2]. The pathogenesis of AIH is complex and involve multiple pathophysiological events.…”