Being a crucial organ in human body, liver executes different types of important functions like detoxification, metabolism and the storage of nutrients (Kalra et al., 2022). Since the organ is continuously getting exposed to different types of environmental pollutants, drugs, toxins and chemicals, liver cells and tissues are highly prone to damage and injury. Chemical-induced injury is a common threat to liver cells which in turn cause liver fibrosis, cirrhosis and at times, liver failure too (Ortega-Alonso and Andrade, 2018). Liver fibrosis is characterized by the accumulation of scarred tissues in the liver and this chronic disease may end up in liver failure and fatal too. This disease occurs as a result of chronic inflammatory liver diseases in which the Hepatic Stellate Cells (HSCs) transform themselves and progress into myofibroblast like cells, depositing extracellular matrix (ECM) and collagen (Friedman et al., 2000). Up to 15% of the HSCs are made up to Vitamin A which gets stored in these cells under healthy conditions. On the other hand, the cytokines (such as TGF-β, TNF-α, and PDGF), reactive oxygen species and a few other factors generated by the injured hepatocytes and triggered Kupffer cells (Wu et al., 2000) tend to activate the HSCs. Thus, the activated HSCs quickly generate the components of ECM, leading to fibrosis. As per the literature in animal models, the number of HSCs increases in case of chronic liver diseases. Further, it also emits desmin, GFAP and CD133 in rare cases, during the upregulation of CD133 + HSCs in chronically-injured liver (Kordes et al., 2007). In the transformation and regeneration of liver cells, the Epidermal Growth Factor (EGF) and its receptor (EGFR) play an important role. Here, EGF is a cell growth-stimulating polypeptide (Natarajan et al., 2007; Tanabe et al., 2008). It has been found that the EGF and EGFR levels are significantly high in the human liver cells diagnosed with cirrhosis. In spite of its importance there is an absence of in-depth insights about EGF and EGFR expression in mouse liver injury models.
Emodin, a naturally-available anthraquinone derivative, is predominantly found in plants, especially Chinese herb Rheum palmatum. This derivative has a number of pharmacological effects including antitumor, antioxidant and anti-inflammatory effects (; Yang et al., 2003; Naqvi et al., 2010; Lee et al., 2011; Wang et al., 2012a). In addition to these, Emodin has anti-cancer, anti-inflammatory, antiviral, antibacterial, anti-allergic, anti-osteoporotic, anti-diabetic, immunosuppressive, neuroprotective, and hepatoprotective activities (Shrimali et al., 2013; Wei et al., 2013). According to Matsuda et al (2008), emodin tend to promote weight loss due to its laxative characteristic. Based on these characteristics, it has been proposed that Emodin can be used in both prevention as well as the treatment of various diseases such as atherosclerosis, counting constipation, asthma, diabetic complications, osteoarthritis, atopic dermatitis, alzheimer’s disease and various types of cancers such as lung carcinoma, breast cancer, hepatocellular carcinoma, pancreatic cancer and lung carcinoma (Dong et al., 2016). In spite of this, the drug has also been reported to have some adverse effects (Akkol et al., 2021).
The liver cells can be protected from further damage and regenerated through Emodin’s pharmacological activities. Various studies have been published earlier upon the effectiveness of Emodin in liver growth and regeneration. For instance, emodin was found to have enhanced the ethanol-induced liver steatosis, mitigated the levels of aspartate aminotransferase, alanine aminotransferase, and hepatic triglycerides, liver collagen type I and α-smooth muscle actin and increased the PPAR-γ mRNA levels (Liu et al., 2014). Emodin has the potential to get rid of the ethanol-induced cytotoxicity in HepG2/CYP2E1 cells. This is possible through the expression of CYP2E1 protein and the reticence of Gamma-glutamyltransferase activity (Qian et al., 2011). In addition to these, when emodin is administered, it tend to reduce the activities of ALT, serum aspartate aminotransferase, hepatic hydroxyproline content and the mRNA/protein levels of various genes such as Smad4, TGF-β1, and α-SMA in the hepatic tissues of mice with CCl4-induced liver fibrogenesis (Dong et al., 2009). In addition to these, emodin dwindled the CCl4-induced liver injury through the downregulation of lipid peroxidation and upregulation of the inflammation (Lee et al., 2012). In addition to these, it was found that Emodin also prevents the liver from getting damaged due to acetaminophen. This is accomplished by reducing the oxidative stress with optimum hepatoprotective ability at 30 mg/kg dosage. Based on these observations, it can be understood that emodin is potential enough to be used as a therapeutic agent in the treatment of different types of liver diseases (Bhadauria, 2010). When unleasing the potential hepatoprotective effects of emodin in chemical-induced liver injury models, it can open new opportunities to develop novel treatment methods and regimens for liver diseases.
The aim of the current study is to determine the hepatoprotective characteristics of emodin extracted from Senna alata (Cassia alata) leaves upon mice with CCl4-induced liver injury. The study findings infer that emodin has excellent hepatoprotective effects as it regulates the levels of different markers in the serum like ALT, AST, ALP, and bilirubin. Further, it also modulates the expression of liver-specific inflammatory markers and mitigates the pathophysiology of the disease.