Non-alcoholic fatty liver disease (NAFLD) is rapidly emerging as the leading cause of liver fibrosis worldwide, according to epidemiological studies (Banerjee et al., 2024). It is a key factor in the progression of chronic liver disease to advanced stages, such as clinically significant cirrhosis (Banerjee et al., 2023), which can eventually lead to hepatic failure and, in some cases, hepatocellular carcinoma (HCC), the fourth leading cause of cancer-related deaths globally (Maurice and Manousou, 2018). Various pathways and their cross-plays contribute to the development and progression of NAFLD to non-alcoholic steatohepatitis (NASH) (Auguet et al., 2014). Despite the significant public health burden posed by NAFLD, its pathophysiology is not yet fully understood. Current treatment options include lifestyle modifications, bariatric surgery, weight loss medications, insulin sensitisers, lipid-lowering agents, antioxidants, and cytoprotective agents. However, there is no FDA-approved drug specifically designed for the treatment of NAFLD and NASH (Beaton, 2012).

Tinospora crispa (TC) (L.) Hook. f. & Thomson is a deciduous climbing plant from the Menispermaceae family, native to tropical rainforests and mixed deciduous forests in Africa and Southeast Asia (Ahmad et al., 2016). It is commonly found in open forests and shrublands in regions such as South Yunnan, Cambodia, Northeastern India, Indonesia, Laos, Malaysia, Myanmar, the Philippines, and Thailand (Paudel et al., 2020). TC is closely related to Tinospora cordifolia, which is well-known in Ayurveda for its benefits against conditions like hyperglycaemia, fatty liver, fever, jaundice, hyperlipidemia, and more (Upadhyay et al., 2010). Historically, the leaves, stems, seeds, rhizomes, and roots of TC have been used in various formulations to treat ailments such as jaundice, rheumatism, urinary disorders, fever, malaria, diabetes, internal inflammation, fractures, scabies, and hypertension. They are also used to reduce thirst, enhance appetite, cool the body, and promote overall health (Ahmad et al., 2016). Given that T. cordifolia is used in Ayurvedic formulations for liver protection in NAFLD, it is plausible that TC could have similar effects due to their shared genus. This hypothesis drove us to investigate whether the phytocompounds in TC could be effective against NAFLD. However, detailed preclinical and clinical studies on TC phytocompounds are necessary to assess their potential efficacy and to identify the specific targets of these compounds within the pathways involved in the pathogenesis and progression of the disease.

Network pharmacology approach distinguishes several disease-related targets and pathways, providing a comprehensive perspective on putative processes (Dai et al., 2025). Molecular docking assesses the binding affinities and interaction patterns of phytochemicals with critical targets, whereas the incorporation of MM/PB(GB)SA scoring enhances this by computing the binding free energy, yielding a more precise evaluation of interaction strength (Chen et al., 2018). Ultimately, MD simulation evaluates the stability and dynamics of these interactions under physiological settings, therefore affirming their dependability. This comprehensive method finds effective phytochemicals and clarifies their molecular processes and pathways, providing insights into their potential for illness mitigation (Halder et al., 2024). This computational study involves network pharmacology followed by molecular docking to establish a network of interaction between the potential targets of NAFLD and the phytoconstituents of TC by analyzing the intersecting targets and related pathways between them to discover following the verification of the underlying mechanisms of the phytochemicals against NAFLD.