Inflammation is a localised response to injury or infection, characterised by swelling, redness, pain, and other discomforts such as fever. Vasodilatory response, an early sign of inflammation, is mediated primarily by nitric oxide, interleukins, cytokines, prostaglandins, and prostacyclin. The cyclooxygenase enzymes COX-1 and COX-2 convert arachidonic acid into prostacyclin and prostaglandins. The actions of histamine, bradykinin, leukotrienes, and platelet-activating factor result in oedema formation, which is another early sign of inflammation. One of the primary goals of inflammation as a defence mechanism for the host is to restore cellular homoeostasis in response to any harmful condition. Thus, the physiological state of homoeostasis is closely linked to the onset of inflammation, which is perceived as a ‘protective reaction’ to any harmful factors that threaten the balance of cellular homoeostasis. However, prolonged inflammation can interfere with normal cellular processes and cause detrimental effects. Consequently, the longer this response lasts, the more harmful its consequences become. Despite its protective role, the inflammatory response must be transient to prevent worsening adverse outcomes (Laroux, 2004, Sherwood and Toliver-Kinsky, 2004, Ahmed, 2011).

Several risk factors are associated with current treatments for inflammation including a history of heart diseases, ulcers, and age-related factors. It is also unclear whether toxicology carryover occurs with some anti-inflammatory substances. To address these challenges, scientists have explored botanical herbs, plants, and trees with notable medicinal properties as alternative treatments (Nath et al., 2020). Biologic therapies and Natural compounds or plant-based treatments that inhibit inflammatory mediators such as prostaglandins, interleukins, and cytokines are essential to mitigating prolonged inflammation and its adverse effects. Biologic therapies targeting Interleukin-17 (IL-17) and Tumor Necrosis Factor (TNF)-α have significantly advanced the management of autoimmune and chronic inflammatory diseases. IL-17 is a key cytokine in neutrophil recruitment and epithelial activation, while TNF-α acts as a master regulator of inflammation, modulating immune cell trafficking, cytokine expression, and apoptosis (Gaffen, 2009, Parameswaran and Patial, 2010). However, their immunosuppressive nature is associated with notable side effects. For instance, TNF-α inhibitors have been linked to an increased risk of serious infections, including the reactivation of latent tuberculosis, while IL-17 inhibitors may cause nasopharyngitis, headaches, and local injection site reactions (Joseph et al., 2021, Berry et al., 2022). These limitations underscore the need for alternative therapeutic strategies that are both effective and better tolerated. In this context, modulation of key inflammatory pathways, particularly IL-17 and TNF-α, through natural compounds offers a promising approach. Such agents may exert multi-targeted effects while potentially minimising systemic toxicity, supporting the search for novel plant-derived anti-inflammatory candidates.

The ancient Indian system of medicine offers a promising avenue for repurposing: it emphasises the use of several plant-based compounds that can target different facets of a disease—leading to perhaps more effective holistic treatments (Patwardhan and Chaguturu, 2016). Among several plants with anti-inflammatory potential, Mitragyna parvifolia (Roxb.) Korth, also known as Kaim, stands out. M parvifolia, a member of the Rubiaceae family, is distributed throughout India, thriving in both deciduous and evergreen forests. The chemical constituents of the plant include indole and oxindole alkaloids, ketones, and aldehydes. Extensively used by tribal communities and Ayurvedic practitioners, M parvifolia is attributed with numerous therapeutic benefits (Shellard and Houghton, 1973, Khare, 2007). The plant’s bark and roots have been utilised in treating gynaecological diseases, fever, colic, burning sensations, muscle discomfort, poisoning, cough, and oedema. Its leaves are known to treat wounds and ulcers, helping to ameliorate pain, reduce swelling, and promote faster healing (Pandey et al., 2006). Many studies have reported anti-inflammatory potential of plant M parvifolia and other species of same genus (Utar et al., 2011, Ahmad et al., 2022). However, the precise mechanisms underlying its anti-inflammatory efficacy remain ambiguous.

Recent advances of in silico studies such as network pharmacology, molecular docking and molecular dynamic simulation, offer a way to elucidate the mechanism of action of plant phytoconstituents in targeting disease associated pathways. Network pharmacology is a cross-disciplinary field that combines bioinformatics, computer modelling, and molecular network data, to explore these mechanisms comprehensively. Molecular docking predicts the primary binding mechanisms of small compounds with the target proteins, while molecular dynamic simulations offer detailed insights into the stability and interactions of these complexes at the atomic level (Cui et al., 2020; Hollingsworth and Dror, 2018; Khairy et al., 2023, Wang et al., 2022).

The study employed an in silico approach to identify the binding affinity and stability of M parvifolia’s phytocompounds with disease targets using network pharmacology, molecular docking, and dynamic simulation techniques to explore the anti-inflammatory mechanism of M parvifolia. Further, in vitro cytotoxicity and anti-inflammatory assays were performed by using M parvifolia supercritical leaf extract. By integrating system biology tools with experimental validation, this study aims to uncover the key targets and pathways responsible for M parvifolia’s anti-inflammatory activity and establish its potential as a natural therapeutic agent.