Multimodal antioxidant and anti-inflammatory activity of Rauwolfia serpentina root extracts in experimental models

BackgroundChronic inflammation and oxidative stress are central drivers of cardiovascular disease progression and remain incompletely addressed by existing pharmacological strategies. Traditional medicinal plants provide a valuable source of multi-target bioactive compounds that may modulate these interconnected pathways. Rauwolfia serpentina, a classical antihypertensive plant in Ayurveda, has been historically valued for cardiovascular indications. Yet, its antioxidant and anti-inflammatory actions beyond blood pressure regulation remain insufficiently characterised in immune-driven inflammatory models. MethodsRoot extracts of R. serpentina prepared using hot and cold ethanol and water were evaluated for antioxidant capacity using DPPH radical scavenging and phosphomolybdenum assays, along with phenolic, flavonoid, and terpenoid quantification. Protective effects against lipid peroxidation were assessed in rat liver and heart homogenates. Anti-inflammatory activity was examined in THP-1 human monocytic cells exposed to lipopolysaccharide (LPS), arachidonic acid (AA), and oxidative stress. Cytokine secretion and gene expression of TNF-, MCP-1, IL-6, and IL-8 were measured by ELISA and qRT-PCR. Intracellular reactive oxygen species and catalase activity were quantified to assess oxidative regulation. LC-MS-based metabolomic profiling was performed to characterise chemical diversity. The principal alkaloid, reserpine, was evaluated separately, and molecular docking was performed to examine its interaction with IKK. ResultsEthanolic extracts of R. serpentinas root, particularly the cold ethanolic fraction, showed superior antioxidant capacity, higher phenolic and flavonoid content, and potent inhibition of lipid peroxidation. These extracts markedly suppressed LPS-induced cytokine release and gene expression in THP-1 cells, with pronounced effects on MCP-1 and IL-6. Oxidative stress induced by arachidonic acid was attenuated through reduced intracellular ROS and preservation of catalase activity. Reserpine reproduced key features of the extract response, demonstrating strong suppression of IL-6 and MCP-1 at both transcriptional and secretory levels. Docking analysis indicated stable binding of reserpine within the IKK catalytic pocket, supporting a plausible mechanism for modulation of the NF-{kappa}B pathway. ConclusionR. serpentina root extracts exhibit coordinated antioxidant and anti-inflammatory activity in immune cell models relevant to cardiovascular inflammation. These effects are extraction-dependent and are partially mediated by reserpine through modulation of oxidative stress and inflammatory signalling pathways. The findings support the translational relevance of R. serpentina as a traditional medicine with mechanistic activity extending beyond antihypertensive action.