<![CDATA[Inflammation is a fundamental immunological response; however, chronic inflammation is implicated in the pathogenesis and progression of various disorders, including cardiometabolic, neurological, autoimmune, and neoplastic diseases. Traditionally, Sungkai (Peronema canescens Jack) has been used for its antipyretic, wound-healing, and anti-edematous properties. Although preliminary studies support some of these traditional uses, the relationship between its phytochemical constituents and underlying anti-inflammatory mechanisms remains insufficiently characterized. This systematic review synthesizes evidence on the phytochemical composition, anti-inflammatory effects, and molecular mechanisms of P. canescens based on preclinical studies published between 2020 and 2026. Following the PRISMA 2020 guidelines, a comprehensive literature search was conducted across PubMed, Scopus, ScienceDirect, Google Scholar, and ProQuest. Ten eligible in vitro and in vivo studies were included and critically appraised using the QUIN and SYRCLE risk-of-bias tools, as appropriate. Acute inflammation was most induced in murine models using carrageenan or lipopolysaccharide (LPS), with leaf extracts being the predominant test material. Reported bioactive constituents included kaempferol, apigenin, naringenin, β-sitosterol, and squalene, together with broader classes of flavonoids, phenolics, terpenoids, steroids, alkaloids, saponins, and tannins. Across the included studies, P. canescens extracts were associated with reductions in paw edema, exudate volume, leukocyte infiltration, and pro-inflammatory mediators, including TNF-α, IL-6, COX-2, and C-reactive protein (CRP). Proposed mechanisms involved modulation of NF-κB signaling and downregulation of COX-2 and inducible nitric oxide synthase (iNOS), thereby reducing prostaglandin and nitric oxide production. Although the available evidence generally supports the anti-inflammatory potential of P. canescens, some heterogeneity in the magnitude of cytokine modulation was observed, likely reflecting differences in extraction methods, doses, and experimental models. Overall, P. canescens shows promise as a multi-target source of anti-inflammatory bioactive compounds. Further studies using standardized extracts, chronic inflammation models, and well-designed clinical trials are required to establish its therapeutic efficacy and safety.]]>
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