The anti-inflammatory effects of Citrus hystrix DC.: a systematic review and meta-analysis of in vitro and in vivo studies

Citrus hystrix DC., commonly known as kaffir lime, has been widely used in traditional medicine for its potential anti-inflammatory properties. However, evidence from experimental studies remains limited. This systematic review and meta-analysis aimed to synthesize existing in vitro and in vivo evidence on the anti-inflammatory effects of C. hystrix and its bioactive compounds. PubMed, EMBASE, and Scopus were searched up to May 27, 2025, for experimental studies evaluating the anti-inflammatory activity of C. hystrix extracts or compounds in vitro or in vivo. Data on inflammatory biomarkers included nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, cyclooxygenase-2 (COX-2), and the inhibition of bovine serum albumin (BSA) denaturation were extracted. Random-effects meta-analysis was performed, with heterogeneity assessed using I² statistics. A total of 1,049 records were identified, of which 9 studies met the inclusion criteria. The included studies comprised both in vitro (n = 7) and in vivo (n = 2) experiments. The systematic review demonstrated that C. hystrix significantly reduced NO production, TNF-α, and IL-6 levels (p < 0.05) compared with controls, indicating strong anti-inflammatory activity. Findings from the meta-analysis revealed that the pooled effect estimate indicated a mean inhibition rate of the bovine serum albumin (BSA) degradation of 46.48% (95% CI: 28.66-64.31; p < 0.001), while the inhibitory effect of C. hystrix on TNF-α was 36.43% (95% CI: 1.18-71.68; p < 0.05). However, substantial heterogeneity (I² > 80%) was observed, which was likely attributable to variations in experimental models, extract types, and dosages used across studies. This systematic review and meta-analysis provided quantitative evidence supporting the anti-inflammatory potential of C. hystrix. The findings highlighted its role in suppressing pro-inflammatory cytokines and mediators in both in vitro and in vivo models. Future research should focus on standardized extract formulations, dose-response relationships, and clinical trials to validate its therapeutic efficacy in humans.