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<p><i>Citrus hystrix</i> 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 <i>C. hystrix</i> and its bioactive compounds. PubMed, EMBASE, and Scopus were searched up to May 27, 2025, for experimental studies evaluating the anti-inflammatory activity of <i>C. hystrix</i> 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 <i>I²</i> statistics. A total of 1,049 records were identified, of which 9 studies met the inclusion criteria. The included studies comprised both in vitro (<i>n</i> = 7) and in vivo (<i>n</i> = 2) experiments. The systematic review demonstrated that <i>C. hystrix</i> significantly reduced NO production, TNF-α, and IL-6 levels (<i>p</i> &lt; 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; <i>p</i> &lt; 0.001), while the inhibitory effect of <i>C. hystrix</i> on TNF-α was 36.43% (95% CI: 1.18–71.68; <i>p</i> &lt; 0.05). However, substantial heterogeneity (<i>I²</i> &gt; 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 <i>C. hystrix</i>. 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月24日

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  • Watunyoo Buakaew,
  • Yordhathai Thongsri,
  • Wiriya Mahikul,
  • Kanchana Usuwanthim

摘要

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.