The Efficacy of Phyllanthus niruri Linn in Modulating Inflammatory and Cancer Stem Cell Markers in Colorectal Cancer: A Stratified Systematic Review and Meta-Analysis

Nurul Ahmad Isnaini (Biomedical Science Study Program, Department of Surgery, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia)
Albertus Ari Adrianto (Department of Digestive Surgery, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia)
Udadi Sadhana (Department of Pathological Anatomy, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia)

Bioscientia Medicina : Journal of Biomedicine and Translational Research
Vol. 9 No. 10 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research

Background: The progression of colorectal cancer (CRC) is driven by a complex interplay between chronic inflammation and a resilient population of cancer stem cells (CSCs). Phyllanthus niruri Linn (PNL), a medicinal plant with established immunomodulatory effects, presents a promising adjuvant therapeutic strategy. This study aimed to move beyond qualitative summaries to quantitatively assess PNL's efficacy by synthesizing evidence on its modulation of key inflammatory and CSC biomarkers. Methods: Following PRISMA guidelines, a systematic search of PubMed, ScienceDirect, Google Scholar, and Scopus (2015–2025) was conducted. Studies quantifying the effects of PNL on Interleukin-8 (IL-8), Cyclooxygenase-2 (COX-2), or CD133 in CRC models were included. Recognizing the profound biological differences between experimental systems, a stratified meta-analysis was performed. Data were pooled using a random-effects model, stratified by study type (in vitro vs. in vivo) and intervention (monotherapy vs. combination therapy). The Standardized Mean Difference (SMD) was the primary effect measure. Results: Seven studies met the inclusion criteria. In a stratified analysis of in vivo models, PNL monotherapy significantly reduced COX-2 (SMD -2.11; 95% CI [-3.10, -1.12]) and IL-8 (SMD -1.95; 95% CI [-3.01, -0.89]). The effect on the CSC marker CD133 was most pronounced in vitro (SMD -2.98; 95% CI [-4.87, -1.09]), while still significant in in vivo models (SMD -2.15; 95% CI [-3.45, -0.85]). The analysis revealed that the biological context (in vitro vs. in vivo) is a significant determinant of the observed effect size. Conclusion: This stratified meta-analysis provides robust, context-specific evidence of PNL's ability to suppress key inflammatory and CSC markers in CRC. The findings reveal that PNL's potent anti-CSC activity observed in vitro is translated into a significant, though attenuated, effect in vivo, highlighting the critical influence of the tumor microenvironment and pharmacokinetics. This work substantiates the dual-pronged therapeutic potential of PNL as a promising bioactive adjuvant in CRC therapy.