Exploring the Clinical Effects of Andrographis paniculata-Derived Compounds, Its Extract, or Derivatives for the Treatment of COVID-19: A Systematic Review and Meta-Analysis

Peerapong Prabhakornritta^1,2,3Neti Waranuch^1,2*Anjana Fuangchan^4*Kantapich Srikham¹Kansak Boonpattharatthiti⁴Cindy Barnig^3,5Siwaporn Boonyasuppayakorn⁶Tasana Pitaksuteepong²Parvapan Bhattarakosol⁶Brice Moulari³Yann Pellequer³Teerapon Dhippayom⁴

• ¹Cosmetics and Natural Products Research Center (CosNat), Naresuan University, Phitsanulok, Thailand
• ²Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, Thailand
• ³Université Marie et Louis Pasteur, EFS, INSERM UMR1098 RIGHT, Besançon, France
• ⁴The Research Unit of Evidence Synthesis (TRUES), Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, Thailand
• ⁵Department of Chest Diseases, University Hospital of Besançon, Besançon, France
• ⁶Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

The COVID-19 pandemic created a global health crisis, with limited effective treatments. Andrographis paniculata (Burm. f.) Nees (AP), with known anti-inflammatory and antiviral properties, has been explored as adjunctive therapy for COVID-19, but its clinical evidence remains inconclusive. We hypothesized that AP-derived compounds may improve symptoms and inflammatory responses in mild-to-moderate COVID-19. This systematic review and meta-analysis aimed to evaluate the clinical and biological effects of AP-derived compounds, its extract (APE), or its derivatives in patients with mild-to-moderate COVID-19.A systematic search was conducted in PubMed, EMBASE, CENTRAL, and EBSCO Open Dissertations from January 2020 to October 2024. Randomized controlled trials (RCTs) examining the effects of single-herb AP products compared to antivirals or supportive care (SC) in patients with mild-to-moderate COVID-19 were included if they reported clinical recovery, fever or cough resolution, C-reactive protein (CRP), or interleukin-6 (IL-6) levels. Risk of bias (RoB) was assessed using Cochrane RoB 2.0. A random-effects model was used to estimate pooled effects of included trials, expressed as relative risk (RR) and mean difference (MD) with 95% confidence intervals (CIs).Six RCTs involving 660 adults aged 18 to 60 were included. Compared to antivirals or SC, singleherb AP products showed no significant improvements in fever resolution (RR 1.12; 95%CI 0.90 to 1.38; I²=0.0%) or cough resolution (RR 0.98; 95%CI 0.74 to 1.31; I²=47.0%). No significant differences were observed in serum CRP (MD -0.04; 95%CI -0.26 to 0.18; I²=0.0%) and IL-6 levels (MD -0.07; 95%CI -0.17 to 0.03; I²=0.0%). While some studies not included in the meta-analysis suggested early reductions in CRP and IL-6, the findings were inconsistent. RoB was high for fever resolution but low for biomarkers. Mild adverse events, primarily liver enzyme elevations, resolved without severe complications.Our systematic review and meta-analysis suggest a potential role for AP extract and its derivatives as adjunctive therapy for COVID-19, with trends indicating possible benefits in symptom improvement and inflammation reduction. These findings highlight the need for further research to explore AP as a complementary therapeutic strategy in COVID-19 management.