Antiproliferative and Anti-Inflammatory Effects of Physalis angulata L. Extract on Various Human Cancer Cell Lines in Vitro Studies: Systematic Review

Abstract

Cancer was a leading cause of mortality worldwide and in Indonesia, with limited access to modern therapies and significant adverse effects associated with chemotherapy. The medicinal plant Physalis angulata L. was investigated as a potential alternative due to its cytotoxic and anti-inflammatory properties against cancer cells. This review aimed to evaluate evidence from studies examining the anticancer potential of isolated compounds from this plant. A systematic search was conducted using PubMed and ScienceDirect databases following PRISMA guidelines, focusing on in vitro studies published within the last ten years. Six studies met the inclusion and exclusion criteria. Data were extracted based on plant parts, isolation methods, tested cell lines, and study outcomes using IC50 values. The results show that all studies produce withanolide fractions through extraction using polar to semi-polar solvents, followed by purification with various chromatographic techniques. The main compounds in Physalis angulata, particularly withanolides such as physalin and physagulide, exhibit moderate to strong anticancer activity across various cancer cell lines (IC₅₀ 0.18–21.75 μM) and demonstrate anti-inflammatory effects by inhibiting iNOS and COX-2 production. Physalins increase reactive oxygen species, leading to mitochondrial damage and activation of apoptosis. Several compounds also inhibit key signaling pathways involved in cell survival, including MAPK, JAK/STAT3, Wnt/β-catenin, and Hedgehog pathways. The anti-inflammatory effects occur through inhibition of the NF-κB pathway, resulting in reduced expression of pro-inflammatory mediators. In conclusion, Physalis angulata L. shows promising anticancer and anti-inflammatory potential in vitro, supporting its development as a candidate for future therapeutic applications. Further studies are required to validate these findings in vivo and in clinical settings.