Molecular and Cellular Mechanisms Underlying the Therapeutic Effects of Genistein in Sepsis: A Systematic Review

Sepsis is known to be a potentially fatal condition associated with immune dysregulation and systemic inflammatory response. Genistein is one of the naturally occurring isoflavones that have been studied extensively as immune modulators. This systematic review identifies the role of genistein in sepsis. A literature search of PubMed, Embase, Scopus, Web of Science, and Google Scholar (to December 2025) revealed articles examining the role of genistein in sepsis-related disorders. Following deduplication (n = 219 of 298), 79 articles were screened, of which 49 articles were removed based upon their titles/abstracts, leaving 30 articles for review. These 30 trials consisted of 10 in vitro studies, 19 animal experiments, and 1 human trial. Throughout the trials, genistein decreased inflammatory factors (TNF-α, IL-6, and IL-1β) and increased antioxidant effects. In animal trials, genistein increased survival rates, reduced organ dysfunction symptoms, and alleviated acute lung injury. In mechanism studies, these actions were mediated through estrogen receptor-alpha (ER-α) signaling that suppressed NF-κB and MAPK signaling pathways. Preclinical data available in the literature (29 studies, of which 10 in vitro and 19 in vivo) do show that genistein could possibly reduce the inflammatory reaction in sepsis in experimental animals. Human experience, to date, appears to be very meagre indeed (n = 1). Before its use in humans, high-quality, randomized controlled clinical trials need to be undertaken to evaluate its efficacy and safety, including the possible side effects.

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