The Pharmacological Spectrum of Hispidulin: A Thorough Systematic Review and Meta-analysis

Phytochemicals have historically played a crucial role in promoting health and well-being. Hispidulin, a plant-derived metabolite, has exhibited several pharmacological applications. Despite existing research on hispidulin, a comprehensive understanding of its mechanistic pathways remains limited. Our objective is to investigate the pharmacological and biochemical cellular effects of this compound through dose analysis in a meta-analysis. Our analysis of 39 studies was conducted in accordance with the PRISMA guidelines. Key biomarkers associated with hispidulin’s pharmacological response include TNF-α, iNOS, Nrf2, HO-1, Bax, and Caspase-3. A subgroup analysis indicated that hispidulin enhanced antioxidant defense mechanisms via the Nrf2 and HO-1 pathways, while reducing pro-inflammatory markers, including TNF-α, IL-1β, and iNOS, at significantly lower doses. Additionally, dose-dependent increases in caspase-3 and Bax expression, along with a reduction in Bcl-2 levels, enhanced cell death. These dose-dependent modulations may benefit therapeutic trials and clinical translation. Our data corroborate hispidulin’s therapeutic potential and its capacity to suppress tumor growth and inflammation more effectively than oxidative effects. The findings suggest that hispidulin possesses therapeutic potential, as it reduced tumor development and inflammation more effectively than oxidative effects.