Executive Summary : | Objective: To evaluate bio-safety and clinical efficacy of the product. Summary: The proposed work presents a novel herbal cream formulation comprising an anti-fungal herbal fraction, isolated from the waste part of dietary medicinal plant as therapeutically active aqueous phase entrapped in oil phase selected for the treatment of multi-drug resistant (MDR) Candida albicans which causes strong infection in genitle organs of female as well as male, called as vulvovaginal candidiasis. Identified herbal fraction has strong efficacy and penetration potential in fluconazole (FCZ)-resistant C. albicans cells. It also has excellent thermodynamic stability ensuring long shelf life. The fraction showed minimum inhibitory concentration (MIC) at 20 ppm, while cream-based formulation exhibits MIC at 75 ppm under in-vitro and pre-clinical studies. This fraction has excellent anticandidal activity in FCZ-resistant C. albicans that is significantly higher than fluconazole and itraconazole, used as positive controls. The fraction triggers apoptosis that leads to the loss of mitochondrial membrane potential, DNA fragmentation, chromosomal condensation and activation of metacaspases. It has also been established that the fraction induces apoptotic cell death in FCZ resistant C. albicans via Ras/cAMP/PKA-Bax/Bcl2 signaling pathway. The four marker phyto-compounds in the bioactive fraction has also been identified and quantified. |