Syzygium Cordatum Biosafety and Antifungal Activity Substantiation

Abstract

Fungal infections are a major neglected tropical disease affecting over 80% or people in the developing world. These mycoses, which include common superficial conditions like candidiasis, as well as life-threatening systemic infections, are often exacerbated by the rise in antifungal resistance, high treatment costs, and undesirable side effects of conventional antifungal drugs such as azoles. This reality has spurred a growing interest in alternative, plant-based therapies, especially those grounded in traditional medicine. Syzygium cordatum, commonly referred to as the “waterberry tree,” is a medicinal plant native to southern Africa and widely used in traditional medicine to manage various mycotic conditions. However, its antifungal properties and biosafety profile remain scientifically unsubstantiated. The primary aim of this study was to investigate the pharmacological activity and biosafety of lyophilized hydroethanolic Syzygium cordatum leaf extracts. The lyophilized extracts were screened for their active secondary metabolites using various classical chemistry techniques. The antifungal efficacy was evaluated using the agar well diffusion method against clinically relevant fungal strains including Candida albicans. Acute toxicity was investigated using an amended OECD guideline 425 and Draize skin sensitivity tests were carried out using New Zealand Albino rabbits. The egg albumin test was employed to determine the anti-inflammatory activity. Metabolomic screening confirmed the presence of various pharmacologically relevant bioactive constituents. The extract showed significant fungal zones of inhibition, comparable to the standard ketoconazole. The extracts had an LD50 over 5000mg/kg body weight and recorded negligible skin irritation potential. The anti-inflammatory activity at 1000 µg/mL was comparable to diclofenac at 250 µg/mL.  Our findings concluded that lyophilized extracts of Syzygium cordatum are toxicologically safe according to the Hodges and Stenner toxicity classification and pose no skin irritation risk. We also confirmed that the various metabolites present impart anti-inflammatory as well as significant anti-fungal benefits which justify the plant’s use in traditional medicine.