Assessment of sub-chronic toxicity and anti-aging effects of a solid self-microemulsifying drug delivery system of Kaempferia parviflora extract in a D-galactose-induced rat model

The pharmacological effects of Kaempferia parviflora have been extensively documented. A solid self-microemulsifying drug delivery system (SMEDDS) has been developed to address limitations such as poor water solubility and low bioavailability. This study evaluated the safety and anti-aging efficacy of the solid SMEDDS containing K. parviflora extract (KPS-SMEDDS) in rats. A sub-chronic toxicity study was performed to assess the safety of KPS-SMEDDS. Healthy rats (n = 10/group) received oral doses of 125, 250, or 500 mg/kg body weight daily for 90 days. Clinical signs, body weight, hematological and biochemical parameters, and major organ histopathology were evaluated. Separately, the anti-aging effects of KPS-SMEDDS were investigated in a different cohort of rats (n = 9/group) with D-galactose-induced aging. Rats received intraperitoneal D-galactose (50 mg/kg/day) and oral KPS-SMEDDS at the same doses for 60 days. Oxidative stress markers, hormone levels, histopathology, and the expression of proteins related to aging, apoptosis, and inflammation were assessed. No significant changes were observed in clinical signs, body weight, organ weights, hematological or biochemical parameters, or histopathology in KPS-SMEDDS-treated rats, indicating its safety. KPS-SMEDDS treatment significantly improved testicular weight, reduced malondialdehyde levels, normalized hormone levels, and restored testicular structure in rats with D-galactose-induced aging. Additionally, it upregulated SIRT-1 and Bcl-2, downregulated SA-β-gal, p53, and caspase-3, and modulated inflammatory cytokines (TNF-α, IL-6, and IL-10). KPS-SMEDDS was well-tolerated in rats and exerted protective effects against D-galactose-induced aging. These findings support its potential as a safe, natural anti-aging agent and highlight the value of formulation enhancement in traditional herbal medicine.