Dynamin-related protein 1 (DRP1) is an essential controller of mitochondrial fission whose activity is tightly controlled to ensure balanced mitochondrial dynamics and maintain internal cellular homeostasis. Growing evidence suggests that DRP1-dependent mitochondrial fission plays a role in drug-induced toxicity (DIT). Therefore, understanding the molecular mechanisms underlying DIT and the precise regulation of DRP1 function will inform the development of potential therapeutic treatments for DIT. This review comprehensively summarizes the diverse DITs and their potential mechanism associated with DRP1-dependent mitochondrial fission and discusses in vivo and in vitro model studies of toxicity protection targeting DRP1.

SGLT2 inhibitors, initially developed for type 2 diabetes management, have primarily demonstrated pleiotropic benefits in cardiovascular, renal, pulmonary, digestive and endocrine/metabolic, et al. Emerging evidence highlights their immunomodulatory effects on macrophages, key players in disease pathogenesis. This review summarizes the mechanisms by which dapagliflozin, empagliflozin, and canagliflozin regulate macrophage polarization, metabolic reprogramming, and inflammatory responses. These drugs suppress pro-inflammatory M1 macrophage activation, promote anti-inflammatory M2 phenotypes, and reduce the release of cytokines (e.g., IL-1β, IL-6,TNF-α) through pathways such as NF-κB, AMPK/mTOR, and JAK/STAT. In cardiovascular diseases, they attenuate atherosclerosis (AS) and myocardial fibrosis by limiting macrophage infiltration and foam cell formation. Renal protection is mediated via reduced macrophage-driven inflammation and fibrosis in diabetic and non-diabetic kidney injury. Additionally, their anti-inflammatory effects extend toothers like non-alcoholic fatty liver disease and inflammatory bowel disease. Collectively, SGLT2 inhibitors exhibit multi-organ protective potential through macrophage modulation, positioning them as promising immunomodulatory agents beyond glucose-lowering therapy.

Tripterygium wilfordii Hook F (TWHF) is a traditional Chinese medicine with multifaceted pharmacological properties, has faced clinical application challenges due to its dose-limiting organ toxicity. Through a systematic analysis of current literature, this review deciphers the dual regulatory role of mitochondrial function in mediating both therapeutic efficacy and adverse effects of TWHF-derived active compounds. We elucidate that processes such as mitochondrial biogenesis, mitochondrial fusion and fission, mitophagy and mitochondrial apoptosis pathways influence the therapeutic efficacy and adverse effects of TWHF active ingredients. In addition, we review innovative dosage forms and derivatives of TWHF that exploit mitochondrial targeting to enhance their pharmacological efficacy. This article offers a concise overview pharmacological and toxicological effects of the principal active components of TWHF, in particular triptolide and celastrol, with a particular emphasis on elucidating the critical role of mitochondria in these processes. Further high-quality basic studies are essential to strengthen the link between mitochondrial function and the active compounds of TWHF, offering more diverse options for their clinical development. Graphical Abstract