Schisandrin B (Sch B) is a dibenzocyclooctadiene lignan derived from plants of the Schisandra genus. Owing to its pronounced lipophilicity, Sch B may readily cross biological membranes and is increasingly discussed in association with the regulation of mitochondrial homeostasis. Mitochondrial dysfunction underlies key pathological processes involved in multi-organ injury and a broad range of chronic diseases, manifested as redox imbalance, reduced mitochondrial membrane potential (ΔΨm), impaired ATP production, mitochondrial DNA (mtDNA) damage, disrupted mitochondrial dynamics, failure of mitochondrial quality control, and amplified inflammation, thereby promoting cell death and tissue remodeling. Accumulating evidence in recent years suggests that Sch B exerts biological effects associated with improved mitochondrial function in multiple models involving the liver, kidney, heart, brain, lung, and tumors. However, previous reviews have primarily focused on overall pharmacological activities or individual diseases, and a cross-organ integrative framework with “mitochondria” as the central axis remains limited. Based on current evidence, the mitochondria-related actions of Sch B can be summarized at several complementary levels: maintaining redox balance; stabilizing ΔΨm and potentially modulating the threshold of the mitochondrial permeability transition pore (mPTP); improving calcium homeostasis and bioenergetic output; reshaping the balance between fusion and fission; context-dependently regulating autophagy/mitophagy and autophagic flux; and bidirectionally influencing mitochondria-mediated apoptotic pathways in distinct cellular settings. At the organ level, the effects of Sch B exhibit a “pathology-driven matching” pattern: in acute stresses such as ischemia–reperfusion, Sch B tends to enhance mitochondrial stress tolerance and promote energy recovery; in toxin/drug-induced injury, it more prominently delays membrane structural disruption and oxidative damage; whereas in metabolic chronic diseases, its actions are associated with metabolic flexibility and the continuity of quality control processes. Despite the cross-organ consistency of Sch B in mitochondrial regulation, its translation remains constrained by factors including in vivo exposure, effective intramitochondrial concentration, delivery and targeting strategies, safety boundaries, and interindividual variability. Therefore, this review proposes a multi-organ mechanistic model centered on “mitochondrial homeostasis regulation,” providing a theoretical basis for understanding the cross-system effects of Sch B and for future drug development and optimization.
Guo et al. (2026) studied this question.