Liver diseases, including viral hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), remain major global health burdens due to their high prevalence and limited therapeutic options. The need for safer and more effective hepatoprotective agents has renewed interest in traditional herbal medicines such as Radix Bupleuri. Its major bioactive constituents, saikosaponins (SSs), exhibit diverse pharmacological activities. This review synthesizes recent advances in the pharmacodynamics, molecular mechanisms, and toxicological characteristics of SSs, emphasizing their dual hepatoprotective and hepatotoxic properties. Relevant literature published from 2000 to 2025 was systematically retrieved from major scientific databases, including PubMed, Web of Science, Google Scholar, and other sources as appropriate, with emphasis on mechanistic studies and in vitro/in vivo evidence. SSs exert hepatoprotective effects through multiple mechanisms, including inhibition of nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling pathways, activation of nuclear receptors, induction of hepatic stellate cell apoptosis and autophagy, and modulation of lipid metabolism via peroxisome proliferator-activated receptor α (PPARα)/sterol regulatory element-binding protein 1c (SREBP1c) signaling. SSs in HCC inhibit Cyclooxygenase-2 and STAT3, promote apoptosis and ferroptosis, suppress angiogenesis, and enhance chemotherapy and radiotherapy sensitivity. However, accumulating evidence indicates that SSs may induce dose-dependent hepatotoxicity through oxidative stress, apoptosis and autophagy injury. These dual pharmacological effects are influenced by CYP regulation, bioavailability, and potential drug-drug interactions. Overall, SSs represent promising yet complex therapeutic candidates. Optimization of dosing strategies, clarification of mechanistic determinants, and development of advanced delivery systems are essential for their safe clinical translation. Future research should incorporate multi-omics approaches, physiologically relevant liver models, and rigorously designed clinical trials to establish standardized Saikosaponin-based therapies for liver diseases.

Polypharmacy is prevalent among older adults with sarcopenia and may negatively impact clinical outcomes. Although sarcopenia is associated with polypharmacy, the effect of deprescribing on muscle health in hospitalized patients with sarcopenia remains poorly understood. This study aimed to investigate the association between deprescribing during hospitalization and muscle strength and mass at discharge in sarcopenic patients after stroke. This study retrospectively analyzed data from a cohort of sarcopenic patients aged ≥65 years admitted to a convalescent rehabilitation ward after stroke. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia 2019 criteria. Deprescribing was defined as a reduction in the number of medications during hospitalization. The primary outcome was handgrip strength at discharge, and the secondary outcome was skeletal muscle mass index (SMI) at discharge. Multiple linear regression analyses were performed to examine the association between deprescribing and outcomes, adjusting for potential confounders. Of the 970 patients enrolled, 217 older patients, with a mean age of 81.8 years (males, 45.6%), were diagnosed with sarcopenia and included in the analysis. The median number of medications at admission was 5 (interquartile range 3–8), and 23.0% of patients experienced deprescribing during hospitalization. Deprescribing during hospitalization was independently associated with higher handgrip strength (β = 0.122, p = 0.009) and SMI (β = 0.138, p = 0.009) at discharge. Deprescribing was positively associated with improved muscle strength and mass at discharge in sarcopenic patients after stroke. These findings suggest that medication review and deprescribing may be beneficial strategies in the rehabilitation of sarcopenic stroke patients.

Shear stress (SS) generated by blood flow elicits endothelial cell (EC) responses through mechanotransduction pathways. In particular, ATP released by SS is instrumental in regulating vascular dynamics. Cyclooxygenase-2 (COX-2), typically induced by inflammatory responses, is also constitutively expressed in vascular ECs under SS and exerts antithrombotic and vasodilatory effects. However, the mechanism whereby SS-induced ATP release regulates COX-2 expression remains incompletely understood. In this study, we investigated whether extracellular ATP released by SS under disturbed flow conditions promotes COX-2 expression in the mouse brain microvascular EC line bEnd.3. SS applied by disturbed flow via orbital shaking triggered ATP release and upregulated COX-2 expression. Moreover, stimulation by exogenous ATP and uridine 5'-triphosphate (UTP) increased COX-2 expression, which was suppressed by the P2Y₂ receptor antagonist AR-C118925XX. Disturbed flow-induced COX-2 expression was consistently attenuated by AR-C118925XX. Mechanistically, P2Y₂ receptor–mediated upregulation of COX-2 was dependent on the Gq/protein kinase C/extracellular signal-regulated kinases 1/2 signaling cascade. These findings suggest that SS-induced ATP released from ECs contributes to maintaining the expression of endothelial COX-2, highlighting the role of P2Y₂ receptor signaling in endothelial mechanotransduction.