Journal of ethnopharmacology · 2025
Zhishe Tongluo capsule ameliorates experimental ischemic brain injury through regulating the CALB2/Ca2+/PKC pathway and glycerophospholipid metabolism.
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Li Yu, Zhang Jingjing, Zhang Yi, Xu He, Zhao Ye, Tian Jixiang, Yang Hongjun, Zhang Fangbo
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke (IS) is a leading cause of death and disability. However, clinical treatment options remain limited. A traditional Chinese formula called Zhishe Tongluo capsule (ZSTL) is used for treating IS in the clinic, and it has better efficacy to benefit Qi and activate blood. However, the precise efficacy and mechanism remain undetermined.
AIM OF THE STUDY: To elucidate the protective effect and possible mechanism of ZSTL against IS.
MATERIALS AND METHODS: The permanent middle cerebral artery occlusion (pMCAO) rat model was constructed to evaluate the neurological function, cerebral infarct area, and pathological change after ZSTL treatment. Furthermore, quantitative proteomics and metabolomics were used to screen the potential targets and metabolic pathways associated with IS pathogenesis and ZSTL treatment. The oxygen-glucose deprivation (OGD)-induced PC12 cells were established to assess the apoptosis rate and Ca2+ level after ZSTL intervention. Both animal and cellular experiments detected the levels of inflammatory cytokines, the activities of oxidative stress-related enzymes, and the potential targets of ZSTL against IS. Additionally, the binding affinity between ZSTL's potential targets and chemical constituents was determined by molecular docking.
RESULTS: The in vivo experiment revealed that ZSTL treatment significantly improved neurological deficits, ameliorated cerebral injuries, suppressed inflammatory reaction, and oxidative stress. The in vitro analysis demonstrated that ZSTL pretreatment effectively inhibited apoptosis, inflammation, oxidative stress, and calcium overload, thus protecting PC12 cells against OGD-induced damage. Proteomics analysis illustrated that ZSTL could modulate CALB2 expression. Furthermore, WB confirmed that ZSTL inhibited CALB2/Ca2+/PKC pathway in vivo and in vitro experiments. Molecular docking analysis revealed that CALB2 and PKC exhibit high binding affinity for the ZSTL's chemical constituents. Metabolomics analysis demonstrated that glycerophospholipid metabolism plays a vital role in ZSTL-mediated neuroprotection. Pearson correlation analysis showed that the CALB2/Ca2+/PKC pathway was closely associated with glycerophospholipid metabolism.
CONCLUSION: ZSTL alleviates experimental ischemic brain injury through regulating the CALB2/Ca2+/PKC pathway and glycerophospholipid metabolism. This investigation provides experimental evidence for the clinical application of ZSTL in treating IS and offers novel therapeutic insights for IS treatment.
AIM OF THE STUDY: To elucidate the protective effect and possible mechanism of ZSTL against IS.
MATERIALS AND METHODS: The permanent middle cerebral artery occlusion (pMCAO) rat model was constructed to evaluate the neurological function, cerebral infarct area, and pathological change after ZSTL treatment. Furthermore, quantitative proteomics and metabolomics were used to screen the potential targets and metabolic pathways associated with IS pathogenesis and ZSTL treatment. The oxygen-glucose deprivation (OGD)-induced PC12 cells were established to assess the apoptosis rate and Ca2+ level after ZSTL intervention. Both animal and cellular experiments detected the levels of inflammatory cytokines, the activities of oxidative stress-related enzymes, and the potential targets of ZSTL against IS. Additionally, the binding affinity between ZSTL's potential targets and chemical constituents was determined by molecular docking.
RESULTS: The in vivo experiment revealed that ZSTL treatment significantly improved neurological deficits, ameliorated cerebral injuries, suppressed inflammatory reaction, and oxidative stress. The in vitro analysis demonstrated that ZSTL pretreatment effectively inhibited apoptosis, inflammation, oxidative stress, and calcium overload, thus protecting PC12 cells against OGD-induced damage. Proteomics analysis illustrated that ZSTL could modulate CALB2 expression. Furthermore, WB confirmed that ZSTL inhibited CALB2/Ca2+/PKC pathway in vivo and in vitro experiments. Molecular docking analysis revealed that CALB2 and PKC exhibit high binding affinity for the ZSTL's chemical constituents. Metabolomics analysis demonstrated that glycerophospholipid metabolism plays a vital role in ZSTL-mediated neuroprotection. Pearson correlation analysis showed that the CALB2/Ca2+/PKC pathway was closely associated with glycerophospholipid metabolism.
CONCLUSION: ZSTL alleviates experimental ischemic brain injury through regulating the CALB2/Ca2+/PKC pathway and glycerophospholipid metabolism. This investigation provides experimental evidence for the clinical application of ZSTL in treating IS and offers novel therapeutic insights for IS treatment.