Journal of ethnopharmacology · 2025
From traditional tonic herb to molecular therapy: The natural peptide G-6-Y from Eleutherococcus sessiliflorus protects against drug-induced liver injury.
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Ding Xuying, Wang Siya, Yu Miao, Wang Leiyi, Huang Qucheng, Zheng Jiaxin, Zuo Yuanyuan, Liu Chang
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Eleutherococcus sessiliflorus, a traditional medicinal herb from Northeast China, has long been used to strengthen the liver and improve vitality. Modern pharmacological studies reveal its antioxidant and hepatoprotective properties, but its bioactive peptides remain poorly characterized.
AIM OF THE STUDY: This study aimed to investigate the hepatoprotective effects and mechanisms of a natural antioxidant peptide (G-6-Y) derived from Eleutherococcus sessiliflorus against acetaminophen (APAP)-induced drug-induced liver injury (DILI).
MATERIALS AND METHODS: A natural peptide, G-6-Y (Gly-Lys-Lys-Thr-Trp-Tyr), was identified and synthesized based on prior isolation from Eleutherococcus sessiliflorus. In vitro and in vivo experiments were conducted using AML12 hepatocytes and APAP-induced DILI mice. Biochemical assays, histopathology, ROS detection, TUNEL staining, Western blotting, immunohistochemistry, and transcriptomic analyses were employed to evaluate oxidative stress, apoptosis, and inflammatory responses.
RESULTS: G-6-Y significantly alleviated APAP-induced hepatic injury by reducing serum ALT and AST levels and improving histopathological architecture. It decreased ROS accumulation, restored antioxidant enzyme activities (SOD, CAT, GPx), and suppressed pro-inflammatory cytokine release (IL-1β, IL-6, TNF-α). Mechanistically, G-6-Y downregulated CYP2E1 expression, preserved mitochondrial membrane potential, and inhibited mitochondrial-dependent apoptosis by modulating Bax/Bcl-2 balance and reducing cleaved-caspase-3 activation. Transcriptomic and qRT-PCR analyses further confirmed that G-6-Y regulates genes involved in antioxidant defense and mitochondrial apoptotic pathways.
CONCLUSIONS: G-6-Y, a natural bioactive peptide derived from E. sessiliflorus, exhibits potent antioxidant, anti-inflammatory, and anti-apoptotic effects, protecting hepatocytes from APAP-induced injury through CYP2E1 suppression and mitochondrial stabilization. These findings highlight G-6-Y as a promising natural therapeutic candidate or functional food ingredient for preventing and treating DILI and support the modern pharmacological development of Eleutherococcus sessiliflorus resources.
AIM OF THE STUDY: This study aimed to investigate the hepatoprotective effects and mechanisms of a natural antioxidant peptide (G-6-Y) derived from Eleutherococcus sessiliflorus against acetaminophen (APAP)-induced drug-induced liver injury (DILI).
MATERIALS AND METHODS: A natural peptide, G-6-Y (Gly-Lys-Lys-Thr-Trp-Tyr), was identified and synthesized based on prior isolation from Eleutherococcus sessiliflorus. In vitro and in vivo experiments were conducted using AML12 hepatocytes and APAP-induced DILI mice. Biochemical assays, histopathology, ROS detection, TUNEL staining, Western blotting, immunohistochemistry, and transcriptomic analyses were employed to evaluate oxidative stress, apoptosis, and inflammatory responses.
RESULTS: G-6-Y significantly alleviated APAP-induced hepatic injury by reducing serum ALT and AST levels and improving histopathological architecture. It decreased ROS accumulation, restored antioxidant enzyme activities (SOD, CAT, GPx), and suppressed pro-inflammatory cytokine release (IL-1β, IL-6, TNF-α). Mechanistically, G-6-Y downregulated CYP2E1 expression, preserved mitochondrial membrane potential, and inhibited mitochondrial-dependent apoptosis by modulating Bax/Bcl-2 balance and reducing cleaved-caspase-3 activation. Transcriptomic and qRT-PCR analyses further confirmed that G-6-Y regulates genes involved in antioxidant defense and mitochondrial apoptotic pathways.
CONCLUSIONS: G-6-Y, a natural bioactive peptide derived from E. sessiliflorus, exhibits potent antioxidant, anti-inflammatory, and anti-apoptotic effects, protecting hepatocytes from APAP-induced injury through CYP2E1 suppression and mitochondrial stabilization. These findings highlight G-6-Y as a promising natural therapeutic candidate or functional food ingredient for preventing and treating DILI and support the modern pharmacological development of Eleutherococcus sessiliflorus resources.