Bioorganic chemistry · 2025
Ginsenoside Rd and chrysophanol: Modulating the serine-glycine-one-carbon pathway to enhance neuroprotection in intracerebral hemorrhage.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Zhao Xingping, Zhou Huifen, Pan Zhiyong, Guo JianWen, Yang Jiehong, Wan HaiTong
Аннотация
BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized by oxidative stress, inflammatory cascades, and metabolic dysregulation. Ginsenoside Rd (G-Rd) and chrysophanol (Chr), two natural compounds with antioxidative and anti-inflammatory properties, have demonstrated neuroprotective potential, however, their mechanisms in ICH remain unclear.
OBJECTIVE: This study aimed to investigate the protective effects of G-Rd and Chr against heme-induced injury in HT22 cells and in a rat model of ICH, with a focus on oxidative stress, inflammation, apoptosis, and metabolic regulation.
METHODS: In vitro, HT22 cells were exposed with heme (10 μmol/L, 12 h) to simulate ICH injury, followed by treatment with G-Rd and Chr (80 μmol/L). Reactive oxygen species (ROS), apoptosis, mitochondrial membrane potential, and inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10) were assessed using flow cytometry, fluorescence microscopy, and ELISA. In vivo, ICH was induced in rats via collagenase injection. Neurological function, hematoma volume, histopathology, and metabolic enzymes (SOD, MDA, NAD+, Ca2+-ATPase) were evaluated. Western blotting was used to analyze key enzymes in the serine-glycine-one‑carbon (SGOC) pathway.
RESULTS: G-Rd and Chr significantly suppressed ROS production (P < 0.05), downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6; P < 0.01), and inhibited apoptosis (P < 0.01) in HT22 cells. Both compounds restored mitochondrial membrane potential and alleviated cellular damage. In the ICH rat model, combined treatment improved neurological scores by 45 % (P < 0.01), decreased hematoma volume by 38 % (P < 0.01), and restored metabolic homeostasis through modulation of SGOC pathway enzymes (PHGDH, PSAT1, PSPH, SHMT2; P < 0.05). Synergistic effects were observed in both hematoma resolution and neuroprotection.
CONCLUSION: G-Rd and Chr confer neuroprotection in ICH through antioxidative, anti-inflammatory, anti-apoptotic, and metabolic regulatory mechanisms. Their synergistic efficacy underscores their promise as therapeutic candidates, meriting further investigation of their molecular targets and translational potential.
OBJECTIVE: This study aimed to investigate the protective effects of G-Rd and Chr against heme-induced injury in HT22 cells and in a rat model of ICH, with a focus on oxidative stress, inflammation, apoptosis, and metabolic regulation.
METHODS: In vitro, HT22 cells were exposed with heme (10 μmol/L, 12 h) to simulate ICH injury, followed by treatment with G-Rd and Chr (80 μmol/L). Reactive oxygen species (ROS), apoptosis, mitochondrial membrane potential, and inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10) were assessed using flow cytometry, fluorescence microscopy, and ELISA. In vivo, ICH was induced in rats via collagenase injection. Neurological function, hematoma volume, histopathology, and metabolic enzymes (SOD, MDA, NAD+, Ca2+-ATPase) were evaluated. Western blotting was used to analyze key enzymes in the serine-glycine-one‑carbon (SGOC) pathway.
RESULTS: G-Rd and Chr significantly suppressed ROS production (P < 0.05), downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6; P < 0.01), and inhibited apoptosis (P < 0.01) in HT22 cells. Both compounds restored mitochondrial membrane potential and alleviated cellular damage. In the ICH rat model, combined treatment improved neurological scores by 45 % (P < 0.01), decreased hematoma volume by 38 % (P < 0.01), and restored metabolic homeostasis through modulation of SGOC pathway enzymes (PHGDH, PSAT1, PSPH, SHMT2; P < 0.05). Synergistic effects were observed in both hematoma resolution and neuroprotection.
CONCLUSION: G-Rd and Chr confer neuroprotection in ICH through antioxidative, anti-inflammatory, anti-apoptotic, and metabolic regulatory mechanisms. Their synergistic efficacy underscores their promise as therapeutic candidates, meriting further investigation of their molecular targets and translational potential.