PDF(Pubmed)
Abstract：
UNASSIGNED: Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice.
UNASSIGNED: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers.
UNASSIGNED: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (-31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation.
UNASSIGNED: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.
UNASSIGNED: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers.
UNASSIGNED: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (-31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation.
UNASSIGNED: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.
摘要：
■葛根(P.lobata),一种双重用途的食品和药品，在酒精解毒和肝脏保护方面表现出有限的功效，与以前的研究主要集中在葛根素干。在这项研究中,我们研究了新鲜的根源性外泌体样纳米囊泡（P-ELNs）减轻酒精中毒的潜在作用和机制，对C57BL/6J小鼠具有促进酒精代谢和保护肝脏的作用。
■我们使用差速离心从新鲜的P.lobata根中分离了P-ELN，并通过透射电子显微镜对其进行了表征，纳米级粒度，ζ电位分析,和生化化验。在用P-ELN预处理的急性酒精中毒（AAI）小鼠中，我们评估了它们对正确反射（LORR）丧失的时间和持续时间的影响，肝脏酒精代谢酶活性，肝脏和血清酒精含量，和铁凋亡相关标记。
■P-ELN，富含蛋白质，脂质，和小RNA，表现出理想的尺寸（150.7±82.8nm）和负表面电荷（-31mV）。用10mg/(kg。bw）雄性和雌性小鼠的P-ELN显着延长了焦虑时间，缩短了清醒时间，增强乙醛脱氢酶（ALDH）活性，同时抑制乙醇脱氢酶（ADH）活性，肝脏和血清中的酒精含量降低。值得注意的是,与P-ELNs上清液（丰富的葛根素含量）相比，P-ELNs表现出更高的功效，提示葛根素以外的其他活性成分。此外,P-ELN通过抑制谷胱甘肽过氧化物酶4（GPX4）和还原型谷胱甘肽（GSH）的还原来防止铁死亡，并抑制酰基辅酶A合成酶长链家族成员4（ACSL4）的升高，从而减轻病理性肝脏脂质积累。
■P-ELNs表现出独特的外泌体特征并有效缓解酒精中毒，改善酒精代谢，抑制铁性凋亡，保护肝脏免受酒精损伤。因此,P-ELN有望成为解毒的治疗剂，清醒促进，预防酒精性肝损伤。
■我们使用差速离心从新鲜的P.lobata根中分离了P-ELN，并通过透射电子显微镜对其进行了表征，纳米级粒度，ζ电位分析,和生化化验。在用P-ELN预处理的急性酒精中毒（AAI）小鼠中，我们评估了它们对正确反射（LORR）丧失的时间和持续时间的影响，肝脏酒精代谢酶活性，肝脏和血清酒精含量，和铁凋亡相关标记。
■P-ELN，富含蛋白质，脂质，和小RNA，表现出理想的尺寸（150.7±82.8nm）和负表面电荷（-31mV）。用10mg/(kg。bw）雄性和雌性小鼠的P-ELN显着延长了焦虑时间，缩短了清醒时间，增强乙醛脱氢酶（ALDH）活性，同时抑制乙醇脱氢酶（ADH）活性，肝脏和血清中的酒精含量降低。值得注意的是,与P-ELNs上清液（丰富的葛根素含量）相比，P-ELNs表现出更高的功效，提示葛根素以外的其他活性成分。此外,P-ELN通过抑制谷胱甘肽过氧化物酶4（GPX4）和还原型谷胱甘肽（GSH）的还原来防止铁死亡，并抑制酰基辅酶A合成酶长链家族成员4（ACSL4）的升高，从而减轻病理性肝脏脂质积累。
■P-ELNs表现出独特的外泌体特征并有效缓解酒精中毒，改善酒精代谢，抑制铁性凋亡，保护肝脏免受酒精损伤。因此,P-ELN有望成为解毒的治疗剂，清醒促进，预防酒精性肝损伤。
