College of Traditional Chinese Medicine, Zhejiang Pharmaceutical University, No. 666, Siming Road, Fenghua District, Ningbo, Zhejiang Province, 315100, PR China.
Zhejiang Provincial Key Laboratory of Resources Protection and Innovation of Traditional Chinese Medicine, Zhejiang A&F University, No. 666, Wusu Street, Lin'an District, Hangzhou, Zhejiang Province, 311300, PR China.
J Ethnopharmacol. 2024 Jan 10;318(Pt A):116912. doi: 10.1016/j.jep.2023.116912. Epub 2023 Jul 13.
Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum, Sanyeqing) has been used in the prevention and treatment of repetitive Febrile seizures (FS) over the centuries in China.
T. hemsleyanum exerts wide pharmacological action, which has been widely used for treating various diseases, including infantile febrile seizure. However, the systematic study on this herb's material basis and the functional mechanism is lacking. This study intended to systematically elucidate the mechanism of T. hemsleyanum against febrile seizures.
The efficacy of T. hemsleyanum was estimated by using a hot bath as a model of FS, the onset and duration of seizure, morphological structure changes of hippocampal neurons as well as magnetoencephalography were applied to evaluate the effects. Meanwhile, the bioactive components of T. hemsleyanum responsible for the therapeutic effect of T. hemsleyanum on FS were identified by UPLC-MS/MS. Then we systematically elucidated the mechanism of T. hemsleyanum based on metabonomics, transcriptomics, network pharmacological and experimental validation.
In a hyperthermia-induced FS model of rats, T. hemsleyanum significantly increased the seizure latency and decreased seizure duration, alleviating the abnormal delta and gamma band activity during epileptic discharge. Furthermore, ten chemical components of ethanol extracts from T. hemsleyanum were identified by UPLC-MS/MS, including quercetin, kaempferol, and procyanidin B1 and so on, which was consistent with the network pharmacology prediction. The serum metabolomics indicated that T. hemsleyanum mainly acts on inflammation regulation and neuroprotection by the glycerophospholipid metabolism pathway. Ninety-two potential targets of T. hemsleyanum on FS were identified by network pharmacology, and TNF, IL-6, and IL-1β were considered the pivotal targets. In the hippocampus transcriptomics, 17 KEGG pathways were identified after T. hemsleyanum treatment compared with the FS model group, among which 15 pathways overlapped with those identified by network pharmacology, and the PKC-δ/caspase-1 signaling pathway was a critical node. Finally, in vivo experiments also verified T. hemsleyanum inhibited the activation of microglia and resulted in a significant reduction in the level of PKCδ, NLRC4, caspase-1, IL-1β, IL-6 and TNF-α in hippocampus of FS rats.
Our study suggested that the therapeutic effect of T. hemsleyanum on FS might be regulated by inhibiting the neuroinflammation, thus exerting an anticonvulsant effect in vivo, and the mechanism might be related to regulating the PKC-δ/caspase-1 signaling pathway.
藤茶（Tetrastigma hemsleyanum Diels et Gilg，T. hemsleyanum，三叶青）在中国几个世纪以来一直被用于预防和治疗复发性热性惊厥（FS）。
藤茶具有广泛的药理作用，已广泛用于治疗各种疾病，包括婴儿热性惊厥。然而，关于该草药的物质基础和功能机制的系统研究还很缺乏。本研究旨在系统阐明藤茶防治热性惊厥的机制。
采用热水浴作为 FS 模型，评估藤茶的功效，包括惊厥的发作和持续时间、海马神经元的形态结构变化以及脑磁图。同时，采用 UPLC-MS/MS 鉴定出藤茶中负责藤茶治疗 FS 疗效的生物活性成分。然后，我们基于代谢组学、转录组学、网络药理学和实验验证，系统地阐明了藤茶的作用机制。
在大鼠高热诱导的 FS 模型中，藤茶能显著延长惊厥潜伏期，缩短惊厥持续时间，减轻癫痫放电时异常的δ和γ波段活动。此外，通过 UPLC-MS/MS 鉴定出藤茶乙醇提取物中的 10 种化学成分，包括槲皮素、山奈酚、原花青素 B1 等，这与网络药理学预测一致。血清代谢组学表明，藤茶主要通过甘油磷脂代谢途径作用于炎症调节和神经保护。通过网络药理学鉴定出藤茶治疗 FS 的 92 个潜在靶点，其中 TNF、IL-6 和 IL-1β 被认为是关键靶点。在海马转录组学中，与 FS 模型组相比，藤茶处理后鉴定出 17 条 KEGG 通路，其中 15 条与网络药理学鉴定出的通路重叠，PKC-δ/caspase-1 信号通路是一个关键节点。最后，体内实验也验证了藤茶抑制小胶质细胞的激活，导致 FS 大鼠海马中 PKCδ、NLRC4、caspase-1、IL-1β、IL-6 和 TNF-α的水平显著降低。
本研究表明，藤茶治疗 FS 的疗效可能是通过抑制神经炎症来调节的，从而在体内发挥抗惊厥作用，其机制可能与调节 PKC-δ/caspase-1 信号通路有关。
Zotero 插件