Department of Emergency, Rongchang People's Hospital, Chongqing, China.
Pharm Biol. 2023 Dec;61(1):897-906. doi: 10.1080/13880209.2023.2215849.
Plantamajoside (PMS) possesses rich pharmacological characteristics that have been applied to remedy dozens of diseases. However, the understanding of PMS in sepsis remains insufficient.
Role of PMS in sepsis-regulated organ dysfunction and potential mechanisms were investigated.
Thirty C57BL/6 male mice were adaptive fed for three days and used to establish acute sepsis model by caecal ligation and perforation (CLP). These experimental mice were divided into Sham, CLP, CLP + 25 mg PMS/kg body weight (PMS/kg), CLP + 50 mg PMS/kg and CLP + 100 mg PMS/kg ( = 6). The pathological and apoptotic changes of lung, liver and heart tissues were observed via HE and TUNEL staining. The injury-related factors of lung, liver and heart were detected by corresponding kits. ELISA and qRT-PCR were applied to assess IL-6/TNF-α/IL-1β levels. Apoptosis-related and TRAF6/NF-κB-related proteins were determined using Western blotting.
All doses of PMS enhanced the survival rates in the sepsis-induced mouse model. PMS remitted sepsis-mediated lung, liver and heart injury through prohibiting MPO/BALF (70.4%/85.6%), AST/ALT (74.7%/62.7%) and CK-MB/CK (62.3%/68.9%) levels. Moreover, the apoptosis index (lung 61.9%, liver 50.2%, heart 55.7% reduction) and IL-6/TNF-α/IL-1β levels were suppressed by PMS. Furthermore, PMS lowered TRAF6 and p-NF-κB p65 levels, whereas TRAF6 overexpression reversed the protective influences of PMS in organ injury, apoptosis and inflammation triggered by sepsis.
PMS suppressed sepsis-induced organ dysfunction by regulating the TRAF6/NF-κB axis, and PMS treatment may be considered as a novel strategy for sepsis-caused damage in future.
穿心莲内酯（PMS）具有丰富的药理特性，已应用于治疗数十种疾病。然而，人们对 PMS 在脓毒症中的作用了解不足。
研究 PMS 在脓毒症调节的器官功能障碍中的作用及其潜在机制。
将 30 只 C57BL/6 雄性小鼠适应性喂养 3 天，然后通过盲肠结扎穿孔（CLP）建立急性脓毒症模型。这些实验小鼠分为假手术组、CLP 组、CLP+25mg PMS/kg 体重（PMS/kg）组、CLP+50mg PMS/kg 体重和 CLP+100mg PMS/kg 体重（每组 n=6）。通过 HE 和 TUNEL 染色观察肺、肝和心脏组织的病理和凋亡变化。通过相应试剂盒检测肺、肝和心脏的损伤相关因子。采用 ELISA 和 qRT-PCR 检测 IL-6/TNF-α/IL-1β 水平。采用 Western blot 法检测凋亡相关和 TRAF6/NF-κB 相关蛋白。
所有剂量的 PMS 均提高了脓毒症诱导的小鼠模型的存活率。PMS 通过抑制 MPO/BALF（70.4%/85.6%）、AST/ALT（74.7%/62.7%）和 CK-MB/CK（62.3%/68.9%）水平来减轻脓毒症引起的肺、肝和心脏损伤。此外，PMS 还抑制了细胞凋亡指数（肺 61.9%、肝 50.2%、心 55.7%）和 IL-6/TNF-α/IL-1β 水平。此外，PMS 降低了 TRAF6 和 p-NF-κB p65 水平，而 TRAF6 过表达逆转了 PMS 对脓毒症引起的器官损伤、凋亡和炎症的保护作用。
PMS 通过调节 TRAF6/NF-κB 轴抑制脓毒症引起的器官功能障碍，PMS 治疗可能成为未来脓毒症损伤的一种新策略。
