Plantamajoside alleviates acute sepsis-induced organ dysfunction through inhibiting the TRAF6/NF-κB axis

Context: Plantamajoside (PMS) possesses rich pharmacological characteristics that have been applied to remedy dozens of diseases. However, the understanding of PMS in sepsis remains insufficient.

Objective: Role of PMS in sepsis-regulated organ dysfunction and potential mechanisms were investigated.

Materials and methods: 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 (n = 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.

Results: 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.

Discussion and conclusions: 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.

Traditional Chinese medicine; apoptosis; organ damage; systemic inflammation.