Xuebijing injection protects sepsis induced myocardial injury by mediating TLR4/NF-κB/IKKα and JAK2/STAT3 signaling pathways

Abstract

Objective: Compelling evidence has demonstrated that Xuebijing (XBJ) exerted protective effects against SIMI. The aims of this study were to investigate whether TLR4/IKKα-mediated NF-κB and JAK2/STAT3 pathways were involved in XBJ's cardio-protection during sepsis and the mechanisms. Methods: In this study, rats were randomly assigned to three groups: Sham group; CLP group; XBJ group. Rats were treated with XBJ or sanitary saline after CLP. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1β, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis were tested by TUNEL staining. The protein levels of Bax, Bcl-2, Bcl-xl, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3 in the myocardium were assayed by western blotting. And finally, immunofluorescence was used to assess the level of p-JAK2 and p-STAT3 in heart tissue. Results: The results of echocardiography, myocardial enzyme and HE test showed that XBJ could significantly improve SIMI. The IL-1β, IL-6 and TNF-α levels in the serum were markedly lower in the XBJ group than in the CLP group ( p <0.05). TUNEL staining's results showed that XBJ ameliorated CLP-induced cardiomyocyte apoptosis. Meanwhile, XBJ downregulated the protein levels of Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3, as well as upregulated the protein levels of Bcl-2, Bcl-xl ( p <0.05). Conclusions: In here, we observed that XBJ's cardioprotective advantages may be attributable to its ability to suppress inflammation and apoptosis via inhibiting the TLR4/ IKKα-mediated NF-κB and JAK2/STAT3 pathways during sepsis.

Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis

“…Improved autophagic flux-based sepsis therapy options are suggested by a clinical investigation that reveals impaired autophagic flux in septic patients [ 173 ]. Our previous basic studies have revealed that activation of autophagy is protective of multiorgan function in a sepsis model [ 174 , 175 ]. Then, cognitive dysfunction in sepsis-related encephalopathy is ameliorated by activation of PPAR-γ signaling pathway-mediated autophagy in astrocytes, as evidenced by high expression of LC3, ULK1, and low expression of P62 [ 176 ].…”

ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway

“…Given that IL-6 is an established therapeutic target (Martin et al, 2019;Kang et al, 2020) and Stat3 is an emerging target in managing sepsis (Hui et al, 2009;Hou et al, 2021;Lei et al, 2021), this is important for understanding the working mechanism of ACT001 in sepsis. Coincidentally, a recent publication has shown that XBJ can Frontiers in Pharmacology frontiersin.org improve sepsis-induced myocardial damage and inflammation by regulating the NF-κB and JAK2/STAT3 pathways (Kang et al, 2023). Besides, Stattic ameliorates the cecal ligation and puncture-induced cardiac injury in septic mice via the IL-6-STAT3 signaling pathway (Imbaby and Hattori, 2023).…”

High-dose Vitamin C injection ameliorates against sepsis induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats

“…Our previous studies have also demonstrated that autophagy and apoptosis play key roles in the occurrence and development of SIMI [7]. The PI3K/AKT/mTOR [8], MAPK [9] and NF-κB [10] and pathways regulate various biological responses, including proliferation, autophagy, inflammation, and apoptosis [11][12][13][14][15]. Inhibition of PI3K/AKT/mTOR signaling pathway can enhance autophagy and thus reduce oxidative stress and apoptosis in LPS -induced sepsis [16].…”