Compound amino acid combined with high-dose vitamin B6 attenuate traumatic coagulopathy via inhibiting inflammation by HMGB1/TLR4/NF-κB pathway

Abstract

Background: Traumatic coagulopathy (TC) arises primarily from coagulation system failure to maintain adequate hemostasis after serious blood loss or trauma. Circulatory homeostasis restoration is the mainstay of the therapeutic approach to TC, but the effects are significantly inhibited by coagulopathy. Objective: To identify the therapeutic effects and underlying mechanism of compound amino acid (CAA) combined with high-dosage of vitamin B6 (VB6) on TC. Methods: Rabbit traumatic model and cellular model were used to evaluate the effect of CAA combined with high-dosage of VB6 in TC. Blood concentrations of AST and ALT were measured using the Vitros 250 device while blood APTT, PT and TT concentrations were measured using commercial diagnostics kits. Furthermore, qRT-PCR, ELISA and Western blotting were used to determine the expression of clotting factor (II, VII, IX, X and XI), inflammatory factors (TNF-α, IL-6 and IL-1β) and HMGB1/TLR4/NF-κB signaling-related proteins, respectively. Results: In the rabbit traumatic model, CAA combined with high-dosage of VB6 therapy inhibited the high expression of AST and ALT, but increased the expression of coagulation factors. Additionally, in both the rabbit trauma model and cellular injury model, CAA combined with high-dosage of VB6 inhibited the expression of inflammatory factors (IL-6, TNF-α and IL-1β) and proteins (HMGB1, TLR4 and p-p65) in HMGB1/TLR4/NF-κB pathway. Most importantly, overexpression of HMGB1 reversed the effect of CAA and VB6 in HUVECs and EA.hy926 cells injury model. Conclusion: CAA combined with high-dosage of VB6 alleviated TC and inhibited the expression and secretion of inflammatory factors by inhibiting HMGB1-mediated TLR4/NF-κB pathway.

Green Pea (Pisum sativum L.) Hull Polyphenol Extract Alleviates NAFLD through VB6/TLR4/NF-κB and PPAR Pathways

“…53 On the other hand, vitamin B6 exerted anti-inflammatory effects by inhibiting the TLR4/NF-κB signaling pathway. 54 Thus, our results in metabolomics and transcriptomics collectively suggest that EGPH might relieve DSS+HFDinduced NAFLD by increasing hepatic vitamin B6 levels, which can activate or inhibit the PPAR and TLR4/NF-κB signaling pathways.…”

“…Activation of PPAR-α also alleviated mitochondrial dysfunction induced by HFD through the FGF21-AMPK-PGC-1α pathway, thereby preventing cell damage caused by steatosis. , Meanwhile, vitamin B6 could down-regulate the expression of hepatic PPAR-γ protein in hyperlipidemic rats . On the other hand, vitamin B6 exerted anti-inflammatory effects by inhibiting the TLR4/NF-κB signaling pathway . Thus, our results in metabolomics and transcriptomics collectively suggest that EGPH might relieve DSS+HFD-induced NAFLD by increasing hepatic vitamin B6 levels, which can activate or inhibit the PPAR and TLR4/NF-κB signaling pathways.…”

High-Dose Vitamin B6 (Pyridoxine) Displays Strong Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated Monocytes

“…Vitamin B6 was also found to protect mice from toxic effects induced by LPS by preventing IL-1Β protein production via the inhibition of NLRP3 inflammasome activation [ 106 ] and also inhibits activation of NF-κB in LPS-stimulated mouse macrophages [ 107 ]. Furthermore, high-dose B6 combined with compound amino acid was shown to prevent inflammation by inhibiting the HMNGB1/TLR4/NF-κB signalling pathway [ 108 ]. Interestingly, we note that vitamin B6 significantly downregulated NF-κB IL-6 , IL-1β , TNF-α , and NLPR3 , which aligns with these previous studies.…”

Current Prospects of Nutraceuticals in Rabbit Productivity and Health – an Updated Review

“…It is involved in regulating immunity and inflammation via controlling production of inflammatory cytokines (Stach et al, 2021). Recently, Yi et al (2020) indicated that vitamin B6 suppressed the expression of inflammatory cytokines , IL-1β, and tumor necrosis factor-α (TNF-α)] in rabbits. Liu et al (2018) evidenced that dietary supplementation of vitamin B6 (0, 5, 10, 20, and 40 mg/kg) increased BWG and FI and reduced the diarrhea ratio in weaned Rex rabbits.…”