Background: Corydalis saxicola Bunting, affiliated with the Papaveraceae Juss., has been proven to work well in anti-inflammation, hemostasis, and analgesia. This study was designed to observe the effect and potential mechanism of Corydalis saxicola Bunting total alkaloids (CSBTA) on paclitaxel-induced peripheral neuropathy (PIPN). Materials and methods: Rats were injected 2 mg/kg paclitaxel 4 times and administrated with 30 or 120 mg/kg CSBTA. Mechanical and thermal allodynia and hyperalgesia were tested. After 40 days, serum was collected to detect PGE2, TNF-α, and IL-1β by ELISA. The L4-L6 segment spinal cord, DRG, and plantar skin were harvested, and Western-blot or RT-qPCR analyzed protein and gene levels of pro-inflammatory cytokines, p38 MAPK, PKCε, and TRPV1. The PIPN cell model was established with paclitaxel (300 nM, 5 d) in primary DRG neurons. We examined the effect of CSBTA (25 μg/ml or 50 μg/ml) by measuring the mRNA levels in PGE2, TNF-α and CGRP, and the protein expression on the PKCε/p38 MAPK/TRPV1 signaling pathway in the PIPN cell model. Results: The results showed that CSBTA effectively ameliorated allodynia and hyperalgesia, and regulated cytokines' contents (PGE2, TNF-α, and IL-1β) and neuropeptides (CGRP and SP) in different tissues in vivo. In addition, CSBTA significantly decreased cytokine gene levels of DRG neurons (PGE2, TNF-α, and CGRP) and the protein expressions of PKCε/p38 MAPK/TRPV1 signaling pathway in vivo and in vitro. Conclusion: Therefore, CSBTA has a perspective therapeutic effect on the treatment of paclitaxel-induced peripheral neuropathy.

Snake venom contains large amounts of active proteins and peptides. In this study, a novel snake protein, metalloproteinase SP, was successfully isolated from the venom of Agkistrodon acutus by multi-gel chromatography. The isolated protein exhibits anti-platelet aggregation activity. Animal experiments showed that it exhibited defibration, anticoagulation, and antithrombotic effects and contributes to improved blood rheology and antiplatelet aggregation. In vivo experiments demonstrated that it prolonged clotting time, partial thromboplastin time, prothrombin time, thrombin time, fibrinogen time and reduced fibrinogen content of mice. Also, metalloproteinase SP inhibited carrageenan-induced tail thrombosis, ADP-induced acute pulmonary embolism, and ADP, Arachidonic acid (AA), or collagen-induced platelet aggregation. In vitro experiments showed that the protein cleaved the α, β, and γ chains of fibrinogen. Metabolomic analysis upon metalloproteinase SP treatment revealed that 14 metabolites, which are mainly involved in phenylalanine, tyrosine, and tryptophan biosynthesis, responded to metalloproteinase SP treatment. In summary, the isolated snake venom protein inhibits formation of acute pulmonary embolism probably through regulating and restoring perturbed energy, lipid, and amino acid metabolism.

The venom of the Deinagkistrodon acutus snake is composed of numerous bioactive proteins and peptides. In this study, we report the antithrombotic and anticoagulant activities of one of such proteins, herein known as SLPC. This novel protein was isolated and purified via multi-gel chromatography. Its amino acid sequence, structure and function were then determined. This protein was found to exhibit defibration, anticoagulation and general antithrombotic effects based on the results of both in vitro and in vivo studies. Based on same studies, it was found to cleave the α, β, γ chains of fibrinogen and generally improved antiplatelet aggregation and blood rheology. A metabolomic insight of the antithrombotic effects of SLPC was found to be mainly linked to perturbations in the synthesis of unsaturated fatty acids, glycerophospholipid metabolism, arachidonic acid metabolism and other metabolic pathways. In summary, the novel protein SLPC, elicits its antithrombotic effects via degradation of fibrinogen and regulation of various thrombogenic factors in multiple metabolic pathways.