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Mechanism of Mailuo Shutong Pill on anti-superficial thrombophlebitis based on TLR4/MyD88/MAPK signaling pathway
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DOI   10.11656/j.issn.1673-9043.2024.01.04
Key Words   Mailuo Shutong Pill;superficial thrombophlebitis;TLR4/MyD88/MAPK signaling pathway;mechanism
Author NameAffiliationE-mail
WANG Qingguo School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
CAO Ningning Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China  
LI Shirong New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China  
ZHANG Wanjing National Cancer Center, National Clinical Research Center for Cancer, Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang 065001, China  
SUN Chenghong New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China  
YAO Jingchun New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China  
ZHANG Guimin New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China lunanzhangguimin@yeah.net 
XIAO Xuefeng School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China kai1219@163.com 
Abstract
    [Objective] To investigate the mechanism of Mailuo Shutong Pill on superficial thrombophlebitis. [Methods] A total of 36 Japanese white rabbits were randomly divided into normal group, model group, low, medium, high dose of Mailuo Shutong Pill group, and positive drug(Diosmin) group, with 6 rabbits in each group. Except the normal group, the rabbit model of superficial thrombophlebitis was established by injecting 20% mannitol into bilateral auricular vein of other groups. At the same time, the treated groups were respectively administrated through gavage once a day for 14 consecutive days. Pathological changes of rabbit ear tissue were detected by hematoxylin and eosin(HE) staining. The levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The semi-automatic hemagglutination analyzer was used to measure indicators of coagulation function. Expressions levels of toll-like receptor 4(TLR4) and myeloid differentiation factor 88(MyD88) were detected by western blotting. The protein expression and phosphorylation level of extracellular signal-regulated kinase(ERK1/2), p38 mitogen-activated protein kinase(p38MAPK) and c-amino acid terminal kinase(JNK) were detected by western blotting. [Results] The model group demonstrated increase in pathological injury score(P<0.01), significant decline in serum content of inflammatory factors IL-1β, TNF-α and IL-6(P<0.05);shortened activated partial thromboplastin time, prothrombin time(PT), and thrombin time(TT), while increased fibrinogen(FIB) content(P<0.05);increased the protein expression and the phosphorylation levels of TLR4, MyD88, MAPK(p38MAPK, ERK1/2 and JNK, P<0.01) compared with the normal group. While Mailuo Shutong Pill significantly reduced the score of pathological injury and improved the pathological injury of ear tissue(P<0.05 or P<0.01);significantly decreased the expression levels of IL-1β, TNF-α and IL-6 in serum(P<0.05 or P<0.01);prolonged APTT, PT and TT and decreased FIB content(P<0.05 or P<0.01);down-regulated the protein expression and phosphorylation level of TLR4, MyD88, MAPK(p38MAPK, ERK1/2 and JNK, P<0.05 or P<0.01) compared with the model group. [Conclusion] Mailuo Shutong Pill was able to inhibit the inflammatory response and improve blood coagulation function in a model rabbit with superficial thrombophlebitis, and the mechanism may be related to the inhibition of TLR4/MyD88/MAPK signaling pathway activation.

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