Therapeutic Effect of Tetrapanax papyriferus and Hederagenin on Chronic Neuropathic Pain of Chronic Constriction Injury of Sciatic Nerve Rats Based on KEGG Pathway Prediction and Experimental Verification.

EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE(2020)

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摘要
Background. Hederagenin is one of the main components ofTetrapanax papyriferus, and Tetrapanax papyriferusis one of the ingredients of Danggui Sini decoction. To explore whether Tetrapanax papyriferusand hederagenin can alleviate mechanical pain, thermal hyperalgesia, and cold pain at the same time, we comprehensively investigated the effects of two drugs on the levels of p38 MAPK phosphorylation, TRP proteins, and IL1 beta, IL6, and TNF-alpha in serum. Methods. Firstly, we obtained pain-related targets and performed KEGG pathway enrichment on these targets. Then, 42 SD rats were separated randomly into six groups: sham operation group, CCI group, pregabalin group, mecobalamin group,Tetrapanax papyriferusgroup, and hederagenin group. All drugs were given orally. Rats in the sham operation group and CCI group were gavaged with saline. Rats in the pregabalin group were given pregabalin, while rats in the mecobalamin group were given mecobalamin. Rats in theTetrapanax papyriferusgroup were given Tetrapanax papyriferus, while rats in the hederagenin group were given hederagenin. Besides, we conducted behavioral tests including acetone test, hot plate experiment, and von Frey filaments, and then dorsal root ganglion neurons were taken out on the 21st day after operation. Then, western blot, ELISA, and hematoxylin-eosin staining were conducted. Results. Rats in the CCI group were more sensitive to hyperalgesia and allodynia to mechanical and thermal stimuli, as well as cold pain. All four drugs could relieve these pains. Pregabalin, mecobalamin, andTetrapanax papyriferuscan reduce the levels of IL1 beta, IL6, and TNF-alpha in serum compared to those of the CCI group. The expression of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in DRG increased evidently on the 21st day after the operation in the CCI group. All four drugs could reduce the expressions of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in dorsal root ganglion compared to those of the CCI group. Conclusion.Tetrapanax papyriferusand hederagenin relieved sciatica by reducing inflammation levels, inhibiting p38 MAPK phosphorylation, and decreasing the levels of dorsal root ganglion proteins.
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