基于網(wǎng)絡藥理學的山奈酚參與血府逐瘀湯治療2型糖尿病作用機制研究

王松松　黃慧珍　蘇陳穎　林凡　黃明輝　方敏

[關鍵詞] 網(wǎng)絡藥理學;山奈酚;2型糖尿病;治療機制

[中圖分類號] R285? ? ? ? ? [文獻標識碼] A? ? ? ? ? [文章編號] 1673-9701（2021）22-0017-03

Research on the mechanism of kaempferol involving in Xuefu Zhuyu Decoction in the treatment of type 2 diabetes mellitus based on network pharmacology

WANG Songsong? ?HUANG Huizhen? ?SU Chenying? ?LIN Fan? ?HUANG Minghui? ?FANG Min

College of Integrated Traditional Chinese and Western Medicine， Fujian University of Traditional Chinese Medicine，F(xiàn)uzhou? ?350122， China

[Abstract] Objective To investigate the therapeutic mechanism of kaempferol， an important active component of Xuefu Zhuyu Decoction， in the treatment of type 2 diabetes mellitus （T2DM） by means of network pharmacology. Methods The action target of kaempferol was obtained from the public database of traditional Chinese medicine systems pharmacology （TCMSP）， and the related genes of T2DM were searched by GeneCards database， and the intersection of them was taken as the anti-T2DM target of kaempferol. Then， a protein-protein interaction （PPI） network of "nti-T2DM target of kaempferol" was constructed by using STRING platform， and the network topology was analyzed by using Cytoscape 3.7.1 software. Then GO and KEGG enrichment analysis of anti-T2DM target protein of kaempferol was carried out by Omishare platform. Results A total of 54 possible anti-T2DM action target of kaempferol were obtained， among which 6 core anti-T2DM target of kaempferol were AKT1，JUN， PTGS2， TNF， CASP3 and MAPK8. Through GO enrichment analysis， 2831 GO items were obtained， including 2355 items in biological process， 181 items in cell composition， and 295 items of molecular function. Through KEGG enrichment analysis， 140 pathways were obtained（P<0.05）， including AGE-RAGE，TNF，IL-17 and C-type lectin receptor and other signaling pathways. Conclusion Kaempferol may regulate signaling pathways such as AGE-RAGE， TNF and IL-17 through AKT1， TNF and other core targets， and involve in the role of Xuefu Zhuyu Decoction in promoting blood circulation and removing blood stasis and treating T2DM.

[Key words] Network pharmacology; Kaempferol; Type 2 diabetes mellitus; Therapeutic mechanism

T2DM患病率逐年增長且給全球帶來巨大的經(jīng)濟負擔。據(jù)報道，2010—2030年全球成年人患糖尿病的數(shù)量將從2.85億增加到4.39億，增長54%[1]。T2DM患者常伴有并發(fā)癥，如心血管疾病、糖尿病性神經(jīng)病、腎病和視網(wǎng)膜病變等，顯著降低患者的生活質(zhì)量，探尋T2DM的治療新藥具有重要意義[2]。近年來，中醫(yī)藥治療糖尿病的優(yōu)勢日益受到關注，祛瘀活血為其重要治則之一。作為活血化瘀經(jīng)典方——血府逐瘀湯治療T2DM療效顯著，但機制尚不明確[3]。山奈酚是血府逐瘀湯中的一種重要活性成分，具有抗氧化、抗炎、抗癌和保護神經(jīng)等作用[4-5]。它能促進骨骼肌葡萄糖代謝，抑制肝糖異生[6]，改善細胞胰島素敏感性[7]，激活胰腺β細胞的胰島素分泌，具有治療糖尿病的作用[8]。因此，山奈酚可能是血府逐瘀湯改善患者血流、益氣活血、化瘀養(yǎng)陰的重要活性成分，但具體的分子機制有待進一步研究。本研究通過網(wǎng)絡藥理學方法分析山奈酚作用靶標，探討山奈酚參與血府逐瘀湯治療T2DM的作用機制，為臨床應用和后續(xù)研究提供參考，現(xiàn)報道如下。