Pharmacological investigation of indole alkaloids from Alstonia scholaris against chronic glomerulonephritis

doi:10.1016/j.phymed.2023.154958

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	Pharmacological investigation of indole alkaloids from Alstonia scholaris against chronic glomerulonephritis
	Guo,Rui; Shang,Jian-Hua; Ye,Rui-Han; Zhao,Yun-Li; Luo,Xiao-Dong
	2023
发表期刊	PHYTOMEDICINE
ISSN	1618-095X
卷号	118 页码:154958
摘要	Background: As one of the most commonly used folk medicines in Dai ethno-medicine system, Alstonia scholaris (l.) R. Br. has also been used for treat water related diseases, such as chronic kidney disease. However, few study was reported for it on the intervention of chronic glomerulonephritis (CGN). Purpose: To investigate the effect and potential mechanism of indole alkaloids from A. scholaris leaves in ICR mice with adriamycin nephropathy, as well as providing experimental evidence for the further application. Methods: ICR Mice were selected for injections of adriamycin (ADR) to induce the CGN model and administered total alkaloids (TA) and four main alkaloids continuously for 42 and 28 days, respectively. The pharmacological effects were indicated by serum, urine, and renal pathological observations. The targets and pathways of indole alkaloids on CGN intervention were predicted using the network pharmacology approach, and the immortalized mice glomerular podocyte (MPC5) cells model stimulated by ADR was subsequently selected to further verify this by western blotting and RT-qPCR methods. Results: TA and four major compounds dramatically reduced the levels of urinary protein, serum urea nitrogen (BUN), and creatinine (CRE) in ADR - induced CGN mice, while increasing serum albumin (ALB) and total protein (TP) levels as well as ameliorating kidney damage. Moreover, four alkaloids effected on 33 major target proteins and 153 pathways in the CGN, among which, PI3K-Akt as the main pathway, an important pathway for kidney protection by network pharmacology prediction, and then the four target proteins - HRAS, CDK2, HSP90AA1, and KDR were screened. As a result, Val-and Epi can exert a protective effect on ADR-stimulated MPC5 cells injury at a concentration of 50 mu M. Furthermore, the proteins and RNA expression of HRAS, HSP90AA1, and KDR were down-regulated, and CDK2 was up-regulated after the intervention of Val-and Epi, which were supported by Western blotting and RT-qPCR. Additionally, Val-and Epi inhibited ROS production in the MPC5 cells model. Conclusion: This study is the first to confirm the potential therapeutic effect of alkaloids from A. scholaris on CGN. TA with major bioactive components (vallesamine and 19-epi-scholaricine) could exert protective effects against the ADR-induced CGN by regulating four key proteins: HRAS, CDK2, HSP90AA1, and KDR of the PI3K-Akt pathway.
关键词	Alstonia scholaris Indole alkaloids Chronic glomerulonephritis Network pharmacology PI3K-AkT pathway LEAVES IDENTIFICATION CONSTITUENTS EXTRACT MODELS POTENT
DOI	10.1016/j.phymed.2023.154958
收录类别	SCI
WOS记录号	WOS:001047921400001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75397
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Guo,Rui,Shang,Jian-Hua,Ye,Rui-Han,et al. Pharmacological investigation of indole alkaloids from Alstonia scholaris against chronic glomerulonephritis[J]. PHYTOMEDICINE,2023,118:154958.
APA	Guo,Rui,Shang,Jian-Hua,Ye,Rui-Han,Zhao,Yun-Li,&Luo,Xiao-Dong.(2023).Pharmacological investigation of indole alkaloids from Alstonia scholaris against chronic glomerulonephritis.PHYTOMEDICINE,118,154958.
MLA	Guo,Rui,et al."Pharmacological investigation of indole alkaloids from Alstonia scholaris against chronic glomerulonephritis".PHYTOMEDICINE 118(2023):154958.

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