Molecular Mechanism of Tangbikang Granules Against Diabetic Peripheral Neuropathy： Based on Network Pharmacology and Experimental Verification
10.13422/j.cnki.syfjx.20230722
- VernacularTitle:基于网络药理学和实验验证探讨糖痹康颗粒治疗糖尿病周围神经病变的分子机制
- Author:
Yaqi ZHANG
1
;
Lingling QIN
2
;
Huizhong BAI
1
;
Chengfei ZHANG
3
;
Qiue ZHANG
4
;
Xinwei ZUO
1
;
Shengyuan JIANG
1
;
Yi ZHAO
1
;
Tonghua LIU
5
;
Xiaohong MU
1
Author Information
1. Dongzhimen Hospital， Beijing University of Chinese Medicine， Beijing 100700，China
2. Science and Technology Office， Beijing University of Chinese Medicine， Beijing 100029，China
3. School of Life Sciences， Beijing University of Chinese Medicine， Beijing 100029，China
4. School of Traditional Chinese Medicine （TCM）， Beijing University of Chinese Medicine，Beijing 100029， China
5. Beijing Key Laboratory of TCM Health Sciences， Beijing University of Chinese Medicine， Beijing 100029， China
- Publication Type:Journal Article
- Keywords:
Tangbikang granules;
network pharmacology;
diabetic peripheral neuropathy;
animal experiments;
molecular mechanism;
Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）;
SwissTargetPrediction
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(9):81-90
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Tangbikang granules （TBK） against diabetic peripheral neuropathy （DPN） based on network pharmacology and in-vivo experiment. MethodThe active components in medicinals of TBK and their target genes were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The active components of the medicinals which are not included in TCMSP were searched from previous research. After the analysis of drug-likeness by SwissADME， the target genes of them were predicted with SwissTargetPrediction. DPN-related target genes were retrieved from GeneCards. The common targets of the disease and the prescription were the hub genes of TBK against DPN， which were uploaded to Metascape for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. High-sugar and high-fat diet and low-dose streptozotocin （STZ， ip） were employed to induce diabetes in rats， and then the model rats were respectively treated with low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK for 12 weeks. Sensory nerve conduction velocity （SNCV） was evaluated. After hematoxylin and eosin （HE） staining， the sciatic nerve was observed under light microscope to examine the nerve damage. Real-time PCR was performed to detect the gene expression of adenosine monophosphate-activated protein kinase （AMPK） pathway-related targets in rat sciatic nerve， and Western blot to measure the protein expression of AMPK and phosphorylated （p）-AMPK in rat sciatic nerve. ResultThe main active components of TBK， such as quercetin， kaempferol， β-sitosterol， leech pteridine A， stigmasterol， and baicalein were screened out， mainly acting on interleukin-6 （IL-6）， tumor necrosis factor （TNF）， protein kinase B （Akt）， JUN， and HSP90AA1 and signaling pathways such as AMPK， nuclear factor-κB （NF-κB）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）. Molecular docking results showed that β-sitosterol and stigmasterol had high binding affinity with IL-6， TNF， JUN， and HSP90AA1. As for the animal experiment， compared with the normal group， model group had low SNCV of sciatic nerve （P<0.01）， disordered and loose myelinated nerve fibers with axonotmesis and demyelinization， low mRNA expression of AMPKα， AMPKβ， peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）， Sirtuin 3 （SirT3）， mitochondrial transcription factor A （TFAM）， and low p-AMPK/AMPK ratio in sciatic nerve （P<0.05， P<0.01）. Compared with the model group， TBK of the three doses raised the SNCV （P<0.01）， restored nerve morphology and nerve compactness， and increased the mRNA expression of AMPKα， AMPKβ， PGC-1α， SirT3， and TFAM （P<0.05， P<0.01）. The ratio of p-AMPK/AMPK in the high-dose and medium-dose TBK groups was higher than that in the model group （P<0.01）， while the protein expression in the low-dose TBK group was insignificantly different from that in the model group. ConclusionTBK exerts therapeutic effect on DPN through multiple pathways and targets. The mechanism is that it activates and regulates AMPK/PGC-1α/SirT3 signaling， which lays a basis for further study of TBK in the treatment of DPN.
