Exploring the Protective Effect of ShenQi Compound on Skeletal Muscle in Diabetic Macrovasculopathy Mice

Author(s): Yuhong Duan, Hong Gao, Hongxia Su, Aixia Liu, Ya Liu, Haipo Yuan, Chunguang Xie*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 20 , Issue 6 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Objective: ShenQi compound (SQC) is a traditional herbal formula, which has been used to treat Type 2 diabetes mellitus (T2DM) and complications for years. The aim of this study was to explore the preventive and protective effects of SQC recipe on the skeletal muscle of diabetic macrovasculopathy mice, which provides a theoretical basis for the clinical use of this formula.

Methods: We evaluated the effect of SQC in a diabetic vasculopathy mouse model by detecting a series of blood indicators (blood glucose, lipids and insulin) and performing histological observations. Meanwhile, we explored the molecular mechanism of SQC treatment on skeletal muscle by genome expression profiles.

Results: The results indicated that SQC could effectively improve blood glucose, serum lipids (total cholesterol (TC), Triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)) and insulin (INS) levels in diabetic vasculopathy mice, as well as alleviating skeletal muscle tissue damage for diabetic macrovasculopathy. Meanwhile, compared with rosiglitazone, SQC showed a better effect on blood glucose fluctuation. Moreover, the gene microarray analysis indicated that SQC might improve T2DM by affecting biological functions related to cell death and cell adhesion. Moreover, 7 genes (Celsr2, Rilpl1, Dlx6as, 2010004M13Rik, Anapc13, Gm6097, Ddx39b) might be potential therapeutic targets of SQC.

Conclusion: All these results indicate that SQC is an effective preventive and protective drug for skeletal muscle in diabetic macrovasculopathy, and could alleviate skeletal muscle tissue damage through affecting biological functions related to cell death and cell adhesion.

Keywords: Type 2 Diabetes Mellitus, diabetic macrovasculopathy, skeletal muscle, traditional Chinese medicine, gene microarray, ShenQi compound.

Cozma, A.; Sitar-Taut, A.; Orăşan, O.; Leucuta, D.; Alexescu, T.; Stan, A.; Negrean, V.; Sampelean, D.; Pop, D.; Zdrenghea, D.; Vulturar, R.; Fodor, A. Determining factors of arterial stiffness in subjects with metabolic syndrome. Metab. Syndr. Relat. Disord., 2018, 16(9), 490-496.
[http://dx.doi.org/10.1089/met.2018.0057] [PMID: 30183523]
Zhuang, Y.; Zhang, J.; Li, Y.; Gu, H.; Zhao, J.; Sun, Y.; Wang, R.; Zhang, C.; Chen, W.; Weng, J.; Qi, L.; Lu, H.; Zhang, J.; Liu, Q.; He, Y.; Xu, X.B Lymphocytes are predictors of insulin resistance in women with gestational diabetes mellitus. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(3), 358-366.
[http://dx.doi.org/10.2174/1871530319666190101130300] [PMID: 30621567]
Wu, D.; Wu, C.; Zhong, Y. The association between paraoxonase 1 activity and the susceptibilities of diabetes mellitus, diabetic macroangiopathy and diabetic microangiopathy. J. Cell. Mol. Med., 2018, 22(9), 4283-4291.
[http://dx.doi.org/10.1111/jcmm.13711] [PMID: 29981194]
Stuart, C.A.; Wen, G.; Williamson, M.E.; Jiang, J.; Gilkison, C.R.; Blackwell, S.J.; Nagamani, M.; Ferrando, A.A. Altered GLUT1 and GLUT3 gene expression and subcellular redistribution of GLUT4: protein in muscle from patients with acanthosis nigricans and severe insulin resistance. Metabolism, 2001, 50(7), 771-777.
[http://dx.doi.org/10.1053/meta.2001.24202] [PMID: 11436180]
Wray, C.J.; Sun, X.; Gang, G.I.; Hasselgren, P.O. Dantrolene downregulates the gene expression and activity of the ubiquitin-proteasome proteolytic pathway in septic skeletal muscle. J. Surg. Res., 2002, 104(2), 82-87.
[http://dx.doi.org/10.1006/jsre.2002.6416] [PMID: 12020124]
Al-Bayati, A.; Brown, A.; Walker, M. Impaired enhancement of insulin action in cultured skeletal muscle cells from insulin resistant type 2 diabetic patients in response to contraction using electrical pulse stimulation. J. Diabetes Complications, 2019, 33(12)107412
[http://dx.doi.org/10.1016/j.jdiacomp.2019.107412] [PMID: 31575461]
Stanford, K.I.; Goodyear, L.J. Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle. Adv. Physiol. Educ., 2014, 38(4), 308-314.
[http://dx.doi.org/10.1152/advan.00080.2014] [PMID: 25434013]
Meijer, J.W.; Lange, F.; Links, T.P.; van der Hoeven, J.H. Muscle fiber conduction abnormalities in early diabetic polyneuropathy. Clin. Neurophysiol., 2008, 119(6), 1379-1384.
[http://dx.doi.org/10.1016/j.clinph.2008.02.003] [PMID: 18387339]
Zhang, T.; Tan, P.; Wang, L.; Jin, N.; Li, Y.; Zhang, L.; Yang, H.; Hu, Z.; Zhang, L.; Hu, C.; Li, C.; Qian, K.; Zhang, C.; Huang, Y.; Li, K.; Lin, H.; Wang, D. RNALocate: a resource for RNA subcellular localizations. Nucleic Acids Res., 2017, 45(D1), D135-D138.
[PMID: 27543076]
Gao, H.; Duan, Y.; Fu, X.; Xie, H.; Liu, Y.; Yuan, H.; Zhou, M.; Xie, C. Comparison of efficacy of SHENQI compound and rosiglitazone in the treatment of diabetic vasculopathy analyzing multi-factor mediated disease-causing modules. PLoS One, 2018, 13(12)e0207683
[http://dx.doi.org/10.1371/journal.pone.0207683] [PMID: 30521536]
Liu, Y.; Kang, J.; Gao, H.; Zhang, X.; Chao, J.; Gong, G.; Yuan, H.; Xie, C. Exploration of the effect and mechanism of shenqi compound in a spontaneous diabetic rat model. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(5), 622-631.
[http://dx.doi.org/10.2174/1871530319666190225113859] [PMID: 30799801]
Zhang, H.; Xie, C.; Chen, S.; Xie, Y. Effect of Shenqi Compound Formula on PPARgamma in white adipose tissue of rats with macrovascular lesion in early stage of diabetes. J. Tradit. Chin. Med., 2008, 28(2), 134-138.
[http://dx.doi.org/10.1016/S0254-6272(08)60032-1] [PMID: 18652122]
Zhang, Y.; Liu, T.; Chen, L.; Yang, J.; Yin, J.; Zhang, Y.; Yun, Z.; Xu, H.; Ning, L.; Guo, F.; Jiang, Y.; Lin, H.; Wang, D.; Huang, Y.; Huang, J. RIscoper: a tool for RNA-RNA interaction extraction from the literature. Bioinformatics, 2019, 35(17), 3199-3202.
[http://dx.doi.org/10.1093/bioinformatics/btz044] [PMID: 30668649]
Shi, S.; Yin, H.J.; Li, J.; Wang, L.; Wang, W.P.; Wang, X.L. Studies of pathology and pharmacology of diabetic encephalopathy with KK-Ay mouse model. CNS Neurosci. Ther., 2020, 26(3), 332-342.
[http://dx.doi.org/10.1111/cns.13201] [PMID: 31401815]
Tomino, Y. Lessons from the KK-Ay Mouse, a spontaneous animal model for the treatment of human type 2 diabetic nephropathy. Nephrourol. Mon., 2012, 4(3), 524-529.
[http://dx.doi.org/10.5812/numonthly.1954] [PMID: 23573479]
Black, B.L.; Croom, J.; Eisen, E.J.; Petro, A.E.; Edwards, C.L.; Surwit, R.S. Differential effects of fat and sucrose on body composition in A/J and C57BL/6 mice. Metabolism, 1998, 47(11), 1354-1359.
[http://dx.doi.org/10.1016/S0026-0495(98)90304-3] [PMID: 9826212]
Haffner, S.M.; Kennedy, E.; Gonzalez, C.; Stern, M.P.; Miettinen, H. A prospective analysis of the HOMA model. The Mexico City Diabetes Study. Diabetes Care, 1996, 19(10), 1138-1141.
[http://dx.doi.org/10.2337/diacare.19.10.1138] [PMID: 8886564]
Huang, W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
Duckworth, W.; Abraira, C.; Moritz, T.; Reda, D.; Emanuele, N.; Reaven, P.D.; Zieve, F.J.; Marks, J.; Davis, S.N.; Hayward, R.; Warren, S.R.; Goldman, S.; McCarren, M.; Vitek, M.E.; Henderson, W.G.; Huang, G.D.; Investigators, V. Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med., 2009, 360(2), 129-139.
[http://dx.doi.org/10.1056/NEJMoa0808431] [PMID: 19092145]
Caprnda, M.; Mesarosova, D.; Ortega, P.F.; Krahulec, B.; Egom, E.; Rodrigo, L.; Kruzliak, P.; Mozos, I.; Gaspar, L. Glycemic variability and vascular complications in patients with type 2 diabetes mellitus. Folia Med. (Plovdiv), 2017, 59(3), 270-278.
[http://dx.doi.org/10.1515/folmed-2017-0048] [PMID: 28976897]
Hirano, T. Pathophysiology of Diabetic Dyslipidemia. J. Atheroscler. Thromb., 2018, 25(9), 771-782.
[http://dx.doi.org/10.5551/jat.RV17023] [PMID: 29998913]
Lee, J.H.; Chan, J.L.; Yiannakouris, N.; Kontogianni, M.; Estrada, E.; Seip, R.; Orlova, C.; Mantzoros, C.S. Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J. Clin. Endocrinol. Metab., 2003, 88(10), 4848-4856.
[http://dx.doi.org/10.1210/jc.2003-030519] [PMID: 14557464]
Hu, Y.H.; Hou, J.; Zheng, D.Z.; Li, D.D.; Hao, X.Z.; Xie, C.G.; Du, L.; Ni, Q.; Shen, Y.; Li, J. [Protection and mechanism of shenqi compound for diabetic angiopathy model rats]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2014, 34(9), 1078-1085.
[PMID: 25335332]
Carré, J.E.; Affourtit, C. Mitochondrial activity and skeletal muscle insulin resistance in kidney disease. Int. J. Mol. Sci., 2019, 20(11)E2751
[http://dx.doi.org/10.3390/ijms20112751] [PMID: 31195596]
Hadjantonakis, A.K.; Sheward, W.J.; Harmar, A.J.; de Galan, L.; Hoovers, J.M.; Little, P.F. Celsr1, a neural-specific gene encoding an unusual seven-pass transmembrane receptor, maps to mouse chromosome 15 and human chromosome 22qter. Genomics, 1997, 45(1), 97-104.
[http://dx.doi.org/10.1006/geno.1997.4892] [PMID: 9339365]
Cui, T.; Zhang, L.; Huang, Y.; Yi, Y.; Tan, P.; Zhao, Y.; Hu, Y.; Xu, L.; Li, E.; Wang, D. MNDR v2.0: an updated resource of ncRNA-disease associations in mammals. Nucleic Acids Res., 2018, 46(D1), D371-D374.
[PMID: 29106639]
Sivapalaratnam, S.; Motazacker, M.M.; Maiwald, S.; Hovingh, G.K.; Kastelein, J.J.; Levi, M.; Trip, M.D.; Dallinga-Thie, G.M. Genome-wide association studies in atherosclerosis. Curr. Atheroscler. Rep., 2011, 13(3), 225-232.
[http://dx.doi.org/10.1007/s11883-011-0173-4] [PMID: 21369780]
Sahni, A.; Wang, N.; Alexis, J.D. UAP56 is an important regulator of protein synthesis and growth in cardiomyocytes. Biochem. Biophys. Res. Commun., 2010, 393(1), 106-110.
[http://dx.doi.org/10.1016/j.bbrc.2010.01.093] [PMID: 20116367]
Sahni, A.; Wang, N.; Alexis, J.D. UAP56 is a novel interacting partner of Bcr in regulating vascular smooth muscle cell DNA synthesis. Biochem. Biophys. Res. Commun., 2012, 420(3), 511-515.
[http://dx.doi.org/10.1016/j.bbrc.2012.03.022] [PMID: 22446327]
Deshaies, R.J.; Joazeiro, C.A. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem., 2009, 78, 399-434.
[http://dx.doi.org/10.1146/annurev.biochem.78.101807.093809] [PMID: 19489725]
Vogel, G. Nobel Prizes. Gold medal from cellular trash. Science, 2004, 306(5695), 400-401.
[http://dx.doi.org/10.1126/science.306.5695.400b] [PMID: 15486272]
Yunqing, L.; Tianyuan, L.; Tianyu, C.; Zhao, W.; Yuncong, Z.; Puwen, T.; Yan, H.; Jia, Y.; Dong, W. RNAInter in 2020: RNA interactome repository with increased coverage and annotation. Nucleic Acids Res., 2019.
Parisi, A.; Lacour, F.; Giordani, L.; Colnot, S.; Maire, P.; Le Grand, F. APC is required for muscle stem cell proliferation and skeletal muscle tissue repair. J. Cell Biol., 2015, 210(5), 717-726.
[http://dx.doi.org/10.1083/jcb.201501053] [PMID: 26304725]
van Roessel, P.; Elliott, D.A.; Robinson, I.M.; Prokop, A.; Brand, A.H. Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell, 2004, 119(5), 707-718.
[http://dx.doi.org/10.1016/j.cell.2004.11.028] [PMID: 15550251]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 17 July, 2020
Page: [943 - 951]
Pages: 9
DOI: 10.2174/1871530320666200225094756
Price: $65

Article Metrics

PDF: 15