Planta Med 2020; 86(08): 556-564 DOI: 10.1055/a-1147-9196
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York
Network Pharmacological Screening of the Active Ingredients and Hypoglycemic Effect of Isodon rubescens in the Treatment of Diabetes
Xue Jintao
1
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan Province, PR China
,
Yu Shasha
1
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan Province, PR China
,
Wang Jincai
3
Department of Pharmacy, the First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, PR China
,
Li Chunyan
1
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan Province, PR China
2
Sanquan College of Xinxiang Medical University, Xinxiang, Henan Province, PR China
,
Yang Mengya
1
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan Province, PR China
,
Shi Yongli
1
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan Province, PR China
› Author AffiliationsSupported by:
National Natural Science Foundation of China for Youth Program
81703458
Supported by:
the National Natural Science Foundation of China
U1804175
This study was firstly to study the relationship of “ingredient-target-pathway” and the pharmacological effects of Isodon rubescens for the treatment of diabetes. Based on a network pharmacology method, 138 active ingredients of Isodon rubescens were screened from the relative literatures, and their targets were confirmed by comparing these with the hypoglycemic targets in the DrugBank database. Results showed that Isodon rubescens contained 25 hypoglycemic ingredients, such as rabdoternin A, rabdoternin B, and epinodosinol. These ingredients could activate 6 hypoglycemic targets, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), integrin α-L (ITGAL), integrin β-2 (ITGB2), progesterone receptor (PGR), glucocorticoid receptor (NR3C1), and nuclear receptor subfamily 1 group I member 2 (NR1I2). These targets were involved in 94 signaling pathways, such as the Rap1, PI3K-Akt, and HIF-1 signaling pathways. The cell viability showed that the human umbilical vein endothelial cells (HUVECs) treated with alcohol extract (1.00 g/L) and the water extract (0.13 – 0.50 g/L) exhibited high viability compared to the model group (p < 0.05), respectively. 0In animal experiments, the rats treated with water extract of Isodon rubescens showed significant hypoglycemic effects compared to rats in the model group (p < 0.05). Overall, this approach provides an efficient strategy to explore hypoglycemic ingredients of Isodon rubescens and other traditional Chinese medicine.
1
Chamberlain JJ,
Rhinehart AS,
Shaefer CF,
Neuman A.
Diagnosis and management of diabetes: synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med 2016; 164: 542-552
2
Seferovic PM,
Petrie MC,
Filippatos GS,
Anker SD,
Rosano G,
Bauersachs J,
Paulus WJ,
Komajda M,
Cosentino F,
de Boer RA,
Farmakis D,
Doehner W,
Lambrinou E,
Lopatin Y,
Piepoli MF,
Theodorakis MJ,
Wiggers H,
Lekakis J,
Mebazaa A,
Mamas MA,
Tschope C,
Hoes AW,
Seferovic JP,
Logue J,
McDonagh T,
Riley JP,
Milinkovic I,
Polovina M,
van Veldhuisen DJ,
Lainscak M,
Maggioni AP,
Ruschitzka F,
McMurray JJV.
Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2018; 20: 853-872
6
Uusitupa M,
Khan TA,
Viguiliouk E,
Kahleova H,
Rivellese AA,
Hermansen K,
Pfeiffer A,
Thanopoulou A,
Salas-Salvado J,
Schwab U,
Sievenpiper JL.
Prevention of type 2 diabetes by lifestyle changes: a systematic review and meta-analysis. Nutrients 2019; 11: 2611
8
Liu C,
Liu R,
Fan H,
Xiao X,
Chen X,
Xu H,
Lin Y.
Network pharmacology bridges traditional application and modern development of traditional Chinese medicine. Chin Herb Med 2015; 7: 3-17
9
Guo DA,
Bauer R,
Robinson N.
The therapeutic value of natural products derived from Chinese medicine – a systems based perspective. Eur J Integr Med 2014; 6: 617-620
10
Zhang YY,
Jiang HY,
Liu M,
Hu K,
Wang WG,
Du X,
Li XN,
Pu JX,
Sun HD.
Bioactive ent-kaurane diterpenoids from Isodon rubescens
. Phytochemistry 2017; 143: 199-207
11
Duan JL,
Wu YL,
Xu JG.
Assessment of the bioactive compounds, antioxidant and antibacterial activities of Isodon rubescens as affected by drying methods. Nat Prod Res 2019; 33: 746-749
12
Jin B,
Guo J,
Tang J,
Tong Y,
Ma Y,
Chen T,
Wang Y,
Shen Y,
Zhao Y,
Lai C,
Cui G,
Huang L.
An alternative splicing alters the product outcome of a class I terpene synthase in Isodon rubescens
. Biochem Biophys Res Commun 2019; 512: 310-313
13
Bai SP,
Luo GS,
Zhang XY,
Liu W.
An ent-kaurane diterpenoid from Isodon japonica var. glaucocalyx. Acta Crystallogr Sect E Struct Rep Online 2009; 65: o1898
19
Yang K,
Zeng L,
Ge J.
Exploring the pharmacological mechanism of Danzhi Xiaoyao Powder on ER-positive breast cancer by a network pharmacology approach. Evid Based Complement Alternat Med 2018; 2018: 5059743
20
Pang XC,
Kang D,
Fang JS,
Zhao Y,
Xu LJ,
Lian WW,
Liu AL,
Du GH.
Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to alzheimerʼs disease. Chin J Nat Med 2018; 16: 53-62
21
Bi Y,
Zhang L,
Chen S,
Ling Q.
Antitumor mechanisms of Curcumae rhizoma based on network pharmacology. Evid Based Complement Alternat Med 2018; 2018: 1-9
22
Zheng S,
Jiang Y,
Lu M,
Gao B,
Qiao X,
Sun B,
Zhang W,
Xue D.
Network pharmacological screening of herbal monomers that regulate apoptosis-associated genes in acute pancreatitis. Pancreas 2017; 46: 89-96
23
Wang T,
Wang X.
Molecular structure, vibrational and 13C NMR spectra of two ent-kaurenes spirolactone type diterpenoids rabdosinate and rabdosin B: a combined experimental and density functional methods. Spectrochim Acta A Mol Biomol Spectrosc 2015; 135: 568-575
24
Pelot KA,
Hagelthorn LM,
Addison JB,
Zerbe P.
Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant Isodon rubescens is catalyzed by a pair of diterpene synthases. PLoS One 2017; 12: e0176507
25
Han QB,
Zhao AH,
Zhang JX,
Lu Y,
Zhang LL,
Zheng QT,
Sun HD.
Cytotoxic constituents of Isodon rubescens var. lushiensis
. J Nat Prod 2003; 66: 1391-1394
27
Glawe JD,
Patrick DR,
Huang M,
Sharp CD,
Barlow SC,
Kevil CG.
Genetic deficiency of Itgb2 or ItgaL prevents autoimmune diabetes through distinctly different mechanisms in NOD/LtJ mice. Diabetes 2009; 58: 1292-1301
28
Tan H,
Wang W,
Yin X,
Li Y,
Yin R.
Identification of a selective glucocorticoid receptor ligand for the treatment of chronic inflammation in type 2 diabetes mellitus. Exp Ther Med 2014; 8: 1111-1114
29
Berstein LM,
Boyarkina MP,
Tsyrlina EV,
Turkevich EA,
Semiglazov VF.
More favorable progesterone receptor phenotype of breast cancer in diabetics treated with metformin. Med Oncol 2011; 28: 1260-1263
30
He J,
Gao J,
Xu M,
Ren S,
Stefanovic-Racic M,
OʼDoherty RM,
Xie W.
PXR ablation alleviates diet-induced and genetic obesity and insulin resistance in mice. Diabetes 2013; 62: 1876-1887
32
Wang SF,
Aoki M,
Nakashima Y,
Shinozuka Y,
Tanaka H,
Taniwaki M,
Hattori M,
Minato N.
Development of Notch-dependent T-cell leukemia by deregulated Rap1 signaling. Blood 2008; 111: 2878-2886
33
Takahashi H,
Shibasaki T,
Park JH,
Hidaka S,
Takahashi T,
Ono A,
Song DK,
Seino S.
Role of Epac2A/Rap1 signaling in interplay between incretin and sulfonylurea in insulin secretion. Diabetes 2015; 64: 1262-1272
34
Shukla S,
Maclennan GT,
Hartman DJ,
Fu P,
Resnick MI,
Gupta S.
Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int J Cancer 2007; 121: 1424-1432
36
Li B,
Cheung PY,
Wang X,
Tsao SW,
Ling MT,
Wong YC,
Cheung AL.
Id-1 activation of PI3K/Akt/NFkappaB signaling pathway and its significance in promoting survival of esophageal cancer cells. Carcinogenesis 2007; 28: 2313-2320
37
Yang XS,
Liu S,
Liu YJ,
Liu JW,
Liu TJ,
Wang XQ,
Yan Q.
Overexpression of fucosyltransferase IV promotes A431 cell proliferation through activating MAPK and PI3K/Akt signaling pathways. J Cell Physiol 2010; 225: 612-619
40
Xue W,
Liu Y,
Zhao J,
Cai L,
Li X,
Feng W.
Activation of HIF-1 by metallothionein contributes to cardiac protection in the diabetic heart. Am J Physiol Heart Circ Physiol 2012; 302: H2528-H2535 doi:10.1152/ajpheart.00850.2011
43
Jintao X,
Yongli S,
Chunyan L,
Huijie S.
Network pharmacology-based prediction of the active ingredients, potential targets, and signaling pathways in compound Lian-Ge granules for treatment of diabetes. J Cell Biochem 2019; 120: 6431-6440