Investigation of Ginseng-Ophiopogon Injection on Enhancing Physical Function by Pharmacogenomics and Metabolomics Evaluation
- Авторы: Meimei C.1, Jingru Z.1, Huijuan G.1, Candong L.1
-
Учреждения:
- College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine
- Выпуск: Том 27, № 19 (2024)
- Страницы: 2838-2849
- Раздел: Chemistry
- URL: https://kazanmedjournal.ru/1386-2073/article/view/644497
- DOI: https://doi.org/10.2174/0113862073244102231020050502
- ID: 644497
Цитировать
Полный текст
Аннотация
Background:Ginseng-ophiopogon injection (GOI) is a clinically commonly used drug for Qi deficiency syndrome characterized by decreased physical function in China. This study aimed to clarify common pharmacological mechanisms of GOI in enhancing physical function.
Methods:We performed an integrative strategy of weight-loaded swimming tests in cold water (5.5 °C), hepatic glycogen and superoxide dismutase (SOD) detections, GC-TOF/MS-based metabolomics, multivariate statistical techniques, network pharmacology of known targets and constituents, and KEGG pathway analysis of GOI.
Results:Compared with the control group, GOI showed significant increases in the weightloaded swimming time, hepatic levels of glycogen and SOD. Additionally, 34 significantly differential serum metabolites referred to glycolysis, gluconeogenesis and arginine biosynthesis were affected by GOI. The target collection revealed 98 metabolic targets and 50 experimentreported drug targets of ingredients in GOI involved in enhancing physical function. Further, the PPI network analysis revealed that 8 ingredients of GOI, such as ginsenoside Re, ginsenoside Rf, ginsenoside Rg1, and notoginsenoside R1, were well-associated with 48 hub targets, which had good ability in enhancing physical function. Meanwhile, nine hub proteins, such as SOD, mechanistic target of Rapamycin (mTOR), and nitric oxide synthases, were confirmed to be affected by GOI. Finally, 98 enriched KEGG pathways (P(<0.01 and FDR(<0.001) of GOI were obtained from 48 hub targets of the PPI network. Among them, pathways in cancer, Chagas disease, lipid and atherosclerosis, and PI3K-Akt signaling pathway ranked top four.
Conclusions:This study provided an integrative and efficient approach to understanding the molecular mechanism of GOI in enhancing physical function.
Ключевые слова
Об авторах
Chen Meimei
College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine
Email: info@benthamscience.net
Zhu Jingru
College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine
Email: info@benthamscience.net
Gan Huijuan
College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine
Автор, ответственный за переписку.
Email: info@benthamscience.net
Li Candong
College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine
Email: info@benthamscience.net
Список литературы
- Zhang, Y.; Zhang, L.; Zhao, X.; Liu, Y.; Du, S.; Li, J.; Liu, T.; Liu, F.; Su, Z.; Jiang, Y.; Ding, X. Symptom characteristics and prevalence of qi deficiency syndrome in people of varied health status and ages: A multicenter cross-sectional study. J. Trad. Chin. Med. Sci., 2015, 2(3), 173-182. doi: 10.1016/j.jtcms.2016.01.017
- Lu, L.; Zheng, G.; Wang, Y. An overview of systematic reviews of shenmai injection for healthcare. Evid. Based Complement. Alternat. Med., 2014, 2014, 1-9. doi: 10.1155/2014/840650 PMID: 24669229
- Liang, J.; Xu, D.; Wei, Y. Clinical observation of Shenmai injection treatment for cancer related fatigue. Zhongguo Shiyan Fangjixue Zazhi, 2012, 18(17), 279-281.
- Zhang, G.; Zhou, X. Effect of Shenmai injection on blood routine and immune function in elderly patients with lung cancer after chemotherapy. Zhongguo Laonianxue Zazhi, 2018, 38, 5944-5946.
- Pan, Y.; Ren, X.; Zhang, X.; Guan, D.; Zhu, M.; Lin, L. Effects of Shenmai injection on postoperative fatigue in hysterectomy patients. Chinese J. Integr. Tradit. Western Med., 2019, 39(05), 31-35.
- Lee, J.S.; Song, J.H.; Sohn, N.W.; Shin, J.W. Inhibitory effects of ginsenoside Rb1 on neuroinflammation following systemic lipopolysaccharide treatment in mice. Phytother. Res., 2013, 27(9), 1270-1276. doi: 10.1002/ptr.4852 PMID: 23042638
- Kim, D.H.; Kim, D.W.; Jung, B.H.; Lee, J.H.; Lee, H.; Hwang, G.S.; Kang, K.S.; Lee, J.W. Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells. J. Ginseng Res., 2019, 43(2), 326-334. doi: 10.1016/j.jgr.2018.12.002 PMID: 30976171
- Kim, D.H.; Park, C.H.; Park, D.; Choi, Y.J.; Park, M.H.; Chung, K.W.; Kim, S.R.; Lee, J.S.; Chung, H.Y. Ginsenoside Rc modulates Akt/FoxO1 pathways and suppresses oxidative stress. Arch. Pharm. Res., 2014, 37(6), 813-820. doi: 10.1007/s12272-013-0223-2 PMID: 23918648
- Fang, H.; Yang, S.; Luo, Y.; Zhang, C.; Rao, Y.; Liu, R.; Feng, Y.; Yu, J. Notoginsenoside R1 inhibits vascular smooth muscle cell proliferation, migration and neointimal hyperplasia through PI3K/Akt signaling. Sci. Rep., 2018, 8(1), 7595. doi: 10.1038/s41598-018-25874-y PMID: 29765072
- Huang, G.; Zou, B.; Lv, J.; Li, T.; Huai, G.; Xiang, S.; Lu, S.; Luo, H.; Zhang, Y.; Jin, Y.; Wang, Y. Notoginsenoside R1 attenuates glucose-induced podocyte injury via the inhibition of apoptosis and the activation of autophagy through the PI3K/Akt/mTOR signaling pathway. Int. J. Mol. Med., 2017, 39(3), 559-568. doi: 10.3892/ijmm.2017.2864 PMID: 28112381
- Arneth, B.; Arneth, R.; Shams, M. Metabolomics of type 1 and type 2 diabetes. Int. J. Mol. Sci., 2019, 20(10), 2467. doi: 10.3390/ijms20102467 PMID: 31109071
- Tao, Y.; Chen, X.; Cai, H.; Li, W.; Cai, B.; Chai, C.; Di, L.; Shi, L.; Hu, L. Untargeted serum metabolomics reveals Fu-Zhu-Jiang-Tang tablet and its optimal combination improve an impaired glucose and lipid metabolism in type II diabetic rats. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1040, 222-232. doi: 10.1016/j.jchromb.2016.11.012 PMID: 27866845
- Gaggini, M.; Carli, F.; Rosso, C.; Younes, R.; DAurizio, R.; Bugianesi, E.; Gastaldelli, A. Altered metabolic profile and adipocyte insulin resistance mark severe liver fibrosis in patients with chronic liver disease. Int. J. Mol. Sci., 2019, 20(24), 6333. doi: 10.3390/ijms20246333 PMID: 31888144
- Wang, Y.; Bi, C.; Pang, W.; Liu, Y.; Yuan, Y.; Zhao, H.; Zhang, T.; Zhao, Y.; Li, Y. Plasma metabolic profiling analysis of gout party on acute gout arthritis rats based on UHPLCQTOF/MS combined with multivariate statistical analysis. Int. J. Mol. Sci., 2019, 20(22), 5753. doi: 10.3390/ijms20225753 PMID: 31731809
- Sun, Y.; Wang, Y.; Guo, Z.; Du, K.; Meng, D. Systems pharmacological approach to investigate the mechanism of Ohwia caudata for application to alzheimers disease. Molecules, 2019, 24(8), 1499. doi: 10.3390/molecules24081499 PMID: 30999553
- Xinqiang, S.; Yu, Z.; Ningning, Y.; Erqin, D.; Lei, W.; Hongtao, D. Molecular mechanism of celastrol in the treatment of systemic lupus erythematosus based on network pharmacology and molecular docking technology. Life Sci., 2020, 240117063 doi: 10.1016/j.lfs.2019.117063 PMID: 31734262
- Jiang, Y.; Zhong, M.; Long, F.; Yang, R.; Zhang, Y.; Liu, T. Network pharmacology-based prediction of active ingredients and mechanisms of lamiophlomis rotata (benth) kudo against rheumatoid arthritis. Front. Pharmacol., 2019, 10, 1435. doi: 10.3389/fphar.2019.01435 PMID: 31849678
- Pang, H.Q.; Yue, S.J.; Tang, Y.P.; Chen, Y.Y.; Tan, Y.J.; Cao, Y.J.; Shi, X.Q.; Zhou, G.S.; Kang, A.; Huang, S.L.; Shi, Y.J.; Sun, J.; Tang, Z.S.; Duan, J.A. Duan JA integrated metabolomics and network pharmacology approach to explain possible action mechanisms of Xin-Sheng-Hua granule for treating anemia. Front. Pharmacol., 2018, 9, 165. doi: 10.3389/fphar.2018.00165 PMID: 29551975
- Wei, S.; Qian, L.; Niu, M.; Liu, H.; Yang, Y.; Wang, Y.; Zhang, L.; Zhou, X.; Li, H.; Wang, R.; Li, K.; Zhao, Y. The modulatory properties of Li-Ru-Kang treatment on hyperplasia of mammary glands using an integrated approach. Front. Pharmacol., 2018, 9, 651. doi: 10.3389/fphar.2018.00651 PMID: 29971006
- National Pharmacopoeia Committee. Pharmacopoeia of the Peoples Republic of China; Chemical Industry Press: Beijing, China, 2010.
- Qi, B.; Ouyang, J.; Huang, H.; Zhang, L.; Zhang, Z. Effects of ginsenosides-Rb1. on exercise-induced oxidative stress in forced swimming mice. Pharmacogn. Mag., 2014, 10(40), 458-463. doi: 10.4103/0973-1296.141818 PMID: 25422546
- Chen, M.; Yang, F.; Kang, J.; Gan, H.; Lai, X.; Gao, Y. Metabolomic investigation into molecular mechanisms of a clinical herb prescription against metabolic syndrome by a systematic approach. RSC Advances, 2017, 7(87), 55389-55399. doi: 10.1039/C7RA09779D
- Wang, B.; Sun, H.; Wu, X.; Jiang, L.; Guan, L.L.; Liu, J. Arteriovenous blood metabolomics: An efficient method to determine the key metabolic pathway for milk synthesis in the intra-mammary gland. Sci. Rep., 2018, 8(1), 5598. doi: 10.1038/s41598-018-23953-8 PMID: 29618747
- Glymenaki, M.; Barnes, A.; Hagan, S.O.; Warhurst, G.; McBain, A.J.; Wilson, I.D.; Kell, D.B.; Else, K.J.; Cruickshank, S.M. Stability in metabolic phenotypes and inferred metagenome profiles before the onset of colitis-induced inflammation. Sci. Rep., 2017, 7(1), 8836. doi: 10.1038/s41598-017-08732-1 PMID: 28821731
- Li, Z.; Lin, C.; Xu, J.; Wu, H.; Feng, J.; Huang, H. The relations between metabolic variations and genetic evolution of different species. Anal. Biochem., 2015, 477, 105-114. doi: 10.1016/j.ab.2015.02.024 PMID: 25728943
- Lv, Y.; Hou, X.; Zhang, Q.; Li, R.; Xu, L.; Chen, Y.; Tian, Y.; Sun, R.; Zhang, Z.; Xu, F. Untargeted metabolomics study of the in vitro anti-hepatoma effect of saikosaponin d in combination with NRP-1 knockdown. Molecules, 2019, 24(7), 1423. doi: 10.3390/molecules24071423 PMID: 30978940
- KEGG. KEGG Database. 2022. Available From: https://www.kegg.jp/kegg/kegg1.html
- Pubchem. Pubchem database. 2022. Available From: https://pubchemncbinlmnihgov
- Rebhan, M.; Chalifa-Caspi, V.; Prilusky, J.; Lancet, D. GeneCards: Integrating information about genes, proteins and diseases. Trends Genet., 1997, 13(4), 163. doi: 10.1016/S0168-9525(97)01103-7 PMID: 9097728
- Meireles, L.M.C.; Dömling, A.S.; Camacho, C.J. ANCHOR: A web server and database for analysis of protein-protein interaction binding pockets for drug discovery. Nucleic Acids Res., 2010, 38(Web Server), W407-W411. doi: 10.1093/nar/gkq502 PMID: 20525787
- Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504. doi: 10.1101/gr.1239303 PMID: 14597658
- Xia, F.; Zhong, Y.; Li, M.; Chang, Q.; Liao, Y.; Liu, X.; Pan, R. Antioxidant and anti-fatigue constituents of okra. Nutrients, 2015, 7(10), 8846-8858. doi: 10.3390/nu7105435 PMID: 26516905
- Jun, L. GW24-e3722 Ebselen protected myocardium from overtraining-induced oxidative damage in rats. Heart, 2013, 99(3)(Suppl. 3), A97.3-A98. doi: 10.1136/heartjnl-2013-304613.265
- Camic, C.L.; Housh, T.J.; Zuniga, J.M.; Hendrix, R.C.; Mielke, M.; Johnson, G.O.; Schmidt, R.J. Effects of arginine-based supplements on the physical working capacity at the fatigue threshold. J. Strength Cond. Res., 2010, 24(5), 1306-1312. doi: 10.1519/JSC.0b013e3181d68816 PMID: 20386475
- Sun, Y.; Chen, Y.; Xu, M.; Liu, C.; Shang, H.; Wang, C. Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant A549/DDP Cells via the AKT-mTOR-c-Myc Signaling Pathway. BioMed Res. Int., 2020, 2020(7), 1-10. doi: 10.1155/2020/9243681 PMID: 32685545
- Zhang, W.; Tao, X.J.; Cheng, J. Effect of shenmai injection on patients suffering from malnutrition-inflammation complex syndrome during the maintenance hemodialysis. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih, 2009, 29(8), 703-706. PMID: 19848201
- Yuan, H.; Sun, Y.; Chen, Q. Effect of Shenmai injection on acute myocardial infarction and its effect on serum Copeptin,NF-κB and markers of myocardial injury. Yunnan J. Trad. Chin. Med. Mater. Med., 2021, 4, 51-53.
- Zhang, Y.; Zhao, Y.; Ran, Y.; Guo, J.; Cui, H.; Liu, S. Notoginsenoside R1 attenuates sevoflurane-induced neurotoxicity. Transl. Neurosci., 2020, 11(1), 215-226. doi: 10.1515/tnsci-2020-0118 PMID: 33335762
- Apicella, M.; Giannoni, E.; Fiore, S.; Ferrari, K.J.; Fernández-Pérez, D.; Isella, C.; Granchi, C.; Minutolo, F.; Sottile, A.; Comoglio, P.M.; Medico, E.; Pietrantonio, F.; Volante, M.; Pasini, D.; Chiarugi, P.; Giordano, S.; Corso, S. Increased lactate secretion by cancer cells sustains non-cell-autonomous adaptive resistance to MET and EGFR targeted therapies. Cell Metab., 2018, 28(6), 848-865.e6. doi: 10.1016/j.cmet.2018.08.006 PMID: 30174307
- Li, L.; Yang, D.; Li, J.; Niu, L.; Chen, Y.; Zhao, X.; Oduro, P.K.; Wei, C.; Xu, Z.; Wang, Q.; Li, Y. Investigation of cardiovascular protective effect of Shenmai injection by network pharmacology and pharmacological evaluation. BMC Complement. Med. Ther., 2020, 20(1), 112. doi: 10.1186/s12906-020-02905-8 PMID: 32293408
- Chen, F.F.; Lin, L.N.; Miao, J.X. Protective effect of Shenmai injection on lung injury induced by cardiac pulmonary bypass. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih, 2009, 29(5), 414-417. PMID: 19673331
Дополнительные файлы
