Education, Science, Technology, Innovation and Life
Open Access
Sign In

Mechanisms of Yangxin Tongmai Formula against Coronary Heart Disease through the Microbiota Gut Heart Axis

Download as PDF

DOI: 10.23977/medcm.2026.080120 | Downloads: 11 | Views: 78

Author(s)

Hang Xu 1, Xing Chen 1, Lingli Chen 1

Affiliation(s)

1 Hunan University of Chinese Medicine, Changsha, China

Corresponding Author

Lingli Chen

ABSTRACT

Coronary heart disease (CHD) is one of the most common causes of death worldwide. Disruptions in the intestinal microbiota can promote the formation of CHD through different inflammatory reactions. Yangxin Tongmai Formula (YTF) has shown beneficial effects in CHD patients. Therefore, we aimed to investigate differences in the gut microbiota between rats with CHD and healthy rats in order to identify new biomarker of gut microbiota for diagnosis and Chinese herbal medicine treatment of CHD. The study cohort included 72 CHD rats and 16 normal rats. The CHD animal models were established and divided into 9 groups, including three YTF groups, four fecal transplantation groups, the atorvastatin calcium group, and the CHD group. All rats were sacrificed after 3.5 months of feeding and experiments, and blood, fecal, heart, and small intestine were samples collected for biochemical and pathological evaluations. The abundance of the intestinal flora was analyzed by bacterial 16S rRNA sequencing. The occludin protein was detected by western blotting. The result display the CHD model was successfully created.Rats that received YTF showed improvements in the lipid indices. The myocardial tissue cells and intestinal tissues in the medium-dose YTF group were basically complete, making it difficult to observe inflammatory response. The transmission electron microscopy results showed that the tight junctions of the medium-dose YTF group was improved. The operational taxonomic unit comparison showed that the abundance of lactobacilli and bifidobacteria in CHD rats significantly were improved after treatment with YTF. The abundance of beneficial bacteria in CHD rats was significantly increased (P < 0.01) following fecal bacterial transplantation from normal control rats and rats that underwent the YTF treatment. In comparison with the model control group, the relative expression of occludin protein in the medium-dose YTF group was upregulated (P < 0.05). The abundance of the gut microbiota differed significantly between CHD rats and healthy rats. YTF and fecal transplantation successfully alleviated atherosclerosis by remodeling the gut microbiota and the mechanical barrier function of small intestinal tissue. 

KEYWORDS

CHD; Intestinal flora; Biodiversity; Fecal bacterial transplantation; Microbiota-gut-heart axis

CITE THIS PAPER

Hang Xu, Xing Chen, Lingli Chen. Mechanisms of Yangxin Tongmai Formula against Coronary Heart Disease through the Microbiota Gut Heart Axis. MEDS Chinese Medicine (2026). Vol. 8, No. 1, 172-187. DOI: http://dx.doi.org/10.23977/medcm.2026.080120.

REFERENCES

[1] M. Ahmadi, B. Lanphear, The impact of clinical and population strategies on coronary heart disease mortality: an assessment of Rose's big idea, BMC Public Health 22 (2022) 14. https://doi.org/10.1186/s12889-021-12421-0.
[2] H. Kaur, G. Kaur, S.A. Ali, IL-33’s role in the gut immune system: A comprehensive review of its crosstalk and regulation, Life Sciences 327 (2023) 121868. https://doi.org/10.1016/j.lfs.2023.121868.
[3] L.V. Hooper, D.R. Littman, A.J. Macpherson, Interactions Between the Microbiota and the Immune System, Science 336 (2012) 1268–1273. https://doi.org/10.1126/science.1223490.
[4] J.-H. Yoon, J.-S. Do, P. Velankanni, C.-G. Lee, H.-K. Kwon, Gut Microbial Metabolites on Host Immune Responses in Health and Disease, Immune Netw 23 (2023) e6. https://doi.org/10.4110/in.2023.23.e6.
[5] D.A. Schupack, R.A.T. Mars, D.H. Voelker, J.P. Abeykoon, P.C. Kashyap, The promise of the gut microbiome as part of individualized treatment strategies, Nat Rev Gastroenterol Hepatol 19 (2022) 7–25. https://doi.org/10.1038/s41575-021-00499-1.
[6] S. Sanna, A. Kurilshikov, A. Van Der Graaf, J. Fu, A. Zhernakova, Challenges and future directions for studying effects of host genetics on the gut microbiome, Nat Genet 54 (2022) 100–106. https://doi.org/10.1038/s41588-021-00983-z.
[7] Y. Qin, A.S. Havulinna, Y. Liu, P. Jousilahti, S.C. Ritchie, A. Tokolyi, J.G. Sanders, L. Valsta, M. Brożyńska, Q. Zhu, A. Tripathi, Y. Vázquez-Baeza, R. Loomba, S. Cheng, M. Jain, T. Niiranen, L. Lahti, R. Knight, V. Salomaa, M. Inouye, G. Méric, Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort, Nat Genet 54 (2022) 134–142. https://doi.org/10.1038/s41588-021-00991-z.
[8] A.A. Manolis, T.A. Manolis, H. Melita, A.S. Manolis, Gut Microbiota and Cardiovascular Disease: Symbiosis VersusDysbiosis, CMC 29 (2022) 4050–4077. https://doi.org/10.2174/0929867328666211213112949.
[9] T. Yntema, D.P.Y. Koonen, F. Kuipers, Emerging Roles of Gut Microbial Modulation of Bile Acid Composition in the Etiology of Cardiovascular Diseases, Nutrients 15 (2023) 1850. https://doi.org/10.3390/nu15081850.
[10] A. Nesci, C. Carnuccio, V. Ruggieri, A. D’Alessandro, A. Di Giorgio, L. Santoro, A. Gasbarrini, A. Santoliquido, F.R. Ponziani, Gut Microbiota and Cardiovascular Disease: Evidence on the Metabolic and Inflammatory Background of a Complex Relationship, IJMS 24 (2023) 9087. https://doi.org/10.3390/ijms24109087.
[11] J.C. Ibal, Y.-J. Park, M.-K. Park, J. Lee, M.-C. Kim, J.-H. Shin, Review of the Current State of Freely Accessible Web Tools for the Analysis of 16S rRNA Sequencing of the Gut Microbiome, IJMS 23 (2022) 10865. https://doi.org/10.3390/ijms231810865.
[12] A. Regueira‐Iglesias, C. Balsa‐Castro, T. Blanco‐Pintos, I. Tomás, Critical review of 16S rRNA gene sequencing workflow in microbiome studies: From primer selection to advanced data analysis, Molecular Oral Microbiology 38 (2023) 347–399. https://doi.org/10.1111/omi.12434.
[13] M. Choroszy, K. Litwinowicz, R. Bednarz, T. Roleder, A. Lerman, T. Toya, K. Kamiński, E. Sawicka-Śmiarowska, M. Niemira, B. Sobieszczańska, Human Gut Microbiota in Coronary Artery Disease: A Systematic Review and Meta-Analysis, Metabolites 12 (2022) 1165. https://doi.org/10.3390/metabo12121165.
[14] T. Katsimichas, P. Theofilis, K. Tsioufis, D. Tousoulis, Gut Microbiota and Coronary Artery Disease: Current Therapeutic Perspectives, Metabolites 13 (2023) 256. https://doi.org/10.3390/metabo13020256.
[15] A. Srivastava, Y. Akhter, D. Verma, A step-by-step procedure for analysing the 16S rRNA-based microbiome diversity using QIIME 2 and comprehensive PICRUSt2 illustration for functional prediction, Arch Microbiol 206 (2024) 467. https://doi.org/10.1007/s00203-024-04177-z.
[16] D.H. Huson, S. Beier, I. Flade, A. Górska, M. El-Hadidi, S. Mitra, H.-J. Ruscheweyh, R. Tappu, MEGAN Community Edition - Interactive Exploration and Analysis of Large-Scale Microbiome Sequencing Data, PLoS Comput Biol 12 (2016) e1004957. https://doi.org/10.1371/journal.pcbi.1004957.
[17] M. Blaxter, J. Mann, T. Chapman, F. Thomas, C. Whitton, R. Floyd, E. Abebe, Defining operational taxonomic units using DNA barcode data, Phil. Trans. R. Soc. B 360 (2005) 1935–1943. https://doi.org/10.1098/rstb.2005.1725.
[18] R.C. Edgar, Search and clustering orders of magnitude faster than BLAST, Bioinformatics 26 (2010) 2460–2461. https://doi.org/10.1093/bioinformatics/btq461.
[19] H. Xu, X. Wang, W. Feng, Q. Liu, S. Zhou, Q. Liu, L. Cai, The gut microbiota and its interactions with cardiovascular disease, Microbial Biotechnology 13 (2020) 637–656. https://doi.org/10.1111/1751-7915.13524.
[20] H. Liu, J. Zhuang, P. Tang, J. Li, X. Xiong, H. Deng, The Role of the Gut Microbiota in Coronary Heart Disease, Curr Atheroscler Rep 22 (2020) 77. https://doi.org/10.1007/s11883-020-00892-2.
[21] W. Zhou, Y. Cheng, P. Zhu, M.I. Nasser, X. Zhang, M. Zhao, Implication of Gut Microbiota in Cardiovascular Diseases, Oxidative Medicine and Cellular Longevity 2020 (2020) 1–14. https://doi.org/10.1155/2020/5394096.
[22] J.-H. Kim, Pharmacological and medical applications of Panax ginseng and ginsenosides: a review for use in cardiovascular diseases, Journal of Ginseng Research 42 (2018) 264–269. https://doi.org/10.1016/j.jgr.2017.10.004.
[23] J. Ren, L. Fu, S.H. Nile, J. Zhang, G. Kai, Salvia miltiorrhiza in Treating Cardiovascular Diseases: A Review on Its Pharmacological and Clinical Applications, Front. Pharmacol. 10 (2019) 753. https://doi.org/10.3389/fphar.2019.00753.
[24] C.-Y. Su, Q.-L. Ming, K. Rahman, T. Han, L.-P. Qin, Salvia miltiorrhiza: Traditional medicinal uses, chemistry, and pharmacology, Chinese Journal of Natural Medicines 13 (2015) 163–182. https://doi.org/10.1016/S1875-5364(15)30002-9.
[25] W. Tan, Y. Li, Y. Wang, Z. Zhang, T. Wang, Q. Zhou, X. Wang, Anti-coagulative and gastrointestinal motility regulative activities of Fructus Aurantii Immaturus and its effective fractions, Biomedicine & Pharmacotherapy 90 (2017) 244–252. https://doi.org/10.1016/j.biopha.2017.03.060.
[26] M. Kang, J.-H. Kim, C. Cho, H.-S. Chung, C.-W. Kang, Y. Kim, M. Shin, M. Hong, H. Bae, Anti-ischemic effect of Aurantii Fructus on contractile dysfunction of ischemic and reperfused rat heart, Journal of Ethnopharmacology 111 (2007) 584–591. https://doi.org/10.1016/j.jep.2007.01.007.
[27] P. Wang, T. Song, R. Shi, M. He, R. Wang, J. Lv, M. Jiang, Triterpenoids From Alisma Species: Phytochemistry, Structure Modification, and Bioactivities, Front. Chem. 8 (2020) 363. https://doi.org/10.3389/fchem.2020.00363.
[28] J. Liu, Q. Zhang, R.-L. Li, S.-J. Wei, C.-Y. Huang, Y.-X. Gao, X.-F. Pu, The traditional uses, phytochemistry, pharmacology and toxicology of Cinnamomi ramulus : a review, Journal of Pharmacy and Pharmacology 72 (2020) 319–342. https://doi.org/10.1111/jphp.13189.
[29] Y.H. Kang, H.M. Shin, Cinnamomi ramulus Ethanol Extract Exerts Vasorelaxation through Inhibition of Ca 2 + Influx and Ca 2 + Release in Rat Aorta, Evidence-Based Complementary and Alternative Medicine 2012 (2012) 1–7. https://doi.org/10.1155/2012/513068.
[30] Z. Wang, E. Klipfell, B.J. Bennett, R. Koeth, B.S. Levison, B. DuGar, A.E. Feldstein, E.B. Britt, X. Fu, Y.-M. Chung, Y. Wu, P. Schauer, J.D. Smith, H. Allayee, W.H.W. Tang, J.A. DiDonato, A.J. Lusis, S.L. Hazen, Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease, Nature 472 (2011) 57–63. https://doi.org/10.1038/nature09922.
[31] Y. Zhang, J. Xu, X. Wang, X. Ren, Y. Liu, Changes of intestinal bacterial microbiota in coronary heart disease complicated with nonalcoholic fatty liver disease, BMC Genomics 20 (2019) 862. https://doi.org/10.1186/s12864-019-6251-7.
[32] A.C. Loughrey, E.W. Chew, Endocarditis caused by Veillonella dispar, Journal of Infection 21 (1990) 319–321. https://doi.org/10.1016/0163-4453(90)94197-8.
[33] Y. Dong, R. Xu, X. Chen, C. Yang, F. Jiang, Y. Shen, Q. Li, F. Fang, Y. Li, X. Shen, Characterization of gut microbiota in adults with coronary atherosclerosis, PeerJ 11 (2023) e15245. https://doi.org/10.7717/peerj.15245.
[34] A.A. Salyers, J.R. Vercellotti, S.E. West, T.D. Wilkins, Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon, Appl Environ Microbiol 33 (1977) 319–322. https://doi.org/10.1128/aem.33.2.319-322.1977.
[35] T.S. Stappenbeck, L.V. Hooper, J.I. Gordon, Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells, Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 15451–15455. https://doi.org/10.1073/pnas.202604299.
[36] D. Festi, R. Schiumerini, C. Birtolo, L. Marzi, L. Montrone, E. Scaioli, A.R. Di Biase, A. Colecchia, Gut Microbiota and Its Pathophysiology in Disease Paradigms, Dig Dis 29 (2011) 518–524. https://doi.org/10.1159/000332975.
[37] K. Harris, A. Kassis, G. Major, C.J. Chou, Is the Gut Microbiota a New Factor Contributing to Obesity and Its Metabolic Disorders?, Journal of Obesity 2012 (2012) 1–14. https://doi.org/10.1155/2012/879151.
[38] K. Winek, U. Dirnagl, A. Meisel, The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke, Neurotherapeutics 13 (2016) 762–774. https://doi.org/10.1007/s13311-016-0475-x.
[39] J.M. Brown, S.L. Hazen, The Gut Microbial Endocrine Organ: Bacterially Derived Signals Driving Cardiometabolic Diseases, Annu. Rev. Med. 66 (2015) 343–359. https://doi.org/10.1146/annurev-med-060513-093205.
[40] W.H.W. Tang, T. Kitai, S.L. Hazen, Gut Microbiota in Cardiovascular Health and Disease, Circulation Research 120 (2017) 1183–1196. https://doi.org/10.1161/CIRCRESAHA.117.309715.
[41] Z. Wang, A.B. Roberts, J.A. Buffa, B.S. Levison, W. Zhu, E. Org, X. Gu, Y. Huang, M. Zamanian-Daryoush, M.K. Culley, A.J. DiDonato, X. Fu, J.E. Hazen, D. Krajcik, J.A. DiDonato, A.J. Lusis, S.L. Hazen, Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis, Cell 163 (2015) 1585–1595. https://doi.org/10.1016/j.cell.2015.11.055.

Downloads: 10791
Visits: 969104

Sponsors, Associates, and Links


All published work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright © 2016 - 2031 Clausius Scientific Press Inc. All Rights Reserved.