The signaling pathways of atherosclerosis regulated by Taohong Siwu Decoction

Kaijie Yan , Sihe Gong , Yanni Li , Zhonghong Shi , Yimin Bao , Jing Leng , Ke Ning

Chinese Journal of Natural Medicines ›› 2026, Vol. 24 ›› Issue (3) : 279 -288.

PDF (3415KB)
Chinese Journal of Natural Medicines ›› 2026, Vol. 24 ›› Issue (3) :279 -288. DOI: 10.1016/S1875-5364(26)61103-X
Review
research-article
The signaling pathways of atherosclerosis regulated by Taohong Siwu Decoction
Author information +
History +
PDF (3415KB)

Abstract

Taohong Siwu Decoction (THSWD), a traditional Chinese medicinal formulation, has been demonstrated to significantly modulate key signaling pathways implicated in atherosclerosis (AS). This review examines the complex mechanisms through which THSWD influences critical pathways, including nuclear factor kappa-B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (AKT), Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR), that play pivotal roles in AS pathogenesis. By synthesizing experimental evidence and existing literature, the review summarizes how THSWD and its bioactive constituents regulate these signaling cascades to ameliorate AS. Furthermore, it highlights the distinctive therapeutic advantages of traditional Chinese medicine (TCM) compounds in managing chronic diseases driven by multi-target and multifactorial mechanisms. Analyzing disease targets from the perspective of signaling pathways enhances the scientific validation of clinical efficacy for such formulations, thereby offering novel insights for future research.

Keywords

Atherosclerosis / Traditional Chinese medicine / Taohong Siwu Decoction / Signaling pathways

Cite this article

Download citation ▾
Kaijie Yan, Sihe Gong, Yanni Li, Zhonghong Shi, Yimin Bao, Jing Leng, Ke Ning. The signaling pathways of atherosclerosis regulated by Taohong Siwu Decoction. Chinese Journal of Natural Medicines, 2026, 24(3): 279-288 DOI:10.1016/S1875-5364(26)61103-X

登录浏览全文

4963

注册一个新账户 忘记密码

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 82104430 and 82274133), the Shanghai Sailing Program (No. 21YF1447600), and the Future Plan for Traditional Chinese Medicine Development of Science and Technology of Shanghai Municipal Hospital of Traditional Chinese Medicine (No. WL-HBQN-2022002K).

Acknowledgements

We gratefully acknowledge the use of BioRender for the creation of the scientific illustrations in this study.

Declaration of competing interest

These authors have no conflict of interest to declare.

References

[1]

Zhang B. Effect of medicated serum prepared with Taohong Siwu Decoction on expressions of TNF-Α MCP-1 and IL-1Β of human umbilical vein endothelial cells treated with lipopolysaccharide. Liaoning J Tradit Chin Med. 2014; 41:2280-2283. https://doi.org/10.13192/j.issn.1000-1719.2014.11.004.

[2]

Han L, Peng DY, Xu F, et al. Studies on anti-platelet activationand partial mechanism of Taohong Siwu Decoction. China J Chin Mater Med. 2010; 35(19):2609-2612. https://doi.org/10.4268/cjcmm20101924.

[3]

Lai LN, Zhou XQ. Discussion on the mechanism of Taohong Siwu Decoction in treating dyslipidemia based on network pharmacology. J Liaoning Univ Tradit Chin Med. 2021; 23(4):72-78. https://doi.org/10.13194/j.issn.1673-842x.2021.04.017.

[4]

Luo ZR, Li H, Xiao ZX, et al. Taohong Siwu Decoction exerts a beneficial effect on cardiac function by possibly improving the microenvironment and decreasing mitochondrial fission after myocardial infarction. Cardiol Res Pract. 2019; 2019:5198278. https://doi.org/10.1155/2019/5198278.

[5]

Li RS, Li DY, Chen WN, et al. Taohong Siwu Decoction regulated functions of endothelial cells and treated arteriosclerosis obliterans: an experimental study. Chin J Integr Med. 2014; 34(2):191-196. https://doi.org/10.7661/CJIM.2014.02.0191.

[6]

Kattoor AJ, Pothineni NVK, Palagiri D, et al.Oxidative stress in atherosclerosis. Curr Atheroscler Rep. 2017; 19(11):42. https://doi.org/10.1007/s11883-017-0678-6.

[7]

Wei SG. Observation on the clinical efficacy of Taohong Siwu Decoction combined with conventional drugs in the treatment of coronary atherosclerotic heart disease and angina pectoris. Cardiovasc Dis J Integr Tradit Chin West Med. 2018; 6(29):111-112. https://doi.org/10.16282/j.cnki.cn11-9336/r.2018.29.084.

[8]

Wang CB, Hu XH, Li L. Clinical observation of Taohong Siwu Decoction combined with cilostazol in treating ASO of lower extremity. Acta Chin Med Pharmacol. 2020; 48(11):63-67. https://doi.org/10.19664/j.cnki.1002-2392.200199.

[9]

Yang QH. 47 Cases of coronary artery disease and angina treated in modified Peach Seed and Safflower Decoction of Four Drugs. J Henan Univ Chin Med. 2008; 4:77-78. https://doi.org/10.16368/j.issn.1674-8999.2008.04.021.

[10]

Liu L, Duan JA, Su SL, et al. Effect of different fractions of Taohong Siwu Decoction on ADP-induced platelet aggregation and thrombin activity. China J Chin Mater Med. 2016; 41(4):716-721. https://doi.org/10.4268/cjcmm20160429.

[11]

Liu L, Duan JA, Tang Y, et al. Taoren-Honghua herb pair and its main components promoting blood circulation through influencing on hemorheology, plasma coagulation and platelet aggregation. J Ethnopharmacol. 2012; 139(2):381-387. https://doi.org/10.1016/j.jep.2011.11.016.

[12]

Yang Y, Huang XL, Jiang ZM, et al. New research progress for chemical compositions and pharmacological effect of Honghua (Carthami Flos). Chin Arch Tradit Chin Med. 2023; 41(10):119-126. https://doi.org/10.13193/j.issn.1673-7717.2023.10.024.

[13]

Li WX, Tang YP, Chen YY, et al. Advances in the chemical analysis and biological activities of chuanxiong. Molecules. 2012; 17(9):10614-10651. https://doi.org/10.3390/molecules170910614.

[14]

Lyu CL, Li HH, Shi YJ, et al. Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers. China J Chin Mater Med. 2022; 47(19):5140-5157. https://doi.org/10.19540/j.cnki.cjcmm.20220225.203.

[15]

Yan BJ, Shen ML, Fang JY, et al. Advancement in the chemical analysis of Paeoniae Radix (Shaoyao). J Pharm Biomed Anal. 2018; 160:276-288. https://doi.org/10.1016/j.jpba.2018.08.009.

[16]

Ge N, Yan GL, Sun H, et al. Research progress on effective constituents in Radix Rehmanniae Praeparata. Chin Tradit Herb Drugs. 2023; 54(1):292-302. https://doi.org/10.7501/j.issn.0253-2670.2023.01.031.

[17]

Liu T, Zhang LY, Joo DH, et al. NF-κB signaling in inflammation. Signal Transduct Targeted Ther. 2017; 2:17023. https://doi.org/10.1038/sigtrans.2017.23.

[18]

Sun SC. The non-canonical NF-κB pathway in immunity and inflammation. Nat Rev Immunol. 2017; 17(9):545-558. https://doi.org/10.1038/nri.2017.52.

[19]

Baker RG, Hayden MS, Ghosh S. NF-κB, inflammation, and metabolic disease. Cell Metab. 2011; 13(1):11-22. https://doi.org/10.1016/j.cmet.2010.12.008.

[20]

Zhang H, Sun SC. NF-κB in inflammation and renal diseases. Cell Biosci. 2015; 5:63. https://doi.org/10.1186/s13578-015-0056-4.

[21]

Monaco C, Andreakos E, Kiriakidis S, et al. Canonical pathway of nuclear factor κB activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis. Proc Natl Acad Sci USA. 2004; 101(15):5634-5639. https://doi.org/10.1073/pnas.0401060101.

[22]

Zhou P, Luo Y, Xing N, et al. Research progress of pathogenesis of atherosclerosis induced by tumor necrosis factorα. World Chin Med. 2015; 10(8):1163-1168. https://doi.org/10.3969/j.issn.1673-7202.2015.08.008.

[23]

Kanters E, Pasparakis M, Gijbels MJ, et al. Inhibition of NF-κB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 2003; 112(8):1176-1185. https://doi.org/10.1172/jci18580.

[24]

Shen AL, Shi H, Peng DY, et al. Regulation of NF-κB signal pathway and protection of cardiac structure and function of type 2 diabetes mellitus rat by treating with Taohong Siwu Decoction. China J Tradit Chin Med Pharm. 2019; 34(4):1359-1362.

[25]

Wang WJ, Deng XY, Wang W. Mechanism of Taohong Siwu Decoction in treating soft tissue injury based on UPLC-Q-TOF-MS, network pharmacology and experimental verification. China J Chin Mater Med. 2021; 46(12):3043-3051. https://doi.org/10.19540/j.cnki.cjcmm.20210311.403.

[26]

Wang JY, Chen WN, Jia LQ, et al. Effects of Erchen Decoction and Taohong Siwu Decoction on Nox4/NF-κB/HIF-1α signaling pathway in aorta of ApoE-/- atherosclerosis mice. China J Tradit Chin Med Pharm. 2019; 34(6):2417-2420. https://doi.org/10.37155/2717-5693-0102-2.

[27]

Yuan GZ, Han AB, Wu J, et al. Bao Yuan Decoction and Tao Hong Si Wu Decoction improve lung structural remodeling in a rat model of myocardial infarction: possible involvement of suppression of inflammation and fibrosis and regulation of the TGF-β1/Smad3 and NF-κB pathways. Biosci Trends. 2018; 12(5):491-501. https://doi.org/10.5582/bst.2018.01242.

[28]

Wu FF, Zhang XW. Protective effect of peach kernel extract on coronary heart disease model rats through nuclear factor-κB/cyclooxygenase-2 pathway. Med J Wuhan Univ. 2020; 41(5):725-731. https://doi.org/10.14188/j.1671-8852.2019.0996.

[29]

Bhaskar S, Helen A. Quercetin modulates toll-like receptor-mediated protein kinase signaling pathways in oxLDL-challenged human PBMCs and regulates TLR-activated atherosclerotic inflammation in hypercholesterolemic rats. Mol Cell Biochem. 2016; 423(1-2):53-65. https://doi.org/10.1007/s11010-016-2824-9.

[30]

Jia ZQ, Nallasamy P, Liu DM, et al. Luteolin protects against vascular inflammation in mice and TNF-α-induced monocyte adhesion to endothelial cells via suppressing IΚBα/NF-κB signaling pathway. J Nutr Biochem. 2015; 26(3):293-302. https://doi.org/10.1016/j.jnutbio.2014.11.008.

[31]

Jung KJ, Go EK, Kim JY, et al. Suppression of age-related renal changes in NF-kappaB and its target gene expression by dietary ferulate. J Nutr Biochem. 2009; 20(5):378-388. https://doi.org/10.1016/j.jnutbio.2008.04.008.

[32]

Liu L, Ning ZQ, Shan S, et al. Phthalide lactones from Ligusticum chuanxiong inhibit lipopolysaccharide-induced TNF-alpha production and TNF-alpha-mediated NF-kappaB activation. Planta Med. 2005; 71(9):808-813. https://doi.org/10.1055/s-2005-871231.

[33]

Li WF, Zhi WB, Liu F, et al. Paeoniflorin inhibits VSMCs proliferation and migration by arresting cell cycle and activating HO-1 through MAPKs and NF-κB pathway. Int Immunopharmacol. 2018; 54:103-111. https://doi.org/10.1016/j.intimp.2017.10.017.

[34]

Gao F, He QF, Wu SH, et al. Catalpol ameliorates LPS-induced inflammatory response by activating AMPK/mTOR signaling pathway in rat intestinal epithelial cells. Eur J Pharmacol. 2023; 960:176125. https://doi.org/10.1016/j.ejphar.2023.176125.

[35]

Chen SS, Liu HH, Wang SM, et al. The neuroprotection of verbascoside in Alzheimer’s disease mediated through mitigation of neuroinflammation via blocking NF-κB-p 65 signaling. Nutrients. 2022; 14(7):1417. https://doi.org/10.3390/nu14071417.

[36]

Zhang JX, Wang XL, Vikash V, et al. ROS andROS-mediated cellular signaling. Oxid Med Cell Longev. 2016; 2016:4350965. https://doi.org/10.1155/2016/4350965.

[37]

Sarbassov DD, Guertin DA, Ali SM, et al. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005; 307(5712):1098-1101. https://doi.org/10.1126/science.1106148.

[38]

Linton MF, Moslehi JJ, Babaev VR. Akt signaling in macrophage polarization, survival, and atherosclerosis. Int J Mol Sci. 2019; 20(11):2703. https://doi.org/10.3390/ijms20112703.

[39]

Hirsch E, Ciraolo E, Ghigo A, et al. Taming the PI3K team to hold inflammation and cancer at bay. Pharmacol Ther. 2008; 118(2):192-205. https://doi.org/10.1016/j.pharmthera.2008.02.004.

[40]

Romashkova JA, Makarov SS. NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature. 1999; 401(6748):86-90. https://doi.org/10.1038/43474.

[41]

Mantovani A, Garlanda C, Locati M. Macrophage diversity and polarization in atherosclerosis: a question of balance. Arterioscler Thromb Vasc Biol. 2009; 29(10):1419-1423. https://doi.org/10.1161/atvbaha.108.180497.

[42]

Williams HJ, Fisher EA, Greaves DR. Macrophage differentiation and function in atherosclerosis: opportunities for therapeutic intervention? J Innate Immun. 2012; 4(5-6):498-508. https://doi.org/10.1159/000336618.

[43]

Arranz A, Doxaki C, Vergadi E, et al. Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proc Natl Acad Sci U S A. 2012; 109(24):9517-9522. https://doi.org/10.1073/pnas.1119038109.

[44]

Seimon T, Tabas I. Mechanisms and consequences of macrophage apoptosis in atherosclerosis. J Lipid Res. 2009; 50(Suppl):S382-S387. https://doi.org/10.1194/jlr.R800032-JLR200.

[45]

Michell BJ, Griffiths JE, Mitchelhill KI, et al. The Akt kinase signals directly to endothelial nitric oxide synthase. Curr Biol. 1999; 9(15):845-848. https://doi.org/10.1016/s0960-9822(99)80371-6.

[46]

Wang JY, Qu NN, Jia LQ, et al. Effect and mechanism of serum containing of Erchen Decoction and Taohong Siwu Decoction on ox-LDL induced endothelial cell damage. Chin J Arterioscler. 2018; 26(10):987-992. https://doi.org/10.3969/j.issn.1007-3949.2018.10.004.

[47]

Han L, Liang J, Zhang YY, et al. Effects of Taohong Siwu Decoction on the VEGF, NO expression and PI3K/Akt pathway alterations in uterine tissue of postpartum rats with blood stasis syndrome. China J Tradit Chin Med Pharm. 2016; 31(5):1625-1629.

[48]

Porta C, Paglino C, Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol. 2014; 4:64. https://doi.org/10.3389/fonc.2014.00064.

[49]

Lu XL, Zhao CH, Yao XL, et al. Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway. Biomed Pharmacother. 2017; 85:658-671. https://doi.org/10.1016/j.biopha.2016.11.077.

[50]

Che JB, Liang B, Zhang Y, et al. Kaempferol alleviates ox-LDL-induced apoptosis by up-regulation of autophagy via inhibiting PI3K/Akt/mTOR pathway in human endothelial cells. Cardiovasc Pathol. 2017; 31:57-62. https://doi.org/10.1016/j.carpath.2017.08.001.

[51]

Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010; 11(5):373-384. https://doi.org/10.1038/ni.1863.

[52]

Goulopoulou S, McCarthy CG, Webb RC. Toll-like receptors in the vascular system: sensing the dangers within. Pharmacol Rev. 2016; 68(1):142-167. https://doi.org/10.1124/pr.114.010090.

[53]

Kawasaki T, Kawai T.Toll-like receptor signaling pathways. Front Immunol. 2014; 5:461. https://doi.org/10.3389/fimmu.2014.00461.

[54]

Yamamoto M, Sato S, Hemmi H, et al. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol. 2003; 4(11):1144-1150. https://doi.org/10.1038/ni986.

[55]

Laurent YC, Carrie W, Tamara AP, et al. Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via toll-like receptors, and neutrophil infiltration of atherosclerotic lesions. Circulation. 2008; 118(18):1837-1847. https://doi.org/10.1161/circulationaha.108.793869.

[56]

Chen TW, Huang WJ, Qian JF, et al. Macrophage-derived myeloid differentiation protein 2 plays an essential role in ox-LDL-induced inflammation and atherosclerosis. EBioMedicine. 2020; 53:102706. https://doi.org/10.1016/j.ebiom.2020.102706.

[57]

Schoneveld AH, Hoefer I, Sluijter JPG, et al. Atherosclerotic lesion development and Toll like receptor 2 and 4 responsiveness. Atherosclerosis. 2008; 197(1):95-104. https://doi.org/10.1016/j.atherosclerosis.2007.08.004.

[58]

Huang RZ, Hu ZC, Chen XR, et al. The transcription factor SUB1 is a master regulator of the macrophage TLR response in atherosclerosis. Adv Sci (Weinh). 2021; 8(19):e2004162. https://doi.org/10.1002/advs.202004162.

[59]

Ye ZS, Jin MY, Wang SJ, et al. Subcutaneous injection of dendritic cells aggravates atherosclerosis in ApoE-knockout mice by activation of TLR4. Mol Med Rep. 2017; 16(5):6041-6049. https://doi.org/10.3892/mmr.2017.7339.

[60]

Wang MM, Liu ZQ, Hu SS, et al. Taohong Siwu Decoction ameliorates ischemic stroke injury via suppressing pyroptosis. Front Pharmacol. 2020; 11:590453. https://doi.org/10.3389/fphar.2020.590453.

[61]

Fan WC, Lyu LT, Bai DY, et al. Study on improvement effect of Taohong Siwu Decoction on joint swelling in rat models with rheumatoid arthritis and its mechanism. New J Tradit Chin Med. 2023; 55(1):53-57. https://doi.org/10.13457/j.cnki.jncm.2023.01.011.

[62]

Chang FJ, Zhou P, Li GY, et al. TaohongSiwuDecoctionamelioratesatherosclerosisinratspossiblythroughtoll-likereceptor4/myeloiddifferentiationprimaryresponseprotein88/nuclearfactor-κBsignalpathway. J Tradit Chin Med. 2024; 44(1):103-112. https://doi.org/10.19852/j.cnki.jtcm.20231215.003.

[63]

Yang LJ, Yang KL, Zhong WL, et al. Study on anti-arteriosclerosis mechanism of ligustrazine and ferulic acid based on network pharmacology. Drug Eval Res. 2021; 44(12):2555-2562. https://doi.org/10.7501/j.issn.1674-6376.2021.12.005.

[64]

Li H, Jiao Y, Xie M. Paeoniflorin ameliorates atherosclerosis by suppressing TLR4-mediated NF-κB activation. Inflammation. 2017; 40(6):2042-2051. https://doi.org/10.1007/s10753-017-0644-z.

[65]

Liang QC, Chen YT, Li CX, et al. Quercetin attenuates Ox-LDL-induced calcification in vascular smooth muscle cells by regulating ROS-TLR4 signaling pathway. J South Med Univ. 2018; 38(8):980-985. https://doi.org/10.3969/j.issn.1673-4254.2018.08.13.

[66]

Zhong XM, Zhang L, Li YM, et al. Kaempferol alleviates ox-LDL-induced apoptosis by up-regulation of miR-26a-5p via inhibiting TLR4/NF-κB pathway in human endothelial cells. Biomed Pharmacother. 2018; 108:1783-1789. https://doi.org/10.1016/j.biopha.2018.09.175.

[67]

Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs. Oncogene. 2007; 26(22):3100-3112. https://doi.org/10.1038/sj.onc.1210392.

[68]

Muslin AJ. MAPK signalling in cardiovascular health and disease: molecular mechanisms and therapeutic targets. Clin Sci (Lond). 2008; 115(7):203-218. https://doi.org/10.1042/cs20070430.

[69]

Meier R, Rouse J, Cuenda A, et al. Cellular stresses and cytokines activate multiple mitogen-activated-protein kinase kinase homologues in PC12 and KB cells. Eur J Biochem. 1996; 236(3):796-805. https://doi.org/10.1111/j.1432-1033.1996.00796.x.

[70]

Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011; 75(1):50-83. https://doi.org/10.1128/mmbr.00031-10.

[71]

Yoon S, Seger R. The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors. 2006; 24(1):21-44. https://doi.org/10.1080/02699050500284218.

[72]

Cuadrado A, Nebreda AR. Mechanisms and functions of p 38 MAPK signalling. Biochem J. 2010; 429(3):403-417. https://doi.org/10.1042/bj20100323.

[73]

Pietersma A, Tilly BC, Gaestel M, et al. P38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level. Biochem Biophys Res Commun. 1997; 230(1):44-48. https://doi.org/10.1006/bbrc.1996.5886.

[74]

Goebeler M, Kilian K, Gillitzer R, et al. The MKK6/p38 stress kinase cascade is critical for tumor necrosis factor-alpha-induced expression of monocyte-chemoattractant protein-1 in endothelial cells. Blood. 1999; 93(3):857-865. https://doi.org/10.1182/blood.V93.3.857.403k03_857_865.

[75]

Liao LZ, Zhou Q, Song Y, et al. Ceramide mediates Ox-LDL-induced human vascular smooth muscle cell calcification via p38 mitogen-activated protein kinase signaling. PLoS One. 2013; 8(12):e82379. https://doi.org/10.1371/journal.pone.0082379.

[76]

Senokuchi T, Matsumura T, Sakai M, et al. Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase mediate macrophage proliferation induced by oxidized low-density lipoprotein. Atherosclerosis. 2004; 176(2):233-245. https://doi.org/10.1016/j.atherosclerosis.2004.05.019.

[77]

Xu Y, Zhang Y, Xu Y, et al. Activation of CD 137 signaling promotes macrophage apoptosis dependent on p38 MAPK pathway-mediated mitochondrial fission. Int J Biochem Cell Biol. 2021; 136:106003. https://doi.org/10.1016/j.biocel.2021.106003.

[78]

Tang LF, Chang H, Wang DD, et al. Active components and potential mechanism of Taohong Siwu Decoction in regulating ischemic stroke based on target cell trapping combined with network pharmacology, molecular docking, and experimental validation. China J Chin Mater Med. 2023; 48(17):4761-4773. https://doi.org/10.19540/j.cnki.cjcmm.20230423.403.

[79]

Luo G, Xiang L, Xiao L. Quercetin alleviates atherosclerosis by suppressing oxidized LDL-induced senescence in plaque macrophage via inhibiting the p38MAPK/p16 pathway. J Nutr Biochem. 2023; 116:109314. https://doi.org/10.1016/j.jnutbio.2023.109314.

[80]

Wu YL, Wang F, Fan LH, et al. Baicalin alleviates atherosclerosis by relieving oxidative stress and inflammatory responses via inactivating the NF-κB and p38 MAPK signaling pathways. Biomed Pharmacother. 2018; 97:1673-1679. https://doi.org/10.1016/j.biopha.2017.12.024.

[81]

Lu Q, Qiu TQ, Yang H. Ligustilide inhibits vascular smooth muscle cells proliferation. Eur J Pharmacol. 2006; 542(1-3):136-140. https://doi.org/10.1016/j.ejphar.2006.04.023.

[82]

Bai JR, Zhang YS, Tang C, et al. Gallic acid: pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomed Pharmacother. 2021; 133:110985. https://doi.org/10.1016/j.biopha.2020.110985.

[83]

Liu M, Feng J, Du Q, et al. Paeoniflorin attenuates myocardial fibrosis in isoprenaline-induced chronic heart failure rats via inhibiting P38 MAPK pathway. Curr Med Sci. 2020; 40(2):307-312. https://doi.org/10.1007/s11596-020-2178-0.

[84]

Saxton RA, Sabatini DM. MTOR signaling in growth, metabolism, and disease. Cell. 2017; 168(6):960-976. https://doi.org/10.1016/j.cell.2017.02.004.

[85]

Schalm SS, Fingar DC, Sabatini DM, et al. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr Biol. 2003; 13(10):797-806. https://doi.org/10.1016/s0960-9822(03)00329-4.

[86]

Fu W, Hall MN. Regulation of mTORC2 signaling. Genes(Basel). 2020; 11(9):1045. https://doi.org/10.3390/genes11091045.

[87]

Guertin DA, et al. Ablation in mice of the mTORC components raptor, rictor, or mLST 8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell. 2006; 11(6):859-871. https://doi.org/10.1016/j.devcel.2006.10.007.

[88]

Laplante M, Sabatini DM.MTOR signaling at a glance. J Cell Sci. 2009; 122(Pt 20):3589-3594. https://doi.org/10.1242/jcs.051011.

[89]

Yang G, Murashige DS, Humphrey SJ, et al. A positive feedback loop between Akt and mTORC2 via SIN1 phosphorylation. Cell Rep. 2015; 12(6):937-943. https://doi.org/10.1016/j.celrep.2015.07.016.

[90]

Perrotta C, Cattaneo MG, Molteni R, et al. Autophagy in the regulation of tissue differentiation and homeostasis. Front Cell Dev Biol. 2020; 8:602901. https://doi.org/10.3389/fcell.2020.602901.

[91]

Kim J, Kundu M, Viollet B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011; 13(2):132-141. https://doi.org/10.1038/ncb2152.

[92]

Wang XC, Li LX, Niu XL, et al. MTOR enhances foam cell formation by suppressing the autophagy pathway. DNA Cell Biol. 2014; 33(4):198-204. https://doi.org/10.1089/dna.2013.2164.

[93]

Martina JA, Chen Y, Gucek M, et al. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy. 2012; 8(6):903-914. https://doi.org/10.4161/auto.19653.

[94]

Araki K, Turner AP, Shaffer VO, et al. MTOR regulates memory CD 8 T-cell differentiation. Nature. 2009; 460(7251):108-112. https://doi.org/10.1038/nature08155.

[95]

Kaldirim M, Lang A, Pfeiler S, et al. Modulation of mTOR signaling in cardiovascular disease to target acute and chronic inflammation. Front Cardiovasc Med. 2022; 9:907348. https://doi.org/10.3389/fcvm.2022.907348.

[96]

Xu ZH, Xu JB, Qian WW, et al. Repair effect and mechanism of Taohong Siwu Decoction on rotator cuff injury in rabbits. China Pharmacy. 2021; 32(24):2975-2979. https://doi.org/10.6039/j.issn.1001-0408.2021.24.06.

[97]

Cao H, Jia QL, Shen DZ, et al. Quercetin has a protective effect on atherosclerosis via enhancement of autophagy in ApoE-/- mice. Exp Ther Med. 2019; 18(4):2451-2458. https://doi.org/10.3892/etm.2019.7851.

[98]

Wu HF, Song AW, Hu WJ, et al. The anti-atherosclerotic effect of paeonol against vascular smooth muscle cell proliferation by up-regulation of autophagy via the AMPK/mTOR signaling pathway. Front Pharmacol. 2017; 8:948. https://doi.org/10.3389/fphar.2017.00948.

[99]

Marinou K, Christodoulides C, Antoniades C, et al.Wnt signaling in cardiovascular physiology. Trends Endocrinol Metab. 2012; 23(12):628-636. https://doi.org/10.1016/j.tem.2012.06.001.

[100]

Catalano A, Bellone F, Morabito N, et al. Sclerostin and vascular pathophysiology. Int J Mol Sci. 2020; 21(13):4779. https://doi.org/10.3390/ijms21134779.

[101]

Kong P, Cui ZY, Huang XF, et al. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Signal Transduct Target Ther. 2022; 7(1):131. https://doi.org/10.1038/s41392-022-00955-7.

[102]

Sharma BR, Kanneganti TD. NLRP3 inflammasome in cancer and metabolic diseases. Nat Immunol. 2021; 22(5):550-559. https://doi.org/10.1038/s41590-021-00886-5.

[103]

Loirand G, Guérin P, Pacaud P. Rho kinases in cardiovascular physiology and pathophysiology. Circ Res. 2006; 98(3):322-334. https://doi.org/10.1161/01.RES.0000201960.04223.3c.

[104]

Kloc M, Uosef A, Kubiak JZ, et al. Role of macrophages and RhoA pathway in atherosclerosis. Int J Mol Sci. 2020; 22(1):216. https://doi.org/10.3390/ijms22010216.

[105]

Baldini C, Moriconi FR, Galimberti S, et al. The JAK-STAT pathway: an emerging target for cardiovascular disease in rheumatoid arthritis and myeloproliferative neoplasms. Eur Heart J. 2021; 42(42):4389-4400. https://doi.org/10.1093/eurheartj/ehab447.

[106]

Sega FVD, Fortini F, Aquila G, et al. Notch signaling regulates immune responses in atherosclerosis. Front Immunol. 2019; 10:1130. https://doi.org/10.3389/fimmu.2019.01130.

[107]

Martos-Rodríguez CJ, Albarrán-Juárez J, Morales-Cano D, et al. Fibrous caps in atherosclerosis form by Notch-dependent mechanisms common to arterial media development. Arterioscler Thromb Vasc Biol. 2021; 41(9):e427-e439. https://doi.org/10.1161/atvbaha.120.315627.

[108]

Dabravolski SA, Khotina VA, Omelchenko AV, et al. The role of the VEGF family in atherosclerosis development and its potential as treatment targets. Int J Mol Sci. 2022; 23(2):931. https://doi.org/10.3390/ijms23020931.

[109]

Li RJ, Dai YY, Qin C, et al. Application of traditional Chinese medicine in treatment of Helicobacter pylori infection. World J Clin Cases. 2021; 9(35):10781-10791. https://doi.org/10.12998/wjcc.v9.i35.10781.

[110]

Kim J, Kim J, Kim DW, et al. Wnt5a induces endothelial inflammation via β-catenin-independent signaling. J Immunol. 2010; 185(2):1274-1282. https://doi.org/10.4049/jimmunol.1000181.

[111]

Bikkavilli RK, Feigin ME, Malbon CC. P38 mitogen-activated protein kinase regulates canonical Wnt-beta-catenin signaling by inactivation of GSK3beta. J Cell Sci. 2008; 121(Pt 21):3598-3607. https://doi.org/10.1242/jcs.032854.

[112]

Gurung P, Malireddi RKS, Anand PK, et al. Toll or interleukin-1 receptor (TIR) domain-containing adaptor inducing interferon-β (TRIF)-mediated caspase-11 protease production integrates Toll-like receptor 4 (TLR4) protein- and Nlrp3 inflammasome-mediated host defense against enteropathogens. J Biol Chem. 2012; 287(41):34474-34483. https://doi.org/10.1074/jbc.M112.401406.

[113]

Wolfrum S, Dendorfer A, Rikitake Y, et al. Inhibition of Rho-kinase leads to rapid activation of phosphatidylinositol 3-kinase/protein kinase Akt and cardiovascular protection. Arterioscler Thromb Vasc Biol. 2004; 24(10):1842-1847. https://doi.org/10.1161/01.Atv.0000142813.33538.82.

[114]

Hu X, Li J, Fu M, et al. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021; 6(1):402. https://doi.org/10.1038/s41392-021-00791-1.

[115]

Hildebrand D, Uhle F, Sahin D, et al. The interplay of Notch signaling and STAT3 in TLR-activated human primary monocytes. Front Cell Infect Microbiol. 2018; 8:241. https://doi.org/10.3389/fcimb.2018.00241.

[116]

Luo GA, Wang YM, Fan XM, et al. Research strategy and practice from clinical reality, targeting at signaling pathways for the innovative compound drug——the sixth discussion on the proposal of holistic systems medicine. WST-MTCM. 2018; 20(7):1047-1068. https://doi.org/10.11842/wst.2018.07.001.

[117]

Luo GA, Liang QL, Liu QF, et al. Chemomics-integrated global systems biology: a holistic methodology of study on compatibility and mechanism of formulas in traditional Chinese medicine. World Sci Technol-Mod Tradit Chin Med. 2007; 1:10-15, 24. https://doi.org/10.3969/j.issn.1674-3849.2007.01.005.

[118]

Luo CY, Luo PZ, Wang GB, et al.Characteristics and advantages of traditional Chinese medicine based on complexity science. Chin J Basic Med Tradit Chin Med. 2018; 24(10):1368-1372. https://doi.org/10.19945/j.cnki.issn.1006-3250.2018.10.012.

PDF (3415KB)

4

Accesses

0

Citation

Detail

Sections
Recommended

/