The Role of Natural Compounds for Atherosclerosis Treatment: Lessons Learned from The Use of Curcumin

Anastasia V. Poznyak ^1*, Victoria A. Khotina ², Roghayyeh Vakili-Ghartavol ³, Alexander L Golovyuk ⁴, Dmitriy Yu Serdyukov ⁵, Victor Y Glanz ², Vasily N. Sukhorukov ², Alexander N. Orekhov ^2*

Curcumin has various pharmacological effects on atherosclerosis. This review discussed the promising therapeutic potential, of curcumin as anti-inflammatory, lipid regulation, and endothelial function for cardiovascular disease.

Abstract

Relationships between the occurrence of various diseases that have certain similarities are of particular interest to scientists and clinicians. On the one hand, such an analysis can help to better understand the underlying mechanisms and, on the other hand, to cope with the disease/diseases more effectively. In this review, we look at the relationship between NAFLD and atherosclerosis. The main and obvious intersection in their pathogenesis is, of course, lipid metabolism disorders. However, this is not the only relationship. In addition to the similarity of pathogenesis, we considered the possibility of one disease to serve as a risk factor for the development of the second. We devoted a separate chapter to the methods of treatment of these two pathologies.

Keywords: Curcumin; Natural compound; Phytotherapy; Atherosclerosis; Cardiovascular disease.

References

Alidadi, M., Liberale, L., Montecucco, F., Majeed, M., Al-Rasadi, K., Banach, M., Jamialahmadi, T., & Sahebkar, A. (2021). Protective Effects of Curcumin on Endothelium: An Updated Review. Advances in experimental medicine and biology, 1291, 103–119. https://doi.org/10.1007/978-3-030-56153-6_6

Alidadi, M., Sahebkar, A., Eslami, S., Vakilian, F., Jarahi, L., Alinezhad-Namaghi, M., Arabi, S. M., Vakili, S., Tohidinezhad, F., Nikooiyan, Y., & Norouzy, A. (2021). The Effect of Curcumin Supplementation on Pulse Wave Velocity in Patients with Metabolic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Advances in experimental medicine and biology, 1308, 1–11. https://doi.org/10.1007/978-3-030-64872-5_1

Amalraj, A., Pius, A., Gopi, S., & Gopi, S. (2016). Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives - A review. Journal of traditional and complementary medicine, 7(2), 205–233. https://doi.org/10.1016/j.jtcme.2016.05.005

Baratzadeh, F., Butler, A. E., Kesharwani, P., Moallem, S. A., & Sahebkar, A. (2022). Effects of curcumin on low-density lipoprotein oxidation: From experimental studies to clinical practice. EXCLI journal, 21, 840–851. https://doi.org/10.17179/excli2022-4878

Benameur, T., Frota Gaban, S. V., Giacomucci, G., Filannino, F. M., Trotta, T., Polito, R., Messina, G., Porro, C., & Panaro, M. A. (2023). The Effects of Curcumin on Inflammasome: Latest Update. Molecules (Basel, Switzerland), 28(2), 742. https://doi.org/10.3390/molecules28020742

Bielak-Zmijewska, A., Grabowska, W., Ciolko, A., Bojko, A., Mosieniak, G., Bijoch, L., & Sikora, E. (2019). The Role of Curcumin in the Modulation of Ageing. International journal of molecular sciences, 20(5), 1239. https://doi.org/10.3390/ijms20051239

Burge, K., Gunasekaran, A., Eckert, J., & Chaaban, H. (2019). Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms of Protection. International journal of molecular sciences, 20(8), 1912. https://doi.org/10.3390/ijms20081912

Cao, J., Ye, B., Lin, L., Tian, L., Yang, H., Wang, C., Huang, W., & Huang, Z. (2017). Curcumin Alleviates oxLDL Induced MMP-9 and EMMPRIN Expression through the Inhibition of NF-κB and MAPK Pathways in Macrophages. Frontiers in pharmacology, 8, 62. https://doi.org/10.3389/fphar.2017.00062

Chauhan, W., & Zennadi, R. (2023). Keap1-Nrf2 Heterodimer: A Therapeutic Target to Ameliorate Sickle Cell Disease. Antioxidants (Basel, Switzerland), 12(3), 740. https://doi.org/10.3390/antiox12030740

Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2017). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204–7218. https://doi.org/10.18632/oncotarget.23208

Chen, X., Zou, D., Chen, X., Wu, H., & Xu, D. (2021). Hesperetin inhibits foam cell formation and promotes cholesterol efflux in THP-1-derived macrophages by activating LXRα signal in an AMPK-dependent manner. Journal of physiology and biochemistry, 77(3), 405–417. https://doi.org/10.1007/s13105-020-00783-9

El Hadri, K., Smith, R., Duplus, E., & El Amri, C. (2021). Inflammation, Oxidative Stress, Senescence in Atherosclerosis: Thioredoxine-1 as an Emerging Therapeutic Target. International journal of molecular sciences, 23(1), 77. https://doi.org/10.3390/ijms23010077

Feng, D., Zou, J., Su, D., Mai, H., Zhang, S., Li, P., & Zheng, X. (2019). Curcumin prevents high-fat diet-induced hepatic steatosis in ApoE-/- mice by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation. Nutrition & metabolism, 16, 79. https://doi.org/10.1186/s12986-019-0410-3

Fessler, S. N., Chang, Y., Liu, L., & Johnston, C. S. (2023). Curcumin Confers Anti-Inflammatory Effects in Adults Who Recovered from COVID-19 and Were Subsequently Vaccinated: A Randomized Controlled Trial. Nutrients, 15(7), 1548. https://doi.org/10.3390/nu15071548

Gupta, S. C., Patchva, S., & Aggarwal, B. B. (2013). Therapeutic roles of curcumin: lessons learned from clinical trials. The AAPS journal, 15(1), 195–218. https://doi.org/10.1208/s12248-012-9432-8

Handono, K., Pratama, M. Z., Endharti, A. T., & Kalim, H. (2015). Treatment of low doses curcumin could modulate Th17/Treg balance specifically on CD4+ T cell cultures of systemic lupus erythematosus patients. Central-European journal of immunology, 40(4), 461–469. https://doi.org/10.5114/ceji.2015.56970

Hasan, S. T., Zingg, J. M., Kwan, P., Noble, T., Smith, D., & Meydani, M. (2014). Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice. Atherosclerosis, 232(1), 40–51. https://doi.org/10.1016/j.atherosclerosis.2013.10.016

Hassaniazad, M., Eftekhar, E., Inchehsablagh, B. R., Kamali, H., Tousi, A., Jaafari, M. R., Rafat, M., Fathalipour, M., Nikoofal-Sahlabadi, S., Gouklani, H., Alizade, H., & Nikpoor, A. R. (2021). A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients. Phytotherapy research : PTR, 35(11), 6417–6427. https://doi.org/10.1002/ptr.7294

He, Y., Wang, R., Zhang, P., Yan, J., Gong, N., Li, Y., & Dong, S. (2021). Curcumin inhibits the proliferation and migration of vascular smooth muscle cells by targeting the chemerin / CMKLR1 / LCN2 axis. Aging, 13(10), 13859–13875. https://doi.org/10.18632/aging.202980

Hewlings, S. J., & Kalman, D. S. (2017). Curcumin: A Review of Its Effects on Human Health. Foods (Basel, Switzerland), 6(10), 92. https://doi.org/10.3390/foods6100092

Huang, Y., Xu, W., & Zhou, R. (2021). NLRP3 inflammasome activation and cell death. Cellular & molecular immunology, 18(9), 2114–2127. https://doi.org/10.1038/s41423-021-00740-6

Kunnumakkara, A. B., Bordoloi, D., Padmavathi, G., Monisha, J., Roy, N. K., Prasad, S., & Aggarwal, B. B. (2017). Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. British journal of pharmacology, 174(11), 1325–1348. https://doi.org/10.1111/bph.13621

Leopold, J. A., & Loscalzo, J. (2018). Emerging Role of Precision Medicine in Cardiovascular Disease. Circulation research, 122(9), 1302–1315. https://doi.org/10.1161/CIRCRESAHA.117.310782

Lewinska, A., Wnuk, M., Grabowska, W., Zabek, T., Semik, E., Sikora, E., & Bielak-Zmijewska, A. (2015). Curcumin induces oxidation-dependent cell cycle arrest mediated by SIRT7 inhibition of rDNA transcription in human aortic smooth muscle cells. Toxicology letters, 233(3), 227–238. https://doi.org/10.1016/j.toxlet.2015.01.019

Li, X., Chen, Q., Chu, C., You, H., Jin, M., Zhao, X., Zhu, X., Zhou, W., & Ji, W. (2014). Ovalbumin-induced experimental allergic asthma is Toll-like receptor 2 dependent. Allergy and asthma proceedings, 35(2), e15–e20. https://doi.org/10.2500/aap.2014.35.3735

Lin, X. L., Liu, M. H., Hu, H. J., Feng, H. R., Fan, X. J., Zou, W. W., Pan, Y. Q., Hu, X. M., & Wang, Z. (2015). Curcumin enhanced cholesterol efflux by upregulating ABCA1 expression through AMPK-SIRT1-LXRα signaling in THP-1 macrophage-derived foam cells. DNA and cell biology, 34(9), 561–572. https://doi.org/10.1089/dna.2015.2866

Lu, L., Sun, X., Qin, Y., & Guo, X. (2018). The Signaling Pathways Involved in the Antiatherosclerotic Effects Produced by Chinese Herbal Medicines. BioMed research international, 2018, 5392375. https://doi.org/10.1155/2018/5392375

Ma, F., Liu, F., Ding, L., You, M., Yue, H., Zhou, Y., & Hou, Y. (2017). Anti-inflammatory effects of curcumin are associated with down regulating microRNA-155 in LPS-treated macrophages and mice. Pharmaceutical biology, 55(1), 1263–1273. https://doi.org/10.1080/13880209.2017.1297838

Makuch, S., Wiecek, K., & Wozniak, M. (2021). The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis. Pharmaceuticals (Basel, Switzerland), 14(4), 309. https://doi.org/10.3390/ph14040309

Mazidi, M., Karimi, E., Meydani, M., Ghayour-Mobarhan, M., & Ferns, G. A. (2016). Potential effects of curcumin on peroxisome proliferator-activated receptor-γ in vitro and in vivo. World journal of methodology, 6(1), 112–117. https://doi.org/10.5662/wjm.v6.i1.112

Meng, N., Gong, Y., Zhang, J., Mu, X., Song, Z., Feng, R., & Zhang, H. (2019). A novel curcumin-loaded nanoparticle restricts atherosclerosis development and promotes plaques stability in apolipoprotein E deficient mice. Journal of biomaterials applications, 33(7), 946–954. https://doi.org/10.1177/0885328218815328

Prasad, S., Tyagi, A. K., & Aggarwal, B. B. (2014). Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer research and treatment, 46(1), 2–18. https://doi.org/10.4143/crt.2014.46.1.2

Preusch, M. R., Vanakaris, A., Bea, F., Ieronimakis, N., Shimizu, T., Konstandin, M., Morris-Rosenfeld, S., Albrecht, C., Kranzhöfer, A., Katus, H. A., Blessing, E., & Kranzhöfer, R. (2010). Rosuvastatin reduces neointima formation in a rat model of balloon injury. European journal of medical research, 15(11), 461–467. https://doi.org/10.1186/2047-783x-15-11-461

Qin, S., Huang, L., Gong, J., Shen, S., Huang, J., Ren, H., & Hu, H. (2017). Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in patients with cardiovascular risk factors: a meta-analysis of randomized controlled trials. Nutrition journal, 16(1), 68. https://doi.org/10.1186/s12937-017-0293-y

Rózanski, G., Tabisz, H., Zalewska, M., Niemiro, W., Kujawski, S., Newton, J., Zalewski, P., & Slomko, J. (2023). Meta-Analysis of Exploring the Effect of Curcumin Supplementation with or without Other Advice on Biochemical and Anthropometric Parameters in Patients with Metabolic-Associated Fatty Liver Disease (MAFLD). International journal of environmental research and public health, 20(5), 4266. https://doi.org/10.3390/ijerph20054266

Sharifi-Rad, J., Rayess, Y. E., Rizk, A. A., Sadaka, C., Zgheib, R., Zam, W., Sestito, S., Rapposelli, S., Neffe-Skocinska, K., Zielinska, D., Salehi, B., Setzer, W. N., Dosoky, N. S., Taheri, Y., El Beyrouthy, M., Martorell, M., Ostrander, E. A., Suleria, H. A. R., Cho, W. C., Maroyi, A., … Martins, N. (2020). Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications. Frontiers in pharmacology, 11, 01021. https://doi.org/10.3389/fphar.2020.01021

Simental-Mendía, L. E., Pirro, M., Gotto, A. M., Jr, Banach, M., Atkin, S. L., Majeed, M., & Sahebkar, A. (2019). Lipid-modifying activity of curcuminoids: A systematic review and meta-analysis of randomized controlled trials. Critical reviews in food science and nutrition, 59(7), 1178–1187. https://doi.org/10.1080/10408398.2017.1396201

Smirnova, E., Moniruzzaman, M., Chin, S., Sureshbabu, A., Karthikeyan, A., Do, K., & Min, T. (2023). A Review of the Role of Curcumin in Metal Induced Toxicity. Antioxidants (Basel, Switzerland), 12(2), 243. https://doi.org/10.3390/antiox12020243

Sohn, S. I., Priya, A., Balasubramaniam, B., Muthuramalingam, P., Sivasankar, C., Selvaraj, A., Valliammai, A., Jothi, R., & Pandian, S. (2021). Biomedical Applications and Bioavailability of Curcumin-An Updated Overview. Pharmaceutics, 13(12), 2102. https://doi.org/10.3390/pharmaceutics13122102

Surma, S., Sahebkar, A., Urbanski, J., Penson, P. E., & Banach, M. (2022). Curcumin - The Nutraceutical With Pleiotropic Effects? Which Cardiometabolic Subjects Might Benefit the Most?. Frontiers in nutrition, 9, 865497. https://doi.org/10.3389/fnut.2022.865497

Tabanelli, R., Brogi, S., & Calderone, V. (2021). Improving Curcumin Bioavailability: Current Strategies and Future Perspectives. Pharmaceutics, 13(10), 1715. https://doi.org/10.3390/pharmaceutics13101715

Wongcharoen, W., Jai-Aue, S., Phrommintikul, A., Nawarawong, W., Woragidpoonpol, S., Tepsuwan, T., Sukonthasarn, A., Apaijai, N., & Chattipakorn, N. (2012). Effects of curcuminoids on frequency of acute myocardial infarction after coronary artery bypass grafting. The American journal of cardiology, 110(1), 40–44. https://doi.org/10.1016/j.amjcard.2012.02.043

Yu, Y. M., & Lin, H. C. (2010). Curcumin prevents human aortic smooth muscle cells migration by inhibiting of MMP-9 expression. Nutrition, metabolism, and cardiovascular diseases : NMCD, 20(2), 125–132. https://doi.org/10.1016/j.numecd.2009.03.001

Zeng, L., Yang, T., Yang, K., Yu, G., Li, J., Xiang, W., & Chen, H. (2022). Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial. Frontiers in immunology, 13, 891822. https://doi.org/10.3389/fimmu.2022.891822

Zhang, F., Yu, W., Hargrove, J. L., Greenspan, P., Dean, R. G., Taylor, E. W., & Hartle, D. K. (2002). Inhibition of TNF-alpha induced ICAM-1, VCAM-1 and E-selectin expression by selenium. Atherosclerosis, 161(2), 381–386. https://doi.org/10.1016/s0021-9150(01)00672-4

Zhao, Y., Chen, B., Shen, J., Wan, L., Zhu, Y., Yi, T., & Xiao, Z. (2017). The Beneficial Effects of Quercetin, Curcumin, and Resveratrol in Obesity. Oxidative medicine and cellular longevity, 2017, 1459497. https://doi.org/10.1155/2017/1459497

Zhu, Y., Li, Q., & Jiang, H. (2020). Gut microbiota in atherosclerosis: focus on trimethylamine N-oxide. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, 128(5), 353–366. https://doi.org/10.1111/apm.13038

Ziólkiewicz, A., Kasprzak-Drozd, K., Rusinek, R., Markut-Miotla, E., & Oniszczuk, A. (2023). The Influence of Polyphenols on Atherosclerosis Development. International journal of molecular sciences, 24(8), 7146. https://doi.org/10.3390/ijms24087146