Cyanidin and Human Health: Mechanisms and Applications
Özet
Cyanidin, a naturally occurring anthocyanidin, exhibits broad therapeutic potential through its antioxidant, anti-inflammatory, and signaling-modulatory properties. Its structure allows interaction with key pathways, including NF-κB, MAPK, Nrf2, and CREB/BDNF, supporting systemic benefits across metabolic, cardiovascular, neurological, gastrointestinal, ocular, and oncological systems. In metabolism, cyanidin enhances insulin sensitivity, glucose uptake, lipid balance, thermogenesis, and adipose tissue browning, while reducing pro-inflammatory cytokines, thereby improving body weight, glycemic control, and fat distribution. Cardiovascular effects include vasodilation, ACE inhibition, platelet modulation, and atherosclerosis prevention, whereas neuroprotective actions mitigate oxidative stress and neuroinflammation, enhancing learning and memory. Cyanidin maintains gut barrier integrity, modulates microbiota, and produces bioactive metabolites such as protocatechuic acid, contributing to systemic antioxidant and anti-inflammatory effects. Its anticancer potential spans multiple tumor types, regulating cell cycle progression, apoptosis, angiogenesis, and metastasis, with glycosylated derivatives demonstrating synergistic effects with chemotherapeutics and modulation of key oncogenic pathways. Preclinical and dietary studies indicate a favorable safety profile, although limited bioavailability remains a challenge, prompting research into advanced delivery strategies. Overall, cyanidin represents a multifunctional natural compound with promising applications in disease prevention and therapy, warranting further clinical investigation to optimize its efficacy and translational potential.
Referanslar
Tena, N., Martín, J., & Asuero, A. G. State of the art of anthocyanins: Antioxidant activity, sources, bioavailability, and therapeutic effect in human health. Antioxidants. 2020; 9(5), 451.
Ye, X., Chen, W., Yan, F., Zheng, X., & Tu, P. Cyanidin-3-O-glucoside enhances GLP-1 secretion via PPARβ/δ-β-catenin-TCF-4 pathway in type 2 diabetes mellitus. npj Science of Food. 2025; 9(1), 81.
Maslov, D. L., Ipatova, O. M., Tsvetkova, T. A., & Prozorovskiĭ, V. N. Hypoglycemic effect of an extract from Aronia melanocarpa leaves. Voprosy meditsinskoi khimii. 2002; 48(3), 271-277.
Pilaczynska-Szczesniak, L., Skarpanska-Steinborn, A., Deskur, E., Basta, P., & Horoszkiewicz-Hassan, M. The influence of chokeberry juice supplementation on the reduction of oxidative stress resulting from an incremental rowing ergometer exercise. International journal of sport nutrition and exercise metabolism. 2005; 15(1), 48-58.
Broncel1ABDEFG, M., Koziróg1ABDEF, M., Duchnowicz2ABD, P., Koter-Michalak2ABD, M., Sikora3ACD, J., & Chojnowska-Jezierska1ABG, J. Aronia melanocarpa extract reduces blood pressure, serum endothelin, lipid, and oxidative stress marker levels in patients with metabolic syndrome. Med Sci Monit. 2010; 16(1), 34.
Qin, B., & Anderson, R. A. An extract of chokeberry attenuates weight gain and modulates insulin, adipogenic and inflammatory signalling pathways in epididymal adipose tissue of rats fed a fructose-rich diet. British Journal of Nutrition. 2012; 108(4), 581-587.
Shi, M., O'Keefe, L., Simcocks, A. C., Su, X. Q., & McAinch, A. J. The effect of cyanidin-3-O-β-glucoside and peptides extracted from yoghurt on glucose uptake and gene expression in human primary skeletal muscle myotubes from obese and obese diabetic participants. Journal of Functional Foods. 2018; 51, 55-64.
Shi, M., Mathai, M. L., Xu, G., McAinch, A. J., & Su, X. Q. The effects of supplementation with blueberry, cyanidin-3-O-β-glucoside, yoghurt and its peptides on obesity and related comorbidities in a diet-induced obese mouse model. Journal of functional foods. 2019; 56, 92-101.
Daveri, E., Cremonini, E., Mastaloudis, A., Hester, S. N., Wood, S. M., Waterhouse, A. L., & Oteiza, P. I. Cyanidin and delphinidin modulate inflammation and altered redox signaling improving insulin resistance in high fat-fed mice. Redox biology. 2018; 18, 16-24.
Tian, L., Ning, H., Shao, W., Song, Z., Badakhshi, Y., Ling, W., & Jin, T. Dietary cyanidin-3-glucoside attenuates high-fat-diet–induced body-weight gain and impairment of glucose tolerance in mice via effects on the hepatic hormone FGF21. The Journal of nutrition. 2020; 150(8), 2101-2111.
Zhao, R., Xiang, B., Dolinsky, V. W., Xia, M., & Shen, G. X. Saskatoon berry powder reduces hepatic steatosis and insulin resistance in high fat-high sucrose diet-induced obese mice. The Journal of Nutritional Biochemistry. 2021; 95, 108778.
Tsuda, T., Ueno, Y., Yoshikawa, T., Kojo, H., & Osawa, T. Microarray profiling of gene expression in human adipocytes in response to anthocyanins. Biochemical pharmacology. 2006; 71(8), 1184-1197.
Scazzocchio, B., Varì, R., Filesi, C., D’Archivio, M., Santangelo, C., Giovannini, C., & Masella, R. Cyanidin-3-O-β-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPARγ activity in human omental adipocytes. Diabetes. 2011; 60(9), 2234-2244.
Tsuda, T., Horio, F., Uchida, K., Aoki, H., & Osawa, T. Dietary cyanidin 3-O-β-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. The Journal of nutrition. 2003; 133(7), 2125-2130.
Lim, S. M., Lee, H. S., Jung, J. I., Kim, S. M., Kim, N. Y., Seo, T. S., & Kim, E. J. Cyanidin-3-O-galactoside-enriched Aronia melanocarpa extract attenuates weight gain and adipogenic pathways in high-fat diet-induced obese C57BL/6 mice. Nutrients. 2019; 11(5), 1190.
Han, S., Yang, Y., Lu, Y., Guo, J., Han, X., Gao, Y., & Zhan, J. Cyanidin-3-O-glucoside regulates the expression of Ucp1 in brown adipose tissue by activating Prdm16 gene. Antioxidants. 2021; 10(12), 1986.
You, Y., Yuan, X., Liu, X., Liang, C., Meng, M., Huang, Y., & Zhan, J. Cyanidin‐3‐glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function. Molecular Nutrition & Food Research. 2017; 61(11), 1700261.
You, Y., Han, X., Guo, J., Guo, Y., Yin, M., Liu, G., & Zhan, J. Cyanidin-3-glucoside attenuates high-fat and high-fructose diet-induced obesity by promoting the thermogenic capacity of brown adipose tissue. Journal of Functional Foods. 2018; 41, 62-71.
Tomay, F., Marinelli, A., Leoni, V., Caccia, C., Matros, A., Mock, H. P., & Petroni, K. Purple corn extract induces long-lasting reprogramming and M2 phenotypic switch of adipose tissue macrophages in obese mice. Journal of Translational Medicine. 2019; 17(1), 237.
Jia, Y., Wu, C., Kim, Y. S., Yang, S. O., Kim, Y., Kim, J. S., & Lee, S. J. A dietary anthocyanin cyanidin-3-O-glucoside binds to PPARs to regulate glucose metabolism and insulin sensitivity in mice. Communications Biology. 2020; 3(1), 514.
Guo, H., Liu, G., Zhong, R., Wang, Y., Wang, D., & Xia, M. Cyanidin-3-O-β-glucoside regulates fatty acid metabolism via an AMP-activated protein kinase-dependent signaling pathway in human HepG2 cells. Lipids in health and disease. 2012; 11(1), 10.
Yu, R. Q., Wu, X. Y., Zhou, X., & Zhu, J. Cyanidin-3-glucoside attenuates body weight gain, serum lipid concentrations and insulin resistance in high-fat diet-induced obese rats. Zhongguo dangdai erke zazhi. 2014; 534-538.
Biswas, D., Sarkar, S., De Silva, A. B. K. H., D'Souza, K., Kienesberger, P., Rupasinghe, H. V., & Pulinilkunnil, T. Cyanidin-3-O-glucoside rich extract from haskap berry improves glucose homeostasis and insulin sensitivity in diet-induced obese mice. Canadian Journal of Diabetes. 2018; 42(5), S55.
Pei, L., Wan, T., Wang, S., Ye, M., Qiu, Y., Jiang, R., & Yang, L. Cyanidin-3-O-β-glucoside regulates the activation and the secretion of adipokines from brown adipose tissue and alleviates diet induced fatty liver. Biomedicine & Pharmacotherapy. 2018; 105, 625-632.
Sikora, J., Broncel, M., & Mikiciuk-Olasik, E. Aronia melanocarpa Elliot reduces the activity of angiotensin i‐converting enzyme—in vitro and ex vivo studies. Oxidative Medicine and Cellular Longevity. 2014; 2014 (1), 739721.
Poreba, R., Skoczynska, A., Gac, P., Poreba, M., Jedrychowska, I., Affelska-Jercha, A., & Andrzejak, R. Drinking of chokeberry juice from the ecological farm Dzieciolowo and distensibility of brachial artery in men with mild hypercholesterolemia. Annals of Agricultural and Environmental Medicine. 2009; 16(2), 305-308.
Tan, J., Li, Y., Hou, D. X., & Wu, S. The effects and mechanisms of cyanidin-3-glucoside and its phenolic metabolites in maintaining intestinal integrity. Antioxidants. 2019; 8(10), 479.
Zhu, Y., Sun, H., He, S., Lou, Q., Yu, M., Tang, M., & Tu, L. Metabolism and prebiotics activity of anthocyanins from black rice (Oryza sativa L.) in vitro. Plos one. 2018; 13(4), e0195754.
Min, S. W., Ryu, S. N., & Kim, D. H. Anti-inflammatory effects of black rice, cyanidin-3-O-β-D-glycoside, and its metabolites, cyanidin and protocatechuic acid. International immunopharmacology. 2010; 10(8), 959-966.
Deepa, P., Hong, M., Sowndhararajan, K., & Kim, S. A Review of the Role of an Anthocyanin, Cyanidin-3-O-β-glucoside in Obesity-Related Complications. Plants. 2023; 12(22), 3889.
Rahman, S., Mathew, S., Nair, P., Ramadan, W. S., & Vazhappilly, C. G. Health benefits of cyanidin-3-glucoside as a potent modulator of Nrf2-mediated oxidative stress. Inflammopharmacology. 2021; 29(4), 907-923.
Tang, Z. Cyanidin-3-glucoside: Targeting Atherosclerosis through Gut Microbiota and Anti-Inflammation. Frontiers in Nutrition. 2025; 12, 1627868.
Jiao, X., Shen, Y., Deng, H., Zhang, Q., & Zhao, J. Cyanidin-3-O-galactoside from Aronia melanocarpa attenuates high-fat diet-induced obesity and inflammation via AMPK, STAT3, and NF-κB p65 signaling pathways in Sprague-Dawley rats. Journal of functional foods. 2021; 85, 104616.
Yang HongPeng, Y. H., Jiang YuGang, J. Y., Pang Wei, P. W., Chen DaoMei, C. D., Lu Hao, L. H., & Lu ShiJun, L. S. Study on the effect of anthocyanin from blueberry on improving learning and memory in aged mice. 2009
Yang, H., Pang, W., Lu, H., Cheng, D., Yan, X., Cheng, Y., & Jiang, Y. Comparison of metabolic profiling of cyanidin-3-O-galactoside and extracts from blueberry in aged mice. Journal of agricultural and food chemistry. 2011; 59(5), 2069-2076.
Lee, H. Y., Weon, J. B., Jung, Y. S., Kim, N. Y., Kim, M. K., & Ma, C. J. Cognitive‐Enhancing Effect of Aronia melanocarpa Extract against Memory Impairment Induced by Scopolamine in Mice. Evidence‐Based Complementary and Alternative Medicine. 2016; 2016(1), 6145926.
Skemiene, K., Pampuscenko, K., Rekuviene, E., & Borutaite, V. (2020). Protective effects of anthocyanins against brain ischemic damage. Journal of Bioenergetics and Biomembranes, 52(2), 71-82.
Wen, H., Cui, H., Tian, H., Zhang, X., Ma, L., Ramassamy, C., & Li, J. Isolation of neuroprotective anthocyanins from black chokeberry (Aronia melanocarpa) against amyloid-β-induced cognitive impairment. Foods. 2020; 10(1), 63.
Shim, S. H., Kim, J. M., Choi, C. Y., Kim, C. Y., & Park, K. H. Ginkgo biloba extract and bilberry anthocyanins improve visual function in patients with normal tension glaucoma. Journal of medicinal food. 2012; 15(9), 818-823.
Miyake, S., Takahashi, N., Sasaki, M., Kobayashi, S., Tsubota, K., & Ozawa, Y. Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract: cellular and molecular mechanism. Laboratory investigation. 2012; (1), 102-109.
Safdar, M. A., Aslam, R. M. N., Shakeel, A., Shiza, Waqar, M., Jmail, A., & Gul, H. (2023). Cyanidin as potential anticancer agent targeting various proliferative pathways. Chemical Biology & Drug Design, 101(2), 438-452.
Wallace, T. C., & Giusti, M. M. (Eds.) Anthocyanins in health and disease. CRC Press, Taylor & Francis. 2014.
Chen, P. N., Kuo, W. H., Chiang, C. L., Chiou, H. L., Hsieh, Y. S., & Chu, S. C. Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression. Chemico-biological interactions. 2006; 163(3), 218-229.
Lala, G., Malik, M., Zhao, C., He, J., Kwon, Y., Giusti, M. M., & Magnuson, B. A. Anthocyanin-rich extracts inhibit multiple biomarkers of colon cancer in rats. Nutrition and cancer. 2006; 54(1), 84-93.
Ding, M., Feng, R., Wang, S. Y., Bowman, L., Lu, Y., Qian, Y., & Shi, X. Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. Journal of Biological Chemistry. 2006; 281(25), 17359-17368.
Wu, C. F., Wu, C. Y., Lin, C. F., Liu, Y. W., Lin, T. C., Liao, H. J., & Chang, G. R. The anticancer effects of cyanidin 3-O-glucoside combined with 5-fluorouracil on lung large-cell carcinoma in nude mice. Biomedicine & Pharmacotherapy. 2022; 151, 113128.
Pratheeshkumar, P., Son, Y. O., Wang, X., Divya, S. P., Joseph, B., Hitron, J. A., & Shi, X. Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin. Toxicology and applied pharmacology. 2014; 280(1), 127-137.
Liu, M., Du, Y., Li, H., Wang, L., Ponikwicka-Tyszko, D., Lebiedzinska, W., & Li, X. Cyanidin-3-o-glucoside pharmacologically inhibits tumorigenesis via estrogen receptor β in melanoma mice. Frontiers in oncology. 2019; 9, 1110.
Li, X., Mu, J., Lin, Y., Zhao, J., & Meng, X. Combination of cyanidin‐3‐O‐glucoside and cisplatin induces oxidative stress and apoptosis in HeLa cells by reducing activity of endogenous antioxidants, increasing bax/bcl‐2 mRNA expression ratio, and downregulating Nrf2 expression. Journal of Food Biochemistry. 2021; 45(7), e13806.
Majerik Behinska, K., Balkova, E., Mihal, M., Roychoudhury, S., & Kolesarova, A. The therapeutic potential of cyanidin-3-O-glucoside relating to female reproductive health. Frontiers in Pharmacology. 2025; 16, 1599688.