{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:20:58Z","timestamp":1787023258360,"version":"build-2736575974"},"reference-count":40,"publisher":"Begell House","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Crit Rev Eukaryot Gene Expr"],"published-print":{"date-parts":[[2025]]},"abstract":"<p>Myocardial fibrosis is a critical pathological process in the progression of heart failure and other cardiovascular diseases. Kaempferol (KMP), a natural flavonoid, has antioxidant and anti-inflammatory properties. This study investigates the effects of KMP on myocardial fibrosis. Isoproterenol injection was used to establish myocardial fibrosis mouse model. Cardiac function was assessed by echocardiography. Histology analysis was conducted using Masson assay and Sirius red staining. The expression of survival of motor neuron 1 (&amp;alpha;-SMA) and Collagen III was detected using immunohistochemistry. RNA expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cytokine release was detected using enzyme-linked immunosorbent assay. Protein expression was detected using Western blot. We found that KMP treatment improved cardiac function as well as suppressed myocardial fibrosis. Moreover, KMP treatment decreased expression of fibrosis-related genes and attenuated inflammation in fibrotic hearts. Furthermore, KMP treatment inhibited the expression of coagulation factor VII (FVII), the overexpression of which promoted inflammation response and myocardial fibrosis. In summary, KMP exerts protective effects against myocardial fibrosis via downregulating FVII. These findings suggest that KMP may be a promising therapeutic candidate for myocardial fibrosis.<\/p>","DOI":"10.1615\/critreveukaryotgeneexpr.v35.i6.10","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T06:17:41Z","timestamp":1758089861000},"page":"1-10","source":"Crossref","is-referenced-by-count":1,"title":["Kaempferol Inhibits Myocardial Fibrosis by Downregulating FVII"],"prefix":"10.1615","volume":"35","author":[{"given":"Ming","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengbo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"613","reference":[{"key":"2","doi-asserted-by":"crossref","unstructured":"Schlittler M, Pramstaller PP, Rossini A, De Bortoli M. Myocardial fibrosis in hypertrophic cardiomyopathy: A perspective from fibroblasts. Int J Mol Sci. 2023;24(19):14845.","DOI":"10.3390\/ijms241914845"},{"key":"3","doi-asserted-by":"crossref","unstructured":"Chen L, Li H, Liu X, Zhang N, Wang K, Shi A, Gao H, Akdis D, Saguner AM, Xu X, Osto E, Van de Veen W, Li G, Bayes-Genis A, Duru F, Song J, Li X, Hu S. PBX\/Knotted 1 homeobox-2 (PKNOX2) is a novel regulator of myocardial fibrosis. Signal Transduct Target Ther. 2024;9:94.","DOI":"10.1038\/s41392-024-01804-5"},{"key":"4","doi-asserted-by":"crossref","unstructured":"Ravassa S, Lopez B, Treibel TA, San Jose G, Losada-Fuentenebro B, Tapia L, Bayes-Genis A, Diez J, Gonzalez A. Cardiac Fibrosis in heart failure: Focus on non-invasive diagnosis and emerging therapeutic strategies. Mol Aspects Med. 2023;93:101194.","DOI":"10.1016\/j.mam.2023.101194"},{"key":"5","doi-asserted-by":"crossref","unstructured":"Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.","DOI":"10.1056\/NEJMoa1812792"},{"key":"6","doi-asserted-by":"crossref","unstructured":"Periferakis A, Periferakis K, Badarau IA, Petran EM, Popa DC, Caruntu A, Costache RS, Scheau C, Caruntu C, Costache DO. Kaempferol: Antimicrobial properties, sources, clinical, and traditional applications. Int J Mol Sci. 2022;23(23):15054.","DOI":"10.3390\/ijms232315054"},{"key":"7","doi-asserted-by":"crossref","unstructured":"Chen M, Xiao J, El-Seedi HR, Wozniak KS, Daglia M, Little PJ, Weng J, Xu S. Kaempferol and atherosclerosis: From mechanism to medicine. Crit Rev Food Sci Nutr. 2024;64:2157-75.","DOI":"10.1080\/10408398.2022.2121261"},{"key":"8","doi-asserted-by":"crossref","unstructured":"Hussain MS, Altamimi ASA, Afzal M, Almalki WH, Kazmi I, Alzarea SI, Gupta G, Shahwan M, Kukreti N, Wong LS, Kumarasamy V, Subramaniyan V. Kaempferol: Paving the path for advanced treatments in aging-related diseases. Exp Gerontol. 2024;188:112389.","DOI":"10.1016\/j.exger.2024.112389"},{"key":"9","doi-asserted-by":"crossref","unstructured":"Yang Y, Chen Z, Zhao X, Xie H, Du L, Gao H, Xie C. Mechanisms of Kaempferol in the treatment of diabetes: A comprehensive and latest review. Front Endocrinol. 2022;13:990299.","DOI":"10.3389\/fendo.2022.990299"},{"key":"10","doi-asserted-by":"crossref","unstructured":"Ruan GY, Ye LX, Lin JS, Lin HY, Yu LR, Wang CY, Mao XD, Zhang SH, Sun PM. An integrated approach of network pharmacology, molecular docking, and experimental verification uncovers kaempferol as the effective modulator of HSD17B1 for treatment of endometrial cancer. J Transl Med. 2023;21:204.","DOI":"10.1186\/s12967-023-04048-z"},{"key":"11","doi-asserted-by":"crossref","unstructured":"Zhang S, Liu C, Li W, Zhang Y, Yang Y, Yang H, Zhao Z, Xu F, Cao W, Li X, Wang J, Kong L, Du G. Kaempferol promotes angiogenesis through HIF-1alpha\/VEGF-A\/Notch1 pathway in ischemic stroke rats. Neurochem Int. 2025;185:105953.","DOI":"10.1016\/j.neuint.2025.105953"},{"key":"12","doi-asserted-by":"crossref","unstructured":"He X, Wu T, He H, Chen L, Han K, Zheng J, Zhang Z, Yuan S, Wang Y, Zhang Y, Zhang X, Xie C. Study of kaempferol in the treatment of rheumatoid arthritis through modulation of the NLRP3\/CASP1\/GSDMD axis and T-cell activation: Based on network pharmacology, single-cell analysis, and experimental validation. Int Immunopharmacol. 2024;143:113357.","DOI":"10.1016\/j.intimp.2024.113357"},{"key":"13","doi-asserted-by":"crossref","unstructured":"Kamisah Y, Jalil J, Yunos NM, Zainalabidin S. Cardioprotective properties of kaempferol: A review. Plants. 2023;12(11):2096.","DOI":"10.3390\/plants12112096"},{"key":"14","doi-asserted-by":"crossref","unstructured":"Kaur S, Mendonca P, Soliman KFA. The anticancer effects and therapeutic potential of kaempferol in triple-negative breast cancer. Nutrients. 2024;16(15):2392.","DOI":"10.3390\/nu16152392"},{"key":"15","doi-asserted-by":"crossref","unstructured":"Nasanbat B, Uchiyama A, Amalia SN, Inoue Y, Yokoyama Y, Ogino S, Torii R, Hosoi M, Motegi SI. Kaempferol therapy improved MC903 induced-atopic dermatitis in a mouse by suppressing TSLP, oxidative stress, and type 2 inflammation. J Dermatol Sci. 2023;111:93-100.","DOI":"10.1016\/j.jdermsci.2023.06.008"},{"key":"16","doi-asserted-by":"crossref","unstructured":"Dong X, Zhou S, Nao J. Kaempferol as a therapeutic agent in Alzheimer's disease: Evidence from preclinical studies. Ageing Res Rev. 2023;87:101910.","DOI":"10.1016\/j.arr.2023.101910"},{"key":"17","doi-asserted-by":"crossref","unstructured":"Wu X, Li X, Yang C, Diao Y. Target characterization of kaempferol against myocardial infarction using novel in silico docking and DARTS prediction strategy. Int J Mol Sci. 2021;22(23):12908.","DOI":"10.3390\/ijms222312908"},{"key":"18","doi-asserted-by":"crossref","unstructured":"Liu Y, Gao L, Guo S, Liu Y, Zhao X, Li R, Yan X, Li Y, Wang S, Niu X, Yao L, Zhang Y, Li L, Yang H. Kaempferol alleviates angiotensin II-induced cardiac dysfunction and interstitial fibrosis in mice. Cell Physiol Biochem. 2017;43:2253-63.","DOI":"10.1159\/000484304"},{"key":"19","doi-asserted-by":"crossref","unstructured":"Yue Z, Zhang Y, Zhang W, Zheng N, Wen J, Ren L, Rong X, Bai L, Wang R, Zhao S, Liu E, Wang W. Kaempferol alleviates myocardial ischemia injury by reducing oxidative stress via the HDAC3-mediated Nrf2 signaling pathway. J Adv Res. In press 2024.","DOI":"10.1016\/j.jare.2024.10.037"},{"key":"20","doi-asserted-by":"crossref","unstructured":"Krishna PS, Nenavath RK, Sudha Rani S, Anupalli RR. Cardioprotective action of Amaranthus viridis methanolic extract and its isolated compound Kaempferol through mitigating lipotoxicity, oxidative stress and inflammation in the heart. 3 Biotech. 2023;13:317.","DOI":"10.1007\/s13205-023-03680-2"},{"key":"21","doi-asserted-by":"crossref","unstructured":"Gastol J, Paszek E, Bryk-Wiazania A, Matejko B, Undas A. Good metabolic control is associated with decreased circulating factor VIIa- antithrombin complexes in type 2 diabetes: A cross-sectional study. Cardiovasc Diabetol. 2024;23:398.","DOI":"10.1186\/s12933-024-02480-z"},{"key":"22","doi-asserted-by":"crossref","unstructured":"Li Y, Liu H, Ye S, Zhang B, Li X, Yuan J, Du Y, Wang J, Yang Y. The effects of coagulation factors on the risk of endometriosis: A Mendelian randomization study. BMC Med. 2023;21:195.","DOI":"10.1186\/s12916-023-02881-z"},{"key":"23","doi-asserted-by":"crossref","unstructured":"Kroone C, Tieken C, Kocaturk B, Paauwe M, Blok EJ, Unlu B, van den Berg YW, Stanganello E, Kapteijn MY, Swier N, Zhang X, Duits DEM, Lin Y, Oostenbrink LVE, van den Akker RFP, Mosnier LO, Hawinkels LJ, van Vlijmen BJM, Ruf W, Kuppen PJ, Cannegieter SC, Buijs JT, Versteeg HH. Tumor-expressed factor VII is associated with survival and regulates tumor progression in breast cancer. Blood Adv. 2023;7:2388-400.","DOI":"10.1182\/bloodadvances.2022008455"},{"key":"24","doi-asserted-by":"crossref","unstructured":"Zhang Y, Jiang Q, Liang X, Qian Q, Xiong J, Liu C, Xu J, Wang N, Xu Y, Zhou P, Lu S, Zhou Q, Yuan Y, Fan X, Liu J, Chen S. Coagulation factor VII fine-tunes hepatic steatosis by blocking AKT-CD36-mediated fatty acid uptake. Diabetes. 2024;73:682-700.","DOI":"10.2337\/db23-0814"},{"key":"25","doi-asserted-by":"crossref","unstructured":"Zelaya H, Grunz K, Nguyen TS, Habibi A, Witzler C, Reyda S, Gonzalez-Menendez I, Quintanilla-Martinez L, Bosmann M, Weiler H, Ruf W. Nucleic acid sensing promotes inflammatory monocyte migration through biased coagulation factor VIIa signaling. Blood. 2024;143:845-57.","DOI":"10.1182\/blood.2023021149"},{"key":"26","doi-asserted-by":"crossref","unstructured":"Li YY, Wang H, Zhang YY. FVII gene R353Q polymorphism and coronary heart disease: A meta-analysis including 3258 subjects. J Thromb Thrombolysis. 2021;52:324-30.","DOI":"10.1007\/s11239-020-02363-6"},{"key":"27","doi-asserted-by":"crossref","unstructured":"Barg AA, Livnat T, Kenet G. Factor XI deficiency: Phenotypic age-related considerations and clinical approach towards bleeding risk assessment. Blood. 2024;143:1455-64.","DOI":"10.1182\/blood.2023020721"},{"key":"28","doi-asserted-by":"crossref","unstructured":"Wei LK, Griffiths LR, Kooi CW, Irene L. Meta-analysis of factor V, factor VII, factor XII, and factor XIII-A gene polymorphisms and ischemic stroke. Medicina. 2019;55(4):101.","DOI":"10.3390\/medicina55040101"},{"key":"29","doi-asserted-by":"crossref","unstructured":"Xu H, Noria F, Sandoval-Cooper MJ, Menchen H, Donahue DL, Ploplis VA, Castellino FJ. Severe deficiency of coagulation factor VII results in spontaneous cardiac fibrosis in mice. J Pathol. 2009;217:362-71.","DOI":"10.1002\/path.2454"},{"key":"30","doi-asserted-by":"crossref","unstructured":"Wu HT, Lin XX, Yang XL, Ding Y, Wang JL, Liu CL, Yu WZ. Kaempferol attenuates inflammation in lipopolysaccharide-induced gallbladder epithelial cells by inhibiting the MAPK\/NF-kappaB signaling pathway. Chem Biol Drug Des. 2024;103:e14519.","DOI":"10.1111\/cbdd.14519"},{"key":"31","doi-asserted-by":"crossref","unstructured":"Paulus WJ, Zile MR. From systemic inflammation to myocardial fibrosis: The heart failure with preserved ejection fraction paradigm revisited. Circ Res. 2021;128:1451-67.","DOI":"10.1161\/CIRCRESAHA.121.318159"},{"key":"32","doi-asserted-by":"crossref","unstructured":"Chen R, Zhang H, Tang B, Luo Y, Yang Y, Zhong X, Chen S, Xu X, Huang S, Liu C. Macrophages in cardiovascular diseases: Molecular mechanisms and therapeutic targets. Signal Transduct Target Ther. 2024;9:130.","DOI":"10.1038\/s41392-024-01840-1"},{"key":"33","doi-asserted-by":"crossref","unstructured":"Tang XL, Liu JX, Dong W, Li P, Li L, Hou JC, Zheng YQ, Lin CR, Ren JG. Protective effect of kaempferol on LPS plus ATP-induced inflammatory response in cardiac fibroblasts. Inflammation. 2015;38:94-101.","DOI":"10.1007\/s10753-014-0011-2"},{"key":"34","doi-asserted-by":"crossref","unstructured":"Bakhshii S, Khezri S, Ahangari R, Jahedsani A, Salimi A. Protection of clozapine-induced oxidative stress and mitochondrial dysfunction by kaempferol in rat cardiomyocytes. Drug Dev Res. 2021;82:835-43.","DOI":"10.1002\/ddr.21790"},{"key":"35","doi-asserted-by":"crossref","unstructured":"Ajisebiola BS, Oladele JO, Adeyi AO. Kaempferol from Moringa oleifera demonstrated potent antivenom activities via inhibition of metalloproteinase and attenuation of Bitis arietans venom-induced toxicities. Toxicon. 2023;233:107242.","DOI":"10.1016\/j.toxicon.2023.107242"},{"key":"36","doi-asserted-by":"crossref","unstructured":"Maneesai P, Potue P, Khamseekaew J, Sangartit W, Rattanakanokchai S, Poasakate A, Pakdeechote P. Kaempferol protects against cardiovascular abnormalities induced by nitric oxide deficiency in rats by suppressing the TNF-alpha pathway. Eur J Pharmacol. 2023;960:176112.","DOI":"10.1016\/j.ejphar.2023.176112"},{"key":"37","unstructured":"Qi Y, Ying Y, Zou J, Fang Q, Yuan X, Cao Y, Cai Y, Fu S. Kaempferol attenuated cisplatin-induced cardiac injury via inhibiting STING\/NF-kappaB-mediated inflammation. Am J Transl Res. 2020;12:8007-18."},{"key":"38","doi-asserted-by":"crossref","unstructured":"Zhou ZY, Ma J, Zhao WR, Shi WT, Zhang J, Hu YY, Yue MY, Zhou WL, Yan H, Tang JY, Wang Y. Qiangxinyin formula protects against isoproterenol-induced cardiac hypertrophy. Phytomedicine. 2024;130:155717.","DOI":"10.1016\/j.phymed.2024.155717"},{"key":"39","doi-asserted-by":"crossref","unstructured":"Friso S, Lotto V, Choi SW, Girelli D, Pinotti M, Guarini P, Udali S, Pattini P, Pizzolo F, Martinelli N, Corrocher R, Bernardi F, Olivieri O. Promoter methylation in coagulation F7 gene influences plasma FVII concentrations and relates to coronary artery disease. J Med Genet. 2012;49:192-9.","DOI":"10.1136\/jmedgenet-2011-100195"},{"key":"40","doi-asserted-by":"crossref","unstructured":"Alehagen U, Dahlstrom U, Lindahl TL. Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure. Blood Coagul Fibrinolysis. 2010;21:62-9.","DOI":"10.1097\/MBC.0b013e328332aa2b"},{"key":"41","doi-asserted-by":"crossref","unstructured":"Garlapati V, Luo Q, Posma J, Aluia M, Nguyen TS, Grunz K, Molitor M, Finger S, Harms G, Bopp T, Ruf W, Wenzel P. Macrophage-expressed coagulation factor vii promotes adverse cardiac remodeling. Circ Res. 2024;135:841-55.","DOI":"10.1161\/CIRCRESAHA.123.324114"}],"container-title":["Critical Reviews in Eukaryotic Gene Expression"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.dl.begellhouse.com\/download\/article\/4125dd170d2d24fa\/CRE-58859.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T06:18:07Z","timestamp":1758089887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.dl.begellhouse.com\/journals\/6dbf508d3b17c437,1795a7ae0f352901,4125dd170d2d24fa.html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.1615\/critreveukaryotgeneexpr.v35.i6.10","relation":{},"ISSN":["1045-4403"],"issn-type":[{"value":"1045-4403","type":"print"}],"subject":[],"published":{"date-parts":[[2025]]}}}