{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:25:19Z","timestamp":1787653519370,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Cold hypersensitivity in hands and feet (CHHF) affects 20\u201352% of East Asian populations, is more prevalent in women, and is managed with vasodilators in Western medicine or herbal therapies in traditional East Asian medicine. This study was conducted to compare the pharmacological characteristics of two heat-clearing (HCHs, Scutellariae Radix and Coptidis Rhizoma) and two blood-tonifying (BTHs, Angelicae Sinensis Radix and Paeoniae Radix Alba) herbs used for CHHF. Candidate herbs were selected based on herbology classifications, PubMed searches, and the Korean Medicine Clinical Practice Guideline for CHHF. A total of 61 active compounds and 323 corresponding protein targets with CHHF were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), standardized via UniProt, and intersected with CHHF-related genes from GeneCards. Protein\u2013protein interaction networks were constructed, core targets identified, and functional enrichment analyses performed using Reactome databases. A total of 166 herb\u2013CHHF common targets were identified, including 24 shared across all four herbs. HCHs were primarily enriched in hemostasis-, immune-, and signaling-related pathways, whereas BTHs were associated with immune regulation, metabolism, and neuronal modulation. Notably, Scutellariae Radix and Paeoniae Radix Alba showed substantial overlap in enriched pathways. These findings suggest that HCHs and BTHs may be associated with distinct yet potentially relevant molecular mechanisms in CHHF. However, because the present analysis was conducted at the single-herb level, these findings cannot be directly generalized to the clinical use of multi-herb formulas and should be interpreted as hypothesis-generating.<\/jats:p>","DOI":"10.3390\/life16091406","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:04:55Z","timestamp":1787652295000},"page":"1406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology-Based Exploration of Complementary Molecular Mechanisms of Heat-Clearing (Scutellariae Radix, Coptidis Rhizoma) and Blood-Tonifying Herbs (Angelicae Sinensis Radix, Paeoniae Radix Alba) in Cold Hypersensitivity in Hands and Feet"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5376-2689","authenticated-orcid":false,"given":"Eunsu","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Korean Medicine, College of Korean Medicine, Sangji University, Wonju-si 26339, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunseo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Korean Medicine, College of Korean Medicine, Sangji University, Wonju-si 26339, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2343-4704","authenticated-orcid":false,"given":"Jihyun","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Korean Medicine, College of Korean Medicine, Sangji University, Wonju-si 26339, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Korean Medicine, College of Korean Medicine, Sangji University, Wonju-si 26339, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jina","family":"Youth","sequence":"additional","affiliation":[{"name":"Department of Korean Medicine, College of Korean Medicine, Sangji University, Wonju-si 26339, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Seo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Korean Language & Literature, College of Humanities, Sogang University, Seoul 04107, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6896-1778","authenticated-orcid":false,"given":"Young-Cheol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Herbology, College of Korean Medicine, Sangji University, Wonju-si 26339, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.14406\/acu.2021.004","article-title":"A Review of Acupuncture Treatment Methods for Cold Hypersensitivity of Hands and Feet","volume":"38","author":"Choi","year":"2021","journal-title":"Korean J. Acupunct."},{"key":"ref_2","unstructured":"The Society of Sasang Constitution and Immune Medicine, and The Society of Korean Medicine Obstetrics and Gynecology (2021). Clinical Practice Guideline of Korean Medicine\u2014Cold Hypersensitivity in Hands and Feet, Development Project Group of Clinical Practice Guideline of Korean Medicine of National Institute for Korean Medicine Development."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1089\/acm.2018.0009","article-title":"Herbal Medicines for Cold Hypersensitivity in the Hands and Feet: A Systematic Review and Meta-Analysis","volume":"24","author":"Yu","year":"2018","journal-title":"J. Altern. Complement. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1375\/twin.15.2.166","article-title":"Feeling of cold hands and feet is a highly heritable phenotype","volume":"15","author":"Hur","year":"2012","journal-title":"Twin Res. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Park, S.Y., Lee, Y.Y., Kim, M.H., and Kim, C.E. (2024). Deciphering the Systemic Impact of Herbal Medicines on Allergic Rhinitis: A Network Pharmacological Approach. Life, 14.","DOI":"10.3390\/life14050553"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113915","DOI":"10.1016\/j.biopha.2022.113915","article-title":"Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2\/System xc-\/GPX4 axis","volume":"157","author":"He","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4103\/2225-4110.126635","article-title":"Anti-inflammatory and Antimicrobial Effects of Heat-Clearing Chinese Herbs: A Current Review","volume":"4","author":"Muluye","year":"2014","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10577","DOI":"10.1038\/s41598-024-60260-x","article-title":"Cold hypersensitivity in the hands and feet is associated with erectile dysfunction in young Taiwanese men","volume":"14","author":"Chang","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13020-024-01022-9","article-title":"The role of Chinese herbal medicine in the regulation of oxidative stress in treating hypertension: From therapeutics to mechanisms","volume":"19","author":"Jin","year":"2024","journal-title":"Chin. Med."},{"key":"ref_10","first-page":"e21681","article-title":"Raynaud\u2019s Phenomenon: Reviewing the Pathophysiology and Management Strategies","volume":"14","author":"Nawaz","year":"2022","journal-title":"Cureus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14500","DOI":"10.1038\/s41598-017-14202-5","article-title":"T cells upon activation promote endothelin 1 production in monocytes via IFN-gamma and TNF-alpha","volume":"7","author":"Shinagawa","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_12","first-page":"4","article-title":"Investigation on the mechanism of p38MAPK in the failure of autogenous arteriovenous fistula caused by stenosis","volume":"72","author":"He","year":"2021","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1161\/ATVBAHA.124.321434","article-title":"CXCR3-CXCL11 Signaling Restricts Angiogenesis and Promotes Pericyte Recruitment","volume":"44","author":"Lee","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"H1075","DOI":"10.1152\/ajpheart.2000.278.4.H1075","article-title":"Silent alpha(2C)-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries","volume":"278","author":"Chotani","year":"2000","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100884","DOI":"10.1016\/j.xgen.2025.100884","article-title":"alpha2 adrenoceptors, cold-induced vasoconstriction, and Raynaud\u2019s phenomenon","volume":"5","author":"Flavahan","year":"2025","journal-title":"Cell Genom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105454","DOI":"10.1016\/j.compbiomed.2022.105454","article-title":"Mechanisms underlying the therapeutic effects of Qingfeiyin in treating acute lung injury based on GEO datasets, network pharmacology and molecular docking","volume":"145","author":"Wang","year":"2022","journal-title":"Comput. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3724\/SP.J.1009.2013.00110","article-title":"Traditional Chinese medicine network pharmacology: Theory, methodology and application","volume":"11","author":"Li","year":"2013","journal-title":"Chin. J. Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, W., Huai, Y., Miao, Z., Qian, A., and Wang, Y. (2019). Systems Pharmacology for Investigation of the Mechanisms of Action of Traditional Chinese Medicine in Drug Discovery. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00743"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104074","DOI":"10.1016\/j.compbiomed.2020.104074","article-title":"Network pharmacology-based investigation on the mechanisms of action of Morinda officinalis How. in the treatment of osteoporosis","volume":"127","author":"Liu","year":"2020","journal-title":"Comput. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113435","DOI":"10.1016\/j.jpba.2020.113435","article-title":"An integrative metabolomics and network pharmacology method for exploring the effect and mechanism of Radix Bupleuri and Radix Paeoniae Alba on anti-depression","volume":"189","author":"Zhang","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_21","unstructured":"National Editorial Committee for the Joint Textbook of Herbology (2020). Herbology, Yeonglimsa."},{"key":"ref_22","first-page":"179","article-title":"A Study on the \u2018Harmonizing All Medicinals\u2019 Property of Gancao","volume":"33","author":"Shin","year":"2020","journal-title":"J. Korean Med. Class."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"519031","DOI":"10.1155\/2012\/519031","article-title":"A systems biology approach to uncovering pharmacological synergy in herbal medicines with applications to cardiovascular disease","volume":"2012","author":"Wang","year":"2012","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.jare.2024.12.040","article-title":"Evaluating current status of network pharmacology for herbal medicine focusing on identifying mechanisms and therapeutic effects","volume":"76","author":"Lee","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e33528","DOI":"10.1097\/MD.0000000000033528","article-title":"Mechanism of Danggui Sini underlying the treatment of peripheral nerve injury based on network pharmacology and molecular docking: A review","volume":"102","author":"Zhang","year":"2023","journal-title":"Medicine"},{"key":"ref_26","first-page":"9980981","article-title":"Network Pharmacology Combined with Bioinformatics to Investigate the Mechanisms and Molecular Targets of Astragalus Radix-Panax notoginseng Herb Pair on Treating Diabetic Nephropathy","volume":"2021","author":"Zhao","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"523","DOI":"10.3233\/THC-248046","article-title":"Exploring active ingredients and mechanisms of Coptidis Rhizoma-ginger against colon cancer using network pharmacology and molecular docking","volume":"32","author":"Zeng","year":"2024","journal-title":"Technol. Health Care"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4683254","DOI":"10.1155\/2020\/4683254","article-title":"Investigation on the Mechanism of Qubi Formula in Treating Psoriasis Based on Network Pharmacology","volume":"2020","author":"Zhou","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"117323","DOI":"10.1016\/j.jep.2023.117323","article-title":"A network pharmacology approach and experimental validation to investigate the anticancer mechanism of Qi-Qin-Hu-Chang formula against colitis-associated colorectal cancer through induction of apoptosis via JNK\/p38 MAPK signaling pathway","volume":"319","author":"Wu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","article-title":"The Reactome Pathway Knowledgebase 2024","volume":"52","author":"Milacic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3109\/09537104.2012.719090","article-title":"The contribution of platelets to the pathogenesis of Raynaud\u2019s phenomenon and systemic sclerosis","volume":"24","author":"Pauling","year":"2013","journal-title":"Platelets"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"H243","DOI":"10.1152\/ajpheart.01305.2004","article-title":"Reactive oxygen species from smooth muscle mitochondria initiate cold-induced constriction of cutaneous arteries","volume":"289","author":"Bailey","year":"2005","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1191\/1358863x05vm639ra","article-title":"Mechanisms of Raynaud\u2019s disease","volume":"10","author":"Cooke","year":"2005","journal-title":"Vasc. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3831\/KPI.2016.19.002","article-title":"Historical Medical Value of Donguibogam","volume":"19","author":"Song","year":"2016","journal-title":"J. Pharmacopunct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7416","DOI":"10.1038\/s41598-018-25813-x","article-title":"Majority of Chinese Medicine Herb Category \u201cQing Re Yao\u201d Have Multiple Mechanisms of Anti-inflammatory Activity","volume":"8","author":"Guan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/23328940.2015.1008890","article-title":"Responses of the hands and feet to cold exposure","volume":"2","author":"Cheung","year":"2015","journal-title":"Temperature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1758-2946-6-13","article-title":"TCMSP: A database of systems pharmacology for drug discovery from herbal medicines","volume":"6","author":"Ru","year":"2014","journal-title":"J. Cheminform."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12938-017-0359-2","article-title":"Rational confederation of genes and diseases: NGS interpretation via GeneCards, MalaCards and VarElect","volume":"16","author":"Rappaport","year":"2017","journal-title":"Biomed. Eng. Online"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yu, H., Chen, J., Xu, X., Li, Y., Zhao, H., Fang, Y., Li, X., Zhou, W., Wang, W., and Wang, Y. (2012). A systematic prediction of multiple drug-target interactions from chemical, genomic, and pharmacological data. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037608"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kim, S.K., Lee, M.K., Jang, H., Lee, J.J., Lee, S., Jang, Y., Jang, H., and Kim, A. (2024). TM-MC 2.0: An enhanced chemical database of medicinal materials in Northeast Asian traditional medicine. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-023-04331-y"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1038\/s41598-018-19333-x","article-title":"Gene annotation bias impedes biomedical research","volume":"8","author":"Haynes","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.2147\/DDDT.S450739","article-title":"Network Pharmacology and Molecular Docking Identify the Potential Mechanism and Therapeutic Role of Scutellaria baicalensis in Alzheimer\u2019s Disease","volume":"18","author":"Peng","year":"2024","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_43","first-page":"753","article-title":"5,7,2,5-tetrahydroxy-8,6-dimethoxyflavone up-regulates miR-145 expression and inhibits proliferation of gastric cancer cells","volume":"18","author":"Wei","year":"2021","journal-title":"Arch. Med. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhou, Z., Li, T., Qin, H., Wang, X., He, S., Fan, Z., Ye, Q., and Du, Y. (2025). Acacetin as a natural cardiovascular therapeutic: Mechanisms and preclinical evidence. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1493981"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cao, P., Xie, P., Wang, X., Wang, J., Wei, J., and Kang, W.Y. (2017). Chemical constituents and coagulation activity of Agastache rugosa. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1592-8"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bu, J., Mahan, Y., Zhang, S., Wu, X., Zhang, X., Zhou, L., and Zhang, Y. (2024). Acacetin inhibits inflammation by blocking MAPK\/NF-\u03baB pathways and NLRP3 inflammasome activation. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1286546"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Peng, B., Hu, Q., He, R., Hou, H., Lian, D., Chen, Y., Li, H., Song, L., Gao, Y., and Chen, T. (2023). Baicalein alleviates fibrosis and inflammation in systemic sclerosis by regulating B-cell abnormalities. BMC Complement. Med. Ther., 23.","DOI":"10.1186\/s12906-023-03885-1"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9310","DOI":"10.18632\/aging.102371","article-title":"Baicalein attenuates OVA-induced allergic airway inflammation through the inhibition of the NF-\u03baB signaling pathway","volume":"11","author":"Xu","year":"2019","journal-title":"Aging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"102772","DOI":"10.1016\/j.tice.2025.102772","article-title":"Baicalin and baicalein against myocardial ischemia-reperfusion injury: A review of the current documents","volume":"93","author":"Nasiri","year":"2025","journal-title":"Tissue Cell"},{"key":"ref_50","first-page":"177","article-title":"Identification and verification of effective components of Huanghuai for dysfunctional uterine bleeding based on network pharmacology and molecular docking","volume":"13","author":"Yao","year":"2020","journal-title":"Chin. Herb. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wu, W., Liu, W., Wu, N., Qu, C., Chu, W., and Jin, J. (2025). \u03b2-sitosterol alleviated HFD-induced atherosclerosis by regulating the MAPK\/Nrf2\/NLRP3 pathway in ApoE\u2212\/\u2212 mice. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0332990"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Fan, Y., Shen, J., Liu, X., Cui, J., Liu, J., Peng, D., and Jin, Y. (2023). \u03b2-Sitosterol Suppresses Lipopolysaccharide-Induced Inflammation and Lipogenesis Disorder in Bovine Mammary Epithelial Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914644"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7946","DOI":"10.1111\/jcmm.14725","article-title":"Coptisine from Coptis chinensis exerts diverse beneficial properties: A concise review","volume":"23","author":"Wu","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"113941","DOI":"10.1016\/j.biopha.2022.113941","article-title":"Coptisine protects against hyperuricemic nephropathy through alleviating inflammation, oxidative stress and mitochondrial apoptosis via PI3K\/Akt signaling pathway","volume":"156","author":"Liu","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Balykina, A., Naida, L., Kirkg\u00f6z, K., Nikolaev, V.O., Fock, E., Belyakov, M., Whaley, A., Whaley, A., Shpakova, V., and Rukoyatkina, N. (2024). Antiplatelet Effects of Flavonoid Aglycones Are Mediated by Activation of Cyclic Nucleotide-Dependent Protein Kinases. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094864"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"156432","DOI":"10.1016\/j.phymed.2025.156432","article-title":"Norwogonin attenuates LPS-induced acute lung injury through inhibiting Src\/AKT1\/NF-\u03baB signaling pathway","volume":"139","author":"Cao","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12959-025-00709-9","article-title":"Oroxylin A reverses SHP-2 oxidative inactivation in GPVI signaling to suppress platelet activation and thrombus formation","volume":"23","author":"Chen","year":"2025","journal-title":"Thromb. J."},{"key":"ref_58","first-page":"6478","article-title":"Stigmasterol alleviates airway inflammation in OVA-induced asthmatic mice via inhibiting the TGF-\u03b21\/Smad2 and IL-17A signaling pathways","volume":"16","author":"Huang","year":"2024","journal-title":"Aging"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e1303","DOI":"10.1002\/iid3.1303","article-title":"Wogonin ameliorates the proliferation, inflammatory response, and pyroptosis in keratinocytes via NOD-like receptor family pyrin domain containing 3\/Caspase-1\/Gasdermin-D pathway","volume":"12","author":"Ma","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"172517","DOI":"10.1016\/j.ejphar.2019.172517","article-title":"Anticoagulant effect of wogonin against tissue factor expression","volume":"859","author":"Wu","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sul, O.J., and Ra, S.W. (2021). Quercetin Prevents LPS-Induced Oxidative Stress and Inflammation by Modulating NOX2\/ROS\/NF-kB in Lung Epithelial Cells. Molecules, 26.","DOI":"10.3390\/molecules26226949"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Jiang, Y.H., Jiang, L.Y., Wang, Y.C., Ma, D.F., and Li, X. (2020). Quercetin Attenuates Atherosclerosis via Modulating Oxidized LDL-Induced Endothelial Cellular Senescence. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00512"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e2200716","DOI":"10.1002\/mnfr.202200716","article-title":"(+)-Catechin Attenuates Multiple Atherosclerosis-Associated Processes In Vitro, Modulates Disease-Associated Risk Factors in C57BL\/6J Mice and Reduces Atherogenesis in LDL Receptor Deficient Mice by Inhibiting Inflammation and Increasing Markers of Plaque Stability","volume":"67","author":"Chan","year":"2023","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Cheng, A.W., Tan, X., Sun, J.Y., Gu, C.M., Liu, C., and Guo, X. (2019). Catechin attenuates TNF-\u03b1 induced inflammatory response via AMPK-SIRT1 pathway in 3T3-L1 adipocytes. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217090"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Dong, H., Song, G., Wang, Z., Wu, X., Wang, Q., and Wang, Y.H. (2025). Kaempferol as a multifaceted immunomodulator: Implications for inflammation, autoimmunity, and cancer. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1671519"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1080\/13880209.2021.1961823","article-title":"Kaempferol-induced GPER upregulation attenuates atherosclerosis via the PI3K\/AKT\/Nrf2 pathway","volume":"59","author":"Feng","year":"2021","journal-title":"Pharm. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2346163","DOI":"10.1155\/mi\/2346163","article-title":"Paeoniflorin Alleviates LPS-Induced Inflammation and Acute Myocardial Injury by Inhibiting PI3K\/Akt\/ERK-Mediated HIF-1\u03b1 and TLR4\/MyD88\/NF-\u03baB Inflammatory Signaling","volume":"2025","author":"Guo","year":"2025","journal-title":"Mediat. Inflamm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/ddr.21647","article-title":"Paeoniflorin alleviates lipopolysaccharide-induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation","volume":"81","author":"Fang","year":"2020","journal-title":"Drug Dev. Res."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/9\/1406\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:10:28Z","timestamp":1787652628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/9\/1406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":68,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["life16091406"],"URL":"https:\/\/doi.org\/10.3390\/life16091406","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]}}}