{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T20:23:52Z","timestamp":1788121432857,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81793289"],"award-info":[{"award-number":["81793289"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["02. DY11.03.19.03"],"award-info":[{"award-number":["02. 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DY11.03.19.03"]}]},{"name":"National Key Clinical Specialty Discipline Construction Program of China","award":["320.6750.2021-2-75"],"award-info":[{"award-number":["320.6750.2021-2-75"]}]},{"name":"special fund for clinical research of Wu Jieping Medical Foundation","award":["81793289"],"award-info":[{"award-number":["81793289"]}]},{"name":"special fund for clinical research of Wu Jieping Medical Foundation","award":["02. DY11.03.19.03"],"award-info":[{"award-number":["02. DY11.03.19.03"]}]},{"name":"special fund for clinical research of Wu Jieping Medical Foundation","award":["320.6750.2021-2-75"],"award-info":[{"award-number":["320.6750.2021-2-75"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The Yiqi Qubai (YQ) formula is a hospital preparation for treating vitiligo in China that has had reliable efficacy for decades. The formula consists of four herbs; however, the extraction process to produce the formula is obsolete and the active ingredients and mechanisms remain unknown. Therefore, in this paper, fingerprints were combined with the chemometrics method to screen high-quality herbs for the preparation of the YQ standard decoction (YQD). Then, the YQD preparation procedure was optimized using response surface methodology. A total of 44 chemical constituents, as well as 36 absorption components (in rat plasma) of YQD, were identified via UPLC-Q-TOF\/MS. Based on the ingredients, the quality control system of YQD was optimized by establishing the SPE-UPLC-Q-TOF\/MS identification method and the HPLC quantification method. Network pharmacological analysis and molecular docking showed that carasinaurone, calycosin-7-O-\u03b2-d-glucoside, methylnissolin-3-O-glucoside, genkwanin, akebia saponin D, formononetin, akebia saponin B, and apigenin may be the key active components for treating vitiligo; the core targets associated with them were AKT1, MAPK1, and mTOR, whereas the related pathways were the PI3K-Akt, MAPK, and FoxO signaling pathways. Cellular assays showed that YQD could promote melanogenesis and tyrosinase activity, as well as the transcription and expression of tyrosinase-associated proteins (i.e., TRP-1) in B16F10 cells. In addition, YQD also increased extracellular tyrosinase activity. Further efficacy validation showed that YQD significantly promotes melanin production in zebrafish. These may be the mechanisms by which YQD improves the symptoms of vitiligo. This is the first systematic study of the YQ formula that has optimized the standard decoction preparation method and investigated the active ingredients, quality control, efficacy, and mechanisms of YQD. The results of this study lay the foundations for the clinical application and further development of the YQ formula.<\/jats:p>","DOI":"10.3390\/ph16121716","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T11:24:43Z","timestamp":1702293883000},"page":"1716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Systematic Study of Yiqi Qubai Standard Decoction for Treating Vitiligo Based on UPLC-Q-TOF\/MS Combined with Chemometrics, Molecular Docking, and Cellular and Zebrafish Assays"],"prefix":"10.3390","volume":"16","author":[{"given":"Lijun","family":"Cui","sequence":"first","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200331, China"},{"name":"School of Pharmacy, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China"},{"name":"School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Fourth People\u2019s Hospital Affiliated to Tongji University School of Medicine, Shanghai 200434, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China"},{"name":"School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China"},{"name":"School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefen","family":"Lou","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200331, China"},{"name":"Department of Pharmacy, Shanghai Fourth People\u2019s Hospital Affiliated to Tongji University School of Medicine, Shanghai 200434, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-5896","authenticated-orcid":false,"given":"Guorong","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200331, China"},{"name":"Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China"},{"name":"School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1111\/j.1365-4632.2011.05377.x","article-title":"A review of the worldwide prevalence of vitiligo in children\/adolescents and adults","volume":"51","author":"Schallreuter","year":"2012","journal-title":"Int. J. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1159\/000506103","article-title":"Vitiligo: A Review","volume":"236","author":"Bergqvist","year":"2020","journal-title":"Dermatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.det.2019.08.005","article-title":"Phototherapy for Vitiligo","volume":"38","author":"Zubair","year":"2020","journal-title":"Dermatol. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1111\/exd.13807","article-title":"Vitiligo surgery: A journey from tissues via cells to the stems","volume":"28","author":"Razmi","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/j.jid.2020.12.028","article-title":"Efficacy and Safety of Tacrolimus 0.1% for the Treatment of Facial Vitiligo: A Multicenter Randomized, Double-Blinded, Vehicle-Controlled Study","volume":"141","author":"Seneschal","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1111\/1346-8138.15858","article-title":"Efficacy and safety of i.v. methylprednisolone pulse therapy for vitiligo: A retrospective study of 58 therapy experiences for 33 vitiligo patients","volume":"48","author":"Tsuchiyama","year":"2021","journal-title":"J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Picardo, M., Dell\u2019Anna, M.L., Ezzedine, K., Hamzavi, I., Harris, J.E., Parsad, D., and Taieb, A. (2015). Vitiligo. Nat. Rev. Dis. Primers, 1.","DOI":"10.1038\/nrdp.2015.11"},{"key":"ref_8","first-page":"822","article-title":"Research Progress on Treatment of Vitiligo with Traditional Chinese Medicine","volume":"28","author":"Chen","year":"2022","journal-title":"J. Basic Chin. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s11655-008-0303-1","article-title":"Clinical observation on the effect of Zengse Pill in treating patients with vitiligo of qistagnancy and blood-stasis syndrome type","volume":"14","author":"Shi","year":"2008","journal-title":"Chin. J. Integr. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chen, Z., Liu, L., Gao, C., Chen, W., Vong, C.T., Yao, P., Yang, Y., Li, X., Tang, X., and Wang, S. (2020). Astragali Radix (Huangqi): A promising edible immunomodulatory herbal medicine. J. Ethnopharmacol., 258.","DOI":"10.1016\/j.jep.2020.112895"},{"key":"ref_11","first-page":"71","article-title":"Treatment of vitiligo based on the principle of pacifying liver by resolving stasis and activating blood circulation, plus exorcising \u201cwind\u201d. An observation on therapeutic effects in 100 cases","volume":"2","author":"Zhu","year":"1982","journal-title":"J. Tradit Chin. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1080\/09546634.2017.1303570","article-title":"A combination of Yiqiqubai granule and 308-nm excimer laser in treatment of segmental vitiligo: A prospective study of 233 patients","volume":"28","author":"Zhang","year":"2017","journal-title":"J. Dermatol. Treat."},{"key":"ref_13","unstructured":"Yang, K.Y. (2016). The Effect of 308 nm Excimer Light Combined with Yiqiqubai Granule on the Treatment of Vitiligo. [Master\u2019s Thesis, Shanghai Jiaotong University]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jep.2009.04.048","article-title":"Ethnobotany, phytochemistry and pharmacology of the genus Caragana used in traditional Chinese medicine","volume":"124","author":"Meng","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ma, B., Yang, S., Tan, T., Li, J., Zhang, X., Ouyang, H., He, M., and Feng, Y. (2021). An integrated study of metabolomics and transcriptomics to reveal the anti-primary dysmenorrhea mechanism of Akebiae Fructus. J. Ethnopharmacol., 270.","DOI":"10.1016\/j.jep.2020.113763"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Huang, Y.X., Wang, J., Wang, Y., Kuang, W., Xie, M.J., and Zhang, M. (2023). Pharmacological mechanism and clinical study of Qiming granules in treating diabetic retinopathy based on network pharmacology and literature review. J. Ethnopharmacol., 302.","DOI":"10.1016\/j.jep.2022.115861"},{"key":"ref_17","first-page":"2792","article-title":"Effects of extract of Yiqiqubai Compound on mushroom tyrosinase activity and melanogenesis","volume":"28","author":"Wu","year":"2013","journal-title":"Chin. J. Tradit. Chin. Med. Pharm."},{"key":"ref_18","unstructured":"Commission, C.P. (2016, August 05). Technical Requirements for Quality Control and Standard Formulation of Chinese Herbal Formula Granules (Draft for Comment). Available online: http:\/\/www.chp.org.cn\/view\/ff808081559d1ea301565ac24962560d?a=XWJX."},{"key":"ref_19","first-page":"1367","article-title":"Research strategies in standard decoction of medicinal slices","volume":"41","author":"Chen","year":"2016","journal-title":"Chin. J. Chin. Mater. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Liang, W., Chen, W., Wu, L., Li, S., Qi, Q., Cui, Y., Liang, L., Ye, T., and Zhang, L. (2017). Quality Evaluation and Chemical Markers Screening of Salvia miltiorrhiza Bge. (Danshen) Based on HPLC Fingerprints and HPLC-MS(n) Coupled with Chemometrics. Molecules, 22.","DOI":"10.3390\/molecules22030478"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Li, B., Lima, M., Nie, Y., Xu, L., Liu, X., Yuan, H., Chen, C., Dias, A.C., and Zhang, X. (2021). HPLC-DAD Fingerprints Combined with Multivariate Analysis of Epimedii Folium from Major Producing Areas in Eastern Asia: Effect of Geographical Origin and Species. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.761551"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shi, W., Wu, Z., Wu, J., Jia, M., Yang, C., Feng, J., Lou, Y., and Fan, G. (2023). A comprehensive quality control evaluation for standard decoction of Smilax glabra Roxb based on HPLC-MS-UV\/CAD methods combined with chemometrics analysis and network pharmacology. Food Chem., 410.","DOI":"10.1016\/j.foodchem.2022.135371"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fan, X., Hong, T., Yang, Q., Wang, D., Peng, J., Xiao, W., Yang, X., Hu, X., Yu, C., and Du, S. (2022). Quality assessment of fried licorice based on fingerprints and chemometrics. Food Chem., 378.","DOI":"10.1016\/j.foodchem.2022.132121"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Molagoda, I.M.N., Karunarathne, W.A.H.M., Park, S.R., Choi, Y.H., Park, E.K., Jin, C.-Y., Yu, H., Jo, W.S., Lee, K.T., and Kim, G.-Y. (2020). GSK-3\u03b2-Targeting Fisetin Promotes Melanogenesis in B16F10 Melanoma Cells and Zebrafish Larvae through \u03b2-Catenin Activation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010312"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R81","DOI":"10.1016\/j.cub.2014.11.013","article-title":"Zebrafish stripes as a model for vertebrate colour pattern formation","volume":"25","author":"Singh","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3892\/mmr.2020.11139","article-title":"Syntenin regulates melanogenesis via the p38 MAPK pathway","volume":"22","author":"Sun","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Alshammari, F., Alam, M.B., Naznin, M., Javed, A., Kim, S., and Lee, S.H. (2023). Profiling of Secondary Metabolites of Optimized Ripe Ajwa Date Pulp (Phoenix dactylifera L.) Using Response Surface Methodology and Artificial Neural Network. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020319"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1080\/13880209.2020.1844760","article-title":"Screening study of blood-supplementing active components in water decoction of Angelica sinensis processed with yellow rice wine based on response surface methodology","volume":"58","author":"Ji","year":"2020","journal-title":"Pharm. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1023\/A:1015803321609","article-title":"Optimized formulation of magnetic chitosan microspheres containing the anticancer agent, oxantrazole","volume":"9","author":"Hassan","year":"1992","journal-title":"Pharm. Res."},{"key":"ref_30","first-page":"530","article-title":"Optimization of multiple evariables: Application of central composite design and overall desirability","volume":"35","author":"Wei","year":"2020","journal-title":"Chin. Pharm. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1515\/BC.2000.009","article-title":"Adjuvant and haemolytic activities of 47 saponins derived from medicinal and food plants","volume":"381","author":"Oda","year":"2000","journal-title":"Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1248\/cpb.54.595","article-title":"Triterpenoid Saponins from the Fruits of Akebiae quinata","volume":"54","author":"Jiang","year":"2006","journal-title":"Chem. Pharm. Bull."},{"key":"ref_33","unstructured":"Commission, C.P. (2020). Pharmacopoeia of the People\u2019s Republic of China, China Medical Science Press."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.bmcl.2011.12.012","article-title":"Antioxidative oligostilbenes from Caragana sinica","volume":"22","author":"Jin","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1002\/rcm.8480","article-title":"A four-step filtering strategy based on ultra-high-performance liquid chromatography coupled to quadrupole-time-of-flight tandem mass spectrometry for comprehensive profiling the major chemical constituents of Akebiae Fructus","volume":"33","author":"Ma","year":"2019","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Xue, Z., and Yang, B. (2016). Phenylethanoid Glycosides: Research Advances in Their Phytochemistry, Pharmacological Activity and Pharmacokinetics. Molecules, 21.","DOI":"10.3390\/molecules21080991"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chen, W., Zheng, Y., Yan, L., Yuan, M., Ouyang, L., Li, J., Zhou, G., and Zhong, R. (2019). Validated UHPLC-MS\/MS method for simultaneous determination of four triterpene saponins from Akebia trifoliata extract in rat plasma and its application to a pharmacokinetic study. Biomed. Chromatogr., 33.","DOI":"10.1002\/bmc.4585"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Li, P., Peng, J., Li, Y., Gong, L., Lv, Y., Liu, H., Zhang, T., Yang, S., Liu, H., and Li, J. (2021). Pharmacokinetics, Bioavailability, Excretion and Metabolism Studies of Akebia Saponin D in Rats: Causes of the Ultra-Low Oral Bioavailability and Metabolic Pathway. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.621003"},{"key":"ref_39","first-page":"216","article-title":"Selection of quality control components from Astragali Radix based on multi-component metabolism in rats","volume":"41","author":"Liu","year":"2018","journal-title":"Drug Eval. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12940","DOI":"10.3390\/molecules190912940","article-title":"Effect of chlorogenic acid on melanogenesis of B16 melanoma cells","volume":"19","author":"Li","year":"2014","journal-title":"Molecules"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jin, N., Liu, Y., Xiong, P.Y., Zhang, Y.Y., Mo, J.W., Huang, X.S., and Zhou, Y. (2022). Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking. Pharmaceuticals, 15.","DOI":"10.3390\/ph15091038"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tiwari, P., Ali, S.A., Puri, B., Kumar, A., and Datusalia, A.K. (2023). Tinospora cordifolia Miers enhances the immune response in mice immunized with JEV-vaccine: A network pharmacology and experimental approach. Phytomedicine, 119.","DOI":"10.1016\/j.phymed.2023.154976"},{"key":"ref_43","first-page":"176","article-title":"Progress in Microbial Conversion and Functional Activity of Soy Isoflavones","volume":"42","author":"Chen","year":"2021","journal-title":"Shipin Yanjiu Yu Kaifa"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"623","DOI":"10.2147\/DDDT.S180960","article-title":"Amine derivatives of furocoumarin induce melanogenesis by activating Akt\/GSK-3\u03b2\/\u03b2-catenin signal pathway","volume":"13","author":"Zang","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"391","DOI":"10.7150\/ijbs.17318","article-title":"Novel approaches to vitiligo treatment via modulation of mTOR and NF-\u03baB pathways in human skin melanocytes","volume":"13","author":"Wan","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Shin, S., Ko, J., Kim, M., Song, N., and Park, K. (2021). Morin Induces Melanogenesis via Activation of MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells. Molecules, 26.","DOI":"10.3390\/molecules26082150"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1002\/mnfr.201500822","article-title":"Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma","volume":"60","author":"Meyskens","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"10852","DOI":"10.1039\/D0FO01909G","article-title":"Akebia Saponin D suppresses inflammation in chondrocytes via the NRF2\/HO-1\/NF-\u03baB axis and ameliorates osteoarthritis in mice","volume":"11","author":"Gu","year":"2020","journal-title":"Food Funct."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Huang, J., Chen, X., and Xie, A. (2021). Formononetin ameliorates IL-13-induced inflammation and mucus formation in human nasal epithelial cells by activating the SIRT1\/Nrf2 signaling pathway. Mol. Med. Rep., 24.","DOI":"10.3892\/mmr.2021.12472"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.neuro.2021.05.014","article-title":"Formononetin attenuates H2O2-induced cell death through decreasing ROS level by PI3K\/Akt-Nrf2-activated antioxidant gene expression and suppressing MAPK-regulated apoptosis in neuronal SH-SY5Y cells","volume":"85","author":"Sugimoto","year":"2021","journal-title":"Neurotoxicology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.intimp.2015.09.006","article-title":"Antitumor and immunomodulatory activity of genkwanin on colorectal cancer in the APC(Min\/+) mice","volume":"29","author":"Wang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Niu, C., Yin, L., and Aisa, H.A. (2018). Novel Furocoumarin Derivatives Stimulate Melanogenesis in B16 Melanoma Cells by Up-Regulation of MITF and TYR Family via Akt\/GSK3\u03b2\/\u03b2-Catenin Signaling Pathways. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030746"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lei, Z., Yu, S., Ding, Y., Liang, J., Halifu, Y., Xiang, F., Zhang, D., Wang, H., Hu, W., and Li, T. (2020). Identification of key genes and pathways involved in vitiligo development based on integrated analysis. Medicine, 99.","DOI":"10.1097\/MD.0000000000021297"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Singh, M., Mansuri, M.S., Kadam, A., Palit, S.P., Dwivedi, M., Laddha, N.C., and Begum, R. (2021). Tumor Necrosis Factor-alpha affects melanocyte survival and melanin synthesis via multiple pathways in vitiligo. Cytokine, 140.","DOI":"10.1016\/j.cyto.2021.155432"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"600","DOI":"10.2174\/1574893614666191003125540","article-title":"Docking Techniques in Toxicology: An Overview","volume":"15","author":"Gupta","year":"2020","journal-title":"Curr. Bioinform."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2174\/1389450119666181022153016","article-title":"Molecular Docking: Challenges, Advances and its Use in Drug Discovery Perspective","volume":"20","author":"Saikia","year":"2019","journal-title":"Curr. Drug Targets"},{"key":"ref_57","first-page":"2232","article-title":"Challenges and prospect in research of Chinese materia medica network pharmacology","volume":"51","author":"Meng","year":"2020","journal-title":"Chin. Tradit. Herb. Drugs"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/12\/1716\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:36:48Z","timestamp":1760132208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/12\/1716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,11]]},"references-count":57,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ph16121716"],"URL":"https:\/\/doi.org\/10.3390\/ph16121716","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,11]]}}}