{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T19:47:33Z","timestamp":1787600853017,"version":"build-2736575974"},"reference-count":46,"publisher":"Maad Rayan Publishing Company","issue":"2","content-domain":{"domain":["apb.tbzmed.ac.ir"],"crossmark-restriction":false},"short-container-title":["Adv Pharm Bull"],"published-print":{"date-parts":[[2024,7,25]]},"abstract":"<jats:p>Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (anti-VEGF) drugs, such as aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Methods: Various experiments were conducted to assess the Kavain\u2019s toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a laser-induced CNV mice model. To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Results: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P&lt;0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P&lt;0.05). These effects were statistically significantly enhanced in the Kavain plus aflibercept groups (P&lt;0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE)\/choroid complexes (P&lt;0.05). Mechanistically, Kavain decreased the activity of the hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1)\/VEGF-A\/ VEGF receptor 2 (VEGFR2) signaling pathway. Conclusion: Our study is the first to demonstrate Kavain\u2019s potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis.<\/jats:p>","DOI":"10.34172\/apb.2024.036","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T05:48:27Z","timestamp":1710568107000},"page":"469-482","update-policy":"https:\/\/doi.org\/10.34172\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1\u03b1\/VEGF-A\/VEGFR2 Signaling Pathway and Inhibiting Inflammation"],"prefix":"10.34172","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8393-2708","authenticated-orcid":true,"given":"Xi","family":"Chen","sequence":"first","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."},{"name":"Department of Ophthalmology, Northern Jiangsu People\u2019s Hospital, Yangzhou, 225001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Qin","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Bai","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsong","family":"Ren","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Nie","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumiao","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangyu","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Huang","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0681-5713","authenticated-orcid":true,"given":"Juxue","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China."},{"name":"Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 211166, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-3296","authenticated-orcid":true,"given":"Jin","family":"Yao","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0541-4635","authenticated-orcid":true,"given":"Qin","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"20123","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(18)32291-8"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1172\/jci144469"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.852519"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02433-x"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.06.130"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04225-0"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1097\/iae.0000000000003708"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2015.48"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109606"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2147-8"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082842"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03422-9"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16278"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1038\/nri3459"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-023-02634-5"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.03.009"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.11.029"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202204994"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23081907"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49383-8"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12784"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3354"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2017.08.003"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.0c00411"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.s64100"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2018.1556361"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2021.1973459"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.135"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11092445"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103632"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012005"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-020-09717-x"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2009.00838.x"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.3390\/nu12103044"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.22.13333"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.16.9.4604"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2020.1781193"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.3390\/cells10040878"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-1113-z"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.03.018"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02227.x"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11061562"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-25811-0"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-37619-7"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.11.12.8"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38563-w"}],"container-title":["Advanced Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/apb.tbzmed.ac.ir\/PDF\/apb-14-469.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/apb.tbzmed.ac.ir\/PDF\/apb-14-469.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T11:21:18Z","timestamp":1725362478000},"score":1,"resource":{"primary":{"URL":"https:\/\/apb.tbzmed.ac.ir\/Article\/apb-42520"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,11]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,7,25]]},"published-print":{"date-parts":[[2024,7,25]]}},"URL":"https:\/\/doi.org\/10.34172\/apb.2024.036","relation":{},"ISSN":["2228-5881","2251-7308"],"issn-type":[{"value":"2228-5881","type":"print"},{"value":"2251-7308","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,11]]},"assertion":[{"value":"Tabriz University of Medical Sciences","name":"journal_owner","label":"Journal Owner"},{"value":"Tabriz University of Medical Sciences","name":"journal_publisher","label":"Journal Publisher"},{"value":"2023-12-05","order":1,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}