{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:25:36Z","timestamp":1787574336133,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Oxidative stress is a key mechanism underlying nicotine-induced male reproductive dysfunction, yet evidence-based phytopharmacological interventions remain limited. Uncaria gambir Roxb., a catechin-rich medicinal plant from West Sumatra, Indonesia, exhibits strong antioxidant potential; however, a comprehensive multi-regional evaluation combined with in vivo androgenic assessment is lacking. This study aimed to characterize the antioxidant activity, phytochemical composition (HPLC-DAD), and antimicrobial properties of gambir extracts from three production regions (Halaban, Mungka, and Pesisir Selatan), to evaluate catechin pharmacokinetics in silico (PASS Online; SwissADME), and to assess dose-dependent effects in male Wistar rats exposed to nicotine (n = 36). The Halaban extract showed the highest antioxidant activity (IC50 = 6.99 \u00b1 0.28 \u00b5g mL\u22121) and catechin content (7.91 \u00b1 0.07 mg g\u22121). All extracts demonstrated broad-spectrum antimicrobial activity. PASS analysis predicted strong membrane integrity agonism (Pa = 0.950) and HMOX1 induction (Pa = 0.778), while SwissADME indicated favorable pharmacokinetic properties, including full Lipinski compliance and high gastrointestinal absorption. In the in vivo study, gambir Halaban extract at 300 mg kg\u22121 day\u22121 significantly increased follicle-stimulating hormone, luteinizing hormone, and testosterone levels compared to controls (p &lt; 0.05), exceeding baseline values and indicating HPG axis stimulation. A non-linear (hormetic) response was observed, with reduced efficacy at higher doses. These findings highlight bioactive-rich gambir as a promising multi-target natural antioxidant for mitigating oxidative-stress-related reproductive dysfunction, warranting further mechanistic and translational studies.<\/jats:p>","DOI":"10.3390\/ijms27177533","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"7533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hormetic Antioxidant Effects of Uncaria gambir on Male Reproductive Function: A Comprehensive Experimental and Computational Analysis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1035-6150","authenticated-orcid":false,"given":"Hendri","family":"Devita","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Health and Applied Science, Lincoln University College, No. 2, Jalan Stadium SS7\/15, Kelana Jaya, Petaling Jaya 47301, Selangor, Malaysia"},{"name":"Midwifery Program, Faculty of Health Science, Baiturrahmah University, Padang 25586, West Sumatra, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2215-3900","authenticated-orcid":false,"given":"Idris Adewale","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Health and Applied Science, Lincoln University College, No. 2, Jalan Stadium SS7\/15, Kelana Jaya, Petaling Jaya 47301, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-2939","authenticated-orcid":false,"given":"Yudha Endra","family":"Pratama","sequence":"additional","affiliation":[{"name":"Centre for Probiotic Biotechnology, Baiturrahmah University, Padang 25586, West Sumatra, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1478-5019","authenticated-orcid":false,"given":"Maryam Abimbola","family":"Mikail","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Health and Applied Science, Lincoln University College, No. 2, Jalan Stadium SS7\/15, Kelana Jaya, Petaling Jaya 47301, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148233","DOI":"10.1016\/j.foodchem.2026.148233","article-title":"Chemical Basis for the Antioxidant Activity of Piper Nigrum: Integrative Profiling of Volatile Components from Multi-Origin Black and White Pepper","volume":"507","author":"Lin","year":"2026","journal-title":"Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103363","DOI":"10.1016\/j.sjbs.2022.103363","article-title":"Trends and Challenges in Phytotherapy and Phytocosmetics for Skin Aging","volume":"29","author":"Ahmed","year":"2022","journal-title":"Saudi J. 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