{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T17:04:01Z","timestamp":1784653441865,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Hypertension-associated kidney injury is driven by oxidative stress, inflammation, fibrosis, and gut-derived uremic toxins via the gut\u2013kidney axis. Spent coffee grounds (SCG) represent a sustainable source of bioactive polyphenols with potential nephroprotective effects. This study aimed to characterize a bioactivity-guided SCG polyphenol fraction and evaluate its therapeutic potential. Methods: Bioactivity-guided fractionation was performed to enrich active polyphenols, followed by in silico target prediction and in vivo validation using L-NAME-induced hypertensive rats treated for 8 weeks. Renal function, oxidative stress, inflammatory and fibrotic markers, gut-derived metabolites, and endothelial function were assessed. Results: The enriched fraction was dominated by chlorogenic acid derivatives and showed predicted interactions with NF-\u03baB, Keap1\/Nrf2, TGF-\u03b2 receptor, ACE, and AT1 receptor. In hypertensive rats, treatment significantly lowered blood pressure, improved renal function, reduced oxidative stress, inflammation, fibrosis, and gut-derived uremic toxins, while restoring Nrf2 activity, short-chain fatty acid production, and endothelial function. Across multiple biological endpoints, the polyphenol-enriched fraction consistently demonstrated greater efficacy than the crude extract. Conclusions: SCG polyphenol fraction shows strong nephroprotective potential via gut\u2013kidney axis modulation and NF-\u03baB\/Nrf2\/TGF-\u03b2 regulation, supporting its development as a low-cost therapeutic candidate.<\/jats:p>","DOI":"10.3390\/antiox15070889","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:00:17Z","timestamp":1784548817000},"page":"889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Spent Coffee Grounds\u2019 Polyphenol Fraction and Its Potential as a Low-Cost Tool for Bioactivity-Guided Nephroprotective Modulation of Gut\u2013Kidney Axis and NF-\u03baB\/Nrf2\/TGF-\u03b2 Signaling in Hypertension-Associated Kidney Injury"],"prefix":"10.3390","volume":"15","author":[{"given":"Fahrul","family":"Nurkolis","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia"},{"name":"Medical Research Center of Indonesia, Surabaya 60281, Indonesia"},{"name":"Institute for Research and Community Service, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta 55281, Indonesia"},{"name":"Fahrul Institute for Innovation and Research (FIIR), Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante Saksono","family":"Harbuwono","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Referral Hospital, Jakarta 10430, Indonesia"},{"name":"Metabolic, Cardiovascular, and Aging Cluster, Faculty of Medicine Universitas Indonesia, The Indonesian Medical Education and Research Institute, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Wardhani","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension Division, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing Gadjah Mada University\/Dr. Sardjito General Hospital, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0544-2807","authenticated-orcid":false,"given":"Edwin","family":"Hadinata","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Medicine, Universitas Ciputra Surabaya, Surabaya 60219, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti Nur","family":"Rohmah","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension Division, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing Gadjah Mada University\/Dr. Sardjito General Hospital, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metalia","family":"Puspitasari","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension Division, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing Gadjah Mada University\/Dr. Sardjito General Hospital, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2287-3633","authenticated-orcid":false,"given":"Lucia","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples Federico II, Piazza Carlo di Borbone I, 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7555-0486","authenticated-orcid":false,"given":"Raffaele","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Naples Federico II, Piazza Carlo di Borbone I, 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny Pratama","family":"Kuswadi","sequence":"additional","affiliation":[{"name":"Nephrology and Hypertension Division, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing Gadjah Mada University\/Dr. Sardjito General Hospital, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond Rubianto","family":"Tjandrawinata","sequence":"additional","affiliation":[{"name":"School of Bioscience, Technology and Innovation, Atma Jaya Catholic University of Indonesia, Jakarta 12930, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eka","family":"Ginanjar","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5045-6562","authenticated-orcid":false,"given":"Pringgodigdo","family":"Nugroho","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia\/Dr. Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-3327","authenticated-orcid":false,"given":"Antonello","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano, 49, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lai, Y., Long, H., Liang, Z., Wu, C., Wu, L., Liu, 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