{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:35:29Z","timestamp":1780554929607,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Science and Technology, Taiwan","award":["MOST 110-2314-B-182-020-MY3"],"award-info":[{"award-number":["MOST 110-2314-B-182-020-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Garlic (Allium sativum) is a functional food, having hydrogen sulfide (H2S)-releasing capacity, which exhibits considerable effects on hypertension and gut microbiota. H2S is strongly associated with hypertension and chronic kidney disease (CKD). Maternal CKD leads to hypertension in adult rat progeny, which was linked to disruption of the gut microbiota. This study validated the benefits of perinatal garlic oil supplementation against offspring hypertension induced by maternal CKD via modulation of H2S signaling, nitric oxide (NO), and the gut microbiota. Before pregnancy, female rats received a 0.5% adenine diet for 3 weeks to develop an animal model to mimic human CKD. Garlic oil (100 mg\/kg\/day) or vehicle was administered to pregnant rats by oral gavage during gestation and lactation. Perinatal garlic oil supplementation protected against maternal CKD-induced hypertension in offspring at 12 weeks of age. The beneficial effects of garlic oil are associated with enhanced H2S signaling, increased NO bioavailability, and shifts in gut microbiota. Perinatal garlic oil supplementation reduces abundance of genera Variovorax, Nocardia, Sphingomonas, and Rhodococcus. Our findings provide insight into the role of early H2S-targeted intervention as a preventive strategy in hypertension for further translational research.<\/jats:p>","DOI":"10.3390\/nu14214624","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T03:53:07Z","timestamp":1667447587000},"page":"4624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Perinatal Garlic Oil Supplementation Averts Rat Offspring Hypertension Programmed by Maternal Chronic Kidney Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7059-6407","authenticated-orcid":false,"given":"You-Lin","family":"Tain","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 330, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8007-6077","authenticated-orcid":false,"given":"Chih-Yao","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 811, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3560-7470","authenticated-orcid":false,"given":"Guo-Ping","family":"Chang-Chien","sequence":"additional","affiliation":[{"name":"Institute of Environmental Toxin and Emerging-Contaminant, Cheng Shiu University, Kaohsiung 833, Taiwan"},{"name":"Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung 833, Taiwan"},{"name":"Super Micro Mass Research and Technology Center, Cheng Shiu University, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sufan","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Environmental Toxin and Emerging-Contaminant, Cheng Shiu University, Kaohsiung 833, Taiwan"},{"name":"Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung 833, Taiwan"},{"name":"Super Micro Mass Research and Technology Center, Cheng Shiu University, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-528X","authenticated-orcid":false,"given":"Chien-Ning","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.niox.2014.01.002","article-title":"The physiological role of hydrogen sulfide and beyond","volume":"41","author":"Kimura","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1089\/ars.2009.2657","article-title":"Interactions of multiple gas-transducing systems: Hallmarks and uncertainties of CO, NO, and H2S gas biology","volume":"13","author":"Kajimura","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.pharep.2017.10.007","article-title":"The smell of renal protection against chronic kidney disease: Hydrogen sulfide offers a potential stinky remedy","volume":"70","author":"Dugbartey","year":"2018","journal-title":"Pharmacol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1089\/ars.2013.5312","article-title":"Hydrogen Sulfide Signaling in the Gastrointestinal Tract","volume":"20","author":"Linden","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R592","DOI":"10.1152\/ajpregu.00421.2012","article-title":"Thiosulfate: A readily accessible source of hydrogen sulfide in oxygen sensing","volume":"305","author":"Olson","year":"2013","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.niox.2015.01.005","article-title":"Hydrogen sulfide in renal physiology, disease and transplantation\u2014The smell of renal protection","volume":"46","author":"Koning","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/MNH.0000000000000206","article-title":"Hydrogen sulfide in hypertension","volume":"25","author":"Hillebrands","year":"2016","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1017\/S2040174414000580","article-title":"Evolution of DOHaD: The impact of environmental health sciences","volume":"6","author":"Haugen","year":"2015","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1093\/ndt\/gfp320","article-title":"Kidney function and future risk for adverse pregnancy outcomes: A population-based study from HUNT II, Norway","volume":"24","author":"Munkhaugen","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1556\/2060.105.2018.1.6","article-title":"What we do and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman\u2019s Day","volume":"105","author":"Piccoli","year":"2018","journal-title":"Physiol. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41581-018-0018-2","article-title":"The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease","volume":"14","author":"Yang","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., Yang, H.W., Hou, C.Y., Chang-Chien, G.P., Lin, S., and Tain, Y.L. (2020). Maternal Adenine-Induced Chronic Kidney Disease Programs Hypertension in Adult Male Rat Offspring: Implications of Nitric Oxide and Gut Microbiome Derived Metabolites. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197237"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., Hou, C.Y., Chang-Chien, G.P., Lin, S., and Tain, Y.L. (2022). Dietary Supplementation with Cysteine during Pregnancy Rescues Maternal Chronic Kidney Disease-Induced Hypertension in Male Rat Offspring: The Impact of Hydrogen Sulfide and Microbiota-Derived Tryptophan Metabolites. Antioxidants, 11.","DOI":"10.3390\/antiox11030483"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/em.20474","article-title":"Biological properties of garlic and garlic-derived Organosulfur compounds","volume":"50","author":"Iciek","year":"2009","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2147\/IBPC.S51434","article-title":"Potential of garlic (Allium sativum) in lowering high blood pressure: Mechanisms of action and clinical relevance","volume":"7","author":"Ried","year":"2014","journal-title":"Integr. Blood Press. Control"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., and Tain, Y.L. (2018). Hydrogen Sulfide in Hypertension and Kidney Disease of Developmental Origins. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051438"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2001116","DOI":"10.1002\/mnfr.202001116","article-title":"Maternal Garlic Oil Supplementation Prevents High-Fat Diet-Induced Hypertension in Adult Rat Offspring: Implications of H2S-Generating Pathway in the Gut and Kidneys","volume":"65","author":"Hsu","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1161\/01.HYP.37.5.1199","article-title":"Gender differences in the regulation of blood pressure","volume":"37","author":"Reckelhoff","year":"2001","journal-title":"Hypertension"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., Hou, C.Y., Chang-Chien, G.P., Lin, S., and Tain, Y.L. (2020). Maternal N-Acetylcysteine Therapy Prevents Hypertension in Spontaneously Hypertensive Rat Offspring: Implications of Hydrogen Sulfide-Generating Pathway and Gut Microbiota. Antioxidants, 9.","DOI":"10.3390\/antiox9090856"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tain, Y.L., Hou, C.Y., Chang-Chien, G.P., Lin, S.F., and Hsu, C.N. (2022). Perinatal Propionate Supplementation Protects Adult Male Offspring from Maternal Chronic Kidney Disease-Induced Hypertension. Nutrients, 14.","DOI":"10.3390\/nu14163435"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.pharmthera.2007.03.002","article-title":"The L-arginine paradox: Importance of the L-arginine\/asymmetrical dimethylarginine ratio","volume":"114","author":"Scalera","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., and Tain, Y.L. (2021). Targeting the Renin\u2013Angiotensin\u2013Aldosterone System to Prevent Hypertension and Kidney Disease of Developmental Origins. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052298"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., and Tain, Y.L. (2021). Preventing Developmental Origins of Cardiovascular Disease: Hydrogen Sulfide as a Potential Target?. Antioxidants, 10.","DOI":"10.3390\/antiox10020247"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.ajog.2016.07.036","article-title":"Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal N(G)-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring","volume":"215","author":"Tain","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., and Tain, Y.L. (2019). Regulation of Nitric Oxide Production in the Developmental Programming of Hypertension and Kidney Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030681"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1097\/00004872-200310000-00015","article-title":"The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase","volume":"21","author":"Zhong","year":"2003","journal-title":"J. Hypertens."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e000387","DOI":"10.1161\/JAHA.113.000387","article-title":"Plasma free H2S levels are elevated in patients with cardiovascular disease","volume":"2","author":"Peter","year":"2013","journal-title":"J. Am. Heart Assoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1007\/s00431-020-03897-w","article-title":"The prognostic implications of perioperative endogenous hydrogen sulfide and nitric oxide levels in children with congenital heart disease complicated by pulmonary arterial hypertension","volume":"180","author":"Tan","year":"2021","journal-title":"Eur. J. Pediatr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1161\/ATVBAHA.120.314084","article-title":"Reactive Sulfur Species: A New Redox Player in Cardiovascular Pathophysiology","volume":"40","author":"Kolluru","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yang, G., and Wu, L. (2017). Trend in H2S Biology and Medicine Research\u2014A Bibliometric Analysis. Molecules, 22.","DOI":"10.3390\/molecules22122087"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Palmu, J., Lahti, L., and Niiranen, T. (2021). Targeting Gut Microbiota to Treat Hypertension: A Systematic Review. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18031248"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1161\/HYPERTENSIONAHA.118.11175","article-title":"Attenuation of Microbiotal Dysbiosis and Hypertension in a CRISPR\/Cas9 Gene Ablation Rat Model of GPER1","volume":"72","author":"Waghulde","year":"2018","journal-title":"Hypertension"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1093\/ajh\/hpab084","article-title":"Associations Between Peripheral Blood Microbiome and the Risk of Hypertension","volume":"34","author":"Jing","year":"2021","journal-title":"Am. J. Hypertens."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Han, Y., Huang, Z., Zhang, H., He, L., Sun, L., Liu, Y., Liu, F., and Xiao, L. (2020). Nocardiosis in glomerular disease patients with immunosuppressive therapy. BMC Nephrol., 21.","DOI":"10.1186\/s12882-020-02179-9"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00726-009-0445-2","article-title":"Luminal sulfide and large intestine mucosa: Friend or foe?","volume":"39","author":"Blachier","year":"2010","journal-title":"Amino Acids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/imr.12567","article-title":"Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease","volume":"279","author":"Pickard","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Shang, A., Cao, S.Y., Xu, X.Y., Gan, R.Y., Tang, G.Y., Corke, H., Mavumengwana, V., and Li, H.B. (2019). Bioactive Compounds and Biological Functions of Garlic (Allium sativum L.). Foods, 8.","DOI":"10.3390\/foods8070246"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/21\/4624\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:09:37Z","timestamp":1760144977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/21\/4624"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,2]]},"references-count":38,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["nu14214624"],"URL":"https:\/\/doi.org\/10.3390\/nu14214624","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,2]]}}}