{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:21:56Z","timestamp":1774329716914,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia, through Grant Agreements with the University of Kragujevac\u2014Faculty of Medical Sciences","award":["No. 451-03-47\/2023-01\/200111"],"award-info":[{"award-number":["No. 451-03-47\/2023-01\/200111"]}]},{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia, through Grant Agreements with the University of Kragujevac\u2014Faculty of Medical Sciences","award":["14\/22"],"award-info":[{"award-number":["14\/22"]}]},{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia, through Grant Agreements with the University of Kragujevac\u2014Faculty of Medical Sciences","award":["01\/24"],"award-info":[{"award-number":["01\/24"]}]},{"name":"Junior Projects of the Faculty of Medical Sciences, University of Kragujevac, Serbia","award":["No. 451-03-47\/2023-01\/200111"],"award-info":[{"award-number":["No. 451-03-47\/2023-01\/200111"]}]},{"name":"Junior Projects of the Faculty of Medical Sciences, University of Kragujevac, Serbia","award":["14\/22"],"award-info":[{"award-number":["14\/22"]}]},{"name":"Junior Projects of the Faculty of Medical Sciences, University of Kragujevac, Serbia","award":["01\/24"],"award-info":[{"award-number":["01\/24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to prepare, characterize and assess the antioxidant activity of yellow bedstraw extracts (YBEs), focusing on identifying extracts with high antioxidant capacity. The selected extract was loaded into an oral liquid formulation and further investigated for its therapeutic potential in reducing blood pressure and associated complications in spontaneously hypertensive Wistar kyoto rats (SHR). Rats were divided into untreated SHR and SHR treated with a YBE-based oral formulation over four weeks. After treatment, blood pressure was measured, and cardiac function was assessed using the Langendorff technique to simulate ex vivo ischemic conditions. Prooxidant levels were assessed in plasma while antioxidant activity was evaluated in red blood cells. Histological analyses of heart, kidney, and liver samples were conducted to assess pathological changes induced by hypertension. Our results showed that the oral formulation loaded with ethanol YBE effectively reduced blood pressure, preserved myocardial function under ischemic stress, and decreased oxidative stress markers in blood. Importantly, our formulation with YBE demonstrated potential in attenuating structural kidney damage associated with hypertension. Overall, these findings suggest a cardioprotective effect of orally administered YBE formulation, highlighting its potential as an herbal supplement. However, clinical studies are warranted to validate these findings and explore the extract\u2019s suitability for clinical use.<\/jats:p>","DOI":"10.3390\/ijms25158346","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T08:02:27Z","timestamp":1722412947000},"page":"8346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hypotensive and Cardioprotective Potential of Yellow Bedstraw Extract-Based Oral Liquid in Spontaneously Hypertensive Rats"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-6085","authenticated-orcid":false,"given":"Jovana","family":"Bradic","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3048-4264","authenticated-orcid":false,"given":"Anica","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9906-436X","authenticated-orcid":false,"given":"Aleksandar","family":"Kocovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slobodanka","family":"Mitrovic","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0071-8376","authenticated-orcid":false,"given":"Vladimir","family":"Jakovljevic","sequence":"additional","affiliation":[{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"},{"name":"Department of Human Pathology, Sechenov First Moscow State Medical University, 8 Trubetskaya Street St., 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5386-8116","authenticated-orcid":false,"given":"Nevena","family":"Lazarevic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Bolevich","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Sechenov First Moscow State Medical University, 8 Trubetskaya Street St., 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Simanic","sequence":"additional","affiliation":[{"name":"Specialized Hospital for Rehabilitation and Orthopedic Prosthetics, Sokobanjska 17, 11000 Beograd, Serbia"},{"name":"Department of Physical Medicine and Rehabilitation, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica St., 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11906-020-1017-9","article-title":"Pathophysiology of hypertensive heart disease: Beyond left ventricular hypertrophy","volume":"22","author":"Nwabuo","year":"2020","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1097\/CM9.0000000000002863","article-title":"Global, regional, and national burden of hypertensive heart disease among older adults in 204 countries and territories between 1990 and 2019: A trend analysis","volume":"136","author":"Yang","year":"2023","journal-title":"Chin. Med. J."},{"key":"ref_3","unstructured":"(2024, July 17). Hypertension, World Health Organization (WHO). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hypertension."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Masenga, S.K., and Kirabo, A. (2023). Hypertensive heart disease: Risk factors, complications and mechanisms. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1205475"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Russo, E., Bussalino, E., Macci\u00f2, L., Verzola, D., Saio, M., Esposito, P., Leoncini, G., Pontremoli, R., and Viazzi, F. (2023). Non-Haemodynamic Mechanisms Underlying Hypertension-Associated Damage in Target Kidney Components. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119422"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Erdmann, J., Kujaci\u0144ski, M., and Wici\u0144ski, M. (2021). Beneficial Effects of Ursolic Acid and Its Derivatives-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions. Nutrients, 13.","DOI":"10.3390\/nu13113900"},{"key":"ref_7","first-page":"525","article-title":"Iridoids, flavonoids and monoterpene glycosides from Galium verum subsp","volume":"30","author":"Demirezer","year":"2006","journal-title":"Verum. Turk. J. Chem."},{"key":"ref_8","first-page":"331","article-title":"Antioxidant properties of Galium verum L. (Rubiaceae) extracts","volume":"5","author":"Isak","year":"2010","journal-title":"Cent. Eur. J. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Turcov, D., Barna, A.S., Trifan, A., Blaga, A.C., Tanas\u0103, A.M., and Suteu, D. (2022). Antioxidants from Galium verum as Ingredients for the Design of New Dermatocosmetic Products. Plants, 11.","DOI":"10.3390\/plants11192454"},{"key":"ref_10","first-page":"1238","article-title":"Effects of extracts of ginkgo biloba leaves on apelin concentration and expressions in plasma and myocardium of rats with myocardial ischemia injury","volume":"32","author":"Xiong","year":"2009","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/19476337.2019.1702104","article-title":"Bioactive compounds and antioxidant capacity of tea infusion prepared from whole and ground medicinal herb parts","volume":"18","author":"Islam","year":"2020","journal-title":"CyTA\u2014J. Food"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Munteanu, I.G., and Apetrei, C. (2021). Analytical Methods Used in Determining Antioxidant Activity: A Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073380"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rankovic, M., Krivokapic, M., Bradic, J., Petkovic, A., Zivkovic, V., Sretenovic, J., Jeremic, N., Bolevich, S., Kartashova, M., and Jeremic, J. (2021). New Insight Into the Cardioprotective Effects of Allium ursinum L. Extract against Myocardial Ischemia-Reperfusion Injury. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.690696"},{"key":"ref_14","first-page":"2142","article-title":"Galium verum\u2014A review","volume":"5","year":"2018","journal-title":"Indo Am. J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mocan, A., Diuzheva, A., B\u0103d\u0103r\u0103u, S., Moldovan, C., Andruch, V., Carradori, S., Campestre, C., Tartaglia, A., De Simone, M., and Vodnar, D. (2019). Liquid Phase and Microwave-Assisted Extractions for Multicomponent Phenolic Pattern Determination of Five Romanian Galium Species Coupled with Bioassays. Molecules, 24.","DOI":"10.3390\/molecules24071226"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Laanet, P.R., Saar-Reismaa, P., J\u00f5ul, P., Bragina, O., and Vaher, M. (2023). Phytochemical Screening and Antioxidant Activity of Selected Estonian Galium Species. Molecules, 28.","DOI":"10.3390\/molecules28062867"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"012010","DOI":"10.1088\/1755-1315\/718\/1\/012010","article-title":"The effect of different type of solvents on the antioxidant activity of fucoxanthin extract from brown seaweed Sargassum duplicatum","volume":"718","author":"Savira","year":"2021","journal-title":"IOP Conf. Ser. Earth Environ. Sci. (EES)"},{"key":"ref_18","first-page":"10640","article-title":"Correlation between Total Phenols Content, Antioxidant Power and Cytotoxicity","volume":"11","author":"Mohyelden","year":"2021","journal-title":"Biointerface Res. Appl. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Semenescu, A.D., Moac\u0103, E.A., Iftode, A., Dehelean, C.A., Tchiakpe-Antal, D.S., Vlase, L., Vlase, A.M., Muntean, D., and Chioiba\u015f, R. (2023). Phytochemical and Nutraceutical Screening of Ethanol and Ethyl Acetate Phases of Romanian Galium verum Herba (Rubiaceae). Molecules, 28.","DOI":"10.3390\/molecules28237804"},{"key":"ref_20","first-page":"1085","article-title":"Comparative study of polyphenolic content, antioxidant and antimicrobial activity of four Galium species (Rubiaceae)","volume":"9","author":"Vlase","year":"2014","journal-title":"Dig. J. Nanomater. Biostruct"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Antoniak, K., Studzi\u0144ska-Sroka, E., Szyma\u0144ski, M., Dudek-Makuch, M., Cielecka-Piontek, J., and Korybalska, K. (2023). Antiangiogenic, Anti-Inflammatory and Antioxidant Properties of Bidens tripartite Herb, Galium verum Herb and Rumex hydrolapathum Root. Molecules, 28.","DOI":"10.3390\/molecules28134966"},{"key":"ref_22","unstructured":"Aulton, M.E., and Taylor, K.M. (2013). Aulton\u2019s Pharmaceutics\u2014The Design and Manufacture of Medicine, Churchill Livingstone Elsevier. [5th ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cbi.2016.08.019","article-title":"Protective Effects of Ursolic Acid against Hepatotoxicity and Endothelial Dysfunction in Mice with Chronic High Choline Diet Consumption","volume":"258","author":"Li","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.biopha.2018.10.044","article-title":"Cardio-protective and antioxidant properties of caffeic acid and chlorogenic acid: Mechanistic role of angiotensin converting enzyme, cholinesterase and arginase activities in cyclosporine induced hypertensive rats","volume":"109","author":"Agunloye","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Behl, T., Bungau, S., Kumar, K., Zengin, G., Khan, F., Kumar, A., Kaur, R., Venkatachalam, T., Tit, D.M., and Vesa, C.M. (2020). Pleotropic Effects of Polyphenols in Cardiovascular System. Biomed. Pharmacother., 130.","DOI":"10.1016\/j.biopha.2020.110714"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1536\/ihj.54.176","article-title":"Chlorogenic acid attenuates ventricular remodeling after myocardial infarction in mice","volume":"54","author":"Kanno","year":"2013","journal-title":"Int. Heart J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"323","DOI":"10.5483\/BMBRep.2017.50.6.182","article-title":"Effects of chlorogenic acid on intracellular calcium regulation in lysophosphatidylcholine-treated endothelial cells","volume":"50","author":"Jung","year":"2017","journal-title":"BMB Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.aca.2009.01.037","article-title":"Measurement of xanthine oxidase inhibition activity of phenolics and flavonoids with a modified cupric reducing antioxidant capacity (CUPRAC) method","volume":"636","author":"Apak","year":"2009","journal-title":"Anal. Chim. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e191062","DOI":"10.1590\/s2175-97902022e191062","article-title":"The effects of methanol extract of Galium verum L. on cardiac redox state in hypertensive rats","volume":"58","author":"Milevic","year":"2022","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jbt.21832","article-title":"Molecular and biochemical evidence on the protective effects of quercetin in isoproterenol-induced acute myocardial injury in rats","volume":"31","author":"Kumar","year":"2017","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, Y.M., Zhang, Z.Y., and Wang, R.X. (2020). Protective Mechanisms of Quercetin against Myocardial Ischemia Reperfusion Injury. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00956"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mattera, R., Benvenuto, M., Giganti, M.G., Tresoldi, I., Pluchinotta, F.R., Bergante, S., Tettamanti, G., Masuelli, L., Manzari, V., and Modesti, A. (2017). Effects of Polyphenols on Oxidative Stress-Mediated Injury in Cardiomyocytes. Nutrients, 9.","DOI":"10.3390\/nu9050523"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1021\/np200060p","article-title":"Uncoupling and antioxidant effects of ursolic acid in isolated rat heart mitochondria","volume":"74","author":"Liobikas","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Amponsah-Offeh, M., Diaba-Nuhoho, P., Speier, S., and Morawietz, H. (2023). Oxidative Stress, Antioxidants and Hypertension. Antioxidants, 12.","DOI":"10.3390\/antiox12020281"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1080\/10520295.2019.1703220","article-title":"Antioxidant and anti-apoptotic effects of vitexilactone on cisplatin-induced nephrotoxicity in rats","volume":"95","author":"Deniz","year":"2020","journal-title":"Biotech. Histochem."},{"key":"ref_36","first-page":"262","article-title":"Effect of different ethanol concentrations, using different extraction techniques, on the antioxidant capacity of Lebanese Eryngium creticum","volume":"3","author":"Hijazi","year":"2015","journal-title":"J. Pharm. Chem. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1080\/13880200601113131","article-title":"Antioxidant activity and total phenolic content of some Brazilian species","volume":"45","author":"Brighente","year":"2007","journal-title":"Pharm. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.foodchem.2013.07.097","article-title":"Quantitative determination of plant phenolics in Urtica dioica extracts by high-\u0440erformance liquid chromatography coupled with tandem mass spectrometric detection","volume":"143","author":"Bekvalac","year":"2014","journal-title":"Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9268","DOI":"10.1021\/jf902205m","article-title":"Plantain (Plantago L.) species as novel sources of flavonoid antioxidants","volume":"57","author":"Beara","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1752-153X-5-34","article-title":"Antioxidant activity relationship of phenolic compounds in Hypericum perforatum L.","volume":"5","author":"Jovin","year":"2011","journal-title":"Chem. Cent. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8959","DOI":"10.1038\/s41598-022-13025-3","article-title":"Evaluation of color changes during stability studies using spectrophotometric chromaticity measurements versus visual examination","volume":"12","author":"Sakiroff","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1177\/0018578719844704","article-title":"Formulation and Stability Study of Omeprazole Oral Liquid Suspension for Pediatric Patients","volume":"55","author":"Boscolo","year":"2020","journal-title":"Hosp. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Jakovljevic, V., Milic, P., Bradic, J., Jeremic, J., Zivkovic, V., Srejovic, I., Nikolic Turnic, T., Milosavljevic, I., Jeremic, N., and Bolevich, S. (2018). Standardized Aronia melanocarpa Extract as Novel Supplement against Metabolic Syndrome: A Rat Model. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010006"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1681\/ASN.2008111204","article-title":"siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury","volume":"20","author":"Molitoris","year":"2009","journal-title":"J. Am. Soc. Nephrol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8346\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:26:48Z","timestamp":1760110008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,30]]},"references-count":44,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158346"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158346","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,30]]}}}