{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:22:49Z","timestamp":1760059369019,"version":"build-2065373602"},"reference-count":78,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: This study aimed to explore the therapeutic potential of a dietary regimen of banaba leaf extract (BNB), policosanol (PCO, Raydel\u00ae), and their combination (BNB+PCO), to mitigate high cholesterol (HC) and high galactose (HG) diet-induced dyslipidemia, hyperglycemia, oxidative stress, senescence, and organ damage in zebrafish (Danio rerio). Methodology: Zebrafish (n = 28\/group) were fed with HC (4% w\/w)+HG (30% w\/w) or HC+HG supplemented either with BNB (0.1% w\/w) or PCO (0.1% w\/w) or BNB+PCO (0.1% w\/w each). Following 6 weeks of dietary intervention, biochemical and histopathological examinations across the groups were performed. Results: Post 6 weeks of consumption, the BNB+PCO group exhibited a significant 40% decrease in body weight (BW) relative to the BW of the HC+HG group, while the BNB or PCO groups displayed nonsignificant changes in BW. Both BNB and PCO reduced HC+HG-induced dyslipidemia and hyperglycemia; however, co-administration (BNB+PCO) demonstrated a significantly greater therapeutic effect in countering these conditions compared to either BNB or PCO alone. A similar effect of the BNB+PCO combination was observed on the elevation of plasma sulfhydryl content, paraoxonase (PON), and ferric ion reduction activity (FRA), with notably ~1.2-times (p &lt; 0.01) higher levels compared to their corresponding values observed in the BNB or PCO groups. Significantly diminished plasma AST, ALT, hepatic interleukin 6 (IL-6) levels, and fatty liver changes were observed in response to BNB+PCO, compared to either BNB or PCO alone. Also, BNB+PCO displayed a higher curative effect against HC+HG-induced impairment of tissue regeneration than BNB or PCO alone. A notable effect of BNB+PCO was perceived in protecting kidneys, testis, and ovary damage. Consistently, BNB+PCO showed a profound impact on mitigating HC+HG elevated reactive oxygen species (ROS) generation, apoptosis, cellular senescence, and accumulation of brain-binding lipid proteins (BLBPs) and 4-hydroxynoneal (4-HNE) in the brain. Conclusions: The findings highlight the synergistic effects of the BNB and PCO combination to mitigate the adversity posed by the consumption of the HC+HG diet.<\/jats:p>","DOI":"10.3390\/ph18060860","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T09:13:01Z","timestamp":1749460381000},"page":"860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Effect of Banaba Leaf Extract and Policosanol (Raydel\u00ae) Ameliorate High Cholesterol and High Galactose-Diet Induced Adverse Events in Zebrafish"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-4140","authenticated-orcid":false,"given":"Kyung-Hyun","family":"Cho","sequence":"first","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Hyuk","family":"Lee","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunki","family":"Lee","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashutosh","family":"Bahuguna","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krismala","family":"Djayanti","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheolmin","family":"Jeon","sequence":"additional","affiliation":[{"name":"Raydel Research Institute, Medical Innovation Complex, Daegu 41061, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1002\/iub.262","article-title":"Galactose toxicity in animals","volume":"61","author":"Lai","year":"2009","journal-title":"IUBMB Life"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1111\/jcmm.13472","article-title":"Effects of d-galactose-induced ageing on the heart and its potential interventions","volume":"22","author":"Palee","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Conte, F., van Buuringen, N., Voermans, N.C., and Lefeber, D.J. (2021). Galactose in human metabolism, glycosylation and congenital metabolic diseases: Time for a closer look. Biochim. Biophys. Acta (BBA) Gen. Subj., 1865.","DOI":"10.1016\/j.bbagen.2021.129898"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Khalid, M., Petroianu, G., and Adem, A. (2022). Advanced glycation end products and diabetes mellitus: Mechanisms and perspectives. Biomolecules, 12.","DOI":"10.3390\/biom12040542"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106891","DOI":"10.1016\/j.vascn.2020.106891","article-title":"Characterization of an i.p. D-galactose-induced cataract model in rats","volume":"107","author":"Zhong","year":"2021","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_6","first-page":"56","article-title":"High fat diet for induced dyslipidemia and cardiac pathological alterations in Wistar rats compared to Sprague Dawley rats","volume":"31","author":"Udomkasemsab","year":"2019","journal-title":"Clin. Investig. Arterioscler."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.cgh.2018.04.023","article-title":"Treatment of dyslipidemia in common liver diseases","volume":"16","author":"Speliotes","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"612","DOI":"10.4093\/dmj.2023.0067","article-title":"Dyslipidemia in patients with chronic kidney disease: An updated overview","volume":"47","author":"Suh","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.tjog.2019.05.003","article-title":"Dyslipidemia involvement in the development of polycystic ovary syndrome","volume":"58","author":"Liu","year":"2019","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"48","DOI":"10.4103\/2230-8210.126532","article-title":"Study of pattern of dyslipidemia and its correlation with cardiovascular risk factors in patients with proven coronary artery disease","volume":"18","author":"Mahalle","year":"2014","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/s41374-021-00626-1","article-title":"Steatosis, inflammasome upregulation, and fibrosis are attenuated in miR-155 deficient mice in a high fat-cholesterol-sugar diet-induced model of NASH","volume":"101","author":"Bala","year":"2021","journal-title":"Lab. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.pcad.2022.05.003","article-title":"Benefits and drawbacks of statins and non-statin lipid lowering agents in carotid artery disease","volume":"73","author":"Paraskevas","year":"2022","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1161\/CIRCRESAHA.118.312782","article-title":"Statin toxicity","volume":"124","author":"Ward","year":"2019","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.1021\/jf801566r","article-title":"Cholesterol\u2014Lowering nutraceuticals and functional foods","volume":"56","author":"Chen","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Luo, Y., Zeng, Y., Peng, J., Zhang, K., Wang, L., Feng, T., Nhamdriel, T., and Fan, G. (2023). Phytochemicals for the treatment of metabolic diseases: Evidence from clinical studies. Biomed. Pharmacother., 165.","DOI":"10.1016\/j.biopha.2023.115274"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100058","DOI":"10.1016\/j.ccmp.2022.100058","article-title":"A review of the effects of policosanol on metabolic syndrome","volume":"2","author":"Olatunji","year":"2022","journal-title":"Clin. Complement. Med. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1700280","DOI":"10.1002\/mnfr.201700280","article-title":"Efficacy and safety of sugarcane policosanol on dyslipidemia: A meta-analysis of randomized controlled trials","volume":"62","author":"Gong","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"889","DOI":"10.3892\/ijmm.2017.2907","article-title":"Consumption of policosanol enhances HDL functionality via CETP inhibition and reduces blood pressure and visceral fat in young and middle-aged subjects","volume":"39","author":"Kim","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_19","first-page":"117","article-title":"Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus","volume":"29","author":"Crespo","year":"1999","journal-title":"Int. J. Clin. Pharmacol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"926087","DOI":"10.1155\/2014\/926087","article-title":"Policosanol attenuates statin-induced increases in serum proprotein convertase subtilisin\/kexin type 9 when combined with atorvastatin","volume":"2014","author":"Guo","year":"2014","journal-title":"Evid. Based Compl. Alt."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.amjms.2018.06.014","article-title":"Efficacy and safety of policosanol plus fenofibrate combination therapy in elderly patients with mixed dyslipidemia: A randomized, controlled clinical study","volume":"356","author":"Wang","year":"2018","journal-title":"Am. J. Med. Sci."},{"key":"ref_22","first-page":"207","article-title":"\u201cCopycat-policosanols\u201d versus genuine policosanol","volume":"38","author":"Canavaciolo","year":"2007","journal-title":"Rev. CENIC Cienc. Qu\u00edm."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Cho, K.-H., Baek, S.H., Nam, H.-S., Kim, J.-E., Kang, D.-J., Na, H., and Zee, S. (2023). Cuban sugar cane wax alcohol exhibited enhanced antioxidant, anti-glycation and anti-inflammatory activity in reconstituted high-density lipoprotein (rHDL) with improved structural and functional correlations: Comparison of various policosanols. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043186"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cho, K.-H., Bahuguna, A., Kim, J.-E., and Lee, S.H. (2024). Efficacy assessment of five policosanol brands and damage to vital organs in hyperlipidemic zebrafish by six-week supplementation: Highlighting the toxicity of red yeast rice and safety of Cuban policosanol (Raydel\u00ae). Pharmaceuticals, 17.","DOI":"10.3390\/ph17060714"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1089\/jmf.2019.4491","article-title":"Policosanol attenuates cholesterol synthesis via AMPK activation in hypercholesterolemic rats","volume":"22","author":"Nam","year":"2019","journal-title":"J. Med. Food"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12944-018-0682-z","article-title":"Policosanol composition, antioxidant and anti-arthritic activities of milk thistle (Silybium marianum L.) oil at different seed maturity stages","volume":"17","author":"Harrabi","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/ptr.3664","article-title":"A review of the efficacy and safety of banaba (Lagerstroemia speciosa L.) and corosolic acid","volume":"26","author":"Stohs","year":"2012","journal-title":"Phytother. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mousa, A.M., El-Sammad, N.M., Abdel-Halim, A.H., Anwar, N., Khalil, W.K.B., Nawwar, M., Hashim, A.N., Elsayed, E.A., and Hassan, S.K. (2019). Lagerstroemia speciosa (L.) pers leaf extract attenuates lung tumorigenesis via alleviating oxidative stress, inflammation and apoptosis. Biomolecules, 9.","DOI":"10.3390\/biom9120871"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.tifs.2017.11.012","article-title":"Dietary triterpenes in the treatment of type 2 diabetes: To date","volume":"72","author":"Teng","year":"2018","journal-title":"Trends Food Sci. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"100548","DOI":"10.1016\/j.obmed.2024.100548","article-title":"Multifaceted therapeutic potential of corosolic acid: A novel bioactive compound","volume":"49","author":"Singh","year":"2024","journal-title":"Obes. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cho, K.-H., Lee, S.H., Lee, Y., Bahuguna, A., and Kim, J.-E. (2025). Synergistic efficacy of policosanol (Raydel\u00ae) and banaba leaf extract to treat hyperglycemia and dyslipidemia in streptozotocin-induced diabetic and hyperlipidemic zebrafish (Danio rerio): Protection of liver and kidney with enhanced tissue regeneration. Pharmaceuticals, 18.","DOI":"10.3390\/ph18030362"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41573-021-00210-8","article-title":"Zebrafish disease models in drug discovery: From preclinical modelling to clinical trials","volume":"20","author":"Patton","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hoo, J.Y., Kumari, Y., Shaikh, M.F., Hue, S.M., and Goh, B.H. (2016). Zebrafish: A versatile animal model for fertility research. BioMed Res. Int., 2016.","DOI":"10.1155\/2016\/9732780"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sanni, O., Fasemore, T., and Nkomozepi, P. (2024). Non-genetic-induced zebrafish model for type 2 diabetes with emphasis on tools in model validation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010240"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"42","DOI":"10.12997\/jla.2021.10.1.42","article-title":"Zebrafish as an emerging model for dyslipidemia and associated diseases","volume":"10","author":"Ka","year":"2021","journal-title":"J. Lipid Atheroscler."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhang, C., Willett, C., and Fremgen, T. (2003). Zebrafish: An animal model for toxicological studies. Current Protocols in Toxicology, John Wiley & Sons. Unit 1.7.","DOI":"10.1002\/0471140856.tx0107s17"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.trsl.2013.09.004","article-title":"Zebrafish models of dyslipidemia: Relevance to atherosclerosis and angiogenesis","volume":"163","author":"Fang","year":"2014","journal-title":"Transl. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mokgalaboni, K., Lebelo, L.S., Modjadji, P., and Ghaffary, S. (2023). Okra ameliorates hyperglycaemia in pre-diabetic and type 2 diabetic patients: A systematic review and meta-analysis of the clinical evidence. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1132650"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mokgalaboni, K., Phoswa, W.N., Mokgalabone, T.T., Dlamini, S., Ndhlala, A.R., Modjadji, P., and Lebelo, S.L. (2024). Effect of Abelmoschus esculentus L. (Okra) on dyslipidemia: Systematic review and meta-analysis of clinical studies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252010922"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"293","DOI":"10.20307\/nps.2019.25.4.293","article-title":"Physiological activities of policosanol extracted from sugarcane wax","volume":"25","author":"Jang","year":"2019","journal-title":"Nat. Prod. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.20945\/2359-3997000000199","article-title":"High-sugar diet leads to obesity and metabolic diseases in ad libitum-fed rats irrespective of caloric intake","volume":"64","author":"Evangelista","year":"2020","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Aragno, M., and Mastrocola, R. (2017). Dietary sugars and endogenous formation of advanced glycation end products: Emerging mechanisms of disease. Nutrients, 9.","DOI":"10.20944\/preprints201702.0047.v1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3390\/endocrines4030044","article-title":"Anti-dyslipidemic and anti-diabetic properties of corosolic acid: A narrative review","volume":"4","author":"Cannarella","year":"2023","journal-title":"Endocrines"},{"key":"ref_44","unstructured":"Throne Research (2004). Monograph. Policosanol. Altern. Med. Rev., 9, 312\u2013317."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.nutres.2017.05.013","article-title":"Hexacosanol reduces plasma and hepatic cholesterol by activating AMP-activated protein kinase and suppression of sterol regulatory element-binding protein-2 in HepG2 and C57BL\/6J mice","volume":"43","author":"Lee","year":"2017","journal-title":"Nutr. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Imerb, N., Thonusin, C., Pratchayasakul, W., Arunsak, B., Nawara, W., Ongnok, B., Aeimlapa, R., Charoenphandhu, N., Chattipakorn, N., and Chattipakorn, S.C. (2022). D-galactose-induced aging aggravates obesity-induced bone dyshomeostasis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-12206-4"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S267","DOI":"10.4103\/2230-8210.104057","article-title":"Antioxidants and diabetes","volume":"16","author":"Bajaj","year":"2012","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"111709","DOI":"10.1016\/j.diabres.2024.111709","article-title":"The effects of policosanol supplementation on blood glucose: A systematic sreview and dose-response meta-analysis of randomized controlled trials","volume":"212","author":"Amini","year":"2024","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_49","first-page":"181","article-title":"Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice","volume":"23","author":"Yang","year":"2016","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3164\/jcbn.15-3","article-title":"Advanced glycation end products: Modifiable environmental factors profoundly mediate insulin resistance","volume":"57","author":"Ottum","year":"2015","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0975-3575(10)80109-9","article-title":"In Vitro antioxidant studies of Lagerstroemia speciosa leaves","volume":"2","author":"Pareek","year":"2010","journal-title":"Pharmacogn. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.apjtb.2017.08.010","article-title":"Nrf2 activator corosolic acid meliorates alloxan induced diabetic nephropathy in mice","volume":"7","author":"Tidke","year":"2017","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_53","first-page":"125","article-title":"Antioxidant effect of Lagerstroemia speciosa Pers (Banaba) leaf extract in streptozotocin-induced diabetic mice","volume":"49","author":"Saumya","year":"2011","journal-title":"Indian J. Exp. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Cho, K.-H., Kim, J.-E., Nam, H.-S., Kang, D.-J., and Baek, S.-H. (2023). Comparison of policosanols via incorporation into reconstituted high-density lipoproteins: Cuban policosanol (Raydel\u00ae) exerts the highest antioxidant, anti-glycation, and anti-inflammatory activity. Molecules, 28.","DOI":"10.3390\/molecules28186715"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wang, K., Ge, Y., Yang, Y., Li, Z., Liu, J., Xue, Y., Zhang, Y., Pang, X., Ngan, A.H.W., and Tang, B. (2024). Vascular endothelial cellular mechanics under hyperglycemia and its role in tissue regeneration. Regen. Biomater., 11.","DOI":"10.1093\/rb\/rbae004"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Accipe, L., Abadie, A., Neviere, R., and Bercion, S. (2023). Antioxidant activities of natural compounds from caribbean plants to enhance diabetic wound healing. Antioxidants, 12.","DOI":"10.3390\/antiox12051079"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"111372","DOI":"10.1016\/j.exger.2021.111372","article-title":"D-galactose-induced liver aging model: Its underlying mechanisms and potential therapeutic interventions","volume":"150","author":"Azman","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.ejphar.2016.09.031","article-title":"Corosolic acid protects hepatocytes against ethanol-induced damage by modulating mitogen-activated protein kinases and activating autophagy","volume":"791","author":"Guo","year":"2016","journal-title":"Eur. J. Pharm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1097\/00041552-200205000-00009","article-title":"Hyperlipidemia in kidney disease causes and consequences","volume":"11","author":"Sahadevan","year":"2002","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Liu, C.-Y., Chang, T.-C., Lin, S.-H., Wu, S.-T., Cha, T.-L., and Tsao, C.-W. (2020). Metformin ameliorates testicular function and spermatogenesis in male mice with high-fat and high-cholesterol diet-induced obesity. Nutrients, 12.","DOI":"10.3390\/nu12071932"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"175072","DOI":"10.1016\/j.ejphar.2022.175072","article-title":"L-theanine protects rat kidney from D-galactose-induced injury via inhibition of the AGEs\/RAGE signaling pathway","volume":"927","author":"Zeng","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8916","DOI":"10.18632\/aging.202709","article-title":"Protective effects of ginseng stem-leaf saponins on D-galactose-induced reproductive injury in male mice","volume":"13","author":"Zhang","year":"2021","journal-title":"Aging"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4161\/oxim.3.2.11148","article-title":"Advanced glycation end products, oxidative stress and diabetic nephropathy","volume":"3","author":"Yamagishi","year":"2010","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.3109\/13880209.2015.1093510","article-title":"Chlorogenic acid protects D-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice","volume":"54","author":"Feng","year":"2016","journal-title":"Pharm. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Garavaglia, M.L., Giustarini, D., Colombo, G., Reggiani, F., Finazzi, S., Calatroni, M., Landoni, L., Portinaro, N.M., Milzani, A., and Badalamenti, S. (2022). Blood thiol redox state in chronic kidney disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052853"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41419-020-02751-z","article-title":"Oxidized-LDL inhibits testosterone biosynthesis by affecting mitochondrial function and the p38 MAPK\/COX-2 signaling pathway in Leydig cells","volume":"11","author":"Jing","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_67","first-page":"1190","article-title":"Impact of caffeic acid on the testicular damages in D-galactose-induced aging model in mice","volume":"25","author":"Khoshdel","year":"2022","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.biopha.2018.04.003","article-title":"Impact of stress on female reproductive health disorders: Possible beneficial effects of shatavari (Asparagus racemosus)","volume":"103","author":"Pandey","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"117830","DOI":"10.1016\/j.lfs.2020.117830","article-title":"The role of advanced glycation end products in human infertility","volume":"255","author":"Zhu","year":"2020","journal-title":"Life Sci."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"D\u2019Cunha, N.M., Sergi, D., Lane, M.M., Naumovski, N., Gamage, E., Rajendran, A., Kouvari, M., Gauci, S., Dissanayka, T., and Marx, W. (2022). The effects of dietary advanced glycation end-products on neurocognitive and mental disorders. Nutrients, 14.","DOI":"10.3390\/nu14122421"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.bbr.2015.12.041","article-title":"Oral administration of D-galactose induces cognitive impairments and oxidative damage in rats","volume":"302","author":"Budni","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.physbeh.2015.11.016","article-title":"Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat","volume":"154","author":"Qu","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Guo, Q., Kawahata, I., Cheng, A., Jia, W., Wang, H., and Fukunaga, K. (2022). Fatty acid-binding proteins: Their roles in ischemic stroke and potential as drug targets. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179648"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Wang, F.-X., Li, H.-Y., Li, Y.-Q., and Kong, L.-D. (2020). Can medicinal plants and bioactive compounds combat lipid peroxidation product 4-HNE-induced deleterious effects?. Biomolecules, 10.","DOI":"10.3390\/biom10010146"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/s41392-023-01673-4","article-title":"Gut liver brain axis in diseases: The implications for therapeutic interventions","volume":"8","author":"Yan","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1042\/CS20160927","article-title":"Kidney-brain axis inflammatory crosstalk: From bench to bedside","volume":"131","author":"Miranda","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_77","unstructured":"(2024, November 11). How Does the Liver Affect Brain Health?. Available online: https:\/\/www.alzdiscovery.org\/cognitive-vitality\/blog\/how-does-the-liver-affect-brain-health#ref-4."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"prot4986","DOI":"10.1101\/pdb.prot4986","article-title":"Hematoxylin and eosin staining of tissue and cell sections","volume":"2008","author":"Fischer","year":"2008","journal-title":"Cold Spring Harb. 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