{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:21:02Z","timestamp":1791685262582,"version":"4.3.4"},"reference-count":30,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T00:00:00Z","timestamp":1544054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373135"],"award-info":[{"award-number":["81373135"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771690"],"award-info":[{"award-number":["81771690"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovative Talents in Science and Technology of fund program of universities of Henan","award":["15HASTIT040"],"award-info":[{"award-number":["15HASTIT040"]}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["182300410318"],"award-info":[{"award-number":["182300410318"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1\u2014a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (30 mg\/kg\/day, oral) with resveratrol (20 mg\/kg\/day, oral) reduced serum total cholesterol by 27.4% \u00b1 2.2%, and low-density lipoprotein-cholesterol by 31.6% \u00b1 3.2%, which was more effective than that of the resveratrol (8.4% \u00b1 2.3%, 6.6% \u00b1 2.1%) or berberine (10.5% \u00b1 1.95%, 9.8% \u00b1 2.58%) monotherapy (p &lt; 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 \u00b5mol\/L or 20 \u00b5mol\/L berberine combined with 25 \u00b5mol\/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.<\/jats:p>","DOI":"10.3390\/ijms19123903","type":"journal-article","created":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T03:46:14Z","timestamp":1544154374000},"page":"3903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6360-140X","authenticated-orcid":false,"given":"Xiaofei","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China"},{"name":"Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China"},{"name":"Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China"},{"name":"Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China"},{"name":"Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/35007508","article-title":"Obesity as a medical problem","volume":"404","author":"Kopelman","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0140-6736(09)61794-3","article-title":"The metabolic syndrome","volume":"375","author":"Eckel","year":"2010","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/0140-6736(91)91164-P","article-title":"Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians","volume":"337","author":"McKeigue","year":"1991","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s11684-013-0262-6","article-title":"Mechanisms of insulin resistance in obesity","volume":"7","author":"Ye","year":"2013","journal-title":"Front. 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