Anti-hypercholesterolemic Effects and a Good Safety Profile of SCM-198 in Animals: From ApoE Knockout Mice to Rhesus Monkeys
Although several lipid-lowering agents have been introduced for the treatment of atherosclerosis (AS), currently marketed medications have not solved the problem completely. This study aims to investigate the effects of leonurine (SCM-198) on dyslipidemia in mammals with ApoE knockout (ApoE-/-) mice...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01468/full |
| _version_ | 1818589909810675712 |
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| author | Rinkiko Suguro Rinkiko Suguro Siyao Chen Di Yang Zunyuan Yang Lei Miao Weijun Wu Wen Zeng Xinhua Liu Yi Zhun Zhu Yi Zhun Zhu |
| author_facet | Rinkiko Suguro Rinkiko Suguro Siyao Chen Di Yang Zunyuan Yang Lei Miao Weijun Wu Wen Zeng Xinhua Liu Yi Zhun Zhu Yi Zhun Zhu |
| author_sort | Rinkiko Suguro |
| collection | DOAJ |
| description | Although several lipid-lowering agents have been introduced for the treatment of atherosclerosis (AS), currently marketed medications have not solved the problem completely. This study aims to investigate the effects of leonurine (SCM-198) on dyslipidemia in mammals with ApoE knockout (ApoE-/-) mice, New Zealand white rabbits and senile Rhesus monkeys fed with high fat diet were dosed daily with leonurine or atorvastatin. The serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined. Moreover, in Rhesus monkeys, bodyweight, arterial ultrasound of right common carotid artery, Apolipoprotein A1 (ApoA1) and ApoB levels, hematologic and toxicological examinations were detected. Serum TC and TG in both mice and rabbits were significantly reduced by SCM-198 and atorvastatin. In the 10 mg/kg SCM-198 group of monkeys, maximum TC reduction of 24.05% was achieved at day 150, while 13.16% LDL reduction achieved at day 60, without arterial morphologic changes or adverse events. Atorvastatin (1.2 mg/kg) showed similar effects as SCM-198 in improving lipid profiles in monkeys, yet its long-term use could induce tolerance. Furthermore, leonurine suppressed genes expression of fatty acid synthesis, such as fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD-1), sterol regulatory element-binding protein (SREBF) in liver in high fat diet feeding ApoE-/- mice. SCM-198, with a reliable safety profile, is of high value in improving lipid profiles in mammals, providing an alternative to a substantial population who are statin-intolerant. |
| first_indexed | 2024-12-16T09:48:09Z |
| format | Article |
| id | doaj.art-d789ad7dbf664c74bdb0e6cd658d5890 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-16T09:48:09Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d789ad7dbf664c74bdb0e6cd658d58902022-12-21T22:36:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-12-01910.3389/fphar.2018.01468414998Anti-hypercholesterolemic Effects and a Good Safety Profile of SCM-198 in Animals: From ApoE Knockout Mice to Rhesus MonkeysRinkiko Suguro0Rinkiko Suguro1Siyao Chen2Di Yang3Zunyuan Yang4Lei Miao5Weijun Wu6Wen Zeng7Xinhua Liu8Yi Zhun Zhu9Yi Zhun Zhu10Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, ChinaSchool of Pharmacy, Macau University of Science and Technology – State Key Laboratory of Quality Research in Chinese Medicine, Taipa, MacauDepartment of Cardiac Surgery, Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, ChinaSichuan Primed Co., Ltd., Chengdu, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, ChinaSichuan Primed Co., Ltd., Chengdu, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, ChinaSchool of Pharmacy, Macau University of Science and Technology – State Key Laboratory of Quality Research in Chinese Medicine, Taipa, MacauAlthough several lipid-lowering agents have been introduced for the treatment of atherosclerosis (AS), currently marketed medications have not solved the problem completely. This study aims to investigate the effects of leonurine (SCM-198) on dyslipidemia in mammals with ApoE knockout (ApoE-/-) mice, New Zealand white rabbits and senile Rhesus monkeys fed with high fat diet were dosed daily with leonurine or atorvastatin. The serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined. Moreover, in Rhesus monkeys, bodyweight, arterial ultrasound of right common carotid artery, Apolipoprotein A1 (ApoA1) and ApoB levels, hematologic and toxicological examinations were detected. Serum TC and TG in both mice and rabbits were significantly reduced by SCM-198 and atorvastatin. In the 10 mg/kg SCM-198 group of monkeys, maximum TC reduction of 24.05% was achieved at day 150, while 13.16% LDL reduction achieved at day 60, without arterial morphologic changes or adverse events. Atorvastatin (1.2 mg/kg) showed similar effects as SCM-198 in improving lipid profiles in monkeys, yet its long-term use could induce tolerance. Furthermore, leonurine suppressed genes expression of fatty acid synthesis, such as fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD-1), sterol regulatory element-binding protein (SREBF) in liver in high fat diet feeding ApoE-/- mice. SCM-198, with a reliable safety profile, is of high value in improving lipid profiles in mammals, providing an alternative to a substantial population who are statin-intolerant.https://www.frontiersin.org/article/10.3389/fphar.2018.01468/fullleonurineSCM-198atherosclerosisdyslipidemiaRhesus monkeys |
| spellingShingle | Rinkiko Suguro Rinkiko Suguro Siyao Chen Di Yang Zunyuan Yang Lei Miao Weijun Wu Wen Zeng Xinhua Liu Yi Zhun Zhu Yi Zhun Zhu Anti-hypercholesterolemic Effects and a Good Safety Profile of SCM-198 in Animals: From ApoE Knockout Mice to Rhesus Monkeys Frontiers in Pharmacology leonurine SCM-198 atherosclerosis dyslipidemia Rhesus monkeys |
| title | Anti-hypercholesterolemic Effects and a Good Safety Profile of SCM-198 in Animals: From ApoE Knockout Mice to Rhesus Monkeys |
| title_full | Anti-hypercholesterolemic Effects and a Good Safety Profile of SCM-198 in Animals: From ApoE Knockout Mice to Rhesus Monkeys |
| title_fullStr | Anti-hypercholesterolemic Effects and a Good Safety Profile of SCM-198 in Animals: From ApoE Knockout Mice to Rhesus Monkeys |
| title_full_unstemmed | Anti-hypercholesterolemic Effects and a Good Safety Profile of SCM-198 in Animals: From ApoE Knockout Mice to Rhesus Monkeys |
| title_short | Anti-hypercholesterolemic Effects and a Good Safety Profile of SCM-198 in Animals: From ApoE Knockout Mice to Rhesus Monkeys |
| title_sort | anti hypercholesterolemic effects and a good safety profile of scm 198 in animals from apoe knockout mice to rhesus monkeys |
| topic | leonurine SCM-198 atherosclerosis dyslipidemia Rhesus monkeys |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01468/full |
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