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Article

Anti-Diabetic Effect of a Shihunine-Rich Extract of Dendrobium loddigesii on 3T3-L1 Cells and db/db Mice by Up-Regulating AMPK–GLUT4–PPARα

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
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Molecules 2019, 24(14), 2673; https://doi.org/10.3390/molecules24142673
Received: 24 June 2019 / Revised: 19 July 2019 / Accepted: 22 July 2019 / Published: 23 July 2019
(This article belongs to the Special Issue Plant Bioactives in Preventing Chronic Diseases)
The stems of Dendrobium loddigesii, a Chinese herb, are often used to treat diabetes and its polar extract is rich in shihunine, a water-soluble Orchidaceae alkaloid, but little is known about the anti-diabetes effects and mechanism of shihunine. This study investigated the anti-diabetic effect of a shihunine-rich extract of D. loddigesii (DLS) based on 3T3-L1 cells and db/db mice. The underlying mechanisms were primarily explored using Western blot analysis and immunohistochemical staining. The 3T3-L1 cell experiments showed that DLS can reduce the intracellular accumulation of oil droplets as well as triglycerides (p < 0.001) and promote the 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2deoxyglucose (2-NBDG) uptake of 3T3-L1 cells (p < 0.001). The animal experiments confirmed that after 8 weeks of DLS treatment, the body weight, fasting blood sugar, and serum lipid levels of mice were significantly lowered, and the oral glucose tolerance test and serum insulin level were significantly improved compared to the no-treatment diabetes mellitus group. Further histomorphology observation led to the conclusion that the quantities of islet cells were significantly increased and the increase in adipose cell size was significantly suppressed. The immunohistochemical test of pancreatic tissue revealed that DLS inhibited the expression of cleaved cysteine aspartic acid-specific protease 3 (cleaved caspase-3). Western blot experiments showed that DLS had agonistic effects on adenosine monophosphate (AMP)-activated protein kinase phosphorylation (p-AMPK) and increased the expression levels of peroxisome proliferator-activated receptor α (PPARα) and glucose transporter 4 (GLUT4) in liver or adipose tissues. These data suggest that the shihunine-rich extract of D. loddigesii is an anti-diabetic fraction of D. loddigesii. Under our experimental condition, DLS at a dose of 50 mg/kg has good anti-diabetic efficacy. View Full-Text
Keywords: shihunine-rich extract of Dendrobium loddigesii; type 2 diabetes mellitus; db/db mice; 3T3-L1 cells; cleaved caspase-3/AMPK/GLUT4/PPARα; toxic activity shihunine-rich extract of Dendrobium loddigesii; type 2 diabetes mellitus; db/db mice; 3T3-L1 cells; cleaved caspase-3/AMPK/GLUT4/PPARα; toxic activity
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MDPI and ACS Style

Li, X.-W.; Huang, M.; Lo, K.; Chen, W.-L.; He, Y.-Y.; Xu, Y.; Zheng, H.; Hu, H.; Wang, J. Anti-Diabetic Effect of a Shihunine-Rich Extract of Dendrobium loddigesii on 3T3-L1 Cells and db/db Mice by Up-Regulating AMPK–GLUT4–PPARα. Molecules 2019, 24, 2673. https://doi.org/10.3390/molecules24142673

AMA Style

Li X-W, Huang M, Lo K, Chen W-L, He Y-Y, Xu Y, Zheng H, Hu H, Wang J. Anti-Diabetic Effect of a Shihunine-Rich Extract of Dendrobium loddigesii on 3T3-L1 Cells and db/db Mice by Up-Regulating AMPK–GLUT4–PPARα. Molecules. 2019; 24(14):2673. https://doi.org/10.3390/molecules24142673

Chicago/Turabian Style

Li, Xue-Wen, Meixiang Huang, Kakei Lo, Wei-Li Chen, Ying-Yan He, Yongli Xu, Huizhen Zheng, Haiyan Hu, and Jun Wang. 2019. "Anti-Diabetic Effect of a Shihunine-Rich Extract of Dendrobium loddigesii on 3T3-L1 Cells and db/db Mice by Up-Regulating AMPK–GLUT4–PPARα" Molecules 24, no. 14: 2673. https://doi.org/10.3390/molecules24142673

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