Dataset Information

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

ABSTRACT: 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 ? (PPAR?) 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.

SUBMITTER: Li XW

PROVIDER: S-EPMC6680686 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Li Xue-Wen XW Huang Meixiang M Lo Kakei K Chen Wei-Li WL He Ying-Yan YY Xu Yongli Y Zheng Huizhen H Hu Haiyan H Wang Jun J

Molecules (Basel, Switzerland) 20190723 14

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 immunohistoc ...[more]

PMID: 31340585

Similar Datasets

Project description:Oral therapeutics used to treat type 2 diabetes and cardiovascular disease often fail to prevent the progression of disease and their comorbidities. Rooibos (Aspalathus linearis), an endemic South African plant used as an herbal tea, has demonstrated positive effects on glycemia and hypercholesterolemia. However, the treatment efficacy of rooibos extract in combination with conventional hypoglycemic and hypolipidemic medications on blood glucose and lipid profiles has not been established. This study aimed to investigate the effects of combining an aspalathin-rich green rooibos extract (Afriplex GRT™) with pioglitazone and atorvastatin, on blood glucose and lipid levels in obese diabetic (db/db) mice. Six-week-old male db/db mice and their nondiabetic lean littermate controls (db+) were divided into 8 experimental groups (n = 6/group). Db/db mice were treated daily either with pioglitazone (25 mg/kg), atorvastatin (80 mg/kg) and GRT (100 mg/kg), a combination of either drug with GRT or a combination of GRT-pioglitazone and atorvastatin for 5 weeks. Untreated vehicle controls were given dimethyl sulfoxide (0.1%) and phosphate buffered saline solution. At termination, serum and liver tissue were collected for lipid and gene expression analysis. Treatment with GRT, pioglitazone and atorvastatin combination effectively lowered fasting plasma glucose (FPG) levels in db/db mice (p = 0.02), whilst increasing body weight, liver weight, and reducing retroperitoneal fat weight. Atorvastatin monotherapy was effective at reducing cholesterol (from 4.00 ± 0.12 to 2.93 ± 0.13, p = 0.0003), LDL-C (from 0.58 ± 0.04 to 0.50 ± 0.00, p = 0.04), HDL-C (from 2.86 ± 0.05 to 2.50 ± 0.04, p = 0.0003) and TG (from 2.77 ± 0.50 to 1.48 ± 0.23, p = 0.04), compared to the untreated diabetic control. The hypotriglyceridemic effect of atorvastatin was enhanced when used in combination with both GRT and pioglitazone. The addition of pioglitazone to GRT significantly lowered FPG and TG. In db/db mice, Apoa1 was significantly downregulated in the liver, whilst Pparγ was significantly upregulated compared to their db+ counterparts. GRT monotherapy downregulated Apoa1 expression (p = 0.02). Atorvastatin combined with GRT significantly downregulated mRNA expression of Apoa1 (p = 0.03), whilst upregulating the expression of Pparγ (p = 0.03), Pparα (p = 0.002), Srebp1 (p = 0.002), and Fasn (p = 0.04). The GRT-pioglitazone-atorvastatin combination therapy downregulated Apoa1 (p = 0.006), whilst upregulating Fasn (p = 0.005), Pparα (p = 0.041), and Srebp1 (p = 0.03). Natural products can improve the efficacy of current drugs to prevent diabetes-associated complications. GRT in combination with pioglitazone enhanced the reduction of FPG, whilst the addition of atorvastatin to the combination, significantly lowered triglyceride levels. However, when GRT was used in combination with atorvastatin only cholesterol levels were affected. Although these results confirm both glucose- and lipoprotein-lowering biological effects of GRT in combination with pioglitazone and atorvastatin, increased expression of genes involved in lipogenesis, cholesterol, and fatty acid transport, β-oxidation, and synthesis and storage of fatty acids, may exacerbate the hepatotoxic effects of atorvastatin.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets