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 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.
Highlights
Type 2 diabetes mellitus (T2DM) is a metabolic disease with a high prevalence, and can seriously damage people’s health [1,2]
The polar extract of D. loddigesii is rich in shihunine [27,28] and little is known about its pharmacological activity
To clarify the anti-diabetic effect of D. loddigesii, a shihunine-rich extract (DLS) was prepared from D. loddigesii and its anti-diabetic effects were researched in 3T3-L1 cells and db/db mice
Summary
Type 2 diabetes mellitus (T2DM) is a metabolic disease with a high prevalence, and can seriously damage people’s health [1,2]. The clinical symptoms of T2DM are hyperglycemia, insulin resistance, hyperlipidemia, and a relative deficiency of insulin secretion because of pancreatic β-cell dysfunction [3]. Obesity is the most critical factor in the emergence of metabolic diseases and insulin resistance [4]. Obesity results in insulin resistance and β-cell dysfunction, which are unable to fully compensate for the reduced insulin sensitivity of liver tissue, adipose tissue, and skeletal muscle, triggering T2DM [5,6,7]. Preventing obesity and improving insulin resistance are regarded as one of the important strategies of treating T2DM.
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