Antidiabetic Activities of Extract from Malva verticillata Seed via the Activation of AMP-Activated Protein Kinase

• Published in: Journal of microbiology and biotechnology Vol. 21; no. 9; pp. 921 - 929
• Main Author: Jeong, Yong-Tae
• Format: Journal Article
• Language: English
• Published: Seoul Korean Society for Applied Microbiology 01.09.2011; 한국미생물·생명공학회
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Biological and medical sciences; Biotechnology; Cell Line; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - metabolism; Enzyme Activation - drug effects; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - isolation & purification; Hypoglycemic Agents - pharmacology; Malva - chemistry; Mice; Mice, Inbred C57BL; Phosphorylation - drug effects; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Seeds - chemistry; 생물학; Enzyme; Transferases; Non-specific serine/threonine protein kinase; Rodentia; L6 myotube; Activation; Extract; Glucose; Myotube; cAMP-dependent protein kinase; Uptake; Malva verticillata; Vertebrata; Mammalia; Mouse; glucose uptake; β-sitosterol; db/db mice; AMPK
• ISSN: 1017-7825; 1738-8872
• DOI: 10.4014/jmb.1104.04015

Stimulation of AMP-activated protein kinase (AMPK) signaling followed by increase of glucose uptake in L6 myotubes were studied with organic solvent extract of Malva verticillata (MV) seeds. Ethanol extract of M. verticillata seeds (MVE) significantly increased the phosphorylation level of AMPK, acetyl-CoA carboxylase (ACC), and glucose uptake in L6 myotube cells. The MVE was fractionated with n-hexane (MVE-H), chloroform (MVE-C), ethylacetate (MVE-E), n-butanol (MVE-B), and water (MVE-W). MVE-H (150 microgram/ml) showed the highest phosphorylating activity and increased glucose uptake by 2.3-fold. Oral administration of MVE-H (40 mg/kg) for 4 weeks to type 2 diabetic (db/db) mice reduced non-fasting and fasting blood glucose levels by 17.1% and 23.3%, respectively. Phosphorylation levels of AMPK and ACC in the soleus muscle and liver tissue of db/db mice were significantly increased by the administration of MVE-H. MVE-H was further fractionated using preparative HPLC to identify the AMPK-activating compounds. The NMR and GC-MS analyses revealed that β-sitosterol was a major effective compound in MVE-H. Phosphorylation levels of AMPK and ACC, and glucose uptake were significantly increased by the treatment of MVE-S (β-sitosterol) isolated from M. verticillata to L6 cells, and these effects were attenuated by an AMPK inhibitor (Compound C) pretreatment. These results, taken together, demonstrate that increased glucose uptake in L6 myotubes by MVE-H treatment is mainly accomplished through the activation of AMPK. Our finding suggests that the extract isolated from M. verticillata seed would be beneficial for the treatment of metabolic disease including type 2 diabetes and hyperlipidemia.