PMID- 30648577 OWN - NLM STAT- MEDLINE DCOM- 20200323 LR - 20220809 IS - 2224-6614 (Electronic) IS - 1021-9498 (Print) VI - 27 IP - 1 DP - 2019 Jan TI - Identification of baicalin from Bofutsushosan and Daisaikoto as a potent inducer of glucose uptake and modulator of insulin signaling-associated pathways. PG - 240-248 LID - 10.1016/j.jfda.2018.07.002 [doi] AB - Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia that can lead to long-term complications including heart diseases, stroke, retinopathy, and renal failure. Treatment strategies include stimulating glucose uptake and controlling blood glucose level. Bofutsushosan (BOF) and Daisaikoto (DAI) are two herb-based kampo medicines that have been demonstrated to improve metabolism-associated disorders including obesity, hyperlipidemia, and nonalcoholic fatty liver. Given their bioactivities against metabolic syndromes, we explored in this study the effect of BOF and DAI extracts on glucose absorption and used them as source to identify phytochemical stimulator of glucose absorption. Glucose uptake and mechanistic studies were evaluated in differentiated C2C12 skeletal muscle cells, and HPLC analysis was used to determine the molecular bioactive constituents. Our results indicated that the ethanolic extracts of BOF and DAI (BOFEE and DAIEE, respectively) enhanced the glucose uptake ratio in the differentiated C2C12 cells, and further analysis identified the flavone baicalin as a major constituent capable of efficiently stimulating glucose absorption. Mechanistic studies revealed that the effect from baicalin involved the activation of IRS-1 and GLUT-4, and implicated the AMPK, PI3K/Akt, and MAPK/ERK signaling cascades. Due to its potency, we suggest that baicalin merit further evaluation as a potential candidate anti-hyperglycemic agent for the treatment and management of T2DM. CI - Copyright (c) 2018. Published by Elsevier Taiwan LLC. FAU - Kuo, Yu-Ting AU - Kuo YT AD - Department of Medical Imaging, Chi Mei Medical Center, No. 901 Zhonghua Road, Yongkang District, Tainan, 710, Taiwan. FAU - Lin, Chih-Chan AU - Lin CC AD - Department of Medical Research, Chi Mei Medical Center, No. 901 Zhonghua Road, Yongkang District, Tainan, 710, Taiwan. FAU - Kuo, Hsiao-Tzu AU - Kuo HT AD - Department of Nutritional Health, Chia-Nan University of Pharmacy and Science, 60 Erh-Jen 1st Road, Jen-Te Hsiang, Tainan, 717, Taiwan. FAU - Hung, Jui-Hsiang AU - Hung JH AD - Department of Biotechnology, Chia-Nan University of Pharmacy and Science, 60 Erh-Jen 1st Road, Jen-Te Hsiang, Tainan, 717, Taiwan. FAU - Liu, Ching-Hsuan AU - Liu CH AD - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, Taiwan. AD - Department of Microbiology & Immunology, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, B3H 4R2, Canada. FAU - Jassey, Alagie AU - Jassey A AD - International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, Taiwan. FAU - Yen, Ming-Hong AU - Yen MH AD - Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan. FAU - Wu, Shu-Jing AU - Wu SJ AD - Department of Nutritional Health, Chia-Nan University of Pharmacy and Science, 60 Erh-Jen 1st Road, Jen-Te Hsiang, Tainan, 717, Taiwan. FAU - Lin, Liang-Tzung AU - Lin LT AD - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, Taiwan. AD - Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180814 PL - China (Republic : 1949- ) TA - J Food Drug Anal JT - Journal of food and drug analysis JID - 101630927 RN - 0 (Drugs, Chinese Herbal) RN - 0 (Flavonoids) RN - 0 (Glucose Transporter Type 4) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (bofu-tsusho-san) RN - 0 (daisaikoto) RN - 347Q89U4M5 (baicalin) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Cell Line MH - Drugs, Chinese Herbal/chemistry/*pharmacology MH - Flavonoids/analysis/*pharmacology MH - Glucose/*metabolism MH - Glucose Transporter Type 4/genetics/metabolism MH - Hypoglycemic Agents/chemistry/*pharmacology MH - Insulin/*metabolism MH - Mice MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - Signal Transduction/drug effects PMC - PMC9298638 OTO - NOTNLM OT - Anti-hyperglycemia OT - Baicalin OT - Bofutsushosan OT - Daisaikoto OT - Glucose uptake COIS- Conflicts of interest The authors declared that no competing interests exist. EDAT- 2019/01/17 06:00 MHDA- 2020/03/24 06:00 PMCR- 2018/08/14 CRDT- 2019/01/17 06:00 PHST- 2018/04/11 00:00 [received] PHST- 2018/06/20 00:00 [revised] PHST- 2018/07/19 00:00 [accepted] PHST- 2019/01/17 06:00 [entrez] PHST- 2019/01/17 06:00 [pubmed] PHST- 2020/03/24 06:00 [medline] PHST- 2018/08/14 00:00 [pmc-release] AID - j.jfda.2018.07.002 [pii] AID - jfda-27-01-240 [pii] AID - 10.1016/j.jfda.2018.07.002 [doi] PST - ppublish SO - J Food Drug Anal. 2019 Jan;27(1):240-248. doi: 10.1016/j.jfda.2018.07.002. Epub 2018 Aug 14.