title: Reversal of muscle atrophy by Zhimu-Huangbai herb-pair via Akt/mTOR/FoxO3 signal pathway in streptozotocin-induced diabetic mice.
abstract: Skeletal muscle atrophy is one of the serious complications of diabetes. Zhimu-Huangbai herb-pair (ZB) is widely used in Chinese traditional medicine formulas for treating Xiaoke (known as diabetes) and its complications. However, the effect of ZB on reversal of muscle atrophy and the underlying mechanisms remain unknown. In this research, we investigated the effect and possible mechanisms of ZB on skeletal muscle atrophy in diabetic mice. Animal model of diabetic muscle atrophy was developed by high fat diet (HFD) feeding plus streptozotocin (STZ) injection. After oral adminstration of ZB for 6 weeks, the effects of ZB on reversal of muscle atrophy and the underlying mechanisms were evaluated by biochemical, histological and western blot methods. The skeletal muscle weight, strength, and cross-sectional area of diabetic mice were significantly increased by ZB treatment. Biochemical results showed that ZB treatment reduced the serum glucose level, and elevated the serum insulin-like growth factor 1 (IGF-1) and insulin levels significantly compared with untreated diabetic group. The western blot results showed that ZB activated the mTOR signal pathway, shown as increased phosphorylations (p-) of Akt, mTOR, Raptor, S6K1 and reduced Foxo3 expression compared with the model group. ZB could reverse muscle atrophy in diabetic mice. This may be through activation of mTOR signaling pathway that promotes protein synthesis, and inactivation foxo3 protein that inhibits protein degradation. These findings suggested that ZB may be considered as a potential candidate drug in treatment of diabetic muscle atrophy.
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Jinbao
authors: J
authors: Zhang
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin JF-Pharmaland Technology Development Co., Ltd., Tianjin, China.
authors: Pengwei
authors: P
authors: Zhuang
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Yan
authors: Y
authors: Wang
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Lili
authors: L
authors: Song
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Mixia
authors: M
authors: Zhang
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Zhiqiang
authors: Z
authors: Lu
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Lu
authors: L
authors: Zhang
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Jing
authors: J
authors: Wang
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Paulos N
authors: PN
authors: Alemu
authors: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Yanjun
authors: Y
authors: Zhang
authors: Tianjin JF-Pharmaland Technology Development Co., Ltd., Tianjin, China.
authors: Hongjun
authors: H
authors: Wei
authors: Tianjin JF-Pharmaland Technology Development Co., Ltd., Tianjin, China.
authors: Hongyan
authors: H
authors: Li
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D053580:Muscle Strength / Q000187:drug effects; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D007328:Insulin; D008055:Lipids; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases