Fuzi attenuates diabetic neuropathy in rats and protects schwann cells from apoptosis induced by high glucose.
Radix aconite lateralis preparata (Fuzi), a folk medicine, has long been used for the treatment of diabetes and paralysis in China. We examined the effect of Fuzi alone on diabetic rats and Schwann cells in high glucose and the components responsible for its activity. The major constituents of FZE were identified by HPLC-MS/MS data. Male Sprague Dawley rats (n = 36) were randomly divided into control, diabetic, FZE 1.75 g/kg, FZE 3.50 g/kg, FZE 7.00 g/kg, and methylcobalamin groups. After two weeks treatment, nerve conduction velocity and paw withdrawal latency were measured. In vitro, the Schwann cells were grouped according to exposure: normal glucose (NG), normal glucose plus mannitol (NG+M), high glucose (HG), and HG plus different concentrations of FZE (0.1 µg/ml, 1.0 µg/ml, and 10.0 µg/ml). Oxygen free radicals and apoptosis were evaluated through DCFH2DA, DHE and annexin-PE/7-AAD assay, respectively. Apoptosis factors (Bax, Bcl-2, CytoC, caspase-3, and caspase-9) were analyzed using immunofluorescence. Nine alkaloids were identified. The results from animal model showed that FZE was effective in accelerating nerve conduction velocity and shortening paw withdrawal latency in diabetic rats. And in vitro, FZE was also found to protect Schwann cells against high glucose injury. FZE could significantly decrease the apoptotic ratio, superoxide anion and peroxide level. Furthermore, the apoptosis factors, including Bax, Bcl-2, CytoC, caspase-3, and caspase-9 were ameliorated in FZE treated groups. The HPLC-MS(n) method is simple and suitable for the identification of alkaloids in Fuzi. FZE has a protective effect in diabetic neuropathic rats, which is probably achieved by the antiapoptotic effect of FZE on Schwann cells. Apoptosis factor data imply that FZE protected Schwann cells through the mitochondria pathway. Alkaloids are major components contributing to the protective effect.
Beijing University of Chinese Medicine, Beijing, China.
Jing
J
Han
Beijing University of Chinese Medicine, Beijing, China.
Peng
P
Tan
Minzu University of China, Beijing, China.
Zhiyong
Z
Li
Beijing University of Chinese Medicine, Beijing, China.
Yan
Y
Wu
Beijing University of Chinese Medicine, Beijing, China.
Chun
C
Li
Beijing University of Chinese Medicine, Beijing, China.
Yong
Y
Wang
Beijing University of Chinese Medicine, Beijing, China.
Beibei
B
Wang
Beijing University of Chinese Medicine, Beijing, China.
Shuang
S
Zhao
Beijing University of Chinese Medicine, Beijing, China.
Yonggang
Y
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects* / Q000473:pathology; D053719:Tandem Mass Spectrometry
D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C575009:fuzi drug herbal; D005947:Glucose