8.Tu-Xian Decoction ameliorates diabetic cognitive impairment by inhibiting DAPK-1.
Danyang WANG ; Bin YAN ; An WANG ; Qing SUN ; Junyi PANG ; Yangming CUI ; Guoqing TIAN
Chinese Journal of Natural Medicines (English Ed.) 2023;21(12):950-960
Tu-Xian decoction (TXD), a traditional Chinese medicine (TCM) formula, has been frequently administered to manage diabetic cognitive impairment (DCI). Despite its widespread use, the mechanisms underlying TXD's protective effects on DCI have yet to be fully elucidated. As a significant regulator in neurodegenerative conditions, death-associated protein kinase-1 (DAPK-1) serves as a focus for understanding the action of TXD. This study was designed to whether TXD mediates its beneficial outcomes by inhibiting DAPK-1. To this end, a diabetic model was established using Sprague-Dawley (SD) rats through a high-fat, high-sugar (HFHS) diet regimen, followed by streptozotocin (STZ) injection. The experimental cohort was stratified into six groups: Control, Diabetic, TC-DAPK6, high-dose TXD, medium-dose TXD, and low-dose TXD groups. Following a 12-week treatment period, various assessments-including blood glucose levels, body weight measurements, Morris water maze (MWM) testing for cognitive function, brain magnetic resonance imaging (MRI), and histological analyses using hematoxylin-eosin (H&E), and Nissl staining-were conducted. Protein expression in the hippocampus was quantified through Western blotting analysis. The results revealed that TXD significantly improved spatial learning and memory abilities, and preserved hippocampal structure in diabetic rats. Importantly, TXD administration led to a down-regulation of proteins indicative of neurological damage and suppressed DAPK-1 activity within the hippocampal region. These results underscore TXD's potential in mitigating DCIvia DAPK-1 inhibition, positioning it as a viable therapeutic candidate for addressing this condition. Further investigation into TXD's molecular mechanisms may elucidate new pathways for the treatment of DCI.
Animals
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Rats
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Brain/metabolism*
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Cognitive Dysfunction/drug therapy*
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Diabetes Mellitus, Experimental/metabolism*
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Hippocampus
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Rats, Sprague-Dawley
9.Effect of sour TCM compound recipe on insulin resistance in experimental rats with diabetes mellitus type 2.
Ya-bing ZHOU ; Ruo-yin LUO ; Li ZHAO
Chinese Journal of Integrated Traditional and Western Medicine 2005;25(5):441-444
OBJECTIVETo study the effect of sour TCM compound Recipe (SCCR) on insulin resistance in experimental rats with diabetes mellitus type 2 (DM2), under the guidance of TCM doctrine of "sour restrains sweet".
METHODSModel rats of DM2 were established by 8 weeks' feeding with high calorie forage combined with intraperitoneal injection of small dose of streptozotocin, and treated with SCCR (15 g/kg of crude drug/day). Levels of fasting blood glucose (FBG), serum insulin, free fatty acids (FFA), tumor necrosis factor a (TNF-alpha), combining capacity and constant of insulin receptor in liver were determined before treatment and 4, 8 and 12 weeks after treatment, and the insulin sensitive index was calculated. The data were compared with those in the model group (untreated), sweet TCM compound recipe group and bitter TCM compound group (treated with sweet and bitter Chinese drugs respectively) and the control group (treated with dimethyldiguanide).
RESULTSSCCR could markedly reduce the FBG, serum FFA and TNF-alpha levels in rat model of DM2, stimulate the secretion of insulin, raise the combining capacity and constant of insulin receptor in liver and improve the insulin sensitivity, as compared with the effect of sweet or bitter Chinese compound recipe, the difference was significant (P < 0.05).
CONCLUSIONSCCR could improve the glucose metabolic disorder and ameliorate the degree of insulin resistance in DM2 model rats, with the effect superior to those with sweet or bitter taste, which illustrates primarily that the therapeutic principle of "sour restrains sweet" of TCM is true of science in a certain degree and having its guiding significance in clinical practice.
Animals ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Compounding ; Drugs, Chinese Herbal ; therapeutic use ; Insulin Resistance ; Male ; Phytotherapy ; Rats
10.Effects of insulin treatment on intracellular lipid content in livers and insulin resistance in type 2 diabetic rats.
Yong-bo WANG ; Lu-lu CHEN ; Min ZHOU ; Bao-ping WANG
Chinese Journal of Hepatology 2005;13(6):451-454
OBJECTIVETo study effects of insulin treatment on intracellular lipid content in livers and insulin resistance of type 2 diabetic rats.
METHODSType 2 diabetic rats were induced by injecting streptozotocin (25 mg/kg) and fat rich food. Then according to the results of the oral glucose tolerance test (OGTT) and glucose-induced insulin secretion test (IST), the rats were divided into two groups: control group (DC) and insulin treated group (DI). Normal rats (NC) served as controls. The treatment of each group with either NPH insulin (4 approximately 6 U . kg-1. d-1), or saline continued for 4 weeks. Body weight, OGTT, IST, blood lipids, intracellular lipids in liver and liver histology were studied. The insulin sensitivity index (ISI) was applied to assess the status of insulin resistance.
RESULTSBlood lipid and intracellular lipids in livers in the DC were higher than those in NC (t = 2.59 approximately 15.77, P < 0.05) and the ISI was lower (t = 3.16, P < 0.05), with many fatty droplets appearing in the livers. In comparison to DC, DI showed that blood lipids were decreased, but lipids in livers were markedly increased (TG, TC, FFA increased 55.7%, 19.87%, 22.2%, respectively), and fatty droplets in hepatocytes were larger, but the ISI did not change significantly.
CONCLUSIONInsulin treatment can make blood glucose normal, increase the intracellular lipid content in the liver, and not increase the insulin resistance significantly.
Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Insulin ; therapeutic use ; Insulin Resistance ; Lipid Metabolism ; Liver ; metabolism ; Male ; Rats ; Rats, Wistar
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