ABSTRACT
Objective To make a system evaluation regarding the effect and safety of the"Nourishing Kidney and Activating Blood"method in the treatment of diabetic cognitive impairment.Methods According to the requirements of evidence-based medicine,the domestic and foreign databases were searched comprehensively,and the time limit was from the establishment of databases to June 2022,so as to find out the clinical randomized controlled trials of"Nourishing Kidney and Activating Blood"method in treating diabetic cognitive impairment.Revman5.3 was used for meta-analysis and risk bias evaluation,TSA0.9 for sequential analysis,Stata15.0 for publication bias evaluation,and GRADE3.6 for evidence quality evaluation.Results Eventually,14 RCTs were included with a sample size of 1126 cases.Meta-analysis showed that compared with conventional western medicine treatment,the"Nourishing Kidney and Activating Blood"method could significantly improve the effective rate of treating cognitive dysfunction in diabetes[OR=5.06,95%CI(3.38,7.57),P<0.00001],and significantly improve the total MoCA score of patients[MD=2.11,95%CI(1.76,2.47),P<0.00001],MMSE score[MD=1.86,95%CI(1.13,2.59),P<0.00001],MQ score[MD=13.40,95%CI(11.23,15.57),P<0.00001]and HDS score[MD=-3.36,95%CI(2.61,4.11),P<0.00001].Meanwhile,the"Nourishing Kidney and Activating Blood"method could reduce the level of glycosylated hemoglobin in DCI patients[MD=-0.84,95%CI(-1.37,-0.32),P=0.002].However,since the drugs used in the control group have no hypoglycemic effect,this conclusion needs to be further verified.In addition,the ability of the"Nourishing Kidney and Activating Blood"method to improve CDR score[MD=-0.01,95%CI(-0.08,0.07),P=0.84],ADL score[MD=2.10,95%CI(-1.62,5.82),P=0.27],TCM syndrome score[MD=-4.46,95%CI(-10.94,2.02),P=0.18]and reduce adverse reactions[OR=0.36,95%CI(0.08,1.60),P=0.18]was equivalent to that of conventional western medicine.Begg's test and Egger's test suggested that there might be some publication bias in the research.Metaninf command chart and sequential analysis of experiments indicated that the stability of research results was relatively good.The quality evaluation of evidence showed that the evidence of effective rate,glycosylated hemoglobin,MoCA scale score,MMSE score and MQ score was medium quality,the evidence of fasting blood glucose,CDR score and HDS score was low quality,and the evidence of ADL score,TCM syndrome score and adverse reactions was extremely low quality.Conclusion The existing literature evidence showed that the"Nourishing Kidney and Activating Blood"method had a good clinical effect in treating diabetic cognitive impairment,and it could reduce the blood glucose level and improve the cognitive function of patients,with certain safety.However,the above conclusions still needed more large samples and multi-center RCT to be further verified due to the limitation of the quality and quantity of the included literature.
ABSTRACT
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.
Subject(s)
Animals , Rats , Brain/metabolism , Cognitive Dysfunction/drug therapy , Diabetes Mellitus, Experimental/metabolism , Hippocampus , Rats, Sprague-DawleyABSTRACT
Cognitive dysfunction is one of the common central nervous systems (CNS) complications of diabetes mellitus, which seriously affects the quality of life of patients and results in a huge economic burden. The glymphatic system dysfunction mediated by aquaporin-4 (AQP4) loss or redistribution in perivascular astrocyte endfeet plays a crucial role in diabetes-induced cognitive impairment (DCI). However, the mechanism of AQP4 loss or redistribution in the diabetic states remains unclear. Accumulating evidence suggests that peripheral insulin resistance target tissues and CNS communication affect brain homeostasis and that exosomal miRNAs are key mediators. Glucose and lipid metabolism disorder is an important pathological feature of diabetes mellitus, and skeletal muscle, liver and adipose tissue are the key target insulin resistance organs. In this review, the changes in exosomal miRNAs induced by peripheral metabolism disorders in diabetes mellitus were systematically reviewed. We focused on exosomal miRNAs that could induce low AQP4 expression and redistribution in perivascular astrocyte endfeet, which could provide an interorgan communication pathway to illustrate the pathogenesis of DCI. Furthermore, the mechanisms of exosome secretion from peripheral insulin resistance target tissue and absorption to the CNS were summarized, which will be beneficial for proposing novel and feasible strategies to optimize DCI prevention and/or treatment in diabetic patients.
ABSTRACT
Objective To explore the regulatory effeet of Qifu Yin ( QFY) on JAK2/STAT3 pathway in rats with type 2 diabetic cognitive impairment.Methods A small dose of STZ combined with high-fat and high- sugar feed was used to build the model.After success, they were divided into model group, QFY low-dose, high-dose group, and metformin group.After four weeks of intervention, fasting blood glucose ( FBG ) was measured; Morris water maze was used to detect spatial learning and memory ability in rats; Nissl staining and immunofluorescence staining were respectively used to detect the degree of brain injury and the expression of lba-1 , a marker of microglia .EL1SA was used to detect the expression of TNF-cx, IL6, ILK) and BDNF.Western blot was employed to detect the expression of JAK2/STAT3 pathway.Results Compared with the control group, the model group showed significant increase in blood glucose, decreased spatial learning and memory capacity, severely damaged hipp-ocampal neurons, increased activated microglia, significantly higher levels of TNF-cx, 1L6, p-JAK2/JAK2 and p-STAT3/STAT3, and signif icantly lower levels of ILK) and BDNF.Compared with the model group, QFY group effectively reduced FBG, inhibited the con-tinuous rise of FBG, improved learning and memory a- bility, improved hippocampal neuronal damage, reduced activated microglia, reduced TNF-cx, 1L6, p- JAK2/JAK2 and p-STAT3/STAT3 levels, and increased ILK) and BDNF levels.Conclusion QFY has been shown to improve type 2 diabetic cognitive impairment , and the mechanism may be related to the inhibition of blood glucose rise and regulation of the JAK2/STAT3 pathway, thereby inhibiting microglia activation.