Autologous transplantation of green tea epigallocatechin-3-gallate pretreated adipose-derived stem cells increases cardiac regenerative capability through C-X-C motif chemokine receptor 4 expression in the treatment of rats with diabetic cardiomyopathy.

Cardiomyopathy is one of complications related to diabetes. Stem cell transplantation shows potential in diabetic cardiomyopathy treatment. Epigallocatechin-3-gallate (EGCG) is one of the major components found in green tea. Although stem cell transplantation and green tea EGCG supplementation show therapeutic effects on cardiomyopathy, the detailed cellular mechanisms in stem cell transplantation coupled with EGCG treatment remain unclear. This study investigates whether adipose-derived stem cells (ADSC) pretreated with EGCG show better protective effect on diabetic cardiomyopathy than ADSC without EGCG pretreatment. A cell model indicated that ADSC pretreated with EGCG increased cell functions including colony formation, migration and survival markers. All of these functions are blocked by small interfering C-X-C motif chemokine receptor 4 (siCXCR4) administration. These findings suggest that ADSC pretreatment with EGCG increases cell functions through CXCR4 expression. A diabetic animal model was designed to verify the above findings, including Sham, DM (diabetes mellitus), DM+ADSC (DM rats receiving autologous transplantation of ADSC) and DM+E-ADSC (DM rats receiving EGCG pretreated ADSC). Compared to the Sham, we found that all of pathophysiological signalings were activated in the DM group, including functional changes (decrease in ejection fraction and fractional shortening), structural changes (disarray and fibrosis) and molecular changes (increases in apoptotic, fibrotic, hypertrophic markers and decreases in survival and longevity markers). E-ADSC (DM+E-ADSC) transplantation shows significant improvement in the above pathophysiological signalings greater than ADSC (DM+ADSC). Therefore, ADSC pretreated with EGCG may contribute to clinical applications for diabetic patients with cardiomyopathy.

The efficacy and safety of traditional Chinese medicine treating diabetic cardiomyopathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic cardiomyopathy, secondary to diabetes, is the main cause of death in patients with diabetes. In China, traditional Chinese medicine has achieved good performance in treating diabetic cardiomyopathy. However, to date, no systematic review or meta-analysis has been published on the treatment of diabetic cardiomyopathy by traditional Chinese medicine. METHODS: This study strictly followed the preferred guidelines for systematic review. Two researchers searched seven databases: EMbase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database, and WANFANG Database. The retrieval time limit ranged from the establishment of the database to August 2022. All clinical randomized controlled trials that met the inclusion and exclusion criteria were included in this study. Statistical analysis was performed using RevMan 5.3. RESULTS: This study analyzed the clinical efficacy and safety of traditional Chinese medicine in the treatment of diabetic cardiomyopathy. CONCLUSION: The results of this study provide evidence-based medical evidence for the clinical use of traditional Chinese medicine in the treatment of diabetic heart disease in the future.

Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy.

ABSTARCT: Diabetic complications are among the largely exigent health problems currently. Cardiovascular complications, including diabetic cardiomyopathy (DCM), account for more than 80% of diabetic deaths. Investigators are exploring new therapeutic targets to slow or abate diabetes because of the growing occurrence and augmented risk of deaths due to its complications. Research on rodent models of type 1 and type 2 diabetes mellitus, and the use of genetic engineering techniques in mice and rats have significantly sophisticated for our understanding of the molecular mechanisms in human DCM. DCM is featured by pathophysiological mechanisms that are hyperglycemia, insulin resistance, oxidative stress, left ventricular hypertrophy, damaged left ventricular systolic and diastolic functions, myocardial fibrosis, endothelial dysfunction, myocyte cell death, autophagy, and endoplasmic reticulum stress. A number of molecular and cellular pathways, such as cardiac ubiquitin proteasome system, FoxO transcription factors, hexosamine biosynthetic pathway, polyol pathway, protein kinase C signaling, NF-κB signaling, peroxisome proliferator-activated receptor signaling, Nrf2 pathway, mitogen-activated protein kinase pathway, and micro RNAs, play a major role in DCM. Currently, there are a few drugs for the management of DCM and some of them have considerable adverse effects. So, researchers are focusing on the natural products to ameliorate it. Hence, in this review, we discuss the pathogical, molecular, and cellular mechanisms of DCM; the current diagnostic methods and treatments; adverse effects of conventional treatment; and beneficial effects of natural product-based therapeutics, which may pave the way to new treatment strategies. Graphical Abstract.

Waon Therapy for Managing Chronic Heart Failure　- Results From a Multicenter Prospective Randomized WAON-CHF Study.

BACKGROUND: Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. METHODS AND RESULTS: In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. CONCLUSIONS: Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

Management of cardiorenal metabolic syndrome in diabetes mellitus: a phytotherapeutic perspective.

Cardiorenal syndrome (CRS) is a complex disease in which the heart and kidney are simultaneously affected and their deleterious declining functions are reinforced in a feedback cycle, with an accelerated progression. Although the coexistence of kidney and heart failure in the same individual carries an extremely bad prognosis, the exact cause of deterioration and the pathophysiological mechanisms underlying the initiation and maintenance of the interaction are complex, multifactorial in nature, and poorly understood. Current therapy includes diuretics, natriuretic hormones, aquaretics (arginine vasopressin antagonists), vasodilators, and inotropes. However, large numbers of patients still develop intractable disease. Moreover, the development of resistance to many standard therapies, such as diuretics and inotropes, has led to an increasing movement toward utilization and development of novel therapies. Herbal and traditional natural medicines may complement or provide an alternative to prevent or delay the progression of CRS. This review provides an analysis of the possible mechanisms and the therapeutic potential of phytotherapeutic medicines for the amelioration of the progression of CRS.

Role of sulfurous mineral water and sodium hydrosulfide as potent inhibitors of fibrosis in the heart of diabetic rats.

This study examined the downstream signaling whereby hyperglycemia may lead to myocardial fibrosis and apoptosis in the left ventricle of diabetic rats. The effects of sulfurous mineral water or sodium hydrosulfide (NaHS) as possible modulators were also examined. Sulfurous mineral water (as drinking water) and NaHS (14µmol/kg/day, IP) were administered for 7 week to rats with streptozotocin (STZ)-induced diabetes. Hyperglycemia, overproduction of glycated hemoglobin (HbA1C) and serum decline in insulin, C-peptide and insulin like growth factor-I (IGF-I) were observed in diabetic rats. Up-regulation of gene expressions of nuclear factor (NF-κB), profibrogenic growth factor such as transforming growth factor-ß1 (TGF-ß1), matrix metalloproteniase-2 (MMP-2), procollagen-1 and Fas ligand (Fas-L) were observed in the left ventricle of diabetic rats. A linear positive correlation between TGF-ß1 and MMP-2 was also detected in diabetic group. An increase in hydroxyproline level and a disturbance in oxidative balance were detected in heart of diabetic rats. Sulfurous mineral water and NaHS treatment possibly, by improving cardiac GSH level, counteracted the enhanced expression of NF-κB, the profibrogenic and apoptotic parameters. Histopathological examination was in accordance with the biochemical and molecular findings of this study. We suggest a novel therapeutic approach of sulfurous mineral water and exogenous supplementation of H(2)S in diabetic cardiomyopathy.