Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to heart failure and death, for which there is no effective treatment. Rhynchophylline (Rhy) is the main effective component of the Chinese herbal medicine Uncaria rhynchophylla, which mainly acts on the cardiovascular and nervous systems. However, its role in protecting against DCM remains unexplored. The present study sought to reveal the mechanism of Rhy in improving type 2 diabetes mellitus (T2DM) myocardial lesions from the perspective of regulating calcium homeostasis in cardiomyocytes. We prepared a mouse model of T2DM using a high-fat diet combined with low doses of streptozotocin. The T2DM mice were given 40 mg/kg of Rhy for 8 weeks. The results showed that Rhy can attenuate cardiac pathological changes, slow down the heart rate, decrease serum cardiac enzyme levels, reduce cardiomyocyte apoptosis, enhance cardiomyocyte contractility, and raise the calcium transient amplitude in T2DM mice. Further, Rhy downregulated the phosphorylation level of ryanodine receptor 2, upregulated the phosphorylation level of phospholamban, protected mitochondrial structure and function, and increased adenosine triphosphate levels in the cardiac tissue of T2DM mice. Our results demonstrated that Rhy may protect against myocardial damage in T2DM mice and promote cardiomyocyte contraction, and its mechanism of action seems to be related to the regulation of intracellular calcium homeostasis.

Background: Tianhuang formula (THF) is a Chinese medicine prescription that is patented and clinically approved, has been shown to improve energy metabolism, but the underlying mechanism remains poorly understood. The purpose of this study is to clarify the potential mechanisms of THF in the treatment of type 2 diabetes mellitus (T2DM). Methods: A murine model of T2DM was induced by high-fat diet (HFD) feeding combined with low-dose streptozocin (STZ) injections, and the diabetic mice were treated with THF by gavaging for consecutive 10 weeks. Fasting blood glucose (FBG), serum insulin, blood lipid, mitochondrial Ca2+ (mCa2+) levels, mitochondrial membrane potential (MMP) as well as ATP production were analyzed. The target genes and proteins expression of visceral adipose tissue (VAT) was tested by RT-PCR and western blot, respectively. The underlying mechanism of the regulating energy metabolism effect of THF was further explored in insulin resistance model of 3T3-L1 adipocytes cultured with dexamethasone (DXM). Results: THF restored impaired glucose tolerance and insulin resistance in diabetic mice. Serum levels of lipids were significantly decreased, as well as fasting blood glucose and insulin in THF-treated mice. THF regulated mCa2+ uptake, increased MMP and ATP content in VAT. THF increased the mRNA and protein expression of AMPK, phosphorylated AMPK (p-AMPK), MICU1, sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). THF could increase the mCa2+ level of 3T3-L1 adipocytes and regulate mitochondrial function. The protein expression of AMPK, p-AMPK, mCa2+ uniporter (MCU) and MICU1 decreased upon adding AMPK inhibitor compound C to 3T3-L1 adipocytes and the protein expression of MCU and MICU1 decreased upon adding the MCU inhibitor ruthenium red. Conclusions: These results demonstrated that THF ameliorated glucose and lipid metabolism disorders in T2DM mice through improvement of AMPK/MICU1 pathway-dependent mitochondrial function in adipose tissue.

Background Tianhuang formula (THF) is a Chinese medicine prescription that is patented and clinically approved, and has been shown to improve energy metabolism, but the underlying mechanism remains poorly understood. The purpose of this study is to clarify the potential mechanisms of THF in the treatment of type 2 diabetes mellitus (T2DM). Methods A murine model of T2DM was induced by high-fat diet (HFD) feeding combined with low-dose streptozocin (STZ) injections, and the diabetic mice were treated with THF by gavaging for consecutive 10 weeks. Fasting blood glucose (FBG), serum insulin, blood lipid, mitochondrial Ca2+ (mCa2+) levels and mitochondrial membrane potential (MMP), as well as ATP production were analyzed. The target genes and proteins expression of visceral adipose tissue (Vat) was tested by RT-PCR and western blot, respectively. The underlying mechanism of the regulating energy metabolism effect of THF was further explored in the insulin resistance model of 3T3-L1 adipocytes cultured with dexamethasone (DXM). Results THF restored impaired glucose tolerance and insulin resistance in diabetic mice. Serum levels of lipids were significantly decreased, as well as fasting blood glucose and insulin in THF-treated mice. THF regulated mCa2+ uptake, increased MMP and ATP content in VAT. THF increased the mRNA and protein expression of AMPK, phosphorylated AMPK (p-AMPK), MICU1, sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). THF could increase the mCa2+ level of 3T3-L1 adipocytes and regulate mitochondrial function. The protein expression of AMPK, p-AMPK, mCa2+ uniporter (MCU) and MICU1 decreased upon adding AMPK inhibitor compound C to 3T3-L1 adipocytes and the protein expression of MCU and MICU1 decreased upon adding the MCU inhibitor ruthenium red. Conclusions These results demonstrated that THF ameliorated glucose and lipid metabolism disorders in T2DM mice through the improvement of AMPK/MICU1 pathway-dependent mitochondrial function in adipose tissue.