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Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion. [ABSTRACT FROM AUTHOR]

Tang Luo Ning (TLN), a traditional Chinese compound prescription, has been used clinically to treat diabetic peripheral neuropathy (DPN) in China. However, the exact mechanisms remain unclear. The objective of this study is to unravel the effects of TLN on mitochondrial dynamics of DPN in streptozotocin-induced rat models and Schwann cells cultured in 150 mM glucose. Mitochondrial function was determined by Ca2+ and ATP levels of streptozotocin (STZ)-induced DPN rats and mitochondria structure, mitochondrial membrane potential (MMP), and mtDNA of high glucose incubated SCs. Mitochondrial dynamics protein including mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), optic atrophy 1 (Opa1), and dynamin-related protein 1 (Drp1) were investigated using Western blot or immunofluorescence. Myelin basic protein (MBP), myelin protein zero (MPZ), and sex-determining region Y (SRY)-box 10 (Sox10) were measured to represent schwannopathy. Our results showed that TLN increased ATP levels (0.38 of model, 0.69 of HTLN, 0.61 of LTLN, P ＜0.01; 0.52 of 150 mM glucose, 1.00 of 10% TLN, P ＜0.01, 0.94 of 1% TLN, P ＜0.05), MMP (0.56 of 150 mM glucose, P ＜0.01, 0.75 of 10% TLN, P ＜0.05, 0.83 of 1% TLN, P ＜0.01), and mtDNA (0.32 of 150 mM glucose, 0.43 of 10% TLN, P ＜0.01) while decreased Ca2+ (1.54 of model, 1.06 of HTLN, 0.96 of LTLN, P ＜0.01) to improve mitochondrial function in vivo and in vitro. TLN helps maintain balance of mitochondrial dynamics: it reduces the mitochondria number (1.60 of 150 mM glucose, 1.10 of 10% TLN, P ＜0.01) and increases the mitochondria coverage (0.51 of 150 mM glucose, 0.80 of 10% TLN, 0.87 of 1% TLN, P ＜0.01), mitochondrial network size (0.51 of 150 mM glucose, 0.95 of 10% TLN, 0.94 of 1% TLN, P ＜0.01), and branch length (0.63 of 150 mM glucose, P ＜0.01, 0.73 of 10% TLN, P ＜0.05, 0.78 of 1% TLN, P ＜0.01). Further, mitochondrial dynamics–related Mfn1 (0.47 of model, 0.82 of HTLN, 0.77 of LTLN, P ＜0.01; 0.42 of 150 mM glucose, 0.56 of 10% TLN, 0.57 of 1% TLN, P ＜0.01), Mfn2 (0.40 of model, 0.84 of HTLN, 0.63 of LTLN, P ＜0.01; 0.46 of 150 mM glucose, 1.40 of 10% TLN, 1.40 of 1% TLN, P ＜0.01), and Opa1 (0.58 of model, 0.71 of HTLN, 0.90 of LTLN, P ＜0.01; 0.69 of 150 mM glucose, 0.96 of 10% TLN, 0.98 of 1% TLN, P ＜0.05) were increased, while Drp1 (1.39 of model, 0.96 of HTLN, 1.18 of LTLN, P ＜0.01; 1.70 of 150 mM glucose, 1.20 of 10% TLN, 1.10 of 1% TLN, P ＜0.05), phosphorylated Drp1 (2.61 of model, 1.44 of HTLN, P ＜0.05; 2.80 of 150 mM glucose, 1.50 of 10% TLN, 1.30 of 1% TLN, P ＜0.01), and Drp1 located in mitochondria (1.80 of 150 mM glucose, 1.00 of 10% TLN, P ＜0.05) were decreased after treatment with TLN. Additionally, TLN improved schwannopathy by increasing MBP (0.50 of model, 1.05 of HTLN, 0.94 of HTLN, P ＜0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, P ＜0.01, 0.72 of 1% TLN, P ＜0.05), Sox101 (0.41 of model, 0.99 of LTLN, P ＜0.01; 0.48 of 150 mM glucose, 0.65 of 10% TLN, P ＜0.05, 0.69 of 1% TLN, P ＜0.01), and MPZ (0.48 of model, 0.66 of HTLN, 0.55 of HTLN, P ＜0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, P ＜0.01, 0.75 of 1% TLN, P ＜0.05) expressions. In conclusion, our study indicated that TLN's function on DPN may link to the improvement of the mitochondrial dynamics, which provides scientific evidence for the clinical application. [ABSTRACT FROM AUTHOR]

Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion. [ABSTRACT FROM AUTHOR]

Tang Luo Ning (TLN), a traditional Chinese compound prescription, has been used clinically to treat diabetic peripheral neuropathy (DPN) in China. However, the exact mechanisms remain unclear. The objective of this study is to unravel the effects of TLN on mitochondrial dynamics of DPN in streptozotocin-induced rat models and Schwann cells cultured in 150 mM glucose. Mitochondrial function was determined by Ca2+ and ATP levels of streptozotocin (STZ)-induced DPN rats and mitochondria structure, mitochondrial membrane potential (MMP), and mtDNA of high glucose incubated SCs. Mitochondrial dynamics protein including mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), optic atrophy 1 (Opa1), and dynamin-related protein 1 (Drp1) were investigated using Western blot or immunofluorescence. Myelin basic protein (MBP), myelin protein zero (MPZ), and sex-determining region Y (SRY)-box 10 (Sox10) were measured to represent schwannopathy. Our results showed that TLN increased ATP levels (0.38 of model, 0.69 of HTLN, 0.61 of LTLN, P ＜0.01; 0.52 of 150 mM glucose, 1.00 of 10% TLN, P ＜0.01, 0.94 of 1% TLN, P ＜0.05), MMP (0.56 of 150 mM glucose, P ＜0.01, 0.75 of 10% TLN, P ＜0.05, 0.83 of 1% TLN, P ＜0.01), and mtDNA (0.32 of 150 mM glucose, 0.43 of 10% TLN, P ＜0.01) while decreased Ca2+ (1.54 of model, 1.06 of HTLN, 0.96 of LTLN, P ＜0.01) to improve mitochondrial function in vivo and in vitro. TLN helps maintain balance of mitochondrial dynamics: it reduces the mitochondria number (1.60 of 150 mM glucose, 1.10 of 10% TLN, P ＜0.01) and increases the mitochondria coverage (0.51 of 150 mM glucose, 0.80 of 10% TLN, 0.87 of 1% TLN, P ＜0.01), mitochondrial network size (0.51 of 150 mM glucose, 0.95 of 10% TLN, 0.94 of 1% TLN, P ＜0.01), and branch length (0.63 of 150 mM glucose, P ＜0.01, 0.73 of 10% TLN, P ＜0.05, 0.78 of 1% TLN, P ＜0.01). Further, mitochondrial dynamics–related Mfn1 (0.47 of model, 0.82 of HTLN, 0.77 of LTLN, P ＜0.01; 0.42 of 150 mM glucose, 0.56 of 10% TLN, 0.57 of 1% TLN, P ＜0.01), Mfn2 (0.40 of model, 0.84 of HTLN, 0.63 of LTLN, P ＜0.01; 0.46 of 150 mM glucose, 1.40 of 10% TLN, 1.40 of 1% TLN, P ＜0.01), and Opa1 (0.58 of model, 0.71 of HTLN, 0.90 of LTLN, P ＜0.01; 0.69 of 150 mM glucose, 0.96 of 10% TLN, 0.98 of 1% TLN, P ＜0.05) were increased, while Drp1 (1.39 of model, 0.96 of HTLN, 1.18 of LTLN, P ＜0.01; 1.70 of 150 mM glucose, 1.20 of 10% TLN, 1.10 of 1% TLN, P ＜0.05), phosphorylated Drp1 (2.61 of model, 1.44 of HTLN, P ＜0.05; 2.80 of 150 mM glucose, 1.50 of 10% TLN, 1.30 of 1% TLN, P ＜0.01), and Drp1 located in mitochondria (1.80 of 150 mM glucose, 1.00 of 10% TLN, P ＜0.05) were decreased after treatment with TLN. Additionally, TLN improved schwannopathy by increasing MBP (0.50 of model, 1.05 of HTLN, 0.94 of HTLN, P ＜0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, P ＜0.01, 0.72 of 1% TLN, P ＜0.05), Sox101 (0.41 of model, 0.99 of LTLN, P ＜0.01; 0.48 of 150 mM glucose, 0.65 of 10% TLN, P ＜0.05, 0.69 of 1% TLN, P ＜0.01), and MPZ (0.48 of model, 0.66 of HTLN, 0.55 of HTLN, P ＜0.01; 0.60 of 150 mM glucose, 0.78 of 10% TLN, P ＜0.01, 0.75 of 1% TLN, P ＜0.05) expressions. In conclusion, our study indicated that TLN's function on DPN may link to the improvement of the mitochondrial dynamics, which provides scientific evidence for the clinical application. [ABSTRACT FROM AUTHOR]