Guan Xin Dan Shen formulation protects db/db mice against diabetic cardiomyopathy via activation of Nrf2 signaling.

Guan Xin Dan Shen formulation (GXDSF) is a widely used treatment for the management of coronary heart disease in China and is composed of three primary components: Dalbergiae odoriferae Lignum, Salviae miltiorrhizae Radix et Rhizoma and Panax notoginseng Radix et Rhizoma. However, the potential use of GXDSF for the management of diabetic cardiomyopathy (DCM) has not been previously assessed. The present study aimed to assess the effects of GXDSF on DCM, as well as the underlying mechanism. In the present study, db/db mice were used. Following treatment with GXDSF for 10 weeks, fasting blood glucose, insulin sensitivity, serum lipid levels and cardiac enzyme levels were detected. Cardiac pathological alterations and cardiac function were assessed by performing hematoxylin and eosin staining and echocardiograms, respectively. TUNEL assays were conducted to assess cardiomyocyte apoptosis. Additionally, reverse transcription­quantitative PCR and western blotting were performed to evaluate the expression of apoptosis­associated genes and proteins, respectively. In the model group, the db/db mice displayed obesity, hyperlipidemia and hyperglycemia, accompanied by noticeable myocardial hypertrophy and diastolic dysfunction. Following treatment with GXDSF for 10 weeks, serum triglyceride levels were lower and insulin sensitivity was enhanced in db/db mice compared with the model group, which indicated improvement in condition. Cardiac hypertrophy and dysfunction were also improved in db/db mice following treatment with GXDSF, resulting in significantly increased left ventricular ejection fraction and fractional shortening compared with the model group. Following treatment with metformin or GXDSF, model­induced increases in levels of myocardial enzymes were decreased in the moderate and high dose groups. Moreover, the results indicated that, compared with the model group, GXDSF significantly inhibited cardiomyocyte apoptosis in diabetic heart tissues by increasing Bcl­2 expression and decreasing the expression levels of Bax, cleaved caspase­3 and cleaved caspase­9. Mechanistically, GXDSF enhanced Akt phosphorylation, which upregulated antioxidant enzymes mediated by nuclear factor erythroid 2­related factor 2 (Nrf2) signaling. Collectively, the results of the present study indicated that GXDSF attenuated cardiac dysfunction and inhibited cardiomyocyte apoptosis in diabetic mice via activation of Akt/Nrf2 signaling. Therefore, GXDSF may serve as a potential therapeutic agent for the management of DCM.

The effects of acarbose therapy on reductions of myocardial infarction and all-cause death in T2DM during 10-year multifactorial interventions (The Beijing Community Diabetes Study 24).

To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The study population of Beijing Community Diabetes Study (BCDS) were type 2 diabetes (T2DM) living in 21 communities in Beijing. All patients received comprehensive intervention in accordance with the Chinese guidelines for the prevention and treatment of diabetes. Professors in endocrinology from top tier hospitals regularly visited the communities for consultations, which was a feature of this study. A total of 1797 T2DM in BCDS study had complete screening data, including blood glucose, blood pressure, lipid profiles and acarbose continuous therapy. After 10-year follow-up, the risks of CVD outcomes were assessed according to whether patients had received acarbose therapy or not. All patients were followed-up to assess the long-term effects of the multifactorial interventions. At baseline, compared with the acarbose therapy free in T2DM, there was no significant difference in achieving the joint target control in patients with acarbose therapy. From the beginning of 8th year follow-up, the joint target control rate in patients with acarbose therapy was significantly higher than that of acarbose therapy free. During the 10-year follow-up, a total of 446 endpoint events occurred, including all-cause death, cardiovascular events, cerebrovascular events. The incidences of myocardial infarction (from the 4th year of follow-up) and all-cause death (from the 2nd year of follow-up) in patients who received acarbose therapy were significantly lower than that of acarbose therapy free respectively. In Cox multivariate analyses, there were significant differences in incidences of myocardial infarction and all-cause death between afore two groups during the 10-year follow-up, and the adjusted HRs were 0.50 and 0.52, respectively. After multifactorial interventions, T2DM with acarbose therapy revealed significant reductions of myocardial infarction and all-cause death. The long-term effects of with acarbose therapy on improving joint target control might be one of the main reasons of myocardial infarction and all-cause death reduction.Trial Registration: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

[Effect of Guanxin Danshen Formulation on diabetic kidney disease in db/db mice through regulation of Nrf2 pathway].

Diabetic kidney disease(DKD) has become a primary cause of end-stage kidney disease, without any effective treatment available. In this study, we assessed the protective effect of Guanxin Danshen Formulation(GXDSF) on diabetic nephropathy in db/db mice. The db/m and db/db mice were randomly divided into 4 groups: control group, model group, metformin group, and GXDSF group. After 8 weeks' treatment with GXDSF, metformin or normal saline, the mice were sacrificed, and the blood and kidney tissues were collected for the further analysis. Compared with the model group, TG, TCH and LDL levels significantly decreased in the GXDSF group. The results from HE and PAS staining showed that db/db mice exhibited abnormal kidney tissues with increased glomerular volume, basement-membrane thickening and mesangial cell proliferation, which could be significantly alleviated by GXDSF treatment. GXDSF treatment also reduced serum creatinine and BUN. Meanwhile, GXDSF treatment markedly elevated GSH-PX levels, while reduced LDH and MDA levels in the kidney tissues. Western blot assay showed that GXDSF evidently up-regulated protein levels of ERα and p-Akt, and subsequently promoted HO-1 expression mediated by Nrf2. These data collectively indicated that GXDSF protects db/db mice against DN by regulating ERα and Nrf2-mediated HO-1 expression.

[Intervention of Qingshen Granule for Immune Inflammation of Chronic Renal Failure Patients with Damp-heat Syndrome].

Objective To observe the effect of Qingshen Granule (QG) on the immune function of chronic renal failure (CRF) patients with damp-heat syndrome (DHS). Methods A total of 162 CRF patients were assigned to the treated group and the control group by random digit table, 81 in each group. All patients were treated with conventional Western medical therapy. Those in the treated group addition- ally took QG, one package each time (10 g) , thrice per day. The therapeutic course for all was 12 weeks. The clinical efficacy was observed in the two groups. The contents of peripheral blood CD4 ⁺ T cells, CD8 ⁺ T cells, Thl7 cells, and nuclear factor-κB p65 (NF-κBp65) activity were detected using flow cy- tometry. Expressions of serum IL-17, tumor necrosis factor receptor-associated factor 6 (TRAF6), ma- trix metalloproteinase-9 (MMP-9) , matrix metalloproteinase inhibitor-I (TIMP-1 ) , collagen N (Col-V) were detected using ELISA. Results Finally 156 patients completed the trial (77 cases in the treated group and 79 cases in the control group). The total clinical curative effective rate was significantly higher in the treated group (80. 52%, 62/77) than in the control group (68. 35%, 54/79) with statistical differ- ences between the two groups (x² = 54. 849, P <0. 05). Compared with before treatment in the same group, the levels of peripheral blood CD4 ⁺ /CD8 ⁺ , Thl7 cell content, NF-κB p65 activity, serum levels of IL-17, TRAF6, and TIMP-1 , TIMP-1/MMP-9 ratio, Col-IV level all decreased in the treated group after treat- ment (P <0. 05) ; serum MMP-9 level decreased .(P <0. 05) and TIMP-1 /MMP-9 ratio increased (P <0. 05) in the control group. Compared with the control group, CD4⁺/CD8 ⁺ T cell ratio, Th17 cell content, NF-κB p65 activity decreased more obviously in the treated group after treatment (P <0. 05). Serum levels of IL- 17, TRAF6, TIMP-1, TIMP-1/MMP-9 ratio, and Col-IV all decreased (P <0.05) and MMP-9 level increased (P <0. 05) in the treated group (P <0. 05). Conclusion QG could adjust immune dysfunction and disar- ranged immunity mediated inflammatory response, and attenuate renal fibrosis in CKD patients with DHS.

[Sesquiterpenes of Chloranthus serratus Root].

OBJECTIVE: To study sesquiterpenes from the root of Chloranthus serratus. METHODS: The sesquiterpenes of Chloranthus serratus were isolated and purified by various chromatographic techniques, such as silica gel, Sephadex LH-20 and preparative HPLC. The structures of these isolated compounds were identified by spectroscopic analysis. RESULTS: Ten sesquiterpenes were isolated and identified as follows: 1ß, 8ß-dihydroxy-eudesman-4 (15), 7 (11) -dien-8α, 12-olide (I), curcolonol (II), 4ß, 8ß-dihydroxy-5α (H) -eudesm-7 (11) -en-8, 12-olide (III), 1ß, 8,ß-dihydroxy-eudesman-3, 7 (11) -dien-8α, 12-olide (IV), multistalactone E (V), zedoarofuran (VI), 8ß,9α-dihydroxylindan-4(5), 7(11) -dien-8α,12-olide(VII), serralactone A (VIII), 8-epi-ivangustin (IX), and chloranthalactone E (X ). CONCLUSION: Compounds I, II, IV - VII, IX and X are isolated from Chloranthus serratus for the first time.

[Clinical efficacy observation on paroxysmal atrial fibrillation treated by acupuncture combined with Wenxin granule].

OBJECTIVE: To compare the difference of clinical efficacy in the treatment of paroxysmal atrial fibrillation (PAF) between acupuncture combined with Wenzin granule and simple Wenxin granule therapy. METHODS: Sixty hospitalized cases of PAF were randomized into a medication group and a medication--acupuncture group. Wenxin granule was given to the patients in the two groups 3 times a day, 9 g each time, 4 weeks as a treatment course. Meanwhile, acupuncture was added to the medication--acupuncture group at bilateral Neiguan (PC 6), Shenmen (HT 7), Ximen (PC 4) with uneven reinforcing-reducing manipulation every 15 min, 1 min each time. The needle was retained for 30 minutes. The acupuncture was given once daily for continuously 4 weeks. The therapeutic efficacy of the two groups was assessed after treatment. METHODS: In the medication+acupuncture group, 18 cases were markedly effective, 10 cases were effective and 2 cases were failed, the total effective rate was 93.3%; in the medication group, 15 cases were markedly effective, 8 cases were effective and 7 cases were failed, the total effective rate was 76.7%. There were statistical significances in clinical efficacy between the two groups (P<0.05). CONCLUSION: Acupuncture combined with Wenxin granule has a better effect than simple Wenxin granule therapy in the treatment of paroxysmal atrial fibrillation.

IAA stimulates pollen tube growth and mediates the modification of its wall composition and structure in Torenia fournieri.

The effects of several hormones on pollen tube growth were compared in Torenia fournieri and it was found that IAA was the most effective, stimulating pollen tube growth and causing the shank part of pollen tubes to be slender and straighter. The role of IAA was investigated by studying the changes in ultrastructure and PM H(+)-ATPase distribution in the pollen tubes and the modification of the tube wall. Using the fluorescent marker FM4-64, together with transmission electron microscopy, it was shown that secretory vesicles and mitochondria increased in IAA-treated tubes. Immunolocalization and fluorescence labelling, together with Fourier-transform infrared analysis, detected that IAA enhanced the level of PM H(+)-ATPase and the synthesis of pectins, and reduced the cellulose density in pollen tubes. Importantly, to observe the orientation of cellulose microfibrils in pollen tubes in situ, atomic force microscopy was used to examine the 'intact' tube wall. Atomic force microscopy images showed that cellulose microfibrils were parallel to each other in the subapical region of IAA-treated tubes, but disorganized in control tubes. All results provided new insights into the functions of cellulose microfibrils in pollen tube growth and direction, and revealed that the IAA-induced changes of pollen tubes were attributed to the increase in secretory vesicles, mitochondria, and PM H(+)-ATPase, and the modification of pectin and cellulose microfibrils in the tube wall.