Amelioration of cardiac dysfunction and ventricular remodeling after myocardial infarction by danhong injection are critically contributed by anti-TGF-ß-mediated fibrosis and angiogenesis mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI) is a standardized product extracted from Radix et Rhizoma Salviae Miltiorrhizae and Flos Carthami , which has been long applied mainly used to treat ischemic encephalopathy and cardiac diseases including myocardial infarction and angina in clinical practice. AIM OF THE STUDY: Aim of this study was to investigate the salutary effects of DHI by slowing ventricular remodeling and improving cardiac function after myocardial infarction (MI) in rats. MATERIALS AND METHODS: In this study, Male Sprague-Dawley rats were subjected to ligation on left anterior descending coronary artery to establish MI models and valsartan was selected as positive control. Cardiac function examination was conducted at the 1st, 3rd, 7th, 14th and the 28th days after LAD. Haematoxylin and Eosin (HE) staining and Masson staining were conducted to observe cardiac pathology and morphological changes levels of VEGF, TGF-ß, MMP-2, and MMP-9 in the myocardial tissue were determined in gene and protein expressions. RESULTS: After 3 days post-treatment and thereafter, EF and FS in DHI group were greater than that of model group (p<0.05). Compared with the MI group, ratio of infarct was markedly decreased in treated-DHI group(p<0.05). TGF-ß1 protein and fibrosis-related proteins MMP-2 and MMP-9 were up-regulated after MI, and they were significantly suppressed by the administration of DHI(p<0.05 and p<0.01, respectively). Moreover, DHI improved the mRNA expression of VEGF and increased the blood vessel density of myocardial infarct border zone. DHI decreased the expression of cell apoptosis protein of caspase-3 and increased the anti-apoptotic protein, bcl-2. CONCLUSIONS: We provided direct evidences that DHI improves cardiac remodeling and preserves ventricular function post-MI in rats. DHI conferred cardio-protection in rats with MI via anti-myocardial apoptosis, angiogenesis, reduction of myocardial fibrosis and many other aspects of joint actions.

Danshensu alleviates cardiac ischaemia/reperfusion injury by inhibiting autophagy and apoptosis via activation of mTOR signalling.

The traditional Chinese medicine Danshensu (DSS) has a protective effect on cardiac ischaemia/reperfusion (I/R) injury. However, the molecular mechanisms underlying the DSS action remain undefined. We investigated the potential role of DSS in autophagy and apoptosis using cardiac I/R injury models of cardiomyocytes and isolated rat hearts. Cultured neonatal rat cardiomyocytes were subjected to 6 hrs of hypoxia followed by 18 hrs of reoxygenation to induce cell damage. The isolated rat hearts were used to perform global ischaemia for 30 min., followed by 60 min. reperfusion. Ischaemia/reperfusion injury decreased the haemodynamic parameters on cardiac function, damaged cardiomyocytes or even caused cell death. Pre-treatment of DSS significantly improved cell survival and protected against I/R-induced deterioration of cardiac function. The improved cell survival upon DSS treatment was associated with activation of mammalian target of rapamycin (mTOR) (as manifested by increased phosphorylation of S6K and S6), which was accompanied with attenuated autophagy flux and decreased expression of autophagy- and apoptosis-related proteins (including p62, LC3-II, Beclin-1, Bax, and Caspase-3) at both protein and mRNA levels. These results suggest that alleviation of cardiac I/R injury by pre-treatment with DSS may be attributable to inhibiting excessive autophagy and apoptosis through mTOR activation.

Danzhi Qing'e (DZQE) activates AMPK pathway and regulates lipid metabolism in a rat model of perimenopausal hyperlipidaemia.

What is the central question of this study? Does Danzhi Qing'e (DZQE) regulate lipid metabolism and improve ovarian function in a rat model of perimenopausal hyperlipidaemia, and could this effect be mediated through the AMPK pathway? What is the main finding and its importance? We revealed that DZQE is a pharmacotherapy that could activate the AMPK pathway to improve ovarian function and lipid metabolism during perimenopause complicated with hyperlipidaemia syndrome in an animal model. Thus, this study provides a novel therapeutic option for treating perimenopausal syndrome and highlights the therapeutic potential of DZQE in perimenopausal rats. Menopause is an important event in a woman's life. During perimenopause, accompanied by development of osteoporosis and dyslipidaemia, ovarian function gradually declines. Dyslipidaemia is a risk factor for cardiovascular disorders, cerebrovascular disease and breast cancer in postmenopausal women. All of these contribute to impairment of liver function, particularly fatty liver disease, because liver dysfunction is associated with ovarian dysfunction and hyperlipidaemia. The aim of this study was to define a therapeutic approach to improve ovarian function and attenuate lipid accumulation in order to prevent perimenopause-induced ovarian dysfunction and hyperlipidaemia. Four-week-old female Wistar rats were injected i.p. with 4-vinylcyclohexene diepoxide (4-VCD) and fed with a high-fat diet (HFD) to serve as a model of perimenopause complicated with hyperlipidaemia. The 4-VCD induces perimenopause, while the HFD causes hyperlipidaemia. Five days after administration of 4-VCD, the 4-VCD + HFD-treated rats were assessed daily for oestrous cycle stage by vaginal cytology. Rats were then assigned into groups, in which 2.5, 5.0 or 10.0 g kg-1 Danzhi Qing'e (DZQE) or estradiol valerate was administered intragastrically for 8 weeks. Expression levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestrogen and testosterone measured by enzyme-linked immunosorbent assay served as biomarkers for perimenopause and ovarian dysfunction. The expression levels of AMPK and acetyl-CoA carboxylase in the liver were determined with Western blotting, and aspartate aminotransferase and alanine aminotransferase were analysed using an automated biochemical analyser to examine liver function. The DZQE improved ovarian function by upregulating oestrogen and testosterone concentrations in serum and downregulating FSH and LH serum concentrations. Moreover, DZQE reduced serum concentrations of triglyceride, total cholesterol and low-density lipoprotein in a dose-dependent manner to regulate lipid levels during perimenopause. Furthermore, DZQE increased AMPK at both the transcriptional and translational levels and decreased the expression of SREBP-1c gene as well as its downstream target gene, fatty acid synthase. Danzhi Qing'e improved dyslipidaemia during menopause and also had an effect on liver function. Danzhi Qing'e is an effective Chinese herbal compound, which improves ovarian function and lipid metabolism in perimenopause complicated with hyperlipidaemia at least in part through the AMPK pathway.

Gastrodin Reduces Blood Pressure by Intervening with RAAS and PPARγ in SHRs.

Gastrodin is a bioactive compound extracted from traditional Chinese medicine, Gastrodia elata Bl. It has a definite effect on reducing blood pressure in hypertensive patients. However, the mechanisms of gastrodin in lowering blood pressure still remain unclear. In this study, 4 weeks of administration of gastrodin (100 mg/kg/d intraperitoneally injected) decreased the systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) (190.2 ± 8.9 versus 169.8 ± 6.4, P < 0.01). Among SHRs receiving gastrodin treatment, angiotensin II (Ang II) and aldosterone (ALD) in serum were significantly decreased (2022.1 ± 53.0 versus 1528.7 ± 93.9, 213.33 ± 35.17 versus 179.65 ± 20.31, and P < 0.01, P < 0.05, resp.) and dramatically downregulated expression of angiotensin type 1 receptor (AT1R) (4.9 ± 0.9 versus 2.6 ± 0.9, P < 0.05) in myocardium in both mRNA and protein levels compared with their corresponding groups without gastrodin treatment. Additionally, gastrodin increased the mRNA expression (0.18 ± 0.07 versus 0.82 ± 0.10, P < 0.01) and protein synthesis (0.40 ± 0.10 versus 0.34 ± 0.10, P < 0.01) of peroxisome proliferator-activated receptor γ (PPARγ) in myocardium tissues. Overall, our data demonstrated that gastrodin was able to decrease the SBP in SHR. Furthermore, this study showed that gastrodin intervened with the renin-angiotensin-aldosterone system (RAAS) and PPARγ effectively, which indicates its antihypertensive mechanism.