Dietary Fatty Acids Alter Lipid Profiles and Induce Myocardial Dysfunction without Causing Metabolic Disorders in Mice.

Oversupply of bulk saturated fatty acids (SFA) induces metabolic disorders and myocardial dysfunction. We investigated whether, without causing metabolic disorders, the uptake of individual dietary SFA species alters lipid profiles and induces myocardial dysfunction. C57BL/6 mice were fed various customized long-chain SFA diets (40% caloric intake from SFA), including a beef tallow (HBD), cocoa butter (HCD), milk fat (HMD) and palm oil diet (HPD), for 6 months. An isocaloric fat diet, containing medium-chain triglycerides, served as a control (CHD). Long-term intake of dietary long-chain SFA differentially affected the fatty acid composition in cardiac phospholipids. All long-chain SFA diets increased the levels of arachidonic acid and total SFA in cardiac phospholipids. The preferential incorporation of individual SFA into the cardiac phospholipid fraction was dependent on the dietary SFA species. Cardiac ceramide content was elevated in all mice fed long-chain SFA diets, while cardiac hypertrophy was only presented in mice fed HMD or HPD. We have demonstrated that the intake of long-chain SFA species differentially alters cardiac lipid profiles and induces cardiac dysfunction, without causing remarkable metabolic disorders.

Antidiabetic Effect of Salvianolic Acid A on Diabetic Animal Models via AMPK Activation and Mitochondrial Regulation.

BACKGROUND/AIMS: Diabetes mellitus (DM) characterized by hyperglycemia contributes to macrovascular and microvascular complications. Salvianolic acid A (SalA) is a polyphenolic compound isolated from the root of Salvia miltiorrhiza Bunge, which is a traditional Chinese medicine widely used to treat cardiovascular diseases. However, little is known about its antidiabetic effect. Our study aimed to investigate the in vivo and in vitro antidiabetic effect of SalA and the underlying mechanisms. METHODS: Alloxan-induced type 1 diabetic mice and high-fat diet (HFD) and low-dose streptozotocin (STZ)-induced type 2 diabetic rats received SalA treatment. Blood glucose, oral glucose tolerance test (OGTT), 24-h food and water intake were monitored. In vitro, glucose consumption and uptake were measured in HepG2 cells and L6 myotubes. Mitochondrial function was detected in hepatic and skeletal muscle mitochondria. AMP-activated protein kinase (AMPK) and Akt were analyzed by western blot. RESULTS: In both type 1 and type 2 diabetic animals, SalA lowered fasting blood glucose (FBG) and fed blood glucose in dose-dependent manner, as well as reduced 24-h food and water intake. In vitro, SalA caused dose-dependent increase in glucose consumption and enhanced glucose uptake. SalA significantly increased ATP production from 10 min to 12 h in HepG2 cells and L6 myotubes. Interestingly, SalA decreased mitochondrial membrane potential (MMP) in HepG2 cells. Furthermore, SalA improved hepatic and skeletal muscle mitochondrial function, increased ATP production, and concurrently decreased MMP. In particularly, SalA activated AMPK phosphorylation through Ca(2+)/calmodulin-dependent protein kinase kinase ß (CaMKKß)/AMPK signaling pathway, independent of liver kinase 1 (LKB1)/AMPK pathway. However, SalA didn't show any effect on insulin secretagogue and activation of PI3K/Akt signaling pathway. CONCLUSION: SalA exhibits the antidiabetic effects in diabetic animal models through improving mitochondrial function, increasing ATP production, and decreasing MMP via CaMKKß/AMPK signaling pathway.

Salvianolic Acid a prevents the pathological progression of hepatic fibrosis in high-fat diet-fed and streptozotocin-induced diabetic rats.

Type 2 diabetes patients have an increased risk of developing hepatic fibrosis. Salvianolic acid A (SalA) has been reported to be a strong polyphenolic anti-oxidant and free radical scavenger. The aim of the present study was to evaluate the effect of SalA on the pathological progression of hepatic fibrosis in high-fat diet (HFD)-fed and streptozotocin (STZ)-induced diabetic rats and to clarify the underlying mechanisms. Type 2 diabetic animal model with hepatic fibrosis was developed by a high-sucrose, HFD and low-dose STZ injection (i.p.). Diabetic rats were randomly divided into SalA group (0.3 mg/kg/day) and diabetic control groups fed with a HFD. After administration for four months, SalA reversed the hyperlipidemia and reduced hepatic triglyceride (TG). Hematoxylin-Eosin (HE) and Picro acid-Sirius red staining results indicated that SalA significantly alleviated the lesions of hepatic steatosis and fibrosis, with the reduction of type I and III collagens. The expression of α-smooth-muscle-actin (α-SMA) and transforming growth factor ß1 (TGF-ß1) in the liver were markedly down-regulated by SalA treatment. TUNEL staining showed that SalA reduced apoptosis in hepatocytes. In addition, SalA improved hepatic mitochondrial respiratory function in diabetic rats. Taken together, these findings demonstrated that SalA could prevent the pathological progression of hepatic fibrosis in HFD-fed and STZ-induced diabetic rats. The underlying mechanisms may be involved in reducing oxidative stress, suppressing α-SMA and TGF-ß1 expression, as well as exerting anti-apoptotic and mitochondria-protective effects.

[Effects of the effective components group of xiaoshuantongluo formula on rat acute blood stasis model].

Effects of the effective components group of Xiaoshuantongluo formula (XECG) on rat acute blood stasis model were studied under the guidance of the concept of effective components group. Rat acute blood stasis model was induced by subcutaneous injection of epinephrine combined with ice water bath. Hemorheology indices such as whole blood viscosity, plasma viscosity, erythrocyte aggregation index and platelet aggregation rate; coagulation parameters including PT, APTT, TT and FIB; 6-keto-PGF1alpha, TXB2 and D-dimer levels were determined to evaluate the effects of XECG. The results showed that XECG significantly reduced ADP-induced platelet aggregation, but showed little influence on the whole blood viscosity, plasma viscosity and erythrocyte aggregation rate. XECG extended PT and TT slightly, but had no effects on APTT and FIB content. D-dimer levels significantly decreased after administration of XECG with a little decrease of TXB2, but the content of 6-keto-PGF1alpha did not change significantly. The results suggest that the role of XECG of anti-aggregation is more prominent.

Cytotoxic activities of extracts and compounds from Viscum coloratum and its transformation products by Rhodobacter sphaeroides.

The bioassay-oriented fractionation of mistletoe crude extracts (MCEE) using 75% ethanol and culture products of mistletoe transformed by Rhodobacter sphaeroides, a photosynthetic bacterium (PSBT), revealed that the high cytotoxic activities were due to the petroleum ether extracts (PEs) and the acid-precipitated proteins from the aqueous extracts (AQs) of MCEE and PSBT. The isolated triterpenes may account for the activities of the PEs of MCEE and PSBT, respectively. Extraction of MCEE using petroleum ether led to the isolation of 3-epi-betulinic acid (1), betulonic acid (2), oleanolic acid (3), and beta-amyrin acetate (4), while petroleum ether extraction of PSBT led to the isolation of 1,3,4,betulinic acid (5), erythrodiol (6), and (3beta)-olean-12-ene-3,23-diol (7). The PE of PSBT exerted higher cytotoxicity than the PE of MCEE, which was due to the different triterpene contents of these two extracts. The cytotoxic activities of all compounds were tested, and the results revealed that compounds 1, 2, 3, 5, 6, and 7 contributed significantly to the cytotoxicities of both PEs. The AQ of the PSBT exerted almost the same cytotoxic activity and lower toxicity compared to the AQ of the MCEE. These findings indicate that mistletoe products biotransformed by R. sphaeroides could be used to treat cancers, since they have lower toxicities and higher antitumor activities compared to standard treatments.