(−)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana prevents diabetes and dyslipidemia in streptozotocin-induced diabetic mice

Abstract

The objective of this study was to evaluate the effects and molecular mechanism of (−)-epicatechin-3-O-β-D-allopyranoside from Davallia formosana (BB) (also known as Gu-Sui-Bu) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. This plant was demonstrated to display antioxidant activities and possess polyphenol contents. Diabetic mice were randomly divided into six groups and were given daily oral gavage doses of either BB (at three dosage levels), metformin (Metf) (at 0.3 g/kg body weight), fenofibrate (Feno) (at 0.25 g/kg body weight) or vehicle (distilled water) and a group of control (CON) mice were gavaged with vehicle over a period of 4 weeks. Treatment with BB led to reduced levels of blood glucose, HbA1C, triglycerides and leptin and to increased levels of insulin and adiponectin compared with the vehicle-treated STZ group. The diabetic islets showed retraction from their classic round-shaped as compared with the control islets. The BB-treated groups (at middle and high dosages) showed improvement in islets size and number of Langerhans islet cells. The membrane levels of skeletal muscular glucose transporter 4 (GLUT4) were significantly higher in BB-treated mice. This resulted in a net glucose lowering effect among BB-treated mice. Moreover, BB enhanced the expression of skeletal muscle phospho-AMPK in treated mice. BB-treated mice increased expression of fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα) and mRNA levels of carnitine palmitoyl transferase Ia (CPT1a). These mice also expressed lower levels of lipogenic genes such as fatty acid synthase (FAS), as well as lower mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and liver adipocyte fatty acid binding protein 2 (aP2). This resulted in a reduction in plasma triglyceride levels. BB-treated mice also expressed lower levels of PPARγ and FAS protein. This led to reduced adipogenesis, fatty acid synthesis and lipid accumulation within adipose tissue, and consequently, to lower triglyceride levels in liver, blood, and adipose tissue. Moreover, BB treatment not only displayed the activation Akt in liver tissue and skeletal muscle, but also in C2C12 myotube to cause an increase in phosphorylation of Akt in the absence of insulin. These results demonstrated that BB act as an activator of AMPK and /or regulation of insulin pathway (Akt), and the antioxidant activity within the pancreas. Therefore, BB treatment ameliorated the diabetic and dyslipidemic state in STZ-induced diabetic mice.

Insulin-independent stimulation of skeletal muscle glucose uptake by low-dose abscisic acid via AMPK activation

“…A different role for Akt phosphorylated on Ser473 alone, or both on Ser473 and on Thr308 might be envisaged also based on the facts that defective Ser473 phosphorylation affects only a subset of Akt targets 34 and that different phosphatases specifically dephosphorylate these residues 35 . Phosphorylation of both Akt and AMPK at Ser473 and Thr172, respectively, with stimulation of muscle glucose uptake has been reported for other natural products 36 : thus, it is tempting to speculate that ABA may be the endogenous hormone responsible for activation of this pathway, the details of which remain to be clarified.…”

Antidiabetic and hypolipidemic activities of eburicoic acid, a triterpenoid compound from Antrodia camphorata, by regulation of Akt phosphorylation, gluconeogenesis, and PPARα in streptozotocin-induced diabetic mice

“…The treatments of cells with TRR or insulin were initiated on day 6 when myotube differentiation was complete, and this part method has been described in our previous publication. 19 in SDS sample buffer (62.5 mM Tris-HCl, 20% glycerol, 2% SDS, 75 M DTT, and 0.05% bromophenol blue), subjected to SDS PAGE and were detected by western blotting with antibodies specic for total-Akt (t-Akt) and phospho-Akt (Ser 473 ) (p-Akt). The density blotting was analyzed using Alpha Easy FC soware (Alpha Innotech Corp., Randburg, South Africa).…”

“…The STZ mice that were found to develop hyperglycemia, dened as fasting blood glucose above 250 mg dL À1 , were considered to have diabetes for this study. 19,20 The STZ-induced diabetic mice (n ¼ 48) were then randomly divided into six groups treated as follows: (1) control vehicle (STZ control group) (with similar volumes); (2) three groups were administered of TRR at either 10, 20, or 40 mg kg À1 (groups TRR1, TRR2, or TRR3, respectively); (3) two comparator groups were treated with fenobrate (Feno) (250 mg kg À1 ), or metformin (Metf) (300 mg kg À1 ). The vehicle, TRR or Feno or Metf was treated by oral gavage once per day for 14 days.…”

“…Mice were monitored for food intake per day according to weighing the amount of put pellet food, and the amount of remaining food aer 24 h, and the difference is represented the food intake per day, and this animal study method has been described in our previous publication with minor modication. 19 2.6. Analysis of blood glucose, triglyceride, total cholesterol, adipocytokine, and HbA1 C levels Blood samples were collected from the retro-orbital sinuses of 10-12 h fasted mice, and the samples (>20 mL) immediately were placed on tinfoil paper and quickly on machines.…”

Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression

“…Several bioactive components extracted from DFE have been identified, including davallic acid [39], flavan-3-ol, and proanthocyanidin allosides [40] as well as (−)-epicatechin 3-O-β-D-allopyranoside [41,42]. Among these identified components, (−)-epicatechin 3-O-β-D-allopyranoside has been demonstrated to show anti-inflammatory activity [1], and prevent diabetes and dyslipidemia via alternation of the AMPK and Akt pathways exhibiting low cytotoxicity in the hosts [41,42]. Additionally, we examined this compound in PCa cells.…”