Herbal Leaves Can Suppress Oxidation of Perilla Oil.

Perilla oil is a valuable food source of α-linolenic acids. However, its high reactivity with oxygen shortens its shelf-life after opening. This study investigated the antioxidative profiles of 15 plant materials, including herbs, and examined methods to suppress the oxidation of perilla oil using these plant materials. These plant materials had wide ranges of phenolic, carotenoid, and chlorophyll contents. They exhibit radical scavenging activities and suppress lipid peroxidation, which show highly positive correlations with the phenolic contents. Dipping most of the plant materials examined in perilla oil suppressed its oxidation, and the peroxide values of the oil mixtures indicated a negative correlation with the carotenoid and chlorophyll contents of the plant materials. The leaves of Angelica, Astragalus, and Thyme herbs exhibited the same effect as that of ascorbyl palmitate, which was used as a positive control after 8 wk of incubation in the dark. The suppression of lipid peroxidation was found to be related to the herbal contents of carotenoids and chlorophylls, rather than phenols. Hence, herbal leaves can suppress the oxidation of perilla oil in the dark. The oxidation of n-3 polyunsaturated fatty acids could be suppressed effectively by utilizing plant materials with abundant carotenoids and chlorophylls.

Identification of novel benzimidazole derivatives as highly potent AMPK activators with anti-diabetic profiles.

Diabetes is a global healthcare problem that affects more than 400 million people worldwide. Treatment for type 1 and 2 diabetes is expected by targeting adenosine monophosphate activated protein kinase, AMPK, a well-known master regulator of glucose. Many pharmaceutical companies have tried to identify AMPK activators but few direct AMPK activators with high potency for the ß2-AMPK isoform, which is important for glucose homeostasis, have been found. In addition, their chemical structure is limited to benzimidazole or indole derivatives bearing an aromatic substituent at the C5 position of the core structure. We describe herein our efforts to identify novel benzimidazole derivatives that directly activate the ß2-AMPK isoform. Our newly designed activator 14d bearing a 1-amino indanyl moiety at the C5 position of the core exhibited high in vitro potency and good pharmacokinetic profiles. A single oral dosing of 14d showed dose-dependent activation of AMPK and blood-glucose-lowering effects was observed in a diabetic animal model. In addition, chronic AMPK activation with 14d led to dose-dependent reduction in HbA1c of the animal model.

Identification of novel indole derivatives as highly potent AMPK activators with anti-diabetic profiles.

AMP-activated protein kinase (AMPK) has been shown to play an important role in the beneficial effects of exercise on glucose and lipid metabolism in skeletal muscle and liver. Therefore, activation of AMPK has been proposed as an attractive strategy for the treatment of metabolic disorders, such as type 2 diabetes. Many of existing AMPK activators bearing diverse chemical structure were reported. However, there have been few reports of direct AMPK activator with high potency for ß2-AMPK isoform, which is thought to be important for glucose homeostasis, and their chemical structure is limited to benzimidazole core. We describe herein our efforts for identification of novel AMPK activator. Our newly designed 4-azaindole derivative 16g exhibited single-digit nM in vitro activity, and chronic treatment with 16g led to dose-dependent improvement in HbA1c as well as decrease in hepatic lipid accumulation in diabetic animal model.

Nickel-catalyzed enantio- and diastereoselective three-component coupling of 1,3-dienes, aldehydes, and silanes using chiral N-heterocyclic carbenes as ligands.

Nickel(0)-catalyzed asymmetric three-component coupling of 1,3-dienes, aldehydes, and silanes has been realized utilizing a chiral N-heterocyclic carbene as a ligand. On the basis of the screening of various NHC precursors, an imidazolium salt having 1-(2,4,6-trimethylphenyl)propyl groups on the nitrogen was designed and synthesized. In this reaction, various coupling products were produced in good yields with high regio-, diastereo- (anti selective in the case of the internal 1,3-diene), and enantioselectivities (up to 97% ee).