Hepatoprotective Activity of Yellow Chinese Chive against Acetaminophen-Induced Acute Liver Injury via Nrf2 Signaling Pathway.

Glutathione, the most abundant intracellular antioxidant, protects cells against reactive oxygen species induced oxidative stress and regulates intracellular redox status. We previously demonstrated that yellow Chinese chive (ki-nira) increased the intracellular glutathione levels. Acetaminophen (APAP) is a commonly used analgesic. However, an overdose of APAP causes severe hepatotoxicity via depletion of the hepatic glutathione. In this study, we investigated the hepatoprotective effects of yellow Chinese chive extract (YCE) against APAP-induced hepatotoxicity in mice. YCE (25 or 100 mg/kg) was administered once daily for 7 d, and then APAP (700 mg/kg) was injected at 6 h before the mice were sacrificed. APAP treatment markedly increased the serum biological markers of liver injury such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase. Pretreatment with YCE significantly prevented the increases in the serum levels of these enzymes. Histopathological evaluation of the livers also revealed that YCE prevented APAP-induced centrilobular necrosis. Pretreatment with YCE dose-dependently elevated glutathione levels, but the difference was not significant. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in APAP-induced hepatotoxicity by regulating the antioxidant defense system. Therefore, we investigated the expression of Nrf2 and its target antioxidant enzyme. YCE led to an increased expression of Nrf2 and its target antioxidant enzymes, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (GPx), cystine uptake transporter (xCT), especially hemeoxygenase-1 (HO-1) in mice livers. These results suggest that YCE could induce HO-1 expression via activation of the Nrf2 antioxidant pathway, and protect against APAP-induced hepatotoxicity in mice.

Inhibitory effects of pomegranate extracts on recombinant human maltase-glucoamylase.

α-Glucosidase inhibitors are currently used in the treatment of type 2 diabetes. In this study, we investigated the inhibitory activities of aril and pericarp extracts from pomegranates obtained various regions against recombinant human maltase-glucoamylase (MGAM). The inhibitory activities of the aril extracts tended to be stronger than those of the pericarp extracts. The Iranian aril extract was the most effective inhibitor. We investigated the polyphenol content of the pomegranate extracts using the Folin-Ciocalteu method. Among the aril extracts, the Iranian aril extract showed the highest polyphenol content. We further evaluated inhibitory activity against α-glucosidase from the rat small intestine. Pomegranate extract used in this study showed slightly different inhibitory activities according to α-glucosidase origin. Iranian aril extract was the most effective inhibitor of α-glucosidases, especially recombinant human MGAM. Bioassay-guided fractionation of the pomegranate arils led to identification of punicalagin and oenothein B as potent inhibitors of α-glucosidase. Oenothein B showed inhibitory activity with a half-maximal inhibitory concentration (IC(50)) value of 174 µM. Its potency was comparable to that of the α-glucosidase inhibitor acarbose with an IC(50) value of 170 µM. Dixon plot kinetic analysis of oenothein B showed a noncompetitive inhibition with a K(i) value of 102 µM. These results suggest that pomegranate arils would be useful for suppressing postprandial hyperglycemia.

Production of dipeptidyl peptidase IV inhibitory peptides from defatted rice bran.

The insulinotropic hormone glucagon-like peptide-1 is metabolised extremely rapidly by the ubiquitous enzyme dipeptidyl peptidase IV (DPP-IV). Therefore, human DPP-IV is a key regulator involved in the prevention and treatment of type 2 diabetes. To simplify the method of producing an inhibitory peptide against DPP-IV, we focused on rice bran (RB) as a source and subjected proteins from defatted RB to enzymatic proteolysis using 2 commercial enzymes. The RB peptides produced with Umamizyme G exhibited 10 times the inhibitory activity as those produced with Bioprase SP. The half-maximal inhibitory concentration (IC(50)) value of the RB peptides was 2.3 ± 0.1mg/ml. Leu-Pro and Ile-Pro were identified as the inhibitory peptides among the RB peptides produced with Umamizyme G. Ile-Pro was the strongest DPP-IV inhibitor among the 15 Xaa-Pro dipeptides and Pro-Ile tested. Ile-Pro competitively inhibited DPP-IV (K(i)=0.11 mM). Mass spectrometry indicated that the contents of Leu-Pro and Ile-Pro in the RB peptides were 2.91 ± 0.52 µg/mg.

Antihypertensive and vasorelaxant effects of water-soluble proanthocyanidins from persimmon leaf tea in spontaneously hypertensive rats.

The antihypertensive and vasorelaxant effects of water-soluble proanthocyanidins, extracted in persimmon leaf tea, were investigated in spontaneously hypertensive rats, rat aortas, and human umbilical vein endothelial cells. Oral administration of proanthocyanidins significantly decreased the systolic blood pressure of the rats after 4 h, as compared with distilled water controls. A vasorelaxant effect on rat aortas was induced by proanthocyanidins, and it was abolished by removal of the endothelium and inhibition of endothelial nitric oxide synthase and soluble guanylyl cyclase activity. The phosphorylation levels of endothelial nitric oxide synthase (Ser-1177) and the upstream kinase Akt (Ser-473) in umbilical cells also increased in a time-dependent manner after the addition of a proanthocyanidin-rich fraction. These results suggest that the antihypertensive effect of proanthocyanidins in persimmon leaf tea is due to vasorelaxation via an endothelium-dependent nitric oxide/cGMP pathway, and that proanthocyanidins might be useful in dietary lowering of blood pressure.

Persimmon leaf extract inhibits the ATM activity during DNA damage response induced by Doxorubicin in A549 lung adenocarcinoma cells.

Persimmon leaf (PL) has been commonly recognized for its wide variety of health benefits. A previous study has reported that persimmon leaf extract (PLE) contained flavonols with the 2″-galloly moiety (PLEg). Galloylated homologues generically show stronger activity in their biological function, so enhanced functions can be expected for PLEg. We investigated in this present study the effect of PLEg on the cellular DNA damage checkpoint signaling to sensitize cancer chemotherapy. Treatment with PLE and PLEg significantly increased the cytotoxicity of doxorubicin (DOX) in A549 adenocarcinoma cells. PLE and PLEg reduced the phosphorylation of checkpoint proteins such as structural maintenance of chromosomes 1 (SMC1), checkpoint kinase 1 (Chk1), and p53 in DOX-treated cells. Moreover, PLE decreased the phosphorylation of ATM (ataxia telangiectasia mutated) in a dose-dependent manner. PLE, and especially PLEg, abrogated the G2/M checkpoint during DOX-induced DNA damage. These results suggest that PLEg specifically inhibited ATM-dependent checkpoint activation by DOX, and that PLEg might be a useful sensitizer in cancer chemotherapy.

Major water-soluble polyphenols, proanthocyanidins, in leaves of persimmon (Diospyros kaki) and their alpha-amylase inhibitory activity.

The amounts and compositions of polyphenol in persimmon leaves and persimmon leaf tea were investigated. The predominant polyphenols in fresh leaves were water-soluble, and the contents reached a maximum (2.40% w/w) in June, and then gradually decreased. Separation of them followed by thiolytic degradation revealed that the major components were unique proanthocyanidin oligomers consisting of four heterogeneous extension units, including epigallocatechin-3-O-gallate. Persimmon leaf tea also contained similar proanthocyanidins with similar compositional units. Oral administration of starch with polyphenol concentrate of persimmon leaf tea resulted in a significant and dose-dependent decrease in the blood glucose level in Wistar rats. This effect is considered to be due to inhibition of pancreas alpha-amylase. These results indicate that persimmon leaf tea containing peculiar proanthocyanidins has a significant role in suppressing blood glucose elevation after starch intake, and that the best harvest time is June.