Naringin prevents ultraviolet‐B radiation‐induced oxidative damage and inflammation through activation of peroxisome proliferator‐activated receptor γ in mouse embryonic fibroblast (NIH‐3T3) cells

The present study, we investigate the preventive role of naringin, a dietary flavonoid, against ultraviolet‐B (UVB) radiation (280‐320 nm) induced oxidative damage and inflammatory responses in mouse embryonic fibroblast cell lines (NIH‐3T3). In this study, 20 mJ/cm ² of UVB radiation induces cell cytotoxicity, reactive oxygen species (ROS) generation, DNA damage, and antioxidants depletion in NIH‐3T3 cells. Treatment with naringin (60 µM) prior UVB exposure prevented the cell cytotoxicity, ROS generation, DNA damage, and antioxidants depletion in NIH‐3T3 cells. Furthermore, naringin prevents UVB‐induced mitogen‐activated protein kinase families and nuclear factor‐κB (NF‐κB)‐mediated activation of inflammatory factors, that is TNF‐α, IL‐6, IL‐10, and COX‐2 in NIH‐3T3 cells. Peroxisome proliferator‐activated receptor γ (PPARγ) is an anti‐inflammatory agent and it suppressed the UVB‐mediated oxidative and inflammatory responses. In this study, naringin activates PPARγ and prevents inflammatory biomarkers in NIH‐3T3 cells. Thus, naringin prevents UVB‐mediated inflammation and oxidative damage in NIH‐3T3 cells probably over controlling NF‐κB expression and activation of PPARγ.     

一株柚皮苷羟基化真菌的筛选及鉴定

柚皮苷是中草药枳实、橘红的主要有效成分,用于心血管疾病的防治。为了开发生物法生产柚皮苷的羟基化衍生物,从土壤中分离筛选到一株能转化柚皮苷为3’-羟基柚皮苷和3’,5’-二羟基柚皮苷的真菌菌株NT-02。通过对菌株NT-02的形态学观察和ITS序列系统发育分析,构建了系统发育树,NT-02菌株与哈茨木霉（Trichoderma harzianum／Hypocreaum lixii）形成一个类群,且有99％的同源性,初步鉴定真菌NT-02为木霉属（Trichoderma）菌株。     

The liver antioxidant status of fattening lambs is improved by naringin dietary supplementation at 0.15% rates but not meat quality

Twenty Assaf lambs fed barley straw plus a concentrate alone (CONTROL group) or enriched with naringin (1.5 g/kg DM, NARINGIN group) were used to assess the effect of this polyphenolic compound on meat quality attributes. Serum samples were collected for 7 weeks, then the animals were slaughtered and the livers and longissimus thoracis et lumborum muscles extracted for analysis. Triacylglycerol levels in the serum samples tended to show (P = 0.087) lower average values for the NARINGIN group when compared with the CONTROL, but no differences were observed when the meat was analysed for the intramuscular fat content. Lower thiobarbituric acid-reactive substances procedure (TBARS) values (P < 0.001) in the liver of the NARINGIN group were detected, probably as a consequence of naringenin accumulation in this organ. No significant differences were observed in the meat samples concerning TBARS or colour evolution during refrigerated storage, as not enough naringenin would have reached the muscle. Independent of naringin administration, the low levels of the most atherogenic oxysterols must be highlighted as the most important quality score in the lamb meat samples studied.     

Comprehensive investigation into the interconversion of C‐2 diastereomers of naringin

Naringin is a flavanone that widely presents on daily diet and traditional medicinal materials. The ratios of naringin C‐2 diastereomers are found different in reported samples, thus suspiciously leading to various functions. In this study, we measured the interconversion of C‐2 diastereomers intensively with ultimate high‐performance liquid chromatography and circular dichroism spectra. We examined the diastereomeric naringins in fresh citrus fruit, Huajuhong decoction pieces, and naringin tablet; evaluated the impact of tablet production procedures in factory; and monitored the rapid racemization in incubation. The results not only confirmed that enzyme, temperature, and pH condition could influence the interconversion but also demonstrated that diverse ratios of diastereomers showed limited influence on metabolic behaviors of naringin in the blood, which consequently cause comparable bioactivities. This study could provide comprehensive understanding of diastereomeric interconversion and provide useful reference for drug development.     

Neuroprotective effect of Citrus kawachiensis (Kawachi Bankan) peels,a rich source of naringin,against global cerebral ischemia/reperfusion injury in mice

Cerebral ischemia/reperfusion is known to induce the generation of reactive oxygen species and inflammatory responses. Numerous studies have demonstrated that naringin (NGIN) has anti-oxidant and anti-inflammatory properties. We previously reported that Citrus kawachiensis contains a large quantity of NGIN in its peel. In the present study, we orally (p.o.) administered dried peel powder of C. kawachiensis to mice of a transient global ischemia model and found in the hippocampus region that it 1) suppressed neuronal cell death, 2) reversed the reduction in the level of phosphorylated calcium-calmodulin-dependent protein kinase II, 3) had the tendency to reverse the reduction in the level of glutathione, and 4) blocked excessive activation of microglia and astrocytes. These results suggested that the dried peel powder of C. kawachiensis had a neuroprotective effect against ischemic brain via anti-oxidative and anti-inflammatory effects. We also showed that these effects of the dried peel powder were more powerful than those obtained with a comparable amount of NGIN alone.     

Evaluation of potential flavonoid inhibitors of glyoxalase-I based on virtual screening and in vitro studies

Glyoxalase-I (GLO-I) is a component of the ubiquitous detoxification system involved in the conversion of methylglyoxal (MG) to d-lactate in the glycolytic pathway. MG toxicity arises from its ability to form advanced glycation end products. GLO-I has been reported to be frequently overexpressed in various types of cancer cells. In this study, we performed structure-based virtual screening of focused flavonoids commercial library to identify potential and specific inhibitors of GLO-I. The compounds were ranked based on Glide extra precision docking score and five hits (curcumin, quercetin, morin, naringin and silibinin) were selected on the basis of their interaction with active site amino acid residues of GLO-I. Mixed mode QM/MM calculation was performed on the top-scoring hit to ascertain the role of zinc ion in ligand binding. In addition, the identified hits were subjected to MM/GBSA binding energy prediction, ADME prediction and similarity studies. The hits were tested in vitro for cell viability, and GLO-I inhibition. Naringin (ST072162) was found to be most potent inhibitor of GLO-I among the identified hits with highest glide XP dock score of ?14.906. These findings suggest that naringin could be a new scaffold for designing inhibitors against GLO-I with potential application as anticancer agents.     

Naringin in Ganshuang Granule suppresses activation of hepatic stellate cells for anti‐fibrosis effect by inhibition of mammalian target of rapamycin

A previous study has demonstrated that Ganshuang granule (GSG) plays an anti‐fibrotic role partially by deactivation of hepatic stellate cells (HSCs). In HSCs activation, mammalian target of rapamycin (mTOR)‐autophagy plays an important role. We attempted to investigate the role of mTOR‐autophagy in anti‐fibrotic effect of GSG. The cirrhotic mouse model was prepared to demonstrate the anti‐fibrosis effect of GSG. High performance liquid chromatography (HPLC) analyses were used to identify the active component of GSG. The primary mouse HSCs were isolated and naringin was added into activated HSCs to observe its anti‐fibrotic effect. 3‐methyladenine (3‐MA) and Insulin‐like growth factor‐1 (IGF‐1) was added, respectively, into fully activated HSCs to explore the role of autophagy and mTOR. GSG played an anti‐fibrotic role through deactivation of HSCs in cirrhotic mouse model. The concentration of naringin was highest in GSG by HPLC analyses and naringin markedly suppressed HSCs activation in vitro, which suggested that naringin was the main active component of GSG. The deactivation of HSCs caused by naringin was not because of the autophagic activation but mTOR inhibition, which was supported by the following evidence: first, naringin induced autophagic activation, but when autophagy was blocked by 3‐MA, deactivation of HSCs was not attenuated or reversed. Second, naringin inhibited mTOR pathway, meanwhile when mTOR was activated by IGF‐1, deactivation of HSCs was reversed. In conclusion, we have demonstrated naringin in GSG suppressed activation of HSCs for anti‐fibrosis effect by inhibition of mTOR, indicating a potential therapeutic application for liver cirrhosis.     

The reduction of naringin content of grapefruit by applications of gibberellic acid

Four different plant growth regulators, gibberellic acid (GA₃), naphthaleneacetic acid (NAA), benzyladenine (BA) and abscisic acid (ABA), were individually mixed in a lanolin paste and applied to immature fruit on grapefruit trees beginning soon after fruit set. The treated fruit was allowed to mature on the tree. Application of 1000 ppm GA₃ in this manner generally increased fruit size, decreased the concentration of the total acid in the juice and decreased the concentration of naringin in the juice sacs compared to that of the controls. GA₃ increased the total soluble solids (brix) in the juice in some experiments. Treatment of fruit with 1000 ppm ABA and BA significantly decreased the size of the fruit and increased the naringin concentration, but had variable effects on the soluble solids content and the acid content. Treatment with 1000 ppm NAA did not produce any significant changes in size, acid content, brix or naringin concentration.RetiredReference to a company or product name does not imply approval or recommendation of the product by the U.S. Department of Agriculture to the exclusion of other products that may be suitable.     

Biological Activities of p-Ethylphenyl and p-Acetylphenyl Phosphates and their Thiono Analogs

Sixteen phosphate or phosphorothioate esters related to neurotoxic tri-p-ethylphenyl phosphate and its active metabolites were synthesized and their biological activities including inhibitory activity against cholinesterases, insecticidal activity, toxicity to mammals and neurotoxicity were examined. Dialkyl p-ethylphenyl phoshates, p-acetylphenyl phosphates and their thiono analogs showed insecticidal activity, but did not show the ataxic sign by any sublethal doses in hens. When a methyl group was introduced on p-acetylphenyl ring, the biological activity changed remarkably by its position. The introduction of a methyl group into o-position made the ester inactive, while the introduction into m-position made it active to insects selectively.