UNASSIGNED: Osteoporosis is a common clinical bone disease that occurs most frequently in middle-aged and elderly people. Various traditional herbal medicine formulations have shown significant benefits in models of osteoporosis. In this study, we aim to investigate the osteogenic efficacy of naringin (NRG) in the osteoporotic state.
UNASSIGNED: We treated Bone marrow stromal cells (BMSCs) with various concentrations of NRG for 3 and 7 days. BMSC proliferation was measured by the MTT assay. The effect of NRG on the osteogenic differentiation of BMSCs was detected by ALP and alizarin red staining. The effect of NRG on the BMP2/Runx2/Osterix signaling pathway was analyzed by using real-time PCR. The effect of NRG on the oestrogen receptor was measured by Enzyme-linked immunosorbent assay. In vivo animal experiments were performed by micro-computed tomography and ALP immunohistochemistry to determine the ectopic osteogenic effect of NRG sustained-release nanoparticles in a mouse model of osteoporosis.
UNASSIGNED: NRG promoted the proliferation and osteogenic differentiation of BMSCs. Moreover, it also activated the BMP2/Runx2/Osterix signaling pathway. When NRG sustained-release nanoparticles were added in vivo in animal experiments, we found that NRG sustained-release nanoparticles had better ectopic osteogenic effects in a mouse model of osteoporosis.
UNASSIGNED: NRG induced osteoblastic differentiation of BMSCs by activating the BMP2/Runx2/Osterix signaling pathway and promoted the regulation of oestrogen receptor pathway protein expression, and NRG sustained-release nanoparticles exerted a more significant in vivo ectopic osteogenic effect in an osteoporosis mouse model. Therefore, naringin is expected to be developed as a novel treatment for inducing osteogenesis, because of its ubiquitous, cost-efficient, and biologically active characteristics. However, further research is needed on how to improve the pharmacokinetic properties of naringin and its specific mechanism.

Coffee became a beverage that was in demand in the world and consequently produced millions of tons of coffee byproducts namely coffee silverskin (CS). Unutilized CS will be waste and cause environmental pollution such as greenhouse gas emissions, landfill waste, and groundwater contamination. This is a research concern at this time, although many studies have been conducted to find newer applications of CS, exploration of its benefits in the health sector is still limited. Therefore, exploring the benefits of CS to prevent or delay aging will be very interesting to develop in functional food industry technology. Therefore, this study aims to report profiling metabolites or phytochemicals, biological activities in terms of antioxidant activity, and potential anti-aging of CS via molecular docking simulation and in vitro modulation of the mTOR/AMPK/SIRT1 pathway. Something new has been obtained from this work, the profile of phytocompounds, and biological activities both in molecular docking simulation and in vitro studies. Some of the compounds observed in Robusta CS extract (rCSE) such as Epicatechin, Kaempferol, and Quercitrin, and Arabica CS extract (aCSE) such as (+)-Catechin dan Naringin have promising potential as inhibitors of iNOS, mTOR, and HIF-1α via molecular docking simulation. Interestingly, the in vitro biological activity assay of antioxidant and anti-aging activity, rCSE showed the same promising potential as the results of a molecular docking simulation. More interestingly, AMPK/SIRT1/mTOR expressions are well modulated by rCSE compared to aCSE significantly (p < 0.05). This makes the rCSE have promising biological activity as a candidate for functional food development and/or treatment agent in combating free radicals that cause the aging process. In vivo studies and human trials are certainly needed to see the further efficacy of the rCSE in the future.

Alzheimer\'s disease (AD) is a neurodegenerative disorder characterized by gradual cognitive decline. Strong antioxidants that inhibit free radicals, such as polyphenols, reduce the likelihood of developing oxidative stress-related degenerative diseases such as AD. Naringin, a flavonoid found in citrus fruit shown to be neuroprotective, reduce oxidative damage and minimize histopathological changes caused by ischemic reperfusion, enhance the long-term memory in AD animal models. This work aimed to comprehend the role of naringin in the defense of the cerebellum against aluminum chloride (AlCl3)-induced AD in rats by investigating the behavioral, neurochemical, immunohistochemical, and molecular mechanisms that underpin its possible neuroprotective effects. Twenty-four adult albino rats were divided into four groups (n = 6/group): (i) Control (C) received saline per oral (p.o.), (ii) Naringin(N)-received naringin (100 mg/kg/d) p.o, (iii) AlCl3-recived AlCl3 (100 mg/kg/d) p.o and (iv) AlCl3 + Naringin (AlCl3 + N) received both AlCl3 and naringin p.o for 21 days. Behavioral tests showed an increase in the time to reach the platform in Morris water maze, indicating memory impairment in the AlCl3-treated group, but co-administration of naringin showed significant improvement. The Rotarod test demonstrated a decrease in muscle coordination in the AlCl3-treated group, while it was improved in the AlCl3 + N group. Neurochemical analysis of the hippocampus and cerebellum revealed that AlCl3 significantly increased lipid peroxidation and oxidative stress and decreased levels of reduced glutathione. Administration of naringin ameliorated these neurochemical changes via its antioxidant properties. Cerebellar immunohistochemical expression for microtubule assembly (tau protein) and oxidative stress (iNOS) increased in A1C13-treated group. On the other hand, the expression of the autophagic marker (LC3) in the cerebellum showed a marked decline in AlCl3-treated group. Western blot analysis confirmed the cerebellar immunohistochemical findings. Collectively, these findings suggested that naringin could contribute to the combat of oxidative and autophagic stress in the cerebellum of AlCl3-induced AD.

Trimethylamine-N-oxide (TMAO), a phospholipid metabolite, can modulate cholesterol synthesis and promote vascular inflammation and endothelial dysfunction, thereby increasing the risk of atherosclerosis (AS). Previously, it was found that naringin reduced damage to human umbilical vein endothelial cells (HUVECs) triggered by oxidized low-density lipoprotein. This article continues to explore the role and mechanism of naringin in protecting HUVECs from TMAO-induced damage. After the construction of TMAO-induced AS model in HUVECs, inflammation, oxidative stress, and endothelial function were examined by real-time quantitative polymerase chain reaction, Western blotting, nitric oxide (NO), reactive oxygen species (ROS), superoxide dismutase, and malondialdehyde (MDA) kits. Results showed that naringin pretreatment inhibited endothelial inflammation and oxidative stress, promoted NO release, and inhibited the degradation of Zona occludens-2, occludin, and vascular endothelial-cadherin, thereby restoring the functional and structural integrity of the endothelium. Furthermore, the addition of mitogen-activated protein kinase (MAPK) agonist demonstrated that the therapeutic effect of naringin was achieved through inactivating TMAO-stimulated MAPK signaling in HUVECs.

This work presents a comparative analysis of the tyrosinase inhibitory effects of five citrus flavonoids, namely hesperetin, hesperidin, neohesperidin, naringenin and naringin. Visbile, fluorescence, and fourier transform infrared (FITR) spectroscopies, and molecular dynamic methods were employed to compare the anti-tyrosinase mechanisms of each flavonoid. Hesperetin, neohesperidin, naringenin and naringin exhibited potent inhibitory activities with IC50 values of 0.74 ± 0.05, 2.19 ± 0.03, 7.50 ± 9.82 and 24.94 ± 8.43 μmol/ml, respectively, all of which were higher than that of kojic acid (0.04 ± 0.02 μmol/ml). The enzymatic kinetics results suggested that hesperetin and naringenin were reversible inhibitors on tyrosinase in the mixed-type manner. H-bond and hydrophobic interactions were found to drive the binding of tyrosinase with hesperetin or naringenin, which subsequently changed the FTIR spectroscopy results by decreasing the α-helix ratio and increasing the β-turn, β-sheet and random coil ratio in tyrosinase. Molecular dynamics simulation not only verified some of the experimental results, but also suggested that the binding of hesperetin and naringenin to tyrosinase was spontaneous. The findings of this study indicate that citrus flavonoids are a promising dietary resource for tyrosinase inhibition. PRACTICAL APPLICATIONS: Hesperetin, hesperidin, neohesperidin, naringenin and naringin were typical citrus flavonoids that have anti-obesity, anti-oxidation, anti-inflammation and anti-diabetes activities. Current study suggested that hesperetin and naringenin were effective reversible inhibitors on tyrosinase in the mixed-type manner. Hesperetin and naringenin might serve as nutritional and chemical agents for regulating the tyrosinase activity to control melanin level in vivo.

暂无摘要。

Naringin is a dietary flavonoid glycoside with multiple bioactivities. It has been involved in numerous metabolism and excretion studies, and its metabolic properties are clear. However, information concerning the excretion profile of its original metabolites are still scarce, and few methods for simultaneous determination of multiple original metabolites of naringin in biological samples have been reported so far. In this study, a rapid and sensitive method for simultaneous determination of ten flavonoid metabolites of naringin in rat urine was developed with an UHPLC-Q-Trap-MS/MS system. One-step protein precipitation method with acetonitrile was used to extract analytes. A rapid chromatographic separation within 11 min was performed on an ACQUITY UPLC® BEH C18 column (2.1 mm × 50 mm, 1.7 μm) using gradient elution with a mobile phase of water and methanol, both with 0.1% formic acid (v/v). MS/MS detection was conducted in negative ion mode and multiple reactions monitoring scanning mode. The analytical method was fully validated and successfully applied to monitor the excretion profiles of naringin in rat urine. Quantitative results revealed the visible individual difference and low urinary recovery of flavonoid metabolites in the excretion of naringin, which may be helpful for further study to understand the in vivo behavior and action mechanism of naringin.

The interaction mechanisms of nimodipine with pepsin, trypsin, α-chymotrypsin, lysozyme and human serum albumin were investigated by multispectral and molecular docking methods. Vitamin C and naringin were the main active components of grapefruit juice, and nimodipine was the typical drug that interacts with this juice. Fluorescence spectroscopy was used to study the interaction of nimodipine with five proteinases (pepsin, trypsin, α-chymotrypsin, lysozyme and human serum albumin) and the effects of vitamin C and naringin on these interactions. The fluorescence quenching results showed that nimodipine can quench the intrinsic fluorescence of these five proteinases by a static quenching procedure. Nimodipine binds to pepsin and α-chymotrypsin, through hydrogen bonding and van der Waals forces, whereas it binds to trypsin, lysozyme and human serum albumin mainly by hydrophobic interactions. The microenvironment of the five proteinases changed. The probability of nonradiative energy transfer between the five proteinases and nimodipine was high. Both vitamin C and naringin reduced the binding constant of nimodipine to the four proteinases (except α-chymotrypsin) and might increase the concentration of free nimodipine. Thus, vitamin C or naringin in fruits or foods could increase the blood concentration of free nimodipine and perhaps a reduction in nimodipine dose was needed.

Naringin has been shown to exert protective effects in an animal model of ulcerative colitis, but detailed mechanisms remain unclear. This study aimed to investigate function and signaling mechanisms underlying naringin-induced therapeutic effects on colitis. Two mouse models were established to mimic human Inflammatory bowel disease (IBD) by treating drinking water with dextran sodium sulphate or intra-colonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Transcriptomics combined with functional experiments were used to investigate underlying mechanisms. Colitis symptoms, including weight loss and high disease activity index were significantly reversed by naringin. The inflammatory response, oxidative reactions, and epithelial cell apoptosis that occur with colitis were also alleviated by naringin. After naringin treatment, transcriptomics results identified 753 differentially expressed mRNAs that were enriched in signaling pathways, including the neuroactive ligand-receptor interaction, calcium signaling, and peroxisome proliferator-activated receptor (PPAR) signaling. The naringin-induced alleviation of colitis was significantly inhibited by the PPAR-γ inhibitor BADGE. In IEC-6 and RAW264.7 cells incubated with lipopolysaccharide (LPS), NF-κB-p65, a downstream protein of PPAR-γ, was significantly increased. Naringin suppressed LPS-induced high expression of NF-κB-p65, which was inhibited by small interfering RNA targeting PPAR-γ. Our study clarifies detailed mechanisms underlying naringin-induced therapeutic effects on mice colitis, and PPAR-γ was found to be the main target of naringin by functional experiments both in vivo and in vitro. Our study supplies new scientific information for the use of naringin in colitis treatment.

The current study was focused on new approaches for debittering of by-products like kinnow pomace and kinnow pulp residue by using various food grade mild chemical methods, such as alkali treatment, acid treatment, and solventogenesis. Whereas in the studied various chemical treatments, the solventogenesis method with acetone resulted in maximum extraction of naringin and limonene from kinnow pomace and pulp residue and showed high acceptability for food product development. The acetone treatment was further optimized by RSM for the maximum extraction of naringin and limonene. Under optimized conditions, the maximum amount of naringin and limonene extracted were found to be 8.955, 2.122 mg/g from kinnow pomace and 9.971, 3.838 mg/g from pulp residue, respectively. This process can not only result in the effective utilization of agro-industrial by-product but also provide a sustainable solution to the environmental pollution caused by kinnow juice industry.