• Journal of the Korean Chemical Society
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• v.67 no.4
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• pp.226-235
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• 2023

Chikungunya fever has a high morbidity rate in humans and is caused by chikungunya virus. There are no treatments available until now for this particular viral disease. The present study was carried out by selecting 19 flavonoids, which are available naturally in fruits, vegetables, tea, red wine and medicinal plants. The molecular docking of selected 19 flavonoids was carried out against the Chikungunya virus capsid protein using the Autodock4.2 software. Binding affinity analysis based on the Intermolecular interactions such as Hydrogen bonding and hydrophobic interactions and drug-likeness properties for all the 19 flavonoids have been carried out and it is found that the top four molecules are Chrysin, Fisetin, Naringenin and Biochanin A as they fit to the chikungunya protein and have binding energy of -8.09, -8.01, -7.6, and 7.3 kcal/mol respectively. This result opens up the possibility of applying these compounds in the inhibition of chikungunya viral protein.

• Journal of Microbiology and Biotechnology
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• v.24 no.5
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• pp.605-613
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• 2014

We have previously shown that paraquat (PQ)-induced oxidative stress causes dramatic damage in various human cell lines. Naringenin (NG) is an active flavanone, which has been reported to have beneficial bioactivities, including antioxidative, anti-inflammatory, and antitumorigenic activities, with a relatively low toxicity to normal cells. In this study, we intended to assess the cytoprotective effect of NG against PQ-induced toxicity in the human bronchial epithelial BEAS-2B cell line. Co-treatment with NG in PQ-treated BEAS-2B cells can reduce PQ-induced cellular toxicity. NG can also decrease the generation of intracellular ROS caused by PQ treatment. We also observed that treatment with NG in PQ-exposed BEAS-2B cells can significantly induce the expression of antioxidant-related genes, including GPX2, GPX3, GPX5, and GPX7. NG co-treatment can also activate the NRF2 transcription factor and promote its nuclear translocation. In addition, NG co-treatment can induce the expression of NRF2-downstream target genes such as that of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). A small interfering RNA study revealed that the knockdown of NRF2 can abrogate NG-mediated protection of the cells from PQ-induced cellular toxicity. We propose that NG effectively alleviates PQ-induced cytotoxicity in human bronchial epithelial BEAS-2B cells through the NRF2-regulated antioxidant defense pathway, and NG might be a good therapeutic candidate molecule in oxidative stress-related diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.51-55
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• 2016

Phytochemical investigation of Pistacia integerrima has highlighted isolation of two known compounds naringenin (1) and dihydrokaempferol (2). A crude extract and these isolated compounds were here evaluated for their effects on reversion of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). The multidrug resistance P-glycoprotein is a target for chemotherapeutic drugs from cancer cells. In the present study rhodamine-123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma cells showed excellent MDR reversing effects in a dose dependent manner. In-silico molecular docking investigations demonstrated a common binding site for Rhodamine123, and compounds naringenin and dihydrokaempferol. Our results showed that the relative docking energies estimated by docking softwares were in satisfactory correlation with the experimental activities. Preliminary interaction profile of P-gp docked complexes were also analysed in order to understand the nature of binding modes of these compounds. Our computational investigation suggested that the compounds interactions with the hydrophobic pocket of P-gp are mainly related to the inhibitory activity. Moreover this study s a platform for the discovery of novel natural compounds from herbal origin, as inhibitor molecules against the P-glycoprotein for the treatment of cancer.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.339-344
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• 2015

Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells.

• Food Science and Biotechnology
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• v.17 no.6
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• pp.1361-1364
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• 2008

The inhibitory effects of naringenin, kaempherol, and apigenin on the production of cholesterol in HepG2 KCLB 88065 and MCF-7 KCLB 30022 cells were evaluated. In this study, quercetin was used as a reference reagent. After incubation for 3 days, fat-soluble contents of both cell types were extracted by using the Folch method and the cholesterol contents in both cultured cells were determined by high performance liquid chromatography. The concentration of cholesterol in untreated each tissue cells was $12.2{\pm}0.11$ and $8.83{\pm}0.12\;mg/g$ of lipid, respectively. The total concentration of each flavonoid was adjusted to 0, 35, or $350{\mu}M$ in the culture broth. As the results, the addition of 2% methanol and dimethyl sulfoxide (DMSO) to the media (control for flavonoid solvents) did not significantly affect cell growth; however, DMSO caused an increase in the production of cholesterol. Each flavonoid inhibited the production of cholesterol in both HepG2 and MCF-7 cells at the concentration of $35{\mu}M$ above. In addition, the inhibitory effect of kaempherol on the production of cholesterol in these cells was greater than the other flavonoids tested and HepG2 cells are more sensitive to flavonoids than MCF-7. From the results, the inhibitory effects of flavonoids on cholesterol production are different depending on the cell type.

• Integrative Medicine Research
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• v.6 no.2
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• pp.149-155
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• 2017

Background: Naringenin (NRG) is a common dietary polyphenolic constituent of fruits. NRG has diverse pharmacological activities, and is used in traditional medicine to treat various diseases including gastrointestinal (GI) disorders. Interstitial cells of Cajal (ICCs) are pacemaker cells of the GI tract. In this study, the authors investigated the effects of NRG on ICCs and on GI motility in vitro and in vivo. Methods: ICCs were dissociated from mouse small intestines by enzymatic digestion. The whole-cell patch clamp configuration was used to record pacemaker potentials in cultured ICC clusters. The effects of NRG on GI motility were investigated by calculating percent intestinal transit rates (ITR) using Evans blue in normal mice. Results: NRG inhibited ICC pacemaker potentials in a dose-dependent manner. In the presence of tetraethylammonium chloride or iberiotoxin, NRG had no effect on pacemaker potentials, but it continued to block pacemaker potentials in the presence of glibenclamide. Preincubation with SQ-22536 had no effect on pacemaker potentials or on their inhibition by NRG. However, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one blocked pacemaker potential inhibition by NRG. In addition, L-NG-nitroarginine methyl ester blocked pacemaker potential inhibition by NRG. Furthermore, NRG significantly suppressed murine ITR enhancement by neostigmine in vivo. Conclusion: This study shows NRG dose-dependently inhibits ICC pacemaker potentials via a cyclic guanosine monophosphate/nitric oxide-dependent pathway and $Ca^{2+}$-activated $K^+$ channels in vitro. In addition, NRG suppressed neostigmine enhancement of ITR in vivo.

• The Korean Journal of Pain
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• v.35 no.3
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• pp.291-302
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• 2022

Background: Spinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known anti-inflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI. Methods: Animals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 µL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups. Results: NAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI. Conclusions: These results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.

• Korean Journal of Environmental Agriculture
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• v.24 no.4
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• pp.391-397
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• 2005

This study was carried out to examine the allelopathic effect of the aqueous extract of Hypochaeris radicata L. on growth of three gramineous forage crops, tall fescue, perennial ryegrass and italian ryegrass. The result on relative elongation ration (RER) of gramineous forage crops treated with the aqueous extract of Hypochaeris radicata L. and the change of quantity generally indicated the inhibitory effect. The inhibitory effect was increased as its concentration was increased. As a result, it is ascertained that the aqueous extract of Hypochaeris radicata L. has allelopathy effect. According to the chemical experiment of the allelochemical substances in Hypochaeris radicata L. by HPLC, there are the differences at each part of plants. However, it is ascertained that there are eleven phenolic compounds, ${\rho}-hydroxybenzoic$ acid, chlorogenic acid, catechin, caffeic acid, syringic acid, salicylic acid, ${\rho}-coumaric$ acid, ferulic acid, hesperidin, trans-cinnamic acid and naringenin. Especially three phenolic acids such as caffeic acid, ferulic acid and naringenin were detected from all part of the plant.

• Journal of Life Science
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• v.29 no.1
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• pp.129-134
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• 2019

In a previous study, we isolated 11 different kinds of compounds from ethyl acetate fractions of lees (jubak) which is a by-product of Korean traditional wine production. These compounds were identified as caffeic acid, coumaric acid, D-mannitol, ferulic acid, hesperetin, hesperidin, naringenin, naringin, sinapic acid, syringic acid, and vanilic acid. To evaluate their anti-inflammatory activities in an in vitro model, nitric oxide (NO) production was measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells after the treatment of these cells with each compound. Among the various chemicals, hesperetin and naringenin showed the highest inhibition of NO production in the LPS-activated RAW 264.7 cells. Hesperetin was chosen for further study because of its strong anti-inflammatory activity and because the mechanisms underlying its anti-inflammatory properties still remain unclear. Our results showed that hesperetin dramatically inhibited NO production in a dose-dependent manner as compared with in an LPS-only treated group, without affecting cell viability. In addition, hesperetin reduced the protein expression of the pro-inflammatory gene inducible nitric oxide synthase (iNOS) in a dose-dependent manner, whereas it did not affect cyclooxygenase-2 (COX-2) expression. Furthermore, hesperetin inhibited phosphorylation of p38 mitogen- activated protein kinase (MAPK) and extracellular signal regulated kinase (ERK) 1/2, whereas it did not affect phosphorylation of c-jun N- terminal kinase (JNK). The results indicated that hesperetin regulated the LPS-induced inflammatory response by suppressing p38 MAPK and ERK1/2 signaling. Overall, our results may help to understand the mechanisms underlying the anti-inflammatory activity mediated by hesperetin.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.153.1-153.1
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• 2001