• YAKHAK HOEJI
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• v.32 no.1
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• pp.80-85
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• 1988

QSAR of Salicylic acid derivatives, as anti-inflammatory agent, classified into Group I (not-having-5-phenyl ones) and Group II (having-5-phenyl ones) were investigated by quantum chemical calculations. The results are below: not significant statistically for both of Group I and Group II, but significant for each Group. $potency=-8.46X_{5}+1.639\;n=5\;r=0.77\;se=0.31\;for\;Group\;I.$ $({\pm}4.05)\;({\pm}0.5)$ where $X_5$ means charge of carbon atom bonded to hydroxyl radical. $potency=0.16X_{19}+7427.38HO-6629.85X_{15}+4977.40X_{10}+351.51X_5+3378.84$ $({\pm}0.17)\;({\pm}10.18)\;({\pm}11.70)\;({\pm}33.78)\;({\pm}4.41)\;({\pm}13.13)$ n=7 r=0.99 se=0.019 for Group II. where $X_{19}$ and $X_{15}$ stand for charges of the para carbon and the first carbon atoms in phenyl radical, respectively and $X_{10}$, charge of carboxylic carbon atom, HO, HOMO energy. It seems to be possible to qualitatively predict potency of drug by Pearson's HSAB theory. It means that drug should possess low LUMO energy and high HOMO energy.

• Journal of Cancer Prevention
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• v.21 no.3
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• pp.135-143
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• 2016

Background: Fraxetin (7,8-dihydroxy-6-methoxy coumarin), a coumarin derivative, has been reported to possess antioxidative, anti-inflammatory and neuroprotective effects. A number of recent observations suggest that the induction of heme oxygenase-1 (HO-1) inhibits inflammation and tumorigenesis. In the present study, we determined the effect of fraxetin on HO-1 expression in HaCaT human keratinocytes and investigated its underlying molecular mechanisms. Methods: Reverse transcriptase-PCR and Western blot analysis were performed to detect HO-1 mRNA and protein expression, respectively. Cell viability was measured by the MTS test. The induction of intracellular reactive oxygen species (ROS) by fraxetin was evaluated by 2′,7′-dichlorofluorescin diacetate staining. Results: Fraxetin upregulated mRNA and protein expression of HO-1. Incubation with fraxetin induced the localization of nuclear factor-erythroid-2-related factor-2 (Nrf2) in the nucleus and increased the antioxidant response element-reporter gene activity. Fraxetin also induced the phosphorylation of Akt and AMP-activated protein kinase $(AMPK){\alpha}$ and diminished the expression of phosphatase and tensin homolog, a negative regulator of Akt. Pharmacological inhibition of Akt and $AMPK{\alpha}$ abrogated fraxetin-induced expression of HO-1 and nuclear localization of Nrf2. Furthermore, fraxetin generated ROS in a concentration-dependent manner. Conclusions: Fraxetin induces HO-1 expression through activation of Akt/Nrf2 or $AMPK{\alpha}/Nrf2$ pathway in HaCaT cells.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.501-508
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• 2019

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and $NF-{\kappa}B$ p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of $CD4^+/CD8^+$ and the secretion of interleukin (IL)-2 and interferon-${\gamma}$, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

• Natural Product Sciences
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• v.27 no.3
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• pp.208-215
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• 2021

𝛽-Patchoulene (𝛽-PAE) is a tricyclic sesquiterpene which performed many potential bioactivities and can be found in patchouli oil but in very low concentration. This study aimed to obtained 𝛽-PAE in high concentration by conversion of patchouli alcohol (PA) in patchouli oil under acid catalyzed reaction. Patchouli oil was fractinated by vacuum distillation at 96 kPa to get the fraction with the highest PA content. H₂SO₄ and ZnCl₂ were used respectively as homogeneous and heterogeneous acid catalysts in the conversion reaction of the selected fraction. Patchouli oil, the fractions and the products were analysed by using GC-MS and FTIR instruments. Moreover, the interaction of 𝛽-PAE to COX-2 protein was studied to understand the antiinflammation activity of 𝛽-PAE. The results showed that patchouli oil contains 25.3% of PA. The selected fraction which has the highest PA content (70.3%) was distilled at 151 - 152 ℃. The application of ZnCl₂ catalyst in conversion reaction did not succeed. In contrast, H₂SO₄ as a catalyst in acetic acid solvent succeeded in converting the overall fraction of PA to 𝛽-PAE. Furthermore, the molecular docking study of 𝛽-PAE against COX-2 enzyme showed van der Waals and alkyl-alkyl stacking interactions on ten amino acid residues.

• Journal of Food Hygiene and Safety
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• v.33 no.6
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• pp.427-437
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• 2018

In this study, 23 ethanolic extracts from 20 medicinal plants were evaluated for biological activities. Results revealed that of 23 samples, seven samples have demonstrated good antimicrobial activity. Minimum inhibitory concentrations were 0.4-2.0 mg/mL, while minimum bactericidal concentrations were mostly high 0.8-2.0 mg/mL for selected seven samples. Five samples revealed > 70 mg gallic acid equivalent (GAE)/g of total phenolic contents. Among test samples, six samples exhibited > 80% inhibition of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and only two samples exhibited > 80% inhibition of 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals. A total of five test samples revealed Trolox equivalent antioxidant capacity more than $1000{\mu}m/g$. The MTT assay indicated that eight test samples exhibited > 90% viability of murine macrophage cells (RAW 264.7) at $250{\mu}g/mL$ and suppressed iNOS mRNA expression at transcriptional level when stimulated by lipopolysaccharide (LPS). Some medicinal plants revealed promising results, and so they have prospective for further more inclusive studies.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1361-1368
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• 2019

Codium fragile is an edible seaweed in Asian countries that has been used as a thrombolytic, anticoagulant, antioxidant, anti-inflammatory, and immune-stimulatory agent. Ginseng has also been known to maintain immune homeostasis and to regulate the immune system via enhancing resistance to diseases and microorganisms. In this study, anionic macromolecules extracted from C. fragile (CFAM) were orally administered with red ginseng extract (100 mg/kg body weight) to cyclophosphamide-induced immunosuppressed male BALB/c mice to investigate the immune-enhancing cooperative effect of Codium fragile and red ginseng. Our results showed that supplementing CFAM with red ginseng extract significantly increased spleen index, T- and B-cell proliferation, NK cell activity, and splenic lymphocyte immune-associated gene expression compared to those with red ginseng alone, even though a high concentration of CFAM with red ginseng decreased immune biomarkers. These results suggest that CFAM can be used as a co-stimulant to enhance health and immunity in immunosuppressed conditions.

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.238-243
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• 2020

Perilla frutescens Britton var. acuta Kudo, an annual plant primarily cultivated in China, Japan, and Korea, has been used as a traditional medicine to treat inflammatory diseases, depression, and many anxiety-related disorders. Previously, we reported the inhibitory effects of n-hexane layer of P. frutescens var. acuta extract against beta-amyloid (Aβ) aggregation, and the isolation of asarone derivatives as active constituents from n-hexane layer. In this study, dichloromethane layer of P. frutescens var. acuta was applied to bioassay-guided isolation methods accompanied with Thioflavin T (Th T) fluorescence assay to investigate the inhibitory effect on Aβ aggregation and disaggregation. As the results, three triterpenoids including ursolic acid (1), tormentic acid (2) and corosolic acid (3) were isolated. All compounds reduced Aβ aggregation and increased disaggregation of preformed Aβ aggregates in a dose-dependent manner. However, the inhibitory effect of three compounds on Aβ aggregation was not correlated with antioxidant activity, which was measured by DPPH assay. Taken together, these results suggest that the triterpenoid derivatives from P. frutescens have the potential to be developed as good therapeutics or preventatives for AD.

• Natural Product Sciences
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• v.28 no.3
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• pp.153-160
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• 2022

Neuroinflammation is known to be associated with brain injury in Alzheimer's disease (AD), and the inhibition of microglial activation, a key player in inflammatory response, is considerd as important target for AD. In this study, the ethanol extract of aerial parts of Forsythia velutina Nakai, a Korean native species, significantly inhibited nitric oxide (NO) production in LPS-stimulated BV2 microglial cells. Thus, the active principles in F. velutina aerial parts were isolated based on activity-guided isolation method. As a result, six compounds were isolated and their structures were elucidated based on NMR data and the comparison with the relevant references as arctigenin (1), matairesinol (2), rengyolone (3), ursolic acid (4), secoisolariciresinol (5), and arctiin (6). Among them, four compounds including arctigenin (1), matairesinol (2), secoisolariciresinol (5), and arctiin (6) significantly inhibited NO production in a dose-dependent manner. In particular, matairesinol (2) and secoisolariciresinol (5) reduced 60% of NO production compared to LPS-treated group. This inhibitory effects of matairesinol (2) and secoisolariciresinol (5) were accompanied with the reduced expression levels of iNOS and COX-2. These results suggest that the extract of F. velutina and its active compounds could be beneficial for neuroinflammatory diseases including AD.

• Natural Product Sciences
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• v.27 no.4
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• pp.293-299
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• 2021

The ethyl acetate fractions prepared from the leaves of Thuja orientalis significantly inhibited nitric oxide (NO) production in lipopolysaccharide-stimulated BV2 microglial cells. According to bioassay-coupled LC-QTOF MS/MS, the components near 22 and 25 mins in the mass chromatogram highly inhibited NO production and were expected to be labdane diterpenes, and the active components were characterized via further isolation. The results of the NO production inhibitory assay of the isolated compounds correlated well with the results of bioassay-coupled LC-QTOF MS/MS. Among the identified constituents, NO production inhibitory activities of 16-hydroxy-labda-8(17),13-diene-15,19-dioic acid butenolide (2) and 15-hydroxypinusolidic acid (3) were newly reported. Taken together, these results demonstrated that LC-QTOF MS/MS coupled with NO production inhibition assay was a powerful tool for accurately predicting new anti-inflammatory constituents in the extracts from natural products. Moreover, it provided a potential basis for broadening the application of bioassay-coupled LC-QTOF MS/MS in natural product research.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.52-52
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• 2021

Persicaria amphibia as an England native plant, is a rhizomatous perennial, one of the rather amphibious plants. Its aquatic form contains water-soluble sugars, starch, and protein. P. amphibia have up to 18% tannins in stems and rhizomes. Previous studies have confirmed the anti-inflammatory activity of live bacteria roots, but no studies on bioactivity are known. DNA damage responses (DDRs) pathways are considered a crucial factor affecting the alleviation of cellular damage. The ataxia-telangiectasia mutated and Rad3 related (ATM) and checkpoint kinase 2 (Chk2) pathways are the main pathways of DNA damage response. Also, p53 is a key integrator of cellular response to oxidative DNA damage, contributing repair, or leading transcription including apoptosis. In the present study, we conducted an investigation into the inhibitory effects of P. amphibia on oxidative DNA damage for confirming potential to complementary medicine and therapies. In conclusion, P. amphibia can provide protective effects against double-stranded DNA break (DSB) caused by oxidative DNA damage.