• Biomolecules & Therapeutics
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• 제21권5호
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• pp.364-370
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• 2013

Resveratrol (trans-3,4'-trihydroxystillbene), a naturally occurring polyphenolic antioxidant found in grapes and red wine, elicits diverse biochemical responses and demonstrates anti-aging, anti-inflammatory, and anti-proliferative effects in several cell types. Previously, resveratrol was shown to regulate differentiation and inflammation in rabbit articular chondrocytes, while the direct production of nitric oxide (NO) in these cells by treatment with the NO donor sodium nitroprusside (SNP) led to apoptosis. In this study, the effect of resveratrol on NO-induced apoptosis in rabbit articular chondrocytes was investigated. Resveratrol dramatically reduced NO-induced apoptosis in chondrocytes, as determined by phase-contrast microscopy, the MTT assay, FACS analysis, and DAPI staining. Treatment with resveratrol inhibited the SNP-induced expression of p53 and p21 and reduced the expression of procaspase-3 in chondrocytes, as detected by western blot analysis. SNP-induced degradation of I-kappa B alpha ($I{\kappa}B-{\alpha}$) was rescued by resveratrol treatment, and the SN50 peptide-mediated inhibition of NF-kappa B (NF-${\kappa}B$) activity potently blocked SNP-induced caspase-3 activation and apoptosis. Our results suggest that resveratrol inhibits NO-induced apoptosis through the NF-${\kappa}B$ pathway in articular chondrocytes.

• 한국응용과학기술학회지
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• 제36권3호
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• pp.766-778
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• 2019

본 연구에서는 초임계 공정에 의해 복령피를 추출하였고, 에탄올 복령피 추출물과 비교하여 항염, 미백, 항산화효과를 측정하였다. 또한 선정된 추출물의 제형과 약물전달 펩티드를 활용하여 효율적인 경피투과 방법을 제시하였다. 복령피의 항암, 항염성분으로 알려진 Pachymic acid를 지표성분으로 HPLC 분석 결과 에탄올 복령피 추출물 보다 초임계 복령피 추출물이 2배 이상 높게 추출되는 것으로 나타났다. 복령피의 항산화효과를 확인하기 위하여 DPPH 소거능과 ABTS 소거능은 복령피 에탄올 추출물이 초임계 복령피 추출물보다 더 낮은 농도에서 $IC_{50}$을 나타내었다. 하지만 RAW 264.7 세포 내 NO(Nitric oxide) 생성량을 측정한 결과에서는, 에탄올 복령피 추출물보다 초임계 복령피 추출물이 동일 농도에서 더 낮은 NO 생성량을 나타냈다. 또한 B16 melanoma 세포에 복령피 추출물을 $20{\mu}g/mL$ 농도를 72시간 처리 후 세포 내외 멜라닌 합성을 확인한 결과에서는, 에탄올 복령피 추출물과 초임계 복령피 추출물 모두 효과가 있었으며 초임계 추출물이 더 낮은 멜라닌 함량을 보였다. NO 생성량 실험에서 활용된 RAW 264.7 세포에서는 $800{\mu}g/mL$농도에서도 독성이 나타나지 않았다. 하지만 B16 melanoma 세포에서는 $50{\mu}g/mL$에서도 에탄올 추출물과 초임계 추출물 모두 60 % 미만의 생존율을 나타냈다. 초임계 복령피 추출물을 대상으로 리포좀 제형과 약물전달 펩티드를 활용하여 Franz diffusion cell 실험 결과에서는, 리포좀 제형과 약물 전달 펩티드가 초임계 복령피 추출물을 경피 투과를 증진시켜 주는 것으로 나타났다. 초임계 복령피 추출물이 다양한 효능의 화장품 소재로서 개발될 가능성이 있다고 판단된다.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.152-159
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• 2019

Multiple sclerosis (MS) is an autoimmune disease characterized by progressive neuronal loss, neuroinflammation, axonal degeneration, and demyelination. Previous studies have reported that 6-shogaol, a major constituent of ginger (Zingiber officinale rhizome), and its biological metabolite, 6-paradol, have anti-inflammatory and anti-oxidative properties in the central nervous system (CNS). In the present study, we investigated whether 6-shogaol and 6-paradol could ameliorate against experimental autoimmune encephalomyelitis (EAE), a mouse model of MS elicited by myelin oligodendrocyte glycoprotein ($MOG_{35-55}$) peptide immunization with injection of pertussis toxin. Once-daily administration of 6-shogaol and 6-paradol (5 mg/kg/day, p.o.) to symptomatic EAE mice significantly alleviated clinical signs of the disease along with remyelination and reduced cell accumulation in the white matter of spinal cord. Administration of 6-shogaol and 6-paradol into EAE mice markedly reduced astrogliosis and microglial activation as key features of immune responses inside the CNS. Furthermore, administration of these two molecules significantly suppressed expression level of tumor necrosis $factor-{\alpha}$, a major proinflammatory cytokine, in EAE spinal cord. Collectively, these results demonstrate therapeutic efficacy of 6-shogaol or 6-paradol for EAE by reducing neuroinflammatory responses, further indicating the therapeutic potential of these two active ingredients of ginger for MS.

• Natural Product Sciences
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• 제19권4호
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• pp.347-354
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• 2013

Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of cordycepin on the antigen-presenting function of antigen-presenting cells (APCs). Dendritic cells (DCs) were cultured in the presence of cordycepin and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through RT-PCR and Western blot analysis. Cordycepin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of cordycepin was also confirmed using mice that had been injected with cordycepin followed by soluble OVA. Furthermore, cordycepin suppressed the mRNA and protein levels of iNOS, COX-2, pro-inflammatory cytokines in a concentration-dependent manner. These results provide an understanding of the mechanism of the T cell response-regulating activity of cordycepin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.

• 대한한의학회지
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• 제42권4호
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• pp.150-163
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• 2021

Objectives: The purpose of this study was to confirm the effects of Liriope platyphylla extract on relieving Gastroesophageal reflux disease (GERD) through regulation of acid secretion. Methods: 8-week-old ICR mice were divided into untreated control group (Ctrl), GERD elecitation group (GERDE), Omeprazole administrate group before GERD elicitation (OMA), and Liriope platyphylla extract administrate group before GERD elicitation (LPA). After inducing GERD, gross observation and histological examination were performed and ATP6V1B1 (ATPase H+ Transporting V1 Subunit B1), GRPR (Gastrin-releasing peptide receptor), COX-1 (Cyclooxygenase 1), 8-OHdG (8-hydroxy-2'-deoxyguanosine), Cathelicidin, p-JNK (phospho c-Jun N-terminal kinase) were observed to confirm the damage defense effect of the esophageal mucosa, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection, and apoptosis regulation Results: OMA and LPA showed lower levels of damage compared to GERDE in gross observation and histological examination. ATP6V1B1, GRPR, and 8-OHdG showed lower positive reactions in OMA and LPA than in GERDE. COX-1 were less positive in GERDE and OMA than in Ctrl, but showed higher secretion in LPA than in Ctrl. Cathelicidin showed a decreased positive reaction in GERDE, OMA and LPA compared to Ctrl, but the decrease in positive reaction was smaller in OMA and LPA compared to GERDE. p-JNK showed increased positive reaction in GERDE, OMA and LPA than in Ctrl, but the increase in the positive reaction was smaller in the OMA and LPA compared to GERDE. Conclusions: The effects of Liriope platyphylla extract on esophageal mucosal damage protection, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection and apoptosis regulation were confirmed.

• 한방안이비인후피부과학회지
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• 제36권4호
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• pp.30-50
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• 2023

Objectives : To investigate the active compounds and therapeutic mechanisms of Atractylodes Lancea(Thunb.) D.C. and Magnolia Officinalis Rehder et Wilson in the treatment of dermatitis accompanied by pruritus, as well as their potential to complement or replace standard drugs. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of research target herbs. Then we explore pathway/terms of the common target proteins among research target herbs, fexofenadine and disease. Results : We selected 9 active compounds are selected from Atractylodes lancea and identified 231 target proteins. Among them, 74 proteins are associated with inflammatory skin diseases that cause pruritus. These proteins are involved in various pathways including, 'Nitric-oxide synthase regulator activity', 'Hydroperoxy icosatetraenoate dehydratase activity, Aromatase activity', 'RNA-directed DNA polymerase activity', 'Arachidonic acid metabolism', 'Peptide hormone processing', 'Chemokine binding' and 'Sterol biosynthetic process'. Additionally, coregenes are involved in 'IL-17 signaling pathway'. Similarly, we selected 2 active compounds from Magnolia officinalis and identified 133 target proteins. Among them, 33 proteins are related to inflammatory skin diseases that cause pruritus. These proteins are primarily involved in 'Vascular associated smooth muscle cell proliferation' and 'Arachidonic acid metabolism'. There is no significant difference between the pathways in which coregenes are involved. Conclusions : It is expected that Atractylodes Lancea will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied pruritus through suppressing inflammation and protecting skin barrier. Meanwhile, it is expected that Magnolia Officinalis will only be able to show indirect anti-inflammation effects. Therefore, Atractylodes Lancea and fexofenadine are believed to complement each other, whereas Magnolia Officialinalis is expected to provide supplementary support on skin disease.

• Journal of Dairy Science and Biotechnology
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• 제41권3호
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• pp.113-125
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• 2023

In this study, we explored the synergistic effects of whey protein concentrate (WPC) and soybean protein components after fermentation with lactic acid bacteria isolated from kimchi, and identified several peptides with desirable physiological functions, proteolysis, and immune effects. Antioxidant activity was determined using 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, 1,1-diphenyl-2-picrylhydrazyl, ferric-reducing antioxidant power, and hydroxyl radical scavenging assays, followed by cross-validation of the four antioxidant activities. These assays revealed that samples with a 8:2 and 9:1 whey to soy ratio possessed higher antioxidant activity than the control samples. Antibacterial potency testing revealed high antibacterial activity in the 9:1 and 8:2 samples. Cytotoxicity testing of samples using 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide revealed that only the 10:0, 1:9, and 0:10 samples had <80% viable cells, indicating no significant cytotoxicity. Nitric oxide (NO) assays revealed that NO expression was reduced in 8:2, 5:5, and 0:10 protein ratio fermentations, indicating low inflammatory reaction stimulatory potential. Cytokine expression was confirmed using an enzyme-linked immunosorbent assay kit. The 8:2 sample had the lowest inflammatory cytokine (interleukin [IL]-1α, IL-6, and tumor necrosis factor-α) levels compared with the lipopolysaccharide-treated group. Amino acid profiling of the 8:2 sample identified 17 amino acids. These results suggest that inoculating and fermenting Lactobacillus plantarum DK203 and Lactobacillus paracasei DK209 with an 8:2 mixture of WPC and soybean protein releases bioactive peptides with excellent anti-inflammatory and antioxidant properties, making them suitable for functional food development.

• Journal of Periodontal and Implant Science
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• 제48권6호
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• pp.347-359
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• 2018

Purpose: Periodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults. Methods: A total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices. Results: The RA group had significantly higher values than the control group for all investigated periodontal indices (P<0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r=0.125, P=0.049), RA disease duration (r=0.253, P<0.001), erythrocyte sedimentation rate (ESR) (r=0.162, P=0.010), and anti-CCP antibody titer (r=0.205, P=0.004). Probing pocket depth (PPD) was correlated with ESR (r=0.139, P=0.027) and anti-Pg antibody titer (r=0.203, P=0.001). Bleeding on probing (BOP) was correlated with DAS28 (r=0.137, P=0.030), RA disease duration (r=0.202, P=0.001), ESR (r=0.136, P=0.030), anti-Pg antibody titer (r=0.177, P=0.005), and anti-CCP antibody titer (r=0.188, P=0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r=0.201, P=0.002; the latter r=0.175, P=0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r=0.148, P=0.020). Conclusions: The GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.

• 한국산학기술학회논문지
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• 제19권12호
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• pp.62-70
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• 2018

본 연구에서는 미백 개선 효과가 알려진 올리고 펩타이드(Lys-Val-Ala-Arg-Pro : KVARP)를 기본 구조로 하여 고체상합성법(SPPS)으로 합성하였다. 합성된 올리고 펩타이드에 게란산(geranic acid), 리포익산(lippoic acid), 살리실산(salicylic acid)를 접합하여 올리고 펩타이드 유도체를 합성하였다. 미백개선 효과는 tyrosinase(티로시아나제) 저해실험으로 측정하였으며, Geranic-KVARP의 $5000{\mu}g/m{\ell}$에서 93%의 저해율로 가장 좋은 효과를 나타내었고, IC50 값은 $68{\mu}g/m{\ell}$로 측정되었다. 주름개선 효과는 elastase(엘라스타아제) 저해 실험으로 측정한 결과 Salicylic-KVARP의 $400{\mu}g/m{\ell}$에서 63%의 저해율을 보였으며, IC50값은 $253{\mu}g/m{\ell}$으로 확인되었다. DPPH법으로 실시한 항산화효과 측정실험에서는 Caffeic-KVARP가 최고 농도인 $400{\mu}g/m{\ell}$에서 95% 이상의 항산화효과를 보였으며 IC50값은 $31{\mu}g/m{\ell}$로 나타났다. Nitric Oxide 저해실험을 통한 항염효과를 측정한 결과 Lipoic-KVARP의 $400{\mu}g/m{\ell}$에서 67%의 저해율을 보였다. 다양한 실험결과로부터 합성된 KVARP유도체 4종은 새로운 의약품 및 화장품 소재로서의 이용할 가능성이 있으며, 산업적인 면에서 응용이 가능하다고 판단된다.

• 생명과학회지
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• 제31권11호
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• pp.987-994
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• 2021

이전 연구에서 흰점박이꽃무지 유충 유래 항균 펩타이드 Protaetiamycine 2와 6의 항염증 효과를 입증하였다. 본 연구에서는 lipopolysaccharide (LPS)로 염증을 유도한 RAW264.7 대식세포에서 흰점박이꽃무지 유충의 새로운 항균 펩타이드인 Protaetiamycine 9의 염증 조절 기전을 검토하였다. 항염증 활성을 확인하기 위하여 RAW 264.7 세포에 독성이 나타나지 않는 범위(25-100 ㎍/ml)로 Protaetiamycine 9를 1시간 동안 전처리한 후, 24시간 동안 LPS (100 ng/ml)로 염증을 유도하였다. Protaetiamycine 9 (25-100 ㎍/ml)는 LPS 자극으로 증가된 nitric oxide (NO) 분비를 농도의존적으로 감소시켰고, 염증 매개 인자의 생성에 관여하는 inducible NO synthase (iNOS) 및 cyclooxygenase-2 (COX-2)의 발현을 유의적으로 억제하였다. Protaetiamycine 9는 LPS로 유도된 inhibitory kappa B alpha (IκB-α)의 분해를 저해하고, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) 및 p38을 포함하는 mitogen-activated protein kinases (MAPKs)의 인산화를 억제함으로써 염증성 사이토카인(interleukin (IL)-6와 IL-1β)의 생성과 유전자 발현을 효과적으로 억제하였다. 따라서, Protaetiamycine 9는 염증반응의 신호전달경로인 NF-κB와 MAPKs의 활성화를 억제함으로써 항염증 효과를 나타내는 것으로 사료된다.