• 대한한의학회지
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• 제43권3호
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• pp.1-15
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• 2022

Objectives: Myrrh have been used as a traditional remedy to treat infectious and inflammatory diseases. However, it is largely unknown whether myrrh ethanol extract could exhibit the inhibitory activities against particulate matter (PM)-induced skin injury on human keratinocytes, HaCaT cells. Therefore, this study was aimed to investigate the inhibitory activity of myrrh ethanol extract on PM-induced skin injury in HaCaT cells. Methods: To investigate the inhibitory effects of myrrh ethanol extract in HaCaT cells, the skin injury model of HaCaT cells was established under PM treatment. HaCaT keratinocyte cells were pre-treated with myrrh ethanol extract for 1 h, and then stimulated with PM. Then, the cells were harvested to measure the cell viability, reactive oxygen species (ROS), pro-inflammatory cytokines including interleukin (IL) 1-beta, IL-6, and tumor necrosis factor (TNF)-𝛼, hyaluronidase, collagen, MMPs. In addition, we examined the mitogen activated protein kinases (MAPKs) and inhibitory kappa B alpha (I𝜅-B𝛼) as inhibitory mechanisms of myrrh ethanol extract. Results: The treatment of myrrh ethanol extract inhibited the PM-induced cell death and ROS production in HaCaT cells. In addition, myrrh ethanol extract treatment inhibited the PM-induced elevation of IL-1beta, IL-6, and TNF-𝛼. Also, myrrh ethanol extract treatment inhibited the increase of hyaluronidase, MMP and decrease of collagen. Furthermore, myrrh ethanol extract treatment inhibited the activation of MAPKs and the degradation of I𝜅-B𝛼. Conclusions: Our result suggest that treatment of myrrh ethanol extract could inhibit the PM-induced skin injury via deactivation of MAPKs and nuclear factor (NF)-𝜅B in HaCaT cells. This study could suggest that myrrh ethanol extract could be a beneficial agent to prevent skin damage or inflammation.

• 한국미생물·생명공학회지
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• 제42권2호
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• pp.170-176
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• 2014

본 연구에서는 Euptelea pleiosperma 에탄올 추출물(EPEE)의 항산화능과 항염증 생리활성을 in vitro assay system 및 cell culture model system을 이용하여 분석하였다. 먼저 EPEE의 항산화능을 DPPH radical scavenging activity로 분석한 결과 radical 소거능의 정도가 양성 대조군으로 사용한 ascorbic acid 보다 높은 활성을 보여 매우 강한 항산화능을 보유함을 확인하였다. 또한 RAW 264.7 세포주를 이용한 $H_2O_2$ 및 LPS의 유도에 의해 생성된 ROS에 대한 소거능을 분석한 결과에서도 농도의존적인 강한 소거능을 보였다. 뿐만 아니라 대표적인 항산화효소 중 하나로 천연물에 의한 항산화능 활성에 의해 주로 발현이 유도되는 hemeoxygenase 1 (HO-1) 및 그 전사 인자인 nuclear factor-E2-related factor 2 (Nrf2)의 단백질 발현이 EPEE의 처리에 의해 유의적으로 증가됨을 보였으며 이러한 HO-1 및 Nrf2의 발현 변화는 상위신호전달계인 MAPKs 및 PI3K/Akt 에 의해 조절될 가능성을 보였다. 한편 EPEE가 LPS에 의해 유도된 NO 생성에 미치는 영향을 분석한 결과 농도의존적인 NO 생성 저해능을 보였으며 이는 NO 생성 단백질인 iNOS의 발현 저해에서 기인함을 확인하였다. 이와 같은 EPEE의 NO 생성 억제 효과는 염증 상위신호전달계인 NF-${\kappa}B$ 및 AP-1의 조절을 통해 일어날 가능성을 보였다. 이러한 결과를 통해 EPEE의 높은 항산화능과 항염증 활성을 처음으로 확인하였으며 향후 기능성 소재로서 유용하게 활용될 수 있을 것으로 판단된다.

• Journal of Nutrition and Health
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• 제54권3호
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• pp.321-333
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• 2021

본 연구에서는 진피-황금 혼합물 (CS)이 급성 역류성 식도염에 미치는 식도 점막 보호 효과를 평가하기 위하여 CS를 경구투여한 후 수술을 통해 역류성 식도염을 유발하였으며, 실험 종료 후 혈액 채취 및 식도 조직을 적출하였다. 동물에게서 적출한 식도 점막의 손상 정도를 육안으로 확인한 결과 CS투여군에서 식도 점막의 손상이 유의하게 감소하였으며, H&E staining을 통해 관찰한 결과 마찬가지로 CS투여군에서 식도 상피의 탈락 및 염증세포의 침윤이 현저하게 감소한 것을 확인하였다. 혈액을 이용하여 역류성 식도염의 원인으로 유효하다고 알려진 ROS의 수치를 확인한 결과, CS투여군에서 ROS 수치가 유의적으로 감소하였으며, western blotting을 통해 NADPH oxidase인 NOX4, p47^phox, p22^phox의 발현을 확인한 결과, 마찬가지로 CS 투여군에서 유의하게 감소하였고, 특히 CS200투여군에서 Normal군과 비슷한 수치를 나타냈다. 또한, CS투여는 염증성 단백질인 MAPK와 NF-κB 경로를 유의적으로 억제하였을 뿐 아니라 tight junction 단백질인 claudin-1과 claudin-4의 발현을 유의하게 조절한 것을 확인하였다. 이상의 결과를 종합해보면 진피-황금 추출물은 산화적 스트레스를 억제함으로써 염증성 단백질의 발현을 조절할 뿐 아니라 tight junction 단백질의 발현을 조절하여 식도 점막을 보호하는 것으로 판단되나 역류성 식도염은 음식물의 섭취와 밀접한 관련이 있는 만큼 추후 동물의 식이 섭취량을 조사하는 등 세부적인 추가 연구가 필요할 것으로 보인다.

• 대한본초학회지
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• 제33권6호
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• pp.35-42
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• 2018

Objectives : The aim of this study was to investigate whether the extract of Coptidis Rhizoma inhibits inflammation in chronic cold stress (CCS)-exposed mice or not. Methods : Coptidis Rhizoma extract (CRE) was made by reflux with distilled water. Male ICR mice (7 weeks old) were divided randomly into 5 groups: (1) control, (2) CCS, (3) CCS+CRE 100 mg/kg, (4) CCS+CRE 300 mg/kg, (5) CCS+CRE 1,000 mg/kg groups. Mice were orally administered once a day for 14 days starting from 1 day before CCS. Group (2)-(5) were exposed to CCS conditions that maintained at $4^{\circ}C$ for 2 h once a day for 14 days. The levels of serum cortisol and hypothalamic prostaglandin E1 (PGE1) and PGE2 were measured by enzyme-linked immunosorbent assay kit. The expression levels of several pro-inflammatory factors like heat shock protein 70 (HSP70), c-fos, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) were measured by western blot analysis in mouse hypothalamus. Results : Oral administration of CRE 1,000 mg/kg significantly suppressed the increase of serum cortisol levels in mice exposed to CCS. CCS-exposed mice had significantly increased the expression of HSP70, c-fos, and NF-kB in hypothalamus, while CRE treatment significantly attenuated the elevation of these pro-inflammatory factors. The ratio of PGE2/PGE1 was also higher in CCS-exposed mice than control group. CRE treatment significantly reduced the increase of PGE2/PGE1 ratio induced by CCS. Conclusion : These findings suggest that Coptidis Rhizoma may work as a potential agent to modulate inflammatory responses under the condition of cold adaptation formed by CCS.

• 대한약침학회지
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• 제27권2호
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• pp.59-69
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• 2024

This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

• Animal Bioscience
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• 제37권1호
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• pp.131-141
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• 2024

Objective: This experiment aimed to explore the protective action of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata on lipopolysaccharide (LPS)-induced liver injury in broilers. Methods: Total 216 healthy broilers were selected in a 21-d trial and assigned randomly to the following 3 treatments: control (CON) group, LPS group, and LPS+IA group. The CON and LPS groups were provided with a basal diet, whereas the LPS+IA group received the basal diet supplemented with 0.6 mg/kg Macleaya cordata IA. Broilers in LPS and LPS+IA groups were intraperitoneally injected with LPS (1 mg/kg body weight) at 17, 19, and 21 days of age, while those in CON group were injected with equivalent amount of saline solution. Results: Results showed LPS injection caused systemic and liver inflammation in broilers, inhibited immune function, and ultimately lead to liver injury. By contrast, supplementation of IA ameliorated LPS-induced adverse change in serum parameters, boosted immunity in LPS+IA group. Furthermore, IA suppressed the elevation of hepatic inflammatory cytokines and caspases levels induced by LPS, as well as the expressions of genes related to the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Conclusion: Dietary inclusion of 0.6 mg/kg Macleaya cordata IA could enhance immune function of body and inhibit liver damage via inactivating TLR4/MyD88/NF-κB signaling pathway in broilers.

• 대한본초학회지
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• 제35권1호
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• pp.35-44
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• 2020

Objectives : The objective of this study was to investigate the therapeutic effect of Corni Fructus 30% ethanol extract (CFE) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : The subjects were divided into 4 groups ; Normal group (N, n=10), MIA-induced osteoarthritis control group (Con, n=10), indomethacin 5 mg/kg treated group (INDO, n=10), CFE 200 mg/kg treated group (CFE, n=10). Blood and articulation tissues were collected after two weeks of drug administration. Oxidative stress was analyzed with reactive oxygen species (ROS), peroxynitrite (ONOO-). And the Nuclear factor erythroid-2 (Nrf2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, glutathione peroxidase-1/2 (GPx-1/2), Nuclear Factor Kappa B p65 (NF-κBp65), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), Interleukin 1β (IL-1β), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated by western blot. Results : The administration of CFE showed a significant reduction of changes in relative hind paw weight distribution. Reactive oxygen species (ROS) and peroxy nitrite (ONOO-) levels of articulation tissues were significantly decreased in CFE compared to the control group. Western blot measurements of Nrf2, HO-1, SOD, catalase, GPx-1/2 showed that the CFE group was increased compared to the Con group. And western blot measurements of NF-κBp65, COX-2, iNOS, TNFα, IL-6, IL-1β showed that the CFE group was reduced compared to the Con group. Also CFE group decreased MMP-1 and increased TIMP-1. Conclusion : Based on the above results, it can be seen that osteoarthritis is improved when Corni Fructus 30% ethanol extract treated.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5589-5597
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• 2013

The aim of this review article was to evaluate the relationship and the possible etiological mechanisms between endometriosis, leiomyoma (LM) and adenomyosis and gynecological cancers, such as ovarian and endometrial cancer and leiomyosarcoma (LMS). MEDLINE was searched for all articles written in the English literature from July 1966 to May 2013. Reports were collected systematically and all the references were also reviewed. Malignant transformation of gynecologic benign diseases such as endometriosis, adenomyosis and LM to ovarian and endometrial cancer remains unclear. Hormonal factors, inflammation, familial predisposition, genetic alterations, growth factors, diet, altered immune system, environmental factors and oxidative stress may be causative factors in carcinogenesis. Early menarche, low parity, late menopause and infertility have also been implicated in the pathogenesis of these cancers. Ovarian cancers and endometriosis have been shown to have common genetic alterations such as loss of heterozygosity (LOH), PTEN, p53, ARID1A mutations. MicroRNAs have also been implicated in malignant transformation. Inflammation releases proinflammatory cytokines, and activates tumor associated macrophages (TAMS) and nuclear factor kappa b (NF-KB) signaling pathways that promote genetic mutations and carcinogenesis. MED12 mutations in LM and smooth muscle tumors of undetermined malignant potential (STUMP) may contribute to malignant transformation to LMS. A hyperestrogenic state may be shared in common with pathogenesis of adenomyosis, LM and endometrial cancer. However, the effect of these benign gynecologic diseases on endometrial cancer should be studied in detail. This review study indicates that endometriosis, LM, adenomyosis may be associated with increased risk of gynecological cancers such as endometrial and ovarian cancers. The patients who have these gynecological benign diseases should be counseled about the future risks of developing cancer. Further studies are needed to investigate the relationship between STUMPs, LMS and LM and characteristics and outcome endometrial carcinoma in adenomyotic patients.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.70-76
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• 2011

Bone remodeling is a dynamic process involving a constant balance between osteoclast-induced bone resorption and osteoblast-induced bone formation. Osteoclasts play a crucial homeostatic role in skeletal modeling and remodeling, and destroy bone in many pathological conditions. Previously, we reported that the hexane soluble fraction of Ficus carica inhibited osteoclast differentiation. Poly unsaturated fatty acids, such as ethyl docosahexaenoate (E-DHA), docosahexaenoic acid (DHA), cis-11,14-eicosadienoic acid (EDA) and eicosapentaenoic acid (EPA), were identified from the hexane soluble fraction of Ficus carica. Among them, E-DHA most potently inhibited osteoclastogenesis in RAW264.7 cells. E-DHA reduced the activities of JNK and NF-$\kappa}B$. E-DHA suppressed the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). Interestingly, DHA increased the activity of alkaline phosphatase and expression of bone morphogenetic protein 2 (BMP2) more than E-DHA in MC3T3-E1 cells, suggesting that DHA may induce osteoblast differentiation. The data suggests that a combination of E-DHA and DHA has potential use in the treatment of diseases involving abnormal bone lysis, such as osteoporosis, rheumatoid arthritis and periodontal bone erosion.

• BMB Reports
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• 제53권6호
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• pp.323-328
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• 2020

Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5'-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.