The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of <i>Fraxinus rhynchophylla</i> Hance Bark on Contact Dermatitis in Mice

<i>Fraxinus rhynchophylla</i> Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of <i>F. rhynchophylla</i> and whether it has a th...

Full description

Bibliographic Details
Main Authors: Sura Kim, Ji-Hyo Lyu, Beodeul Yang, Soyeon Kim, Jung-Hoon Kim, Hyungwoo Kim, Suin Cho
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/7/6091
_version_ 1797607893932965888
author Sura Kim
Ji-Hyo Lyu
Beodeul Yang
Soyeon Kim
Jung-Hoon Kim
Hyungwoo Kim
Suin Cho
author_facet Sura Kim
Ji-Hyo Lyu
Beodeul Yang
Soyeon Kim
Jung-Hoon Kim
Hyungwoo Kim
Suin Cho
author_sort Sura Kim
collection DOAJ
description <i>Fraxinus rhynchophylla</i> Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of <i>F. rhynchophylla</i> and whether it has a therapeutic effect in mice with contact dermatitis (CD). In this study, the active compounds in <i>F. rhynchophylla</i>, their targets, and target gene information for inflammatory dermatosis were investigated using network-based pharmacological analysis. Docking analysis was conducted using AutoDock Vina. In addition, the therapeutic effect of an ethanolic extract of <i>F. rhynchophylla</i> (EEFR) on skin lesions and its inhibitory effects on histopathological abnormalities, inflammatory cytokines, and chemokines were evaluated. Finally, its inhibitory effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways were observed in RAW 264.7 cells. In our results, seven active compounds were identified in <i>F. rhynchophylla</i>, and six were associated with seven genes associated with inflammatory dermatosis and exhibited a strong binding affinity (<−6 kcal/mol) to prostaglandin G/H synthase 2 (PTGS2). In a murine 1-fluoro-2,4-dinitrobenzene (DNFB) model, topical EEFR ameliorated the surface symptoms of CD and histopathological abnormalities. EEFR also reduced the levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues and inhibited PTGS2, the nuclear translocation of NF-κB (p65), and the activation of c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. In conclusion, the bark of <i>F. rhynchophylla</i> has potential use as a therapeutic or cosmetic agent, and the mechanism responsible for its effects involves the suppression of inflammatory mediators, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB)-α degradation, the nuclear translocation of NF-κB, and JNK phosphorylation.
first_indexed 2024-03-11T05:35:58Z
format Article
id doaj.art-91aa98fda2fe4a6ea3825f2ca243abf1
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-11T05:35:58Z
publishDate 2023-03-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-91aa98fda2fe4a6ea3825f2ca243abf12023-11-17T16:46:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247609110.3390/ijms24076091The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of <i>Fraxinus rhynchophylla</i> Hance Bark on Contact Dermatitis in MiceSura Kim0Ji-Hyo Lyu1Beodeul Yang2Soyeon Kim3Jung-Hoon Kim4Hyungwoo Kim5Suin Cho6Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Republic of KoreaResearch Institute for Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Republic of KoreaDivision of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Republic of KoreaDivision of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Republic of KoreaDivision of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Republic of KoreaDivision of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Republic of KoreaDivision of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongnam, Republic of Korea<i>Fraxinus rhynchophylla</i> Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of <i>F. rhynchophylla</i> and whether it has a therapeutic effect in mice with contact dermatitis (CD). In this study, the active compounds in <i>F. rhynchophylla</i>, their targets, and target gene information for inflammatory dermatosis were investigated using network-based pharmacological analysis. Docking analysis was conducted using AutoDock Vina. In addition, the therapeutic effect of an ethanolic extract of <i>F. rhynchophylla</i> (EEFR) on skin lesions and its inhibitory effects on histopathological abnormalities, inflammatory cytokines, and chemokines were evaluated. Finally, its inhibitory effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways were observed in RAW 264.7 cells. In our results, seven active compounds were identified in <i>F. rhynchophylla</i>, and six were associated with seven genes associated with inflammatory dermatosis and exhibited a strong binding affinity (<−6 kcal/mol) to prostaglandin G/H synthase 2 (PTGS2). In a murine 1-fluoro-2,4-dinitrobenzene (DNFB) model, topical EEFR ameliorated the surface symptoms of CD and histopathological abnormalities. EEFR also reduced the levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues and inhibited PTGS2, the nuclear translocation of NF-κB (p65), and the activation of c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. In conclusion, the bark of <i>F. rhynchophylla</i> has potential use as a therapeutic or cosmetic agent, and the mechanism responsible for its effects involves the suppression of inflammatory mediators, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB)-α degradation, the nuclear translocation of NF-κB, and JNK phosphorylation.https://www.mdpi.com/1422-0067/24/7/6091<i>Fraxinus rhynchophylla</i>traditional medicineinflammationskindermatosis
spellingShingle Sura Kim
Ji-Hyo Lyu
Beodeul Yang
Soyeon Kim
Jung-Hoon Kim
Hyungwoo Kim
Suin Cho
The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of <i>Fraxinus rhynchophylla</i> Hance Bark on Contact Dermatitis in Mice
International Journal of Molecular Sciences
<i>Fraxinus rhynchophylla</i>
traditional medicine
inflammation
skin
dermatosis
title The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of <i>Fraxinus rhynchophylla</i> Hance Bark on Contact Dermatitis in Mice
title_full The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of <i>Fraxinus rhynchophylla</i> Hance Bark on Contact Dermatitis in Mice
title_fullStr The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of <i>Fraxinus rhynchophylla</i> Hance Bark on Contact Dermatitis in Mice
title_full_unstemmed The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of <i>Fraxinus rhynchophylla</i> Hance Bark on Contact Dermatitis in Mice
title_short The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of <i>Fraxinus rhynchophylla</i> Hance Bark on Contact Dermatitis in Mice
title_sort related mechanisms predicted through network based pharmacological analysis and the anti inflammatory effects of i fraxinus rhynchophylla i hance bark on contact dermatitis in mice
topic <i>Fraxinus rhynchophylla</i>
traditional medicine
inflammation
skin
dermatosis
url https://www.mdpi.com/1422-0067/24/7/6091
work_keys_str_mv AT surakim therelatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT jihyolyu therelatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT beodeulyang therelatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT soyeonkim therelatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT junghoonkim therelatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT hyungwookim therelatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT suincho therelatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT surakim relatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT jihyolyu relatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT beodeulyang relatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT soyeonkim relatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT junghoonkim relatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT hyungwookim relatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice
AT suincho relatedmechanismspredictedthroughnetworkbasedpharmacologicalanalysisandtheantiinflammatoryeffectsofifraxinusrhynchophyllaihancebarkoncontactdermatitisinmice