

浏览全部资源
扫码关注微信
1.天津中医药大学 研究生院,天津 301617
2.天津市中医药研究院 附属医院,天津 300120
Received:22 August 2023,
Published Online:15 November 2023,
Published:20 February 2024
移动端阅览
李想,董玲玲,郭涛等.基于NF-κB信号通路天然产物治疗特应性皮炎的研究进展[J].中国实验方剂学杂志,2024,30(04):271-280.
LI Xiang,DONG Lingling,GUO Tao,et al.Natural Products Treat Atopic Dermatitis via NF-κB Signaling Pathway: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(04):271-280.
李想,董玲玲,郭涛等.基于NF-κB信号通路天然产物治疗特应性皮炎的研究进展[J].中国实验方剂学杂志,2024,30(04):271-280. DOI: 10.13422/j.cnki.syfjx.20231838.
LI Xiang,DONG Lingling,GUO Tao,et al.Natural Products Treat Atopic Dermatitis via NF-κB Signaling Pathway: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(04):271-280. DOI: 10.13422/j.cnki.syfjx.20231838.
特应性皮炎是由内外多因素共同作用的慢性、复发性、炎症性、瘙痒性皮肤病,位居全球皮肤疾病负担首位。由于传统治疗和生物制剂的不良反应及高成本问题,天然产物的开发备受关注。核转录因子-
κ
B(NF-
κ
B)信号通路是抗炎和免疫调节的重要途径,故基于NF-
κ
B信号通路系统,总结了黄酮类、生物碱、酚类、萜类、香豆素类、糖苷类、蒽醌类等天然产物的药理学作用与分子机制,以期为天然产物的开发提供一定指导。目前众多基础研究显示出天然产物具有较高的安全性和有效性,并通过口服或外用的给药方式及与磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)、丝裂原活化蛋白激酶(MAPK)、核转录因子E
2
相关因子2(Nrf2)、高迁移率族蛋白B1(HMGB1)/晚期糖基化终产物受体(RAGE)、核苷酸结合寡聚结构域样受体蛋白3(NLRP3)等信号通路相互串扰的复杂药理学网络途径,发挥抗炎、抗过敏、抗氧化应激等作用,最终逆转特应性皮炎的病理改变。但值得注意的是,天然产物的临床应用转化尚相对不足,仍需更多更为严谨的临床试验加以验证。现有的基础试验及临床证据证明天然产物可能基于NF-
κ
B信号通路发挥改善特应性皮炎的作用,这对评价天然活性物质的潜在机制提供依据,也为药物的开发提供了更多潜在候选者。
Atopic dermatitis (AD) is a chronic, recurrent, inflammatory, and pruritus skin disease caused by multiple internal and external factors, ranking first in the global burden of skin diseases. Due to the adverse reactions and high costs of conventional treatments and biologics, the development of natural products has attracted much attention. The nuclear factor-
κ
B (NF-
κ
B) signaling pathway is a key pathway for inhibiting inflammation and modulating immunity. This paper summarizes the pharmacological effects and molecular mechanisms of natural products such as flavonoids, alkaloids, phenols, terpenoids, coumarins, glycosides, and anthraquinones via NF-
κ
B signaling pathway, aiming to provide guidance for the development of natural products. Basic studies have shown that natural products have high safety and efficacy. Oral or topical administration of natural products can regulate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK), nuclear factor erythroid 2-related factor 2 (Nrf2), high mobility group box 1 protein (HMGB1)/receptor for advanced glycation endproducts (RAGE), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathways to exert anti-inflammatory, anti-allergy, antioxidant activities, thus reversing the pathological changes of AD. However, it is worth noting that the clinical application of natural products is still insufficient, and more rigorous clinical trials are still needed to verify their effects. The basic experiments and clinical evidence prove that natural products may play a role in alleviating AD, which provide a basis for evaluating the functioning mechanism of natural active substances and enrich the candidates for the development of potential drugs.
LAUGHTER M R , MAYMONE M , MASHAYEKHI S , et al . The global burden of atopic dermatitis:Lessons from the global burden of disease study 1990-2017 [J]. Br J Dermatol , 2021 , 184 ( 2 ): 304 - 309 .
SROKA-TOMASZEWSKA J , TRZECIAK M . Molecular mechanisms of atopic dermatitis pathogenesis [J]. Int J Mol Sci , 2021 , 22 ( 8 ): 4130 .
NAKAHARA T , KIDO-NAKAHARA M , TSUJI G , et al . Basics and recent advances in the pathophysiology of atopic dermatitis [J]. J Dermatol , 2021 , 48 ( 2 ): 130 - 139 .
GOH M S , YUN J S , SU J C . Management of atopic dermatitis:A narrative review [J]. Med J Aust , 2022 , 216 ( 11 ): 587 - 593 .
WU S , PANG Y , HE Y , et al . A comprehensive review of natural products against atopic dermatitis: Flavonoids, alkaloids, terpenes, glycosides and other compounds [J]. Biomed Pharmacother , 2021 , 140 : 111741 .
LEE H , LEE D H , OH J H , et al . Skullcapflavone Ⅱ Suppresses TNF- α /IFN- γ -induced TARC, MDC, and CTSS production in HaCaT cells [J]. Int J Mol Sci , 2021 , 22 ( 12 ): 6428 .
WANG L , XIAN Y F , LOO S , et al . Baicalin ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice through modulating skin barrier function, gut microbiota and JAK/STAT pathway [J]. Bioorg Chem , 2022 , 119 : 105538 .
LEE H S , KIM E N , JEONG G S . Oral administration of liquiritigenin confers protection from atopic dermatitis through the inhibition of t cell activation [J]. Biomolecules , 2020 , 10 ( 5 ): 786 .
HOU D D , GU Y J , WANG D C , et al . Therapeutic effects of myricetin on atopic dermatitis in vivo and in vitro [J]. Phytomedicine , 2022 , 102 : 154200 .
KARUPPAGOUNDER V , ARUMUGAM S , THANDAVARAYAN R A , et al . Modulation of HMGB1 translocation and RAGE/NF- κ B cascade by quercetin treatment mitigates atopic dermatitis in NC/Nga transgenic mice [J]. Exp Dermatol , 2015 , 24 ( 6 ): 418 - 423 .
LEE H N , SHIN S A , CHOO G S , et al . Anti‑inflammatory effect of quercetin and galangin in LPS‑stimulated RAW264.7 macrophages and DNCB‑induced atopic dermatitis animal models [J]. Int J Mol Med , 2018 , 41 ( 2 ): 888 - 898 .
CHOI J K , JANG Y H , LEE S , et al . Chrysin attenuates atopic dermatitis by suppressing inflammation of keratinocytes [J]. Food Chem Toxicol , 2017 , 110 : 142 - 150 .
JIN S E , HA H , SHIN H K , et al . Anti-allergic and anti-inflammatory effects of kuwanon g and morusin on MC/9 mast cells and HaCaT keratinocytes [J]. Molecules , 2019 , 24 ( 2 ): 265 .
LIN C Y , HSIEH Y T , CHAN L Y , et al . Dictamnine delivered by PLGA nanocarriers ameliorated inflammation in an oxazolone-induced dermatitis mouse model [J]. J Control Release , 2021 , 329 : 731 - 742 .
YANG C C , HUNG Y L , KO W C , et al . Effect of neferine on DNCB-induced atopic dermatitis in HaCaT cells and BALB/c mice [J]. Int J Mol Sci , 2021 , 22 ( 15 ): 8237 .
CHEN X , LIN J , LIANG Q , et al . Pseudoephedrine alleviates atopic dermatitis-like inflammatory responses in vivo and in vitro [J]. Life Sci , 2020 , 258 : 118139 .
WANG Y , ZHANG P , ZHANG J , et al . Inhibitory effect of Bisdemethoxycurcumin on DNCB-induced atopic dermatitis in mice [J]. Molecules , 2022 , 28 ( 1 ): 293 .
KARUPPAGOUNDER V , ARUMUGAM S , THANDAVARAYAN R A , et al . Resveratrol attenuates HMGB1 signaling and inflammation in house dust mite-induced atopic dermatitis in mice [J]. Int Immunopharmacol , 2014 , 23 ( 2 ): 617 - 623 .
CARLUCCI C D , HUI Y , CHUMANEVICH A P , et al . Resveratrol protects against skin inflammation through inhibition of mast cell, sphingosine Kinase-1, Stat3 and NF- κ B p65 signaling activation in mice [J]. Int J Mol Sci , 2023 , 24 ( 7 ): 6707 .
DAO T , SONG K , KIM J Y , et al . Igalan from Inula helenium (L.) suppresses the atopic dermatitis-like response in stimulated HaCaT keratinocytes via JAK/STAT3 signaling [J]. Inflamm Res , 2020 , 69 ( 3 ): 309 - 319 .
KANG Y M , KIM H M , LEE M , et al . Effects of echinocystic acid on atopic dermatitis and allergic inflammation of the skin and lungs [J]. Phytomedicine , 2022 , 104 : 154211 .
KANG Y M , KIM H M , LEE M , et al . Oleanolic acid alleviates atopic dermatitis-like responses in vivo and in vitro [J]. Int J Mol Sci , 2021 , 22 ( 21 ): 12000 .
MOON G H , LEE Y , KIM E K , et al . Immunomodulatory and anti-inflammatory effects of asiatic acid in a DNCB-induced atopic dermatitis animal model [J]. Nutrients , 2021 , 13 ( 7 ): 2448 .
KO E , PARK S , LEE J H , et al . Ginsenoside Rh 2 ameliorates atopic dermatitis in NC/Nga mice by suppressing NF-kappaB-mediated thymic stromal lymphopoietin expression and T helper type 2 differentiation [J]. Int J Mol Sci , 2019 , 20 ( 24 ): 6111 .
WU P C , CHUO W H , LIN S C , et al . Sclareol attenuates the development of atopic dermatitis induced by 2,4-dinitrochlorobenzene in mice [J]. Immunopharmacol Immunotoxicol , 2019 , 41 ( 1 ): 109 - 116 .
LIM J S , KIM J Y , LEE S , et al . Bakuchicin attenuates atopic skin inflammation [J]. Biomed Pharmacother , 2020 , 129 : 110466 .
LIM J Y , LEE J H , LEE D H , et al . Umbelliferone reduces the expression of inflammatory chemokines in HaCaT cells and DNCB/DFE-induced atopic dermatitis symptoms in mice [J]. Int Immunopharmacol , 2019 , 75 : 105830 .
JEONG N H , YANG E J , JIN M , et al . Esculetin from Fraxinus rhynchophylla attenuates atopic skin inflammation by inhibiting the expression of inflammatory cytokines [J]. Int Immunopharmacol , 2018 , 59 : 209 - 216 .
KANG J , LEE S , KIM N , et al . Gomisin M2 ameliorates atopic dermatitis-like skin lesions via inhibition of STAT1 and NF- κ B activation in 2,4-dinitrochlorobenzene/dermatophagoides farinae extract-induced BALB/c mice [J]. Molecules , 2021 , 26 ( 15 ): 4409 .
MOON P D , HAN N R , LEE J S , et al . Use of physcion to improve atopic dermatitis-like skin lesions through blocking of thymic stromal lymphopoietin [J]. Molecules , 2019 , 24 ( 8 ): 1484 .
JEONG S I , CHOI B M , JANG S I . Sulforaphane suppresses TARC/CCL17 and MDC/CCL22 expression through heme oxygenase-1 and NF- κ B in human keratinocytes [J]. Arch Pharm Res , 2010 , 33 ( 11 ): 1867 - 1876 .
SUNG Y Y , KIM H K . Crocin ameliorates atopic dermatitis symptoms by down regulation of Th2 response via blocking of NF- κ B/STAT6 signaling pathways in mice [J]. Nutrients , 2018 , 10 ( 11 ): 1625 .
LIU T , ZHANG L , JOO D , et al . NF- κ B signaling in inflammation [J]. Signal Transduct Target Ther , 2017 , 2 : 17023 - 17023 .
MA J , ZHANG Y , SUGAI T , et al . Inhibition of cellular and animal inflammatory disease models by NF- κ B inhibitor DHMEQ [J]. Cells , 2021 , 10 ( 9 ): 2271 .
KO K I , MERLET J J , DERGARABEDIAN B P , et al . NF- κ B perturbation reveals unique immunomodulatory functions in Prx1(+) fibroblasts that promote development of atopic dermatitis [J]. Sci Transl Med , 2022 , 14 ( 630 ): eabj0324 .
YU H , LIN L , ZHANG Z , et al . Targeting NF- κ B pathway for the therapy of diseases:Mechanism and clinical study [J]. Signal Transduct Target Ther , 2020 , 5 ( 1 ): 209 .
TIKKANEN R , NIKOLIC-PATERSON D J . Mitogen-activated protein kinases: Functions in signal transduction and human diseases [J]. Int J Mol Sci , 2019 , 20 ( 19 ): 4844 .
LIN W , SU F , GAUTAM R , et al . Raf kinase inhibitor protein negatively regulates FcεRI-mediated mast cell activation and allergic response [J]. Proc Natl Acad Sci USA , 2018 , 115 ( 42 ): E9859 - E9868 .
FRUMAN D A , CHIU H , HOPKINS B D , et al . The PI3K pathway in human disease [J]. Cell , 2017 , 170 ( 4 ): 605 - 635 .
TANG Z L , ZHANG K , LV S C , et al . LncRNA MEG3 suppresses PI3K/Akt/mTOR signalling pathway to enhance autophagy and inhibit inflammation in TNF- α -treated keratinocytes and psoriatic mice [J]. Cytokine , 2021 , 148 : 155657 .
JIA Y , HU J , AN K , et al . Hydrogel dressing integrating FAK inhibition and ROS scavenging for mechano-chemical treatment of atopic dermatitis [J]. Nat Commun , 2023 , 14 ( 1 ): 2478 .
ZHANG Q , LIU J , DUAN H , et al . Activation of Nrf2/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress [J]. J Adv Res , 2021 , 34 : 43 - 63 .
周鑫 , 刘鹏 , 郭燕玲 , 等 . 基于Nrf2信号通路的中药促进糖尿病创面愈合研究进展 [J]. 中国实验方剂学杂志 , 2022 , 28 ( 3 ): 241 - 249 .
SINGH H , AGRAWAL D K . Therapeutic potential of targeting the HMGB1/RAGE axis in inflammatory diseases [J]. Molecules , 2022 , 27 ( 21 ): 7311 .
冯皓月 , 丁蕊 , 周琦 , 等 . NLRP3炎症小体在糖尿病神经病变中的作用及中医药防治的研究进展 [J]. 中国中药杂志 , 2023 , 48 ( 2 ): 300 - 310 .
LI L , MU Z , LIU P , et al . Mdivi-1 alleviates atopic dermatitis through the inhibition of NLRP3 inflammasome [J]. Exp Dermatol , 2021 , 30 ( 12 ): 1734 - 1744 .
邱玲 , 刘宇 , 郑楠楠 , 等 . 天然产物提取分离技术研究进展 [J]. 药学进展 , 2022 , 46 ( 3 ): 184 - 197 .
ČIŽMÁROVÁ B , HUBKOVÁ B , TOMEČKOVÁ V , et al . Flavonoids as promising natural compounds in the prevention and treatment of selected skin diseases [J]. Int J Mol Sci , 2023 , 24 ( 7 ): 6324 .
TANAKA T . Flavonoids for allergic diseases:Present evidence and future perspective [J]. Curr Pharm Des , 2014 , 20 ( 6 ): 879 - 885 .
KIM N , BAE K B , KIM M O , et al . Overexpression of cathepsin S induces chronic atopic dermatitis in mice [J]. J Invest Dermatol , 2012 , 132 ( 4 ): 1169 - 1176 .
LEE J S , HAN J S , LEE K , et al . The peripheral and central mechanisms underlying itch [J]. BMB Rep , 2016 , 49 ( 9 ): 474 - 487 .
KOEBERLE A , WERZ O . Natural products as inhibitors of prostaglandin E 2 and pro-inflammatory 5-lipoxygenase-derived lipid mediator biosynthesis [J]. Biotechnol Adv , 2018 , 36 ( 6 ): 1709 - 1723 .
ROBIDA P A , CHUMANEVICH A P , GANDY A O , et al . Skin mast cell-driven ceramides drive early apoptosis in pre-symptomatic eczema in mice [J]. Int J Mol Sci , 2021 , 22 ( 15 ): 7851 .
BHATTARAI K R , CHAUDHARY M , KIM H R , et al . Endoplasmic reticulum (ER) stress response failure in diseases [J]. Trends Cell Biol , 2020 , 30 ( 9 ): 672 - 675 .
XIE C , LI Y , GAO J , et al . Esculetin regulates the phenotype switching of airway smooth muscle cells [J]. Phytother Res , 2019 , 33 ( 11 ): 3008 - 3015 .
HAN N R , MOON P D , KIM H M , et al . Cordycepin ameliorates skin inflammation in a DNFB-challenged murine model of atopic dermatitis [J]. Immunopharmacol Immunotoxicol , 2018 , 40 ( 5 ): 401 - 407 .
HUANG I H , CHUNG W H , WU P C , et al . JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review [J]. Front Immunol , 2022 , 13 : 1068260 .
CHU M , TSANG M S , HE R , et al . The active compounds and therapeutic mechanisms of pentaherbs formula for oral and topical treatment of atopic dermatitis based on network pharmacology [J]. Plants (Basel) , 2020 , 9 ( 9 ): 1166 .
HON K L , LEUNG T F , NG P C , et al . Efficacy and tolerability of a Chinese herbal medicine concoction for treatment of atopic dermatitis:A randomized, double-blind, placebo-controlled study [J]. Br J Dermatol , 2007 , 157 ( 2 ): 357 - 363 .
MEHRBANI M , CHOOPANI R , FEKRI A , et al . The efficacy of whey associated with dodder seed extract on moderate-to-severe atopic dermatitis in adults:A randomized, double-blind, placebo-controlled clinical trial [J]. J Ethnopharmacol , 2015 , 172 : 325 - 332 .
SUDINI K , DIETTE G B , BREYSSE P N , et al . A randomized controlled trial of the effect of broccoli sprouts on antioxidant gene expression and airway inflammation in asthmatics [J]. J Allergy Clin Immunol Pract , 2016 , 4 ( 5 ): 932 - 940 .
YUSIN J , WANG V , HENNING S M , et al . The effect of broccoli sprout extract on seasonal grass pollen-induced allergic rhinitis [J]. Nutrients , 2021 , 13 ( 4 ): 1337 .
LIEW K Y , KAMISE N I , ONG H M , et al . Anti-allergic properties of propolis: Evidence from preclinical and clinical studies [J]. Front Pharmacol , 2021 , 12 : 785371 .
IGARASHI G , SEGAWA T , AKIYAMA N , et al . Efficacy of brazilian propolis supplementation for Japanese lactating women for atopic sensitization and nonspecific symptoms in their offspring:A randomized,double-blind,placebo-controlled trial [J]. Evid Based Complement Alternat Med , 2019 , 2019 : 8647205 .
SANCHEZ-RODRIGUEZ E , BIEL-GLESSON S , FERNANDEZ-NAVARRO J R , et al . Effects of virgin olive oils differing in their bioactive compound contents on biomarkers of oxidative stress and inflammation in healthy adults: A randomized double-blind controlled trial [J]. Nutrients , 2019 , 11 ( 3 ): 561 .
CONTE R , DE LUCA I , VALENTINO A , et al . Hyaluronic acid hydrogel containing resveratrol-loaded chitosan nanoparticles as an adjuvant in atopic dermatitis treatment [J]. J Funct Biomater , 2023 , 14 ( 2 ): 82 .
HAMMAD H , LAMBRECHT B N . Barrier epithelial cells and the control of type 2 immunity [J]. Immunity , 2015 , 43 ( 1 ): 29 - 40 .
蔡国强 , 徐志杰 , 权琰 , 等 . 天然产物提取技术研究进展 [J]. 中国野生植物资源 , 2023 , 42 ( 4 ): 78 - 85 .
0
Views
78
下载量
2
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621