The Effect of Osthole on Transient Receptor Potential Channels: A Possible Alternative Therapy for Atopic Dermatitis

References

• Cevikbas F, Lerner EA. Physiology and pathophysiology of itch. Physiol Rev. 2020;100(3):945–982. doi:10.1152/PHYSREV.00017.2019
   PubMed Web of Science ®Google Scholar
• Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109–1122. doi:10.1016/S0140-6736(15)00149-X
   PubMed Web of Science ®Google Scholar
• Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1). doi:10.1038/S41572-018-0001-Z
   PubMedGoogle Scholar
• Napolitano M, Fabbrocini G, Genco L, Martora F, Potestio L, Patruno C. Rapid improvement in pruritus in atopic dermatitis patients treated with upadacitinib: a real‐life experience. J Eur Acad Dermatol Venereol. 2022;36(9):1497–1498. doi:10.1111/jdv.18137
   PubMed Web of Science ®Google Scholar
• Paolino A, Alexander H, Broderick C, Flohr C. Non‐biologic systemic treatments for atopic dermatitis: current state of the art and future directions. Clin Exp Immunol. 2023;53(5):495–510. doi:10.1111/cea.14301
   Google Scholar
• Twycross R, Greaves M, Handwerker H, Qjm EJ. Itch: scratching more than the surface. academic.oup.com; 2003. Available from: https://academic.oup.com/qjmed/article-abstract/96/1/7/1526242. Accessed April 23, 2023.
   Google Scholar
• Parsons M. Histamine and its receptors. Wiley Online Lib. 2006;147(SUPPL. 1):127–135. doi:10.1038/sj.bjp.0706440
   Google Scholar
• Rossbach K, Nassenstein C, Neuroscience MG. Histamine H1, H3 and H4 receptors are involved in pruritus. Elsevier; 2011. Available from: https://www.sciencedirect.com/science/article/pii/S0306452211006609. Accessed April 23, 2023.
   Google Scholar
• Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell. 2010;140(6):771–776. doi:10.1016/j.cell.2010.03.006
   PubMed Web of Science ®Google Scholar
• Steinhoff M, Schmelz M, Szabó IL, Oaklander AL. Clinical presentation, management, and pathophysiology of neuropathic itch. Lancet Neurol. 2018;17(8):709–720. doi:10.1016/S1474-4422(18)30217-5
   PubMed Web of Science ®Google Scholar
• Gouin O, L’Herondelle K, Lebonvallet N, et al. TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization. Protein Cell. 2017;8(9):644–661. doi:10.1007/S13238-017-0395-5
   PubMed Web of Science ®Google Scholar
• Meng J, Wang J, Steinhoff M, Dolly JO. TNFα induces co-trafficking of TRPV1/TRPA1 in VAMP1-containing vesicles to the plasmalemma via Munc18-1/syntaxin1/SNAP-25 mediated fusion. Sci Rep. 2016;6. doi:10.1038/SREP21226
   PubMed Web of Science ®Google Scholar
• Meng J, Moriyama M, Feld M, et al. New mechanism underlying IL-31-induced atopic dermatitis. J Allergy Clin Immunol. 2018;141(5):1677–1689.e8. doi:10.1016/J.JACI.2017.12.1002
   PubMed Web of Science ®Google Scholar
• Cevikbas F, Wang X, Akiyama T, et al. A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: involvement of TRPV1 and TRPA1. J Allergy Clin Immunol. 2014;133(2). doi:10.1016/J.JACI.2013.10.048
   PubMed Web of Science ®Google Scholar
• Larkin C, Chen W, Szabó IL, et al. Novel insights into the TRPV3-mediated itch in atopic dermatitis. J Allergy Clin Immunol. 2021;147(3):1110–1114.e5. doi:10.1016/J.JACI.2020.09.028
   PubMed Web of Science ®Google Scholar
• Wilson SR, Thé L, Batia LM, et al. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell. 2013;155(2):285–295. doi:10.1016/J.CELL.2013.08.057
   PubMed Web of Science ®Google Scholar
• Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol. 2018;40(3):249–259. doi:10.1007/S00281-018-0675-Z
   PubMed Web of Science ®Google Scholar
• Gibson RA, Robertson J, Mistry H, et al. A randomised trial evaluating the effects of the TRPV1 antagonist SB705498 on pruritus induced by histamine, and cowhage challenge in healthy volunteers. PLoS One. 2014;9(7):e100610. doi:10.1371/JOURNAL.PONE.0100610
   PubMed Web of Science ®Google Scholar
• Kim B, Lee S, Shim W. Histamine-induced Ca2+ influx via the PLA2/lipoxygenase/TRPV1 pathway in rat sensory neurons. Elsevier; 2004. Available from: https://www.sciencedirect.com/science/article/pii/S0304394004000370?casa_token=WWJD5UpHlD8AAAAA:mdPx9Ob0ZKz_29E4yMe_W-3kIPluJyZl02YmHPtmKRoVtkm5eEgsXLXxiGS0ZpCPqRFyX2ezZfXc. Accessed April 23, 2023.
   Google Scholar
• Costa R, Marotta DM, Manjavachi MN, et al. Evidence for the role of neurogenic inflammation components in trypsin‐elicited scratching behaviour in mice. Wiley Online Lib. 2008;154(5):1094–1103. doi:10.1038/bjp.2008.172
   Google Scholar
• Sokabe T, Fukumi-Tominaga T. The TRPV4 channel contributes to intercellular junction formation in keratinocytes*♦. ASBMB; 2010. Available from: https://www.jbc.org/article/S0021-9258(19)57581-0/abstract. Accessed April 23, 2023.
   Google Scholar
• Denda M, Sokabe T. Effects of skin surface temperature on epidermal permeability barrier homeostasis. Elsevier; 2007. Available from: https://www.sciencedirect.com/science/article/pii/S0022202X15333030. Accessed April 23, 2023.
   Google Scholar
• Bromma B, Scharein E, Darsow U. Effects of menthol and cold on histamine-induced itch and skin reactions in man. Elsevier; 1995. Available from: https://www.sciencedirect.com/science/article/pii/030439409511362Z. Accessed April 23, 2023.
   Google Scholar
• Wang L, Peng Y, Shi K, et al. Osthole inhibits proliferation of human breast cancer cells by inducing cell cycle arrest and apoptosis. J Biomed Res. 2015;30:132. doi:10.7555/JBR.27.20120115
   Google Scholar
• Che Y, Li J, Li Z, et al. Osthole enhances antitumor activity and irradiation sensitivity of cervical cancer cells by suppressing ATM/NF-κB signaling. Oncol Rep. 2018. doi:10.3892/or.2018.6514
   Web of Science ®Google Scholar
• Xu X, Liu X, Zhang Y, Pizzo SV. Osthole inhibits gastric cancer cell proliferation through regulation of PI3K/AKT. Pizzo S V., ed. PLoS One. 2018;13(3):e0193449. doi:10.1371/journal.pone.0193449
   PubMed Web of Science ®Google Scholar
• Kordulewska NK, Kostyra E, Cieślińska A, Fiedorowicz E, Jarmołowska B. Cytokine production by PBMC and serum from allergic and non-allergic subjects following in vitro histamine stimulation to test fexofenadine and osthole anti-allergic properties. Eur J Pharmacol. 2016;791:763–772. doi:10.1016/j.ejphar.2016.10.020
   PubMed Web of Science ®Google Scholar
• Kordulewska N, Topa J, Cieślińska A, Jarmołowska B. Osthole regulates secretion of pro-inflammatory cytokines and expression of TLR2 and NF-κB in normal human keratinocytes and fibroblasts. J Inflamm Res. 2022;15:1501. doi:10.2147/JIR.S349216
   PubMed Web of Science ®Google Scholar
• Kordulewska NK, Topa J, Stryiński R, Jarmołowska B. Osthole inhibits expression of genes associated with toll-like receptor 2 signaling pathway in an organotypic 3D skin model of human epidermis with atopic dermatitis. Cells. 2021;11(1):88. doi:10.3390/CELLS11010088
   PubMed Web of Science ®Google Scholar
• Kordulewska NK, Cieślińska A, Fiedorowicz E, Jarmołowska B, Kostyra E. High expression of IL-1RI and EP2 receptors in the IL-1β/COX-2 pathway, and a new alternative to non-steroidal drugs—osthole in inhibition COX-2. Int J Mol Sci. 2019;20(1):186. doi:10.3390/ijms20010186
   PubMed Web of Science ®Google Scholar
• Zafar S, Sarfraz I, Rasul A, et al. Osthole: a multifunctional natural compound with potential anticancer, antioxidant and anti-inflammatory activities. Mini-Rev Med Chem. 2020;21(18):2747–2763. doi:10.2174/1389557520666200709175948
   Web of Science ®Google Scholar
• Zhang QY, Tao SY, Lu C, et al. Osthole: a traditional Chinese medicine for ocular anti-angiogenic therapy. Ophthalmic Res. 2020;63(5):483–490. doi:10.1159/000505976
   PubMed Web of Science ®Google Scholar
• Chiang CY, Lee CC, Fan CK, Huang HM, Chiang BL, Lee YL. Osthole treatment ameliorates Th2-mediated allergic asthma and exerts immunomodulatory effects on dendritic cell maturation and function. Cell Mol Immunol. 2017;14(11):935–947. doi:10.1038/cmi.2017.71
   PubMed Web of Science ®Google Scholar
• Wang J, Fu Y, Wei Z, et al. Anti-asthmatic activity of osthole in an ovalbumin-induced asthma murine model. Respir Physiol Neurobiol. 2017;239:64–69. doi:10.1016/J.RESP.2017.01.011
   PubMed Web of Science ®Google Scholar
• Kordulewska NK, Topa J, Rozmus D, et al. Effects of osthole on inflammatory gene expression and cytokine secretion in histamine-induced inflammation in the Caco-2 cell line. Int J Mol Sci. 2021;22(24):13634. doi:10.3390/IJMS222413634
   PubMed Web of Science ®Google Scholar
• Huang R, Chen C, Huang Y, et al. Osthole increases glycosylation of hepatitis B surface antigen and suppresses the secretion of hepatitis B virus in vitro. Hepatology. 1996;24(3):508–515. doi:10.1002/hep.510240307
   PubMed Web of Science ®Google Scholar
• Song F. Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals. World J Gastroenterol. 2006;12(27):4359. doi:10.3748/wjg.v12.i27.4359
   PubMed Web of Science ®Google Scholar
• Zhang J, Xue J, Wang H, Zhang Y, Xie M. Osthole improves alcohol-induced fatty liver in mice by reduction of hepatic oxidative stress. Phytother Res. 2011;25(5):638–643. doi:10.1002/ptr.3315
   PubMed Web of Science ®Google Scholar
• Kordulewska NK, Kostyra E, Matysiewicz M, Cieślińska A, Jarmołowska B. Impact of fexofenadine, osthole and histamine on peripheral blood mononuclear cell proliferation and cytokine secretion. Eur J Pharmacol. 2015;761. doi:10.1016/j.ejphar.2015.05.065
   Web of Science ®Google Scholar
• Kordulewska NK, Kostyra E, Cieślińska A, Matysiewicz M, Fiedorowicz E, Sienkiewicz-Szłapka E. Changes in gene expression induced by histamine, fexofenadine and osthole: expression of histamine H1 receptor, COX-2, NF-κB, CCR1, chemokine CCL5/RANTES and interleukin-1β in PBMC allergic and non-allergic patients. Immunobiology. 2017;222(3):571–581. doi:10.1016/j.imbio.2016.11.004
   PubMed Web of Science ®Google Scholar
• Kordulewska NK, Cieślińska A, Fiedorowicz E, Jarmołowska B, Piskorz-Ogórek K, Kostyra E. Cytokines concentrations in serum samples from allergic children—multiple analysis to define biomarkers for better diagnosis of allergic inflammatory process. Immunobiology. 2018;223(11):648–657. doi:10.1016/j.imbio.2018.07.010
   PubMed Web of Science ®Google Scholar
• Kordulewska NK, Kostyra E, Piskorz-Ogórek K, et al. Serum cytokine levels in children with spectrum autism disorder: differences in pro- and anti-inflammatory balance. J Neuroimmunol. 2019;337:577066. doi:10.1016/j.jneuroim.2019.577066
   PubMed Web of Science ®Google Scholar
• Kordulewska NK, Kostyra E, Chwała B, et al. A novel concept of immunological and allergy interactions in autism spectrum disorders: molecular, anti-inflammatory effect of osthole. Int Immunopharmacol. 2019;72:1–11. doi:10.1016/j.intimp.2019.01.058
   PubMed Web of Science ®Google Scholar
• Patel HK, Barot BS, Parejiya PB, Shelat PK, Shukla A. Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo – part II: rheological characterization and in vivo assessment through dermatopharmacokinetic and pilot clinical studies. Colloids Surf B Biointerfaces. 2014;119:145–153. doi:10.1016/j.colsurfb.2014.02.005
   PubMed Web of Science ®Google Scholar
• Yuan N, Chen Z, Li L. Narrow-band UVB combined with compound clobetasol propionate can improve the therapeutic effect in hand eczema patients. Am J Transl Res. 2021;13(7):8193–8199.
   PubMed Web of Science ®Google Scholar
• Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29(9):45e–445. doi:10.1093/nar/29.9.e45
   PubMed Web of Science ®Google Scholar
• Gao X, Wang Z, Du L. Glial cells and itch: possible targets for novel antipruritic therapies. ACS Chem Neurosci. 2023;14(3):331–339. doi:10.1021/ACSCHEMNEURO.2C00638/ASSET/IMAGES/MEDIUM/CN2C00638_0003.GIF
   PubMed Web of Science ®Google Scholar
• Fang Y, Yang L, He J. Plantanone C attenuates LPS-stimulated inflammation by inhibiting NF-κB/iNOS/COX-2/MAPKs/Akt pathways in RAW 264.7 macrophages. Biomed Pharmacother. 2021;143:112104. doi:10.1016/j.biopha.2021.112104
   PubMed Web of Science ®Google Scholar
• Radha KM, Puri S. Evaluation of nutritional, phytochemical, and mineral composition of selected medicinal plants for therapeutic uses from cold desert of western himalaya. Plants. 2021;10(7):1429. doi:10.3390/plants10071429
   Google Scholar
• Bitton A, Avlas S, Reichman H, et al. A key role for IL-13 signaling via the type 2 IL-4 receptor in experimental atopic dermatitis. Sci Immunol. 2020;5(44). doi:10.1126/SCIIMMUNOL.AAW2938/SUPPL_FILE/AAW2938_SM.PDF
   PubMed Web of Science ®Google Scholar
• Fu X, Hong C. Osthole attenuates mouse atopic dermatitis by inhibiting thymic stromal lymphopoietin production from keratinocytes. Exp Dermatol. 2019;28(5):561–567. doi:10.1111/EXD.13910
   PubMed Web of Science ®Google Scholar
• Yang Q, Kong L, Huang W, et al. Osthole attenuates ovalbumin-induced lung inflammation via the inhibition of IL-33/ST2 signaling in asthmatic mice. Int J Mol Med. 2020;46(4):1389–1398. doi:10.3892/IJMM.2020.4682/HTML
   PubMed Web of Science ®Google Scholar
• Shen W, Shi S, Zhang H. Osthole inhibits ovalbumin (OVA) induced asthma through regulating TLR9/JNK pathway. IJEB. 2020;58:235–241.
   Web of Science ®Google Scholar
• Ferreira S, Torres T. Dupilumab for the treatment of atopic dermatitis. Actas Dermo-Sifiliográficas. 2018;109(3):230–240. doi:10.1016/J.ADENGL.2018.02.019
   PubMed Web of Science ®Google Scholar
• Freitas E, Guttman-Yassky E, Torres T. Tralokinumab for the treatment of atopic dermatitis. Am J Clin Dermatol. 2021;22(5):625–638. doi:10.1007/S40257-021-00613-8
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Blauvelt A, Eichenfield LF, et al. Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis: a phase 2b randomized clinical trial. JAMA Dermatol. 2020;156(4):411–420. doi:10.1001/JAMADERMATOL.2020.0079
   PubMed Web of Science ®Google Scholar
• Tsianakas A, Luger TA. The anti-IL-4 receptor alpha antibody dupilumab: facing a new era in treating atopic dermatitis. Expert Opin Biol Ther. 2015;15(11):1661–1664. doi:10.1517/14712598.2015.1095887
   Web of Science ®Google Scholar
• Akdis CA, Arkwright PD, Brüggen MC, et al. Type 2 immunity in the skin and lungs. Wiley Online Lib. 2020;10(7):9. doi:10.1111/all.14318
   Google Scholar
• Yang N, Ju Y, Huang D, et al. Desensitization of TRPV1 involved in the antipruritic effect of osthole on histamine-induced scratching behavior in mice. Evid Based Complement Alternat Med. 2021;2021:1–10. doi:10.1155/2021/4012812
   Web of Science ®Google Scholar
• Jian T, Yang N, Yang Y, et al. TRPV1 and PLC participate in histamine H4 receptor-induced itch. hindawi.com. Available from: https://www.hindawi.com/journals/np/2016/1682972/. Accessed April 26, 2023.
   Google Scholar
• Shim WS, Tak MH, Lee MH, et al. TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase. J Neurosci. 2007;27(9):2331–2337. doi:10.1523/JNEUROSCI.4643-06.2007
   PubMed Web of Science ®Google Scholar
• Han SK, Mancino V, Simon MI. Phospholipase Cβ 3 Mediates the scratching response activated by the histamine H1 receptor on C-fiber nociceptive neurons. Neuron. 2006;52(4):691–703. doi:10.1016/j.neuron.2006.09.036
   PubMed Web of Science ®Google Scholar
• Gutzmer R, Mommert S, Gschwandtner M, Zwingmann K, Stark H, Werfel T. The histamine H4 receptor is functionally expressed on TH2 cells. J Allergy Clin Immunol. 2009;123(3):619–625. doi:10.1016/J.JACI.2008.12.1110
   PubMed Web of Science ®Google Scholar
• Glatzer F, Gschwandtner M, Ehling S, et al. Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor. J Allergy Clin Immunol. 2013;132(6):1358–1367. doi:10.1016/J.JACI.2013.06.023
   PubMed Web of Science ®Google Scholar
• Glatzer F, Gschwandtner M, Ehling S, et al. Histamine induces proliferation in keratinocytes from atopic dermatitis patients. J Allergy Clin Immunol. 2013;132(6):1358. doi:10.1016/J.JACI.2013.06.023
   PubMed Web of Science ®Google Scholar
• Yu B, Shao Y, Zhang J, et al. Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis. Br J Dermatol. 2010;162(5):1038–1043. doi:10.1111/j.1365-2133.2010.09675.x
   PubMed Web of Science ®Google Scholar
• Mahmoud O, Soares GB, Yosipovitch G. Transient receptor potential channels and itch. Int J Mol Sci. 2023;24(1). doi:10.3390/IJMS24010420
   Web of Science ®Google Scholar
• Cevikbas F, Wang X, Akiyama T. CKJ of allergy and, 2014 undefined. A sensory neuron–expressed IL-31 receptor mediates T helper cell–dependent itch: involvement of TRPV1 and TRPA1. Elsevier; 2014. Available from: https://www.sciencedirect.com/science/article/pii/S0091674913017107?casa_token=WM47qT_DrlkAAAAA:Y3_M05j1zYDJ_b-Vh_uWLMO-Jc8FiotlQvCfKnjx7Yl1Gy7iICBcDEAlrjB43J3YXRL0PUHDIzIX. Accessed April 26, 2023.
   Google Scholar
• Fernandes ES, Vong CT, Quek S, et al. Superoxide generation and leukocyte accumulation: key elements in the mediation of leukotriene B4-induced itch by transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1. THE FASEB Journal. 2013;27(4):1664–1673. doi:10.1096/FJ.12-221218
   PubMed Web of Science ®Google Scholar
• Torres KV, Pantke S, Rudolf D, Eberhardt MM, Leffler A. The coumarin osthole is a non-electrophilic agonist of TRPA1. Neurosci Lett. 2022;789:136878. doi:10.1016/J.NEULET.2022.136878
   PubMed Web of Science ®Google Scholar
• Duchatelet S, Hovnanian A. Olmsted syndrome: clinical, molecular and therapeutic aspects. Orphanet J Rare Dis. 2015;10(1):33. doi:10.1186/S13023-015-0246-5
   PubMedGoogle Scholar
• Yun J, Seo J, Jeong Y, Bae I. TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery. Elsevier; 2011. Available from: https://www.sciencedirect.com/science/article/pii/S0923181110003300?casa_token=3-YhlgP7YAMAAAAA:xzvx2kPNd8s3trMIX6g757gth6yHdK01PWko2FX7pvkwB71-UbOco5YKll1kVgAT1lpvPns16iaE. Accessed April 27, 2023.
   Google Scholar
• Yun J, Seo J, Jang W, Koh H, of IBTJ. Antipruritic effects of TRPV1 antagonist in murine atopic dermatitis and itching models. europepmc.org; 2011. Available from: https://europepmc.org/article/med/21471988. Accessed April 27, 2023.
   Google Scholar
• Yun J, Seo J, Jeong Y, Bae I. TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery. Elsevier; 2011. Available from: https://www.sciencedirect.com/science/article/pii/S0923181110003300?casa_token=5Qk1KVysWUQAAAAA:FueEdq_q0PqJ-IwmywcNTFhr6KLMVUxl9HYfffFlcFHZM70qHwkXE6mMyJWkjMXtELzn1wdByhiR. Accessed April 27, 2023.
   Google Scholar
• Jian T, Yang N, Yang Y, et al. TRPV1 and PLC participate in histamine H4 receptor-induced itch. hindawi.com. Available from: https://www.hindawi.com/journals/np/2016/1682972/. Accessed April 27, 2023.
   Google Scholar
• Oh M, Oh S, Lu J, Lou H. AMTJ of, 2013 undefined. TRPA1-dependent pruritus in IL-13–induced chronic atopic dermatitis. journals.aai.org; 2013. Available from: https://journals.aai.org/jimmunol/article/191/11/5371/39018. Accessed April 27, 2023.
   Google Scholar
• Xiao R, Tian J, Tang J, The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active. Elsevier; 2008. Available from: https://www.sciencedirect.com/science/article/pii/S0143416007001303?casa_token=EL8UtlCGwtsAAAAA:M7LNabS_6B6EAviYRegwiaroP0dtNdq48kI_IDrOZDEVoXmKju-xX5WEhGbIROQUSyNJOgYr3a9G. Accessed April 27, 2023.
   Google Scholar
• Song Z, Chen X, Zhao Q, et al. Hair loss caused by gain-of-function mutant TRPV3 is associated with premature differentiation of follicular keratinocytes. Elsevier. Available from: https://www.sciencedirect.com/science/article/pii/S0022202X21001585. Accessed April 27, 2023.
   Google Scholar
• Larkin C, Chen W, Szabó I. CSJ of A and, 2021 undefined. Novel insights into the TRPV3-mediated itch in atopic dermatitis. jacionline.org; 2021. Available from: https://www.jacionline.org/article/S0091-6749(20)31394-4/abstract. Accessed April 27, 2023.
   Google Scholar
• Buddenkotte J, Stroh C, Engels I. Agonists of proteinase-activated receptor-2 stimulate upregulation of intercellular cell adhesion molecule-1 in primary human keratinocytes via activation of. Elsevier; 2005. Available from: https://www.sciencedirect.com/science/article/pii/S0022202X15321321. Accessed April 27, 2023.
   Google Scholar
• Szöllősi A, Vasas N, Angyal Á, Activation of TRPV3 regulates inflammatory actions of human epidermal keratinocytes. Elsevier; 2018. Available from: https://www.sciencedirect.com/science/article/pii/S0022202X17330221. Accessed April 27, 2023.
   Google Scholar
• Xu H, Delling M, Jun J, Clapham DE. Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neurosci. 2006;9(5):628–635. doi:10.1038/nn1692
   PubMed Web of Science ®Google Scholar
• Doerner J, Hatt H, Voltage- and temperature-dependent activation of TRPV3 channels is potentiated by receptor-mediated PI(4,5)P2 hydrolysis. rupress.org; 2011. Available from: https://rupress.org/jgp/article-abstract/137/3/271/42851. Accessed April 27, 2023.
   Google Scholar
• Du S, Araki I, Kobayashi H, Zakoji H, Sawada N, Takeda M. Differential Expression Profile of Cold (TRPA1) and cool (TRPM8) receptors in human urogenital organs. Urology. 2008;72(2):450–455. doi:10.1016/J.UROLOGY.2007.11.127
   PubMed Web of Science ®Google Scholar
• Liu Y, Mikrani R, He Y, et al. TRPM8 channels: a review of distribution and clinical role. Eur J Pharmacol. 2020:882. doi:10.1016/J.EJPHAR.2020.173312
   Web of Science ®Google Scholar
• Liu B, Jordt SE. Cooling the itch via TRPM8. J Invest Dermatol. 2018;138(6):1254–1256. doi:10.1016/J.JID.2018.01.020
   PubMed Web of Science ®Google Scholar
• Palkar R, Ongun S, Catich E, et al. Cooling relief of acute and chronic itch requires TRPM8 channels and neurons. J Invest Dermatol. 2018;138(6):1391–1399. doi:10.1016/J.JID.2017.12.025
   PubMed Web of Science ®Google Scholar
• Kardon AP, Polgár E, Hachisuka J, et al. Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord. Neuron. 2014;82(3):573–586. doi:10.1016/J.NEURON.2014.02.046
   PubMed Web of Science ®Google Scholar
• Kim JH, Jang YS, Park JY, et al. The activation of transient receptor potential melastatin 8 (TRPM8) receptors induces airway inflammation in bronchial asthma. J Allergy Clin Immunol. 2017;139(2):AB2. doi:10.1016/j.jaci.2016.12.060
   Web of Science ®Google Scholar
• Sun M, Sun M, Zhang J. Osthole: an overview of its sources, biological activities, and modification development. Med Chem Res. 2021;30(10):1767–1794. doi:10.1007/s00044-021-02775-w
   PubMed Web of Science ®Google Scholar
• Fan H, Gao Z, Ji K, et al. The in vitro and in vivo anti-inflammatory effect of osthole, the major natural coumarin from Cnidium monnieri (L.) Cuss, via the blocking of the activation of the NF-κB and MAPK/p38 pathways. Phytomedicine. 2019;58:152864. doi:10.1016/j.phymed.2019.152864
   PubMed Web of Science ®Google Scholar
• Wu SJ. Osthole attenuates inflammatory responses and regulates the expression of inflammatory mediators in HepG2 cells grown in differentiated medium from 3T3-L1 preadipocytes. J Med Food. 2015;18(9):972–979. doi:10.1089/jmf.2014.3314
   PubMed Web of Science ®Google Scholar
• Joshi P, Singh S, Wani A, et al. Osthol and curcumin as inhibitors of human Pgp and multidrug efflux pumps of Staphylococcus aureus: reversing the resistance against frontline antibacterial drugs. Med Chem Commun. 2014;5(10):1540–1547. doi:10.1039/C4MD00196F
   Web of Science ®Google Scholar
• Zheng H, Chen Y, Guo Q, et al. Inhibitory effect of osthole from Cnidium monnieri (L.) Cusson on fusarium oxysporum, a common fungal pathogen of potato. Molecules. 2021;26(13):3818. doi:10.3390/molecules26133818
   PubMed Web of Science ®Google Scholar
• Peng LL, Juan WX, Zhang JY, et al. Antifungal activity of osthol in vitro and enhancement in vivo through Eudragit S100 nanocarriers. Virulence. 2018;9(1):555–562. doi:10.1080/21505594.2017.1356503
   PubMed Web of Science ®Google Scholar
• Rashidpour S, Zahedipour F, Karimi G, Jamialahmadi K. Protective effects of osthole against free radical-induced hemolysis of erythrocytes. Pharm Sci. 2020;27(1):56–62. doi:10.34172/PS.2020.65
   Web of Science ®Google Scholar
• Huang WC, Liao PC, Huang CH, Hu S, Huang SC, Wu SJ. Osthole attenuates lipid accumulation, regulates the expression of inflammatory mediators, and increases antioxidants in FL83B cells. Biomed Pharmacother. 2017;91:78–87. doi:10.1016/j.biopha.2017.04.051
   PubMed Web of Science ®Google Scholar
• Gao L, Wang F, Chen Y, Li F, Han B, Liu D. The antithrombotic activity of natural and synthetic coumarins. Fitoterapia. 2021;154:104947. doi:10.1016/j.fitote.2021.104947
   PubMed Web of Science ®Google Scholar
• Liang HJ, Suk FM, Wang CK, et al. Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice. Chem Biol Interact. 2009;181(3):309–315. doi:10.1016/j.cbi.2009.08.003
   PubMed Web of Science ®Google Scholar
• Luszczki JJ, Wojda E, Andres-Mach M, et al. Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: a comparative study. Epilepsy Res. 2009;85(2–3):293–299. doi:10.1016/j.eplepsyres.2009.03.027
   PubMed Web of Science ®Google Scholar
• Li Y, Sun Z, Xu H, Zhang Q, Zeng C. Osthole inhibits proliferation of kainic acid-activated BV-2 cells by modulating the Notch signaling pathway. Mol Med Rep. 2020. doi:10.3892/mmr.2020.11455
   Google Scholar
• Zhang L, Jiang G, Yao F, et al. Growth inhibition and apoptosis induced by osthole, a natural coumarin, in hepatocellular carcinoma. Cox D, ed. PLoS One. 2012;7(5):e37865. doi:10.1371/journal.pone.0037865
   PubMed Web of Science ®Google Scholar
• Mei J, Wang T, Zhao S, Zhang Y. Osthole inhibits breast cancer progression through upregulating tumor suppressor GNG7. Hou Y, ed. J Oncol. 2021;2021:1–12. doi:10.1155/2021/6610511
   Web of Science ®Google Scholar
• Mark R, Lyu X, Lee JJL, Parra-Saldívar R, Chen WN. Sustainable production of natural phenolics for functional food applications. J Funct Foods. 2019;57:233–254. doi:10.1016/j.jff.2019.04.008
   Web of Science ®Google Scholar