Garlic Activate TRPA Receptor as a potential therapeutic target in skin related diseases

Garlic Activate TRPA Receptor as a potential therapeutic target in skin related diseases


  • Muhammad Aqib Saeed University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
  • Shahnai Basharat University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
  • Momina Shahid University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
  • Aimen Zafar University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
  • Hifza Noor University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
  • Asifa Saleem Institute of Food and Nutrition Science, Pir Mehar Ali Shah Arid Agriculture University, Rawalpindi, Pakistan
  • Imtiaz Ahmad Rana University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
  • Tehreem Jamil University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan



Garlic, TRPA1 channel, Allium, Allyl sulphide, AITC, Skin diseases


Garlic's pungent flavor has made it a prominent component in cuisines throughout the globe for decades. When chopped and put on the tongue or lips, raw garlic triggers unpleasant burning and prickling sensations by unknown processes. In this study, we demonstrate that raw garlic activates TRPA1 and TRPV1, two temperature-activated ion channels that belong to the (TRP) transient receptor potential. The allicin, a volatile component of fresh garlic, is the chemical responsible for TRPA1 and TRPV1 activation. Garlic, a member of the Allium produces organosulfur compounds inclusive of allicin and diallyl disulfide (DADS), which are accountable for garlic's spice and spicy fragrance. Allium extracts have been shown to provide a variety of health advantages, including hypotensive and vasorelaxant properties. Intriguingly, allicin and DADS have structural affinity with allyl isothiocyanate that exhibit ache and inflammation by TRPA1 activation.


McGee H. On food and cooking: the science and lore of the kitchen. Simon and Schuster; 2007 Mar 20.

Jones MG, Hughes J, Tregova A, Milne J, Tomsett AB, Collin HA.Biosynthesis of the flavour precursors of onion and garlic.Journal of Experimental Botany. 2004 Aug 1;55(404):1903-18.

Wang H, Woolf CJ. Pain TRPs. Neuron. 2005 Apr 7;46(1):9-12. 3

Cutler RR, Odent M, Hajj-Ahmad H, Maharjan S, Bennett NJ, Josling PD, Ball V, Hatton P, Dall'Antonia M. In vitro activity of an aqueous allicin extract and a novel allicin topical gel formulation against Lancefield group B streptococci.Journal of antimicrobial chemotherapy. 2009 Jan 1;63(1):151-4. 4

Brewster MS, Gaudet R. How the TRPA1 receptor transmits painful stimuli: Inner workings revealed by electron cryomicroscopy. Bioessays. 2015 Nov;37(11):1184-92. 5

Kimura H. Signaling molecules: hydrogen sulfide and polysulfide. Antioxidants & redox signaling. 2015 Feb 10;22(5):362-76. 6

Viana F. TRPA1 channels: molecular sentinels of cellular stress and tissue damage. The Journal of physiology. 2016 Aug 1;594(15):4151-69. 7

Sághy É, Sipos É, Ács P, Bölcskei K, Pohóczky K, Kemény Á, Sándor Z, Szőke É, Sétáló Jr G, Komoly S, Pintér E. TRPA1 deficiency is protective in cuprizone‐induced demyelination—A new target against oligodendrocyte apoptosis. Glia. 2016 Dec;64(12):2166-80. 8

Lee KI, Lee HT, Lin HC, Tsay HJ, Tsai FC, Shyue SK, Lee TS. Role of transient receptor potential ankyrin 1 channels in Alzheimer’s disease. Journal of Neuroinflammation. 2016 Dec;13(1):1-6. 9

Kádková A, Synytsya V, Krusek J, Zímová L, Vlachová V. Molecular basis of TRPA1 regulation in nociceptive neurons. A review.Physiological research. 2017 Jun 1;66(3). 10

Chen J, Hackos DH. TRPA1 as a drug target—promise and challenges. Naunyn-Schmiedeberg's archives of pharmacology. 2015 Apr;388(4):451-63. 11

Koizumi K, Iwasaki Y, Narukawa M, Iitsuka Y, Fukao T, Seki T, Ariga T, Watanabe T. Diallyl sulfides in garlic activate both TRPA1 and TRPV1. Biochemical and biophysical research communications. 2009 May 8;382(3):545-8. 12

Yassaka RT, Inagaki H, Fujino T, Nakatani K, Kubo T. Enhanced activation of the transient receptor potential channel TRPA1 by ajoene, an allicin derivative. Neuroscience research. 2010 Jan 1;66(1):99-105.

Pozsgai G, Payrits M, Sághy É, Sebestyén-Bátai R, Steen E, Szőke É, Sándor Z, Solymár M, Garami A, Orvos P, Tálosi L. Analgesic effect of dimethyl trisulfide in mice is mediated by TRPA1 and sst4 receptors. Nitric Oxide. 2017 May 1;65:10-21.

Bátai IZ, Horváth Á, Pintér E, Helyes Z, Pozsgai G. Role of transient receptor potential ankyrin 1 ion channel and somatostatin sst4 receptor in the antinociceptive and anti-inflammatory effects of sodium polysulfide and dimethyl trisulfide. Frontiers in endocrinology. 2018 Feb 27;9:55.

El Karim I, McCrudden MT, Linden GJ, Abdullah H, Curtis TM, McGahon M, About I, Irwin C, Lundy FT. TNF-α–induced p38MAPK activation regulates TRPA1 and TRPV4 activity in odontoblast-like cells. The American journal of pathology. 2015 Nov 1;185(11):2994-3002.

Pichette J, Fynn-Sackey N, Gagnon J. Hydrogen sulfide and sulfate prebiotic stimulates the secretion of GLP-1 and improves glycemia in male mice. Endocrinology. 2017 Oct 1;158(10):3416-25.

Sulen A, Gullaksen SE, Bader L, McClymont DW, Skavland J, Gavasso S, Gjertsen BT. Signaling effects of sodium hydrosulfide in healthy donor peripheral blood mononuclear cells. Pharmacological Research. 2016 Nov 1;113:216-27.

Jiang X, Zhu X, Liu N, Xu H, Zhao Z, Li S, Li S, Cai J, Cao J. Diallyltrisulfide inhibits growth of NCI-H460 in vitro and in vivo, and ameliorates cisplatin-induced oxidative injury in the treatment of lung carcinoma in xenograft mice. International journal of biological sciences. 2017;13(2):167.

Wang S, Kobayashi K, Kogure Y, Yamanaka H, Yamamoto S, Yagi H, Noguchi K, Dai Y. Negative regulation of TRPA1 by AMPK in primary sensory neurons as a potential mechanism of painful diabetic neuropathy. Diabetes. 2018 Jan 1;67(1):98-109.

Wang H, Xu Z, Lee BH, Vu S, Hu L, Lee M, Bu D, Cao X, Hwang S, Yang Y, Zheng J. Gain-of-function mutations in TRPM4 activation gate cause progressive symmetric erythrokeratodermia. Journal of Investigative Dermatology. 2019 May 1;139(5):1089-97.

Shigemi Z, Furukawa Y, Hosokawa K, Minami S, Matsuhiro J, Nakata S, Watanabe T, Kagawa H, Nakagawa K, Takeda H, Fujimuro M. Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma. International journal of oncology. 2016 Jan 1;48(1):293-304.

Yazğan Y, Nazıroğlu M. Ovariectomy-induced mitochondrial oxidative stress, apoptosis, and calcium ion influx through TRPA1, TRPM2, and TRPV1 are prevented by 17β-estradiol, tamoxifen, and raloxifene in the hippocampus and dorsal root ganglion of rats. Molecular Neurobiology. 2017 Dec;54(10):7620-38.

Li H, Mani S, Wu L, Fu M, Shuang T, Xu C, Wang R. The interaction of estrogen and CSE/H2S pathway in the development of atherosclerosis. American Journal of Physiology-Heart and Circulatory Physiology. 2017 Mar 1;312(3):H406-14.

Han NR, Kim NR, Kim HM, Jeong HJ. Cysteine prevents menopausal syndromes in Ovariectomized mouse. Reproductive Sciences. 2016 May;23(5):670-9.

Kodji X, Arkless KL, Kee Z, Cleary SJ, Aubdool AA, Evans E, Caton P, Pitchford SC, Brain SD. Sensory nerves mediate spontaneous behaviors in addition to inflammation in a murine model of psoriasis. The FASEB Journal. 2019 Feb;33(2):1578-94.

Cevikbas F, Wang X, Akiyama T, Kempkes C, Savinko T, Antal A, Kukova G, Buhl T, Ikoma A, Buddenkotte J, Soumelis V. A sensory neuron–expressed IL-31 receptor mediates T helper cell–dependent itch: Involvement of TRPV1 and TRPA1. Journal of allergy and clinical immunology. 2014 Feb 1;133(2):448-60.

Caterina MJ, Pang Z. TRP channels in skin biology and pathophysiology. Pharmaceuticals. 2016 Dec;9(4):77.

Zhou Y, Han D, Follansbee T, Wu X, Yu S, Wang B, Shi Z, Domocos DT, Carstens M, Carstens E, Hwang ST. Transient receptor potential ankyrin 1 (TRPA1) positively regulates imiquimod‐induced, psoriasiform dermal inflammation in mice. Journal of Cellular and Molecular Medicine. 2019 Jul;23(7):4819-28.

Kim HO, Cho YS, Park SY, Kwak IS, Choi MG, Chung BY, Park CW, Lee JY. Increased activity of TRPV 3 in keratinocytes in hypertrophic burn scars with postburn pruritus. Wound Repair and Regeneration. 2016 Sep;24(5):841-50.

Luo J, Feng J, Yu G, Yang P, Mack MR, Du J, Yu W, Qian A, Zhang Y, Liu S, Yin S. Transient receptor potential vanilloid 4–expressing macrophages and keratinocytes contribute differentially to allergic and nonallergic chronic itch. Journal of Allergy and Clinical Immunology. 2018 Feb 1;141(2):608-19.

Akiyama T, Ivanov M, Nagamine M, Davoodi A, Carstens MI, Ikoma A, Cevikbas F, Kempkes C, Buddenkotte J, Steinhoff M, Carstens E. Involvement of TRPV4 in serotonin-evoked scratching. Journal of Investigative Dermatology. 2016 Jan 1;136(1):154-60.

Misery L, Santerre A, Batardière A, Hornez N, Nedelec AS, Le Caër F, Bourgeois P, Huet F, Neufang G. Real-life study of anti-itching effects of a cream containing menthoxypropanediol, a TRPM8 agonist, in atopic dermatitis patients. Journal of the European Academy of Dermatology and Venereology: JEADV. 2019 Feb;33(2):e67-9.

Lee YW, Won CH, Jung K, Nam HJ, Choi G, Park YH, Park M, Kim B. Efficacy and safety of PAC‐14028 cream–a novel, topical, nonsteroidal, selective TRPV 1 antagonist in patients with mild‐to‐moderate atopic dermatitis: a phase II b randomized trial. British Journal of Dermatology. 2019 May;180(5):1030-8.

Cohen JA, Edwards TN, Liu AW, Hirai T, Jones MR, Wu J, Li Y, Zhang S, Ho J, Davis BM, Albers KM. Cutaneous TRPV1+ neurons trigger protective innate type 17 anticipatory immunity. Cell. 2019 Aug 8;178(4):919-32.

Zhou Y, Follansbee T, Wu X, Han D, Yu S, Domocos DT, Shi Z, Carstens M, Carstens E, Hwang ST. TRPV1 mediates inflammation and hyperplasia in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice. Journal of dermatological science. 2018 Dec 1;92(3):264-71.

Chen Y, Moore CD, Zhang JY, Hall III RP, MacLeod AS, Liedtke W. TRPV4 moves toward center-fold in rosacea pathogenesis. Journal of Investigative Dermatology. 2017 Apr 1;137(4):801-4.

Yang JM, Wei ET, Kim SJ, Yoon KC. TRPM8 channels and dry eye. Pharmaceuticals. 2018 Dec;11(4):125.

Okada Y, Shirai K, Miyajima M, Reinach PS, Yamanaka O, Sumioka T, Kokado M, Tomoyose K, Saika S. Loss of TRPV4 function suppresses inflammatory fibrosis induced by alkali-burning mouse corneas. PLoS One. 2016 Dec 28;11(12):e0167200.

Kwon JY, Lee HS, Joo CK. TRPV1 antagonist suppresses allergic conjunctivitis in a murine model. Ocular Immunology and Inflammation. 2018 Apr 3;26(3):440-8.

Froghi S, Grant CR, Tandon R, Quaglia A, Davidson B, Fuller B. New insights on the role of TRP channels in calcium signalling and immunomodulation: review of pathways and implications for clinical practice. Clinical reviews in allergy & immunology. 2021 Apr;60(2):271-92.

Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. Journal of clinical & cellular immunology. 2011 Aug 10;2(3).

Dhingra N, Shemer A, Da Rosa JC, Rozenblit M, Fuentes-Duculan J, Gittler JK, Finney R, Czarnowicki T, Zheng X, Xu H, Estrada YD. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. Journal of Allergy and Clinical Immunology. 2014 Aug 1;134(2):362-72.

Boehncke WH, Schön MP. Disease burden and epidemiology.Lancet. 2015;386:983-94.

Szepietowski JC, Reich A. Pruritus in psoriasis: An update. European Journal of Pain. 2016 Jan;20(1):41-6.

Zhang X, He Y. The role of nociceptive neurons in the pathogenesis of psoriasis. Frontiers in Immunology. 2020:1984.

Kubanov A, Katunina OR, Chikin VV. Expression of neuropeptides, neurotrophins, and neurotransmitters in the skin of patients with atopic dermatitis and psoriasis.Bulletin of experimental biology and medicine. 2015 Jul;159(3):318-22.

Nattkemper LA, Tey HL, Valdes-Rodriguez R, Lee H, Mollanazar NK, Albornoz C, Sanders KM, Yosipovitch G. The genetics of chronic itch: gene expression in the skin of patients with atopic dermatitis and psoriasis with severe itch. Journal of Investigative Dermatology. 2018 Jun 1;138(6):1311-7.

Kemény Á, Kodji X, Horváth S, Komlódi R, Szőke É, Sándor Z, Perkecz A, Gyömörei C, Sétáló G, Kelemen B, Bíró T. TRPA1 acts in a protective manner in imiquimod-induced psoriasiform dermatitis in mice. Journal of Investigative Dermatology. 2018 Aug 1;138(8):1774-84.

Furue M, Kadono T. New therapies for controlling atopic itch.The Journal of Dermatology. 2015 Sep;42(9):847-50.

Miyagaki T, Sugaya M. Immunological milieu in mycosis fungoides and S ézary syndrome. The Journal of dermatology. 2014 Jan;41(1):11-8.

Han Q, Liu D, Convertino M, Wang Z, Jiang C, Kim YH, Luo X, Zhang X, Nackley A, Dokholyan NV, Ji RR. miRNA-711 binds and activates TRPA1 extracellularly to evoke acute and chronic pruritus. Neuron. 2018 Aug 8;99(3):449-63.

Sanders KM, Nattkemper LA, Rosen JD, Andersen HH, Hsiang J, Romanelli P, Bernigaud C, Guillot J, Chosidow O, Yosipovitch G. Non-histaminergic itch mediators elevated in the skin of a porcine model of scabies and of human scabies patients. The Journal of investigative dermatology. 2019 Apr;139(4):971-3.

Hashimoto T, Kursewicz CD, Fayne RA, Nanda S, Shah SM, Nattkemper L, Yokozeki H, Yosipovitch G. Pathophysiologic mechanisms of itch in bullous pemphigoid. Journal of the American Academy of Dermatology. 2020 Jul 1;83(1):53-62.

Yang YS, Cho SI, Choi MG, Choi YH, KwAK IS, Park CW, Kim HO. Increased expression of three types of transient receptor potential channels (TRPA1, TRPV4 and TRPV3) in burn scars with post-burn pruritus. Acta Derm Venereol. 2015 Jan 1;95(1):20-4.

Eid SR, Crown ED, Moore EL, Liang HA, Choong KC, Dima S, Henze DA, Kane SA, Urban MO. HC-030031, a TRPA1 selective antagonist, attenuates inflammatory-and neuropathy-induced mechanical hypersensitivity. Molecular pain. 2008 Oct 27;4:1744-8069.

Marone IM, De Logu F, Nassini R, De Carvalho Goncalves M, Benemei S, Ferreira J, Jain P, Li Puma S, Bunnett NW, Geppetti P, Materazzi S. TRPA1/NOX in the soma of trigeminal ganglion neurons mediates migraine-related pain of glyceryl trinitrate in mice. Brain. 2018 Aug 1;141(8):2312-28.

Antoniazzi CT, Nassini R, Rigo FK, Milioli AM, Bellinaso F, Camponogara C, Silva CR, de Almeida AS, Rossato MF, De Logu F, Oliveira SM. Transient receptor potential ankyrin 1 (TRPA1) plays a critical role in a mouse model of cancer pain. International Journal of Cancer. 2019 Jan 15;144(2):355-65.

Bressan E, Touska F, Vetter I, Kistner K, Kichko TI, Teixeira NB, Picolo G, Cury Y, Lewis RJ, Fischer MJ, Zimmermann K. Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia. Pain. 2016 Nov 1;157(11):2504-16.

KortekaasKrohn I, Callebaut I, Alpizar YA, Steelant B, Van Gerven L, Skov PS, Kasran A, Talavera K, Wouters MM, Ceuppens JL, Seys SF. MP 29‐02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite‐allergic rhinitis. Allergy. 2018 May;73(5):1084-93.

Benemei S, De Logu F, Puma SL, Marone IM, Coppi E, Ugolini F, Liedtke W, Pollastro F, Appendino G, Geppetti P, Materazzi S. The anti‐migraine component of butterbur extracts, isopetasin, desensitizes peptidergicnociceptors by acting on TRPA1 cation channel. British journal of pharmacology. 2017 Sep 1;174(17):2897-911.

Gautier M, Dhennin‐Duthille I, Ay AS, Rybarczyk P, Korichneva I, Ouadid‐Ahidouch H. New insights into pharmacological tools to TR (i) P cancer up.British journal of pharmacology. 2014 May;171(10):2582-92.

Zheng J, Liu F, Du S, Li M, Wu T, Tan X, Cheng W. Mechanism for regulation of melanoma cell death via activation of thermo-TRPV4 and TRPV2. Journal of oncology. 2019 Feb 7;2019.

Brusco I, Li Puma S, Chiepe KB, da Silva Brum E, de David Antoniazzi CT, de Almeida AS, Camponogara C, Silva CR, De Logu F, de Andrade VM, Ferreira J. Dacarbazine alone or associated with melanoma‐bearing cancer pain model induces painful hypersensitivity by TRPA1 activation in mice. International Journal of Cancer. 2020 May 15;146(10):2797-809.

Fink C, Uhlmann L, Enk A, Gholam P. Pain management in photodynamic therapy using a nitrous oxide/oxygen mixture: a prospective, within‐patient, controlled clinical trial. Journal of the European Academy of Dermatology and Venereology. 2017 Jan;31(1):70-4.

Maglie R, Antiga E, Payne AS. B-cell targeted therapies in pemphigus. Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Societa Italiana di Dermatologia e Sifilografia. 2020 Oct 5.

Gao S, Kaudimba KK, Guo S, Zhang S, Liu T, Chen P, Wang R. Transient receptor potential ankyrin type-1 channels as a potential target for the treatment of cardiovascular diseases. Frontiers in Physiology. 2020 Jul 30;11:836.

Guo Y, Ying S, Zhao X, Liu J, Wang Y. Increased expression of lung TRPV1/TRPA1 in a cough model of bleomycin-induced pulmonary fibrosis in Guinea pigs. BMC pulmonary medicine. 2019 Dec;19(1):1-1.




How to Cite

Aqib Saeed, M. ., Basharat, S. ., Shahid, M., Zafar, A. ., Noor, H. ., Saleem, A. ., Ahmad Rana, I. ., & Tehreem Jamil. (2022). Garlic Activate TRPA Receptor as a potential therapeutic target in skin related diseases: Garlic Activate TRPA Receptor as a potential therapeutic target in skin related diseases. Pakistan BioMedical Journal, 5(7), 358–365.



Systematic Review

Most read articles by the same author(s)

1 2 > >>