SOOTHING EFFECT OF POGOSTEMON CABLIN EXTRACT 435 receptor 2 modulation. This extract could be used to lessen skin discomfort, especially in case of fragile skin and itching sensation. A CKNOWLEDGMENTS We are grateful to Laura Mouret for the analysis of bioactive compounds present in the pa- tchouli extract, and to Ludivine Mur and Alexia Lebleu for the technical assistance. We wish to thank Anne Clay Viardot for reading the manuscript and for the English language review. Patents: Ashland owns patent applications related to a method for obtaining an extract of patchouli leaves and cosmetics uses thereof, published under numbers FR3091993A1 and W02020156981. Funding: This research was funded by Ashland Inc. Author contributions: Florian Labarrade, Yolene Ferreira, Gilles Oberto, and Catherine Gondran conceived and designed the experiments, and the methodology Florian Labar- rade, Armelle Perrin, Yolene Ferreira, and Gilles Oberto performed the experiments and analyzed the data and Florian Labarrade wrote the paper, with Catherine Gondran revising it critically. Corine Morel was in charge of patchouli extract procurement and analysis. Catherine Gondran and Karine Cucumel supervised the study and handled project administration. All authors read and approved the fi nal manuscript. REFERENCES (1) A. Oláh, A. G. Szöllősi, and T. Bíró, The channel physiology of the skin, Rev. Physiol. Biochem. Pharma- col., 163, 65–131 (2012). (2) T . C. Theoharides, J. M. Stewart, A. Taracanova, P. Conti, and C. C. Zouboulis, Neuroendocrinology of the skin, Rev. Endocr. Metab. Disord., 17, 287–294 (2016). (3) P . Pacher, S. Bátkai, and G. Kunos, The endocannabinoid system as an emerging target of pharmaco- therapy, Pharmacol. Rev., 58, 389–462 (2006). (4) J . Gertsch, R. G. Pertwee, and V. Di Marzo, Phytocannabinoids beyond the Cannabis plant – do they exist? Br. J. Pharmacol., 160, 523–529 (2010). (5) S . Ständer, M. Schmelz, D. Metze, T. Luger, and R. Rukwied, Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fi bers and adnexal structures in human skin, J. Dermatol. Sci., 38, 177–188 (2005). (6) J. Zhang, L. Chen, T. Su, F. Cao, X. Meng, L. Pei, J. Shi, H. L. Pan, and M. Li, Electroacupuncture in- creases CB2 receptor expression on keratinocytes and infi ltrating infl ammatory cells in infl amed skin tissues of rats. J. Pain, 11, 1250–1258 (2010). (7) J. L. Zheng, T. S. Yu, X. N. Li, Y. Y. Fan, W. X. Ma, Y. Du, R. Zhao, and D. W. Guan, Cannabinoid receptor type 2 is time-dependently expressed during skin wound healing in mice, Int. J. Leg. Med., 126, 807–814 (2012). (8) C. D. Río, E. Millán, V. García, G. Appendino, J. DeMesa, and E. Muñoz, The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders, Biochem. Pharmacol., 157, 122–133 (2018). (9) J. S. M ounessa, J. A. Siegel, C. A. Dunnick, and R. P. Dellavalle, The role of cannabinoids in dermatol- ogy, J. Am. Acad. Dermatol., 77, 188–190 (2017). (10) R. Mi l ando and A. Friedman, Cannabinoids: potential role in infl ammatory and neoplastic skin diseases, Am. J. Clin. Dermatol., 20, 167–180 (2019). (11) F. Ga o . L. H. Zhang, T. F. Su, L. Li, R. Zhou, M. Peng, C. H. Wu, X. C. Yuan, N. Sun, X. F. Meng, B. Tian, H. L. Pan, and M. Li, Signaling mechanism of cannabinoid receptor-2 activation-induced β-endorphin release, Mol. Neurobiol., 53, 3616–3625 (2016).

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