Nerol enhances lipid synthesis in human sebocytes via cannabinoid receptor-2-mediated MAPK signaling

  • J Pharmacol Sci. 2025 Jul;158(3):219-230. doi: 10.1016/j.jphs.2025.04.008.
Qi Zhao  1 ,  Zhiwei Liu  1 ,  Yong Wang  1 ,  Tan Li  2 ,  Juan Wang  1 ,  Yaozhao Li  1 ,  Chengliang Li  3 ,  Chuntao Zhai  3 ,  Christos C Zouboulis  4 ,  Xiaolei Ding  5 ,  Qiang Ju  6 ,  Zhenlin Hu  7
Affiliations
  • 1. School of Medicine, Shanghai University, Shanghai, China.
  • 2. Shiseido China Innovation Center, Shanghai, China.
  • 3. LB Cosmeceutical Technology Co., Ltd., Shanghai, China.
  • 4. Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Dessau, Germany.
  • 5. School of Medicine, Shanghai University, Shanghai, China. Electronic address: [email protected].
  • 6. Department of Dermatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. Electronic address: [email protected].
  • 7. School of Medicine, Shanghai University, Shanghai, China. Electronic address: [email protected].
PMID: 40436484 DOI: 10.1016/j.jphs.2025.04.008
Abstract

Purpose: Nerol, a natural monoterpene, is commonly used as a fragrance additive in perfumes and cosmetics due to its pleasant rose-like aromas. Nerol application possesses diverse pharmacological properties, including anti-microbial, antioxidant, antinociceptive and anti-inflammatory activities, but its effects on sebum production and the consequent skin barrier function remain elusive. Here, we explored the effect of nerol on the lipogenesis of sebocytes.

Patients and methods: Immortalized human SZ95 sebocytes were used. The intracellular lipids were quantitatively measured by western blotting or fluorescent Nile Red staining followed by fluorometric analysis, semiquantitative detection or flow cytometry. The cell proliferation and differentiation were detected with CCK8 and flow cytometry, respectively. Moreover, RT-qPCR and immunocytochemistry were used to determine the expression levels of Olfactory Receptor OR2W3 and cannabinoid receptor-2 (CB2) receptors in SZ95 sebocytes.The mechanism was investigated by RNA interference and Western blotting.

Results: Our findings revealed that nerol induced lipid production in SZ95 sebocytes, together with the upregulation of multiple genes related to lipid synthesis, including PPARγ, SREBP-1, and FAS. Nerol also induced sebocyte differentiation, as evidenced by elevated cellular granulation and upregulated differentiation marker genes. Mechanistically, the lipogenic effect of nerol was mediated via CB2, rather than OR2W3 and TRP channels. Moreover, MAPK signaling was involved in neurol's effect.

Conclusion: Collectively, our findings show that nerol exerts a lipogenic effect on human sebocytes in a CB2-dependent manner through the activation of MAPK pathway, suggesting the therapeutic potential of this monoterpene in controlling cutaneous disorders involving sebaceous gland dysfunction and reduced sebum production, such as atopic dermatitis, skin dryness and aging.

Keywords
Cannabinoid receptor-2; Lipogenesis; Nerol; Sebocytes; Sebum.
Products