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  3. Clematis Tangutica (Maxim.) Korsh. extracts promote melanogenesis via PKA/CREB activation and multi-cytokine inhibition: A novel dual targeting strategy for vitiligo therapy

Clematis Tangutica (Maxim.) Korsh. extracts promote melanogenesis via PKA/CREB activation and multi-cytokine inhibition: A novel dual targeting strategy for vitiligo therapy

  • Phytomedicine. 2026 Apr:153:157963. doi: 10.1016/j.phymed.2026.157963.
Miao Guo 1,  Jingfeng Peng 1,  Changsheng Dong 2,  Jihong Lu 3,  Suntao Li 1,  Mo Chen 3,  Jianzheng Zhu 1,  Anying Chen 4,  Yuqi Lu 5,  Lili Jing 3,  Hua Xiao 1,  Dongmei Fu 6,  Xinmiao Liang 7,  Yan Zhang 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 2 Cancer Institute of Traditional Chinese Medicine, Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
  • 3 Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 4 Jiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation Center, Nanchang 330100, China.
  • 5 School of Biological Engineering, Dalian Polytechnic University, Dalian, 116034, China.
  • 6 School of Biological Engineering, Dalian Polytechnic University, Dalian, 116034, China. Electronic address: [email protected].
  • 7 Jiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation Center, Nanchang 330100, China; Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: [email protected].
  • 8 Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address: [email protected].
PMID: 41720011 DOI: 10.1016/j.phymed.2026.157963
Abstract

Background: Dysregulation of melanin contributes to pigmentation disorders including vitiligo, which lacks effective and safe therapeutic options. Despite advances in immunomodulatory therapies, current treatments often fail to address both the loss of melanocytes and the underlying autoimmune pathology driving the disease. Clematis tangutica (Maxim.) Korsh. (C. tangutica), a traditional Chinese Tibetan medicine adapted to high-altitude UV stress, remains unexplored in pigment regulation.

Purpose: This study aimed to assess the effects of C. tangutica leaf and stem extracts (CTLE and CTSE) on melanogenesis and their potential roles in vitiligo, as well as to elucidate the underlying molecular mechanisms.

Methods: The melanogenic effects of CTLE and CTSE were evaluated in B16F10 melanoma cells, zebrafish and a monobenzone-induced vitiligo mouse model. Label-free quantitative proteomics, immunoblotting and immunofluorescence analyses were performed to identify the underlying signaling pathways.

Results: Both CTLE and CTSE significantly enhanced melanogenesis in vitro and in zebrafish. In the vitiligo mouse model, CTSE induced robust repigmentation and reduced pro-inflammatory cytokines, indicating dual melanogenic and immunomodulatory activity. Both extracts upregulated MITF and TYR expression. Proteomic analysis revealed enrichment of the cAMP/PKA/CREB signaling pathway, with increased CREB phosphorylation confirmed by immunoblotting. Pharmacological inhibition of PKA abolished extract-induced melanogenesis, confirming the essential role of cAMP/PKA/CREB signaling.

Conclusion: C. tangutica extract promotes melanogenesis via PKA/CREB activation and uniquely exhibits immunomodulatory activity in a vitiligo model. This study provides the first mechanistic evidence for the dual-targeting potential of C. tangutica, as a natural candidate for vitiligo therapy. Our findings highlight a novel phytotherapeutic strategy pigmentary disorders.

Keywords

CREB; Clematis Tangutica leaf extract; Clematis Tangutica stem extract; Immunomodulatory activity; Melanogenesis.

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