2. Academic Validation
  3. Multi-technology integrated network pharmacology-based study on phytochemicals, active metabolites, and molecular mechanism of Psoraleae Fructus to promote melanogenesis

Multi-technology integrated network pharmacology-based study on phytochemicals, active metabolites, and molecular mechanism of Psoraleae Fructus to promote melanogenesis

  • J Ethnopharmacol. 2024 Jan 11:117755. doi: 10.1016/j.jep.2024.117755.
Xuemei Yu 1,  Yuanyuan Wang 2,  Zhenghua Wu 3,  Mengqi Jia 4,  Ying Xu 5,  Han Qu 6,  Xin Zhao 7,  Shuowen Wang 8,  Lili Jing 9,  Yuefen Lou 10,  Guorong Fan 11,  Yaxing Gui 12
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China. Electronic address: xuemeiyu1226@163.com.
  • 2 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China; Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China. Electronic address: wangyy012399@163.com.
  • 3 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai, 200240, PR China. Electronic address: wuzhenghua526@163.com.
  • 4 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China. Electronic address: jmq0701@163.com.
  • 5 Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China. Electronic address: xuying.23@sjtu.edu.cn.
  • 6 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai, 200240, PR China. Electronic address: quhan1002@sjtu.edu.cn.
  • 7 Department of Pharmacy, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200434, PR China. Electronic address: yoyo0132@163.com.
  • 8 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China. Electronic address: wangshuowensy@163.com.
  • 9 School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai, 200240, PR China. Electronic address: lilijing@sjtu.edu.cn.
  • 10 Department of Pharmacy, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200434, PR China. Electronic address: louyuefen@sina.cn.
  • 11 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China; School of Pharmacy, Shanghai Jiao Tong University, Building 6-312, Shanghai, 200240, PR China. Electronic address: guorfan@163.com.
  • 12 Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China. Electronic address: YaxingGui@shsmu.edu.cn.
PMID: 38218502 DOI: 10.1016/j.jep.2024.117755
Abstract

Ethnopharmacological relevance: According to the Compendium of Materia Medica (Shizhen Li, Ming dynasty) and Welfare Pharmacy (Song dynasty), Psoraleae Fructus (PF), a traditional Chinese medicine (TCM) has a bitter taste and warm nature, which has the effect of treating spleen and kidney deficiency and skin disease. Although PF has been widely used since ancient times and has shown satisfactory efficacy in treating vitiligo, the active substances and the mechanism of PF in promoting melanogenesis remain unclear.

Aim of the study: To explore the active substances and action mechanisms of PF in promoting melanogenesis.

Materials and methods: Firstly, UPLC-UV-Q-TOF/MS was used to characterize the components in PF extract and identify the absorption components and metabolites of PF after oral administration at usual doses in rats. Secondly, the active substances and related targets and pathways were predicted by network pharmacology and molecular docking. Finally, pharmacodynamic and Molecular Biology experiments were used to verify the prediction results.

Results: The experimental results showed that 15 compounds were identified in PF extract, and 44 compounds, consisting of 8 prototype components and 36 metabolites (including isomers) were identified in rats' plasma. Promising action targets (MAPK1, MAPK8, MAPK14) and signaling pathways (MAPK signaling pathway) were screened and refined to elucidate the mechanism of PF against vitiligo based on network pharmacology. Bergaptol and xanthotol (the main metabolites of PF), psoralen (prototype drug), and PF extract significantly increased melanin production in zebrafish embryos. Furthermore, bergaptol could promote the pigmentation of zebrafish embryos more than psoralen and PF extract. Bergaptol significantly increased the protein expression levels of p-P38 and decreased ERK phosphorylation in B16F10 cells, which was also supported by the corresponding inhibitor/activator combination study. Moreover, bergaptol increased the mRNA expression levels of the downstream microphthalmia-associated transcription factor (MITF) and Tyrosinase in B16F10 cells. Our data elucidate that bergaptol may promote melanogenesis by regulating the p-P38 and p-ERK signaling pathway.

Conclusions: This study will lay a foundation for discovering potential new drugs for treating vitiligo and provide feasible ideas for exploring the mechanism of traditional Chinese medicine.

Keywords

Bergaptol; Network pharmacology; Psoraleae Fructus; UPLC-UV-Q-TOF/MS; Vitiligo.

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