Guben-Qushi-Huayu formula and calycosin improve epidermal barrier function in psoriasis by inhibiting small proline-rich protein 1A

  • Phytomedicine. 2025 Oct 10:148:157395. doi: 10.1016/j.phymed.2025.157395.
Lijuan Liu  1 ,  Shiying Zhao  2 ,  Yayun Wu  3 ,  Ya Zhao  4 ,  Chuanjian Lu  5 ,  Ruizhi Zhao  6
Affiliations
  • 1. State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, China; The Second Clinical Medical College, Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, 510006, China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong Province, 510006, China.
  • 2. The Second Clinical Medical College, Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, 510006, China.
  • 3. The Second Clinical Medical College, Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, 510006, China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong Province, 510006, China.
  • 4. State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, China; The Second Clinical Medical College, Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, 510006, China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong Province, 510006, China.
  • 5. State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, China; The Second Clinical Medical College, Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, 510006, China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong Province, 510006, China. Electronic address: [email protected].
  • 6. State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, China; The Second Clinical Medical College, Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, 510006, China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong Province, 510006, China. Electronic address: [email protected].
PMID: 41166908 DOI: 10.1016/j.phymed.2025.157395
Abstract

Background: As a persistent inflammatory skin disease, psoriasis is notably challenging to treat effectively. Guben-Qushi-Huayu formula (GQH) has proven effective in enhancing epidermal barrier function and quality of life in psoriasis patients. However, its underlying mechanisms and active compounds remain elusive.

Purpose: To elucidate the therapeutic target of GQH in epidermal barrier restoration and identify its active compound(s).

Methods: GQH efficacy was evaluated in imiquimod-induced psoriatic mice. RNA Sequencing (RNA-seq) analysis revealed underlying mechanisms, validated by RT-PCR, immunohistochemistry, western blotting, ELISA, and Gene Expression Omnibus database analyses. The role of small proline-rich protein 1A (SPRR1A) was confirmed via siRNA knockdown and overexpression in human keratinocyte (HaCaT) cells. UPLC-MS/MS was used to identify active compounds in GQH-containing serum (GCS). GCS and calycosin on cell viability and migration were assessed in SPRR1A-knockdown HaCaT cells. GCS-SPRR1A binding was evaluated using drug affinity responsive target stability assay, whereas calycosin-SPRR1A binding was evaluated by surface plasmon resonance.

Results: GQH significantly ameliorated psoriatic lesions by reducing inflammation, suppressing keratinocyte hyperproliferation, and restoring epidermal barrier function. RNA-seq analysis revealed GQH's potent regulatory effect on cornified envelope (CE)-related genes, and identified SPRR1A as a key target. Functional validation via SPRR1A knockdown/overexpression in HaCaT cells demonstrated its critical role in modulating keratinocyte migration, proliferation, and inflammatory factor secretion. Significantly, GCS inhibited these pathological processes in HaCaT cells through SPRR1A-dependent mechanisms. UPLC-MS/MS identified eight bioactive compounds in GCS, including calycosin, which directly suppressed keratinocyte proliferation and migration. A high affinity was observed between calycosin and SPRR1A (KD = 4.13×10-6 M).

Conclusion: SPRR1A represents a previously unrecognized druggable target in psoriasis pathogenesis, which can be effectively modulated by both the herbal formula GQH and its purified component calycosin.

Keywords
Calycosin; Epidermal barrier; Guben-Qushi-Huayu formula; Psoriasis; Small proline-rich protein 1A.
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