Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Sihe Tufuling formula alleviates imiquimod-induced psoriasis-like skin lesions in mice by modulating the HIF-1 signaling pathway.
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Kang Yutong, Alimujiang Abudureyimu, Zhou Fan, Chen Liangmian, Wang Hongzhi, Wei Wenjing, Zhao Jingcheng, Zhu Ziqi, Sun Wancheng, Xie Xuejiao, Huo Shixia, Xu Dengqiu, Li Zhijian
Аннотация
OBJECTIVE: Psoriasis is a chronic, immune-mediated dermatological disorder characterized by pathological epidermal hyperplasia, aberrant keratinocyte differentiation, and dermal infiltration of inflammatory cells. Sihe Tufuling (SHTFL), a clinically established traditional Chinese medicine formula, has demonstrated therapeutic efficacy in psoriasis management. This study aimed to investigate the anti-psoriatic activity of SHTFL and its principal herb, Smilax glabra Roxb. (SGR), and to elucidate their underlying mechanisms of action.
METHODS: Ultra-performance liquid chromatography-mass spectrometry was used to identify the major chemical constituents of SHTFL and SGR. An imiquimod (IMQ)-induced psoriasis-like mouse model was employed to assess therapeutic efficacy using the psoriasis area and severity index, spleen index, hematoxylin and eosin staining, immunohistochemistry, immunofluorescence. Transcriptomic sequencing, single-cell RNA sequencing, gene knockdown, immunofluorescence, and quantitative reverse-transcription PCR analyses were performed to investigate the molecular mechanisms involved.
RESULTS: The results of the chemical component identification indicated that flavonoids constitute essential components in both the SHTFL formula and SGR. Treatment with SHTFL and SGR resulted in a significant reduction of the PASI score, skin thickness, splenic index and serum levels of inflammatory cytokines in IMQ-induced mice psoriasis mice. Moreover, both SHTFL and SGR alleviated psoriasis by inhibiting keratinocyte hyperproliferation and the inflammatory response in IMQ-induced mice. Transcriptomic analysis revealed that SHTFL and SGR mitigates keratinocyte hyperproliferation and the inflammatory response by modulating the HIF-1 signaling pathway. Furthermore, HIF-1α knockdown abolished the protective effects of SHTFL in these models.
CONCLUSION: Our results indicate that both SHTFL and SGR hinder the excessive growth of keratinocytes and reduce inflammation in psoriasis by inhibiting the HIF-1 signaling pathway. This evidence backs SHTFL as a promising therapeutic approach for psoriasis.
METHODS: Ultra-performance liquid chromatography-mass spectrometry was used to identify the major chemical constituents of SHTFL and SGR. An imiquimod (IMQ)-induced psoriasis-like mouse model was employed to assess therapeutic efficacy using the psoriasis area and severity index, spleen index, hematoxylin and eosin staining, immunohistochemistry, immunofluorescence. Transcriptomic sequencing, single-cell RNA sequencing, gene knockdown, immunofluorescence, and quantitative reverse-transcription PCR analyses were performed to investigate the molecular mechanisms involved.
RESULTS: The results of the chemical component identification indicated that flavonoids constitute essential components in both the SHTFL formula and SGR. Treatment with SHTFL and SGR resulted in a significant reduction of the PASI score, skin thickness, splenic index and serum levels of inflammatory cytokines in IMQ-induced mice psoriasis mice. Moreover, both SHTFL and SGR alleviated psoriasis by inhibiting keratinocyte hyperproliferation and the inflammatory response in IMQ-induced mice. Transcriptomic analysis revealed that SHTFL and SGR mitigates keratinocyte hyperproliferation and the inflammatory response by modulating the HIF-1 signaling pathway. Furthermore, HIF-1α knockdown abolished the protective effects of SHTFL in these models.
CONCLUSION: Our results indicate that both SHTFL and SGR hinder the excessive growth of keratinocytes and reduce inflammation in psoriasis by inhibiting the HIF-1 signaling pathway. This evidence backs SHTFL as a promising therapeutic approach for psoriasis.