2. Academic Validation
  3. Anti-inflammatory effects and mechanisms of Podophyllum hexandrum rhizomes and fruits in a chronic pelvic inflammatory disease rat model

Anti-inflammatory effects and mechanisms of Podophyllum hexandrum rhizomes and fruits in a chronic pelvic inflammatory disease rat model

  • J Ethnopharmacol. 2026 Feb 28:357:120954. doi: 10.1016/j.jep.2025.120954.
Bo Zhang 1,  An-Ting Yang 1,  Li-Ning Wang 2,  Qi Yu 3,  Cui-Cui Tan 4,  Wen-Hua Chao 4,  Han-Yu Geng 3,  Tian-Xian Pei 5,  Lei Zhang 6,  Shi-Jie Cao 7,  Feng Qiu 8,  Ning Kang 9
Affiliations

Affiliations

  • 1 School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Institute of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 2 School of Chinese Materia Medica, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; School of Pharmacy, Xinjiang Hetian College, Xinjiang, 848000, China.
  • 3 Institute of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 4 Institute of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; School of Chinese Materia Medica, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 5 Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 6 School of Chinese Materia Medica, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 7 Institute of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: [email protected].
  • 8 School of Chinese Materia Medica, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: [email protected].
  • 9 School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; School of Chinese Materia Medica, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: [email protected].
PMID: 41285229 DOI: 10.1016/j.jep.2025.120954
Abstract

Ethnopharmacological relevance: A state-protected Tibetan medicinal plant Sinopodophyllum hexandrum (Royle) T.S. Ying (SH) has traditionally been used to regulate menstruation, manage dystocia, and resolve blood stasis. However, its efficacy against chronic pelvic inflammatory disease (CPID) and the underlying mechanisms remain largely unexplored.

Aim of the research: To investigate the therapeutic effects of SH rhizomes and fruits (SHR and SHF) in a CPID rat model and elucidate their molecular anti-inflammatory mechanisms.

Methods and materials: CPID was induced in rats by phenol mucilage injection combined with mechanical injury. The beneficial effects of SHR and SHF on CPID rats were evaluated via uterine histopathology and analysis of IL-1β, IL-6, and TNF-α, the key inflammatory cytokines. Transcriptomic profiling was performed to identify enriched signaling pathways and differentially expressed genes, which were further validated by western blotting and immunohistochemistry (IHC). Mechanistic studies were also performed using LPS-stimulated RAW264.7 macrophages treated with aqueous SHR or SHF extracts.

Results: SHF and SHR markedly improved morphology of uterine in CPID rats, reducing swelling, uterine index, and inflammatory infiltration. Both treatments downregulated IL-1β and MCP-1 mRNA while upregulated IL-10. Additionally, they decreased peripheral neutrophil, monocyte, and lymphocyte percentages and reduced serum malondialdehyde (MDA) levels, indicating mitigation of systemic oxidative stress. Transcriptomic analysis showed that SHF exerted its effects via activation of MAPK, Ras, and PI3K/Akt pathways, while SHR primarily modulated the PPARγ and JAK2/STAT3 signaling axes. SHF restored p-PI3K/PI3K and Ras expression and reduced p-JNK levels without affecting p-AKT or Akt. SHR significantly upregulated PPARγ and inhibited p-JAK2 and p-STAT3 expression in CPID rats. These effects were consistent in SHR or SHF-treated RAW264.7 cells stimulated with LPS. Furthermore, PI3K inhibition and PPARγ activation attenuated the downregulation of IL-1β and IL-6 induced by SHR and SHF, respectively.

Conclusions: SHR and SHF alleviate CPID by suppressing key pro-inflammatory cytokines through distinct pathways-SHF via PI3K/Ras/MAPK and SHR via PPARγ/JAK2/STAT3. These results show that SH is a promising therapeutic candidate for CPID and underscore its importance in the development and conservation of endangered Tibetan medicinal resources.

Keywords

CPID; PI3K/Ras/JNK pathway; PPARγ/JAK2/STAT3 pathway; Sinopodophyllum hexandrum (Royle) T.S.Ying; The rhizomes and fruits.

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