Frontiers in Immunology
·
2025
·
IF 5.9
Jingwei Liu,Tong Shu,Yiheng Mu,Wanlin Zheng,Xiaohuan Lu,Hong Tao
Background: Human papillomavirus (HPV) infection is a worldwide reproductive system disease. Baofukang suppository, a traditional herbal preparation that includes curdione and borneol, has been reported to treat bacterial vaginosis (BV) and HPV infection in China. However, the therapeutic mechanism is still unknown. This study aims to explore the molecular mechanisms of curdione and borneol in treating HPV infection.Methods: We conducted a retrospective cohort analysis of medical records from a single-center study involving 205 HPV patients, focusing on the correlation between HPV clearance and co-infection with other pathogens, confirming the efficacy of Baofukang suppository. Bioinformatics and network pharmacology approaches were employed to identify therapeutic targets of Baofukang suppository for BV/HPV co-infections. qRT-PCR, Western blot, immunofluorescence staining, and flow cytometry were utilized to validate the therapeutic targets of curdione and borneol, along with the associated immune molecular changes. Finally, the molecular mechanisms and therapeutic efficacy of curdione and borneol were confirmed in vivo using an LPS/TC-1 cervical orthotopic injection model.Results: Curdione and borneol selectively inhibit the secretion of interleukin-6 (IL-6) and interleukin-1β (IL-1β) by macrophages. The reduction in IL-6 and IL-1β levels effectively inhibits the expression of CD274 (Programmed death ligand 1, PD-L1) in infected epithelial cells by inhibiting STAT3 phosphorylation, thereby suppressing their immune evasion capabilities. Furthermore, curdione and borneol enhance the expression of tumor necrosis factor α (TNF-α) and caspase 1 (CASP1) in macrophages, as well as the expression of interleukin 12 (IL-12) and interleukin 23 (IL-23) in dendritic cells (DCs). The expression of these inflammatory factors effectively promotes the migration and differentiation of T cells to the site of infection, completing the clearance of infected epithelial cells.Conclusion: The main components of Baofukang suppository, curdione and borneol, inhibit the progression of HPV infection and the occurrence of cervical cancer by modulating the communication between innate and adaptive immunity, promoting the recruitment and recognition of CD8+ T cells to eliminate HPV-infected epithelial cells.
研究领域:
医学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2026
·
IF 5.2
Qianqian Li,Yufang Ni,Zhaoyang Li,Yuanxia Zou,Huaiying Guo,Honglian Wang,Qiong Zhang,Li Wang,Jianchun Li
Chronic Kidney Disease (CKD) inevitably progresses to End-Stage Renal Disease (ESRD) via tubulointerstitial fibrosis, a process predominantly driven by the transforming growth factor-β (TGF-β)/SMAD family member 3 (Smad3) signaling pathway. Although curdione, a major sesquiterpenoid from Curcumae Rhizoma, exhibits anti-fibrotic activity, its specific mechanism in renal fibrosis remains undefined. Here, we investigated the protective effects of curdione using the Unilateral Ureteral Obstruction (UUO) mouse model and TGF-β1-stimulated renal tubular epithelial cells (TCMK1). We found that curdione (25 and 100 mg/kg) significantly mitigated UUO-induced renal injury and tubular necrosis, suppressed the injury marker kidney injury molecule-1 (KIM-1), and dose-dependently inhibited α-smooth muscle actin (α-SMA), fibronectin (FN), and Collagen I. Consistently, in TGF-β1-stimulated TCMK1 cells, curdione prevented fibrotic morphological changes and suppressed the upregulation of profibrotic markers. Mechanistically, curdione suppressed the expression of Filamin Binding LIM Protein 1 (Fblim1) and the phosphorylation of Smad2/3 in vivo and in vitro . Crucially, Fblim1 overexpression, achieved in vivo via ultrasound microbubble-mediated plasmid delivery and confirmed in vitro , significantly abrogated curdione’s anti-fibrotic effects and restored p-Smad3 levels. Furthermore, molecular docking predicted a strong binding affinity (-6.7 kcal/mol), while cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) assays physically validated that curdione directly binds to Fblim1, enhancing its molecular stability. In conclusion, this study provides convergent evidence at the tissue, cellular, and molecular levels that curdione exerts potent anti-fibrotic and renoprotective effects by directly targeting Fblim1, thereby functionally suppressing the TGF-β1/Smad3 signaling cascade. These findings establish curdione as a promising natural therapeutic candidate for CKD.
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Huihui Wang,Baoping Xie,Shuotao Shi,Rong Zhang,Qi Liang,Zhongqiu Liu,Yuanyuan Cheng
Myocardial infarction (MI) is a common disease with high morbidity and mortality. Curdione is a sesquiterpenoid from Radix Curcumae . The current study is aimed to investigate the protective effect and mechanism of curdione on ferroptosis in MI. Isoproterenol (ISO) was used to induce MI injury in mice and H9c2 cells. Curdione was orally given to mice once daily for 7 days. Echocardiography, biochemical kits, and western blotting were performed on the markers of cardiac ferroptosis. Curdione at 50 and 100 mg/kg significantly alleviated ISO-induced myocardial injury. Curdione and ferrostatin-1 significantly attenuated ISO-induced H9c2 cell injury. Curdione effectively suppressed cardiac ferroptosis, evidenced by decreasing malondialdehyde and iron contents, and increasing glutathione (GSH) level, GSH peroxidase 4 (GPX4), and ferritin heavy chain 1 expression. Importantly, drug affinity responsive target stability, molecular docking, and surface plasmon resonance technologies elucidated the direct target Keap1 of curdione. Curdione disrupted the interaction between Keap1 and thioredoxin1 (Trx1) but enhanced the Trx1/GPX4 complex. In addition, curdione-derived protection against ISO-induced myocardial ferroptosis was blocked after overexpression of Keap1, while enhanced after Keap1 silence in H9c2 cells. These findings demonstrate that curdione inhibited ferroptosis in ISO-induced MI via regulating Keap1/Trx1/GPX4 signaling pathway.
研究领域:
药理学
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心脏病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2026
·
IF 3.4
Hao Yuan,Jianliang Li,Shoujun Chen,Hao Huang,Xuan Jia,Jialu Chen,Xiangyi Huang,Xiaojing Zhao,Xu Wang
To improve the extraction efficiency of hydrophobic bioactive compounds and reduce organic solvent consumption, a deep eutectic solvent-assisted magnetic nanoparticle (DES-MNPs) extraction method was developed for the determination of curdione in Curcuma wenyujin . Ethylene glycol/choline chloride (EG/ChCl) was employed as a hydrogen-bond-rich extraction medium, while dispersed magnetic nanoparticles were introduced to enhance mass transfer and enable rapid magnetic separation. Key extraction parameters were optimized using single-factor experiments combined with a Box-Behnken response surface design. Under the optimized conditions, the curdione concentration reached 0.125 mg/mL, representing a slightly higher yield (11.6%) compared with conventional ultrasound-assisted extraction using 70% ethanol. The improved extraction performance was attributed to the favorable solvation capability of the DES and the enhanced dispersion and mass transfer provided by the magnetic nanoparticles. The applicability of the developed method was further demonstrated through the bioactivity evaluation of the obtained extract, including antibacterial, anti-inflammatory, and antioxidant activities. Overall, this study presents an efficient and environmentally benign sample preparation strategy for the extraction and analysis of hydrophobic natural products from complex plant matrices.
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DOI
PubMed
高影响因子
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