Metabolomic Analysis of Stephania tetrandra–Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway

Xu, Baiyang; Yao, Mengxue; Liu, Zilu; Zhang, Shanshan; Wang, Bin; Han, Yanquan; Gao, Jiarong; Wu, Deling; Wang, Xiaoli

doi:10.3390/ph16010088

Cited by 3 publications

(1 citation statement)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Well-sliced vaginal tissues were dewaxed with xylene, rehydrated with gradient ethanol, and treated with sodium citrate buffer (10 mM, PH 6.0) for 20 min [42]. After cooldown to room temperature, the tissue was incubated in 3% hydrogen peroxide for 10 min to inactivate endogenous peroxidase.…”

Section: Ihcmentioning

confidence: 99%

Transcriptomics Reveals Effect of Pulsatilla Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling

Wu,

Li,

Wang

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes it effective is still unclear. Recent studies have shown that in cases of VVC, neutrophils recruited to the vagina, influenced by heparan sulfate (HS), do not successfully engulf Candida albicans (C. albicans). Instead, they release many inflammatory factors that cause damage to the vaginal mucosa. This study aims to understand the molecular mechanism by which the n-butanol extract of Pulsatilla decoction (BEPD) treats VVC through transcriptomics. High-performance liquid chromatography was used to identify the primary active components of BEPD. A VVC mouse model was induced using an estrogen-dependent method and the mice were treated daily with BEPD (20 mg/kg, 40 mg/kg, and 80 mg/kg) for seven days. The vaginal lavage fluid of the mice was analyzed for various experimental indices, including fungal morphology, fungal burden, degree of neutrophil infiltration, and cytokines. Various assessments were then performed on mouse vaginal tissues, including pathological assessment, immunohistochemistry, immunofluorescence, Western blot (WB), quantitative real-time PCR, and transcriptome assays. Our results showed that BEPD reduced vaginal redness and swelling, decreased white discharge, inhibited C. albicans hyphae formation, reduced neutrophil infiltration and fungal burden, and attenuated vaginal tissue damage compared with the VVC model group. The high-dose BEPD group even restored the damaged vaginal tissue to normal levels. The medium- and high-dose groups of BEPD also significantly reduced the levels of IL-1β, IL-6, TNF-α, and LDH. Additionally, transcriptomic results showed that BEPD regulated several chemokine (CXCL1, CXCL3, and CXCL5) and S100 alarmin (S100A8 and S100A9) genes, suggesting that BEPD may treat VVC by affecting chemokine- and alarmin-mediated neutrophil chemotaxis. Finally, we verified that BEPD protects the vaginal mucosa of VVC mice by inhibiting neutrophil recruitment and chemotaxis in an animal model of VVC via the TLR4/MyD88/NF-κB pathway. This study provides further evidence to elucidate the mechanism of BEPD treatment of VVC.

show abstract

Section: Ihcmentioning

confidence: 99%

Transcriptomics Reveals Effect of Pulsatilla Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling

Wu,

Li,

Wang

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

Metabolomics combined with network pharmacology reveals the protective effect of astragaloside IV on alcoholic liver disease

Hao,

Hu,

Zhao

et al. 2024

Phytomedicine

View full text Add to dashboard Cite

Multi-omics analysis to reveal the synergistic mechanism underlying the multiple ingredients of Stephania tetrandra extract on rheumatoid arthritis through the PI3K/Akt signaling pathway

Chen,

Zhang,

Nie

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

Background:Stephania tetrandra has been used for treating rheumatic diseases for thousands of years in rural areas of China. Several studies have found that tetrandrine and fangchinoline can inactivate the PI3K/Akt signaling pathway by reducing the expression and phosphorylation of AKT. However, the mechanism underlying the therapeutic actions of S. tetrandra on RA is not well known.Methods: In this study, we determined the molecular mechanism of the therapeutic effects of the multiple ingredients of S. tetrandra extract (STE) on collagen-induced arthritic (CIA) rats by integrating pharmacometabolomics, proteomics, and PTMomics.Results: In the multi-omics joint analysis, first, the expression signatures of proteins, PTMs, metabolites, and STE ingredients were profiled in CIA rats PBMCs that underwent STE treatment. Bioinformatics analysis were subsequently probed that STE mainly regulated tryptophan metabolism, inflammatory response, and cell adhesion pathways in CIA rats. The interrelated pathways were further constructed, and the findings revealed that STE attenuated the inflammatory response and proliferation of PBMCs in CIA rats by mediating the key targets of the PI3K/Akt pathway, including Hint1, ACP1, FGR, HSP90@157W + dioxidation, and Prkca@220N + 845.4540 Da. The rheumatic functions of Hint1 and ACP1 were further confirmed by applying a transcriptomic data of RA patients who clinically received abatacept therapy. Furthermore, a cross-ome correlation analysis was performed and major in vivo ingredients of STE, including coclaurine-N-glucuronide, Me,coclaurine-O-glc, N-gluA-schefferine, corydamine, corypamine, tetrandrine, and fangchiniline, were found to act on these targerts to inactivate the PI3K/Akt pathway.Conclusion: These results elucidated the molecular mechanism by which the ingredients of STE mediate the expression of the key targets in the PI3K/Akt pathway, leading to anti-rheumatic functions. The findings of this study provided new insights into the synergistic effect of STE against arthritis in rats.

show abstract

Metabolomic Analysis of Stephania tetrandra–Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway

Cited by 3 publications

References 44 publications

Transcriptomics Reveals Effect of Pulsatilla Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling

Transcriptomics Reveals Effect of Pulsatilla Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling

Metabolomics combined with network pharmacology reveals the protective effect of astragaloside IV on alcoholic liver disease

Multi-omics analysis to reveal the synergistic mechanism underlying the multiple ingredients of Stephania tetrandra extract on rheumatoid arthritis through the PI3K/Akt signaling pathway

Contact Info

Product

Resources

About