Regulation effect of koumine on T-helper cell polarization in rheumatoid arthritis

Yang, Jian; Lin, Yarong; Xiong, Bojun; Chen, Ze-hong; Luo, Yufei; Xu, Ying; Su, Yanping; Huang, Huihui; Yu, Chang‐Xi

doi:10.1016/j.ejphar.2022.175387

Cited by 5 publications

(3 citation statements)

References 57 publications

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“…provided detailed elucidation of koumine’s mechanism of action, revealing its ability to effectively restore the balance of Th subsets and cytokine network systems by inhibiting T cell activation. This process leads to the modulation of Th subset polarization and downstream pro/anti-inflammatory cytokine imbalance, which proves beneficial in RA ( 36 ). Additionally, in thyroid tissue, the recruitment of T helper 1 (Th1) lymphocytes appears to be associated with heightened production of IFN-γ and tumor necrosis factor‐alpha (TNF‐α) ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Investigating the shared genetic architecture between hypothyroidism and rheumatoid arthritis

Peng,

Huang,

Tang

et al. 2024

Front. Immunol.

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BackgroundThere is still controversy regarding the relationship between hypothyroidism and rheumatoid arthritis (RA), and there has been a dearth of studies on this association. The purpose of our study was to explore the shared genetic architecture between hypothyroidism and RA.MethodsUsing public genome-wide association studies summary statistics of hypothyroidism and RA, we explored shared genetics between hypothyroidism and RA using linkage disequilibrium score regression, ρ-HESS, Pleiotropic analysis under a composite null hypothesis (PLACO), colocalization analysis, Multi-Trait Analysis of GWAS (MTAG), and transcriptome-wide association study (TWAS), and investigated causal associations using Mendelian randomization (MR).ResultsWe found a positive genetic association between hypothyroidism and RA, particularly in local genomic regions. Mendelian randomization analysis suggested a potential causal association of hypothyroidism with RA. Incorporating gene expression data, we observed that the genetic associations between hypothyroidism and RA were enriched in various tissues, including the spleen, lung, small intestine, adipose visceral, and blood. A comprehensive approach integrating PLACO, Bayesian colocalization analysis, MTAG, and TWAS, we successfully identified TYK2, IL2RA, and IRF5 as shared risk genes for both hypothyroidism and RA.ConclusionsOur investigation unveiled a shared genetic architecture between these two diseases, providing novel insights into the underlying biological mechanisms and establishing a foundation for more effective interventions.

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Section: Discussionmentioning

confidence: 99%

Investigating the shared genetic architecture between hypothyroidism and rheumatoid arthritis

Peng,

Huang,

Tang

et al. 2024

Front. Immunol.

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“…Two monomers, koumine and gelsemine, are often considered as the main components of pharmacological action in the traditional Gelsemium treatment (Figure 1). They have been shown to have analgesic, [16] anti‐inflammatory, [22,23] anti‐tumor, [24,25] and immunomodulatory functions [26] . These two alkaloids have also been shown to be the main therapeutic components of Gelsemium for psychiatric disorders, including anxiety and cognitive disorders [27,28] .…”

Section: Introductionmentioning

confidence: 99%

The antianxiety effects of koumine and gelsemine, two main active components in the traditional Chinese herbal medicine Gelsemium: A comprehensive review

Long,

Tang,

Zuo

et al. 2023

Brain-X

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The genus Gelsemium belongs to the family Loganiaceae, one of the traditional Chinese herbs. Gelsemium is traditionally used to treat rheumatoid and neuropathic pain. Its root extracts were found to protect against anxiety, especially the alkaloids koumine and gelsemine. Indeed, koumine and gelsemine can act as positive agonists of the glycine receptor (GlyR), which reduces neuronal excitability through chloride influx and can also increase neuroactive steroid content by enhancing 3alpha‐hydroxysteroid oxidoreductase (3α‐HSOR) expression. The latter can activate the excitation‐inhibitory response via the γ‐aminobutyric acid type A receptor (GABAAR), reduce the abnormal corticotropin‐releasing hormone (CRH) increase in the hypothalamus, inhibit adrenocorticotropic hormone (ACTH) secretion, and effectively inhibit the abnormal ACTH and corticosterone increases in the circulation. In addition, koumine and gelsemine inhibited the expression of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, inhibiting the release of inflammatory factors and regulating anxiety‐related neural circuits. Gelsemine also inhibited the overexpression of brain‐derived neurotrophic factor (BDNF) and cAMP response element‐binding protein (CREB) in the hypothalamus to maintain the plasticity of brain neurons and protect neurogenesis to achieve anxiety regulation. In general, this article reviews the recent studies on Gelsemium in the anxiety field, discusses its possible antianxiety mechanism, and confirms the potential of Gelsemium as a therapeutic drug for anxiety‐related diseases.

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“…10 Additionally, our group previously reported promising results indicating that gavage with KME could alleviate paw swelling, pain and joint inflammation in the collagen-induced arthritis (CIA) model, suggesting that KME has a significant therapeutic effect on RA. 11,12 The anti-inflammatory activity of KME has been patented in China (CN101015593A) and the United States (US9078890 B2). More importantly, we completed a preclinical study of KME and are in the process of submitting an IND application to the National Medical Products Administration (NMPA).…”

Section: Introductionmentioning

confidence: 99%

D-Optimal Design and Development of a Koumine-Loaded Microemulsion for Rheumatoid Arthritis Treatment: In vivo and in vitro Evaluation

Hu¹,

Fu²,

Dong³

et al. 2023

IJN

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Introduction: Koumine (KME) is the most abundant active ingredient separated from Gelsemium elegans Benth and exhibits a significant therapeutic effect on rheumatoid arthritis (RA). It is a lipophilic compound with poor aqueous solubility, and there is an urgent need to develop novel dosage forms of KME and promote its clinical application for the treatment of RA. The aim of this study was to design and develop KME-loaded microemulsions (KME-MEs) for the effective management of RA. Methods: The composition of the microemulsion was selected by carrying out a solubility study and generating pseudoternary phase diagrams, and further optimized by D-Optimal design. The optimized KME-MEs was evaluated for particle size, viscosity, drug release, storage stability, cytotoxicity, cellular uptake, Caco-2 cell transport and everted gut sac investigations. In vivo fluorescence imaging and the therapeutic effects of KME and KME-MEs on collagen-induced arthritis (CIA) rats were also evaluated. Results:The optimized microemulsion contained 8% oil, 32% S mix (surfactant/cosurfactant) and 60% water and was used for in vivo and in vitro studies. The optimal KME-MEs exhibited a small globule size of 18.5 ± 0.14 nm and good stability over 3 months, and the release kinetics followed a first-order model. These KME-MEs had no toxic effect on Caco-2 cells but were efficiently internalized into the cytoplasm. Compared to KME, the KME-MEs displayed significantly increased permeability and absorption in Caco-2 cell monolayer assay and ex vivo everted gut sac experiment. As expected, the KME-MEs attenuated the progression of RA in CIA rats and were more effective than free KME with a reduced frequency of administration. Conclusion:The KME-MEs improved the solubility and therapeutic efficacy of KME by employing formulation technology. These results provide a promising vehicle for the oral delivery of KME to treat RA and have attractive potential for clinical translation.

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Regulation effect of koumine on T-helper cell polarization in rheumatoid arthritis

Cited by 5 publications

References 57 publications

Investigating the shared genetic architecture between hypothyroidism and rheumatoid arthritis

Investigating the shared genetic architecture between hypothyroidism and rheumatoid arthritis

The antianxiety effects of koumine and gelsemine, two main active components in the traditional Chinese herbal medicine Gelsemium: A comprehensive review

D-Optimal Design and Development of a Koumine-Loaded Microemulsion for Rheumatoid Arthritis Treatment: In vivo and in vitro Evaluation

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