Wedelolactone: A molecule of interests

Ha, Nguyen Manh; Hợp, Nguyễn Quang; Son, Ninh The

doi:10.1016/j.fitote.2022.105355

Cited by 17 publications

(7 citation statements)

References 81 publications

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“…WDL is an inhibitor of IKK, a key kinase that activates NF-κB by mediating phosphorylation and degradation of IκBα. 26 Previous studies showed that WDL has strong anti-inflammatory and antioxidant abilities, 20 while the regulatory ability to B cell differentiation has never been reported, which needs to be researched further in the future.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide released from gut activates pyroptosis of macrophages via Caspase 11‐Gasdermin D pathway in systemic lupus erythematosus

Xin,

Gao,

Wang

et al. 2024

MedComm

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Noncanonical pyroptosis is triggered by Caspase 4/5/11, which cleaves Gasdermin D (GSDMD), leading to cell lysis. While GSDMD has been studied previously in systemic lupus erythematosus (SLE), the role of pyroptosis in SLE pathogenesis remains unclear and contentious, with limited understanding of Caspase 11‐mediated pyroptosis in this condition. In this study, we explored the level of Caspase 11‐mediated pyroptosis in SLE, identifying both the upstream pathways and the interaction between pyroptosis and adaptive immune responses. We observed increased Caspase 5/11 and GSDMD‐dependent pyroptosis in the macrophages/monocytes of both lupus patients and mice. We identified serum lipopolysaccharide (LPS), released from the gut due to a compromised gut barrier, as the signal that triggers Caspase 11 activation in MRL/lpr mice. We further discovered that pyroptotic macrophages promote the differentiation of mature B cells independently of T cells. Additionally, inhibiting Caspase 11 and preventing LPS leakage proved effective in improving lupus symptoms in MRL/lpr mice. These findings suggest that elevated serum LPS, resulting from a damaged gut barrier, induces Caspase 11/GSDMD‐mediated pyroptosis, which in turn promotes B cell differentiation and enhances autoimmune responses in SLE. Thus, targeting Caspase 11 could be a viable therapeutic strategy for SLE.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide released from gut activates pyroptosis of macrophages via Caspase 11‐Gasdermin D pathway in systemic lupus erythematosus

Xin,

Gao,

Wang

et al. 2024

MedComm

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“…OMT and matrine (MT) are both extracted from ginseng and have very similar structures; however, OMT contains more than one oxygen atom at carbon C-1. Additionally, they have similar anti-inflammatory and antitumor effects [ 37 , 38 ]. Previous studies have demonstrated that MT and RAPA synergistically enhance apoptosis by inhibiting Akt/mTOR signaling, thereby reducing the burden of acute myeloid leukemia in vivo [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Oxymatrine combined with rapamycin to attenuate acute cardiac allograft rejection

Lan,

Zhang,

Ren

et al. 2024

Heliyon

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“…Recent pharmacological research has revealed the diverse potential of Wedelolactone (WEL). It acts as an inhibitor of Na + -K + -ATPase and isomerase type II, which makes it promising for several applications, including liver protection, managing postmenopausal osteoporosis, immunosuppression, and potential anticancer properties [16]. WEL has demonstrated the ability to suppress caspase-11 expression induced by lipopolysaccharide (LPS) and induce apoptosis in prostate cancer cells by targeting protein kinase c epsilon (PKCϵ) [17].…”

Section: Discussionmentioning

confidence: 99%

Wedelolactone attenuates cerebral ischemia-reperfusion injury by blocking GPX4-mediated ferroptosis

2023

Journal of Men's Health

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Cerebral ischemia is currently the third leading cause of death worldwide. Among its complications, cerebral ischemia-reperfusion (I/R) is considered the most inevitable problem. To address this condition, there is a need for the development of more drugs. Wedelolactone, the main active chemical component extracted from dried lotus leaves, exhibits a wide range of pharmacological effects. Here we constructed an oxygen-glucose deprivation/reperfusion (OGD/R) model. Cell counting kit-8 (CCK-8) assays evaluated the impact of Wedelolactone on cell growth. Real-time quantitative polymerase chain reaction (RT-qPCR) assessed its effects on inflammation. We employed 2′,7′-Dichlorofluorescein (DCF) staining and an iron detection kit to measure ferroptosis. Flow cytometry (FCM) and immunoblot assays were utilized to investigate cell apoptosis. The results showed that Wedelactone promoted OGD-induced HT-22 cell viability and alleviated OGD/R-induced cellular inflammation, OGD/R-stimulated ferroptosis and OGD/R-induced apoptosis. Mechanically, Wedelactone inhibited OGD/R-stimulated ferroptosis via mediating glutathione peroxidase 4 (GPX4) expression. In conclusion, Wedelolactone may attenuate cerebral ischemia-reperfusion (CIR)/I by blocking GPX4-mediated ferroptosis.

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Wedelolactone: A molecule of interests

Cited by 17 publications

References 81 publications

Lipopolysaccharide released from gut activates pyroptosis of macrophages via Caspase 11‐Gasdermin D pathway in systemic lupus erythematosus

Lipopolysaccharide released from gut activates pyroptosis of macrophages via Caspase 11‐Gasdermin D pathway in systemic lupus erythematosus

Oxymatrine combined with rapamycin to attenuate acute cardiac allograft rejection

Wedelolactone attenuates cerebral ischemia-reperfusion injury by blocking GPX4-mediated ferroptosis

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