Protective effects of Asiatic acid against pelvic inflammatory disease in rats

Kong, Dejia; Fu, Ping; Zhang, Qin; Ma, Xuexiao; Jiang, Ping

doi:10.3892/etm.2019.7498

Cited by 13 publications

(13 citation statements)

References 30 publications

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“…Emerging evidence suggests that NLRP3 inflammasome activation occurs in endometritis cells, while inhibiting NLRP3 inflammasomes generates a significant ameliorative role in the pathological process of endometritis [27]. Moreover, the activation of the NLRP3 inflammasome aggravates the degree of inflammatory infiltration in gynecological diseases such as endometritis and pelvic inflammatory disease, which indicates that therapeutic interventions via the NLRP3 inflammasome may be a novel strategy for treating PD [28,29]. Therefore further investigation is warranted to explore the role of the NLRP3 inflammasome in PD.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

et al. 2020

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Background: Primary dysmenorrhea (PD) constitutes a common gynecological disease among young women. The NLRP3 inflammasome may be activated and expressed in PD, but the mechanistic link between NLRP3 inflammasome activation and PD is still unclear. Methods: To investigate the potential role of NLRP3 inflammasome activation in the pathogenesis of PD, 30 female Kunming mice without pregnancy were used for experiments. The PD mouse model was constructed by 11 days of successive co-treatment with estradiol and oxytocin. MCC950, a potent and specific small-molecule inhibitor of the NLRP3 inflammasome, was used to treat PD mice. The disease level was assessed by the writhing response and hot water tail-flick test. The levels of prostaglandin E 2 (PGE 2) and prostaglandin F 2 alpha (PGF 2α) in the uterine tissues of mice were detected by ELISA. The expression levels of protein and cytokines, including NLRP3, cysteine aspartic acid-specific protease 1 (caspase-1), interleukin (IL)-1β, IL-18, nuclear factor kappa B (NF-κB) p65, phospho-NF-κB p65, and cyclooxygenase-2 (COX-2) were revealed by western blot analysis. Results: MCC950 greatly ameliorated the writhing response induced by the combination of oxytocin and estradiol, with an increasing length of tail-flick latency. MCC950 also significantly decreased the levels of PGF 2α and PGE 2 , and the expressions of NLRP3, caspase-1, IL-1β, IL-18, phospho-NF-κB p65, NF-κB p65, and COX-2 in the uterus. Conclusions: MCC950 markedly alleviated the pain and pathological damage in PD mice by inhibiting NLRP3 activation. The underlying mechanism may be related to hypoactive uterine inflammation via suppression of NLRP3 activation and the NF-κB/COX-2/PG pathway in uteruses of PD mice.

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Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

et al. 2020

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“…Thus, it is reasonable that pretreatment with asiatic acid alone apparently reduced inflammatory haemorrhage in vivo. Additionally, a recent study reported the effect of asiatic acid on decreasing the inflammatory reaction in cancer [15] . Therefore, effects on vascular integrity may play a role in the beneficial effects of asiatic acid in patients with APL.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, treatment with ATRA combined with asiatic acid did not exhibit a similar effect. One explanation is that asiatic acid blocks the oxidative stress induced by ATO in vascular ECs [ 48 , 15 ]; consequently, the activation or apoptosis of ECs is inhibited. Another possibility is that ATO caused more apoptosis in APL cells [49] .…”

Section: Discussionmentioning

confidence: 99%

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Endothelial damage and a thin intercellular fibrin network promote haemorrhage in acute promyelocytic leukaemia

Wang

Zhou

et al. 2020

EBioMedicine

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Background The role of vascular endothelium in acute promyelocytic leukaemia (APL) remains unknown. We aimed to investigate the mechanisms by which APL cells interact with endothelial cells (ECs) and to further explore how the endothelium affects bleeding as well as therapeutic interventions. Method APL cells and an original APL cell line, NB4 cells, were used for experiments. The effects of leukaemic cells on ECs were analyzed in vitro and in vivo. Moreover, the endothelial barrier function and procoagulant activity were detected. An APL mouse model was established for in vivo studies. Findings APL cells interacted with ECs via ICAM-1 and VCAM-1 receptors to disrupt endothelial integrity. This binding activated MLCK signaling, resulting in the trans-endothelial passage of protein and red blood cells (RBCs). Combined treatment with asiatic acid or anti-adhesion receptor antibody inhibited the response of ECs to APL cells, thereby preventing APL-associated haemorrhage in vitro and in vivo. Activated ECs exhibited a procoagulant phenotype after phosphatidylserine exposure. Plasma from APL patients formed a thin fibrin network between procoagulant ECs, and this intercellular fibrin decreased the passage of albumin and RBCs. Ex vivo addition of fibrinogen further enhanced this barrier function in a dose-dependent manner. Interpretation Endothelial damage induced by leukaemic cell adherence promotes haemorrhaging in APL. Stabilization of ECs, decreasing adhesion receptor expression, and increasing fibrinogen transfusion levels may be a new therapeutic avenue to alleviate this fatal bleeding complication. Funding National Science Foundation of China (81670128, 81873433).

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“…Emerging evidence suggests that NLRP3 inflammasome activation occurs in endometritis cells, while inhibiting NLRP3 inflammasomes generates a significant ameliorative role in the pathological process of endometritis [19]. Moreover, the activation of the NLRP3 inflammasome aggravates the degree of inflammatory infiltration in gynecological diseases such as endometritis and pelvic inflammatory disease, which indicates that therapeutic interventions via the NLRP3 inflammasome may be a novel strategy for treating gynecological diseases [20,21]. However, the role of the NLRP3 inflammasome in PD is still obscure, so further investigation is warranted.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

Tang

Liu

Chen

et al. 2020

Preprint

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Background: Primary dysmenorrhea (PD) constitutes a common gynecological disease among young women. The NLRP3 inflammasome may be activated and expressed in PD, but the mechanistic link between NLRP3 inflammasome activation and PD is still unclear.Methods: To investigate the potential role of NLRP3 inflammasome activation in the pathogenesis of PD, thirty female Kunming mice without pregnancy were used for experiments. The PD mouse model was constructed by 11 days of successive co-treatment with estradiol and oxytocin. MCC950, a potent and specific small-molecule inhibitor of the NLRP3 inflammasome, was used to treat PD mice. The disease level was assessed by the writhing response and hot water tail-flick test. The levels of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2α) in the uterine tissues of mice were detected by ELISA. The expression levels of protein and cytokines, including NLRP3, cysteine aspartic acid-specific protease 1 (caspase-1), interleukin (IL)-1β, IL-18, nuclear factor kappa B (NF-κB) p65, phospho-NF-κB p65, and cyclooxygenase-2 (COX-2) were revealed by western blot analysis.Results: MCC950 greatly ameliorated the writhing response induced by the combination of oxytocin and estradiol, with an increasing length of tail-flick latency. MCC950 also significantly decreased the levels of PGF2α and PGE2, and the expressions of NLRP3, caspase-1, IL-1β, IL-18, phospho-NF-κB p65, NF-κB p65, and COX-2 in the uterus.Conclusions: MCC950 markedly alleviated the pain and pathological damage in PD mice by inhibiting NLRP3 activation. The underlying mechanism may be related to hypoactive uterine inflammation via suppression of NLRP3 activation and the NF-κB/COX-2/PG pathway in uteruses of PD mice.

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Protective effects of Asiatic acid against pelvic inflammatory disease in rats

Cited by 13 publications

References 30 publications

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

Endothelial damage and a thin intercellular fibrin network promote haemorrhage in acute promyelocytic leukaemia

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

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