Potential Cardioprotective Effect of Genipin via Cyclooxidase 2 Suppression and P53 Signal Pathway Attenuation in Induced Myocardial Infarction in Rats

Zhao, Ling; Lu, Hui; Li, Xiafei; Liu, Tian; Pan, Yuxue; Du, Pengchong

doi:10.1097/shk.0000000000002001

Cited by 2 publications

(1 citation statement)

References 37 publications

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“…This bioactive plant component has significant anti-inflammatory effects (7). A previous study found that genipin, which is an iridoid produced from geniposide, exerted cardioprotective effects (8). Nevertheless, whether geniposide is involved in the development of sepsis is not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

GENIPOSIDE IMPROVES CLP-INDUCED SEPSIS MODEL PROGNOSIS BY UPREGULATING PPARγ TO MODULATE MONOCYTE PHENOTYPE AND CYTOKINE NETWORK

Zhang,

He,

Ding

et al. 2023

Shock

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Background We explored the efficacy and main biological mechanism of geniposide intervention in sepsis. Methods A sepsis model was established in male BALB/c mice through cecal ligation and puncture (CLP). Different doses of geniposide (20 or 40 mg/kg) were administered intravenously at 0 and/or 24 h after CLP surgery. The survival rate of different groups was observed. Additionally, the expression levels of CD16 and MHC-II in monocytes were assessed using flow cytometry. The concentration of TNF-α, IL-1β, IL-6, and IL-10 in the serum were measured by ELISA. We also observed the biological effects of geniposide on CD16 and MHC-II expression levels in RAW264.7 cells, as well as the secretion of TNF-α, IL-1β, IL-6, and IL-10, in the LPS-induced RAW264.7 cell model. The PPARγ levels were determined using western blot analysis. Results Intravenous administration of 40 mg/kg of geniposide at 0 h after CLP significantly improved the survival outcomes in the septic mouse model, with no significant benefits from low dosing (20 mg/kg) or delayed administration (24 h). The effective dose of geniposide significantly decreased the serum cytokine TNF-α, IL-1β, IL-6, and IL-10 concentrations in septic mice (P < 0.05). Notably, in vitro assays showed that geniposide specifically increased the IL-10 level. Geniposide significantly reduced the CD16 expression (P < 0.05) and increased MHC-II expression in monocytes (P < 0.05). Additionally, geniposide elevated the PPARγ level in monocytes (P < 0.05). Conclusions High-dose early-stage geniposide administration significantly improved the survival rate in a CLP mouse sepsis model by modulating the monocyte phenotype and regulating the cytokine network (IL-6/IL-10 levels). The pharmacological mechanism of geniposide action might be exerted primarily through PPARγ upregulation.

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Section: Introductionmentioning

confidence: 99%