Ginsenoside Rh2 Inhibits NLRP3 Inflammasome Activation and Improves Exosomes to Alleviate Hypoxia-Induced Myocardial Injury

Abstract

The inflammatory microenvironment after acute myocardial infarction (MI) is a key limiting factor in the clinical application of stem cell transplantation and paracrine exosome therapy. Qishen Yiqi Pills contain a saponin ingredient called Ginsenoside Rh2 (Rh2) which exhibits a certain therapeutic effect on MI. However, the mechanism by which Rh2 alleviates the inflammatory microenvironment and improves the therapeutic efficiency of exosomes remains enigmatic. Here, we found that Rh2 attenuated the adverse effect of oxygen-glucose deprivation (OGD)-induced cellular injury, an in vitro pathological model of MI. Confocal microscopy revealed that DiI-labeled BMSCs-derived exosomes exhibited an increased homing ability of cardiomyocytes, which, in turn, inhibited the nuclear translocation of NF-κB p65 and NLRP3 inflammasome activation, thereby alleviating the inflammatory microenvironment and further facilitating the homing of exosomes to cardiomyocytes by forming a feed-forward enhancement loop. Additionally, we found that Rh2 could regulate the HMGB1/NF-κB signaling pathway to improve the OGD environment of cardiomyocytes, increasing the efficiency of the feed-forward loop. In conclusion, we found that Rh2 can improve the inflammatory microenvironment by enhancing the protection of exosomes against myocardial injury, providing new insights into the indirect modification of exosomes by Rh2 in MI treatment.

A four-compound remedy AGILe protected H9c2 cardiomyocytes against oxygen glucose deprivation via targeting the TNF-α/NF-κB pathway: Implications for the therapy of myocardial infarction

“…The present study found that adenosine mainly targeted PLCG1 in the NF-κB pathway (Figure 5A). Fourthly, ginsenoside Rh2 could inhibit NLRP3 inflammasome activation and alleviate hypoxia-induced myocardial injury possibly through the inhibition of NF-kB signaling (Lian et al, 2013;Yi et al, 2013;Qi et al, 2022). We could not exclude the importance of other chemical compounds in the cardioprotection and the regulation of the TNF-α/NF-κB pathway.…”

“…By normalizing against the concentrations of the corresponding standard compounds (Figure 6B), the concentrations of four compounds in BYDE were calculated as follows: adenosine, 317.81 ± 3.83 ng/g; ginsenoside Rh2, 7,941.13 ± 1750.79 ng/g; iso-liquiritigenin, 2,326.03 ± .86 ng/g; licochalcone A, 10,100.51 ± 623.85 ng/g (n = 3; mean ± SD). Based on these results, four active compounds (i.e., adenosine, ginsenoside Rh2, isoliquiritigenin, licochalcone A) were combined at the same ratio as that in BYDE to form the mixture AGILe while the concentration was normalized to the biologically effective concentration of ginsenoside Rh2 (Qi et al, 2022).…”

Observing Extracellular Vesicles Originating from Endothelial Cells in Vivo Demonstrates Improved Astrocyte Function Following Ischemic Stroke via Aggregation-Induced Emission Luminogens

“…The lipophilic fluorescent trackers DiI and PKH-67 are the most commonly used commercial dyes for tracking EVs. , We concluded that compared with commercial dyes, TTCP had a higher labeling efficiency and a better long-term tracking effect. In addition, PKH-67 could affect the size of EVs, with all dye-labeled EVs showing a significant increase in size, which may hinder EVs from penetrating the blood–brain barrier .…”

Ginsenosides from Panax ginseng as Key Modulators of NF-κB Signaling Are Powerful Anti-Inflammatory and Anticancer Agents

“…Extracellular HMGB1 binds to the receptor for advanced glycation end products (RAGEs) or TLRs, promoting PAMP/DAMP-induced inflammation [ 99 ]. Ginsenoside Rh2 blocks the expression of HMGB1 in an H9C2 rat heart myoblast cell line, which was upregulated through oxygen-glucose deprivation [ 100 ]. This eventually triggers the inhibition of NF-κB subunit translocation to the nucleus and NLPR3 inflammasome activation.…”