miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

Abstract

Oxidized low-density lipoprotein (ox-LdL)-induced vascular endothelial damage, oxidative stress and inflammation play a vital role in the pathophysiology of atherosclerosis. Geniposide is the primary active ingredient from Gardenia jasminoides Ellis associated with anti-oxidative properties and cardioprotective action. However, the therapeutic mechanism of geniposide in atherosclerosis remains unclear. Hence, the present study aimed to elucidate the underlying mechanisms of geniposide in oxidative stress and inflammatory response during ox-LdL injury in human umbilical vein endothelial cells (HUVEcs), focusing particularly on the microRNA (miR)-21/PTEN pathway. The results demonstrated that geniposide pretreatment significantly increased cell viability, decreased lactate dehydrogenase release, increased miR-21 level and decreased PTEN expression under ox-LdL condition. Subsequently, transfection with miR-21 mimic enhanced the protection of geniposide on ox-LdL-induced cytotoxicity and apoptosis (mediated by the upregulation of apoptotic rate and caspase-3 activity), whereas miR-21 inhibitor reversed these effects of geniposide. In addition, geniposide resulted in an anti-oxidant effect as evidenced by the decrease in reactive oxygen species generation, malondialdehyde content and NAdPH oxidase 2 expression, and the increase in superoxide dismutase, glutathione peroxidase and catalase activities in ox-LdL-treated HUVEcs, which were exacerbated by miR-21 mimic and reversed by miR-21 inhibitor. Furthermore, geniposide mitigated the ox-LdL-induced inflammatory response, demonstrated by a downregulation of pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) levels and an upregulation of anti-inflammatory cytokine (IL-10) level. However, miR-21 mimic enhanced, whereas miR-21 inhibitor attenuated, these effects of geniposide. In conclusion, the present results indicated that geniposide protects HUVEcs from ox-LdL injury by inhibiting oxidative stress and inflammation, and that these effects are partly due to the enhancement of the miR-21/PTEN pathway.

Geniposide inhibits proliferation and induces apoptosis of diffuse large B-cell lymphoma cells by inactivating the HCP5/miR-27b-3p/MET axis

“…The TLR4/MyD88/NF-κB pathway is regulated by geniposide in several human diseases, such as diabetic cognitive impairment [34], acute liver injury [35], and HCC [7]. Moreover, miR-21 [36], miR-373 [37], miR-214 [38] and miR-224 [8] are under the regulation of geniposide. Recently, several studies have demonstrated the correlation between geniposide treatment and lncRNAs [9,39,40].…”

Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS

“…Geniposide, a major iridoid compound extracted from the gardenia fruit, Gardenia jasminoides (Rubiaceae), is a traditional Chinese medicine with a broad spectrum of pharmacological activities, such as conferring protection against inflammatory injury and stress [ 222 ]. Recent studies have focused on the potential cardioprotective effects of geniposide, demonstrating that geniposide treatment reduces plaque size and alleviates atherosclerosis-associated inflammatory injury [ 223 ].…”

“…Recent studies have focused on the potential cardioprotective effects of geniposide, demonstrating that geniposide treatment reduces plaque size and alleviates atherosclerosis-associated inflammatory injury [ 223 ]. Geniposide attenuates endothelial injury and ROS generation by decreasing antioxidant enzyme activities, including SOD and CAT, which are directly associated with the enhancement of miR-21 expression in animal models of atherosclerosis [ 222 ]. The protective effect of geniposide on injured cardiomyocytes is also related to the upregulation of miR-145 expression [ 187 ].…”

The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

“…Genipin, a natural product derived from traditional Chinese medicine (TCM) Gardenia jasminoides , has shown anti-angiogenic, anti-proliferative, anti-inflammatory, and anticancer activities ( Jo et al, 2019 ; Zhang C. et al, 2020 ; Zhou et al, 2020 ). Kim et al (2020) have found that genipin can increase the expression of p53 and DRAM, induce apoptosis and autophagy, and enhance the sensitivity of AGS and MKN45 gastric cancer cell lines to OXA.…”