Cardioprotective effects of gypenoside XVII against ischemia/reperfusion injury: Role of endoplasmic reticulum stress, autophagy, and mitochondrial fusion fission balance

Abstract

Gypenoside XVII (GP‐17), a tetracyclic triterpene saponin isolated from the functional food Gynostemma pentaphyllum, has been demonstrated protective effects against cerebrovascular and cardiovascular diseases on multiple disease models. In this study, we established a myocardial infarction (MI) model by ligating the left anterior descending coronary artery, and explored whether GP‐17 prevent myocardial ischemia/reperfusion (I/R) injuries in mice. Compared with the I/R group, GP‐17 significantly improved the cardiac function, reduced the MI, decreased myocardial pathology, activated superoxide dismutase and catalase, and reduced the content of lactate dehydrogenase, creatine kinase, malondialdehyde, and inflammatory factor. The proteomic analysis showed multiple differential proteins between the GP‐17 and I/R groups enriched in endoplasmic reticulum and mitochondria. Western‐Blot showed that GP‐17 significantly decreased the expression of GRP78, ATF6, CHOP, and phosphorylation of PERK, indicating the inhibition of ERS. GP‐17 inhibited the expression of ATG5, LC3A/B, and BAX, illustrating the suppression of autophagy and apoptosis. Moreover, both GP‐17 and 4‐PBA could improve the downregulated Mfn2, meaning that inhibition of ERS regulated the mitochondrial fusion fission balance, thus protected the function of mitochondria. In conclusion, we found that GP‐17 prevented against myocardial I/R injury by inhibit ERS‐induced cell apoptosis, autophagy, oxidative stress, and mitochondrial division.

Effect and possible mechanisms of saponins in Chinese herbal medicine exerts for the treatment of myocardial ischemia-reperfusion injury in experimental animal: a systematic review and meta-analysis

“…Many of these drugs and therapies have been tested today and have proven superior efficacy ( 33 ). Recently, some studies found that saponins from TCM can protect against myocardial ischemia-reperfusion injury through various mechanisms ( 4 , 34 – 36 ).…”

“…Five articles did not report infarct size as mentioned in the inclusion criteria, three lacked a placebo group, and three used saponin conversion products as an intervention. Finally, 17 studies of 386 animals (254 in the saponin treatment group and 132 in the control group) met the predetermined inclusion criteria and were eventually included in our meta-analysis (Figure 1) (4,5,10,13,17,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Table 1 shows comprehensive information for each study.…”

“…Recently, researchers have begun to focus on ferroptosis, apoptosis, and autophagy during MIRI. Several drug and non-drug therapies have emerged to treat I/R injury ( 4 ). However, given that treatments targeting I/R injury would be used only once in most patients, their development, compared to drugs that require longer-term use, is at an obvious disadvantage.…”

Exploring the protective effects of herbal monomers against diabetic retinopathy based on the regulation of autophagy and apoptosis: A review

“…So arjunolic acid and Gyp-17 have a role as a metabolite and an antioxidant. [88,103,104] 3.6. Alkaloids 3.6.1.…”

Gypenoside XVII Reduces Synaptic Glutamate Release and Protects against Excitotoxic Injury in Rats

“…Gypenoside XVII (GP-17; molecular formula: C 48 H 82 O 18 ; molecular weight: 947.2 g/mol; Figure 1A) is a gypenoside monomer found in medicinal plants such as Gynostemma pentaphyllum or Panax notoginseng. Several experimental studies have reported various pharmacological properties to GP-17, including immunoregulatory, anti-inflammatory, neuroprotective, cardioprotective, lipid-lowering, and neuroprotective effects [11][12][13][14][15][16]. Regarding its neuroprotective effect, GP-17 attenuated cerebral infarct volume and alleviated neurological dysfunction in a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model [17].…”