Dayun Sui

Acute cold exposure/rewarming (ACE/R) disrupts cardiovascular homeostasis and causes severe myocardial injury, yet effective countermeasures are scarce. Ginger-processed American ginseng (GPAG), a medicine-food homologous herb, exerts anti-inflammatory, antioxidant, and metabolic-regulatory effects; however, its cardioprotective mechanisms against ACE/R remain unclear. An ACE/R rat model was established by exposing rats to −15 °C for 6 h followed by 24 °C rewarming for 12 h, with 7-day GPAG gavage (1 and 2 g/kg) prior to cold exposure. Integrated multiomics, fecal microbiota transplantation (FMT), and fecal metabolite–cardiomyocyte intervention assays were employed to elucidate the gut-heart axis mechanism. GPAG ameliorated hemorheological disorders, restored cardiac dysfunction, and attenuated myocardial lesions. Mechanistically, GPAG remodels gut microbiota to generate functional metabolites that activate the myocardial AMPK/PGC-1α/PPARα pathway via the gut-heart axis, thereby optimizing cardiac energy metabolism and restoring mitochondrial homeostasis to alleviate ACE/R-triggered myocardial damage.

Myocardial ischemia-reperfusion (MI/R) injury occurs when coronary blood supply is impaired and then re-established, leading to additional injury to the myocardial tissue, including mitochondria oxidative stress and apoptosis. Ginsenoside Rc is one of the main protopanaxadiol-type saponins, and there has been relatively little research on it. Despite research confirming that ginsenoside Rc regulates mitochondrial functions, its potential benefits against MI/R injury have not been explored. In this study, we examined the protective effects of ginsenoside Rc in MI/R injury, along with its underlying mechanisms, using an in vitro H9c2 cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) and an in vivo rat model of MI/R injury. Prior to this, the H9c2 cells or rats were exposed to ginsenoside Rc with or without SIRT1 small interfering RNA (siRNA) or the selective SIRT1 inhibitor EX527. The results showed that after MI/R (or OGD/R) injury, ginsenoside Rc had a cardioprotective effect; improved cardiac function (or cell survival); reduced myocardial infarct size; decreased levels of creatine kinase-MB, cardiac troponin I, and lactate dehydrogenase (LDH) in the serum (or LDH release into culture medium); reduced cardiomyocyte apoptosis; and attenuated mitochondrial oxidative damage. Ginsenoside Rc pre-treatment also upregulated the anti-apoptotic protein Bcl-2 while downregulating the pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the cardioprotective effect of ginsenoside Rc was concomitant with upregulated SIRT1 expression and downregulated Ac-FOXO1 expression. SIRT1 siRNA or SIRT1 inhibitor EX527 abolished the cardioprotective effects of ginsenoside Rc by inhibiting the SIRT1 signaling pathway. In conclusion, our findings demonstrate that ginsenoside Rc ameliorated MI/R injury by reducing mitochondrial oxidative stress and apoptosis, at least in part, by activating SIRT1.

Ginsenoside Re (Re) is the main component of Zhenyuan Capsule (ZYC), which was wildly used in clinic in China for adjunctive treatment of coronary heart disease (CHD) and type II diabetes (T2DM). Nonalcoholic fatty liver disease (NAFLD) is one of the most important complications of T2DM, as well as an important risk factor of CHD. The aim of the present study was to investigate the effects of Re on NAFLD in db/db mice, one of the most recognized gene deficient animal models on T2DM. Sixteen db/db mice and sixteen wild-type mice were divided into four groups and orally administered Re or placebo in equal volume. According to the results, Re showed no obvious effect on blood glucose, lipids, or body weight of db/db mice. Histology pictures of hepatic tissue showed that Re did not improve steatosis, too. However, some evidence suggested that hepatic injury in db/db mice was attenuated by Re administering. Collagen deposition and aminotransferase elevation were significantly downregulated in the DB+Re group compared to those in the DB Group. The mechanisms of the protect effects of Re represented in db/db mice with NAFLD might be inhibiting oxidative stress and the reupregulation of peroxisome proliferator-activated receptor γ (pparγ) expression. The results of this study indicated that ZYC might be able to help T2DM patients with NAFLD to control the progress of NAFLD as an alternation of thiazolidinediones, synthetic agonists of PPARγ, whose side effects and adverse events should not be ignored.

The incidence of maternal hemorrhagic stroke is elevated in women with preeclampsia during pregnancy. Panax ginseng is a traditional medicinal herb with numerous applications, and ginsenosides are the key bioactive compounds in Panax ginseng. This study aims to evaluate the effects of ginsenoside Rg2 on pregnancy outcomes and brain injury after intracerebral hemorrhage (ICH) in a rat model of preeclampsia. Preeclampsia was induced in rats by N(ω)-nitro-L-arginine methyl ester. Then, an ICH model was prepared by intrastriatal injection of bacterial collagenase. Ginsenoside Rg2 markedly elevated the survival ratio of fetuses. The placental and body weights were increased in the ginsenoside Rg2 group. Compared with the preeclampsia group, the Garcia test score of ginsenoside Rg2–treated rats was significantly increased. Ginsenoside Rg2 treatment ameliorated the ICH-induced augmentation of Evans blue extravasation, inhibited the ICH-induced elevation of brain water content, and reduced the interleukin-1β and tumor necrosis factor-α levels in the hemorrhagic hemisphere after ICH in preeclampsia model rats. Furthermore, ginsenoside Rg2 treatment not only inhibited augmentation of TLR-4, MyD88, p-IκBα, and p-NF-κB expression but also abated the reduction of occludin and claudin-5 expression in the hemorrhagic hemisphere. The findings indicated that ginsenoside Rg2 improved pregnancy outcomes in a rat model of preeclampsia without decreasing the blood pressure and urine protein level. The findings also demonstrated that ginsenoside Rg2 ameliorated ICH-induced neurological disorder and blood–brain barrier dysfunction in an animal model of preeclampsia by regulating the TLR4/NF-κB signaling pathway.

Ginsenoside Rc is one of the cardinal bioactive components of Panax ginseng . The present study aimed to investigate whether ginsenoside Rc exerted protective effects against acute cold exposure‐induced myocardial injury in rats. Forty rats were randomly assigned into four groups: Control, model, ginsenoside Rc 10 mg/kg, and 20 mg/kg groups. Rats were intragastrically administrated with ginsenoside Rc (10, 20 mg/kg) or vehicle daily for 7 days. On the seventh day, all rats except the control group were exposed to low temperature. Cardiac function, myocardial enzyme activities, hemorheology, and inflammatory response were detected. Histopathological examination and apoptosis of cardiac tissues were performed. The expressions of silent information regulator 1 (SIRT1), B‐cell lymphoma (Bcl‐2), Bcl‐2‐associated X (Bax), procaspase‐3, and the mRNA (messenger RNA) level of SIRT1 were measured by western blot and real‐time quantitative polymerase chain reaction (PCR) analysis. Ginsenoside Rc significantly improved cardiac function, diminished the activities of lactate dehydrogenase (LDH), aspartate aminotransferase, and creatine kinase isoenzyme (CK‐MB), and regulated abnormal hemorheology in acute cold‐exposed rats ( p < 0.05 or p < 0.01). Furthermore, ginsenoside Rc could attenuate myocardial histological changes and structural abnormalities, decrease apoptotic cells and reduce the mRNA levels and activity of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 ( p < 0.01). In addition, ginsenoside Rc upregulated the expressions of SIRT1, Bcl‐2, and procaspase‐3 and downregulated that of Bax ( p < 0.01). The changes in both the mRNA and protein expression levels of SIRT1 were similar. The results of the current study suggested that ginsenoside Rc could alleviate acute cold exposure‐induced myocardial injury in rats by inhibiting cardiomyocyte apoptosis via regulating SIRT1 expression and attenuating the inflammatory responses. Practical Application: The current study indicated that ginsenoside Rc could alleviate acute cold exposure‐induced myocardial injury in rats. Ginsenoside Rc could be potentially used as a bioactive ingredient in processed functional food products or food supplements to prevent from acute cold exposure‐induced myocardial injury.

Type 2 diabetes mellitus (T2DM) is a major health concern which may cause cardiovascular complications. Insulin resistance (IR), regarded as a hallmark of T2DM, is characterized by endothelial dysfunction. Ginsenoside Rc is one of the main protopanaxadiol-type saponins with relatively less research on it. Despite researches confirming the potent anti-inflammatory and antioxidant activities of ginsenoside Rc, the potential benefits of ginsenoside Rc against vascular complications have not been explored. In the present study, we investigated the effects of ginsenoside Rc on endothelial IR and endothelial dysfunction with its underlying mechanisms using high glucose- (HG-) cultured human umbilical vein endothelial cells (HUVECs) in vitro and a type 2 diabetic model of db/db mice in vivo. The results showed that ginsenoside Rc corrected the imbalance of vasomotor factors, reduced the production of Ang (angiotensin) II, and activated angiotensin-converting enzyme 2 (ACE2)/Ang-(1–7)/Mas axis in HG-treated HUVECs. Besides, ginsenoside Rc improved the impaired insulin signaling pathway and repressed oxidative stress and inflammatory pathways which constitute key factors leading to IR. Interestingly, the effects of ginsenoside Rc on HG-induced HUVECs were abolished by the selective ACE2 inhibitor MLN-4760. Furthermore, ginsenoside Rc exhibited anti-inflammatory as well as antioxidant properties and ameliorated endothelial dysfunction via upregulation of ACE2 in db/db mice, which were confirmed by the application of MLN-4760. In conclusion, our findings reveal a novel action of ginsenoside Rc and demonstrate that ginsenoside Rc ameliorated endothelial IR and endothelial dysfunction, at least in part, via upregulation of ACE2 and holds promise for the treatment of diabetic vascular complications.

Panax ginseng is a traditional medicine used in China to treat many diseases. Polysaccharides are primary active components and have many pharmacological effects. Gastric ulcer is a serious gastrointestinal disease. However, whether polysaccharides influence gastric ulcers is unclear. In this study, the effective gastroprotective impacts and potential mechanisms of Panax ginseng polysaccharides (GPS) on gastric damage induced by ethanol in rats were investigated by macroscopically evaluating gastric mucosal injuries (improved ulcer index (UI)), histopathological staining (H&E and PAS), increased NO and PGE2 levels, and suppression of oxidative stress (increased superoxide dismutase (SOD) and catalase (CAT) and decreased malondialdehyde (MDA)) and inflammation (reduced tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and myeloperoxidase (MPO)). Pretreatment with GPS ameliorated the expression of I-κB/NF-κB and JAK/STAT proteins in the rat stomach exposed to ethanol. The results indicated that GPS prevent ethanol-induced gastric injuries in rats by predominantly suppressing gastric inflammation and oxidative stress through NF-κB and STAT inhibition.

At present, many patients who undergo reperfusion immediately after percutaneous coronary intervention will undergo microvascular obstruction and reduction in myocardial blood flow. This phenomenon is called “no-reflow (NR),” and there is still no effective therapy for NR. Studies showed Panax quinquefolius L. saponins (PQS) have effect on MI/R injury, while the effect and mechanism of PQS on MI/R induced NR are not clear. In this study, we established a MI/R model to investigate whether PQS decrease NR phenomenon via suppression of inflammation. We found that PQS significantly alleviated the symptoms of NR by reducing ischemia, infarction, and NR area; improving cardiac function; preventing pathological morphology changes of myocardium; depressing leukocytes’ aggregation and adhesion; and suppressing the excessive inflammation. Further study demonstrated that PQS remarkably inhibited TLR4, MyD88, p-NF-κB, and NLRP3 inflammasome-associated protein, and these effects could be reversed by LPS. These results indicated that PQS may protect NR by inhibiting the activation of NLRP3 inflammasome via TLR4/MyD88/NF-κB signaling pathway in part, suggesting that PQS exist potential in preventing NR induced by MI/R.

Colorectal carcinoma (CRC) recurrence is often accompanied by metastasis. Most metastasis undergo through epithelial‐mesenchymal transition (EMT). Studies showed that retinol X receptor alpha (RXRα) and 20(S)‐Protopanaxadiol (PPD) have anti‐tumour effects. However, the anti‐metastasis effect of 20(S)‐PPD and the effect of RXRα on EMT‐induced metastasis are few studies on. Therefore, the role of RXRα and 20(S)‐PPD in CRC cell metastasis remains to be fully elucidated. RXRα with clinicopathological characteristics and EMT‐related expression in clinical samples were examined. Then, RXRα and EMT level in SW480 and SW620 cells, overexpressed and silenced RXRα in SW620 cells and SW480 cells, respectively, were evaluated. Finally, 20(S)‐PPD effect on SW620 and SW480 cells was evaluated. The results showed that a lower RXRα expression in cancer tissues, and a moderate negative correlation between RXRα and N stage, and tended to higher level of EMT. SW480 and SW620 cells had the highest and lowest RXRα expression among four CRC cell lines. SW480 had lower EMT level than SW620. Furthermore, 20(S)‐PPD increased RXRα and inhibited EMT level in SW620 cell. Finally, 20(S)‐PPD cannot restore SW480 cells EMT level to normal when RXRα silencing. These findings suggest that 20(S)‐PPD may inhibit EMT process in CRC cells by regulating RXRα expression.