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Ginsenoside Rb1 (Rb1) is a biologically active component of ginseng [This study determined the underlying mechanisms of Rb1 treatment that acted on diabetes-injured lungs in diabetic rats.Streptozotocin (STZ)-induced diabetic rat model was used. Male Sprague-Dawley (SD) rats were divided into four groups (There was decreased activity of SOD (3.53-fold), CAT (2.55-fold) and GSH (1.63-fold) and increased levels of NO (4.47-fold) and MDA (3.86-fold) in the diabetic group from control. Rb1 treatment increased SOD (2.4-fold), CAT (1.9-fold) and GSH (1.29-fold) and decreased the levels of NO (1.76-fold) and MDA (1.51-fold) as compared with diabetic rats. The expression of IL-6 (5.13-fold), IL-1α (2.35-fold), TNF-α (2.35-fold) and TGF-β (2.39-fold) was increased in diabetic rats from control. IL-6 (2.43-fold), IL-1α (2.27-fold), TNF-α (1.68-fold) and TGF-β (2.3-fold) were decreased in the Rb1 treatment group. Diabetes increased the apoptosis rate (2.23-fold vs. control), and Rb1 treatment decreased the apoptosis rate (1.73-fold vs. the diabetic rats). Rb1 and insulin ameliorated lung tissue injury.These findings indicate that Rb1 could be useful for mitigating oxidative damage and inflammatory infiltration in the diabetic lung.

Alcoholic liver disease (ALD) is a serious worldwide health problem. Ginsenoside Rc is a major active ingredient isolated from

Acute myocardial infarction (AMI) leads to anoxia and ischemia of cardiomyocytes, followed by apoptosis. This study investigated the protective effect of ginsenoside Rg1 (Rg1) on myocardial ischemia injury in rats with AMI. Rats were randomly divided into five groups: group A (blank control group), group B (hypoxia/reoxygenation group), group C (hypoxia/reoxygenation + 10 mg/L Rg1), group D (hypoxia/reoxygenation + 20 mg/L Rg1) and group E (hypoxia/reoxygenation + 40 mg/L Rg1). The survival rate, apoptosis rate, expression of cyclin-dependent kinase 4 (CDK4), fibroblast growth factor 9 (FGF9), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), microvessel density and myocardial infarction area of rats in each group were compared. The expressions of CDK4 and FGF9, the contents of SOD and GSH-Px in groups C, D and E injected with Rg1 were significantly promoted compared to group B without Rg1 injection (P lt; 0.05). The survival rate of myocardial cells was significantly increased while the apoptosis rate was significantly decreased in group C, D, E compared to group B (P lt; 0.05). On the 3rd, 7th and 10th day following Rg1 treatment, the infarct area of E group was significantly decreased in three groups C, D, E, and the microvessel density of infarct area was significantly increased compared with group B (P lt; 0.05). So, Rg1 can improve the survival rate of myocardial cells, reduce the apoptosis rate and the area of myocardial infarction, and increase the microvessel density of infarct area, thus playing a protective role in ischemic myocardial cells of AMI rats.

Cardiac fibrosis is a common precursor of ventricular dysfunction and heart failure. We investigated the role of oxidative stress in myocardial fibrosis and the protective effect of panaxatriol saponin (PTS) against myocardial infarction (MI)-induced cardiac fibrosis and explored the underlying mechanisms. In vitro, cell viability was tested using a cell counting kit. The reactive oxygen species (ROS) levels including hydrogen peroxide (H

Ischemic stroke, the most common type of stroke, can lead to a long-term disability with the limitation of effective therapeutic approaches. Ginsenoside-Rd (G-Rd) has been found as a neuroprotective agent. In order to investigate and discuss the neuroprotective function and underlying mechanism of G-Rd in experimental animal models following cerebral ischemic/reperfusion (I/R) injury, PubMed, Embase, SinoMed, and China National Knowledge Infrastructure were searched from their inception dates to May 2022, with no language restriction. Studies that G-Rd was used to treat cerebral I/R damage in vivo were selected. A total of 18 articles were included in this paper, and it was showed that after cerebral I/R damage, G-Rd administration could significantly attenuate infarct volume (19 studies, SMD = − 1.75 − 2.21 to − 1.30 , P < 0.00001 ). Subgroup analysis concluded that G-Rd at the moderate doses of >10- SMD = − 1.50 − 2.00 to − 1.00 , P < 0.00001 ; higher score means better recovery: 8 studies, SMD = 1.57 0.93 to 2.21 , P < 0.00001 ). In addition, this review suggested that G-Rd in vivo can antagonize the reduced oxidative stress, regulate Ca2+, and inhibit inflammatory, resistance to apoptosis, and antipyroptosis on cerebral I/R damage. Collectively, G-Rd is a promising natural neuroprotective agent on cerebral I/R injury with unique advantages and a clear mechanism of action. More clinical randomized, blind-controlled trials are also needed to confirm the neuroprotective effect of G-Rd on cerebral I/R injury.

Diabetes-associated liver injury becomes a dominant hepatopathy, leading to hepatic failure worldwide. The current study was designed to evaluate the ameliorative effects of ginsenoside Rh1 (G-Rh1) on liver injury induced by T2DM. A T2DM model was established using C57BL/6 mice through feeding with HFD followed by injection with streptozotocin at 100 mg·kg

Gastric cancer (GC) is one of the most prevalent malignancies of the digestive tract. Ginsenoside Rh1 was reported to exert effects on GC. The current study set out to explore the mechanism underlying Ginsenoside Rh1 effects on GC. With oxaliplatin (OXA) serving as the positive control, human GC cells AGS were treated with 0, 10, 25, 50, 74, or 100 μM of ginsenoside Rh1 for 48 h. Proliferation, migration, invasion, and apoptosis were subsequently assessed by means of MTT, scratch test, Transwell, and TUNEL, respectively. AGS cells were further jointly treated with Rh1 and the TGF-β/Smad pathway activator Kartogenin, followed by detection of TGF-β/Smad pathway effects on AGS biological behaviours. Moreover, TGF-β/Smad pathway activation was detected with a Western blot assay. Furthermore, xenograft tumour models were established and tumour growth was recorded. Ki-67 expression patterns and apoptosis were detected with immunohistochemistry and TUNEL, respectively. In vitro, Ginsenoside Rh1 repressed AGS cell proliferation, migration, and invasion, and further promoted apoptosis, with a concentration of 50 μM Rh1 exerting the equivalent effects as OXA. In vivo, Ginsenoside Rh1 inhibited GC proliferation and induced tumour cell apoptosis. Mechanistically, Ginsenoside Rh1 reduced TGF-β1 and TGF-β2 levels and Smad2 and Smad3 phosphorylation levels. Collectively, our findings highlighted that ginsenoside Rh1 inhibited GC cell growth and tumour growth in xenograft tumour models via inhibition of the TGF-β/Smad pathway.

Ginseng is known to possess anti-aging potential. Klotho mutant mice exhibit phenotypes that resemble the phenotype of the human aging process. Similar to Klotho deficient mice, patients with chronic kidney disease (CKD) suffer vascular damage and cognitive impairment, which might upregulate the angiotensin II AT1 receptor. Since AT1 receptor expression was more pronounced than endothelin ET-1 expression in the hippocampus of aged Klotho deficient (±) mice, we focused on the AT1 receptor in this study. Ginsenoside Re (GRe), but not ginsenoside Rb1 (GRb1), significantly attenuated the increase in AT1 receptor expression in aged Klotho deficient mice. Both GRe and the AT1 receptor antagonist losartan failed to attenuate the decrease in phosphorylation of JAK2/STAT3 in aged Klotho deficient (±) mice but significantly activated nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling. Both GRe and losartan attenuated the increased NADPH oxidase (NOX) activity and reactive oxygen species (ROS) in aged Klotho deficient mice. Furthermore, of all the antioxidant enzymes, GRe significantly increased glutathione peroxidase (GPx) activity. GRe significantly attenuated the reduced phosphorylation of ERK and CREB in GPx-1 knockout mice; however, genetic overexpression of GPx-1 did not significantly affect them in aged mice. Klotho-, Nrf2-, and GPx-1-immunoreactivities were co-localized in the same cells of the hippocampus in aged Klotho wild-type mice. Both the GPx inhibitor mercaptosuccinate and Nrf2 inhibitor brusatol counteracted the effects of GRe on all neurobehavioral impairments in aged Klotho deficient (±) mice. Our results suggest that GRe attenuates all alterations, such as AT1 receptor expression, NOX-, ROS-, and GPx-levels, and cognitive dysfunction in aged Klotho deficient (±) mice via upregulation of Nrf2/GPx-1/ERK/CREB signaling.

Tingyao Zhao,1,&ast; Xinting Wang,2,&ast; Qian Liu,2 Tianshu Yang,1 Huiyan Qu,1 Hua Zhou2 1Department of Cardiovascular Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Zhou; Huiyan Qu, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 528, Zhangheng Road, Pudong New Area, Shanghai, 201203, People’s Republic of China, Email zhouhua@shutcm.edu.cn; 1520043084@qq.comAbstract: Purpose: This study aimed to elucidate the potential molecular mechanisms by which GSRd improves cardiac inflammation and immune environment after MI.Materials and Methods: The potential target genes of GSRd were predicted using the STITCH database. In vivo, MI mice models were established by left anterior descending ligation and were divided into the sham group, MI + Vehicle group, and MI + GSRd group. DMSO, DMSO, and GSRd 50 μL/day were intraperitoneally injected, respectively. After 28 days, echocardiography, Masson staining, immunofluorescence staining, flow cytometry, RT-PCR, and Western blot were performed. Mice peritoneal macrophages were extracted in vitro, and Western blot was performed after GSRd and/or Akt inhibitor MK2206 intervention.Results: GSRd significantly improved mouse myocardial function, attenuated cardiac fibrosis, and inhibited inflammation and apoptosis in myocardial tissues after myocardial infarction. Meanwhile, GSRd increased non-classical Ly6Clow Mos/Mps while reduced of classical Ly6Chigh Mos/Mps at the same time in myocardial tissues. In addition, GSRd significantly reversed the activity of p-Akt and p-mTOR in the heart Mos/Mps after MI. In vitro studies showed that the activity of p-Akt and p-mTOR in peritoneal macrophages were significantly increased in a dose-dependent manner after GSRd treatment. Furthermore, the AKT inhibitor MK2206 was found to block the enhanced activity of p-Akt and p-mTOR induced by GSRd in peritoneal macrophages.Conclusion: GSRd can enhance the transformation of Ly6Chigh Mos/Mps to Ly6Clow Mos/Mps in mice after MI by activating the Akt/mTOR signaling pathway, inhibiting cardiac dysfunction and promoting cardiac repair.Keywords: myocardial infarction, ginsenoside rd, monocytes/macrophages, Akt/mTOR

In this study, we evaluated gender differences in PD excretion, tissue distribution, and metabolism in rats. In addition, we also evaluated its anti-inflammatory activity and mechanism. The results showed that the concentrations of PD in the stomach, small intestine, and large intestine were the highest. The

Paraquat (PQ), as a widely used herbicide, is highly toxic to human. PQ-induced pulmonary fibrosis is the main reason for respiratory failure and death. In PQ-poisoned mice, we find abundant senescent epithelial cells in the lung tissues, which can contribute to the activation of pulmonary fibroblasts. Ginsenoside Rg1 (Rg1), the main active component of ginseng, possess beneficial properties against aging. In our work, we aimed to investigate the potential protective effects of Rg1 on PQ-induced pulmonary fibrosis and the underlying mechanism. In vivo, the treatment of Rg1 can attenuate PQ-induced pulmonary fibrosis and decrease senescence and senescence associated secretory phenotype (SASP) expression. In vitro, Rg1 can effectively eliminate senescent cells via apoptosis, but not normal cells. In addition, we demonstrate that Rg1 can enhance autophagy activity via inducing the expression of ATG12. Inhibition of autophagy via 3-MA or transfection of the siRNA targeting ATG12 can impair the antiaging effect of Rg1. Taken together, our data implicates that Rg1 can protect pulmonary epithelial cells from PQ-induced cellular senescence in an ATG12 dependent manner, which may provide a preventive and therapeutic strategy for PQ poisoning-induced pulmonary fibrosis.

Obesity, one of the major public health problems worldwide, has attracted increasing attention. Ginsenoside Rb1 is the most abundant active component ofThis paper intends to further explore the mechanism of Rb1 in regulating obesity.The C57BL/6 obese mice were divided into two groups: the control (CTR) and Rb1. The CTR group [intraperitoneally (ip) administered with saline] and the Rb1 group (ip administered with Rb1, 40 mg/kg/d) were treated daily for four weeks.Rb1 reduced the body weight and adipocyte size. Improved glucose tolerance and increased basic metabolic activity were also found in Rb1 treated mice. MSTN was downregulated in differentiated C2C12 cells, 3T3-L1 cells and adipose tissues upon Rb1 treatment. FNDC5 was increased after Rb1 treatment. However, MSTN overexpression attenuated Rb1-mediated decrease accumulation of lipid droplets in differentiated 3T3-L1 adipocytes.Rb1 may ameliorate obesity in part through the MSTN/FNDC5 signalling pathway. Our results showed that Rb1 can be used as an effective drug in the treatment of human obesity.

This study evaluates the effect of ginsenoside Rc on myocardial ischaemic injury.Male Swiss mice were subcutaneously injected with 50 mg/kg isoproterenol once a day for three days. Ginsenoside Rc (10, 20, or 40 mg/kg) was intragastrically administered 1 h after isoproterenol injection. The mice in the control group were subcutaneously injected with normal saline and intragastrically given 0.5% CMC-Na. CK-MB and troponin T were assayed. Histopathological examination of myocardium was conducted. The expression of Nrf2, GCLC, GCLM and HO-1 in heart tissues was evaluated by Western blot.In myocardial ischaemic mice, ginsenoside Rc reduced the levels of CK-MB (197.1 ± 15.7, 189.9 ± 19.0, 184.0 ± 14.4 vs. 221.6 ± 27.9) and troponin T (10.3 ± 1.7, 9.5 ± 1.3, 8.7 ± 1.7 vs. 13.4 ± 2.4). Ginsenoside Rc attenuated the necrosis and inflammatory cells infiltration in myocardium. Furthermore, ginsenoside Rc not only decreased the contents of MDA, TNF-α but also increased GSH level in the heart tissues. The expression of Nrf2, GCLC, GCLM and HO-1 was significantly increased in the animals treated with ginsenoside Rc. ML385, an Nrf2 inhibitor, blocked partially the ginsenoside Rc-mediated cardioprotective effect. Ginsenoside Rc attenuated myocardial ischaemic injury in mice, which may be, in part, through its antioxidative and anti-inflammatory effects.This study indicated that ginsenoside Rc might be a novel candidate for treatment of myocardial ischaemia.

Due to sudden loss of cerebral blood circulation, acute ischemic stroke (IS) causes neuronal energy attenuation or even exhaustion by mitochondrial dysfunction resulting in aggravation of neurological injury. In this study, we investigated if Notoginsenoside R1 ameliorated cerebral energy metabolism by limiting neuronal mitochondrial dysfunction in acute IS. Male Sprague-Dawley rats (260-280 g) were selected and performed by permanent middle cerebral artery occlusion model. In vitro, the oxygen glucose deprivation (OGD) model of Neuro2a (N2a) cells was established. We found Notoginsenoside R1 treatment reduced rats' cerebral infarct volume and neurological deficits, with increased Adenosine triphosphate (ATP) level together with upregulated expression of glucose transporter 1/3, monocarboxylate transporter 1 and citrate synthase in brain peri-ischemic tissue. In vitro, OGD-induced N2a cell death was inhibited, cell mitochondrial morphology was improved. Mitochondrial amount, mitochondrial membrane potential, and mitochondrial DNA copy number were increased by Notoginsenoside R1 administration. Furthermore, mitochondrial energy metabolism-related mRNA array found Atp12a and Atp6v1g3 gene expression were upregulated more than twofold, which were also verified in rat ischemic tissue by quantitative polymerase chain reaction (qPCR) assay. Therefore, Notoginsenoside R1 administration increases cerebral glucose and lactate transportation and ATP levels, ameliorates neuronal mitochondrial function after IS. Notoginsenoside R1 may be a novel protective agent for neuronal mitochondria poststroke.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that can cause cognitive impairment. Ginsenoside Rg1 (Rg1) has a significant neuroprotective effect on animals with memory impairment. However, the mechanism of how Rg1 mediates the Wnt signaling pathway and improves cognitive function by regulating oxidative stress, apoptosis, and neuroinflammation is still unclear. In this study, the spatial memory ability of tree shrews was tested by Morris water maze, the expression levels of amyloid protein (Aβ1-42), ionized calcium-binding adapter molecule 1 (iba-1), nitrotyrosine (NT), and 8-hydroxyguanine (8-OHG) were detected by immunohistochemistry. Subsequently, the activity of catalase (CAT) and the glutathione peroxidase (GSH-Px) was, respectively, measured by the ammonium molybdate method and the 5,5'-dithiobis (2-nitrobenzoic acid). Furthermore, the malondialdehyde (MDA) concentration was determined by the thiobarbituric acid test. Finally, the expression levels of Beta-secretase (BACE1), superoxide dismutase (SOD), BCL2-Associated X (Bax), B-cell lymphoma-2 (Bcl-2), caspase-anti-apoptotic factor Cleaved-caspase-3 (Caspase-3), microtubule-associated proteins 2 (MAP2), Neuronal nuclear antigen (NeuN), as well as the phosphorylation of GSK-3β and β-catenin were detected by Western blot. This study implied that Rg1 reduced the phosphorylation of Tau protein, the deposition of Aβ1-42, and the expression of BACE1. It also showed that Rg1 increased the antioxidant activity of SOD, CAT, GPx, and instead reduced the oxidation products of NT, 8-OHG, and MDA, as wells as the inflammatory factor interleukin-1 and iba-1. It further showed that Rg1 increased the ratio of Bcl-2 to Bax and expression of neuronal markers MAP2 and NeuN, but instead reduced the expression of Caspase-3, GSK-3β, and β-catenin. In conclusion, by regulating the Wnt/GSK-3β/β-catenin signaling pathway, Rg1 of moderate and high dose could alleviate oxidative stress damage, improve neuroinflammation, protect neurons, finally improve the cognitive impairment of the AD tree shrew. This study provides theoretical basis for the Rg1 clinical application in AD.

Myocardial infarction (MI), caused by continuous ischemia and hypoxia of the coronary artery, is one of the major causes of human mortality. This study aimed to investigate the role of notoginsenoside R1 (NGR1) in MI therapy.

Ginsenosides belong to a group of steroid glycosides that are extracted from the plant genus Panax (ginseng). This plant has been used for a long time for the treatment of a variety of disorders in traditional medicine. Recent studies have assessed the biological impact of Ginsenosides in cell culture or animal models. Animal studies have shown their beneficial impacts in the remedy of pathological conditions in different tissues. The ameliorating effects of Ginsenosides in diverse pathogenic conditions can be attributed to their effects on the production of reactive oxygen species. These substances mainly affect the activity of AMPK/AKT and PI3K/AKT pathways. The beneficial effects of Ginsenosides have been appraised in diabetes-related complications, spinal cord injury, cerebral ischemia, myocardial ischemia, and other disorders which are associated with oxidative stress. Moreover, these substances have been shown to interfere with the pathologic conditions during carcinogenesis. In the current study, we explain these impacts in two distinct sections including non-neoplastic conditions and neoplastic conditions.

Graphical abstract, Highlights • PLA2G16 is up-regulated in CRC, and high expression of PLA2G16 is associated with the advanced stages. • PLA2G16 promotes the malignant progression of CRC through the Hippo signaling pathway. • GCK exerts its anti-CRC effects by inhibiting the protein expression of PLA2G16. • Provide a new insights towards the development of effective therapeutic strategies for CRC treatment by targeting PLA2G16., Introduction Colorectal cancer (CRC) is a common malignant tumor with a high global incidence, metastasis rate and low cure rate. Changes in lipid metabolism-related genes can affect the occurrence and development of CRC, and may be a potential therapeutic target for CRC. Therefore, starting from lipid metabolism-related genes to find natural medicines for tumor treatment may become a new direction in CRC research. Objectives This study aimed to investigate the effect of PLA2G16, a key gene involved in lipid metabolism, on the biological function of CRC, and whether the anti-CRC effect of GCK is related to PLA2G16. Methods To explore the role of PLA2G16 in CRC in vitro and in vivo, we performed cell proliferation, migration, invasion and nude mice tumorigenesis assays. As for the mechanism, we designed RNA-seq analysis and verified by western blotting and immunofluorescence experiments. Subsequently, we found the anti-CRC effect of GCK is related to PLA2G16 through western blotting and rescue experiments. Results We showed that PLA2G16 was significantly higher in CRC tissues than the adjacent normal appearing tissues, and high PLA2G16 expression correlates with unfavorable prognosis of CRC patients. Further, PLA2G16 promoted the malignant progression of CRC by inhibiting the Hippo signaling pathway determined by RNA-seq analysis, and GCK exerted anti-CRC effects by inhibiting the protein expression of PLA2G16 in vitro and in vivo. Conclusion Our results suggested that PLA2G16 promote the malignant progression of CRC by inhibiting the Hippo signaling pathway and the anti-CRC effect of GCK is through inhibiting the protein expression of PLA2G16.

Background: Sepsis frequently occurs in patients after infection and is highly associated with death. Septic encephalopathy is characterized by dysfunction of the central nervous system, of which the root cause is a systemic inflammatory response. Sepsis-associated encephalopathy is a severe disease that frequently occurs in children, resulting in high morbidity and mortality. Objectives: In the present study, we aimed to investigate the neuroprotective mechanism of ginsenoside Rg1 in response to septic encephalopathy. Methods: Effects of ginsenoside Rg1 on septic encephalopathy were determined by cell viability, cytotoxicity, ROS responses, apoptosis assays, and histological examination of the brain. Inflammatory activities were evaluated by expression levels of IL-1β, IL-6, IL-10, TNF-α, and MCP-1 using qPCR and ELISA. Activities of signaling pathways in inflammation were estimated by the production of p-Erk1/2/Erk1/2, p-JNK/JNK, p-p38/p38, p-p65/p65, and p-IkBα/IkBα using western blot. Results: LPS simulation resulted in a significant increase in cytotoxicity, ROS responses, and apoptosis and a significant decrease in cell viability in CTX TNA2 cells, as well as brain damage in rats. Moreover, the production of IL-1β, IL-6, IL-10, TNF-α, and MCP-1 was reported to be significantly stimulated in CTX TNA2 cells and the brain, confirming the establishment of in vitro and in vivo models of septic encephalopathy. The damage and inflammatory responses induced by LPS were significantly decreased by treatment with Rg1. Western blot analyses indicated that Rg1 significantly decreased the production of p-Erk1/2/Erk1/2, p-JNK/JNK, p-p38/p38, p-p65/p65, and p- IkBα/IkBα in LPS-induced CTX TNA2 cells and brain. Conclusions: These findings suggested that Rg1 inhibited the activation of NF-κB and MAPK signaling pathways, which activate the production of proinflammatory cytokines and chemokines. The findings of this study suggested that ginsenoside Rg1 is a candidate treatment for septic encephalopathy.

Aim. Trastuzumab (TZM) is a monoclonal antibody drug for HER2-positive breast cancer by targeting epidermal growth factor 2, but it has significant cardiotoxicity. Ginsenoside Rg2 has shown a variety of biological activities. This study was aimed at investigating whether Rg2 attenuates TZM-induced cardiotoxicity. Methods. A model of TZM-induced cardiotoxicity was established in Wistar rats, and the rats were pretreated with Rg2. After echocardiography analysis, the rats were killed and the hearts were dissected for RNAseq analysis. Primary human cardiomyocytes (HCMs) were treated with TZM with or without pretreatment with Rg2 and then subjected to a colony formation assay, flow cytometry analysis, and Western blot analysis for the detection of caspase-3, caspase-9, and BAX. Results. TZM induced LV dysfunction in rats, but Rg2 could attenuate TZM-induced LV dysfunction. The mRNA levels of caspase-3, caspase-9, and BAX were significantly higher in TZM-treated rats. The colony formation ability of HCMs was significantly lower in TZM-treated cells but was recovered after pretreatment with Rg2. The apoptosis rate of HCMs was significantly higher in TZM-treated cells but was significantly lower after pretreatment with Rg2. Moreover, protein levels of caspase-3, caspase-9, and BAX were significantly higher in TZM-treated cells but were significantly lower after pretreatment with Rg2. Conclusion. Ginsenoside Rg2 inhibited TZM-induced cardiotoxicity, and the mechanism may be related to the downregulation of the expression of proapoptotic proteins caspase-3, caspase-9, and BAX and the inhibition of TZM-induced apoptosis in cardiomyocytes. Ginsenoside Rg2 has a potential to be applied in patients with breast cancer to prevent TZM-induced cardiotoxicity.

Reperfusion injury following myocardial ischemia remained a challenge for optimal treatment of myocardial infarction. Ginsenosides Rb (G-Rb), the primary components of ginsenoside, have been reported to exert cardioprotective effects via numerous mechanisms. G-Rb1 mediate cardioprotective effects via various signaling pathways, including mitochondrial apoptotic pathway, PI3K/Akt/mTOR, HIF-1α and GRF91, RhoA, p38α MAPK, and eNOS. G-Rb2 activates the SIRT-1 pathway, while G-Rb3 promotes both JNK-mediated NF-κB and PERK/Nrf2/HMOX1. Generally, ginsenosides Rb1, 2, and 3 modulates oxidative stress, inflammation, and apoptosis, contributing to the improvement of structural, functional and biochemical parameters. In conclusion, G-Rb, particularly G-Rb1, have vast potential as a supplement in attenuating reperfusion injury. Translation into a clinical trial is warranted to confirm the beneficial effects of G-Rb.

To investigate the effects of ginsenosides on the memory impairment in Sprague–Dawley rats (SD rats) after anesthesia through the administration of propofol SPF, SD rats were randomly divided into four groups: control group (Group I), propofol-treated group (Group II), low dose of ginsenosides-treated group (Group III) and high dose of ginsenosides-treated group (Group IV). These rats were subjected to fear memory test in shuttle box, Y-maze test and Morris water maze test. Immediately after the test, the expression levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) were further detected by ELISA method. Ginsenosides could ameliorate the impairment on the functions of fear memory, working memory and spatial memory in rats caused by anesthesia via the injection of Propofol. Furthermore, the expression levels of NGF and BDNF on rat hippocampus were significant increased by the treatment of ginsenosides at both two doses compared with the control group (both P

Long-term alcohol consumption causes the development of neuroinflammation in various brain structures. One of the mechanisms involved in this process is the increased activity of TLR-signaling intracellular pathways. Studies confirm the ability of ginseng extract or its individual ginsenosides to reduce the increased activity of TLR-signaling pathways. The aim of our study was to study the effect of the amount of ginsenosides obtained from the extract of the Panax japonicus cell line on the state of the TLR-signaling system in the nucleus accumbens and hippocampus of the rat brain in a model of long-term alcohol consumption during alcohol withdrawal. The results of the study showed that ginsenosides were able to make changes in the TLR signaling system, which has been altered by long-term alcohol consumption. A significant effect of ginsenosides on the level of TLR3 and TLR4 mRNA in the nucleus accumbens was found, while in the hippocampus, ginsenosides significantly affected the level of TLR7 mRNA. The effect of ginsenosides on the level of mRNA of transcription factors and cytokines involved in TLR-signaling was evaluated. Thus, results of our study confirm that ginsenosides are able to influence the state of TLR-signaling pathways, but this effect is multidirectional in relation to different brain structures. In the future, it seems interesting to evaluate the role of individual ginsenosides in relation to genes of TLR-signaling, as well as the effect of ginsenosides on other brain structures.Dlitel'noe upotreblenie alkogolia sluzhit prichinoĭ razvitiia neĭrovospaleniia v razlichnykh strukturakh golovnogo mozga. Odnim iz mekhanizmov, zadeĭstvovannykh v étom protsesse, iavliaetsia povyshennaia aktivnost' TLR-signal'nykh vnutrikletochnykh puteĭ. Riad issledovateleĭ ukazyvaiut na sposobnost' ékstrakta zhen'shenia ili ego otdel'nykh ginzenozidov snizhat' povyshennuiu aktivnost' signal'nykh puteĭ, oposreduiushchikh éffekty Toll-podobnykh retseptorov (TLR). Tsel'iu raboty byla otsenka vliianiia summy ginzenozidov, poluchennoĭ iz ékstrakta kul'tury kletok zhen'shenia (Panax japonicus), na sostoianie sistemy TLR-signalizatsii v prilezhashchem iadre i gippokampe golovnogo mozga krys na modeli dlitel'noĭ alkogolizatsii v period otmeny alkogolia. Rezul'taty issledovaniia pokazali, chto ginzenozidy sposobny vnosit' izmeneniia v sistemu TLR-signalizatsii, kotoraia byla izmenena dlitel'noĭ alkogolizatsieĭ u krys. V prilezhashchem iadre otmecheno vozdeĭstvie ginzenozidov na soderzhanie mRNK TLR3 i TLR4, togda kak v gippokampe znachimo ginzenozidy povliiali na uroven' mRNK TLR7. Krome togo, bylo otseneno vozdeĭstvie summy ginzenozidov na riad transkriptsionnykh faktorov i tsitokinov — uchastnikov TLR-signalizatsii. Takim obrazom, rezul'taty nastoiashchego issledovaniia podtverdili, chto ginzenozidy mogut vliiat' na ékspressiiu genov, kodiruiushchikh komponenty TLR-signal'nykh puteĭ peredachi signalov, odnako éto vliianie nosit raznonapravlennyĭ kharakter v raznykh strukturakh golovnogo mozga.

We previously found that the levels of metabolite N-acetylglutamine were significantly increased in urine samples of patients with heart failure (HF) and in coronary artery ligation (CAL)-induced HF mice, whereas the expression of its specific metabolic-degrading enzyme aminoacylase-1 (ACY1) was markedly decreased. In the current study, we investigated the role of ACY1 in the pathogenesis of HF and the therapeutic effects of 20(S)-ginsenoside Rg3 in HF experimental models in vivo and in vitro. HF was induced in mice by CAL. The mice were administered Rg3 (7.5, 15, 30 mg · kg

Ulcerative colitis (UC) is dramatically increasing worldwide, cannot be thoroughly cured, and reduces patients' quality of life. Excessive activation of macrophages and over-production of cytokines play an important role in the pathogenesis of UC. Therefore, for its treatment, inhibiting macrophages' hyperactivation would be effective to develop new treatment approaches. Ginsenosides, extracted from ginseng, show an anti-inflammatory effect on the immunologic process. Our study used ginsenosides Rd monomer (GRd) to intervene in DSS-induced colitis mouse models and tested the immunological effect of macrophages.We observed body weights, weights of colons, colonic lengths, and inflammatory scores, as well as histological changes of DSS/DSS-GRd mice. We also isolated intestinal and peritoneal macrophages, performed qRT-PCR and ELISA to detect cytokines production by macrophages, and screened possible involved pathways by Western blotting.Administering 20 mg/Kg GRd to DSS mice for 7-14 days reduced colonic inflammation. Moreover, bothOur data indicate that GRd could down-regulate cytokines production in macrophages and alleviate DSS-colitis in mice, which may be related to NF-κB and P38MAPK pathways. These results suggest that GRd has an anti-inflammatory effect on experimental colitis and may have potential efficacy in the treatment of UC alone or in combination.

Obesity significantly impacts living a normal life by increasing morbidity. Additionally, obesity has been shown to be closely associated with severe inflammation in adipocytes. It is widely reported that berberine (BBR) has an anti-inflammatory effect and can reduce glucose and lipid accumulation, whereas ginsenoside Rb1 (Rb1) has been shown to have a significant inhibitory effect on insulin resistance and lipid peroxidation. In this study, we aimed to explore the synergetic effect of BBR and Rb1 on tumor necrosis factor alpha (TNF-α)-treated adipocytes and the mechanisms underlying it. We found that TNF-α reduced cell viability, facilitated the production of inflammatory factors, induced adipogenesis, activated the nuclear factor kappa B (NF-κB) pathway, and increased the expression of peroxisome proliferator-activated receptor gamma, CCAAT enhancer-binding protein alpha, and sterol regulatory element-binding protein-1 c in adipocytes. However, these effects were significantly alleviated by BBR or Rb1. Additionally, a synergetic effect was observed when BBR and Rb1 were used in combination. The effects of BBR in combination with Rb1 on cell proliferation, inflammation, adipogenesis, and the NF-κB pathway in TNF-α-treated adipocytes were significantly abolished by receptor activator of nuclear factor kappa-Β ligand, which is an activator of the NF-κB pathway. Collectively, the results revealed that BBR and Rb1 have a synergetic protective effect against TNF-α-induced inflammation in adipocytes. The mechanism underlying this synergetic effect was found to be inhibition of the NF-κB signaling pathway.

Ginsenoside compound K (CK) is the major intestinal bacterial metabolite of ginsenosides that exhibits anticancer potential in various cancer cells both in vitro and in vivo. The anticancer types, mechanisms, and effects of CK in the past decade have been summarized in this review. Briefly, CK exerts anticancer effects via multiple molecular mechanisms, including the inhibition of proliferation, invasion, and migration, the induction of apoptosis and autophagy, and anti-angiogenesis. Some signaling pathways play a significant role in related processes, such as PI3K/Akt/mTOR, JNK/MAPK pathway, and reactive oxygen species (ROS). Moreover, the effects of CK combined with nanocarriers for anticancer efficiency are discussed in this review. Furthermore, we aimed to review the research progress of CK against cancer in the past decade, which might provide theoretical support and effective reference for further research on the medicinal value of small molecules, such as CK.

Purpose Diabetic foot ulcers (DFUs) are common complications of high severity for diabetes. Ginsenoside Rg1 (Rg1) has the potential for diabetes and cardiovascular diseases therapy. This research aimed at exploring the regulation of Rg1 on DFUs treatment and the underlying mechanism. Methods Human umbilical vein endothelial cells (HUVECs) incubated with high-glucose culture medium were established for induction of diabetes model. The MTT assay, Annexin V/PI assay and oxidative stress detection were carried out on high-glucose-induced HUVECs. Dual-luciferase reporter assay was performed to prove the interaction of miR-489–3p and Sirt1. DFUs model was established to determine the efficiency of Rg1 and miR-489–3p in wound closure of DFUs in vivo. Results Rg1 promoted cell proliferation, migration and angiogenesis, and reduced cell apoptosis in high-glucose-induced HUVECs. Knockdown of miR-489–3p alleviated the high-glucose-induced damage to HUVECs, while overexpression of miR-489–3p attenuated the protection effects of Rg1. Overexpression Sirt1 promoted wound healing in DFUs and Sirt1 was a direct target of miR-489–3p. In addition, animal experiments demonstrated that Rg1 promoted wound closure by regulating miR-489–3p/Sirt1 axis. Conclusions Rg1 alleviated the DFUs by increasing Sirt1 expression via miR-489–3p downregulation and promoting activation of PI3K/AKT/eNOS signaling.

Long-term exposure to ultraviolet (UV) irradiation, especially UVB, can trigger destructive intracellular effects, including various types of DNA damage, oxidative stress, and inflammatory responses, leading to accelerated skin aging. Ginsenoside Rk1, a rare ginsenoside pertaining to panaxadiol saponins, has been certified to possess underlying anti-inflammatory effects. Nevertheless, the efficiency of Rk1 against the photoaging of human skin and the latent molecular mechanisms are still unclear. Here, UVB-irradiated HaCaT keratinocytes were used as an

Ginsenosides are the main active components of ginseng, including many types and different contents. Among them, minor ginsenosides have better biological functions and pharmacological activities than those of the major ginsenosides. However, minor ginsenosides cannot be obtained in large quantities, but by means of enzymatic transformation technology, some major ginsenosides can be de-glycosylated at a specific position to generate minor ginsenosides. In this study, we report two glycosidase genes associated with the conversion of ginsenoside Rd to ginsenosides F

Aluminum (Al)-induced bone formation and metabolism disorder through inhibition of the TGF-β1/Smad signaling pathway is one of the important mechanisms of bone impairment. Ginsenoside Rg3 (Rg3), a specific biological effector molecule, can provide protection to bones. Previously, we demonstrated that Rg3 can reverse aluminum chloride (AlCl3)-induced oxidative stress and metabolic disorder of bones; however, whether the TGF-β1/Smad signaling pathway is involved in it remains unclear. First, we found that Rg3 attenuated Al-induced bone impairment in vivo and in vitro by relieving structural damage to the femur, increasing MC3T3-E1 cell activity, differentiation, mineralization, inhibition of cell apoptosis, and upregulating the extracellular matrix (ECM) synthesis and the expression of TGF-β1/Smad signaling pathway key factors. Subsequently, in the signal pathway intervention experiment, the protective effect of Rg3 on bone impairment induced by Al was weakened; these results indicate that activating the TGF-β1/Smad signaling pathway is one of the mechanisms of Rg3-attenuated Al-induced bone impairment.

With the progress made in the widespread application of interventional radiology procedures, there has been an increasing number of patients who suffer from cardiovascular diseases and go through imaging and interventional treatment with iodine contrast medium (ICM) year by year. In turn, there has been an increasing amount of concern over acute kidney injury (AKI) brought about by ICM. As evidenced by numerous studies, the initiation of inflammatory response plays a critical role in the development of ICM-induced AKI. Correspondingly, the strategy of targeting renal inflammatory response and cytokine release could provide an effective solution to mitigating the ICM-induced AKI. Moreover, Ginsenoside Rb1 (GRb1) constitutes one of the major active components of ginseng and features a wide range of vital biological functions. Judging from the research findings, GRb1 could impose antioxidant and anti-inflammatory effects on cardiovascular diseases, in addition to lung, liver and kidney diseases. However, reports on whether GRb1 could impose a protective effect against contrast-induced nephropathy (CIN) are absent. In this study, we have examined the therapeutic effects imposed by GRb1 as well as the potential molecular mechanism by establishing an in vivo and in vitro model of CIN. In addition, we have set up a mouse model of CIN through sequential intravenous injection of indomethacin, N(ω)-nitro-Larginine methyl ester (L-NAME), and iopromide. To further enhance the bioavailability of GRb1, we have encapsulated GRb1 with polyethylene glycol (PEG)/poly lactic-co-glycolic acid (PLGA) nanocarriers to generate GRb1 nanoparticles (NPs) conducting the in vivo experiments. During the in vitro experiments, we have adopted GRb1 to treat NRK-52E cells or cells transfected with the high mobility group box 1 gene (HMGB1) overexpression plasmid. As shown by the in vivo experimental results, GRb1 NPs could evidently improve the renal dysfunction in CIN, diminish the extent of apoptosis of tubular epithelial cells, and reduce the expression of high mobility group box 1 (HMGB1) and cytokines (tumor necrosis factor (TNF-α), interleukin (IL) 6 and IL-1β). In addition, GRb1 NPs are found to be capable of preventing the activation of Toll-like receptor 4 (TLR4)/NF-κB signaling pathway triggered by contrast medium. The in vitro experimental results have exactly confirmed the findings of the in vivo experiments. In the meantime, through the observation of the in vitro assays, overexpression of HMGB1 can partially counteract the beneficial effects imposed by GRb1. Judging from our research data, GRb1 could impose a protective effect against CIN by inhibiting inflammatory response via HMGB1/TLR4/NF-κB pathway, whereas HMGB1 constitutes a critical molecular target of GRb1.

Damaged peripheral nerves undergo peripheral neurodegenerative processes that are essential for the nerve regeneration. Peripheral neurodegenerative diseases, including diabetic peripheral neuropathy, are induced by irreversible nerve damage caused by abnormal peripheral nerve degeneration. However, until now, there have been no effective therapeutic treatments for these diseases. Ginsenosides are the most pharmacologically active compounds in Panax ginseng, and are being actively studied. Ginsenosides have a variety of effects, including neuroprotective, antioxidative, anti-cytotoxic, and anti-inflammatory effects. Here, we investigated the efficacy of 18 ginsenosides. We then tested the ability of the most effective ginsenoside, (S)-ginsenosides F1 (sF1), to inhibit peripheral neurodegenerative processes using mouse sciatic ex vivo culture, and several morphological and biochemical indicators. Our results suggest that sF1 could effectively protect Schwann cells against peripheral nerve degeneration.

The biological effects of ginsenosides are limited by their low oral bioavailability. This study aimed to investigate the effects of particle size reduction and dispersants on the dissolution and bioavailability of ginsenosides in ginseng. Fine ginseng powder (FGP), ultrafine ginseng powder (UGP), and ultrafine ginseng powder with β-cyclodextrin as the dispersant (UGPD) were prepared using a planetary ball mill from coarse ginseng powder (CGP, as the control). The particle size, morphology, hydration, thermal properties, and

This study aimed to investigate the therapeutic effect of black ginseng (BG) on non-alcoholic fatty liver disease (NAFLD) using network pharmacology combined with the molecular docking strategy. The saponin composition of BG was analyzed by liquid chromatography-mass spectrometry (LC/MS) instrument. Then the network pharmacology was applied to explore the potential targets and related mechanisms of BG in the treatment of NAFLD. After screening out key targets, molecular docking was used to predict the binding modes between ginsenoside and target. Finally, a methionine and choline deficiency (MCD) diet-induced NAFLD mice model was established to further confirm the therapeutic effect of BG on NAFLD. Twenty-four ginsenosides were annotated based on the MS and tandem MS information. Ten proteins were screened out as key targets closely related to BG treatment of NAFLD. The molecular docking showed that most of the ginsenosides had good binding affinities with AKT1. The validation experiment revealed that BG administration could reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and improve the MCD diet-induced histological changes in liver tissue. Moreover, BG could upregulate the phosphorylation level of AKT in the liver of NAFLD mice, thereby exerting the therapeutic effect on NAFLD. Further studies on the active ginsenosides as well as their synergistic action on NAFLD will be required to reveal the underlying mechanisms in-depth. This study demonstrates that network pharmacological prediction in conjunction with molecular docking is a viable technique for screening the active chemicals and related targets of BG, which can be applied to other herbal medicines.

Ginsenoside Rg1 is an important active substance isolated from the root of ginseng. In previous studies, Rg1 has shown excellent therapeutic effects in antioxidant, anti-inflammatory, and metabolic modulation. However, the therapeutic targets of Rg1 are still unknown. In this study, we investigated the therapeutic effects of Rg1 on oxidative stress-related liver damage. The oxidative stress damage model was achieved by intraperitoneal injection of D-galactose (D-gal) for 42 consecutive days in C57BL/6J mice. Rg1 treatment started on Day 16. Body weight, liver weight, degree of hepatic oxidative stress damage, serum lipid levels, and hepatic lipid and glucose metabolism were measured. Proteomics analysis was used to measure liver protein expression. The differential expression proteins were analyzed with bioinformatics. The results showed that Rg1 treatment attenuated liver damage from oxidative stress, reduced hepatic fat accumulation, promoted hepatic glycogen synthesis, and attenuated peripheral blood low-density lipoprotein (LDL), cholesterol (CHO), and triglycerides (TG) levels. Proteomic analysis suggested that Rg1 may regulate hepatocyte metabolism through ECM–Receptor, the PI3K-AKT pathway. The epidermal growth factor receptor (EGFR) and activator of transcription 1 (STAT1) may be the key protein. In conclusion, this study provides an experimental basis for further clarifying the specific mechanism of Rg1 in the treatment of oxidative stress damage-related liver disease.

Ginsenoside Rh2 is one of the major bioactive ginsenosides in Panax ginseng. Although Rh2 is known to enhance immune cells activity for treatment of cancer, its anti-inflammatory and neuroprotective effects have yet to be determined. In this study, we investigated the effects of Rh2 on spared nerve injury (SNI)-induced neuropathic pain and elucidated the potential mechanisms. We found that various doses of Rh2 intrathecal injection dose-dependently attenuated SNI-induced mechanical allodynia and thermal hyperalgesia. Rh2 also inhibited microglia and astrocyte activation in the spinal cord of a murine SNI model. Rh2 treatment inhibited SNI-induced increase of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1 and IL-6. Expression of miRNA-21, an endogenous ligand of Toll like receptor (TLR)8 was also decreased. Rh2 treatment blocked the mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting of phosphorylated extracellular signal-regulated kinase expression. Finally, intrathecal injection of TLR8 agonist VTX-2337 reversed the analgesic effect of Rh2. These results indicated that Rh2 relieved SNI-induced neuropathic pain via inhibiting the miRNA-21-TLR8-MAPK signaling pathway, thus providing a potential application of Rh2 in pain therapy.

Intrahepatic cholestasis (IC) occurs when the liver and systemic circulation accumulate bile components, which can then lead to lipid metabolism disorders and oxidative damage. Ginsenosides (GS) are pharmacologically active plant products derived from ginseng that possesses lipid-regulation and antioxidation activities. The purpose of this study was to evaluate the possible protective effects of ginsenosides (GS) on lipid homeostasis disorder and oxidative stress in mice with alpha-naphthylisothiocyanate (ANIT)-induced IC and to investigate the underlying mechanisms. A comprehensive strategy via incorporating pharmacodynamics and molecular biology technology was adopted to investigate the therapeutic mechanisms of GS in ANIT-induced mice liver injury. The effects of GS on cholestasis were studied in mice that had been exposed to ANIT-induced cholestasis. The human HepG2 cell line was then used in vitro to investigate the molecular mechanisms by which GS might improve IC. The gene silencing experiment and liver-specific sirtuin-1 (SIRT1) knockout (SIRT1LKO) mice were used to further elucidate the mechanisms. The general physical indicators were assessed, and biological samples were collected for serum biochemical indexes, lipid metabolism, and oxidative stress-related indicators. Quantitative PCR and H&E staining were used for molecular and pathological analysis. The altered expression levels of key pathway proteins (Sirt1, p-AMPK, Nrf2) were validated by Western blotting. By modulating the AMPK protein expression, GS decreased hepatic lipogenesis, and increased fatty acid β-oxidation and lipoprotein lipolysis, thereby improving lipid homeostasis in IC mice. Furthermore, GS reduced ANIT-triggered oxidative damage by enhancing Nrf2 and its downstream target levels. Notably, the protective results of GS were eliminated by SIRT1 shRNA in vitro and SIRT1LKO mice in vivo. GS can restore the balance of the lipid metabolism and redox in the livers of ANIT-induced IC models via the SIRT1/AMPK signaling pathway, thus exerting a protective effect against ANIT-induced cholestatic liver injury.

Type 2 diabetes mellitus (T2DM) is a common metabolic syndrome that decreases insulin sensitivity and mitochondrial biogenesis in the liver. Our previous study demonstrated that ginsenoside Rg5 (Rg5) could attenuate renal injury in diabetic mice but its underlying mechanism in mitochondrial biogenesis and insulin sensitivity remains poorly understood. In this study, we found that Rg5 intervention significantly inhibited blood glucose increases in db/db mice, improved liver function damage and hepatocyte apoptosis, and activated the IRS-1/phosphatidylinositol 3-kinase/AKT insulin metabolism signaling pathway. Rg5 treatment also increased the level of glycogen synthesis and activated sirtuin1 (Sirt1) to increase glucose uptake and insulin sensitivity in insulin-resistant HepG2 (IR-HepG2) cells. Rg5 intervention also effectively improved liver oxidative stress and inflammation in db/db mice and increased mitochondrial biogenesis caused by T2DM. Additionally, the Rg5 treatment increased the mitochondrial mass in IR-HepG2 cells and activated Sirt1 to regulate the Sirt1/PGC-1α/mitofusin-2 mitochondrial biosynthesis pathway. Our findings demonstrated that Rg5 enhanced liver mitochondrial biogenesis and insulin sensitivity in db/db mice by activating the Sirt1/PGC-1α signaling pathway, suggesting the potential of Rg5 as a natural product for T2DM interventions.

Ischemic stroke continues to be a major global health problem associated with considerable mortality and morbidity. Thus, it is still targeted by researchers for developing new strategies or drugs to alleviate the lesion of stroke. In the present study, both the permanent occlusion of the middle cerebral artery (MCAO) model and the restoration of cerebral blood flow after middle cerebral artery occlusion (CI/R) model were set up for evaluating the efficiency of salvianolic acid B and ginsenoside Rg1 combination (SalB-Rg1). SalB-Rg1 decreased infarct area through 3,5-triphenyltetrazolium chloride stain and improved neurological behavior through Longa Score or Left-Biased Swings on both MCAO rats and CI/R rats. Neural protection of SalB-Rg1 against ischemia or ischemic reperfusion injury was evidenced by the inhibition of nucleus pyknosis, liquefaction necrosis through H&E stain and Nissl stain. Furthermore, protection of SalB-Rg1 on blood-brain barrier (BBB) was more significant on CI/R rats, accompanying with the downregulation of matrix metalloproteinase-2 and matrix metalloproteinase-9, and recovery of zonula occludens-1 expression. These results provide compelling evidence that SalB-Rg1 holds the potential to be developed as an optimal therapeutic strategy to alleviate the injury of ischemia or ischemic reperfusion.

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.

Myelin damage and abnormal remyelination processes lead to central nervous system dysfunction. Glial activation-induced microenvironment changes are characteristic features of the diseases with myelin abnormalities. We previously showed that ginsenoside Rg1, a main component of ginseng, ameliorated MPTP-mediated myelin damage in mice, but the underlying mechanisms are unclear. In this study we investigated the effects of Rg1 and mechanisms in cuprizone (CPZ)-induced demyelination mouse model. Mice were treated with CPZ solution (300 mg· kg(−1)· d(−1), ig) for 5 weeks; from week 2, the mice received Rg1 (5, 10, and 20 mg· kg(−1)· d(−1), ig) for 4 weeks. We showed that Rg1 administration dose-dependently alleviated bradykinesia and improved CPZ-disrupted motor coordination ability in CPZ-treated mice. Furthermore, Rg1 administration significantly decreased demyelination and axonal injury in pathological assays. We further revealed that the neuroprotective effects of Rg1 were associated with inhibiting CXCL10-mediated modulation of glial response, which was mediated by NF-κB nuclear translocation and CXCL10 promoter activation. In microglial cell line BV-2, we demonstrated that the effects of Rg1 on pro-inflammatory and migratory phenotypes of microglia were related to CXCL10, while Rg1-induced phagocytosis of microglia was not directly related to CXCL10. In CPZ-induced demyelination mouse model, injection of AAV-CXCL10 shRNA into mouse lateral ventricles 3 weeks prior CPZ treatment occluded the beneficial effects of Rg1 administration in behavioral and pathological assays. In conclusion, CXCL10 mediates the protective role of Rg1 in CPZ-induced demyelination mouse model. This study provides new insight into potential disease-modifying therapies for myelin abnormalities.

The present study investigated, the anti-apoptotic activity of Ginsenoside Rg1 (Rg1) via inhibition of Bax translocation and the subsequent recovery of hematopoietic function. Mitochondrial apoptosis in bone marrow mononuclear cells (BMNCs) was observed in aplastic anemia (AA) patients. To establish a mouse model of AA, BALB/c mice were transplanted with lymph node cells from DBA/2 donor mice via vein injection after treatment with Co60 γ-radiation. After treatment with Rg1 for 14 days, the peripheral blood and Lin–Sca-1 + c-Kit + (LSK) cell counts of the treated group were increased compared with those of the untreated model mice. In in vivo and in vitro tests of LSKs, Rg1 was found to increase mitochondrial number and the ratio of Bcl-2/Bax and to decrease damage to the mitochondrial inner and outer membranes, the mitochondrial Bax level and the protein levels of mitochondrial apoptosis-related proteins AIF and Cyt-C by decreasing the ROS level. Rg1 also improved the concentration–time curve of MAO and COX and levels of ATP, ADP and AMP in an in vitro test. In addition, high levels of Bax mitochondrial translocation could be corrected by Rg1 treatment. Levels of markers of mitochondrial apoptosis in the Rg1-treated group were significantly better than those in the AA model group, implying that Rg1 might improve hematopoietic stem cells and thereby restore hematopoietic function in AA by suppressing the mitochondrial apoptosis mediated by Bax translocation.

Ginsenoside Rg1 is the active ingredient of the plant named genus Panax (ginseng), which exhibited significant bioactivities, including anti-inflammatory, antioxidation, and anti-diabetic effects. Herein, 4-week treatment of ginsenoside Rg1 remarkably decreased blood glucose levels and improved the resistance of insulin, oxidative stress, and inflammation along with lipid profile in T2D rats triggered via high-fat diet and streptozotocin (STZ). Ginsenoside Rg1 supplementation improved the intestinal microbial composition induced by type 2 diabetes (T2D), which increased the proportions of Lachnospiraceae_NK4A136_group and Lachnoclostridium and decreased the proportions of Lactobacillus. Additionally, Spearman's correlation test between the gut microflora and biomedical assays (|r| .5) revealed that the Lachnospiraceae_NK4A136_group, Roseburia, and Romboutsia greatly affect intestinal microbiota, which may play pivotal roles in preventing T2D. Our findings illustrate the use of ginsenoside Rg1 as a dietary supplement along with prospective prebiotics due to its ability to alter the gut microflora and alleviate T2D-linked biochemical abnormalities. PRACTICAL APPLICATIONS: This was the first study to elucidate the influences of ginsenosides Rg1 in improving the intestinal microbiota of T2D in SD rats. The data illustrated that the ginsenosides Rg1 remarkably increased the proportions of SCFAs producing bacteria. Hence, ginsenoside Rg1 could be used as a potential prebiotic in the treatment of T2D through alteration of intestinal microbiota.

Decreased Nicotinamide adenine dinucleotide (NAD

Oxidative stress is a vital contributor to the development and progression of diabetes-accelerated atherosclerosis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known molecule that participates in cellular defense against oxidative stress. Utilizing luciferase reporter assay from 379 natural products, we reported here that Ginsenoside Rb1 played a dual role in inhibiting Kelch-like ECH-associated protein 1 (Keap1) and p47

Nasopharyngeal carcinoma (NPC) is a malignant tumor with high incidence. Notoginsenoside R1 (NGR1) is the main active compound of total Panax notoginseng saponin, and has multiple anti-tumor effects. This study aimed to investigate the effect and mechanism of NGR1 in NPC.NPC cells were treated with different doses of NGR1. The NGR1 function in NPC was evaluated using Cell Counting Kit-8, Transwell, Western blot, flow cytometry, immunofluorescence assay, and quantitative real-time PCR. Meanwhile, the NGR1 mechanism in NPC was assessed by rescue experiments. Furthermore, the NGR1 function in vivo was determined by constructing an NPC xenotransplantation model, TUNEL, and immunohistochemistry assays.NGR1 repressed NPC cell growth and invasion but facilitated NPC cell apoptosis and oxidative stress. Also, NGR1 alleviated inflammation in NPC cells. Mechanistically, NGR1 restrained NPC cell growth and induced oxidative stress in NPC cells, while these effects were abolished after lipopolysaccharide (an activator of the TRAF6/NF-κB pathway) treatment, implying that NGR1 reduced NPC cell growth and induced oxidative stress in NPC cells by the inactivation of TRAF6/NF-κB axis. Moreover, in vivo studies further proved the palliative effect of NGR1 on NPC.NGR1 inhibited NPC cell growth and induced oxidative stress in NPC cells by inactivating TRAF6/NF-κB axis.