Search

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.

Background: Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovascular disease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-induced cardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR) signaling pathway. Methods: Mechanical stress was implemented on rats through abdominal aortic constriction (AAC) procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex Collagen I plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca2+]i, and the expression of CaSR and calcineurin (CaN) were assayed both on rat and cellular level. Results: Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation induced by AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1 treatment inhibited CaSR expression and increase of [Ca2+]i, which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-β1 pathways activation. Mechanistic analysis showed that the CaSR agonist GdCl3 could not further increase the [Ca2+]i and CaN pathway related protein expression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN, inhibited cardiac hypertrophy, cardiac fibrosis, [Ca2+]i and CaN signaling but had no effect on CaSR expression. Conclusion: The activation of CaN pathway and the increase of [Ca2+]i mediated by CaSR are involved in cardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardial injury.

Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer’s disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aβ) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aβ generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aβ deposition by inhibiting NOX2 activation in APP/PS1 mice.

During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood–brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1β-induced macrophages (IIM)-Exos-miR-21 can activate NF-κB signaling pathway and induce the expressions of MMP-1, -3 and -9 and downregulate the levels of tight junction proteins (TJPs) deteriorating the BBB. Rg1 reduced miR-21-5p content in IIM-Exos (RIIM-Exos). The interaction of NMIIA–HSP90 controlled the release of Exos-miR-21, this interaction was restricted by Rg1. Rg1 could inhibit the Exos-miR-21 release in peripheral blood flow to brain, enhancing TIMP3 protein expression, MMPs proteolysis, and restricting TJPs degradation thus protected the BBB integrity. Conclusively, Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease.

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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the protective effect of ginsenoside Rg1 on cardiac injury in the rats with severe acute pancreatitis(SAP），and to elucidate the related molecular mechanisms. Methods: The SD rats were randomly divided into control group，model group and Rg1 treatment group，with 6 rats in each group. The abdominal cavity of the rats in control group was closed after laparotomy；the rats in model group were retrogradely injected with 5% sodium taurocholate (0. 15 μL·kg－1） into the biliopancreatic duct to induce SAP after laparotomy；the rats in Rg1 treatment group were injected with Rg1 (4 mg·kg－1）via the tail vein 30 min before operation of preparing the SAP model；the rats in control group and model group were injected with normal saline 30 min before operation. Enzyme linked immunosorbent assay(ELISA）method was used to detect the levels of serum tumor necrosis factor-α(TNF-α），endotoxin， endothelin 1(ET-1），interleukin-1β(IL-1β）and the activities of serum creatine kinase-MB(CK-MB）， cardiac troponin I(cTnI） and mylase of rats in various groups. Ultrasound imaging system was used to detect the heart rate(HR），left ventricular end-systolic diameter(LVDs）and left ventricular end-diastolic diameter(LVDd）of rats in various groups and calculate the fractional shortening(FS）. Western blotting method was used to detect the expression levels of NADPH oxidase(NOX）2 and NOX4，phosphorylated p38(p-p38），phosphorylated extracellular regulated protein kinase 1/2( p-ERK1/2） and phosphorylated c-Jun N-terminal kinase(p-JNK）proteins in myocardium tissue of rats in various groups. Results: Compared with control group，the levels of TNF- α，endotoxin，IL-1β and ET-1 in serum of the rats in model group were significantly increased (P<0. 05）；the activities of CK-MB，cTnI，and amylase were significantly increased(P<0. 05）. Compared with model group，the levels of TNF- α，endotoxin，IL-1β and ET-1 in serum of the rats in Rg1 treatment group were decreased(P<0. 05），and the activities of CK-MB，cTnI， and amylase were decreased(P<0. 05）. Compared with control group，the HR and LVDs of the rats in model group were significantly increased(P<0. 05），the LVDd had no significant difference(P>0. 05）， and the FS was significantly decreased(P<0. 05）；compared with model group，the LVDs of the rats in Rg1 treatment group were significantly decreased(P<0. 05），the LVDd had no significant difference(P> 0. 05），and the FS was significantly increased (P<0. 05）. The Western blotting results showed that compared with control group ，the expression levels of NOX2 ，NOX4 ，p-p38，p-ERK1/2 and p-JNK proteins in myocardium tissue of the rats in model group were significantly increased (P<0. 05 or P< 0. 01）；compared with model group，the expression levels of NOX2 ，NOX4 ，p-p38 ， p-ERK1/2 and p-JNK proteins in myocardium tissue of the rats in Rg1 treatment group were significantly decreased(P< 0. 05）. Conclusion: Rg1 has a protective effect on cardiac injury in the SAP rats，and its mechanism may be related to reducing myocardial tissue oxidative stress by inhibiring MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To explore the synergic mechanism of ginsenoside Rg1 (Rg1) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs. Methods: The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg1 for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na+], potassium ions [K+] and calcium ions [Ca2+] levels, and Nav1.5, Kv4.2, and RyR2 genes expressions in each group were examined. Results: For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg1 had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ via regulating Nav1.5, RyR2 expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular Na+ (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular K+ (P<0.01) via regulating Nav1.5, Kv4.2, RyR2 expressions in impaired NRCMs. Conclusion: Rg1 inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na+], [K+], and [Ca2+]. [ABSTRACT FROM AUTHOR]

We evaluated the susceptibility of 3 commonly used herbs in the genus Panax to the toxigenic fungi Aspergillus flavus [AF(+)] and A. parasiticus [AP(+)], derived from the ginseng species: American ginseng (Panax quinquefolius), ginseng (Panax ginseng) and notoginseng (Panax notoginseng). We analysed the effects of the internal ingredients of the 3 herbs on toxigenic fungi as well as aflatoxins production. The results showed that the sporulation quantity and aflatoxins level of AF(+) were the highest in notoginseng, while AP(+) were the highest in ginseng. The aqueous extracts of 3 Panax spp. significantly promoted the growth of AF(+) (P <0.05) and had no significant effects on the growth of AP(+), but inhibited the aflatoxins production of AF(+) and AP(+) at 50 mg/mL. Subsequently, ginsenoside Rg1 inhibited the aflatoxins production of AF(+), and the maximum inhibition (41.46 %) was in AFB1. Ginsenoside Rg1 and Rb1 inhibited the production of AP(+) by 56.25 % and 38.83 %, respectively, in AFB1. The study revealed that notoginseng and ginseng were easily contaminated with A. flavus and A. parasiticus, respectively. Among the 4-ginsenosides, Rg1 and Rb1 were the main components in 3-ginseng spp. aqueous extracts, which inhibited the aflatoxins production from A. flavus or A. parasiticus. [ABSTRACT FROM AUTHOR]

Recent research has indicated that Panax notoginseng saponins (PNS) extracted from the radix of Panax notoginseng (Burkill) F. H. Chen exert antidepressant effects. This study aimed to assess the antidepressive effects of ginsenoside Rg1 and PNS in a depression model induced by chronic unpredictable mild stress (CUMS). Over a period of three weeks, rats were administered ginsenoside Rg1 at a dose of 30 mg/kg and PNS at dosages ranging from 100 to 200 mg/kg body weight per day. To assess how ginsenoside Rg1 and PNS influence depression-like behaviours in rats, various assessments were conducted, including coat state evaluation, forced swim test, and elevated plus maze test. The levels of cortisol and testosterone in serum samples were analysed using the liquid chromatography-electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) method. LC-ESI-MS/MS method provides precise and accurate results. The lower limit of quantification values for cortisol and testosterone were determined as 100 and 2 pg/mL, respectively. Our data demonstrated that both ginsenoside Rg1 and PNS significantly reversed depression-like behaviour in rats by improving coat condition, reducing immobility time in the forced swim test, and increasing time spent in the open arms of the elevated plus maze test. Furthermore, ginsenoside Rg1 and PNS exhibited a regulatory effect on cortisol and testosterone levels in plasma. These findings suggest that ginsenoside Rg1 and PNS may be potential antidepressants in clinical treatment.

Background: Hypoxic pulmonary hypertension (HPH) is the main pathological change in vascular remodeling, a complex cardiopulmonary disease caused by hypoxia. Some research results have shown that ginsenoside Rg1 (Rg1) can improve vascular remodeling, but the effect and mechanism of Rg1 on hypoxia-induced pulmonary hypertension are not clear. The purpose of this study was to discuss the potential mechanism of action of Rg1 on HPH., Methods: C57BL/6 mice, calpain-1 knockout mice and Pulmonary artery smooth muscle cells (PASMCs) were exposed to a low oxygen environment with or without different treatments. The effect of Rg1 and calpain-1 silencing on inflammation, fibrosis, proliferation and the protein expression levels of calpain-1, STAT3 and p-STAT3 were determined at the animal and cellular levels., Results: At the mouse and cellular levels, hypoxia promotes inflammation, fibrosis, and cell proliferation, and the expression of calpain-1 and p-STAT3 is also increased. Ginsenoside Rg1 administration and calpain-1 knockdown, MDL-28170, and HY-13818 treatment showed protective effects on hypoxia-induced inflammation, fibrosis, and cell proliferation, which may be associated with the downregulation of calpain-1 and p-STAT3 expression in mice and cells. In addition, overexpression of calpain 1 increased p-STAT3 expression, accelerating the onset of inflammation, fibrosis and cell proliferation in hypoxic PASMCs., Conclusion: Ginsenoside Rg1 may ameliorate hypoxia-induced pulmonary vascular remodeling by suppressing the calpain-1/STAT3 signaling pathway., (© 2024 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Background: The resistance of multiple myeloma (MM) to bortezomib (BTZ) has brought multiple challenges to its clinical use. Numerous ginsenosides have potential anti-tumor effects, however, the research on the role of Rg1 in MM has not been reported., Objective: To examine the inhibitory impact of Rg1 on the growth of MM and reduce the drug resistance of MM to BTZ through in vivo and in vitro experiments, and to explore their potential mechanism., Methods: BTZ drug-resistant cell line RPMI8226R was constructed. Mouse tumor-bearing model was developed by abdominal subcutaneous injection of MM cells. MM cells were treated with AMPK inhibitor Compound C or autophagy inhibitor Chloroquine together with Rg1. RPMI8226R cells were treated with BTZ and Rg1. Cell multiplication was detected using Methylthiazolyldiphenyl-tetrazolium bromide assay. Apoptosis was assessed using flow cytometry. Immunofluorescence assay was employed to assess the autophagy markers LC3. Western blot was utilized to assess the protein expression. Immunohistochemistry was used to detect cell proliferation and apoptosis in tumor tissues., Results: In vitro experiments demonstrated that Rg1 could hinder the proliferation of MM cells, promote apoptosis and enhance autophagy. Rg1 could also increase the sensitivity of RPMI8226R to BTZ. In vivo experiments illustrated that Rg1 could hinder the development of MM cells in mice, weaken the proliferation of tumor cells and enhance their apoptosis. Further study found that the anti-MM impact of Rg1 was linked to AMPK-mTOR pathway, the autophagy degree of RPMI8226R was higher than that of RPMI8226, and that Rg1 could inhibit MM and overcome drug resistance through autophagy induced by AMPK-mTOR pathway., Conclusion: Rg1 has significant anti-MM effect and can overcome BTZ resistance, and its potential mechanism is related to the regulation of autophagy induced by AMPK-mTOR pathway. Rg1 is a promising adjuvant drug for the treatment of MM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Ginsenoside Rg 1 (Rg 1 ) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng . Research has shown that Rg 1 has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood., Methods: Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV-Vis and fluorescence spectra) techniques, potential targets and pathways for Rg 1 against myocardial ischemia (MI) were screened and explored., Results: An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg 1 against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg 1 intervention on H9c2 cells injured by H 2 O 2 showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg 1 on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg 1 was also evaluated., Conclusion: Rg 1 can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg 1 , and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Alzheimer’s disease (AD) is a common neurodegenerative disorder in the elderly characterized by memory loss and cognitive dysfunction. The pathogenesis of AD is complex. One-targeted anti-AD drugs usually fail to delay AD progression. Traditional Chinese medicine records have documented the use of the roots of Panax ginseng (ginseng roots) and its prescriptions to treat dementia. Ginsenoside Rg1, the main ginsenoside component of ginseng roots, exhibits a certain therapeutic effect in the abovementioned diseases, suggesting its potential in the management of AD. Therefore, we combed the pathogenesis of AD and currently used anti-AD drugs, and reviewed the availability, pharmacokinetics, and pharmaceutic studies of ginsenoside Rg1. This review summarizes the therapeutic effects and mechanisms of ginsenoside Rg1 and its deglycosylated derivatives in AD in vivo and in vitro. The main mechanisms include improvement in Aβ and Tau pathologies, regulation of synaptic function and intestinal microflora, and reduction of inflammation, oxidative stress, and apoptosis. The underlying mechanisms mainly involve the regulation of PKC, MAPK, PI3K/Akt, CDK5, GSK-3β, BDNF/TrkB, PKA/CREB, FGF2/Akt, p21WAF1/CIP1, NF-κB, NLRP1, TLR3, and TLR4 signaling pathways. As the effects and underlying mechanisms of ginsenoside Rg1 on AD have not been systematically reviewed, we have provided a comprehensive review and shed light on the future directions in the utilization of ginsenoside Rg1 and ginseng roots as well as the development of anti-AD drugs.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Progressive loss of dopaminergic neurons in the substantia nigra (SN) is one of the major pathological changes. However, the reasons for the dopaminergic neuron loss are still ambiguous and further studies are needed to evaluate the in-depth mechanisms of neuron death. Oxidative stress is a significant factor causing neuronal damage. Dopaminergic neurons in the SN are susceptible to oxidative stress, which is closely associated with iron dyshomeostasis in the brain. Ginsenoside Rg1 from ginseng plays a crucial role in neuroprotective effects through anti-inflammation and attenuating the aggregation of abnormal α-synuclein. In our study, we established a chronic PD mouse model by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine combined with probenecid and explored the effect of Rg1 on the oxidative stress and brain iron homeostasis. Rg1 was verified to improve the level of tyrosine hydroxylase and anti-oxidant stress. In addition, Rg1 maintained the iron-regulated protein homeostasis by increasing the expression of ferritin heavy chain and decreasing ferritin light chain in oligodendrocytes, especially the mature oligodendrocytes (OLs). Furthermore, Rg1 had a positive effect on the myelin sheath protection and increased the number of mature oligodendrocytes, proved by the increased staining of myelin basic protein and CC-1. In conclusion, Rg1 could play a neuroprotective role through remitting the iron-regulated protein dyshomeostasis by ferritin and against lipid peroxidation stress in oligodendrocytes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Inflammation leads to porcine tight junction disruption of small intestinal epithelial cells, resulting in intestinal dysfunction. Herein, we established lipopolysaccharide (LPS)-induced in-vivo and in-vitro inflammatory models. The results revealed that LPS induced tight junction disruption in IPEC-J2 cells by downregulating tight-junction-related protein zonula occludens-1 (ZO-1), occludin and claudin-1 expression, while ginsenoside Rg1 rescued such inhibition and abrogated the upregulated expression of phosphorylation p38 MAPK. The p38 MAPK inhibitor (SB203580) showed a similar effect with Rg1 and attenuated the LPS-induced inhibition of ZO-1, occludin and claudin-1 expression, which is consistent with the reduced expression of NLRP3 inflammasome and IL-1β. Furthermore, the specific inhibitors of NLRP3 and IL-1β result in increased expression of tight-junction-related protein, demonstrating that p38 MAPK signaling was associated with Rg1 suppression of tight junction disruption. Besides, LPS treatment decreased the expression of ZO-1, occludin and claudin-1 through p38 MAPK signaling, and caused abnormal morphological changes in murine ileum. Meanwhile, Rg1 attenuated the decreased expression of ZO-1, occludin and claudin-1 and partially alleviated LPS-induced morphological changes in murine ileum. In summary, these findings characterized a novel mechanism by which Rg1 alleviates LPS-induced intestinal tight junction disruption by inhibiting the p38 MAPK-mediated NLRP3 inflammasome pathway. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disorder in the gastrointestinal tract. Here, we examined the pharmacological effects of ginsenoside Rg1, a natural compound with low bioavailability, on the acute experimental colitis mice induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Acute UC was induced in C57BL/6 mice by 2.5% DSS for 7 days, meanwhile, 2 mg/10 g b.w. ginsenoside Rg1 was administrated to treat the mice. Body weight, colon length, colon tissue pathology, and colon tissue inflammatory cytokines were assessed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. Global metabolomic profiling of the feces was performed, and tryptophan and its metabolites in the serum were detected. The results showed that Rg1 significantly ameliorated DSS-induced colonic injury and colonic inflammation. In addition, Rg1 also partly reversed the imbalance of gut microbiota composition caused by DSS. Rg1 intervention can regulate various metabolic pathways of gut microbiota such as valine, leucine, and isoleucine biosynthesis and vitamin B6 metabolism and the most prominent metabolic alteration was tryptophan metabolism. DSS decreased the levels of tryptophan metabolites in the serum, including indole-3-carboxaldehyde, indole-3-lactic acid, 3-indolepropionic acid, and niacinamide and Rg1 can increase the levels of these metabolites. In conclusion, the study discovered that Rg1 can protect the intestinal barrier and alleviate colon inflammation in UC mice, and the underlying mechanism is closely related to the regulation of gut microbiota composition and microbial tryptophan metabolism. [ABSTRACT FROM AUTHOR]

As a common chronic skin disease, psoriasis is characterized by the involvement of congenital acquired inflammatory immune diseases. In the study, our results indicated the effect of ginsenoside Rg1 on psoriasis‐like skin and the potential protection mechanisms that have not yet been investigated. In vivo, psoriasis‐like skin mice model was induced by imiquimod (IMQ), then was treated by ginsenoside Rg1 for consecutive 4 weeks to evaluate its effect, respectively. In vitro, M5 cocktail treatment of human immortalized keratinocyte HaCaT‐induced psoriasis‐like skin cell model, which was exposed to ginsenoside Rg1. The inflammatory cell infiltration, expression level of keratinocyte proliferation marker Ki67, keratinocyte proliferation, inflammatory cytokines, and ROS/NLRP3 pathway‐related proteins in vivo and in vitro were examined by hematoxylin and eosin, immunohistochemistry, ELISA, CCK‐8, flow cytometry, and western blot. All results demonstrated that ginsenoside Rg1 attenuated the injury of psoriasis‐like skin, which inhibited the proliferation of skin keratinocytes and the activation of NLRP3 inflammasome and the level of inflammatory factors such as IL‐1β and IL‐18, and decreased the level of Ki67, NLRP3, and caspase‐1 in mice and HaCaT. Furthermore, NLRP3 overexpression attenuates the effect of ginsenoside Rg1 on M5 cocktail‐induced proliferation and NLRP3 inflammasomes in HaCaT. These results demonstrated that ginsenoside Rg1 could suppress the ROS/NLRP3 pathway to treat psoriasis‐like skin. Practical applications: This is the very first study to explore the efficacy of ginsenoside Rg1 against psoriasis‐like skin lesions to reveal the underlying mechanism. In this paper, the detection of skin histopathological analysis, CCK‐8, flow cytometry, western blot, and ELISA analysis shows that ginsenoside Rg1 has preventive effect on psoriasis caused by imiquimod or M5 cocktail through inhibiting NLRP3 inflammasome, which helps in the development of novel nutraceutical/functional food against psoriasis and thus could improve the quality of life in psoriasis patients. [ABSTRACT FROM AUTHOR]

Bacterial infection is one of the most frequent complications in the burn and chronic wounds. Inspired by natural existing superhydrophobic surface structures, a novel asymmetric wettable membrane was prepared using the electrospinning technique for facilitating the bacteria‐infected wound healing. Herein, the prepared membrane consists of two layers: The hydrophobic outer layer was composed of poly (lactic‐co‐glycolic) acid (PLGA) and black phosphorus‐grafted chitosan (HACC‐BP), while the hydrophilic inner layer was composed by using a mixture of gelatin (Gel) with ginsenoside Rg1 (Rg1). Biological studies in vitro showed BP@PLGA/Gel (BP@BM) membrane with excellent antibacterial activity could significantly inhibit the adhesion of bacteria, and Rg1 could facilitate the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Compared to Aquacel Ag dressing, the result in vivo revealed that the Rg1/BP@BM could facilitate better wound healing by triggering phosphoinositide 3‐kinase (P‐PI3K/PI3K) and phosphorylation of protein kinase B (P‐AKT/AKT) signaling pathways, upregulating Ki67, CD31, α‐SMA, and TGF‐β1, and downregulating TNF‐α, IL‐1β, and IL‐6, promoting M2 polarization (IL‐10, CD206, and Arg‐1) of macrophages, inhibiting M1 polarization (iNOS) of macrophages. These findings suggested that the asymmetric wettable membrane have the huge potential for wound healing. [ABSTRACT FROM AUTHOR]

Ginsenoside Rg1 is the principal active ingredient in ginseng. The antidepressant effects of Rg1 have been validated; however, the specific underlying mechanism of this effect needs further research. Rats were subjected to the chronic restraint stress (CRS) depression model. Rg1, or a positive control drug, was administered to the rats. Depression-like behaviours were evaluated through behavioural experiments. Cytokine, mRNA, protein, ATP, and mitochondria DNA levels were detected using the indicated methods. Lentivirus-packaged plasmids were injected into the rat brain for GAS5 overexpression or knockdown. In vitro mitochondrial dysfunction was evaluated by detecting mitochondrial reactive oxygen species and mitochondrial membrane potential. Direct interaction between GAS5 and EZH2 was validated by RNA immunoprecipitation and RNA pull-down assay. The enrichment of EZH2 and H3K27me3 was evaluated through chromatin immunoprecipitation quantitative real-time PCR. Rg1 treatment alleviated depression-like behaviours, microglial activation, and mitochondrial dysfunction in CRS rats. Similarly, GAS5 knockdown revealed a similar protective effect of Rg1 treatment. GAS5 overexpression in the rat brain compromised the protective effect of Rg1 treatment. Moreover, Rg1 treatment or GAS5 knockdown attenuated microglial activation and mitochondrial dysfunction in vitro. Mechanically, GAS5 was suppressed SOCS3 and NRF2 expression by facilitating EZH2-mediated transcriptional repression. Rg1 attenuated microglial activation and improved mitochondrial dysfunction in depression by downregulating GAS5 expression. Mechanically, GAS5 might regulate microglial activation and mitochondrial dysfunction via the epigenetic suppression of NRF2 and SOCS3. [ABSTRACT FROM AUTHOR]

Many technologies have been developed for breast reconstruction after lumpectomy. Although the technologies achieved promising success in clinical, there are still many shortages hanging over and trouble the researchers. Tissue engineering technology was introduced to plastic surgery that gave a light to lumpectomy patients in breast reconstruction. The unexpected absorption rate, resulting from limited vascularization and low cell survival rate, is a major factor that leads to unsatisfactory results for the previous studies in our lab. In the study, the laminin-modified alginate synthesized by a new method of low concertation of sodium periodate would be mixed with ADSCs and Rg1 in the medium; and then sprayed into a calcium chloride (CaCl2) solution to prepare into microsphere (abbreviated as ADSC–G-LAMS) by bio-electrospray with a power syringe for the mass production and smaller bead size. The developed ADSC–G-LAMS microspheres had the diameter of 232 ± 42 μm. Sustained-release of the Rg1 retained its biological activity. WST-1, live/dead staining, and chromosome aberration assay were evaluated to confirm the safety of the microspheres. In in vivo study, ADSC–G-LAMS microspheres combined with autologous adipocytes were transplanted into the dorsum of rats by subcutaneous injection. The efficacy was investigated by H&E and immunofluorescence staining. The results showed that the bioactive ADSC–G-LAMS microspheres could integrate well into the host adipose tissue with an adequate rate of angiogenesis by constantly releasing Rg1 to enhance the ADSC or adipocyte survival rate to join tissue growth and repair with adipogenesis for breast reconstruction after lumpectomy.

Objective To investigate the protective effects and primary mechanism of ginsenoside Rg1 on cardiac muscle of aging mice induced by D-galactose (D-gal). Methods C57BL/6 J mice were randomly divided into normal control, model, Rg1 intervention and negative control groups, with 10 animals in each group. D-gal (200 mg/kg) was injected intraperitoneally to the mice for 42 d to establish the model group, and the mice of the Rg1 intervention group was given 40 mg/kg Rg1 per day for 26 d intraperitoneally from the 16th day of model establishment. The mice of the normal control group were given same amount of normal saline for 42 d, and those of the negative control group were treated with normal saline after model establishment. On the 2nd day after treatment, the hearts were taken to measure the organ index. HE staining and transmission electron microscopy were performed to observe the morphology and micro-structures of the heart tissue from each group. The activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total superoxide dismutase (T-SOD), catalase (CAT) and contents of malondialdehyde (MDA) in the myocardial tissue homogenate were tested by enzyme-labeled colorimetry; The expression levels of Nrf2, Keap1 and HO-1 in the heart tissue were detected by Western blotting. Results Compared with the control group, the model group had significantly increased heart index (P < 0.01); larger amount of deposited collagen fibers between myocardial fibers, disordered myofibril bundles, thicker myocardial fibers, and abnormally swollen mitochondria; enhanced AST and LDH activities, declined T-SOD and CAT activities, and increased MDA content (P < 0.05); remarkably down-regulation of Nrf2 and HO-1 (P < 0.05), and no changed Keap1 level. While in the Rg1 intervention group, all the above phenomena were greatly improved after the intervention, with obviously decreased heart index (P < 0.01), not notable morphological changes with normal control mice, reversed AST, LDH, T-SOD and CAT activities and MDA contents(P < 0.05), and elevated protein levels of Nrf2 and HO-1, and decreased level of Keap1 (P < 0.01). Conclusion Rg1 effectively alleviates the damage of D-gal to the morphology and ultrastructure of mouse myocardium, and its mechanism may be related to the inhibition of oxidative stress and the up-regulation of the Nrf2 antioxidant signal pathway.

Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

Ginseng (Panax ginseng C. A. Mey) is a common traditional Chinese medicine used for anti-inflammation, anti-apoptosis, anti-oxidative stress, and neuroprotection. Ginsenosides Rg1, the main active components isolated from ginseng, may be a feasible therapy for spinal cord injury (SCI). SCI causes endothelial cell death and blood vessel rupture, ultimately resulting in long-term neurological impairment. As a result, encouraging spinal angiogenesis may be a feasible therapy for SCI. This investigation aimed to validate the capacity of ginsenoside Rg1 in stimulating angiogenesis within the spinal cord. Rats with SCI were injected intraperitoneally with ginsenoside Rg1. The effectiveness of ginsenoside Rg1 was assessed using the motor function score and the motor-evoked potential (MEP). Immunofluorescence techniques were applied to identify the spinal cord's angiogenesis. Angiogenic factors were examined through Western Blot (WB) and Immunohistochemistry. Oxygen-glucose deprivation (OGD) was employed to establish the hypoxia-ischemia model in vitro, and astrocytes (As) were given ginsenoside Rg1 and co-cultured with spinal cord microvascular endothelial cells (SCMECs). Immunofluorescence, wound healing test, and tube formation assay were used to identify the co-cultured SCMECs' activity. Finally, network pharmacology analysis and siRNA transfection were applied to verify the mechanism of ginsenoside Rg1 promoting angiogenesis. The rats with SCI treated with ginsenoside Rg1 indicated more significant functional recovery, more pronounced angiogenesis, and higher levels of angiogenic factor expression. In vitro, the co-culture system with ginsenoside Rg1 intervention improved SCMECs' capacity for proliferating, migrating, and forming tubes, possibly by promoting the expression of vascular endothelial growth factor (VEGF) in As via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Ginsenoside Rg1 can regulate As to promote angiogenesis, which may help to understand the mechanism of promoting SCI recovery. Schematic illustration of the role of ginsenoside Rg1 in promoting angiogenesis during spinal cord injury. Ginsenoside Rg1 modulates the activity of astrocytes, promoting the secretion of VEGF via the JAK2/STAT3 pathway. This up-regulated expression of VEGF by astrocytes has a subsequent effect on spinal microvascular endothelial cells, leading to enhanced proliferation, migration, and tubulation of these cells, ultimately contributing to angiogenesis in spinal cord injury. [Display omitted] • Ginsenoside Rg1 can be used as a potential therapeutic agent for effective treatment of spinal cord injury. • Ginsenoside Rg1 regulates astrocytes to promote angiogenesis in spinal cord injury. • JAK2-STAT3 is a key signaling pathway for angiogenesis in spinal cord injury. [ABSTRACT FROM AUTHOR]

This study aimed to further elucidate the mechanism of ginsenoside Rg1 in the treatment of cerebral ischemia-reperfusion. In this study, we observed the apoptosis of RM cells (microglia) after oxygen-glucose deprivation/reoxygenation (OGD/R) modeling before and after Rg1 administration, changes in mitochondrial membrane potential, changes in the content of Reactive oxygen species (ROS) and inflammatory vesicles NLR Family Pyrin Domain Containing 3 (NLRP3), and the expression levels of autophagy-related proteins, inflammatory factors, and apoptosis proteins. We further examined the pathomorphological changes in brain tissue, neuronal damage, changes in mitochondrial morphology and mitochondrial structure, and the autophagy-related proteins, inflammatory factors, and apoptosis proteins expression levels in CI/RI rats before and after administration of Rg1 in vivo experiments. In vitro experiments showed that Rg1 induced mitochondrial autophagy, decreased mitochondrial membrane potential, and reduced ROS content thereby inhibiting NLRP3 activation, decreasing secretion of inflammatory factors and RM cell apoptosis by regulating the PTEN induced putative kinase 1(Pink1) /Parkin signaling pathway. In vivo experiments showed that Rg1 induced mitochondrial autophagy, inhibited NLRP3 activation, improved inflammatory response, and reduced apoptosis by regulating the Pink1/Parkin signaling pathway, and Rg1 significantly reduced the area of cerebral infarcts, improved the pathological state of brain tissue, and attenuated the neuronal damage, thus improving cerebral ischemia/reperfusion injury in rats. Our results suggest that ginsenoside Rg1 can ameliorate cerebral ischemia-reperfusion injury by modulating Pink1/ Parkin-mediated mitochondrial autophagy in microglia and inhibiting microglial NLRP3 activation. • Ginsenoside Rg1 significantly improves cerebral hemorrhagic reperfusion injury. • Ginsenoside Rg1 attenuates microglial cell inflammatory response. • Ginsenoside Rg1 reduces mitochondrial autophagy in microglia and inhibits inflammatory vesicle activation. [ABSTRACT FROM AUTHOR]

Chronic renal injury (CRI) is a common pathological damage in chronic renal disease, and the therapeutic options for preventing its progression are limited at present. Ginsenoside Rg1 (Rg1) is reported to have a protective effect on renal injury by improving oxidative stress and inflammation. Lipopolysaccharide (LPS) plays important roles in inducing inflammatory and high-dose LPS is often used to perform acute renal injury. However, little is known about the effect of low-dose LPS on CRI, and the protective effect of Rg1 against chronic LPS-induced CRI. Here, we reported the protective effect and mechanism of Rg1 against LPS-induced CRI in mice. In this study, the results demonstrated that low-dose LPS (0.25 mg/kg) exposure for 14 days significantly induced renal function impairment and renal injury and fibrosis. Meanwhile, LPS exposure significantly increased reactive oxygen species (ROS) generation, NADPH oxidase 4 (NOX4) and NLRP3 inflammasome expression in renal cortex. However, treatment with Rg1, tempol (a superoxide dismutase mimetic), and apocynin (a NOX inhibitor) significantly improved renal function impairment and renal fibrosis, and significantly decreased the levels of TGF-β, IL-1β, KIM-1, β-Gal, and collagen IV in the kidneys. And Rg1 treatment also significantly reduced ROS generation and inhibited the activation of NOX4 and NLRP3 inflammasome. Overall, these results suggest that Rg1 treatment can ameliorate LPS-induced chronic kidney injury and renal fibrosis, the mechanisms may be involved in reducing NOX2-mediated oxidative stress and inhibiting NLRP1 inflammasome.

Background: Morphine dependence, a devastating neuropsychiatric condition, may be closely associated with gut microbiota dysbiosis. Ginsenoside Rg1 (Rg1), an active ingredient extracted from the roots of Panax ginseng C.A. Meyer, has potential health-promoting effects on the nervous system. However, its role in substance use disorders remains unclear. Here, we explored the potential modulatory roles of Rg1 in protection against morphine dependence. Methods: Conditioned place preference (CPP) was used for establishing a murine model of morphine dependence. 16S rRNA gene sequencing and metabolomics were performed for microbial and metabolite analysis. Molecular analysis was tested for evaluating the host serum and brain responses. Results: Rg1 prevented morphine-induced CPP in mice. The 16S rRNA gene-based microbiota analysis demonstrated that Rg1 ameliorated morphine-induced gut microbiota dysbiosis, specifically for Bacteroidetes. Moreover, Rg1 also inhibited gut microbiota-derived tryptophan metabolism and reduced the serotonin, 5-hydroxytryptamine receptor 1B (5-HTR1B), and 5-hydroxytryptamine receptor 2 A (5-HTR2A) levels. However, the Rg1-induced amelioration of CPP was not observed in mice when their gut microbiome was depleted by non-absorbable antibiotics. Subsequently, gavage with Bacteroides vulgatus increased the abundance of Bacteroidetes. B. vulgatus supplementation synergistically enhanced Rg1-alleviated morphine-induced CPP in mice with microbiome knockdown. Co-treatment with B. vulgatus and Rg1 produced suppressive effects against morphine dependency by inhibiting tryptophan metabolism and reducing the serotonin and 5-HTR1B/5-HTR2A levels. Conclusions: The gut microbiota-tryptophan metabolism-serotonin plays an important role in gut–brain signaling in morphine disorders, which may represent a novel approach for drug dependence treatment via manipulation of the gut microbial composition and tryptophan metabolite.

Recombinant protein vaccines, with highly pure ingredients and good safety, are gradually replacing some attenuated and inactivated vaccines in clinical practice. However, since their low immunogenicity of the recombinant proteins, adjuvants are often needed to enhance immune response after vaccination. Aluminum adjuvant has been widely used in some vaccines for decades, it can induce strong humoral immunity, but the deficiency of cellular immunity limits its application for some vaccines. Therefore, it is urgently needed to develop novel adjuvant to increase not only humoral but also cellular immune response. To address this, we designed and prepared a new nano adjuvant (PF3) through microfluidization by the combination of saponin (Ginsenoside Rg1) and oil-in-water nano emulsion (NE) in the present study. As compared to aluminum adjuvant, PF3 had stronger humoral and cellular immune induction effect because of high cellular uptake and activization of immune response pathways. Furthermore, PF3 showed better immune enhancement and acceptable biosafety equivalent to that of aluminum adjuvant. In addition, no obvious changes of PF3 were observed in size and zeta potential after 12 weeks storage at 4 and 37°C, demonstrating its high stability in vitro. This study provided an adjuvant platform to replace traditional aluminum adjuvant in design of recombinant vaccines.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disorder in the gastrointestinal tract. Here, we examined the pharmacological effects of ginsenoside Rg1, a natural compound with low bioavailability, on the acute experimental colitis mice induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Acute UC was induced in C57BL/6 mice by 2.5% DSS for 7 days, meanwhile, 2 mg/10 g b.w. ginsenoside Rg1 was administrated to treat the mice. Body weight, colon length, colon tissue pathology, and colon tissue inflammatory cytokines were assessed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. Global metabolomic profiling of the feces was performed, and tryptophan and its metabolites in the serum were detected. The results showed that Rg1 significantly ameliorated DSS-induced colonic injury and colonic inflammation. In addition, Rg1 also partly reversed the imbalance of gut microbiota composition caused by DSS. Rg1 intervention can regulate various metabolic pathways of gut microbiota such as valine, leucine, and isoleucine biosynthesis and vitamin B6 metabolism and the most prominent metabolic alteration was tryptophan metabolism. DSS decreased the levels of tryptophan metabolites in the serum, including indole-3-carboxaldehyde, indole-3-lactic acid, 3-indolepropionic acid, and niacinamide and Rg1 can increase the levels of these metabolites. In conclusion, the study discovered that Rg1 can protect the intestinal barrier and alleviate colon inflammation in UC mice, and the underlying mechanism is closely related to the regulation of gut microbiota composition and microbial tryptophan metabolism.

Abstract Bacterial infection is one of the most frequent complications in the burn and chronic wounds. Inspired by natural existing superhydrophobic surface structures, a novel asymmetric wettable membrane was prepared using the electrospinning technique for facilitating the bacteria‐infected wound healing. Herein, the prepared membrane consists of two layers: The hydrophobic outer layer was composed of poly (lactic‐co‐glycolic) acid (PLGA) and black phosphorus‐grafted chitosan (HACC‐BP), while the hydrophilic inner layer was composed by using a mixture of gelatin (Gel) with ginsenoside Rg1 (Rg1). Biological studies in vitro showed BP@PLGA/Gel (BP@BM) membrane with excellent antibacterial activity could significantly inhibit the adhesion of bacteria, and Rg1 could facilitate the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Compared to Aquacel Ag dressing, the result in vivo revealed that the Rg1/BP@BM could facilitate better wound healing by triggering phosphoinositide 3‐kinase (P‐PI3K/PI3K) and phosphorylation of protein kinase B (P‐AKT/AKT) signaling pathways, upregulating Ki67, CD31, α‐SMA, and TGF‐β1, and downregulating TNF‐α, IL‐1β, and IL‐6, promoting M2 polarization (IL‐10, CD206, and Arg‐1) of macrophages, inhibiting M1 polarization (iNOS) of macrophages. These findings suggested that the asymmetric wettable membrane have the huge potential for wound healing.

[Display omitted] • LPS can activate the AIM2 inflammasome in the kidney. • AIM2 is regulated by Nrf2 under CKD condition. • Ginsenoside Rg1 can direct binds to Nrf2 protein. • The nephroprotective effect of ginsenoside Rg1 is reliant on Nrf2. Chronic kidney disease (CKD) is a growing global public health issue. Ginsenoside Rg1 (Rg1) has favorable nephroprotective effects, but its role and mechanism in CKD need further investigation. Therefore, we observed the effect of Rg1 on the mouse kidneys after 21 days of low-dose lipopolysaccharide (LPS) exposure. Meanwhile, we investigated the protective mechanism of Rg1 in LPS-induced mesangial cells using the Nrf2 inhibitor ML385. We found that chronic exposure to LPS caused fibrosis in mouse kidneys, accompanied by AIM2 activation and oxidative stress imbalance; however, Rg1 restored the anomalies, accompanied by activation of Nrf2/HO-1 signaling. Finally, our in vitro studies revealed that Rg1′s nephroprotective effects could be inhibited by ML385, and Rg1 can bind Nrf2, suggesting that the protective effects of Rg1 may involve Nrf2 activation and then inhibition of the AIM2. Our study has significant implications for the prevention and treatment of kidney diseases, particularly those related to inflammation. [ABSTRACT FROM AUTHOR]

Ginseng (Panax ginseng C. A. Meyer) is a precious traditional Chinese medicine with multiple pharmacological effects. Ginsenoside Rg1 is a main active ingredient extracted from ginseng, which is known for its age-delaying and antioxidant effects. Increasing evidence indicates that Rg1 exhibits anti-inflammatory properties in numerous diseases and may ameliorate oxidative damage and inflammation in many chronic liver diseases. Chronic inflammatory injury in liver cells is an important pathological basis of many liver diseases. However, its mechanism remains unclear and therapeutic strategies to prevent its development need to be further explored. Thus, our study is to delve the protective effect and mechanism of Rg1 against chronic hepatic inflammatory injuries induced by lipopolysaccharide (LPS). The chronic liver damage model in mice was build up by injecting intraperitoneally with LPS (200 μg/kg) for 21 days. Serum liver function indicators and levels of IL-1β, IL-6 and TNF-α were examined by using corresponding Kits. Hematoxylin and Eosin (H&E), Periodic acid-Schiff (PAS), and Masson stains were utilized to visualize hepatic histopathological damage, glycogen deposition, and liver fibrosis. The nuclear import of p-Nrf2 and the generation of Col4 in the liver were detected by IF, while IHC was employed to detect the expressions of NLRP3 and AIM2 in the hepatic. The Western blot and q-PCR were used to survey the expressions of proteins and mRNAs of fibrosis and apoptosis, and the expressions of Keap1, p-Nrf2 and NLRP3, NLRP1, AIM2 inflammasome-related proteins in mouse liver. The cell viability of human hepatocellular carcinoma cells (HepG2) was detected by Cell Counting Kit-8 to select the action concentration of LPS, and intracellular ROS generation was detected using a kit. The expressions of Nuclear Nrf2, HO-1, NQO1 and NLRP3, NLRP1, and AIM2 inflammasome-related proteins in HepG2 cells were detected by Western blot. Finally, the feasibility of the molecular interlinking between Rg1 and Nrf2 was demonstrated by molecular docking. Rg1 treatment for 21 days decreased the levels of ALT, AST, and inflammatory factors of serum IL-1β, IL-6 and TNF-α in mice induced by LPS. Pathological results indicated that Rg1 treatment obviously alleviated hepatocellular injury and apoptosis, inflammatory cell infiltration and liver fibrosis in LPS stimulated mice. Rg1 promoted Keap1 degradation and enhanced the expressions of p-Nrf2, HO-1 and decreased the levels of NLRP1, NLRP3, AIM2, cleaved caspase-1, IL-1β and IL-6 in livers caused by LPS. Furthermore, Rg1 effectively suppressed the rise of ROS in HepG2 cells induced by LPS, whereas inhibition of Nrf2 reversed the role of Rg1 in reducing the production of ROS and NLRP3, NLRP1, and AIM2 expressions in LPS-stimulated HepG2 cells. Finally, the molecular docking illustrated that Rg1 exhibits a strong affinity towards Nrf2. The findings indicate that Rg1 significantly ameliorates chronic liver damage and fibrosis induced by LPS. The mechanism may be mediated through promoting the dissociation of Nrf2 from Keap1 and then activating Nrf2 signaling and further inhibiting NLRP3, NLRP1, and AIM2 inflammasomes in liver cells. [Display omitted] • Rg1 treatment attenuates LPS-induced chronic liver injury and alleviates fibrosis. • Rg1 treatment attenuates LPS-induced ROS accumulation and hepatocyte inflammation. • Rg1 treatment alleviates LPS-induced chronic liver injury by activating Nrf2 signaling. • Rg1 treatment inhibits LPS-induced hepatocyte NLRP3, NLRP1, and AIM2 inflammasomes. [ABSTRACT FROM AUTHOR]

β-thalassemia, a globally prevalent genetic disorder, urgently requires innovative treatment options. Fetal hemoglobin (HbF) induction stands as a key therapeutic approach. This investigation focused on Ginsenoside Rg1 from the Panax genus for HbF induction. Employing K562 cells and human erythroid precursor cells (ErPCs) derived from neonatal cord blood, the study tested Rg1 at different concentrations. We measured its effects on γ-globin mRNA levels and HbF expression, alongside assessments of cell proliferation and differentiation. In K562 cells, Rg1 at 400 μM significantly increased γ-globin mRNA expression by 4.24 ± 1.08-fold compared to the control. In ErPCs, the 800 μM concentration was most effective, leading to an over 80% increase in F-cells and a marked upregulation in HbF expression. Notably, Rg1 did not adversely affect cell proliferation or differentiation, with the 200 μM concentration showing an increase in γ-globin mRNA by 2.33 ± 0.58-fold, and the 800 μM concentration enhancing HbF expression by 2.59 ± 0.03-fold in K562 cells. Our results underscore Rg1's potential as an effective and safer alternative for β-thalassemia treatment. By significantly enhancing HbF levels without cytotoxicity, Rg1 offers a notable advantage over traditional treatments like Hydroxyurea. While promising, these in vitro findings warrant further in vivo exploration to confirm Rg1's therapeutic efficacy and to unravel its underlying mechanistic pathways. [Display omitted] • Ginsenoside Rg1 identified as a potent HbF inducer for β-thalassemia. • Ginsenoside Rg1 boosts γ-globin and HbF expression without hindering K562 growth. • Ginsenoside Rg1 elevates γ-globin and HbF in ErPCs without affecting proliferation. • Ginsenoside Rg1 promotes erythroid differentiation similarly to HU, minus the cytotoxicity. [ABSTRACT FROM AUTHOR]

Ginsenosides, active substances in Panax ginseng C. A. Meyer (ginseng), extend lifespan in multiple species, ameliorate age-associated damage, and limit functional decline in multiple tissues. However, their active components and their molecular mechanisms are largely unknown. Here, ginsenoside Rg1 (Rg1) promoted longevity in Saccharomyces cerevisiae. Treatment with Rg1 decreased aging-mediated surface wrinkling, enhanced stress resistance, decreased reactive oxygen species’ production and apoptosis, improved antioxidant enzyme activity, and decreased the aging rate. Proteomic analysis indicated that Rg1 delays S. cerevisiae senescence by regulating metabolic homeostasis. Protein–protein interaction networks based on differential protein expression indicated that CDC19, a homologue of pyruvate kinase, and SDH2, the succinate dehydrogenase iron–sulfur protein subunit, might be the effector proteins involved in the regulation by Rg1. Further experiments confirmed that Rg1 improved specific parameters of mitochondrial bioenergetics and core enzymes in the glycolytic pathway. Mutant strains were constructed that demonstrated the relationships between metabolic homeostasis and the predicted target proteins of Rg1. Rg1 could be used in new treatments for slowing the aging process. Our results also provide a useful dataset for further investigations of the mechanisms of ginseng in aging.

Background: Many studies that use food containing Panax genus plants (PGPs) have been conducted but most of them have not mentioned the effective compounds ginsenosides and their composition. Therefore, we conducted a systematic review and meta-analysis of time to exhaustion as an index of exercise endurance with ingestion of PGPs or ginsenosides to reveal their effects. Methods: We performed a systematic review with a comprehensive and structured literature search using seven literature databases, four clinical trial databases, and three general web search engines during 15–22 March 2021. A random-effects model was applied to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) as the difference between the mean in the treatment and placebo groups. We evaluated the risk of bias of individual studies along with the risk of bias tool in the Cochrane handbook. This study was funded by Maruzen Pharmaceuticals Co., Ltd. (Hiroshima, Japan). The protocol for this study was registered with the UMIN-CTR (No. UMIN000043341). Results: Five studies met the inclusion criteria. The number of total participants was 90, with 59 in the ingestion-PGPs group and 64 in the control group, because three studies were crossover-design trials. We found that ingestion of PGPs or ginsenosides significantly improved exercise endurance (SMD [95% CI]: 0.58 [0.22–0.95], I2 = 0%). It was suggested that ginsenoside Rg1 (Rg1) and PGPs extract containing Rg1 were significantly effective in improving exercise endurance (SMD [95% CI]: 0.70 [0.14–1.27], I2 = 30%) by additional analysis. Conclusions: This systematic review suggests that the ingestion of PGPs or ginsenosides, especially Rg1, is effective in improving exercise endurance in healthy adults. However, further high-quality randomized controlled trials are required because imprecision and publication bias cannot be ignored in this systematic review. [ABSTRACT FROM AUTHOR]

The protective mechanism of ginsenoside Rg1 for Alzheimer's disease induced by Amyloid β-Protein has rarely been reported. To evaluate the cerebroprotective effects of ginsenoside Rg1 on Alzheimer's disease rats. Male Sprague Dawley rats were randomly divided into 5 groups (n=10). Alzheimer's disease model was established by injecting Amyloid β-Protein into the hippocampal CA1 area. Rg1 group, specific phosphoinositide 3-kinase inhibitor LY294002 group and Rg1 plus LY294002 group were intraperitoneally injected with corresponding drugs, once daily for 28 consecutive d. The spatial learning and memory abilities were studied by water maze and platform tests respectively. The pathological changes of hippocampal CA1 area were observed by hematoxylin and eosin staining. Neuronal apoptosis was detected by Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling assay. Protein kinase B and Glycogen synthase kinase 3 beta protein expressions were measured by Western blotting. Compared with model group, the learning and memory abilities of Rg1 group were significantly improved (p<0.05), and the abnormal morphology of neurons in Rg1 group and their apoptosis were significantly relieved (p<0.05). Compared with model group, the superoxide dismutase and glutathione peroxidase levels of Rg1 group increased significantly, whereas that of Malondialdehyde decreased significantly (p<0.05). Compared with model group, the Protein kinase B and Glycogen synthase kinase 3 beta phosphorylation levels of Rg1 group significantly increased (p<0.05). LY294002 and Rg1+LY294002 groups had similar results (p>0.05). Ginsenoside Rg1 may mitigate Amyloid β-Protein induced Alzheimer's disease by activating the phosphoinositide 3-kinase/Protein kinase B/Glycogen synthase kinase 3 beta signaling pathway, inhibit neuronal apoptosis in the hippocampus and attenuate oxidative stress, exerting cerebroprotective effects. [ABSTRACT FROM AUTHOR]

This study determined the chemosensitizing potential of ginsenoside Rg1 in triple‐negative MDA‐MB‐231 breast cancer cell lines. Ginsenoside Rg1 (10 µM) treated breast cancer cells were exposed to 8 nM of doxorubicin, and the chemosensitizing potential was measured by cell‐based assays. Ginsenoside Rg1 (10 µM) treatment lowered the doxorubicin IC50 value to 0.01 nM. Furthermore, the ginsenoside pretreatment augments doxorubicin‐mediated reactive oxygen species (ROS) generation and subsequent alterations of mitochondrial membrane potential in MDA‐MB‐231 cell lines. The alkaline comet assay results illustrated an increased % tail DNA during ginsenoside Rg1 plus doxorubicin treatment than doxorubicin alone treatment. In addition, the number of apoptotic cells was also increased in ginsenoside Rg1 plus doxorubicin‐treated cells. Furthermore, the polymerase chain reaction array results illustrate activation of mitogen‐activated protein kinase (MAPK) gene expression (AKT, ERK, and MAPK) during doxorubicin alone treatment and it has been attenuated by ginsenoside Rg1 pretreatment. Moreover, ginsenoside Rg1 treatment before doxorubicin activates the DNA damage response elements (ATM, H2AX, RAD51, and XRCC1) and subsequent apoptosis‐related gene expression (p21, TP53. APAF1, Bax, CASP3, and CASP9) patterns in MDA‐MB‐231 cell lines. The ginsenoside Rg1 plus doxorubicin combination shows less cytotoxicity and ROS generation in MDA10A normal breast cancer cell lines. Therefore, the present results support the chemosensitizing property of ginsenoside Rg1 in triple‐negative breast cancer cell lines. [ABSTRACT FROM AUTHOR]

We previously demonstrated that Panax notoginseng (pNG) root extract treatments exerted neuroprotective effects on brain injuries using middle cerebral artery occlusion in mice. The present study aims to investigate the neuroprotective effects of PNG extract and its ginsenosides Rg1 and Rb1 on ischemic neuronal damage caused by oxygen and glucose deprivation (OGD) in mouse organotypic hippocampal slice cultures (OHSCs). Before the experiments, hippocampal slices collected from 7-day-old Swiss mice were cultured for 7 days. OGD was triggered in OHSCs for 30, 60, or 90 min with the aim of finding the optimal period of OGD for drug testing. PNG extract (10, 30 µg/ml), ginsenosides Rg1 and Rb1 (5, 25 µM), or MK-801 25 µM, a reference drug, was added to the culture medium 24 h before OGD and these treatments were continued for 24 h after the optimum 60-min period of OGD. After 24 h of OGD exposure, the measurement of propidium iodide uptake was analysed in OHSCs to evaluate neuronal cell damage. The results showed that OGD time-dependently increased PI uptake of the OHSCs. PNG 30 µg/ml treatment reduced the OGD-induced neuronal cell damage in OHSCs. Ginsenosides Rg1 25 µM, Rb1 (5, 25 µM), as well as MK-801 (25 µM) significantly inhibited PI uptake 24 h after OGD exposure. However, ginsenoside Rg1 5 µM did not show any significant effects on the OGD-induced neuronal cell damage. These findings indicated that ginsenosides Rg1 and Rb1 contributed to the neuroprotective effects of PNG against ischemic damage in OHSCs and the neuroprotective effect of ginsenoside Rb1 was stronger than that of ginsenoside Rg1.

Aim: The authors aimed to develop Dox@Rg1 nanoparticles with decreased cardiotoxicity to expand their application in cancer. Materials & methods: Dox@Rg1 nanoparticles were developed by encapsulating doxorubicin (Dox) in a self-assembled Rg1. The antitumor effect of the nanoparticles was estimated using 4T1 tumor-bearing mice and the protective effect on the heart was investigated in vitro and in vivo. Results: Different from Dox, the Dox@Rg1 nanoparticles induced increased cytotoxicity to tumor cells, which was decreased in cardiomyocytes by the inhibition of apoptosis. The study in vivo revealed that the Dox@Rg1 nanoparticles presented a perfect tumor-targeting ability and improved antitumor effects. Conclusion: Dox@Rg1 nanoparticles could enhance the antitumor effects and decrease the cardiotoxicity of Dox. Doxorubicin (Dox) is a drug used to treat cancer; however, it can be toxic to the heart. In this study, researchers made nanoparticles containing Dox and a component of ginseng, a root similar to ginger. They tested the nanoparticles in mice with tumors. The nanoparticles appeared to gather at the tumor site in greater amounts than free Dox. In healthy mice, the nanoparticles gathered less in the heart than free Dox. This means that putting Dox into nanoparticles such as these could improve their anticancer effect and decrease harm to the heart. [ABSTRACT FROM AUTHOR]

During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood–brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1 β -induced macrophages (IIM)-Exos-miR-21 can activate NF- κ B signaling pathway and induce the expressions of MMP-1, -3 and -9 and downregulate the levels of tight junction proteins (TJPs) deteriorating the BBB. Rg1 reduced miR-21-5p content in IIM-Exos (RIIM-Exos). The interaction of NMIIA–HSP90 controlled the release of Exos-miR-21, this interaction was restricted by Rg1. Rg1 could inhibit the Exos-miR-21 release in peripheral blood flow to brain, enhancing TIMP3 protein expression, MMPs proteolysis, and restricting TJPs degradation thus protected the BBB integrity. Conclusively, Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease. Rg1 improves cerebral vascular endothelial injury, protects blood–brain barrier and possess therapeutic potential against traumatic brain injury. It restricts the interaction of NMIIA–HSP90 in macrophages resulting in circumscribed secretion of exosome-miR-21 towards brain. [Display omitted] [ABSTRACT FROM AUTHOR]

Senescence limits the characteristics and functionality of mesenchymal stem cells (MSCs), thereby severely restricting their application in tissue engineering. Here, we investigated ways to prevent MSCs from entering a state of senescence. We found that Rg1, an extract of natural ginseng, can reduce the expression of senescence markers in cultured cells in vitro and in various tissues in vivo. Simultaneously, ginsenoside Rg1 improved the antioxidant capacity of cells, and the senescence-inhibiting and antioxidant effect of Rg1 were associated with the activation of the nuclear factor E2-related factor 2 (NRF2) signaling pathway. Furthermore, Rg1 may activate the NRF2 pathway by increasing the interaction between P62 and KEAP1through P62 upregulation and AKT activation. Taken together, our findings indicate that Rg1 prevents cell senescence via NRF2 and AKT, and activation of AKT or NRF2 may thus represent therapeutic targets for preventing cell senescence. [Display omitted] • Ginsenoside Rg1 improves the antioxidant capacity of cells. • Ginsenoside Rg1 ameliorates D-gal-induced senescence through activation of NRF2. • Ginsenoside Rg1 reduces NRF2 degradation by promoting the interaction of P62 with KEAP1. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic alcohol consumption disrupts psychomotor and cognitive functions, most of which are subserved by the dysfunction of hippocampus. Dysregulated excitatory glutamatergic transmission is implicated in repeated alcohol induced psychomotor and cognitive impairment. Ginsenoside Rg1, one of the main active ingredient of the traditional tonic medicine Panax ginseng C.A. Meyer (Araliaceae), has been used to treat cognitive deficits. Particularly, Rg1 has been demonstrated to improve hippocampus-dependent learning in mice and attenuate glutamate-induced excitotoxicity in vitro. Thus, in the present research, we sought to investigate the therapeutic effects of Ginsenoside Rg1 on repeated alcohol induced psychomotor and cognitive deficits in hippocampal-dependent behavioral tasks and unravel the underpinnings of its neuroprotection. Methods Male ICR (CD-1) mice were consecutively intragastrically treated with 20% (w/v) alcohol for 21 days. Then, behavior tests were conducted to evaluate repeated alcohol induced psychomotor and cognitive deficits. Histopathological changes, and biochemical and molecular alterations were assessed to determine the potential neuroprotective mechanism of Rg1. Results The results suggested that Rg1, at the optimal dose of 6 mg/kg, has the potential to ameliorate repeated alcohol induced cognitive deficits by regulating activities of NR2B containing NMDARs and excitotoxic signaling. Conclusion Our findings further provided a new strategy to treat chronic alcohol exposure induced adverse consequences.

Objective To prepare the endothelialization-promoting tissue-engineered blood vessels (TEBVs) with encapsulated Ginsenoside Rg1 (Rg1) to promote endothelialization, and to evaluate its patency and endothelialization after implantation into the rat common carotid artery. Methods CCK-8 assay and flow cytometry were used to detect the effects of Rg1 on the proliferation and apoptosis of endothelial cells (ECs) after 48 hours' treatment, and the optimal dose of the agent was also determined. ECs was divided into control group, Rg1 treatment group (15.63 μmol/L Rg1), and Rg1+XL184 (15.63 μmol/L Rg1+0.5 μg/mL XL184, VEGFR2 inhibitor) treatment group. Cell proliferation and wound healing of ECs were examined after the treatment for 48 h. Chitosan coated Rg1-(2-hydroxypropyl)-cyclodextrin particles (Rg1-HGC/CS NPs, abbreviated as NPs) were prepared and modified to the lumen of blood vessels (after decellularization and collagen treatment), and then Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS) and scanning electron microscopy (SEM) were used to detect these obtained samples. ECs were co-cultured with acellular vessels and TEBVs for 48 h to observe the biocompatibility. For in vivo study, the acellular vessels were divided into collagen group (collagen treatment), blank CS group (collagen and chitosan treatment), and NPs group (modified with NPs). Then these vessel samples were transplanted into the left common carotid artery of SD rats respectively. Ultrasound and micro-CT scanning were performed to observe the vascular patency in 30 and 90 d after transplantation. HE and Masson staining and immunofluorescence assay for CD31 and vWF were used to observe the endothelialization in each group in 90 d after transplantation. Results Rg1 promoted the proliferation and migration of ECs via VEGFR2 (P < 0.05), and showed no significant effect on apoptosis. The prepared NPs were about 130 nm in diameter and uniform in shape (PDI < 0.3), and could be successfully modified to the lumen of blood vessels. The co-cultured study showed that endothelialization-promoting TEBVs displayed better biocompatibility for favorable of cell adhesion and growth. In 30 and 90 d after transplantation, radiological studies displayed that the NPs-treated vessels showed better vascular patency than the other groups. HE and Masson staining indicated that in 90 d after transplantation, the collagen and blank CS groups had blood vessels deformed, without normal structures and blocked due to the thrombosis and collagen fibrosis, while the NPs group had intact blood vessels and better patency. Immunofluorescence assay for CD31 and vWF showed that the lumen in the vessles from the NPs group had ECs well-covered, suggesting better endothelialization when compared with other groups. Conclusion Endothelialization-promoting TEBVs shows better promoting effect on endothelialization, and is helpful in maintenance of long-term patency of blood vessels after transplantation.

After cerebral infarction, the regeneration of microvascular played an important role in the recovery. Ginsenoside Rg1 (Rg1) had good effects on promoting angiogenesis and neuro-protection in cerebral infarction treatment. However, the blood-brain barrier (BBB) restricted Rg1 to enter into cerebral tissue. Transferrin receptor (TfR) was over-expressed in the BBB. In this study, we fabricated a TfR targeting nano-carrier (PATRC) to penetrate the BBB for treatment of cerebral infarction. A TfR targeted peptide was conjugated with the nano-carrier wrapped hydrophobic Rg1. The nanoscale size (132 ± 12 nm), polydispersity index (PDI =0.29) and the zeta potential (−38mv) were tested with dynamic light scattering optical system. Surface morphology (ellipse, mean diameter 122 ± 26 nm) was detected by transmission electron microscope (TEM). PATRC implement cell targeting ability on rat brain microvascular endothelial cells RBE4 in vitro detected by immunofluorescence and flow cytometry methods. Comparing with Rg1 threated group, the PATRC exhibited more prominent ability on the tube formation ability (p

Background/Aim Ginsenoside Rg1 exerts a beneficial effect in many kidney diseases. But little work has been done to confirm whether ginsenoside Rg1 could also exert a protective effect on anti-glomerular basement membrane (anti-GBM) glomerular nephritis (GN). We aimed to explore the role of ginsenoside Rg1 in attenuating anti-GBM GN in vitro and in vivo and investigate the mechanism under its action.Methods Interleukin-1β (IL-1β) treated podocytes were used as a cell model. A total of 20 mice were used to build the Anti-GBM GN mice model. Real-time PCR analysis (RT-PCR), Western blot analysis and ELISA assay were conducted to detect related indicators in this study. The statistical analysis was performed using GraphPad Prism software 6.0.Results Ginsenoside Rg1 attenuates IL-1β-induced inflammation and apoptosis in podocytes. NRF2 expression can be inhibited by IL-1β, whereas reversed by ginsenoside Rg1. NRF2 inhibitor ML385 can significantly reverse the effects of ginsenoside Rg1 on inflammation and apoptosis induced by IL-1β, and block the inhibitory effect of ginsenoside Rg1 on IL-1β activated MAPK pathway. In addition, ginsenoside Rg1 could improve anti-GBM GN injury in vivo.Conclusion Ginsenoside Rg1 inhibits the anti-GBM GN damage through regulating NRF2 pathway in vitro and in vivo. Our findings provide new insight and mechanism of ginsenoside Rg1 to prevent anti-GBM GN.

The levels of lipopolysaccharide (LPS) are increased in the brain and blood of Alzheimer’s disease (AD) patients and contribute to neuroinflammation and neurodegeneration in AD. Ginsenoside Rg1 (Rg1) is reported to possess neuroprotective effects on neurodegenerative diseases by improving oxidative stress and inflammation. However, the protective effect and mechanism of Rg1 in neuroinflammation and neuronal damage in LPS-induced mice remain unclear. In this study, the results demonstrated that exposure to LPS for 14 days significantly induced cognitive impairment, neuronal injury and NLRP1 inflammasome activation, significantly increased ROS generation and NADPH oxidase 2 (NOX2) expression and elevated the levels of p-PLC, calcineurin (CN) and nuclear factor of activated T cells 1 (NFAT1) in the hippocampus. Treatment with Rg1, tempol (a superoxide dismutase mimic) and apocynin (an inhibitor of NOX) significantly improved cognitive impairment and neuronal damage, inhibited the activation of NLRP1 inflammasome, reduced ROS generation and NOX2 expression and decreased the levels of p-PLC, CN and NFAT1 in the hippocampus. Additionally, the calcium imaging results suggested that Rg1 administration significantly inhibits [Ca2+]i overload and maintains calcium homeostasis in LPS-induced HT22 cells. These results suggest that Rg1 treatment can improve LPS-induced activation of the NLRP1 inflammasome and neuronal damage through inhibiting NOX2, [Ca2+]i overload and CN-NFAT1 activation.