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Spinal cord injury (SCI) is a severe neurological condition that frequently leads to significant sensory, motor, and autonomic dysfunction. This study sought to delineate the potential mechanistic underpinnings of extracellular vesicles (EVs) derived from ginsenoside Rg1‐pretreated neuronal cells (Rg1‐EVs) in ameliorating SCI. These results demonstrated that treatment with Rg1‐EVs substantially improved motor function in spinal cord‐injured mice. Rg1‐EVs enhance microglial polarization toward the M2 phenotype and repressed oxidative stress, thereby altering immune responses and decreasing inflammatory cytokine secretion. Moreover, Rg1‐EVs substantially diminish reactive oxygen species accumulation and enhanced neural tissue repair by regulating mitochondrial function. Proteomic profiling highlighted a significant enrichment of MYCBP2 in Rg1‐EVs, and functional assays confirmed that MYCBP2 knockdown counteracted the beneficial effects of Rg1‐EVs in vitro and in vivo. Mechanistically, MYCBP2 is implicated in the ubiquitination and degradation of S100A9, thereby promoting microglial M2‐phenotype polarization and reducing oxidative stress. Overall, these findings substantiated the pivotal role of Rg1‐EVs in neuronal protection and functional recovery following SCI through MYCBP2‐mediated ubiquitination of S100A9. This research offers novel mechanistic insights into therapeutic strategies against SCI and supports the clinical potential of Rg1‐EVs. [ABSTRACT FROM AUTHOR]

Background: Presenilin (PSEN, PS) is essential for γ-secretase function, and mutations can disrupt amyloid-β (Aβ) production in familial Alzheimer's disease. Targeting γ-secretase is complex due to its broad involvement in physiological processes. Objective: Our aim was to create a novel knockin (KI) mouse model expressing PSEN1 D385A mutation and investigate the efficacy of a Geniposide and Ginsenoside Rg1 combination (NeuroProtect modified formula, NP-2) in restoring γ-secretase activity. Methods: Using gene manipulation, we established the PS1 D385A KI mouse model and confirmed the mutation, mRNA, and protein levels using Southern blotting, northern blotting, and western blotting, respectively. In vitro γ-secretase assay was conducted to measure γ-secretase activity, while histological analyses examined neurogenesis effects. NP-2 administration evaluated its impact on γ-secretase activity. Results: The PS1 D385A KI homozygotes displayed severe cerebral hemorrhage, postnatal lethality, developmental disorders, reduced proliferation of neural progenitor cells, and disrupted γ-secretase function. The mutation abolished PS1 protein self-shearing, leading to compromised γ-secretase activity. NP-2 intervention effectively restored γ-secretase activity in the heterozygous mice. Conclusions: PS1 D385A mutant disrupted PS1 protein self-cleaving, impairing γ-secretase activity in KI mice. NP-2 restored γ-secretase function, offering potential for novel AD treatment strategies despite the challenges posed by γ-secretase's complex role in physiological processes. [ABSTRACT FROM AUTHOR]

Depression is an inflammation-associated disease that results in major depression as inflammation increases and progresses. Ginsenoside Rg1 (Rg1), the major bioactive ingredient derived from ginseng, possesses remarkable anti-depressant and antiinflammatory effects. Our previous studies showed that the pathogenesis of depression was concomitant with the acceleration of connexin43 (Cx43) ubiquitin degradation, while Rg1 could upregulate Cx43 expression to attenuate depression. However, whether the ubiquitination of Cx43 is the specific correlation between depression and inflammation, and how Rg1 ameliorates neuroinflammation to attenuate depression, are still under investigation. In in vivo experiments, Rg1 treatment significantly ameliorated depression-like behaviors in rats subjected to chronic unpredictable stress (CUS). Moreover, these CUS rats treated with Rg1 exhibited attenuated neuroinflammation, together with the suppression of Cx43 ubiquitination. In in vitro experiments, Rg1 reduced the secretion of inflammatory cytokines and the ubiquitination of Cx43 in lipopolysaccharide-induced glial cells. Furthermore, treatment with ubiquitin-proteasome inhibitor MG132 suppressing the ubiquitination of Cx43 ameliorated lipopolysaccharide-induced neuroinflammation. The results suggest that Rg1 attenuates depression-like behavioral performances in CUSexposed rats; and the main mechanism of the antidepressant-like effects of Rg1 appears to involve protection against neuroinflammation via suppression of Cx43 ubiquitination. In conclusion, Rg1 could ameliorate neuroinflammation via suppression of Cx43 ubiquitination to attenuate depression, which represents the perspective of an innovative therapy of Rg1 in the treatment of inflammation-associated depression. [ABSTRACT FROM AUTHOR]

Sepsis-induced acute lung injury (SALI) poses a significant threat with high incidence and mortality rates. Ginsenoside Rg1 (GRg1), derived from Ginseng in traditional Chinese medicine, has been found to reduce inflammation and protect lung epithelial cells against tissue damage. However, the specific roles and mechanisms by which GRg1 mitigates SALI have yet to be fully elucidated. In this context, we employed a relevant SALI mouse model, alongside network pharmacology, molecular docking, and molecular dynamics simulation to pinpoint GRg1's action targets, complemented by in vitro assays to explore the underlying mechanisms. Our research shows that GRg1 alleviates CLP-induced SALI, decreasing lung tissue damage and levels of serum proinflammatory factor IL-6, TNF-α, and IL-1β, also enhancing the survival rate of CLP mice. A total of 116 common targets between GRg1 and ALI, with specific core targets including AKT1, VEGFA, SRC, IGF1, ESR1, STAT3, and ALB. Further in vitro experiments assessed GRg1's intervention effects on MLE-12 cells exposed to LPS, with qRT-PCR analysis and molecular dynamics simulations confirming AKT1 as the key target with the favorable binding activity for GRg1. Western blot results indicated that GRg1 increased the Bcl-2/Bax protein expression ratio to reduce apoptosis and decreased the high expression of cleaved caspase-3 in LPS-induced MLE-12 cells. More results showed significant increases in the phosphorylation of PI3K and AKT1. Flow cytometric analysis using PI and Annexin-V assays further verified that GRg1 decreased the apoptosis rate in LPS-stimulated MLE-12 cells (from 14.85 to 6.54%, p < 0.05). The employment of the AKT1 inhibitor LY294002 confirmed these trends, indicating that AKT1's inhibition negates GRg1's protective effects on LPS-stimulated MLE-12 cells. In conclusion, our research highlights GRg1's potential as an effective adjunct therapy for SALI, primarily by inhibiting apoptosis in alveolar epithelial cells and reducing pro-inflammatory cytokine secretion, thus significantly enhancing the survival rates of CLP mice. These beneficial effects are mediated through targeting AKT1 and activating the PI3K-AKT pathway. [ABSTRACT FROM AUTHOR]

Ginseng, an important medicinal plant, is characterized by its main active component, ginsenosides. Among more than 40 ginsenosides, Rg1 is one of the ginsenosides used for measuring the quality of ginseng. Therefore, the identification and characterization of genes for Rg1 biosynthesis are important to elucidate the molecular basis of Rg1 biosynthesis. In this study, we utilized 39,327 SNPs and the corresponding Rg1 content from 344 core ginseng cultivars from Jilin Province. We conducted a genome-wide association study (GWAS) combining weighted gene co-expression network analysis (WGCNA), SNP-Rg1 content association analysis, and gene co-expression network analysis; three candidate Rg1 genes (PgRg1-1, PgRg1-2, and PgRg1-3) and one crucial candidate gene (PgRg1-3) were identified. Functional validation of PgRg1-3 was performed using methyl jasmonate (MeJA) regulation and RNAi, confirming that this gene regulates Rg1 biosynthesis. The spatial–temporal expression patterns of the PgRg1-3 gene and known key enzyme genes involved in ginsenoside biosynthesis differ. Furthermore, variations in their networks have a significant impact on Rg1 biosynthesis. This study established an accurate and efficient method for identifying candidate genes, cloned a novel gene controlling Rg1 biosynthesis, and identified 73 SNPs significantly associated with Rg1 content. This provides genetic resources and effective tools for further exploring the molecular mechanisms of Rg1 biosynthesis and molecular breeding. [ABSTRACT FROM AUTHOR]

Abstract Sepsis-induced acute lung injury (SALI) poses a significant threat with high incidence and mortality rates. Ginsenoside Rg1 (GRg1), derived from Ginseng in traditional Chinese medicine, has been found to reduce inflammation and protect lung epithelial cells against tissue damage. However, the specific roles and mechanisms by which GRg1 mitigates SALI have yet to be fully elucidated. In this context, we employed a relevant SALI mouse model, alongside network pharmacology, molecular docking, and molecular dynamics simulation to pinpoint GRg1's action targets, complemented by in vitro assays to explore the underlying mechanisms. Our research shows that GRg1 alleviates CLP-induced SALI, decreasing lung tissue damage and levels of serum proinflammatory factor IL-6, TNF-α, and IL-1β, also enhancing the survival rate of CLP mice. A total of 116 common targets between GRg1 and ALI, with specific core targets including AKT1, VEGFA, SRC, IGF1, ESR1, STAT3, and ALB. Further in vitro experiments assessed GRg1's intervention effects on MLE-12 cells exposed to LPS, with qRT-PCR analysis and molecular dynamics simulations confirming AKT1 as the key target with the favorable binding activity for GRg1. Western blot results indicated that GRg1 increased the Bcl-2/Bax protein expression ratio to reduce apoptosis and decreased the high expression of cleaved caspase-3 in LPS-induced MLE-12 cells. More results showed significant increases in the phosphorylation of PI3K and AKT1. Flow cytometric analysis using PI and Annexin-V assays further verified that GRg1 decreased the apoptosis rate in LPS-stimulated MLE-12 cells (from 14.85 to 6.54%, p

Background: Ginsenoside Rg1 (Rg1) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng. Research has shown that Rg1 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 Rg1 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 Rg1 against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg1 intervention on H9c2 cells injured by H2O2 showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg1 on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg1 was also evaluated. Conclusion: Rg1 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, Rg1, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.

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.

BACKGROUND: Rotator cuff muscle degeneration (muscle atrophy, fibrosis and fatty infiltration) is a common condition after rotator cuff tears, which seriously affects shoulder function and surgical outcomes. Ginsenoside Rg1 has biological effects such as anti-oxidation, anti-apoptosis and lipid-lowering. However, the effect of ginsenoside Rg1 on muscle degeneration after rotator cuff tear has not been reported. OBJECTIVE: To investigate the effect of ginsenoside Rg1 on muscle degeneration after massive rotator cuff tear in mice. METHODS: Sixty C57BL/6J mice were randomly divided into sham group, model group, ginsenoside Rg1 low dose group and ginsenoside Rg1 high dose group, with 15 mice in each group. The skin of the right shoulder of mice in the sham group was cut and sutured. Massive rotator cuff tear mouse models of the right shoulder were established in the other three groups. Supraspinatus tendon and suprascapular nerve compression were administrated. Mice in the sham and model groups were intraperitoneally injected with 0.5 mL of saline after operation, while those in the ginsenoside Rg1 low and high dose groups were intraperitoneally injected with ginsenoside Rg1 30 and 60 mg/kg respectively, once a day, for 6 weeks. Mice were assessed for limb function by gait analysis the day after the last injection. After euthanasia, the supraspinatus muscle on the operated side was taken to measure the muscle atrophy rate and muscle contractility. Muscle tissue was stained with oil red O and Masson. RT-PCR was used to detect the expression of atrophy, fibrosis, and fatty infiltration related genes. RESULTS AND CONCLUSION: Compared with the model group, low- and high-dose ginsenoside Rg1 significantly increased paw print area and step length (P < 0.05). Compared with the model group, low- and high-dose ginsenoside Rg1 significantly increased myofiber cross-sectional area and supraspinatus contractility (P < 0.05), and significantly decreased wet muscle mass reduction ratio, fatty infiltration area ratio, and collagen fiber area ratio (P < 0.05). Compared with the model group, low- and high-dose ginsenoside Rg1 significantly decreased the expression of atrophy, fibrosis, and fatty infiltration related genes (P < 0.05). There was no significant difference in paw print area, supraspinatus muscle contractility, and myofiber cross-sectional area between ginsenoside Rg1 low and high dose groups (P > 0.05), and all other indexes were better in the ginsenoside Rg1 high dose group than in the ginsenoside Rg1 low dose group (P < 0.05). To conclude, ginsenoside Rg1 could significantly reduce muscle atrophy, fibrosis and fatty infiltration following massive rotator cuff tear in mice, which is beneficial to improve muscle strength and limb function. [ABSTRACT FROM AUTHOR]

Ginsenoside Rg1(Rg1), a monomer of a tetracyclic triterpenoid derivative, possesses diverse medicinal properties attributed to its unique chemical structure and may have beneficial effects on fetal development. This study aimed to investigate the protective effects of prenatal exposure to Rg1 against Methimazole-induced gestational hypothyroidism on reflexive behaviors, conditioned fear, and cortical antioxidant levels in mouse offspring.40 female virgin mice and 12 male NMRI mice were assigned to four groups: group 1 served as the control, group 2 received Methimazole(MMI) at a concentration of 0.02% in their drinking water, group 3 received Rg1(150 mg/kg), and group 4 received both MMI and Rg1.Groups of 2–4 were administered the substances from days 1–9 of gestation. After delivery, pups were selected, and reflexive motor behaviors and conditioned fear were assessed. Additionally, levels of brain tissue catalase(CAT), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GPx) levels were measured. Furthermore, postpartum immobility time in the forced swimming test (FST), tail suspension test (TST), and the number of squares crossed in the open field test (OFT)were determined. The results demonstrated that maternal exposure to Rg1 improved ambulation score, hind-limb suspension score, grip strength, front-limb suspension, hind-limb foot angle, negative geotaxis, surface righting, and conditioned fear in hypothyroidism-induced offspring(P

Objective To explore the mechanism of ginsenoside Rg1 in alleviating heat stress-induced testicular injury in mice. Methods A total of 20 C57BL/6 male mice (6~8 weeks old) were randomly divided into 4 groups (n=5). The mice from the control group and heat stress (HS) group were intraperitoneally injected with 10 mL/(kg·d) 0.9 % normal saline for 14 d, while those in the HS+Rg1 group and the Rg1 group were given an intraperitoneal injection of 20 mg/(kg·d) for 14 d, and then on the 7th day after administration, the mice in the HS group and the HS+Rg1 group had the lower abdomen put into a 43 ℃ water bath for 30 min as a single heat stress after being anesthetized with 4% chloral hydrate. Mouse spermatocytes GC-2spd(ts) were divided into control group (routine culture for 48 h), HS group (placed in a 43 ℃ water bath for 30 min after 36 h of conventional culture, and cultured till the end of 48 h), HS+Rg1 group (50 μmol/L Rg1 treatment followed by heat stress injury), and Rg1 group (no heat stress injury). In 1 d after modeling, the eyeball blood samples were collected to detect serum testosterone with ELISA, and the testicles were extracted to observe the morphology and weighed to calculate the testicular index. HE staining was used to observe the histopathology of testis, and corresponding reagents and kits was employed to detect the content of malondialdehyde (MDA) and activities of catalase (CAT) and superoxide dismutase (SOD) in testis tissue. After the epididymal sperm were collected, the sperm concentration and motility were analyzed by computer-assisted sperm analysis (CASA) system. In in vitro experiments, cell apoptosis was detected with TUNEL staining, the protein levels of Nrf2, Keap1, HO-1, Bax, Bcl-2 and Caspase3 were detected with Western blotting, and the mRNA levels of GCLC, GCLM and NQO1 were detected by RT-qPCR. Results Rg1 prevented the decreases in testicular weight and testicular index caused by heat stress, reduced the damage of testicular tissue structure, prevented the decrease of sperm concentration and vitality, antagonized the decreasd number of Leydig cells and serum testosterone level, reduced the accumulation of MDA in testicular tissue, and enhanced the activities of CAT and SOD. Rg1 treatment alleviated the apoptosis of GC-2spd(ts) cells, down-regulated the expression of Bax, Caspase3 and Keap1 proteins, enhanced the expression of Bcl-2, Nrf2 and HO-1 proteins, and increased the transcriptional levels of Nrf2 target genes GCLC, GCLM and NQO1. Conclusion Rg1 has no significant effect on the structure and function of mouse testes, but it can effectively improve the ability of mouse testes to resist heat stress injury, which may be related to the activation of Nrf2 signaling pathway, the improvement of antioxidant enzyme activity, and the reduction of apoptosis of spermatogenic cells.

Background: Sepsis-induced acute lung injury (ALI) is one of the serious life-threatening complications of sepsis and is pathologically associated with mitochondrial dysfunction. Ginsenoside Rg1 has good therapeutic effects on ALI. Herein, the pharmacological effects of Rg1 in sepsis-induced ALI were investigated. Methods: Sepsis-induced ALI models were established by CLP operation and LPS treatment. HE staining was adopted to analyze lung pathological changes. The expression and secretion of cytokines were measured by RT-qPCR and ELISA. Cell viability and apoptosis were assessed by MTT assay, flow cytometry and TUNEL staining. ROS level and mitochondrial membrane potential (MMP) were analyzed using DHE probe and JC-1 staining, respectively. FBXO3 m6A level was assessed using MeRIP assay. The interactions between FBXO3, YTHDF1, and PGC-1α were analyzed by Co-IP or RIP. Results: Rg1 administration ameliorated LPS-induced epithelial cell inflammation, apoptosis, and mitochondrial dysfunction in a dose-dependent manner. Mechanically, Rg1 reduced PGC-1α ubiquitination modification level by inhibiting FBXO3 expression m6A-YTHDF1 dependently. As expected, Rg1's mitigative effect on LPS-induced inflammation, apoptosis and mitochondrial dysfunction in lung epithelial cells was abolished by FBXO3 overexpression. Moreover, FBXO3 upregulation eliminated the restoring effect of Rg1 on CLP-induced lung injury in rats. Conclusion: Rg1 activated PGC-1α/Nrf2 signaling pathway by reducing FBXO3 stability in an m6A-YTHDF1-dependent manner to improve mitochondrial function in lung epithelial cells during sepsis-induced ALI progression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our previous studies have confirmed that H2O2 and ginsenoside Rg1 can cause changes in reactive oxygen species levels in human periodontal ligament cells, but the correlation of reactive oxygen species with apoptosis and autophagy remains unclear. OBJECTIVE: To explore the effect and mechanism of ginsenoside Rg1 on H2O2-induced apoptosis and autophagy of human periodontal ligament cells. METHODS: Human periodontal ligament cells were divided into control group, H2O2 group and H2O2+Rg1 group. Ginsenoside Rg1 (50 μmol/L) was preincubated for 24 hours and H2O2 was treated for 2 hours (500 μmol/L). CCK-8 assay was used to detect the proliferation ability of the cells. A fluorescent probe DCFH-DA was used to detect the reactive oxygen species level of the cells. qRT-PCR and western blot assay were used to detect heme oxygenase 1, apoptosisrelated factor Caspase-3, Bax, anti-apoptotic factor Bcl-2, autophagy Beclin-1, P62, LC3, pathway-related factors phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) mRNA and protein expression. RESULTS AND CONCLUSION: (1) Compared with the control group, the proliferation activity of human periodontal ligament cells in the H2O2 group decreased. Compared with the H2O2 group, the proliferation activity of human periodontal ligament cells increased in the H2O2+Rg1 group. (2) Compared with the control group, the expression of reactive oxygen species and heme oxygenase-1 increased in the H2O2 group. Compared with the H2O2 group, the expression of reactive oxygen species and heme oxygenase-1 decreased in the H2O2+Rg1 group. (3) Compared with the control group, the expression of Caspase-3, Bax, Beclin-1 and LC3 increased, while the expression of Bcl-2 and P62 decreased in human periodontal ligament cells of the H2O2 group. Compared with the H2O2 group, the expressions of Caspase-3, Bax, Beclin-1 and LC3 decreased, and the expressions of Bcl-2 and P62 increased in the H2O2+Rg1 group. (4) Compared with the control group, the expressions of PI3K, AKT and mTOR decreased in human periodontal ligament cells of the H2O2 group. Compared with the H2O2 group, the expressions of PI3K, AKT and mTOR increased in human periodontal ligament cells of the H2O2+Rg1 group. (5) These results suggest that ginsenoside Rg1 can inhibit H2O2-induced apoptosis and autophagy in human periodontal ligament cells by reducing the content of reactive oxygen species and down-regulating the related factor expression of the PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Background: Small extracellular vesicles (sEVs) obtained from human umbilical cord mesenchymal stromal cells (MSCs) have shown cardioprotective efficacy in doxorubicin-induced cardiotoxicity (DIC). However, their clinical application is limited due to the low yield and high consumption. This study aims to achieve large-scale production of sEVs using a three-dimensional (3D) bioreactor system. In addition, sEVs were developed to deliver Ginsenoside Rg1 (Rg1), a compound derived from traditional Chinese medicine, Ginseng, that has cardioprotective properties but limited bioavailability, to enhance the treatment of DIC. Methods: The 3D bioreactor system with spinner flasks was used to expand human umbilical cord MSCs and collect MSC-conditioned medium. Subsequently, sEVs were isolated from the conditioned medium using differential ultra-centrifugation (dUC). The sEVs were loaded with Ginsenoside Rg1 by electroporation and evaluated for cardioprotective efficacy using Cell Counting Kit-8 (CCK-8) analysis, Annexin V/PI staining and live cell count of H9c2 cells under DIC. Results: Using the 3D bioreactor system with spinner flasks, the expansion of MSCs reached ~600 million, and the production of sEVs was up to 2.2 × 1012 particles in five days with significantly reduced bench work compared to traditional 2D flasks. With the optimized protocol, the Ginsenoside Rg1 loading efficiency of sEVs by electroporation was ~21%, higher than sonication or co-incubation. Moreover, Rg1-loaded sEVs had attenuated DOX-induced cardiotoxicity with reduced apoptosis compared to free Ginsenoside Rg1 or sEVs. Conclusions: The 3D culture system scaled up the production of sEVs, which facilitated the Rg1 delivery and attenuated cardiomyocyte apoptosis, suggesting a potential treatment of DOX-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a tincture from the roots of Panax ginseng C.A.Mey. (ginseng tincture), when used as a sensory additive in feed for horses, dogs and cats. The product is a water/ethanol (40:60 v/v) solution, with a dry matter content of no more than 6% and a content of 0.01%–0.5% (w/w) for the sum of the two triterpene saponins ginsenoside Rb1 and ginsenoside Rg1. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the tincture is safe for horses, dogs and cats at the maximum proposed use level of 48.6, 228.7 and 162 mg/kg complete feed, respectively. The Panel also concluded that the additive is considered safe for consumers when used at the proposed conditions of use in feed for horses. Ginseng tincture should be considered as an irritant to skin and eyes, and as a dermal and respiratory sensitiser. The use of the ginseng tincture as a flavour in feed for horses was not expected to pose a risk for the environment. Since the roots of P. ginseng and its preparations were recognised to flavour food and their function in feed would be essentially the same, no demonstration of efficacy was considered necessary. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) is a cardiac complication resulting from long‐term uncontrolled diabetes, characterized by myocardial fibrosis and abnormal cardiac function. This study aimed at investigating the potential of ginsenoside RG1 (RG1)‐induced mesenchymal stem cells (MSCs) in alleviating DCM. A DCM mouse model was constructed, and the effects of RG1‐induced MSCs on myocardial function and fibrosis in diabetic mice were evaluated. RG1‐induced MSCs were cocultured with high glucose‐treated fibroblasts for subsequent functional and mechanism assays. It was discovered that RG1‐induced MSCs secrete exosomes that induce macrophage M2 polarization. Mechanistically, exosomes derived from RG1‐induced MSCs transferred circNOTCH1 into macrophages, activating the NOTCH signaling pathway. A competing endogenous RNA (ceRNA) regulatory axis consisting of circNOTCH1, miR‐495‐3p, and NOTCH1 was found to contribute to DCM alleviation.. This study unveiled that exosomal circNOTCH1 secreted by RG1‐induced MSCs can alleviate DCM by activating the NOTCH signaling pathway to induce macrophage M2 polarization. This finding may contribute to the development of new therapeutic approaches for DCM. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is a common manifestation in patients with T2DM mellitus (T2DM). Ginsenoside Rg1 (GRg1) is the main active substance extracted from ginseng or Panax notoginseng. Methods: T2DM was induced by feeding rats with a high-sugar and high-fat diet combined with a low-dose intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) on an empty stomach. Subsequently, different concentrations of GRg1 (25, 50, 100 mg/kg/d) were used to intervene for 8 weeks and explore its therapeutic effects and potential mechanisms on cognitive impairment in T2DM rats. Results: Our data suggested that administration of GRg1 improved insulin resistance, specifically manifesting in a reduction of insulin resistance index by approximately 57.1 % with high doses of GRg1 (100 mg/kg/d). Besides, it has been observed to lower cholesterol, triglycerides, and low-density lipoprotein by approximately 20–50 % in T2DM rats. In addition, GRg1 treatment dramatically improved the spatial memory and learning ability in T2DM rats. Furthermore, administration of GRg1 to the T2DM rats dose-dependently up-regulated ERKs phosphorylation and blunted phosphorylation of JNKs and p38. Furthermore, GRg1 treatment also dose-dependently increased the expression of Bcl-2 but inhibited the expression of Bax and Caspase 3 expression in T2DM rats brain cortex and hippocampus neurons. Conclusion: GRg1 effectively improves mild cognitive impairment in T2DM rats by inhibiting oxidative stress and reducing the apoptosis of neurons in the cerebral cortex and hippocampus.

Abstract Spinal cord injury (SCI) is a severe neurological condition that frequently leads to significant sensory, motor, and autonomic dysfunction. This study sought to delineate the potential mechanistic underpinnings of extracellular vesicles (EVs) derived from ginsenoside Rg1‐pretreated neuronal cells (Rg1‐EVs) in ameliorating SCI. These results demonstrated that treatment with Rg1‐EVs substantially improved motor function in spinal cord‐injured mice. Rg1‐EVs enhance microglial polarization toward the M2 phenotype and repressed oxidative stress, thereby altering immune responses and decreasing inflammatory cytokine secretion. Moreover, Rg1‐EVs substantially diminish reactive oxygen species accumulation and enhanced neural tissue repair by regulating mitochondrial function. Proteomic profiling highlighted a significant enrichment of MYCBP2 in Rg1‐EVs, and functional assays confirmed that MYCBP2 knockdown counteracted the beneficial effects of Rg1‐EVs in vitro and in vivo. Mechanistically, MYCBP2 is implicated in the ubiquitination and degradation of S100A9, thereby promoting microglial M2‐phenotype polarization and reducing oxidative stress. Overall, these findings substantiated the pivotal role of Rg1‐EVs in neuronal protection and functional recovery following SCI through MYCBP2‐mediated ubiquitination of S100A9. This research offers novel mechanistic insights into therapeutic strategies against SCI and supports the clinical potential of Rg1‐EVs.

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.

Background: Mechanisms of synaptic plasticity in retinal ganglion cells (RGCs) are complex and the current knowledge cannot explain. Growth and regeneration of dendrites together with synaptic formation are the most important parameters for evaluating the cellular protective effects of various molecules. The effect of ginsenoside Rg1 (Rg1) on the growth of retinal ganglion cell processes has been poorly understood. Therefore, we investigated the effect of ginsenoside Rg1 on the neurite growth of RGCs. Methods: Expression of proteins and mRNA were detected by Western blot and qPCR. cAMP levels were determined by ELISA. In vivo effects of Rg1 on RGCs were evaluated by hematoxylin and eosin, and immunohistochemistry staining. Results: This study found that Rg1 promoted the growth and synaptic plasticity of RGCs neurite by activating the cAMP/PKA/CREB pathways. Meanwhile, Rg1 upregulated the expression of GAP43, Rac1 and PAX6, which are closely related to the growth of neurons. Meantime, H89, an antagonist of PKA, could block this effect of Rg1. In addition, we preliminarily explored the effect of Rg1 on enhancing the glycolysis of RGCs, which could be one of the mechanisms for its neuroprotective effects. Conclusion: Rg1 promoted neurite growth of RGCs through cAMP/PKA/CREB pathways. This study may lay a foundation for its clinical use of optic nerve diseases in the future.

Objective: This study aimed to further elucidate the mechanism of ginsenoside Rg1 in the treatment of cerebral ischemia-reperfusion. Methods: 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. Results: 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. Conclusion: 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.

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1β-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1β, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1β to simulate IVDD environment and divided into the control group, IL-1β group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway–related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1β, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1β-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1β-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) is a pathological state closely associated with various diseases, with hepatic insulin resistance playing a pivotal role. Insulin resistance can be improved by Ginsenoside Rg1 (GRg1), which is known as one of the most biologically active compounds found in ginseng. Nevertheless, the precise role and mechanisms of GRg1 in ameliorating hepatic insulin resistance are still unknown. Objectives: We wanted to demonstrate the impact of GRg1 on hepatic insulin resistance and explore the underlying mechanisms in our work. Materials and Methods: We mimicked insulin resistance conditions by culturing HepG2 cells in 30 mM glucose for 24 h. The effects of GRg1 on cellular glucose consumption and the key kinases of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) pathway were evaluated. To assess if the PI3K/AKT/GSK-3β pathway is crucial for GRg1's protective effect against insulin resistance, the compound LY294002, which inhibits PI3K, was employed. Results: In HepG2 cells, GRg1 markedly increased glucose uptake while exhibiting no cytotoxicity. Additionally, GRg1 activated the PI3K/AKT/GSK-3β pathway, as indicated by the increased phosphorylation of insulin receptor substrates-1 (IRS-1), AKT, and GSK-3β. Treatment with LY294002 significantly reversed the promotive effects of GRg1 on cellular glucose consumption and PI3K/AKT/GSK-3β pathway activation. Conclusion: Taken together, our present study revealed GRg1 exerted a protective effect against hepatic insulin resistance induced by high glucose through PI3K/AKT/GSK-3β pathway, suggesting its potential as a beneficial therapeutic medication. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegeneration with protein deposits, altered proteolysis, and inflammatory and oxidative processes as major hallmarks. Despite the continuous search for potential therapeutic treatments, no cure is available to date. The use of natural molecules as adjuvants in the treatment of Alzheimer's disease is a very promising strategy. In this regard, ginsenosides from ginseng root show a variety of biological effects. Here, we dissected the role of ginsenosides Rg1 and Rg2 in modulating autophagy and oxidative stress in neuroblastoma cells overexpressing Aβ(1-42). Key hallmarks of these cellular processes were detected through immunomethods and fluorometric assays. Our findings indicate that ginsenosides are able to upregulate autophagy in neuronal cells as demonstrated by increased levels of LC3II and Beclin-1 proteins and decreased amounts of p62. Simultaneously, an activation of lysosomal hydrolases was observed. Furthermore, autophagy activation promoted the clearance of Aβ(1-42). Rg1 and Rg2 also reduced oxidative stress sources and macromolecule oxidation, promoting NRF2 nuclear translocation and the expression of antioxidant enzymes. Our data further clarify the mechanisms of action of Rg1 and Rg2, indicating new insights into their role in the management of disorders like Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Introduction. During sepsis, the kidney is one of the most vulnerable organs. Sepsis-associated acute kidney injury (S-AKI) is hallmarked by renal inflammation, apoptosis, and oxidative injury. Ginsenoside Rg1 (Rg1) is a natural product that possesses abundant pharmacological actions and protects against many sepsis-related diseases. Nevertheless, its role and related mechanism in S-AKI remain to be determined. Materials and methods. S-AKI was induced using lipopolysaccharide (LPS, 10 mg/kg) via a single intraperitoneal injection. Rg1 (200 mg/kg) was intraperitoneally administered for 3 consecutive days before LPS treatment. For histopathological examination, murine kidney tissues were stained with hematoxylin and eosin. Tubular injury score was calculated to evaluate kidney injury. Serum creatinine and BUN levels were measured for assessing renal dysfunction. The levels and activities of oxidative stress markers (MDA, 4-HNE, PC, GSH, SOD, and CAT) in renal tissue were measured by corresponding kits. Renal cell apoptosis was detected by TUNEL staining. The protein levels of apoptosis-related markers (Bcl-2, Bax, and Cleaved caspase-3), proinflammatory factors, SIRT1, IκBα, p-NF-κB p65, and NF-κB p65 in kidneys were determined using western blotting. Immunofluorescence staining was employed to assess p-NF-κB p65 expression in renal tissues. Results. LPS-induced injury of kidneys and renal dysfunction in mice were ameliorated by Rg1. Rg1 also impeded LPS-evoked renal cell apoptosis in kidneys. Moreover, Rg1 attenuated LPS-triggered inflammation and oxidative stress in kidneys by inhibiting proinflammatory cytokine release, enhancing antioxidant levels and activities, and reducing lipid peroxidation. However, all these protective effects of Rg1 in LPS-induced AKI mice were reversed by EX527, an inhibitor of sirtuin 1 (SIRT1). Mechanistically, Rg1 upregulated SIRT1 protein expression, increased SIRT1 activity, and inactivated NF-κB signaling in the kidney of LPS-induced AKI mice, which was also reversed by EX527. Conclusions. Rg1 ameliorates LPS-induced kidney injury and suppresses renal inflammation, apoptosis, and oxidative stress in mice via regulating the SIRT1/NF-κB signaling. [ABSTRACT FROM AUTHOR]

Ginsenoside Rg1 (Rg1), a monomer saponin component, is one of the components with the highest content in total saponins of Panaxnotoginseng. It had various pharmacological effects. The bioavailability of oral tablets is only 1–20 %, and it is eliminated quickly in the blood. The development of new dosage forms and new routes of administration of ginsenoside Rg1 with sustained release and high bioavailability has become a significant problem to be solved. The Rg1 liposomes study used a thin film dispersion ultrasound method for its preparation. This study focused the pharmacokinetic parameters of ginsenoside Rg1 liposomes in rats through the lung perfusion method. Ginsenoside Rg1 liposomes were round and uniform in shape, the particle size was 2–3 μm, and the encapsulation efficiency of ginsenoside Rg1 liposome was 51.2 %. Results showed that, after pulmonary administration of ginsenoside Rg1, the time of ginsenoside Rg1 detected by Rg1 liposomes was longer than that of Rg1 solution, the relative bioavailability of ginsenoside Rg1 liposome lung administration AUC liposome/AUC solution = 122.67 %. These results provided the scientific theoretical and experimental basis for further development of new dosage forms and new routes of administration of ginsenoside Rg1.

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 Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a tincture from the roots of Panax ginseng C.A.Mey. (ginseng tincture), when used as a sensory additive in feed for horses, dogs and cats. The product is a water/ethanol (40:60 v/v) solution, with a dry matter content of no more than 6% and a content of 0.01%–0.5% (w/w) for the sum of the two triterpene saponins ginsenoside Rb1 and ginsenoside Rg1. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the tincture is safe for horses, dogs and cats at the maximum proposed use level of 48.6, 228.7 and 162 mg/kg complete feed, respectively. The Panel also concluded that the additive is considered safe for consumers when used at the proposed conditions of use in feed for horses. Ginseng tincture should be considered as an irritant to skin and eyes, and as a dermal and respiratory sensitiser. The use of the ginseng tincture as a flavour in feed for horses was not expected to pose a risk for the environment. Since the roots of P. ginseng and its preparations were recognised to flavour food and their function in feed would be essentially the same, no demonstration of efficacy was considered necessary.

Background: Ginsenoside Rg1 has been studied to improve systemic inflammatory injury induced by sepsis, but its mechanism is not fully understood. The objective of this study was to explore the potential molecular mechanism by which Rg1 ameliorates septic intestinal barrier function impairment. Results: Rg1 administration or miR-30e-5p upregulation alleviated LPS-induced apoptosis of Caco2 cells, decreased LDH and inflammatory cytokines levels, enhanced cell proliferation, promoted tight junction protein expression, and inhibited p65 phosphorylation. These beneficial effects of Rg1 were compensated by miR-30e-5p knockdown or FBXO11 overexpression. Animal studies have also yielded consistent results. Mechanistically, Rg1 performed this role by upregulating miR-30e-5p and inhibiting FBXO11 expression. Conclusions: Rg1 protects intestinal barrier function in sepsis by regulating the miR-30e-5p/FBXO11 axis. These data provide new insights into the development of targeted agents for septic intestinal injury and the understanding of Rg1's therapeutic mechanisms. How to cite:: Zhu W, Fan D, Zhou Z, et al. Ginsenoside protects intestinal barrier function and improves epithelium injury in sepsis by regulating the miR-30e-5p/FBXO11 axis. Electron J Biotechnol 2023;66. https://doi.org/10.1016/j.ejbt.2023.07.001.

Objective To determine the effects of main components (Rg1, Re and R1) of Panax notoginseng saponins on platelet activation and aggregation induced by shear stress. Methods A narrow microfluidic chip model was established, and used to evaluate the effects of Rg1, Re and R1 at different concentrations (0.05, 0.1, 0.25 and 0.5 mg/mL) on shear-induced platelet aggregation under different shear rates (1 500, 4 500 and 9 000 s-1). Flow cytometry was used to quantitatively detect the shear-induced platelet activation (P-selectin and PAC-1) after the treatment of Rg1, Re and R1. PL-12 analyzer was performed to measure the effects of Rg1, Re and R1 on platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP). Results Rg1, Re and R1 inhibited platelet aggregation induced by high shear stress in a concentration-dependent manner (P < 0.01), but had no such inhibitory effect under lower shear stress. Among the 3 components, Re had the strongest inhibitory effect, and their IC50 value was 0.1, 0.07, and 0.2 mg/mL, respectively. No synergistic effect was observed when the 3 components were used together at the same dose. Rg1, Re and R1 inhibited the expression of P-selectin and PAC-1 (P < 0.01), which was consistent with the results of the aggregation experiment. In addition, the 3 components also could inhibit platelet aggregation induced by AA and ADP. Conclusion The main components of Panax notoginseng saponins exert their antiplatelet activity by inhibiting shear-induced platelet aggregation.

Diabetic kidney disease (DKD) is a severe complication of type 2 diabetes mellitus (T2DM). However, the pathogenesis of DKD remains unclear, and effective treatment strategies are still lacking. Ginsenoside Rg1 (Rg1) has been reported to improve DKD, but the mechanism is unclear. NADPH oxidase 4 (NOX4) is an essential reactive oxygen species (ROS) source in the kidney. The mitogen-activated protein kinase (MAPK) signaling may exacerbate renal fibrosis. Therefore, we hypothesized that Rg1 might alleviate renal injury and fibrosis by inhibiting NOX4 and MAPK signaling in T2DM-induced DKD. We found that Rg1 significantly improves lipid deposition, fibrosis, and ROS production and reduces NOX4, p22phox, p47phox, p-ERK, p-JNK, and p-P38 MAPK expressions in the T2DM mice kidneys. We also found that the high-fat diet treatment in mice and the palmitate (PA) and PA + HG (high glucose) exposure in human mesangial cells could significantly induce lipid deposition, ROS production, fibrosis, and the activation of NOX4–MAPK signaling. The results suggest that high lipid and glucose may play a significant role in DKD progression, while Rg1 may attenuate renal fibrosis by inhibiting NOX4–MAPK signaling. [ABSTRACT FROM AUTHOR]

Objective: To investigate influences of ginsenoside Rg1 regulating miR-144-3p on neuroinflammation and bloodbrain barrier damage in rats with experimental cerebral hemorrhage, and its regulation on formyl peptide receptor 2 (FPR2)/p38 path‐way. Methods: Ninety SD rats were randomly divided into control group, cerebral hemorrhage group, ginsenoside Rg1 low-dose group (10 mg/kg), ginsenoside Rg1 high-dose group (40 mg/kg), ginsenoside Rg1 high-dose+ago-miR-144-3p group (40 mg/kg ginsenoside Rg1+ago-miR-144-3p), with 18 mice in each group. Except for control group, experimental intracerebral hemorrhage rat model was constructed by injecting collagenase Ⅱ into right caudate nucleus, and then each group was given intraperitoneal administration and intracerebral injection as required. Neurological damage in rats was scored; rat brain water content was determined by dry-wet specific gravity method; levels of TNF-α, IL-6 and IL-1β in rat brain tissues homogenate were determined by ELISA; ultrastructure around cerebral edema was observed by electron microscope; permeability of blood-brain barrier in rats was determined by Evans blue (EB) method; expressions of miR-144-3p/FPR2/p38 pathway were determined by qRT-PCR and Western blot. Results: Compared with control group, blood-brain barrier damage was aggravated in cerebral hemorrhage group, neurological function damage score, brain water content, miR-144-3p, TNF-α, IL-6, IL-1β, p38 mRNA, p-p38/p38 expressions in brain homogenate were increased (P< 0.05), FPR2 mRNA and protein expressions were decreased (P<0.05); compared with cerebral hemorrhage group, blood-brain barrier damage was reduced in ginsenoside Rg1 low-dose group and ginsenoside Rg1 high-dose group, neurological function damage score, brain water content, miR-144-3p, TNF-α, IL-6, IL-1β, p38 mRNA, p-p38/p38 expressions in brain homogenate were decreased (P< 0.05)，FPR2 mRNA and protein expressions were increased (P<0.05); ago-miR-144-3p was able to reverse protective effects of ginsenoside Rg1 on blood-brain barrier and neuroinflammation in rats (P<0.05). Conclusion: Ginsenoside Rg1 may inhibit blood-brain barrier damage and neuroinflammation in rats by regulating miR-144-3p/FPR2/p38 axis. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometritis in dairy cows refers to a process of local inflammatory reaction in the endometrium due to microbial invasion of the damaged endometrium. The aim of this study was to determine the therapeutic effect of ginsenoside Rg1 on the endometritis-induced fibrosis process. The experimental data from this study indicate that ginsenoside Rg1 is able to alleviate the epithelial–mesenchymal transition (EMT) process induced by the lipopolysaccharides (LPS) of bovine endometrial epithelial cell line (BEND) cells, which is related to the inhibition of ginsenoside Rg1 on reactive oxygen species (ROS) accumulation, thereby restraining NLRP3 inflammatory factors from expression. Experiments on mice showed that ginsenoside Rg1 alleviates endometrial fibrosis in mice. The aforementioned results can serve as powerful preclinical evidence for the potential of ginsenoside Rg1 to become an alternative drug for curing endometrial fibrosis. Abnormal function and the fibrosis of endometrium caused by endometritis in cows may lead to difficult embryo implantation and uterine cavity adhesions. Emerging evidence indicates that ginsenoside Rg1 can effectively resist inflammation and pathological fibrosis in different organs. It is hypothesized that ginsenoside Rg1 may possess the potential to mitigate endometrial fibrosis induced by lipopolysaccharides (LPS) in dairy cows. Herein, a model of LPS-stimulated fibrosis was constructed using bovine endometrial epithelial cell line (BEND) cells and ICR mice. Western blotting was used to detect the protein level, and reactive oxygen species (ROS) content was measured by means of DCFH-DA. The uterine tissue structure was stained with H&E and Masson staining. The murine endometrium was assessed for oxidative stress by detecting the concentration of MDA together with the activity of enzymatic antioxidants SOD and CAT. Ginsenoside Rg1 interfered with NLRP3 activation by reducing ROS generation. After the application of ROS inhibitor NAC and NLRP3 inhibitor MCC950, ginsenoside Rg1 could interfere in the ROS/NLRP3 inflammasome signaling pathway by suppressing the epithelial–mesenchymal transition (EMT) of BEND cells. Our in vivo data showed that ginsenoside Rg1 relieved endometrial fibrosis of the mouse model of LPS-induced endometritis by restraining the ROS/NLRP3 inflammasome signaling pathway. Ginsenoside Rg1 inhibits LPS-induced EMT progression in BEND cells probably by inhibiting the activation of ROS-NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Objectives: High reactive oxygen species (ROS) levels lead to cell death, and the testes are among the most vulnerable organs to oxidative damage. Rg1, an active ingredient extracted from the natural medicine ginseng, has potential anti-inflammatory, antioxidant and antiapoptotic properties. Our previous studies showed that Rg1 can effectively improve spermatogenic function in mice, but the specific mechanism remains unclear. The purpose of this study was to investigate the effect of Rg1 on oxidative stress and spermatogonium apoptosis in D-gal-induced testicular toxicity and elucidate the associated mechanism. Methods: Male C57BL/6 mice at 6–8 weeks of age were intraperitoneally injected with D-gal (200 mg/kg) for 42 days to establish a testicular injury model, and on day 16, 40 mg/kg Rg1-rich saline was injected intraperitoneally. Concurrently, we established an in vitro model of D-gal-damaged spermatogonia, which was treated with Rg1. Results: We found that treatment with the ginsenoside Rg1 reduced D-gal-induced oxidative stress and spermatogonium apoptosis in vivo and in vitro. Mechanistically, we found that Rg1 activated Akt/bad signaling and reduced D-gal-induced spermatogonium apoptosis. Discussion: We provide evidence showing that the antioxidant effect of Rg1 is mediated by the Akt/GSK-3β/NRF2 axis. Based on these findings, we consider Rg1 a potential treatment for testicular oxidative damage. [ABSTRACT FROM AUTHOR]

Ulceration colitis (UC) is a chronic and recurrent inflammatory disorder in the gastro-intestinal tract. The purpose of our study is to explore the potential mechanisms of ginsenoside Rg1 (GS Rg1) on dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced RAW 264.7 cells. Acute colitis was induced in male C57BL/6 mice. In vitro model of LPS-induced RAW 264.7 cells to simulate enteritis model. The disease activity index (DAI), colon length, body weight and histopathological analysis were performed in vivo. Pro-inflammatory cytokines and markers for oxidative and anti-oxidative stress, MPO level were measured in vivo and in vitro. Nuclear erythroid 2-related factor 2 (Nrf2) and NF-κB p65 protein levels were analyzed using western blotting. Our results indicated that the UC models were established successfully by drinking DSS water. GS Rg1 significantly attenuated UC-related symptoms, including preventing weight loss, decreasing DAI scores, and increasing colon length. GS Rg1 ameliorated the DSS-induced oxidative stress. IL-1ß, IL-6, and TNF-a levels were significantly increased in serum and cell supernatant effectively, while treatment with the GS Rg1 significantly reduced these factors. GS Rg1 reduced MPO content in the colon. GS Rg1 treatment increased SOD and decreased MDA levels in the serum, colon, and cell supernatant. GS Rg1 restored the Nrf-2/HO-1/NF-κB pathway in RAW 264.7 cells and UC mice, and these changes were blocked by Nrf-2 siRNA. Overall, GS Rg1 ameliorated inflammation and oxidative stress in colitis via Nrf-2/HO-1/NF-κB pathway. Thus, GS Rg1 could serve as a potential therapeutic agent for the treatment of UC. [ABSTRACT FROM AUTHOR]

With the ageing of society's population, neurodegenerative diseases have become an important factor affecting the quality of life and mortality in the elderly. Since its physiopathological processes are complex and the authorized medications have recently been shown to have several adverse effects, the development of safe and efficient medications is urgently needed. In this study, we looked at how ginsenoside Rg1 works to postpone neural stem cell ageing and brain ageing, giving it a solid scientific foundation for use as a therapeutic therapy for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Objective: To explore effect of ginsenoside Rg1 on nuclear factor-κB(NF-κB) phosphorylation and inflammationrelated pathways in rats with myocardial injury caused by sepsis. Methods: Rat sepsis myocardial injury model was established by cecal ligation and puncture(CLP). Sixty rats were randomly divided into sham operation(sham) group, CLP group, ginsenoside Rg1 low-dose(CLP+Rg1L ) group, ginsenoside Rg1 medium-dose(CLP+Rg1M) group, ginsenoside Rg1 high-dose(CLP+Rg1H ) group and risatovir(CLP+TAK-242) group, with 10 rats in each group. Sepsis cardiomyocyte model in vitro was constracted by LPS. H9C2 cells were divided into control group, LPS group, LPS+Rg1L group, LPS+Rg1M group, LPS+Rg1H group, LPS+TAK-242 group. Right common carotid artery cannulation method was used to detect mean arterial blood pressure(MABP), heart rate×left ventricular development pressure(LVDP×HR), and maximal increase/decrease rate of left ventricular pressure(±dp/dtmax) in each group. Myocardial histopathological changes was observed by HE staining. Apoptosis of myocardial tissues and H9C2 cells were detected by Annexin VFITC/PI double staining. Creatine kinase(CK), lactate dehydrogenase(LDH), aspartate aminotransferase(AST), cardiac troponin Ⅰ(cTnⅠ), tumor necrosis factor-α(TNF-α), IL-6, IL-1β levels in rat serum and H9C2 cells were detected by ELISA. Proliferation ability of H9C2 cells was detected by CCK-8 and EdU staining. RT-qPCR detected myocardial tissues Toll-like receptor 4(TLR4), NF- κB p65, p38 mitogen activated protein kinase(p38MAPK) mRNA expressions. Western blot detected protein expressions of TLR4, NF-κB p65, p-NF-κB p65, p38MAPK, p-p38MAPK and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3) in myocardial tissues. Results: Ginsenoside Rg1 could increase levels of MABP, LVDP×HR and ±dp/dtmax, decrease activities of CK, LDH and AST, and decrease levels of cTnⅠ, TNF-α, IL-6, IL-1β, TLR4, NF-κB p65, p38MAPK mRNA and TLR4, NF-κB p65, p-p38MAPK/p38MAPK, NLRP3 proteins(P<0.05), promote cardiomyocyte proliferation, inhibit apoptosis and inflammation, and improve myocardial injury. Conclusion: Ginsenoside Rg1 can inhibit myocardial tissue cell apoptosis and inflammation, improve cardiac function, and reduce myocardial injury caused by sepsis, whose mechanism may be related to TLR4/NF- κB and p38MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

BACKGROUND: Brain aging can decline learning and memory functions, and the mechanism is not clear. Recent studies have found that ginsenoside Rb1 can improve the learning and memory ability of Alzheimer’s disease model mice, and its mechanism may be related to the improvement of postsynaptic density protein 95 expression. OBJECTIVE: To investigate whether ginsenoside Rg1 can improve the learning and memory function and postsynaptic density protein 95 expression in the hippocampus of D-galactose-induced aging mice through brain-derived neurotrophic factor/TrkB signaling pathway. METHODS: Fifty male SPF Kunlun mice were randomly divided into five groups, A, B, C, D, and E, with 10 mice in each group. Group A: normal blank control group with no treatment; group B: brain aging model was established through subcutaneous injection of D-galactose solution 300 mg/kg per day; group C: at 1 hour after modeling, donepezil hydrochloride was intragastrically administered daily; group D: at 1 hour after modeling, ginsenoside Rg1 was intragastrically given; group E: at 1 hour after modeling, ginsenoside Rg1 (30 mg/kg per day) was intragastrically given and selective TrkB blocker ANA-12 was intraperitoneally injected every 2 days. Mice in each group were administered according to the corresponding dose and frequency for 6 weeks. The following contents were observed: learning and memory ability (open field test, novel object recognition test, and Morris water maze test); morphological observation of brain tissue using hematoxylin-eosin staining and Nissl staining; and western blot detection of postsynaptic density protein 95 and brain-derived neurotrophic factor protein expression in mouse hippocampus. RESULTS AND CONCLUSION: Compared with group A, the learning and memory abilities of mice in group B were significantly decreased (P < 0.05); compared with group B, the learning and memory abilities of mice were significantly improved in groups C and D (P < 0.05); compared with group D, the learning and memory abilities of mice were significantly decreased in group E (P < 0.05). Results of hematoxylin-eosin staining and Nissl staining showed that: compared with group A, the number of normal neurons in the hippocampal CA1 region was reduced and the expression of Nissl bodies was significantly reduced in group B; compared with group B, the number of normal neurons increased and the number of Nissl corpuscle granules increased significantly in groups C and D; compared with group D, the number of normal neurons was reduced and the expression of Nissl bodies were significantly reduced in group E. Western blot results indicated that compared with group A, the expressions of postsynaptic density protein 95 and brain-derived neurotrophic factor in the hippocampus of mice were significantly decreased in group B (P < 0.05); compared with group B, the expressions of postsynaptic density protein 95 and brain-derived neurotrophic factor were significantly increased in groups C and D (P < 0.05); compared with group D, the expression of postsynaptic density protein 95 was significantly decreased in group E (P < 0.05), while the expression of brain-derived neurotrophic factor had no statistical difference (P > 0.05). To conclude, ginsenoside Rg1 can improve D-galactose-induced neuronal damage and learning and memory abilities in brain aging mice and promote the expression of postsynaptic density protein 95 in the hippocampus. The brain-derived neurotrophic factor/TrKB signaling pathway may be one of its mechanisms. [ABSTRACT FROM AUTHOR]

This research was devoted to estimating the outcomes of ginsenoside Rg1 on learning and memory ability and neuronal apoptosis in epileptic rats through ERK/CREB/BDNF pathway. The epileptic rats induced by lithium chloride were stochastically separated into model subgroup, ginsenoside Rg1 different dose subgroups. The ginsenoside Rg1 subgroups were given 20, 30 and 40 mg/kg ginsenoside Rg1 by gavage individually. Another 6 normal rats were selected as the control subgroup. The seizures of each subgroup were estimated. Morris water maze was utilized for estimating the changes of cognitive function changes of rats. The injury and apoptosis of hippocampal neurons in each subgroup were detected by Nissl and TUNEL assays. HE staining was applied for the structural and pathomorphological changes of hippocampal neurons detection. The oxidative stress level in hippocampus of rats was estimated by ELISA. DCFH-DA probe was applied for the changes of reactive oxygen species (ROS) in brain tissue detection. The Bcl-2, Bax, ERK, p-ERK, CREB, p-CREB and BDNF levels in cerebral cortex were estimated by western blot, and PD98059, a blocker of ERK pathway, was used to intervene. In the control subgroup, Nissl bodies were abundant and evenly distributed, and cortical neurons were arranged neatly. In the model subgroup, the cytoplasmic staining of cortical neurons was insufficient and the arrangement of neurons was disordered. After treatment with ginsenoside Rg1, the morphology of neurons in the cerebral cortex was restored. The frequency of seizures, duration of seizures, Racine grade, escape latency, target quadrant residence time, MDA, TNF-α and ROS levels of cerebral cortex in the model subgroup boosted notablely versus the control subgroup. The frequency of crossing the original platform, the activity of SOD, the IL-10, p-ERK/ERK, p-CREB/CREB and BDNF levels in cerebral cortex were notablely lessened. The above-mentioned indexes in the ginsenoside Rg1 subgroup were notablely improved versus the model subgroup, and the three proteins levels in the PD98059 intervention subgroup were notablely lower. Ginsenoside Rg1 can improve cognitive dysfunction in epileptic rats, which may be concerned with ERK/CREB/BDNF pathway activation in cerebral cortex and lessening oxidative stress and inflammation. • Ginsenoside Rg1 can be used as a potential therapeutic agent for effective treatment of epilepsyã€. • Ginsenoside Rg1 has a protective effect on epilepsy induced by lithium chloride-pilocarpine. • Ginsenoside Rg1 lessened the seizure grade of epileptic rats and reduced the expression of oxidative stress and inflammatory factors. [ABSTRACT FROM AUTHOR]

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The imbalance of follicular helper T (Tfh) cell subset is closely related to the occurrence of inflammatory bowel disease (IBD). Ginsenoside Rg1 (G-Rg1), the main component of ginseng, has excellent immunomodulatory and anti-inflammatory effects. Here, mice colitis was induced by dextran sulfate sodium and treated with G-Rg1 (200 mg/kg/day) for 14 days. Results showed that G-Rg1 can significantly alleviate symptoms of colitis in mice, regulate the balance of Tfh cell subsets, promote the secretion of IL-4 and IL-10, and inhibit the expression of IFN-γ, IL-17A, and IL-21. Molecular docking analysis revealed that G-Rg1 has excellent binding activity with target genes of the TLR/MyD88 signaling pathway, and and can reduce the expression levels of proteins such as TLR2, MyD88, IRAK4, TRAF6, and TAK1. These findings suggest that G-Rg1 can effectively regulate the balance of Tfh cell subsets, and its potential mechanism is related to the inhibition of the TLR/MyD88 signaling pathway.

AIM: To construct an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion (I/R) injury in 661W cells and the protective effect of ginsenoside Rg1. METHODS: The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro. Apoptosis, intracellular reactive oxygen species (ROS) levels and superoxide dismutase (SOD) levels were measured at different time points during the reperfusion injury process. The injury model was pretreated with graded concentrations of ginsenoside Rg1. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of cytochrome C (cyt C)/B-cell lymphoma-2 (Bcl2)/Bcl2 associated protein X (Bax), heme oxygenase-1 (HO-1), caspase9, nuclear factor erythroid 2-related factor 2 (nrf2), kelch-like ECH-associated protein 1 (keap1) and other genes. Western blot was used to detect the expression of nrf2, phosphorylated nrf2 (pnrf2) and keap1 protein levels. RESULTS: Compared to the untreated group, the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased (P

Background: Ginsenoside Rg1, a bioactive component of Ginseng, has demonstrated anti-inflammatory, anti-cancer, and hepatoprotective effects. It is known that the epithelial–mesenchymal transition (EMT) plays a key role in the activation of hepatic stellate cells (HSCs). Recently, Rg1 has been shown to reverse liver fibrosis by suppressing EMT, although the mechanism of Rg1-mediated anti-fibrosis effects is still largely unclear. Interestingly, Smad7, a negative regulator of the transforming growth factor β (TGF-β) pathway, is often methylated during liver fibrosis. Whether Smad7 methylation plays a vital role in the effects of Rg1 on liver fibrosis remains unclear. Methods: Anti-fibrosis effects were examined after Rg1 processing in vivo and in vitro. Smad7 expression, Smad7 methylation, and microRNA-152 (miR-152) levels were also analyzed. Results: Rg1 significantly reduced the liver fibrosis caused by carbon tetrachloride, and reduced collagen deposition was also observed. Rg1 also contributed to the suppression of collagenation and HSC reproduction in vitro. Rg1 caused EMT inactivation, reducing Desmin and increasing E-cadherin levels. Notably, the effect of Rg1 on HSC activation was mediated by the TGF-β pathway. Rg1 induced Smad7 expression and demethylation. The over-expression of DNA methyltransferase 1 (DNMT1) blocked the Rg1-mediated inhibition of Smad7 methylation, and miR-152 targeted DNMT1. Further experiments suggested that Rg1 repressed Smad7 methylation via miR-152-mediated DNMT1 inhibition. MiR-152 inhibition reversed the Rg1-induced promotion of Smad7 expression and demethylation. In addition, miR-152 silencing led to the inhibition of the Rg1-induced EMT inactivation. Conclusion: Rg1 inhibits HSC activation by epigenetically modulating Smad7 expression and at least by partly inhibiting EMT.

Background: Obesity is a risk factor for aging and many diseases, and the disorder of lipid metabolism makes it prominent. This study aims to investigate the effect of ginsenoside Rg1 on aging, lipid metabolism and stress resistance Methods: Rg1 was administered to Caenorhabditis elegans (C. elegans) cultured in NGM or GNGM. The lifespan, locomotory activity, lipid accumulation, cold and heat stress resistance and related mRNA expression of the worms were examined. Gene knockout mutants were used to clarify the effect on lipid metabolism of Rg1. GFP-binding mutants were used to observe the changes in protein expression Results: We reported that Rg1 reduced lipid accumulation and improved stress resistance in C. elegans. Rg1 significantly reduced the expression of fatty acid synthesis-related genes and lipid metabolism-related genes in C. elegans. However, Rg1 did not affect the fat storage in fat-5/fat-6 double mutant or nhr-49 mutant. Combined with network pharmacology, we clarified the possible pathways and targets of Rg1 in lipid metabolism. In addition, Rg1-treated C. elegans showed a higher expression of anti-oxidative genes and heat shock proteins, which might contribute to stress resistance Conclusion: Rg1 reduced fat accumulation by regulating lipid metabolism via nhr-49 and enhanced stress resistance by its antioxidant effect in C. elegans.

Ginseng, an important medicinal plant, is characterized by its main active component, ginsenosides. Among more than 40 ginsenosides, Rg1 is one of the ginsenosides used for measuring the quality of ginseng. Therefore, the identification and characterization of genes for Rg1 biosynthesis are important to elucidate the molecular basis of Rg1 biosynthesis. In this study, we utilized 39,327 SNPs and the corresponding Rg1 content from 344 core ginseng cultivars from Jilin Province. We conducted a genome-wide association study (GWAS) combining weighted gene co-expression network analysis (WGCNA), SNP-Rg1 content association analysis, and gene co-expression network analysis; three candidate Rg1 genes (PgRg1-1, PgRg1-2, and PgRg1-3) and one crucial candidate gene (PgRg1-3) were identified. Functional validation of PgRg1-3 was performed using methyl jasmonate (MeJA) regulation and RNAi, confirming that this gene regulates Rg1 biosynthesis. The spatial–temporal expression patterns of the PgRg1-3 gene and known key enzyme genes involved in ginsenoside biosynthesis differ. Furthermore, variations in their networks have a significant impact on Rg1 biosynthesis. This study established an accurate and efficient method for identifying candidate genes, cloned a novel gene controlling Rg1 biosynthesis, and identified 73 SNPs significantly associated with Rg1 content. This provides genetic resources and effective tools for further exploring the molecular mechanisms of Rg1 biosynthesis and molecular breeding.

Background: Small extracellular vesicles (sEVs) obtained from human umbilical cord mesenchymal stromal cells (MSCs) have shown cardioprotective efficacy in doxorubicin-induced cardiotoxicity (DIC). However, their clinical application is limited due to the low yield and high consumption. This study aims to achieve large-scale production of sEVs using a three-dimensional (3D) bioreactor system. In addition, sEVs were developed to deliver Ginsenoside Rg1 (Rg1), a compound derived from traditional Chinese medicine, Ginseng, that has cardioprotective properties but limited bioavailability, to enhance the treatment of DIC. Methods: The 3D bioreactor system with spinner flasks was used to expand human umbilical cord MSCs and collect MSC-conditioned medium. Subsequently, sEVs were isolated from the conditioned medium using differential ultra-centrifugation (dUC). The sEVs were loaded with Ginsenoside Rg1 by electroporation and evaluated for cardioprotective efficacy using Cell Counting Kit-8 (CCK-8) analysis, Annexin V/PI staining and live cell count of H9c2 cells under DIC. Results: Using the 3D bioreactor system with spinner flasks, the expansion of MSCs reached ~600 million, and the production of sEVs was up to 2.2 × 1012 particles in five days with significantly reduced bench work compared to traditional 2D flasks. With the optimized protocol, the Ginsenoside Rg1 loading efficiency of sEVs by electroporation was ~21%, higher than sonication or co-incubation. Moreover, Rg1-loaded sEVs had attenuated DOX-induced cardiotoxicity with reduced apoptosis compared to free Ginsenoside Rg1 or sEVs. Conclusions: The 3D culture system scaled up the production of sEVs, which facilitated the Rg1 delivery and attenuated cardiomyocyte apoptosis, suggesting a potential treatment of DOX-induced cardiotoxicity.

Objective To explore the effects of ginsenoside Rg1 on blood-brain barrier, neuroinflammation and behavioral function of traumatic brain injury (TBI) mouse model. MethodsThe experiment was divided into two parts. In the first part, 27 SPF male BALB/c mice were randomly divided into blank group, sham operation group and TBI model group, with 9 mice in each group. TBI model group was made by controlled cortical impact (CCI) after craniotomy, while sham operation group was only performed craniotomy without any treatment, and the blank group was not treated at all. The effect of modeling was evaluated after operation. In the second part, 50 male BALB/c mice were randomly divided into sham operation group, three different drug dosage groups and solvent (DMSO) control group, with 8 mice in each group. The drug treatment groups were injected with ginsenoside Rg1 at the doses of 10, 20 and 40 mg/kg respectively 6 hours after TBI model had been successfully established, while the DMSO control group was given the same amount of 1% DMSO for one week, twice a day. Modified neurological severity scores (mNSS) were performed on the 1st, 3rd, 7th and 14th day after modeling, and the blood-brain barrier leakage was detected by Western blotting on the 3rd day after modeling. On the 14th and 16th day, the elevated cross maze test and water maze test were used to detect the neurobehavioral function. On the 28th day after anesthesia and perfusion, the brains were taken out, and the neuroinflammation such as activation of microglia and astrocytes was observed by immunofluorescence staining. Results The expression level of MMP-9, a marker of blood-brain barrier, decreased in ginsenoside Rg1 treatment group (P