Overview of Panax ginseng and its active ingredients protective mechanism on cardiovascular diseases.

ETHNIC PHARMACOLOGICAL RELEVANCE: Panax ginseng is a traditional Chinese herbal medicine used to treat cardiovascular diseases (CVDs), and it is still widely used to improve the clinical symptoms of various CVDs. However, there is currently a lack of summary and analysis on the mechanism of Panax ginseng exerts its cardiovascular protective effects. This article provides a review of in vivo and in vitro pharmacological studies on Panax ginseng and its active ingredients in reducing CVDs damage. AIM OF THIS REVIEW: This review summarized the latest literature on Panax ginseng and its active ingredients in CVDs research, aiming to have a comprehensive and in-depth understanding of the cardiovascular protection mechanism of Panax ginseng, and to provide new ideas for the treatment of CVDs, as well as to optimize the clinical application of Panax ginseng. METHODS: Enrichment of pathways and biological terms using the traditional Chinese medicine molecular mechanism bioinformatics analysis tool (BATMAN-TCM). The literature search is based on electronic databases such as PubMed, ScienceDirect, Scopus, CNKI, with a search period of 2002-2023. The search terms include Panax ginseng, Panax ginseng ingredients, ginsenosides, ginseng polysaccharides, ginseng glycoproteins, ginseng volatile oil, CVDs, heart, and cardiac. RESULTS: 132 articles were ultimately included in the review. The ingredients in Panax ginseng that manifested cardiovascular protective effects are mainly ginsenosides (especially ginsenoside Rb1). Ginsenosides protected against CVDs such as ischemic reperfusion injury, atherosclerosis and heart failure mainly through improving energy metabolism, inhibiting hyper-autophagy, antioxidant, anti-inflammatory and promoting secretion of exosomes. CONCLUSION: Panax ginseng and its active ingredients have a particularly prominent effect on improving myocardial energy metabolism remodeling in protecting against CVDs. The AMPK and PPAR signaling pathways are the key targets through which Panax ginseng produces multiple mechanisms of cardiovascular protection. Extracellular vesicles and nanoparticles as carriers are potential delivery ways for optimizing the bioavailability of Panax ginseng and its active ingredients.

Crosstalk among Oxidative Stress, Autophagy, and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells: A Mixed Computational and Experimental Study.

OBJECTIVE: Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1), a component derived from medicinal plants, is known for its pharmacological benefits in IS, but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. METHODS: An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools, including gene set enrichment analysis (GSEA), Gene Ontology (GO) classification and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction network analysis, and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. RESULTS: Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically, GRb1 was found to modulate the interplay between oxidative stress, apoptosis, and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62), autophagy related 5 (ATG5), and hypoxia-inducible factor 1-alpha (HIF-1α) were identified, highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. CONCLUSION: GRbl protects BMECs against OGD/R injury by influencing oxidative stress, apoptosis, and autophagy. The identification of SQSTM1/p62, ATG5, and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS, providing a foundation for future research into its mechanisms and applications in IS treatment.

Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis.

Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), a process associated with ferroptosis. Ginsenoside Rb1 (GRb1), a major active component extracted from Panax ginseng, inhibits HSC activation. However, the potential role of GRb1 in mediating HSC ferroptosis remains unclear. This study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro, using CCl4-induced liver fibrosis mouse model and primary HSCs, LX-2 cells. The findings revealed that GRb1 effectively inactivated HSCs in vitro, reducing alpha-smooth muscle actin (α-SMA) and Type I collagen (Col1A1) levels. Moreover, GRb1 significantly alleviated CCl4-induced liver fibrosis in vivo. From a mechanistic standpoint, the ferroptosis pathway appeared to be central to the antifibrotic effects of GRb1. Specifically, GRb1 promoted HSC ferroptosis both in vivo and in vitro, characterized by increased glutathione depletion, malondialdehyde production, iron overload, and accumulation of reactive oxygen species (ROS). Intriguingly, GRb1 increased Beclin 1 (BECN1) levels and decreased the System Xc-key subunit SLC7A11. Further experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by GRb1. Moreover, BECN1 could directly interact with SLC7A11, initiating HSC ferroptosis. In conclusion, the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in vitro. Overall, this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation, at least partly through its modulation of BECN1 and SLC7A11.

Multi-layered effects of Panax notoginseng on immune system.

Recent research has demonstrated the immunomodulatory potential of Panax notoginseng in the treatment of chronic inflammatory diseases and cerebral hemorrhage, suggesting its significance in clinical practice. Nevertheless, the complex immune activity of various components has hindered a comprehensive understanding of the immune-regulating properties of Panax notoginseng, impeding its broader utilization. This review evaluates the effect of Panax notoginseng to various types of white blood cells, elucidates the underlying mechanisms, and compares the immunomodulatory effects of different Panax notoginseng active fractions, aiming to provide the theory basis for future immunomodulatory investigation.

Ginsenoside Rb1 mitigates acute catecholamine surge-induced myocardial injuries in part by suppressing STING-mediated macrophage activation.

Stress cardiomyopathy (SCM) is associated with cardiovascular mortality rates similar to acute coronary syndrome. Myocardial injuries driven by inflammatory mechanisms may in part account for the dismal prognosis of SCM. Currently, no inflammation-targeted therapies are available to mitigate SCM-associated myocardial injuries. In this study, acute catecholamine surge-induced SCM was modeled by stimulating the ovariectomized (OVX) mice with isoproterenol (ISO). The effects of ginsenoside Rb1 (Rb1) on SCM-associated myocardial injuries were assessed in the OVX-ISO compound mice. RAW 264.7 macrophages stimulated with calf thymus DNA (ctDNA) or STING agonist DMXAA were adopted to further understand the anti-inflammatory mechanisms of Rb1. The results show that estrogen deprivation increases the susceptibility to ISO-induced myocardial injuries. Rb1 mitigates myocardial injuries and attenuates cardiomyocyte necrosis as well as myocardial inflammation in the OVX-ISO mice. Bioinformatics analysis suggests that cytosolic DNA-sensing pathway is closely linked with ISO-triggered inflammatory responses and cell death in the heart. In macrophages, Rb1 lowers ctDNA-stimulated production of TNF-α, IL-6, CCL2 and IFN-ß. RNA-seq analyses uncover that Rb1 offsets DNA-stimulated upregulation in multiple inflammatory response pathways and cytosolic DNA-sensing pathway. Furthermore, Rb1 directly mitigates DMXAA-stimulated STING activation and inflammatory responses in macrophages. In conclusion, the work here demonstrates for the first time that Rb1 protects against SCM-associated myocardial injuries in part by counteracting acute ISO stress-triggered cardiomyocyte necrosis and myocardial inflammation. Moreover, by evidencing that Rb1 downregulates cytosolic DNA-sensing machineries in macrophages, our findings warrant further investigation of therapeutic implications of the anti-inflammatory Rb1 in the treatment of SCM.

So Shiho Tang Reduces Inflammation in Lipopolysaccharide-Induced RAW 264.7 Macrophages and Dextran Sodium Sulfate-Induced Colitis Mice.

So Shiho Tang (SSHT) is a traditional herbal medicine commonly used in Asian countries. This study evaluated the anti-inflammatory effect of SSHT and the associated mechanism using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and murine dextran sodium sulfate (DSS)-induced ulcerative colitis models. Pre-treatment of RAW 264.7 macrophages with SSHT significantly reduced LPS-induced inflammation by decreasing nitrite production and regulating the mitogen-activated protein kinase pathway. Meanwhile, in mice, DSS-induced colitis symptoms, including colon shortening and body weight loss, were attenuated by SSHT. Moreover, representative compounds of SSHT, including glycyrrhizic acid, ginsenoside Rb1, baicalin, saikosaponin A, and saikosaponin B2, were quantified, and their effects on nitrite production were measured. A potential anti-inflammatory effect was detected in LPS-induced RAW 264.7 cells. Our findings suggest that SSHT is a promising anti-inflammatory agent. Its representative components, including saikosaponin B2, ginsenoside Rb1, and baicalin, may represent the key active compounds responsible for eliciting the anti-inflammatory effects and can, therefore, serve as quality control markers in SSHT preparations.

Ginsenoside Rb1 attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis.

Ginsenoside Rb1 (Rb1), an active component isolated from traditional Chinese medicine Ginseng, is beneficial to many cardiovascular diseases. However, whether it can protect against doxorubicin induced cardiotoxicity (DIC) is not clear yet. In this study, we aimed to investigate the role of Rb1 in DIC. Mice were injected with a single dose of doxorubicin (20 mg/kg) to induce acute cardiotoxicity. Rb1 was given daily gavage to mice for 7 days. Changes in cardiac function, myocardium histopathology, oxidative stress, cardiomyocyte mitochondrion morphology were studied to evaluate Rb1's function on DIC. Meanwhile, RNA-seq analysis was performed to explore the potential underline molecular mechanism involved in Rb1's function on DIC. We found that Rb1 treatment can improve survival rate and body weight in Dox treated mice group. Rb1 can attenuate Dox induced cardiac dysfunction and myocardium hypertrophy and interstitial fibrosis. The oxidative stress increase and cardiomyocyte mitochondrion injury were improved by Rb1 treatment. Mechanism study found that Rb1's beneficial role in DIC is through suppressing of autophagy and ferroptosis. This study shown that Ginsenoside Rb1 can protect against DIC by regulating autophagy and ferroptosis.

Safety and efficacy of a feed additive consisting of a tincture derived from the roots of Panax ginseng C.A.Mey. (ginseng tincture) for horses, dogs and cats (FEFANA asbl).

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.

Ginsenoside Rb1 ameliorates lipotoxicity-induced myocardial injury in diabetes mellitus by regulating Mfn2.

PURPOSE: Diabetic cardiomyopathy is a prevalent cardiovascular complication of diabetes mellitus. This study aimed to investigate the effects of ginsenoside Rb1 (GRb1) on the diabetic myocardium. METHODS: Leptin receptor-deficient db/db mice and palmitic acid (PA)-treated cardiomyocyte models were utilized. Cardiac systolic and diastolic function, mitochondrial morphology, and respiratory chain function were determined. The expression of mitochondrial dynamics proteins was measured. Mitofusin 2 (Mfn2) overexpression and inhibition were achieved by lentiviral infection and small interfering RNA (siRNA) transfection. RESULTS: In comparison to non-diabetic mice, db/db mice exhibited significant increases in body weight, blood glucose, blood lipids, and cardiac free fatty acid levels. This was accompanied by myocardial hypertrophy and left ventricular diastolic dysfunction, which were significantly ameliorated by GRb1 intervention. Stimulation with PA increased oxidative stress and apoptosis, and decreased viability in H9c2 cardiomyocytes. PA also reduced sarcomere contractility and relaxation in adult mice ventricular myocytes. PA-induced cellular and mitochondrial damage were reversed with GRb1 treatment. The cardiac tissue of db/db mice and PA-treated cardiomyocytes exhibited a decrease in Mfn2 expression, which was markedly improved by GRb1. Mfn2 overexpression reversed PA-induced mitochondrial fragmentation and functional damage in cardiomyocytes, while inhibition of Mfn2 expression by siRNA transfection blocked the protective effects of GRb1. CONCLUSION: GRb1 alleviated myocardial lipid accumulation and mitochondrial injury, and attenuated ventricular diastolic dysfunction in diabetic mice. The regulation of Mfn2 was involved in the protective effects of GRb1 against lipotoxic myocardial injury.

Ginsenoside Rb1, Compound K and 20(S)-Protopanaxadiol Attenuate High-Fat Diet-Induced Hyperlipidemia in Rats via Modulation of Gut Microbiota and Bile Acid Metabolism.

Hyperlipidemia, characterized by elevated serum lipid concentrations resulting from lipid metabolism dysfunction, represents a prevalent global health concern. Ginsenoside Rb1, compound K (CK), and 20(S)-protopanaxadiol (PPD), bioactive constituents derived from Panax ginseng, have shown promise in mitigating lipid metabolism disorders. However, the comparative efficacy and underlying mechanisms of these compounds in hyperlipidemia prevention remain inadequately explored. This study investigates the impact of ginsenoside Rb1, CK, and PPD supplementation on hyperlipidemia in rats induced by a high-fat diet. Our findings demonstrate that ginsenoside Rb1 significantly decreased body weight and body weight gain, ameliorated hepatic steatosis, and improved dyslipidemia in HFD-fed rats, outperforming CK and PPD. Moreover, ginsenoside Rb1, CK, and PPD distinctly modified gut microbiota composition and function. Ginsenoside Rb1 increased the relative abundance of Blautia and Eubacterium, while PPD elevated Akkermansia levels. Both CK and PPD increased Prevotella and Bacteroides, whereas Clostridium-sensu-stricto and Lactobacillus were reduced following treatment with all three compounds. Notably, only ginsenoside Rb1 enhanced lipid metabolism by modulating the PPARγ/ACC/FAS signaling pathway and promoting fatty acid ß-oxidation. Additionally, all three ginsenosides markedly improved bile acid enterohepatic circulation via the FXR/CYP7A1 pathway, reducing hepatic and serum total bile acids and modulating bile acid pool composition by decreasing primary/unconjugated bile acids (CA, CDCA, and ß-MCA) and increasing conjugated bile acids (TCDCA, GCDCA, GDCA, and TUDCA), correlated with gut microbiota changes. In conclusion, our results suggest that ginsenoside Rb1, CK, and PPD supplementation offer promising prebiotic interventions for managing HFD-induced hyperlipidemia in rats, with ginsenoside Rb1 demonstrating superior efficacy.

Ginsenoside Rb1 Inhibits the Proliferation of Lung Cancer Cells by Inducing the Mitochondrial-mediated Apoptosis Pathway.

BACKGROUND: Lung cancer is one of the more common malignant tumors posing a great threat to human life, and it is very urgent to find safe and effective therapeutic drugs. The antitumor effect of ginsenosides has been reported to be a treatment with a strong effect and a high safety profile. OBJECTIVE: This paper aimed to investigate the inhibitory effect of ginsenoside Rb1 on 95D and NCI-H460 lung cancer cells and its pathway to promote apoptosis. METHODS: We performed the CCK-8 assay, fluorescence staining assay, flow cytometry, scratch healing assay, and Transwell assay to detect the effects of different concentrations of ginsenoside Rb1 on the antitumor activity of 95D and NCI-H460 cells and Western Blot detected the mechanism of antitumor effect. RESULTS: Ginsenoside Rb1 treatment significantly increased the inhibition and apoptosis rates of 95D and NCIH460 cells and inhibited the cell cycle transition from S phase to G2/M. Rb1 induces apoptosis by altering the levels of P53, Bax, Cyto-c, Caspase-8, Caspase-3, Cleaved Caspase-3, Bcl-2, MMP-2, and MMP-9 proteins and activating the external apoptotic pathway. CONCLUSION: Ginsenoside Rb1 inhibits proliferation and migration and induces apoptosis of 95D and NCI-H460 lung cancer cells by regulating the mitochondrial apoptotic pathway to achieve antitumor activity.

Integration of 16S rRNA sequencing and metabolomics to investigate the modulatory effect of ginsenoside Rb1 on atherosclerosis.

Background: /aims: Atherosclerosis (AS) is the common pathological basis of a variety of cardiovascular diseases (CVD), and has become the main cause of human death worldwide, and the incidence is increasing and younger trend. Ginsenoside Rb1 (Rb1), an important monomer component of the traditional Chinese herb ginseng, known for its ability to improve blood lipid disorders and anti-inflammatory. In addition, Rb1 was proved to be an effective treatment for AS. However, the effect of Rb1 on AS remains to be elucidated. The aim of this study was to investigate the mechanisms of Rb1 in ameliorating AS induced by high-fat diet (HFD). Materials and methods: In this study, we developed an experimental AS model in Sprague-Dawley rats by feeding HFD with intraperitoneal injection of vitamin D3. The potential therapeutic mechanism of Rb1 in AS rats was investigated by detecting the expression of inflammatory factors, microbiome 16S rRNA gene sequencing, short-chain fatty acids (SCFAs) targeted metabolomics and untargeted metabolomics. Results: Rb1 could effectively alleviate the symptoms of AS and suppress the overexpression of inflammation-related factors. Meanwhile, Rb1 altered gut microbial composition and concentration of SCFAs characterized by Bacteroidetes, Actinobacteria, Lactobacillus, Prevotella, Oscillospira enrichment and Desulfovibrio depletion, accompanied by increased production of acetic acid and propionic acid. Moreover, untargeted metabolomics showed that Rb1 considerably improved faecal metabolite profiles, particularly arachidonic acid metabolism and primary bile acid biosynthesis. Conclusion: Rb1 ameliorated the HFD-induced AS, and the mechanism is related to improving intestinal metabolic homeostasis and inhibiting systemic inflammation by regulating gut microbiota.

Exploring the anti-atherosclerosis mechanism of ginsenoside Rb1 by integrating network pharmacology and experimental verification.

Ginsenoside Rb1 is the major active constituent of ginseng, which is widely used in traditional Chinese medicine for the atherosclerosis treatment by anti-inflammatory, anti-oxidant and reducing lipid accumulation. We explored cellular target and molecular mechanisms of ginsenoside Rb1 based on network pharmacology and in vitro experimental validation. In this study, we predicted 17 potential therapeutic targets for ginsenoside Rb1 with atherosclerosis from public databases. We then used protein-protein interaction network to screen the hub targets. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that the effects of ginsenoside Rb1 were meditated through multiple targets and pathways. Next, molecular docking results revealed that in the 10 core targets, CCND1 has the highest binding energy with ginsenoside Rb1. Vascular cell proliferation plays a critical role in atherosclerosis development. However, the effect and direct target of ginsenoside Rb1 in regulating vascular cell proliferation in atherosclerosis remains unclear. Edu straining results indicated that ginsenoside Rb1 inhibited the cell proliferation of endothelial cells, macrophages, and vascular smooth muscle cells. The protein immunoprecipitation (IP) analysis showed that ginsenoside Rb1 inhibited the vascular cell proliferation by suppressing the interaction of CCDN1 and CDK4. These findings systematically reveal that the anti-atherosclerosis mechanism of ginsenoside Rb1 by integrating network pharmacology and experimental validation, which provide evidence to treat atherosclerosis by using ginsenoside Rb1 and targeting CCND1.

Ginsenoside Rb1 Deters Cell Proliferation, Induces Apoptosis, Alleviates Oxidative Stress, and Antimetastasis in Oral Squamous Carcinoma Cells.

There are numerous therapeutic applications for ginsenoside Rb1 (GRb1), the primary saponin derived from ginseng root. According to earlier research, ginsenoside Rb1 causes apoptosis and reduces the cell cycle. Its adverse effects, especially those on the development of the embryo, still need to be thoroughly studied. A host's lifestyle choices, including smoking, drinking too much alcohol, using tobacco products, and having an HPV infection, can increase the risk of oral squamous cell carcinoma (OSCC), one of the most prevalent malignancies of the oral cavity. To address this challenge, this investigation focuses on the design of GRb1 for treating OSCC. In vitro cytotoxicity studies confirmed that GRb1 was more effective in PCI-9A and PCI-13 cells, with reduced toxicity in non-cancerous cells. Further verification of cellular morphology was achieved through various biochemical staining methods. The mechanism of cell death was investigated by Annexin V-FITC and PI methods. Additionally, the antimetastatic attributes of GRb1 have been evaluated using both migration scratch and Transwell migration assays, which have collectively revealed excellent antimetastatic potential. The DNA fragmentation of the PCI-9A and PCI-13 cells was assessed using a comet assay. Ginsenoside Rb1 improved ROS levels and caused mitochondrial membrane potential alterations and DNA damage, which resulted in apoptosis. OSCC administration significantly reduced the levels of SOD, GSH, GPx, and CAT, increasing the levels of PCI-9A and PCI-13 cells, while GRb1 improved this situation. Therefore, we propose that Ginsenoside Rb1 could be an alternative therapeutic strategy for OSCC therapy.

Protective effect of ginsenoside Rb1 against aconitine cardiotoxicity studied by myocardial injury, action potential, and calcium signaling.

Aconitine is the main active component of Aconitum plants. Although aconitine has effects that include strengthening the heart, analgesia, anti-tumor, and immune-regulating effects, aconitine has both efficacy and toxicity, especially cardiotoxicity. Severe effects can include arrhythmia and cardiac arrest, which limits the clinical application of aconitine-containing traditional Chinese medicine. Ginsenoside Rb1(Rb1) is mainly found in plants, such as ginseng and Panax notoginseng, and has cardiovascular-protective and anti-arrhythmia effects. This study aimed to investigate the detoxifying effects of Rb1 on aconitine cardiotoxicity and the electrophysiological effect of Rb1 on aconitine-induced arrhythmia in rats. Pathological analysis, myocardial enzymatic indexes, and Western blotting were used to investigate the ameliorating effect of Rb1 on aconitine cardiotoxicity. Optical mapping was used to evaluate the effect of Rb1 on action potential and calcium signaling after aconitine-induced arrhythmia. Rb1 inhibited pathological damage caused by aconitine, decreased myocardial enzyme levels, and restored the balance of apoptotic protein expression by reducing the expression of Bax and cleaved caspase 3 and increasing the expression of Bcl-2, thereby reducing myocardial damage caused by aconitine. Rb1 also reduced the increase in heart rate caused by aconitine, accelerated action potential conduction and calcium signaling, and reduced the dispersion of action potential and calcium signal conduction. Rb1 reduced the cardiotoxicity of aconitine by attenuating aconitine-induced myocardial injury and inhibiting the aconitine-induced retardation of ventricular action potential and calcium signaling in rats.

A novel approach combining network pharmacology and experimental validation to study the protective effect of ginsenoside Rb1 against cantharidin-induced hepatotoxicity in mice.

Cantharidin (CTD) is a widely used anticancer compound, but its clinical use is mainly limited due to hepatotoxicity. Ginsenoside Rb1 (GRb1) shows potential hepatoprotective effects. Nonetheless, the protective effect and underlying mechanism of GRb1 against CTD-induced hepatotoxicity in mice have not been investigated. This study aims to elucidate the effect and mechanism of GRb1 on CTD-induced hepatotoxicity using network pharmacology and in vivo experiments. Network pharmacology studies have shown that 263 targets were the main mechanisms by which GRb1 alleviates CTD-induced hepatotoxicity. KEGG enrichment analysis revealed that 75 hub genes were mainly enriched in TNF, IL-17 and apoptosis signalling pathways. Molecular docking analysis showed that GRb1 exhibited high affinity with Akt1, Tnf, Il6, Bcl2 and Caspase3. In addition, results from animal studies demonstrated that GRb1 could ameliorate CTD-induced hepatotoxicity by inhibiting protein expression of Caspase-3, Caspase-8, Bcl-2/Bax, GRP78, ATF6, ATF4, CHOP, IRE1α and PERK. This research revealed the mechanism of GRb1 against CTD-induced hepatotoxicity by inhibiting apoptosis and endoplasmic reticulum stress (ERS) and it may provide a scientific rationale for the potential use of GRb1 in the treatment of hepatotoxicity induced by CTD.

Ginsenoside Rb1 alleviates lipopolysaccharide-induced inflammation in human dental pulp cells via the PI3K/Akt, NF-κB, and MAPK signalling pathways.

AIM: Among numerous constituents of Panax ginseng, a constituent named Ginsenoside Rb1 (G-Rb1) has been studied to diminish inflammation associated with diseases. This study investigated the anti-inflammatory properties of G-Rb1 on human dental pulp cells (hDPCs) exposed to lipopolysaccharide (LPS) and aimed to determine the underlying molecular mechanisms. METHODOLOGY: The KEGG pathway analysis was performed after RNA sequencing in G-Rb1- and LPS-treated hDPCs. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis were used for the assessment of cell adhesion molecules and inflammatory cytokines. Statistical analysis was performed with one-way ANOVA and the Student-Newman-Keuls test. RESULTS: G-Rb1 did not exhibit any cytotoxicity within the range of concentrations tested. However, it affected the levels of TNF-α, IL-6 and IL-8, as these showed reduced levels with exposure to LPS. Additionally, less mRNA and protein expressions of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were shown. With the presence of G-Rb1, decreased levels of PI3K/Akt, phosphorylated IκBα and p65 were also observed. Furthermore, phosphorylated ERK and JNK by LPS were diminished within 15, 30 and 60 min of G-Rb1 exposure; however, the expression of non-phosphorylated ERK and JNK remained unchanged. CONCLUSIONS: G-Rb1 suppressed the LPS-induced increase of cell adhesion molecules and inflammatory cytokines, while also inhibiting PI3K/Akt, phosphorylation of NF-κB transcription factors, ERK and JNK of MAPK signalling in hDPCs.

Carbon quantum dots of ginsenoside Rb1 for application in a mouse model of intracerebral Hemorrhage.

After intracerebral hemorrhage (ICH) occurs, the overproduction of reactive oxygen species (ROS) and iron ion overload are the leading causes of secondary damage. Removing excess iron ions and ROS in the meningeal system can effectively alleviate the secondary damage after ICH. This study synthesized ginsenoside Rb1 carbon quantum dots (RBCQDs) using ginsenoside Rb1 and ethylenediamine via a hydrothermal method. RBCQDs exhibit potent capabilities in scavenging ABTS + free radicals and iron ions in solution. After intrathecal injection, the distribution of RBCQDs is predominantly localized in the subarachnoid space. RBCQDs can eliminate ROS and chelate iron ions within the meningeal system. Treatment with RBCQDs significantly improves blood flow in the meningeal system, effectively protecting dying neurons, improving neurological function, and providing a new therapeutic approach for the clinical treatment of ICH.

Ginsenoside Rb1 prevents age-related endothelial senescence by modulating SIRT1/caveolin-1/enos signaling pathway.

Background: Advancing age is one of the independent risk factors for cardiovascular disorders. The Compendium of Materia Medica, a classic book on traditional Chinese medicine, states that ginseng "harmonizes the five internal organs, calming the spirit and prolonging the years of life." Considered one of the primary bioactive compounds derived from Panax ginseng, ginsenoside Rb1 (g-Rb1) has been scientifically suggested to possess anti-senescence efficacy. More research is needed to explore the vascular pharmacological activity and potential clinical application value of g-Rb1. Aims of the study: Our previous study demonstrated that g-Rb1 could mitigate cellular senescence via the SIRT1/eNOS pathway. This study was performed to explore the exact mechanisms by which g-Rb1 modulates the SIRT1/eNOS pathway. Materials and methods: We used human primary umbilical vein endothelial cells (HUVECs) to establish a replicative ageing model. Real-time (RT‒PCR), western blotting, small interfering RNA (siRNA), and immunoprecipitation were conducted to detect the effect of g-Rb1 on the SIRT1/caveolin-1/eNOS axis. Results: G-Rb1 increased NO production and alleviated replicative senescence of HUVECs. The application of g-Rb1 elevated the mRNA and protein abundance of both SIRT1 and eNOS while concomitantly suppressing the expression of caveolin-1. Inhibition of SIRT1 and eNOS by siRNAs suppressed the anti-senescence function of g-Rb1, while caveolin-1 siRNA could enhance it. G-Rb1 decreased the acetylation level of caveolin-1 and increased NO production, which was suppressed by SIRT1 siRNA. Both g-Rb1 and caveolin-1 siRNA could reduce the acetylation level of eNOS and increase NO production. Conclusion: G-Rb1 prevents age-related endothelial senescence by modulating the SIRT1/caveolin-1/eNOS signaling pathway.

Progress of Ginsenoside Rb1 in neurological disorders.

Ginseng is frequently used in traditional Chinese medicine to treat neurological disorders. The primary active component of ginseng is ginsenoside, which has been classified into more than 110 types based on their chemical structures. Ginsenoside Rb1 (GsRb1)-a protopanaxadiol saponin and a typical ginseng component-exhibits anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-autophagy properties in the nervous system. Neurological disorders remain a leading cause of death and disability globally. GsRb1 effectively treats neurological disorders. To contribute novel insights to the understanding and treatment of neurological disorders, we present a comprehensive review of the pharmacokinetics, actions, mechanisms, and research development of GsRb1 in neurological disorders.