RG3

Abstract

Ginsenoside Rg3 (GRg3), a bioactive compound extracted from ginseng, has demonstrated the ability to inhibit Aβ production and deposition. In this study, PEGylated GRg3-loaded niosomes were developed and characterized for potential AD treatment. Their efficacy was assessed using in vitro and in vivo models, as well as molecular dynamics simulations of self-assembly. Our formulation achieved a relatively high encapsulation efficiency of 83.02% and a controlled release profile, with 75.73% of the drug released over 48 h. In vitro, co-administration of Aβ with free or PEGylated GRg3-loaded niosomes markedly reduced the levels of Total Antioxidant Capacity, Malondialdehyde (MDA), and caspase-3 gene expression compared to the Aβ-only group. In vivo evaluations revealed that treatment with the niosomal formulation did not significantly alter behavioral parameters, MDA levels, or Superoxide Dismutase activity. However, catalase activity was significantly higher than in the control group. Histopathological and immunohistochemical analyses showed reduced neurovascular damage and preservation of blood-brain barrier (BBB) and hippocampal integrity in the treated group. MD simulations confirmed the spontaneous self-assembly of surfactant molecules into a bilayer structure with successful incorporation of GRg3. Our findings underscore the potential of PEGylated niosomes as efficient nanocarriers for GRg3 delivery in the AD treatment.

Abstract

Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by insulin resistance and pancreatic β-cell dysfunction. While human umbilical cord mesenchymal stem cells (HUCMSCs) show therapeutic potential, their efficacy can be limited by the harsh in vivo microenvironment. 20(R)-Rg3, a ginsenoside with anti-inflammatory and antioxidant properties, may enhance HUCMSCs' function, but the combined effect and mechanism of this "cell-molecule" strategy remain unclear. This study aimed to investigate the therapeutic effects and underlying mechanisms of a combination therapy using 20(R)-Rg3 and HUCMSCs in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mouse model. Diabetic mice were treated with PBS, HUCMSCs alone, or HUCMSCs pre-treated with 20(R)-Rg3. Fasting blood glucose and body weight were monitored. Insulin resistance was assessed via oral glucose tolerance tests (OGTTs) and intraperitoneal insulin tolerance tests (IPITTs). Serum biochemical parameters (lipids, liver and kidney function, insulin, C-peptide) were analyzed. Histopathological examination (H&E, PAS) of the liver, kidney, and pancreas was performed, alongside immunofluorescence for islet hormones. Transcriptomic analysis (RNA-seq) was conducted on HUCMSCs with or without 20(R)-Rg3 pretreatment to elucidate potential signaling pathways. Results demonstrated that the combination significantly reduced hyperglycemia and improved insulin sensitivity more effectively than HUCMSCs alone. It also ameliorated dyslipidemia, enhanced liver and kidney function, promoted glycogen synthesis, and facilitated pancreatic islet "regeneration". Transcriptomic analysis indicated that the synergistic effect is primarily mediated through activation of the PI3K/Akt signaling pathway. These findings suggest that 20(R)-Rg3 potentiates the therapeutic efficacy of HUCMSCs, providing a promising combinatorial strategy for T2DM treatment.

Abstract

Paclitaxel (PTX) kills tumor cells by stabilizing microtubules to induce apoptosis, but its efficacy is limited by resistance mediated by the anti-apoptotic protein survivin. Targeted inhibition of survivin with siRNA could synergistically enhance PTX-induced apoptosis; however, nucleic acid-based therapeutics, such as siRNA, exhibit high instability and susceptibility to degradation, making their efficacy highly dependent on specialized delivery systems. Thus, co-delivery systems for PTX and siRNA are critical to achieving synergistic antitumor activity. Natural products present several advantages, including wide availability, high biocompatibility, and multi-target synergistic effects, offering promising approaches for constructing a co-delivery system. In this study, a co-delivery system integrating siRNA and PTX based on natural products was developed. Ginsenoside Rg3 (Rg3) not only serves as the structural backbone but also enhances tumor-targeting capability and inhibits tumor cell migration. The edible cationic polymer chitooligosaccharide (COS) efficiently encapsulates siRNA, ensuring safe and efficient delivery. This co-delivery system based on natural synergy enables multi-level cooperation: Rg3 mediates targeted transport, PTX triggers apoptosis, and COS-assisted siRNA silences survivin, thereby ensuring precise targeting and promoting complete tumor apoptosis, highlighting a promising strategy for the application of natural products in cancer therapy.

Abstract

Fei Wei formula (FW) has been integrated into clinical practice, demonstrating significant therapeutic efficacy for idiopathic pulmonary fibrosis (IPF). However, its underlying mechanism remains unclear. Pulmonary endothelial cells are a partial source of fibroblasts through endothelial mesenchymal transition (EndoMT), which contributes to pulmonary fibrosis.

Abstract

Allergic rhinitis (AR) is positively correlated with pyroptosis induced by NLR family pyrin domain containing 3 (NLRP3). Here, the effect of ginsenoside Rg3 on pyroptosis in the progression of AR was evaluated.

Abstract

20(R)-ginsenoside Rg3 can reduce the effects of oxidative stress and cell death in cerebral ischemia‒reperfusion injury (CIRI). Neuroinflammation is crucial post-CIRI, but how 20(R)-Rg3 affects ischemia‒reperfusion-induced neuroinflammation is unclear. To study 20(R)-Rg3's effects on neuroinflammation and neuronal preservation in stroke models and explore toll-like receptor 4/myeloid differentiation factor-88/nuclear factor kappa B (TLR4/MyD88/NF-κB) pathway mechanisms. Middle cerebral artery occlusion/reperfusion (MCAO/R) rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuron injury were treated with 20(R)-Rg3; survival, cytokine levels, and pathway protein expressions were assessed; efficacy with the TLR4 inhibitor was also evaluated. In MCAO/R rats, 20(R)-Rg3 administration reduced inflammatory damage to brain tissue. 20(R)-Rg3 dose-dependently improved neuronal survival and attenuated inflammatory processes in OGD/R neurons. The expression levels of TLR4, MyD88, and phosphorylated NF-κB p65 are upregulated in MCAO/R rat brain tissue and OGD/R-induced neurons, and these effects are reversed by 20(R)-Rg3 treatment. In addition, 20(R)-Rg3 enhanced the anti-inflammatory efficacy of the TLR4 inhibitor TAK-242 and reduced inflammation in OGD/R-exposed neurons. 20(R)-Rg3 attenuates neuroinflammation and protects neurons via inhibiting TLR4/MyD88/NF-κB pathway in vitro and in vivo, suggesting it is a potential therapeutic for ischemic stroke.

Abstract

Numerous people experiencing acute myocardial infarction are also experiencing myocardial ischemia-reperfusion injury (MIRI). Pyroptosis is a core mechanism in MIRI. Tongxinluo (TXL) has a significant protective effect on endothelial cell function. This study utilized network pharmacology to investigate how TXL improves ischemia/reperfusion injury through targeting dysfunction of endothelial cells. Network pharmacology analysis identified 40 key targets through which TXL improves I/R by regulating endothelial dysfunction. We administered TXL (1.5 g/kg/d, oral gavage) to C57BL/6 mice for 7 days before inducing I/R injury, and used 400 μg/ml TXL for in vitro H/R injury in HUVECs. We extensively investigated the effects of TXL on pyroptosis in heart tissue and explored the underlying mechanism through biochemical assays, histopathology, and Western blot analysis. Network pharmacology analysis revealed that TXL targets primarily act on pyroptosis and inflammatory pathways. TXL pretreatment significantly improved cardiac function with increased EF% and decreased LVESV and LVEDV compared to the model group. Myocardial enzymes (CK, CKMB, LDH, cTnI) were markedly reduced by TXL pretreatment. TXL significantly decreased IL-18 and IL-1β levels in serum and reduced neutrophil infiltration in the ischemic area. TXL administration notably downregulated the expression of pyroptosis-related factors (NF-κB, NLRP3, cleaved-Caspase1, GSDMD) in both MIRI mouse model and H/R-treated HUVECs. Molecular docking showed that ginsenoside Rg3, a key TXL component, can directly interact with NLRP3 and GSDMD. TXL has a significant protective effect on endothelial cell function during I/R injury through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD signaling pathway, preserving microcirculation barrier integrity.

Abstract

Osimertinib, established as the frontline treatment for advanced non-small cell lung cancer (NSCLC), can effectively prolong progression-free survival. However, it faces the problem of reduced treatment persistence due to acquired drug resistance. Meanwhile, tumor hypoxia is also a key driver of drug resistance. This study proposes a hybrid protein oxygen nanocarrier combined with osimertinib and ginsenoside Rg3 to address the drug resistance issue of NSCLC through multiple mechanisms.

Abstract

Oligoasthenozoospermia (OA) is the main factor leading to male infertility. According to traditional Chinese medicine, ginseng and its derivatives can improve male sperm quality by nourishing the kidneys and replenishing qi. Ginsenosides have been recognized as the principal pharmacologically active constituents of Panax ginseng, and are generally categorized into highly polar and rare ginsenosides. Rare ginsenosides can be generated through thermal transformation of the highly polar forms, yielding structurally related compounds collectively referred to as heat-transformed saponins (HTS). HTS comprising Rg6, F4, Rg3, Rk1, and Rg5-demonstrate substantial bioactivity at a dose of 50 mg/kg without observable toxicity. However, their effects on oligoasthenospermia (OA) and the associated molecular mechanisms remain poorly defined.

Abstract

This study investigates how mP6/Rg3 micelles modulate ABCB1 expression to induce ferroptosis in oral cancer stem cells (CSC) and enhance oral cancer outcomes.

Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss owing to choroidal neovascularization (CNV) and retinal vascular abnormalities. Current anti-VEGF therapies often exhibit limited efficacy in approximately 50% of patients owing to the complex pathological microenvironment, including elevated reactive oxygen species (ROS) levels. This study aimed to develop a multitargeted therapeutic strategy for AMD by leveraging the antioxidant and anti-angiogenic properties of ginsenoside Rg3 (Rg3).

Abstract

The utilization of organophosphorus pesticides (OPs) has been demonstrated to exert a substantial positive influence on crop yield enhancement. However, due to the multitude of exposure routes and the persistence of these compounds, humans are routinely exposed to pesticides on a daily basis through dermal contact, inhalation, and ingestion. This has serious consequences for the health of living organisms. The existing research on the effects of organophosphorus pesticides on organisms primarily encompasses the impact on vital organs such as the liver, kidneys, heart, various blood parameters, and potential neurotoxicity, teratogenicity, carcinogenicity, and mutagenic effects. However, there is a paucity of research addressing the alleviation of brain tissue damage in OP pesticide poisoning through the microbial-intestinal-brain axis.

Abstract

The clinical progress of tumor nucleotide vaccines is limited due to insufficient recognition and killing of tumor cells with low antigen expression by cytotoxic T lymphocytes (CTL). Here, natural cholesterol analogs are screened to assemble self-adjuvant lipid nanoparticles (LNPs) for antigens tagging tumor cells and dendritic cells (DC) activation. First, a library of ginsenosides are collected, and then screened according to their anti-tumor immunity. Then, ginsenoside-Rg3 based-LNPs loaded with antigens (Rg3-LNPs) are identified as the optimal formulation by investigating the physicochemical and biological properties. Finally, Rg3-LNPs and granulocyte-macrophage colony-stimulating factor (GM-CSF) are co-loaded into a macroporous hydrogel for long-term immune response. Rg3-LNPs could accumulate into both tumors and LNs. Rg3-LNPs targeted tumor cells with high glucose transporter-1 expression via the targeting ligand Rg3, and anchored antigens on the tumor cell surface, thus promoting the recognition of CTL to tumor cells; Rg3-LNPs can accumulate into the LNs to promote DC activation and antigen presentation, thus stimulating CTL activation. Besides, Rg3, as an adjuvant, cooperated with GM-CSF to remodel the tumor microenvironment, thus promoting the killing of CTL to tumor cells. Collectively, this work highlights the importance of tagging antigens to tumor cells in tumor vaccine and has great clinical value for immune-escaping tumors.

Abstract

Cytokine synergy induced by the activation of multiple Toll-like receptors (TLRs) may result in uncontrollable life-threatening inflammation, the so-called cytokine storm. Owing to the complexity of the crosstalk for individual TLR signaling pathways, analyses of transcriptional changes in addition to differentially expression genes (DEGs) are needed. In the present study, we aimed to create algorithms to obtain a profile of synergistic cytokine production and to evaluate the anti-cytokine synergistic activity of ginsenoside Rg3. RAW264.7 macrophages were activated by TLR2/3 dual ligands; Rg3 was used as an intervention. After interleukin (IL)-6 secretion was detected as a preliminary readout for cytokine synergy, RNA sequencing-based bioinformatic analysis was performed, followed by qPCR and western blotting verification. Specifically, nonadditive transcriptional responses (DIFs) were applied as a measure of synergistic genes, and an anti-synergy score was created as a measure of the antagonistic effect of Rg3. A mouse model of TLR2/3 costimulation was subsequently established to evaluate the anti-cytokine synergistic effect of Rg3 in vivo. The results show that Rg3 alleviates synergistic cytokine production both in vitro and in vivo. Nuclear factor kappa B (NF-κB) and interferon regulatory factor 3 (IRF3) are novel targets of Rg3 related to its anti-cytokine synergistic effects. Our strategy of nonadditive transcriptional change analysis will be helpful for performing high-throughput screening for drugs with anti-cytokine synergy activities.

Abstract

To investigate the protective effect of ginsenoside Rg3 on lipopolysaccharide-induced galial-neuronal interaction injury model.