Ginsenoside Research Articles

Ginsenoside Rg5 nanomedicine composited hydrogel with metabolic regulation and immunomodulation properties for tunneling diabetic wounds therapy

Diabetic wounds behaved delayed healing mainly due to impaired metabolism, dysregulated inflammation, and unique tunneling morphology. Herein, a customized nanocomposite hydrogel for diabetic wounds therapy was designed, demonstrating injectability, shape-adaptivity, and mechanical durability that adapt to the tunneling wound morphology. The hydrogel performed controlled drug release for metabolic regulation and immunomodulatory under topical administration. This hydrogel consists of oxidized anredera cordifolia polysaccharide (OACS), adipic dihydrazide grafted collagen fiber (CF-ADH), and ginsenoside Rg5 loaded polyethyleneimine grafted F127 nanoparticles (F127-PEI@Rg5 NPs). Triple dynamic bonds contributed to the fast cross-linking reconstitution during shape-remodeling, including the acylhydrazone and amine bonds formed from CF-ADH and F127-PEI@Rg5 NPs with OACS, and the electrostatic interactions between the inherent carboxyl groups and protonated amino groups in the materials. The nanolization and two-step loading of Rg5 leaded to improved bioavailability and prolonged drug action time. As a result, this hydrogel exhibited expected regulation for key enzymes in glycolysis, and relieved insulin resistance, thus providing an adequate energy supply for tissue remolding. Additionally, it increased macrophages number and promoted macrophages polarization, thus breaking the prolonged inflammation of diabetic wounds. In vivo experiments showed that the healing period was shortened by 34%, suggesting a promising dressing for diabetic wounds.

Ginsenoside Rg5 alleviates Ang II–induced cardiac inflammation and remodeling by inhibiting the JNK/AP-1 pathway

Increased level of Angiotensin II (Ang II) contributes to hypertensive heart failure via -hemodynamic and non-hemodynamic actions. Ginsenoside Rg5 (Rg5) occurs naturally in ginseng, which has shown various benefits for cardiovascular diseases. This study evaluated Rg5′s effects on Ang II-caused cardiac remodeling and heart failure. C57BL/6 mice developed hypertensive cardiac failure after four weeks of Ang II infusion. The mice were administered Rg5 via oral gavage for the last two weeks to investigate the potential mechanism of Rg5. RNA sequencing of heart tissues was performed for mechanistic studies. It was discovered that Rg5 inhibited cardiac inflammation, myocardial fibrosis, and hypertrophy, and prevented cardiac malfunction in mice challenged with Ang II, without altering blood pressure. RNA sequencing showed that Rg5′s cardioprotective effect involves the JNK/AP-1 signaling pathway. Rg5 diminished inflammation in mice hearts and cultured cardiomyocytes by blocking Ang II-activated JNK/AP-1 pathway. In the absence of JNK or AP-1 in cardiomyocytes, the anti-inflammatory effects of Rg5 were nullified. The study found that Rg5 preserved the hearts of Ang II-induced mice by reducing JNK-mediated inflammatory responses, suggesting that Rg5 is an effective therapy for hypertensive heart failure.

Does Panax notoginseng (Sanqi) inhibit H22 tumor growth via improving the host’s cellular immunity?

Ginsenoside Rg3 has many functions, including anti-tumor activity, antioxidant activity, and immune system modulatory activity. Interestingly, There are two stereoisomers exist in Rg3, 20(S)-ginsenoside Rg3 [20(S)-Rg3] and 20(R)-ginsenoside Rg3 [20(R)-Rg3], respectively. These two isomers have different pharmacological effects due to their stereospecificity. In this study, we compared their effect of stimulating the ConA to induce lymphocyte proliferation and increase the cytokines IL-2 and IFN-γ levels in mice and improve the cellular immunity of the host. The study predicted that ginsenoside (Rg3) could increase Th1-type cytokines interleukin-2 and interferon-γ and stimulate ConA-induced lymphocyte proliferation in mice, thereby improving cellular immunity in H22 mice. The effects of the Rg3 R-form were significantly greater than Rg3 S-form.

Does Panax notoginseng (Sanqi) inhibit H22 tumor growth via improving the host’s cellular immunity?

Ginsenoside Rg3 has many functions, including anti-tumor activity, antioxidant activity, and immune system modulatory activity. Interestingly, There are two stereoisomers exist in Rg3, 20(S)-ginsenoside Rg3 [20(S)-Rg3] and 20(R)-ginsenoside Rg3 [20(R)-Rg3], respectively. These two isomers have different pharmacological effects due to their stereospecificity. In this study, we compared their effect of stimulating the ConA to induce lymphocyte proliferation and increase the cytokines IL-2 and IFN-γ levels in mice and improve the cellular immunity of the host. The study predicted that ginsenoside (Rg3) could increase Th1-type cytokines interleukin-2 and interferon-γ and stimulate ConA-induced lymphocyte proliferation in mice, thereby improving cellular immunity in H22 mice. The effects of the Rg3 R-form were significantly greater than Rg3 S-form.

Ginsenoside F1 preparation from ginsenosides Re and Rg1 mixture of ginseng leaves by a 6-O-glycoside-ginsenosidase from Aspergillus sp. g383 strain

Ginsenoside F1 was prepared from ginseng-leaf ginsenosides Re and Rg1 using a 6-O-glycoside-ginsenosidase from Aspergillus sp.g383 strain. From 500 g ginseng leaves, a 25.1 g mixture of 54.2% Re and 45.8% Rg1 were extracted. The enzyme molecular weight was 54.5 kDa; the optimal temperature was 45 °C; and optimal pH, 5.0; Re's V max and Km were 11.6 mM/h and 10.9 mM, respectively; Rg1's were 7.69 mM and 0.917 mM/h. The 6-O-glycoside-ginsenosidase conversion rates of Re and Rg1 into F1 were faster than those of the other enzymes. In the preparation of ginsenoside F1, 2.5% mixture of Re and Rg1 from ginseng leaf-part was reacted at 45 °C for 36 h by crude enzyme at a low cost. From a 25 g mixture of Re and Rg1, 13.8 g ginsenoside F1 was obtained. The purity of F1 was 95%, and the molar yield from Re and Rg1 was 75%. F1 weight-yield from ginseng-leaves was 2.76%. Furthermore, ginseng-leaves were used to obtain extra ginsrnoside Re and ginseng-leaf PPD-ginsenosides. Thus, the ginsenosides F1, which could be used safely in ginseng food, cosmetics or drugs, were successfully produced by a non-GMO crude-enzyme from a Re and Rg1 mixture of ginseng-leaves.

Inhibition of Salvianolic Acid B and Ginsenoside Rg1 on Hemorrhagic Transformation after Stroke

Abstract Objective Application of recanalization on stroke patients is not only limited with time window, but also accompanied with the risk of hemorrhagic transformation. In present study, the effects of salvianolic acid B and ginsenoside Rg1 combination (SalB/Rg1) on time window and hemorrhagic transformation against ischemic stroke was evaluated on middle cerebral artery occlusion (MCAO) mice. Methods The protection and time window of SalB/Rg1 were estimated through infarct volume, neurobehavioral deficits, and histomorphological examination. The prohibition of SalB/Rg1 against hemorrhagic transformation was detected on MCAO mice stimulated with dextrose and reperfusion. Hemorrhagic transformation was assessed by the Heidelberg Bleeding Classification. The mechanism of SalB/Rg1 against hemorrhagic transformation was identified by immunofluorescence staining and in situ gelatin zymography. Results First, SalB/Rg1 significantly reduced infarct volume and improved neurobehavior in a dose-dependent manner. Then, the protective time window up to 9 hours was detected for SalB/Rg1 against stroke. Both the dose-dependent efficiency and longtime protection of SalB/Rg1 were further identified based on cytoarchitecture through histopathological stain. Second, SalB/Rg1 downregulated hemorrhagic score, infarct volume, and abnormal neurobehavior. Finally, the inhibition of SalB/Rg1 against hemorrhagic transformation was found to accompany with its protection on the integrity of neurovascular unit. Around the edge area of infarction, SalB/Rg1 attenuated the astrocyte activation, maintained the abundance of junction protein (claudin-5) between endothelial cells, considerably decreased matrix metallopeptidase 9 activity through in situ gelatin zymography. Conclusion SalB/Rg1 is a promising strategy for further development against stroke, especially against hemorrhagic transformation.

20(R)-ginsenoside Rg3-loaded polyurethane/marine polysaccharide based nanofiber dressings improved burn wound healing potentials

The management of deep burn injuries is extremely challenging, ascribed to their delayed wound healing rate, susceptibility for bacterial infections, pain, and increased risk of hypertrophic scarring. In our current investigation, a series of composite nanofiber dressings (NFDs) based on polyurethane (PU) and marine polysaccharides (i.e., hydroxypropyl trimethyl ammonium chloride chitosan, HACC and sodium alginate, SA) were accomplished by electrospinning and freeze-drying protocols. The 20(R)-ginsenoside Rg3 (Rg3) was further loaded into these NFDs to inhibit the formation of excessive wound scars. The PU/HACC/SA/Rg3 dressings showed a sandwich-like structure. The Rg3 was encapsulated in the middle layers of these NFDs and slowly released over 30 days. The PU/HACC/SA and PU/HACC/SA/Rg3 composite dressings demonstrated superior wound healing potentials over other NFDs. These dressings also displayed favorable cytocompatibility with keratinocytes and fibroblasts and could dramatically accelerate epidermal wound closure rate following 21 days of the treatment of a deep burn wound animal model. Interestingly, the PU/HACC/SA/Rg3 obviously reduced the excessive scar formation, with a collagen type I/III ratio closer to the normal skin. Overall, this study represented PU/HACC/SA/Rg3 as a promising multifunctional wound dressing, which promoted the regeneration of burn skins and attenuated scar formation.

Ginsenoside Rg5 promotes muscle regeneration via p38MAPK and Akt/mTOR signaling

BackgroundSkeletal muscles play a key role in physical activity and energy metabolism. The loss of skeletal muscle mass can cause problems related to metabolism and physical activity. Studies are being conducted to prevent such diseases by increasing the mass and regeneration capacity of muscles. Ginsenoside Rg5 has been reported to exhibit a broad range of pharmacological activities. However, studies on the effects of Rg5 on muscle differentiation and growth are scarce. MethodsTo investigate the effects of Rg5 on myogenesis, C2C12 myoblasts were induced to differentiate with Rg5, followed by immunoblotting, immunostaining, and qRT-PCR for myogenic markers and promyogenic signaling (p38MAPK). Immunoprecipitation confirmed that Rg5 increased the interaction between MyoD and E2A via p38MAPK. To investigate the effects of Rg5 on prevention of muscle mass loss, C2C12 myotubes were treated with dexamethasone to induce muscle atrophy. Immunoblotting, immunostaining, and qRT-PCR were performed for myogenic markers, Akt/mTOR signaling for protein synthesis, and atrophy-related genes (Atrogin-1 and MuRF1). ResultsRg5 promoted C2C12 myoblast differentiation through phosphorylation of p38MAPK and MyoD/E2A heterodimerization. Furthermore, Rg5 stimulated C2C12 myotube hypertrophy via phosphorylation of Akt/mTOR. Phosphorylation of Akt induces FoxO3a phosphorylation, which reduces the expression of Atrogin-1 and MuRF1. ConclusionThis study provides an understanding of how Rg5 promotes myogenesis and hypertrophy and prevents dexamethasone-induced muscle atrophy. The study is the first, to the best of our knowledge, to show that Rg5 promotes muscle regeneration and to suggest that Rg5 can be used for therapeutic intervention of muscle weakness and atrophy, including cancer cachexia.

Ginsenoside Rg1 Inhibits Microglia Pyroptosis Induced by Lipopolysaccharide Through Regulating STAT3 Signaling [Retraction

[This retracts the article DOI: 10.2147/JIR.S326888.].

Ginsenoside Rg3 Protects Mouse Islet β-Cells Injured by High Glucose.

To investigate the effect of Ginsenoside Rg3 on insulin secretion in mouse MIN6 cells and the possible mechanism. The cultured mouse pancreatic islet MIN6 cells were divided into control group (NC), Rg3 group (Rg3, 50μg/L), high glucose group (HG, 33mmol/L), High glucose and Rg3 group (HG + Rg3), after 48h of continuous culture, CCK-8 was used to detect cell viability; mouse insulin enzyme-linked immunoassay kit to detect insulin release; ATP content detection kit to detect ATP; DCFH-DA to detect intracellular reactive oxygen species (ROS) levels; total glutathione (T-GSH)/oxidized glutathione (GSSG) assay kit to detect the ratio of GSH/GSSG; Using the mitochondrial membrane channel pore (MPTP) fluorescence detection kit in MIN6 cells and collect the intensity of green fluorescence; Western blot to detect the expression of antioxidant proteins Glutathione reductase (GR). The results showed that compared with the NC group, the cell viability of the HG was decreased (P < 0.05), insulin release decreased (P < 0.001), ATP content decreased significantly (P < 0.001), and ROS content increased (P < 0.01), the GSH/GSSH ratio of pancreatic islet cells decreased (P < 0.05),the green fluorescence intensity decreased (P < 0.001), indicating that the permeability of mitochondria increased and the content of antioxidant protein in the cells decreased (P < 0.05). Compared with the HG group, the cell viability of the HG + Rg3 group was significantly increased (P < 0.05), the amount of insulin released was significantly increased (P < 0.001), ATP content was significantly increased (P < 0.01), and the ROS content was significantly decreased (P < 0.01), GSH/GSSH ratio increased significantly (P < 0.05), the green fluorescence intensity was increased (P < 0.001), indicating that the permeability of mitochondria decreased and antioxidant protein GR content increased significantly (P < 0.05). Taken together, our results suggest that Rg3 has an antioxidant protective effect on mouse pancreatic islet cells damaged by high glucose and maintains pancreatic islet cell function and promotes insulin secretion.

Uncovering the Q-marker and potential mechanisms of Qishan Formula for lung cancer based on multi-technology

Qishan Formula (QSF) is mainly used to treat lung cancer and its side effects of radiotherapy and chemotherapy. Although the clinical efficacy of QSF has been recognized, its mechanism of action and active ingredients are still unclear. This study aims to explore the potential Q-Marker of QSF and reveal its anti-lung cancer mechanism. Firstly, the fingerprints of 10 batches of QSF were established, and the potential Q-markers were screened by chemometrics, then network pharmacology and molecular docking methods were used to explore its anti-lung cancer mechanism. Finally, the potential Q-markers were quantitatively by UPLC-QDA. The results showed that 48 common peaks were identified by the established fingerprint, and calycosin, ginsenoside Rg1, atractylenolide III, atractylenolide I and ginsenoside Rb1 were screened as potential Q-Markers of QSF by chemometrics. Network pharmacology and molecular docking found that the potential Q-Markers may regulate various signaling pathways through targets such as FOS, IL6, EGFR, ESR1, MAPK1, and MAPK3, and play a therapeutic role in lung cancer. Besides, the established UPLC-QDA can also perform quality control for Q-Markers of QSF. This study can provide academic ideas and lay a foundation for the comprehensive quality control and mechanism research of QSF and other compound preparation.

Ginsenoside Rg1 regulates autophagy and endoplasmic reticulum stress via the AMPK/mTOR and PERK/ATF4/CHOP pathways to alleviate alcohol‑induced myocardial injury.

It has been reported that ginsenoside Rg1 (G‑Rg1) can alleviate alcoholic liver injury, cardiac hypertrophy and myocardial ischemia, as well as reperfusion injury. Therefore, the present study aimed to investigate the role of G‑Rg1 in alcohol‑induced myocardial injury, as well as to elucidate its underlying mechanisms of action. For this purpose, H9c2 cells were stimulated with ethanol. Subsequently, H9c2 cell viability and apoptosis were determined using a Cell Counting Kit‑8 assay and flow cytometric analysis, respectively. The levels of lactate dehydrogenase and caspase‑3 in the H9c2 cell culture supernatant were detected using corresponding assay kits. In addition, the expression of green fluorescent protein (GFP)‑light chain 3 (LC3) and that of C/EBP homologous protein (CHOP) were evaluated using GFP‑LC3 assay and immunofluorescence staining, respectively. The expression levels of apoptosis‑, autophagy‑, endoplasmic reticulum stress (ERS)‑ and adenosine 5'‑monophosphate‑activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway‑related proteins were detected using western blot analysis. The results revealed that treatment with G‑Rg1 enhanced the viability and suppressed the apoptosis of ethanol‑stimulated H9c2 cells. G‑Rg1 also attenuated autophagy and ERS in ethanol‑stimulated H9c2 cells. In addition, the levels of phosphorylated (p)‑protein kinase R (PKR)‑like ER kinase (PERK), p‑eukaryotic translation initiation factor 2a, activating transcription factor 4 (ATF4), CHOP, caspase‑12 and p‑AMPK were downregulated, while the p‑mTOR level was upregulated in ethanol‑stimulated H9c2 cells treated with G‑Rg1. Furthermore, the co‑treatment of G‑Rg1‑treated ethanol‑stimulated H9c2 cells with AICAR, an AMPK agonist, or CCT020312, a PERK agonist, inhibited cell viability and promoted cell apoptosis, autophagy and ERS. Overall, the results of the present study suggest that G‑Rg1 suppresses autophagy and ERS via inhibiting the AMPK/mTOR and PERK/ATF4/CHOP pathways to alleviate ethanol‑induced H9c2 cell injury.

Ginsenoside Rg1 ameliorates hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and inflammation by regulating CCN1

Pulmonary arterial hypertension (PAH) is a chronic obstructive disease characterized by vascular remodeling. Studies have confirmed that ginsenoside Rg1 can improve pulmonary hypertension to a certain extent, but the potential mechanism by which it improves hypoxia-induced PAH remains unclear. The aim of this study was to investigate the therapeutic effect of ginsenoside Rg1 on hypoxia-induced PAH. The results showed that hypoxia promoted inflammation, EndMT, and vascular remodeling, which were accompanied by decreased CCN1 levels and increased p-NFκB p65, TGF-β1, and p-Smad 2/3 levels. Treatment with ginsenoside Rg1, recombinant CCN1, BAY-11-7082, and SB-431542 could prevent hypoxia-induced vascular remodeling, reduce the expression of the hypoxia-induced inflammatory cytokines TNF-α and IL-1β, inhibit the expression of the mesenchymal markers α-SMA and Vimentin and restore the expression of the endothelial markers CD31 and VE-cadherin to improve hypoxia-induced EndMT, which may be associated with the upregulation of CCN1 protein expression and downregulation of p-NFκB p65, TGF-β1, and p-Smad 2/3 in rats and cells. siRNA CCN1 transfection increased the expression of p-NFκB p65, TGF-β1, and p-Smad 2/3 and accelerated the occurrence and development of inflammation and EndMT after hypoxia. In summary, our study indicated that hypoxia-induced EndMT and inflammation play a role in hypoxic pulmonary hypertension (HPH). Ginsenoside Rg1 treatment could reverse hypoxia-induced EndMT and inflammation by regulating CCN1 and has potential value in the prevention and treatment of HPH.

Xiaoxuming decoction cutting formula reduces LPS-stimulated inflammation in BV-2 cells by regulating miR-9-5p in microglia exosomes.

The Background: Stroke is one of the leading causes of morbidity and mortality, and the inflammatory mechanism plays a crucial role in stroke-related brain injury and post-ischemic tissue damage. Xiaoxuming decoction (XXMD) is the first prescription for the treatment of "zhongfeng" (a broad concept referring to stroke) in the Tang and Song Dynasties of China and has a significant position in the history of stroke treatment. Through the study of ancient medical records and modern clinical evidence, it is evident that XXMD has significant efficacy in the treatment of stroke and its sequelae, and its pharmacological mechanism may be related to post-stroke inflammation. However, XXMD contains 12 medicinal herbs with complex composition, and therefore, a simplified version of XXMD, called Xiaoxuming decoction cutting (XXMD-C), was derived based on the anti-inflammatory effects of the individual herbs. Therefore, it is necessary to explore and confirm the anti-inflammatory mechanism of XXMD-C. Aim of the study: Based on the previous experiments of our research group, it was found that both XXMD and XXMD-C have anti-inflammatory effects on LPS-induced microglia, and XXMD-C has a better anti-inflammatory effect. Since miRNAs in exosomes also participate in the occurrence and development of cardiovascular diseases, and traditional Chinese medicine can regulate exosomal miRNAs through intervention, this study aims to explore the anti-inflammatory mechanism of XXMD-C in the treatment of post-stroke inflammation through transcriptome sequencing, providing a basis for the application of XXMD-C. Materials and methods: XXMD-C was extracted using water and filtered through a 0.22μm membrane filter. The main chemical components of the medicinal herbs in XXMD-C were rapidly qualitatively analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Cell viability was determined using the CCK-8 assay, and an LPS-induced BV-2 cell inflammation model was established. The expression of inflammatory cytokines was detected using ELISA and Western blot (WB). Extracellular vesicles were extracted using ultracentrifugation, and identified using transmission electron microscopy (TEM), nanoparticle tracking analysis, and WB. Differential miRNAs were screened using smallRNA-seq sequencing, and validated using RT-PCR and Western blot. Results: The UPLC-Q-TOF-MS analysis revealed that representative components including ephedrine, pseudoephedrine, cinnamaldehyde, baicalin, baicalein, wogonin, and ginsenoside Rg1 were detected in XXMD-C. The results of ELISA and WB assays showed that XXMD-C had a therapeutic effect on LPS-induced inflammation in BV-2 cells. TEM, nanoparticle tracking analysis, and WB results demonstrated the successful extraction of extracellular vesicles using high-speed centrifugation. Differential miRNA analysis by smallRNA-seq identified miR-9-5p, which was validated by RT-PCR and WB. Inhibition of miR-9-5p was found to downregulate the expression of inflammatory factors including IL-1β, IL-6, iNOS, and TNF-α. Conclusion: The study found that XXMD-C has anti-neuroinflammatory effects. Through smallRNA-seq sequencing of extracellular vesicles, miR-9-5p was identified as a key miRNA in the mechanism of XXMD-C for treating neuroinflammation, and its in vivo anti-inflammatory mechanism deserves further investigation.

The role of calcium-sensing receptor in ginsenoside Rg1 promoting reendothelialization to inhibit intimal hyperplasia after balloon injury

Calcium-sensing receptor (CaSR) is a G protein-coupled receptor, widely distributed in various tissues, including vascular endothelial cells and smooth muscle cells, which plays an important role in the migration and homing of stem/progenitor cells and the proliferation of tissue cells. Restenosis after Percutaneous coronary intervention (PCI) seriously affects its prognosis and application. Our previous research has found that ginsenoside Rg1 (GS-Rg1) can inhibit the occurrence of restenosis after balloon injury of the common carotid artery in rats, but the mechanism is still unclear. In this study, it was found that GS-Rg1 (4, 8, 16 mg/kg) inhibited vascular restenosis caused by balloon injury, and mobilize endothelial progenitor cells (EPCs) to promote reendothelialization and inhibit intimal hyperplasia, which significantly reduced after administration of CaSR antagonist NPS 2143. Interestingly, CaSR and its downstream JNK, P38 were highly expressed in the proliferative intima and participated in the abnormal proliferation of vascular smooth muscle cells mediated by smooth muscle progenitor cells (SMPCs). GS-Rg1 inhibited intimal hyperplasia, while it decreased the expression of CaSR, JNK, and P38. This might relate to the distribution of CaSR and the facilitation of GS-Rg1 on the vascular endothelial repair. It is concluded that CaSR plays a key role in GS-Rg1 promoting reendothelialization to inhibit intimal hyperplasia after balloon Injury.

Kaixin Jieyu Granule attenuates neuroinflammation-induced depressive-like behavior through TLR4/PI3K/AKT/FOXO1 pathway: a study of network pharmacology and experimental validation

BackgroundKaixin Jieyu Granule (KJG), an improved formula of Kai-xin-san and Si-ni-san, is a highly effective formula with demonstrated efficacy in preventing depression in previous studies. However, the underlying molecular mechanisms of KJG’s antidepressant effects on inflammatory molecules remain unclear. This study aimed to explore the therapeutic effects of KJG on depression using network pharmacology and experimental validation.MethodsWe employed a multi-faceted approach, combining high-performance liquid chromatography (HPLC), network pharmacology, and molecular docking, to unravel the underlying mechanisms of KJG’s anti-depressant effects. To confirm our findings, we conducted at least two independent in vivo experiments on mice, utilizing both the chronic unpredictable mild stress (CUMS)-induced and lipopolysaccharide (LPS)-induced models. Furthermore, the results of in vivo experiments were verified by in vitro assays. Behavioral tests were utilized to evaluate depression-like behaviors, while Nissl staining was used to assess morphological changes in the hippocampus. Pro-inflammatory cytokines and pathway-related protein expressions were determined using a combination of immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), and Western Blotting (WB).ResultsOur network-based approaches indicated that ginsenoside Rg1 (GRg1) and saikosaponin d (Ssd) are the major constituents of KJG that exert an anti-depressant effect by regulating TLR4, PI3K, AKT1, and FOXO1 targets through the toll-like receptor, PI3K/AKT, and FoxO pathways. In vivo, KJG can attenuate depression-like behaviors, protect hippocampal neuronal cells, and reduce the production of pro-inflammatory mediators (TNF-α, IL-6, and IL-1β) by repressing TLR4 expression, which was regulated by the inhibition of FOXO1 through nuclear exportation. Furthermore, KJG increases the expression levels of PI3K, AKT, p-PI3K, p-AKT, and p-PTEN. Our in vitro assays are consistent with our in vivo studies. On the other hand, the above effects can be reversed by applying TAK242 and LY294002.ConclusionOur findings suggest that KJG can exert anti-depressant effects by regulating neuroinflammation through the PI3K/AKT/FOXO1 pathway by suppressing TLR4 activation. The study’s findings reveal novel mechanisms underlying the anti-depressant effects of KJG, presenting promising avenues for the development of targeted therapeutic approaches for depression.

Amino acid modified OCMC-g-Suc-β-CD nanohydrogels carrying lapatinib and ginsenoside Rg1 exhibit high anticancer activity in a zebrafish model.

Nanohydrogels show great potential as efficient drug carriers due to their biocompatibility, low toxicity, and high water absorbability. In this paper, we prepared two O-carboxymethylated chitosan (OCMC)-based polymers functionalized with β-cyclodextrin (β-CD) and amino acid. The structures of the polymers were characterized by Fourier Transform Infrared (FTIR) Spectroscopy. Morphological study was carried out on a Transmission Electron Microscope (TEM), and the results indicated that the two polymers had irregular spheroidal structure with some pores distributed on their surface. The average particle diameter was below 500nm, and the zeta potential was above +30mV. The two polymers were further used for preparing nanohydrogels loaded with anticancer drugs lapatinib and ginsenoside Rg1, and the resulting nanohydrogels showed high drug loading efficiency and pH-sensitive (pH = 4.5) drug release behavior. In vitro cytotoxicity investigation revealed that the nanohydrogels exhibited high cytotoxicity against lung cancer (A549) cells. In vivo anticancer investigation was performed in a transgenic Tg(fabp10:rtTA2s-M2; TRE2:EGFP-kras V12) zebrafish model. The results showed that the synthesized nanohydrogels significantly inhibited the expression of EGFP-kras v12 oncogene in zebrafish liver, and the L-arginine modified OCMC-g-Suc-β-CD nanohydrogels loading lapatinib and ginsenoside Rg1 showed the best results.

The effect of ginsenosides on liver injury in preclinical studies: a systematic review and meta-analysis.

Background: Liver injury is a severe liver lesion caused by various etiologies and is one of the main areas of medical research. Panax ginseng C.A. Meyer has traditionally been used as medicine to treat diseases and regulate body functions. Ginsenosides are the main active components of ginseng, and their effects on liver injury have been extensively reported. Methods: Preclinical studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan Fang Data Knowledge Service Platforms. The Stata 17.0 was used to perform the meta-analysis, meta-regression, and subgroup analysis. Results: This meta-analysis included ginsenosides Rb1, Rg1, Rg3, and compound K (CK), in 43 articles. The overall results showed that multiple ginsenosides significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), affected oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), and catalase (CAT), and reduced levels of inflammatory factor, such as factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6). Additionally, there was a large amount of heterogeneity in the meta-analysis results. Our predefined subgroup analysis shows that the animal species, the type of liver injury model, the duration of treatment, and the administration route may be the sources of some of the heterogeneity. Conclusion: In a word, ginsenosides have good efficacy against liver injury, and their potential mechanisms of action target antioxidant, anti-inflammatory and apoptotic-related pathways. However, the overall methodological quality of our current included studies was low, and more high-quality studies are needed to confirm their effects and mechanisms further.

Structural-Activity Relationship of Rare Ginsenosides from Red Ginseng in the Treatment of Alzheimer's Disease.

Rare ginsenosides are the major components of red ginseng. However, there has been little research into the relationship between the structure of ginsenosides and their anti-inflammatory activity. In this work, BV-2 cells induced by lipopolysaccharide (LPS) or nigericin, the anti-inflammatory activity of eight rare ginsenosides, and the target proteins expression of AD were compared. In addition, the Morris water maze test, HE staining, thioflavins staining, and urine metabonomics were used to evaluate the effect of Rh4 on AD mice. Our results showed that their configuration influences the anti-inflammatory activity of ginsenosides. Ginsenosides Rk1, Rg5, Rk3, and Rh4 have significant anti-inflammatory activity compared to ginsenosides S-Rh1, R-Rh1, S-Rg3, and R-Rg3. Ginsenosides S-Rh1 and S-Rg3 have more pronounced anti-inflammatory activity than ginsenosides R-Rh1 and R-Rg3, respectively. Furthermore, the two pairs of stereoisomeric ginsenosides can significantly reduce the level of NLRP3, caspase-1, and ASC in BV-2 cells. Interestingly, Rh4 can improve the learning ability of AD mice, improve cognitive impairment, reduce hippocampal neuronal apoptosis and Aβ deposition, and regulate AD-related pathways such as the tricarboxylic acid cycle and the sphingolipid metabolism. Our findings conclude that rare ginsenosides with a double bond have more anti-inflammatory activity than those without, and 20(S)-ginsenosides have more excellent anti-inflammatory activity than 20(R)-ginsenosides.

Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury through inhibiting the inflammatory activation of microglia.

It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.