Ginsenoside Rh2 Research Articles

Ginsenoside Rh2 attenuates the progression of non-small cell lung cancer by sponging miR-28-5p/STK4 axis and inactivating Wnt/β-catenin signaling.

Ginsenoside Rh2 (G-Rh2) exerts anti-tumor activity in non-small cell lung cancer (NSCLC). microRNAs (miRNAs, miRs) play pivotal roles in NSCLC. We aimed to investigate whether G-Rh2 inhibited NSCLC progression by targeting miRNA. Cell viability, apoptosis and cycle were determined by Cell Counting Kit-8, 6-diamidino-2-phenylindole (DAPI) staining and flow cytometry. The potential target miRNAs of G-Rh2 were screened by real-time quantitative polymerase chain reaction (RT-qPCR). The difference in miR-28-5p expression between lung adenocarcinoma (LUAD) tissues and normal tissues or lung squamous cell carcinoma (LUSC) tissues and normal tissues was retrieved from TCGA-LUAD and TCGA-LUSC, respectively. Kaplan-Meier Plotter was conducted to analyze the survival rate for different serine/threonine-protein kinase 4 (STK4) expressions with different prognostic risks. immunohistochemistry of STK4 expression in non-tumor and tumor tissues was analyzed from the HPA database. RT-qPCR and Western blot were adopted for detecting mRNA and protein expression. TargetScan V7.2, miRanda and PITA were adopted for predicting targets of miR-28-5p, overlapped genes were subjected to GO analysis. The interactions of miR-28-5p-Wnt and miR-28-5p-STK4 were detected by TOP/FOP luciferase reporter assay and dual luciferase reporter assay, respectively. Current study observed that G-Rh2 reduced miR-28-5p expression in NSCLC cells dose-dependently. miR-28-5p was upregulated in NSCLC tissues and cells. The target genes of miR-28-5p were enriched in negative regulation of Wnt signaling. miR-28-5p inhibitor inactivated Wnt signaling, inhibited cell viability and cell cycle, while enhanced cell apoptosis of NSCLC cells by targeting STK4. G-Rh2 exerted the similar effects with miR-28-5p inhibitor by reducing miR-28-5p. G-Rh2 and miR-28-5p inhibitor exerted a synergistic effect on inhibiting NSCLC tumor growth. In conclusion, G-Rh2 attenuates NSCLC development by affecting miR-28-5p/STK4 axis and inactivating Wnt signaling. Taken together, we project out a novel therapeutic target for NSCLC.

Ginsenoside Rh4 inhibits breast cancer growth through targeting histone deacetylase 2 to regulate immune microenvironment and apoptosis

High expression of histone deacetylase 2 (HDAC2) is recognized as a marker of invasive breast cancer (BC). HDAC2 is not only responsible for enhancing tumor cell growth, development, and anti-apoptosis, but also plays a significant role in regulating PD-L1 on the surface of tumor cells. Continuous expression of PD-L1 allows tumor cells to escape immune surveillance. There is not much research on how HDAC2 affects the immune system in breast cancer. Ginsenoside Rh4 (Rh4) is a major rare saponin in heat-treated ginseng, which is widely applied in treating and preventing various diseases because of its potent medicinal value and stable safety. However, it is unclear how Rh4 affects the tumor immune microenvironment in breast cancer. Therefore, this paper aims to investigate the effect of Rh4 on HDAC2 in breast cancer, specifically the effect of HDAC2 on apoptosis and the immune microenvironment to inhibit breast cancer growth. According to our study, ginsenoside Rh4 has been shown to significantly suppress breast cancer cell proliferation without any adverse effects. The molecular docking results of Rh4 and HDAC2 indicate a binding energy of −6.06 kcal/mol, suggesting the potential of Rh4 as a targeting modulator of HDAC2. Mechanistically, Rh4 induces apoptosis of breast cancer cells by the HDAC2-mediated caspase pathway and inhibits the HDAC2-mediated JAK/STAT pathway to regulate the immune microenvironment, which inhibits breast cancer growth. Specifically, Rh4 was shown for the first time to blockade immune checkpoints (PD-1/PD-L1) and increase levels of T-lymphocytes in the tumor. In a word, our study establishes a theoretical framework for applying Rh4 as an immune checkpoint inhibitor as part of breast cancer treatment.

Anti-Porphyromonas gingivalis nanotherapy for maintaining bacterial homeostasis in periodontitis

Periodontitis is caused by oral flora imbalance, which leads to immune imbalance. Porphyromonas gingivalis is a keystone pathogen in periodontitis, causing the blooming of inflammophilic microbes, and becoming dormant to resist antibiotics. Targeted interventions are needed to destroy this pathogen and collapse its inflammophilic flora. Therefore, a targeting nanoagent antibody-conjugated liposomal drug carrier with ginsenoside Rh2 (A-L-R) was developed for pleiotropic benefits. A-L-R showed high quality in high-performance liquid chromatography (HPLC), Fourier transform infrared (FTIR), and transmission electron microscope (TEM) detection. Only P. gingivalis was influenced by A-L-R, as shown by live/dead cell staining and a series of antimicrobial effects assays. With fluorescence in situ hybridization (FISH) staining and in propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR), the clearance of P. gingivalis by A-L-R was more than for other groups, and only the proportion of P. gingivalis was reduced by A-L-R in monospecies culture. Moreover, in a periodontitis model, A-L-R targeted P. gingivalis with high efficiency and low toxicity, maintaining homeostasis with a relatively stable oral microflora. This targeting nanomedicine offers new strategies for periodontitis therapy, providing a foundation for the prevention and treatment of periodontitis.

Ginsenoside Rh3 induces pyroptosis and ferroptosis through the Stat3/p53/NRF2 axis in colorectal cancer cells.

Ginsenoside Rh3 (GRh3) is a seminatural product obtained by chemical processing after isolation from Chinese herbal medicine that has strong antitumor activity against human tumors. However, its antitumor role remains to be elucidated. The aim of this study is to explore the mechanisms underlying the tumor suppressive activity of GRh3 from the perspective of pyroptosis and ferroptosis. GRh3 eliminates colorectal cancer (CRC) cells by activating gasdermin D (GSDMD)-dependent pyroptosis and suppressing solute carrier family 7 member 11 (SLC7A11), resulting in ferroptosis activation through the Stat3/p53/NRF2 axis. GRh3 suppresses nuclear factor erythroid 2-related factor 2 (NRF2) entry into the nucleus, leading to the decrease of heme oxygenase 1 (HO-1) expression, which in turn promotes NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and caspase-1 expression. Finally, caspase-1 activates GSDMD-dependent pyroptosis. Furthermore, GRh3 prevents NRF2 from entering the nucleus, which suppresses SLC7A11, causing the depletion of glutathione (GSH) and accumulation of iron, lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and eventually leading to ferroptosis in CRC cells. In addition, GRh3 effectively inhibits the proliferation of CRC cells in vitro and in nude mouse models. Collectively, GRh3 triggers pyroptotic cell death and ferroptotic cell death in CRC cells via the Stat3/p53/NRF2 axis with minimal harm to normal cells, showing great anticancer potential.

Ginsenoside Rh1 ameliorates the asthma and allergic inflammation via inhibiting Akt, MAPK, and NF-κB signaling pathways in vitro and in vivo

AimsOverproduction of pro-inflammatory cytokines and its-mediated immune cell infiltration play a crucial role in asthma progression. In this study, we investigated the role of ginsenoside Rh1 (Rh1) in ovalbumin (OVA)/lipopolysaccharide (LPS)-induced allergic asthma both in vitro and in vivo. Materials and main methodsThe phorbol ester (PMA) and LPS were used to induce inflammation in lung airway cells and macrophage activation, respectively. Western blotting, quantitative reverse transcription-PCR, and immunofluorescence (IF) assays were performed to elucidate the underlying molecular mechanisms. To evaluating the effects of Rh1 in vivo, OVA and LPS were used to establish allergic asthma models. Key findingsRh1 significantly suppressed PMA-induced lung inflammation and macrophage activation by suppressing pro-inflammatory cytokines (TNF-α, IL-1β, MCP-1), ICMA-1, and matrix metallopeptidase 9 (MMP9) in A549 cells. Rh1 abolished the PMA-induced inflammation by suppressing MAPK, Akt, and NF-κB p65. Pretreatment with Rh1 blocked PMA-mediated translocation of NF-κB, a key marker of pro-inflammatory cytokine release, into the nucleus. Similar to PMA-induced lung inflammation, Rh1 suppressed LPS-induced macrophage activation by suppressing NF-κB p65 activation and inducible nitric oxide synthase protein and mRNA expression. Consistent with in vitro data, LPS injection enhanced the number of immune cells induced by OVA in bronchoalveolar lavage fluid, whereas 20 mg/kg Rh1 significantly decreased OVA/LPS-mediated immune cell induction. In addition, Rh1 inhibited eosinophil, macrophage, and neutrophil maturation through by IL-4 and OVA-specific IgE production. SignificanceRh1 protects against OVA/LPS-induced allergic asthma by suppressing immune cell infiltration by blocking the activation of MAPK, Akt, and NF-κB signaling pathways.

20(S)-Ginsenoside Rh1 inhibits cisplatin-induced hearing loss by inhibiting the MAPK signaling pathway and suppressing apoptosis in vitro

As an anticancer drug, cisplatin is widely used, but its clinical application is restricted due to its severe side effects of ototoxicity. Therefore, this study was dedicated to assessing the benefit of ginsenoside extract, 20(S)-Ginsenoside Rh1 (Rh1), on cisplatin-induced ototoxicity. HEI-OC1 cells and neonatal cochlear explants were cultured. Cleaved caspase-3, TUNEL, and MitoSOX Red were observed in vitro by immunofluorescence staining. CCK8 and LDH cytotoxicity assays were detected to measure cell viability and cytotoxicity. Our results showed that Rh1 significantly increased cell viability, reduced cytotoxicity, and alleviated cisplatin-induced apoptosis. In addition, Rh1 pretreatment decreased the excessive accumulation of intracellular reactive oxygen species. Mechanistic studies indicated that Rh1 pretreatment reversed the increase of apoptotic protein expression, accumulation of mitochondrial ROS, and activation of the MAPK signaling pathway. These results suggested that Rh1 can act as an antioxidant and anti-apoptotic agent against cisplatin-induced hearing loss by suppressing the excessive accumulation of mitochondrial ROS, activation of MAPK signaling pathway and apoptosis.

Ginsenoside Rh2 suppresses colon cancer growth by targeting the miR-150-3p/SRCIN1/Wnt axis

Ginsenoside Rh2, which is extracted from ginseng, exerts antitumor activity. Recent studies suggest that Rh2 may suppress the growth of colon cancer (CC) in vitro. However, the underlying mechanism remains unclear. In this study, we identified the relative levels of miR-150-3p in CC tissues and cells by a comprehensive strategy of data mining, computational biology, and real-time reverse transcription PCR (qRT-PCR) experiments. The regulatory effects of miR-150-3p/SRCIN1 on the proliferative and invasive abilities of CC cells are evaluated by CCK-8, EdU, wound healing, and transwell assays. Cell cycle- and apoptosis-related protein levels are assessed by western blot analysis. An in vivo tumor formation assay was conducted to explore the effects of miR-150-3p on tumor growth. Furthermore, bioinformatics and dual luciferase reporter assays are applied to determine the functional binding of miRNA to mRNA of the target gene. Finally, the relationship between Rh2 and miR-150-3p was further verified in SW620 and HCT-116 cells. miR-150-3p is downregulated in CC tissues and cell lines. Functional assays indicate that the upregulation of miR-150-3p inhibits tumor growth both in vivo and in vitro. In addition, SRCIN1 is upregulated in CC and predicts a poor prognosis, and it is the direct target for miR-150-3p. Moreover, the miR-150-3p mimic decreases Topflash/Fopflash-dependent luciferase activity, resulting in the inhibition of Wnt pathway activity. Rh2 can suppress the growth of CC by increasing miR-150-3p expression. Rh2 alleviates the accelerating effect on Wnt pathway activity, cell proliferation/migration, and colony formation caused by miR-150-3p inhibition. Rh2 inhibits the miR-150-3p/SRCIN1/Wnt axis to suppress colon cancer growth.

Regulatory effect of eight Chinese herbal medicines on glucose and lipid metabolism and their potential active components based on HCBP6 target

With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.

The ginsenoside Rh2 protects porcine oocytes against aging and oxidative stress by regulating SIRT1 expression and mitochondrial activity

Post-ovulatory aging, a major problem faced by oocytes cultured in vitro, causes oxidative damage and mitochondrial dysfunction in oocytes. The ginsenoside Rh2 is one of the main monomeric components of ginseng, but its effects on porcine oocytes are unknown. In the present study, in vitro aging (IVA) and accelerated induction of aging using H2O2 resulted in DNA damage and an increased incidence of abnormal spindle formation in porcine oocytes. Rh2 supplementation increased the antioxidant capacity, reduced the occurrence of early apoptosis, and improved the development of in vitro fertilized blastocysts. It also rescued the abnormal aggregation of mitochondria and the decrease of the mitochondrial membrane potential under mitochondrial dysfunction. Meanwhile, Rh2 enhanced mRNA expression of the anti-aging and mitochondrial biogenesis-related genes silent information regulator of transcription 1 (SIRT1) and peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α), and the antioxidant gene superoxide dismutase 1 (SOD1). The protection of porcine oocytes against aging and oxidative stress by Rh2 was confirmed using the SIRT1-specific inhibitor EX-527. Our results reveal that Rh2 upregulates SIRT1/PGC-1α to enhance mitochondrial function in porcine oocytes and improve their quality. Our study indicates that Rh2 can be used to prevent mitochondrial dysfunction in oocytes.

Network pharmacology, molecular docking, and experimental verification reveal the mechanism of San-Huang decoction in treating acute kidney injury.

Background: Cisplatin is an effective anti-tumor drug. However, its usage is constrained by side effects such as nephron toxicity. Cisplatin-induced acute kidney injury (AKI) appears in approximately 20%-30% of cases. Hence, finding an effective protective strategy is necessary. San-Huang decoction (SHD) is a Chinese herbal decoction with good efficacy in treating chronic kidney disease (CKD). Nevertheless, the mechanism of SHD on AKI remains unclear. Consequently, we proposed to explore the potential mechanism of SHD against cisplatin-induced AKI. Methods: Active compounds, core target proteins, and associated signaling pathways of SHD were predicted through network pharmacology. Then confirmed by molecular docking. In vivo experiment, Cisplatin + SHD group was treated with SHD (6.5g/kg/day) for 6days before building the model. An AKI model was established with a single intraperitoneal injection of cisplatin at 20mg/kg. After 72h of cisplatin injection, all mice were sacrificed to collect blood and kidney tissues for verification of network pharmacology analysis. Results: We found that calycosin, rhein, and ginsenoside Rh2 may be SHD's primary active compounds in treating cisplatin-induced AKI, and AKT, TNF-α, IL-6, IL-1β, caspase-3, and MMP9 are the core target proteins. The relationship between the compound and target protein was further confirmed by molecular docking. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses predicted that SHD has an anti-inflammatory role through the TNF and IL-17 signaling pathway. Moreover, Western blot and immunohistochemistry validated the potential molecular mechanisms of SHD, predicted from network pharmacology analysis. The mechanism of cisplatin-induced AKI involves apoptosis and inflammation. In apoptosis, Caspase-3, caspase-8, caspase-9, and Bax proteins were down-regulated, while Bcl-2 was up-regulated by SHD. The differential expression of MMP protein is involved in the pathological process of AKI. MMP9 protects from glomerular tubule damage. MMP9 and PI3K/AKT anti-apoptosis pathway were up-regulated by SHD. In addition, we discovered that SHD alleviated AKI by inhibiting the NF-κB signaling pathway. Conclusion: SHD plays a critical role in anti-inflammation and anti-apoptosis via inhibiting the NF-κB signaling pathway and activating PI3K/AKT anti-apoptosis pathway, indicating that SHD is a candidate herbal drug for further investigation in treating cisplatin-induced AKI.

Construction of plant cell factory for biosynthesis of ginsenoside Rh2 in tobacco

Construction of plant cell factory for biosynthesis of ginsenoside Rh2 in tobacco

Recent Advances in Yeast Recombinant Biosynthesis of the Triterpenoid Protopanaxadiol and Glycosylated Derivatives Thereof.

Plant natural products are a seemingly endless resource for novel chemical structures. However, their extraction often results in high prices, fluctuation in both quantity and quality, and negative environmental impact. The latter might result from the extraction procedure but more often from the high amount of plant biomass required. With the advent of synthetic biology, producing natural plant products in large quantities using yeasts as hosts has become possible. Here, we focus on the recent advances in metabolic engineering of the yeasts species Saccharomyces cerevisiae and Yarrowia lipolytica for the synthesis of ginsenoside triterpenoids, namely, dammarenediol-II, protopanaxadiol, protopanaxatriol, compound K, ginsenoside Rh1, ginsenoside Rh2, ginsenoside Rg3, and ginsenoside F1. A discussion is provided on advanced synthetic biology, bioprocess strategies, and current challenges for the biosynthesis of ginsenoside triterpenoids. Finally, future directions in metabolic and process engineering are summarized and may help reify sustainable ginsenoside production.

Effects of solid-state fermentation using R. oligosporus on the phytochemical composition of wild-simulated ginseng leaf and its biological properties

Wild-simulated ginseng (WSG) grown in the mountains without specific facilities is widely used as functional foods in Asian countries due to its bioactive compounds, such as ginsenosides. However, long-time cultivation, lower survival rate, and small size of WSG limit its use in the food industry. In this study, WSG leaves, which can be harvested annually, were fermented using R. oligosporus for 0–10 days. The phytochemical compounds of fermented WSG leaves, including squalene, phenols, saponins, and most ginsenosides (except for Rb1), were increased. L-carnitine was newly synthesized in WSG leaves, with a content of 165.1 μg/g measured after 10 days of fermentation. Moreover, the minor ginsenosides Rg2, Rg3, Rh1, F1, F2, and CK increased by 1.32-, 1.58-, 1.42-, 1.91-, 1.49-, and 4.43-fold compared to non-fermented WSG leaves. The highest antioxidant activities, as measured by FRAP and ORAC assays of WSG leaves, were obtained after 3 days of fermentation. Furthermore, the suppression of NO release in LPS-stimulated RAW264.7 cells and lipid accumulation in mouse 3T3-L1 cells of fermented WSG leaves was greater than in WSG leaves. From these results, fermented WSG leaves have potential applications as functional materials in the food industry.

Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model

Blocking immune checkpoints, programmed death-1 (PD-1) and its ligand PD-L1, has proven a promising anticancer strategy for enhancing cytotoxic T cell activity. Although we previously demonstrated that ginsenoside Rg3, Rh2, and compound K block the interaction of PD-1 and PD-L1, the antitumor effect through blockade of this interaction by Korean Red Ginseng alone is unknown. Therefore, we determined the effects of Korean Red Ginseng extract (RGE) on the PD-1/PD-L1 interaction and its antitumor effects using a humanized PD-1/PD-L1-expressing colorectal cancer (CRC) mouse model. RGE significantly blocked the interaction between human PD-1 and PD-L1 in a competitive ELISA. The CD8+ T cell-mediated tumor cell killing effect of RGE was evaluated using murine hPD-L1-expressing MC38 cells and tumor-infiltrating hPD-1-expressing CD8+ T cells isolated from hPD-L1 MC38 tumor-bearing hPD-1 mice. RGE also reduced the survival of hPD-L1 MC38 cells in a cell co-culture system using tumor-infiltrating CD8+ T cells as effector cells combined with hPD-L1 MC38 target cells. RGE or Keytruda (positive control) treatment markedly suppressed the growth of hPD-L1 MC38 allograft tumors, increased CD8+ T cell infiltration into tumors, and enhanced the production of Granzyme B. RGE exhibits anticancer effects through the PD-1/PD-L1 blockade, which warrants its further development as an immunotherapy.

A four-compound remedy AGILe protected H9c2 cardiomyocytes against oxygen glucose deprivation via targeting the TNF-α/NF-κB pathway: Implications for the therapy of myocardial infarction.

Myocardial infarction (MI) is a highly prevalent and lethal disease worldwide. Prevention and timely recovery are critical for the control of the recurrence and heart failure in MI survivors. The present study was designed to investigate the cardioprotective activity of the herbal medicine formula Baoyuan Decoction (BYD) and identify the active compounds and molecular targets. The ethanolic BYD extract (BYDE) was prepared by water extraction and ethanol precipitation of four herbal medicines, Astragali Radix, Ginseng Radix et Rhizoma, Cinnamomi Cortex, and Glycyrrhizae Radix et Rhizoma. Initially, BYDE was validated for the cardioprotective effectiveness in a mouse model of ischemia injury and rat cardiomyocyte H9C2 cells. As results, BYDE effectively reduced infarct size from 56% to 37% and preserved cardiac functions in mouse MI model while protected H9C2 cells against oxygen glucose deprivation. Subsequent network pharmacology analysis revealed that 122 bioactive ingredients, including flavonoids and saponins from the UPLC-MS/MS profile of BYDE, might target 37 MI-related proteins, including inflammatory and apoptotic mediators (e.g., TNF, NFKB1, CASPs, TNFRSF1A, CXCL12, BCL2A1). Pathway enrichment analysis suggested that BYDE might control the cardiac inflammation via targeting the tumor necrosis factor-alpha (TNF-α)/nuclear factor-κB (NF-κB) pathway while the selected targets were also implicated in IL-17 signaling pathway, lipid and atherosclerosis. Consequently, adenosine, ginsenoside Rh2, isoliquiritigenin, and licochalcone A were selected to generate the four-compound mixture AGILe and validated for the inhibitory effects on the TNF-α/NF-κB pathway. The results of the present study suggested that the mixture AGILe might be a potential cardioprotective remedy against MI.

Comparison of the metabolomic and proteomic profiles associated with triterpene and phytosterol accumulation between wild and cultivated ginseng

Wild ginseng is thought to be superior in its medicinal quality to cultivated ginseng, potentially owing to the differences in active components. This study was designed accordingly to assess the differences in secondary metabolite components and their synthesis in wild and cultivated ginseng by using quantitative proteomics combined with secondary metabolomics approaches. A total of 72 secondary metabolites were found to be differentially abundant, of which dominant abundant in wild ginseng primarily included triterpenoid saponins (ginsenosides) and phytosterols. Ginsenoside diversity was increased in wild ginseng, particularly with respect to rare ginsenosides. Ginsenoside Rk1, F1, Rg5, Rh1, PPT, Rh2, and CK enriched in wild ginseng were validated by HPLC. In addition to ginsenosides, stigmasterol and β-sitosterol were accumulated in wild ginseng. 102 differentially expressed proteins between wild and cultivated ginseng were identified using iTRAQ labeling technique. Among them, 25 were related to secondary metabolism, mainly involved in sesquiterpene and triterpene biosynthesis, which was consistent with metabolomics results. Consistently, the activity levels of HMGR, FDPS, SS, SE, DS, CYP450, GT and CAS, which are key enzymes related to ginsenoside and phytosterol biosynthesis, were confirmed to be elevated in wild ginseng.The biosynthesis of ginsenosides and phytosterols in wild ginseng is higher than that in cultivated ginseng, which may be related to natural growth without artificial domestication. To some extent, this study explained the accumulation of pharmacodynamic components and overall quality of ginseng, which could provide reference for the germplasm improvement and planting of ginseng.

Seven basement membrane-specific expressed genes are considered potential biomarkers for the diagnosis and treatment of diabetic nephropathy.

Diabetic nephropathy (DN) is a diabetes-related chronic vasculitis. DN diminishes kidney function over time and, of course, leads to end stage renal disease in people (ESRD). In spite of the advances in diagnostic and treatment methods for DN, DN continues to impose a significant physical and psychological burden on patients, severely impacting their quality of life, making the hunt for novel therapeutic targets necessary. The Gene Expression Omnibus (GEO) microarray datasets GSE1009, GSE30122, GSE142153, and GSE96804 were downloaded to identify differentially expressed genes (DEGs) in kidney tissues from patients in the DN group and normal controls. These three datasets were examined for genes associated with basement membranes (BMs) with differential gene expression. The target genes were then subjected to gene ontology (GO) annotation and Kyoto Gene and Genome Encyclopedia (KEGG) pathway enrichment analysis. BM-related genes underwent PPI network analysis and screening of the top 10 hub genes, along with immune infiltration analysis and column line graph model development. Finally, we conducted DN therapeutic medication prediction and the creation of something like a miRNA network for genetic markers with BMs. Seven candidate BM-related genes (COL4A1, COL4A2, COL6A2, COL6A3, FN1, ITGQ4, and LAMB1) with acceptable helps the healthcare were discovered. Enrichment analysis of diabetes-related genes event occurred the role of biological processes including extracellular matrix organization, extracellular structural organization, and collagen-containing extracellular matrix, as well as the PI3K-Akt signaling pathway and the AGE-RAGE signaling pathway, in diabetic complications. These genes may also be associated in immune cells and autoimmune activities, such as Macrophages and MHC class I, in order to impact the immune process in DN. In the meanwhile, based on these seven BM-related genes, we discovered that Ginsenoside Rh1 was very significant for drug targeting. This research identified seven BM-related genes as possible diagnostic and therapeutic biomarkers for DN. Analysis of inflammatory infiltration indicated that these genes may be important in inflammatory processes through Macrophages and MHC class I, hence impacting the course and development of DN illness. The development of a correlated column line graph model for it also shown excellent predictive capabilities. In addition, we have found pharmaceuticals, such as Ginsenoside Rh1, that may provide fresh insights into the personalized management of patients with DN.

Analysis of Metabolic Differences in the Water Extract of Shenheling Fermented by Lactobacillus fermentum Based on Nontargeted Metabolomics

Objective: To explore the characteristics of metabolites in Shenheling (SHL) fermented by Lactobacillus fermentum. Methods: In this study, ultrahigh-performance liquid chromatography-quadrupole electrostatic field orbit trap mass spectrometry (UHPLC-QE-MS) was used to qualitatively, quantitatively, and differentially analyze the metabolites of SHL before and after fermentation. Results: A total of 102 significant differential metabolites in nine categories were analyzed before and after fermentation. It mainly includes 29 terpenoids, 17 alkaloids, 14 organic acids and derivatives, 10 flavonoids, 9 phenylpropanoids, 6 phenols, 3 aromaticity, and 3 amino acid derivatives. Further screening found that the content of most active substances, such as alkaloids, organic acids, and flavonoids, increased significantly. These metabolites play an important role in improving the taste and efficacy of SHL. After fermentation, the contents of differential metabolites, such as panaquinquecol 2, ginsenoside Rh3, ginsenoside Rg3, dehydronuciferin, nicotinic acid, 5-hydroxytryptophan, azelaic acid, dihydrokaempferol, and chrysin, were increased, which increased the effects of antioxidation, anti-obesity, hypoglycemic, antibacterial, and improved immunity compared with those before fermentation. KEGG pathway analysis identified 10 metabolic pathways. Isoquinoline alkaloid biosynthesis, vitamin B6 metabolism, beta-alanine metabolism, nicotinate, and nicotinamide metabolism, purine metabolism, pantothenate and CoA biosynthesis, glyoxylate and dicarboxylate metabolism, tyrosine metabolism, citrate cycle (TCA cycle), phenylpropanoid biosynthesis, etc. Conclusions: Fermentation significantly changed the metabolites in SHL and played an important role in improving its taste, aroma quality, antioxidant, anti-obesity, and other health care functional components.

Gastroprotective effects of ginsenoside Rh4 against ethanol-induced gastric mucosal injury by inhibiting the MAPK/NF-κB signaling pathway.

Ginsenoside Rh4, a bioactive component extracted from Panax ginseng, exhibits various pharmacological activities, such as anti-inflammatory, anti-oxidation, anti-diabetes, anti-obesity, antitumor and immunity enhancement. However, the gastroprotective effect of ginsenoside Rh4 remains unknown. The present study evaluated the gastroprotective effect and potential mechanism of ginsenoside Rh4 in an ethanol-induced gastric ulcer model. Ginsenoside Rh4 (15, 30, and 60 mg kg-1) and omeprazole (30 mg kg-1) were administered orally for 7 days. The results showed that pretreatment with ginsenoside Rh4 reduced the gastric injury area and percentage of mucosal lesions in gastric tissue. Besides, treatment with ginsenoside Rh4 increased superoxide dismutase (SOD) activity, glutathione (GSH) and nitric oxide (NO) levels, reduced the content of malonaldehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), mediated the prostaglandin E-2-cyclooxygenase-2 (PGE2-Cox-2) pathway, and mitigated inflammation and oxidative stress via blockade of proinflammatory mitogen-activated protein kinase-nuclear factor κB (MAPK/NF-κB) signaling pathways. Furthermore, ginsenoside Rh4 significantly enhanced the protein expression of B-cell lymphoma gene 2 (Bcl-2), decreased the protein expression of Bcl-2-associated X protein (Bax) and tumor necrosis factor receptor superfamily member 6 (Fas), and inhibited the number of apoptotic cells in gastric tissues. The present work demonstrated that ginsenoside Rh4 exerted a considerable gastroprotective effect against ethanol-induced gastric ulcers in rats.

Dietary phytochemicals: As a potential natural source for treatment of Alzheimer's Disease

Alzheimer's disease (AD) is a common neurodegenerative disease, which seriously impairs human health and life. At present, scientists have proposed more than a dozen hypotheses about the pathogenesis of AD, including the tau propagation hypothesis. However, the exact ultimate pathogenic factor of AD remains unknown. Based on the current hypotheses, some anti-AD drugs (e.g., donepezil and Ketamine) have been developed and used in clinical treatment, which fall into two main categories, acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonists, the former representative drug is donepezil, and the latter representative drug is memantine. Since these drugs have undesirable side effects, it is necessary to find safer alternatives for AD treatment. Interestingly, dietary phytochemicals have the advantages of wide source, safety, and high biological activity, which is the natural route for screening anti-AD drugs. In this study, several representatives’ dietary phytochemicals with anti-AD effect, including resveratrol, lycopene, gallic acid, berberine, ginsenoside Rg1, pseudoginsenoside-F11, ginsenoside Rh2, artemisinin, and torularhodin were selected from the published data over the last 10 years and their potential molecular mechanisms and clinical applications reviewed in the treatment of AD.