BACKGROUND: The endoplasmic reticulum (ER) stress is a crucial toxic signaling event triggered by chronic exposure to Ultraviolet B radiation (UVB), which significantly exacerbate photodamage responses in the irradiated skin. Therefore, the identification of agents capable of inhibiting ER stress could serve as a promising therapeutic strategy for addressing the unmet clinical needs in the treatment of UVB-induced photodamage.
METHODS: A UVB-irradiated mouse model was used and topical administration of Panax ginseng extract was carried out for a duration of 9 weeks. Vitamin E was used as a positive control. After 9 weeks of administration, the skin appearance, epidermal hyperplasia, infiltration of inflammatory cells, apoptosis, and collagen content were measured. The keratinocytes were irradiated with 6 mJ/cm2 UVB to establish an in vitro model. The levels of ER stress and apoptosis were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence.
RESULTS: Among the 14 extracts derived from 13 distinct plant species that were screened, Panax ginseng, Prunus mume, and Camellia japonica showed inhibitory effect on UVB-induced ER stress. Notably, Panax ginseng effectively inhibits collagen degradation and apoptosis in both irradiated keratinocytes and Balb/C mice skin. Furthermore, the silencing of VMP1 significantly impeded the cellular protective effect of Panax ginseng extract on UVB-irradiated keratinocytes, indicating that Panax ginseng exerts its protective effects through targeted promotion of VMP1.
CONCLUSIONS: Our data suggest that Panax ginseng extract possess a therapeutical effect on UVB radiation-induced photodamage by promoting VMP1-mediated inhibition of ER stress.

BACKGROUND: Chinese herbal medicines have been utilized for thousands of years to prevent and treat diseases. Accurate identification is crucial since their medicinal effects vary between species and varieties. Metabolomics is a promising approach to distinguish herbs. However, current metabolomics data analysis and modeling in Chinese herbal medicines are limited by small sample sizes, high dimensionality, and overfitting.
OBJECTIVE: This study aims to use metabolomics data to develop HerbMet, a high-performance artificial intelligence system for accurately identifying Chinese herbal medicines, particularly those from different species of the same genus.
METHODS: We propose HerbMet, an AI-based system for accurately identifying Chinese herbal medicines. HerbMet employs a 1D-ResNet architecture to extract discriminative features from input samples and uses a multilayer perceptron for classification. Additionally, we design the double dropout regularization module to alleviate overfitting and improve model\'s performance.
RESULTS: Compared to 10 commonly used machine learning and deep learning methods, HerbMet achieves superior accuracy and robustness, with an accuracy of 0.9571 and an F1-score of 0.9542 for distinguishing seven similar Panax ginseng species. After feature selection by 25 different feature ranking techniques in combination with prior knowledge, we obtained 100% accuracy and an F1-score for discriminating P. ginseng species. Furthermore, HerbMet exhibits acceptable inference speed and computational costs compared to existing approaches on both CPU and GPU.
CONCLUSIONS: HerbMet surpasses existing solutions for identifying Chinese herbal medicines species. It is simple to use in real-world scenarios, eliminating the need for feature ranking and selection in classical machine learning-based methods.

The geographical origin of Panax ginseng significantly influences its nutritional value and chemical composition, which in turn affects its market price. Traditional methods for analyzing these differences are often time-consuming and require substantial quantities of reagents, rendering them inefficient. Therefore, hyperspectral imaging (HSI) in conjunction with X-ray technology were used for the swift and non-destructive traceability of Panax ginseng origin. Initially, outlier samples were effectively rejected by employing a combined isolated forest algorithm and density peak clustering (DPC) algorithm. Subsequently, random forest (RF) and support vector machine (SVM) classification models were constructed using hyperspectral spectral data. These models were further optimized through the application of 72 preprocessing methods and their combinations. Additionally, to enhance the model\'s performance, four variable screening algorithms were employed: SelectKBest, genetic algorithm (GA), least absolute shrinkage and selection operator (LASSO), and permutation feature importance (PFI). The optimized model, utilizing second derivative, auto scaling, permutation feature importance, and support vector machine (2nd Der-AS-PFI-SVM), achieved a prediction accuracy of 93.4 %, a Kappa value of 0.876, a Brier score of 0.030, an F1 score of 0.932, and an AUC of 0.994 on an independent prediction set. Moreover, the image data (including color information and texture information) extracted from color and X-ray images were used to construct classification models and evaluate their performance. Among them, the SVM model constructed using texture information from X -ray images performed the best, and it achieved a prediction accuracy of 63.0 % on the validation set, with a Brier score of 0.181, an F1 score of 0.518, and an AUC of 0.553. By implementing mid-level fusion and high-level data fusion based on the Stacking strategy, it was found that the model employing a high-level fusion of hyperspectral spectral information and X-ray images texture information significantly outperformed the model using only hyperspectral spectral information. This advanced model attained a prediction accuracy of 95.2 %, a Kappa value of 0.912, a Brier score of 0.027, an F1 score of 0.952, and an AUC of 0.997 on the independent prediction set. In summary, this study not only provides a novel technical path for fast and non-destructive traceability of Panax ginseng origin, but also demonstrates the great potential of the combined application of HSI and X-ray technology in the field of traceability of both medicinal and food products.

The Bacillus velezensis strain NT35, which has strong biocontrol ability, was isolated from the rhizosphere soil of Panax ginseng. The antifungal effects of the NT35 strain against the mycelium and spore growth of Ilyonectria robusta, which causes ginseng rusty root rot, were determined. The inhibitory rate of I. robusta mycelial growth was 94.12% when the concentration of the NT35 strain was 107 CFU·mL-1, and the inhibitory rates of I. robusta sporulation and spore germination reached 100 and 90.31%, respectively, when the concentration of the NT35 strain was 104 and 108 CFU·mL-1, respectively. Strain NT35 had good prevention effects against ginseng rust rot indoors and in the field with the control effect 51.99%, which was similar to that of commercial chemical and biocontrol agents. The labeled strain NT35-Rif160-Stre400 was obtained and colonized ginseng roots, leaves, stems and rhizosphere soil after 90 days. Bacillus velezensis NT35 can induce a significant increase in the expression of five defensive enzyme-encoding genes and ginsenoside biosynthesis-related genes in ginseng. In the rhizosphere soil, the four soil enzymes and the microbial community improved during different periods of ginseng growth in response to the biocontrol strain NT35. The NT35 strain can recruit several beneficial bacteria, such as Luteimonas, Nocardioides, Sphingomonas, and Gemmatimonas, from the rhizosphere soil and reduce the relative abundance of Ilyonectria, Fusarium, Neonectria and Dactylonectria, which cause root rot and rusty root rot in ginseng plants. The disease indices were significantly negatively correlated with the abundances of Sphingomonas and Trichoderma. Additionally, Sphingomonadales, Sphingomonadaceae and actinomycetes were significantly enriched under the NT35 treatment according to LEfSe analysis. These results lay the foundation for the development of a biological agent based on strain NT35.

MicroRNA (miRNA) is a class of non-coding endogenous small-molecule, single-stranded RNAs, and it is involved in post-transcriptional gene expression regulation in plants and plays an important role in plant growth and development. Among them, miRNA156 regulates members of target SPL gene family and thus participates in plant growth and development, hormonal response and adversity stress. However, it has not been reported in ginseng. In this study, based on the previous analysis of the SPL gene family, the age-related and stably expressed SPL gene PgSPL24-09 was obtained in roots. The binding site of miRNA156 to this gene was analyzed using target gene prediction tools, and the interactions between miRNA156 and PgSPL24-09 gene were verified by dual luciferase reporter gene assay and RT-qPCR. At the same time, miRNA156 silencing vector and overexpression vector were constructed and transformed into ginseng adventitious roots and Arabidopsis thaliana to analyze the molecular mechanism of miRNA156-SPL module in regulating the growth of ginseng adventitious roots. This study provides a theoretical basis for the in-depth study of the molecular role of miRNAs in ginseng growth, and also lays the foundation for the study of the role of miRNA156-SPL module in regulating the growth and development of ginseng.

BACKGROUND: Panax ginseng (P. ginseng) C.A. Meyer. Has been studied for decades for its various biological activities, especially in terms of immune-regulatory properties. Traditionally, it has been known that root, leaves, and fruits of P. ginseng were eaten for improving body\'s Qi and homeostasis. Also, these were used to protect body from various types of infectious diseases. However, molecular mechanisms of immunomodulatory activities of ginseng berries have not been systemically studied as often as other parts of the plant.
OBJECTIVE: The aim of this research is to discover the regulatory effects of P. ginseng berries, more importantly, their ginsenosides, on innate immune responses and to elucidate the molecular mechanism.
METHODS: Ginseng berry concentrate (GBC) was orally injected into BALB/c mice for 30 days, and spleens were extracted for evaluation of immune-regulatory effects. Murine macrophage RAW264.7 cells were used for detailed molecular mechanism studies. Splenic natural killer (NK) cells were isolated using the magnetic-activated cell sorting (MACS) system, and the cytotoxic activity of isolated NK cells was measured using a lactate dehydrogenase (LDH) release assay. The splenic immune cell population was determined by flow-cytometry. NF-κB promoter activity was assessed by in vitro luciferase assay. Expression of inflammatory proteins and cytokines of the spleen and RAW264.7 cells were evaluated using western blotting and real-time PCR, respectively.
RESULTS: The GBC enhanced cytotoxic activity of NK cells and the immune-regulation-related splenic cell population. Moreover, GBC promoted NF-κB promoter activity and stimulated the NF-κB signaling cascade. In spleen and RAW264.7 cells, expression of pro-inflammatory cytokines was increased upon GBC application, while expression of anti-inflammatory cytokines decreased.
CONCLUSIONS: These results suggest that P. ginseng berry can stimulate innate immune responses and help maintain a balanced immune condition, mostly due to the action of its key ginsenoside Re, along with other protopanaxadiol- and protopanaxatriol-type ginsenosides. Such finding will provide a new insight into the field of well-being diet research as well as non-chemical immune modulator, by providing nature-derived and plant-based bioactive materials.

Iron plays a crucial role in plant chlorophyll synthesis, respiration, and plant growth. However, excessive iron content can contribute to ginseng poisoning. We previously discovered that the application of silicon (Si) and potassium (K) can mitigate the iron toxicity on ginseng. To elucidate the molecular mechanism of how Si and K alleviate iron toxicity stress in ginseng. We investigated the physiological and transcriptional effects of exogenous Si and K on Panax ginseng. The results suggested that the leaves of ginseng with Si and K addition under iron stress increased antioxidant enzyme activity or secondary metabolite content, such as phenylalanine amino-lyase, polyphenol oxidase, ascorbate peroxidase, total phenols and lignin, by 6.21%-25.94%, 30.12%-309.19%, 32.26%-38.82%, 7.81%-23.66%, and 4.68%-48.42%, respectively. Moreover, Si and K increased the expression of differentially expressed genes (DEGs) associated with resistance to both biotic and abiotic stress, including WRKY (WRKY1, WRKY5, and WRKY65), bHLH (bHLH35, bHLH66, bHLH128, and bHLH149), EREBP, ERF10 and ZIP. Additionally, the amount of DEGs of ginseng by Si and K addition was enriched in metabolic processes, single-organism process pathways, signal transduction, metabolism, synthesis and disease resistance. In conclusion, the utilization of Si and K can potentially reduce the accumulation of iron in ginseng, regulate the expression of iron tolerance genes, and enhance the antioxidant enzyme activity and secondary metabolite production in both leaves and roots, thus alleviating the iron toxicity stress in ginseng.

The aim of this paper is to study the malonyl ginsenosides in the fresh roots of Panax ginseng. D101 macroporous adsorption resin, ODS, and preparative HPLC were employed to separate the chemical components from the 70% ethanol extract of the fresh roots of P. ginseng, and the structures of the separated compounds were identified based on the data of high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Two malonyl ginsenosides were isolated from the fresh roots of P. ginseng and identified as 3-O-\\[6-O-malonyl-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl\\]-20-O-\\[ β-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranosyl\\]-dammar-24-ene-3β,12β,20S-triol(1) and 3-O-\\[6-O-malonyl-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl\\]-20-O-\\[ β-D-xylopyranosyl-(1→2)-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranosyl\\]-dammar-24-ene-3β,12β,20S-triol(2), respectively. Compounds 1 and 2 are new compounds isolated from fresh roots of P. ginseng for the first time and named as malonyl ginsenoside-Ra_1 and malonyl ginsenoside-Ra_2, respectively.

In our study, a method based on affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was established to select Glucagon-like peptide-1 receptor (GLP-1R) agonists from natural products, and as an example, the GLP-1R agonists from Panax ginseng was selected using our established method. As a result, total five GLP-1R agonists were selected from Panax ginseng for the first time. Our results indicated that activating GLP-1R to promote insulin secretion probably was another important hypoglycemia mechanism for ginsenosides in Panax ginseng, which had great influence on the study of the anti-diabetes effect of ginsenosides.

Panax species include Panax ginseng Meyer, Panax quinquefolium L., Panax notoginseng, Panax japonicum, Panax trifolium, and Panax pseudoginseng, which contain bioactive components (BCs) such as ginsenosides and polysaccharides. Recently, growing evidence has revealed the pharmacological effects of Panax species and their BCs on allergic airway diseases (AADs), including allergic asthma (AA) and allergic rhinitis (AR). AADs are characterized by damaged epithelium, sustained acquired immune responses with enforced Th2 responses, allergen-specific IgE production, and enhanced production of histamine and leukotrienes by activated mast cells and basophils. In this review, we summarize how Panax species and their BCs modulate acquired immune responses involving interactions between dendritic cells and T cells, reduce the pro-inflammatory responses of epithelial cells, and reduce allergenic responses from basophils and mast cells in vitro. In addition, we highlight the current understanding of the alleviative effects of Panax species and their BCs against AA and AR in vivo. Moreover, we discuss the unmet needs of research and considerations for the treatment of patients to provide basic scientific knowledge for the treatment of AADs using Panax species and their BCs.