Current evidence suggests a beneficial role of herbal products in free radical-induced diseases. Panax notoginseng (Burk.) F. H. Chen has long occupied a leading position in traditional Chinese medicine because of the ergogenic, nootropic, and antistress activities, although these properties are also acknowledged in the Western world. The goal of this paper is to review the pharmacological and toxicological properties of P. notoginseng and discuss its potential therapeutic effect. A literature search was carried out on Pubmed, Scopus, and the Cochrane Central Register of Controlled Trials databases. The following search terms were used: \"notoginseng\", \"gut microbiota\", \"immune system\", \"inflammation\", \"cardiovascular system\", \"central nervous system\", \"metabolism\", \"cancer\", and \"toxicology\". Only peer-reviewed articles written in English, with the full text available, have been included. Preclinical evidence has unraveled the P. notoginseng pharmacological effects in immune-inflammatory, cardiovascular, central nervous system, metabolic, and neoplastic diseases by acting on several molecular targets. However, few clinical studies have confirmed the therapeutic properties of P. notoginseng, mainly as an adjuvant in the conventional treatment of cardiovascular disorders. Further clinical studies, which both confirm the efficacy of P. notoginseng in free radical-related diseases and delve into its toxicological aspects, are mandatory to broaden its therapeutic potential.

Sepsis-induced acute lung injury (SALI) poses a significant threat with high incidence and mortality rates. Ginsenoside Rg1 (GRg1), derived from Ginseng in traditional Chinese medicine, has been found to reduce inflammation and protect lung epithelial cells against tissue damage. However, the specific roles and mechanisms by which GRg1 mitigates SALI have yet to be fully elucidated. In this context, we employed a relevant SALI mouse model, alongside network pharmacology, molecular docking, and molecular dynamics simulation to pinpoint GRg1\'s action targets, complemented by in vitro assays to explore the underlying mechanisms. Our research shows that GRg1 alleviates CLP-induced SALI, decreasing lung tissue damage and levels of serum proinflammatory factor IL-6, TNF-α, and IL-1β, also enhancing the survival rate of CLP mice. A total of 116 common targets between GRg1 and ALI, with specific core targets including AKT1, VEGFA, SRC, IGF1, ESR1, STAT3, and ALB. Further in vitro experiments assessed GRg1\'s intervention effects on MLE-12 cells exposed to LPS, with qRT-PCR analysis and molecular dynamics simulations confirming AKT1 as the key target with the favorable binding activity for GRg1. Western blot results indicated that GRg1 increased the Bcl-2/Bax protein expression ratio to reduce apoptosis and decreased the high expression of cleaved caspase-3 in LPS-induced MLE-12 cells. More results showed significant increases in the phosphorylation of PI3K and AKT1. Flow cytometric analysis using PI and Annexin-V assays further verified that GRg1 decreased the apoptosis rate in LPS-stimulated MLE-12 cells (from 14.85 to 6.54%, p < 0.05). The employment of the AKT1 inhibitor LY294002 confirmed these trends, indicating that AKT1\'s inhibition negates GRg1\'s protective effects on LPS-stimulated MLE-12 cells. In conclusion, our research highlights GRg1\'s potential as an effective adjunct therapy for SALI, primarily by inhibiting apoptosis in alveolar epithelial cells and reducing pro-inflammatory cytokine secretion, thus significantly enhancing the survival rates of CLP mice. These beneficial effects are mediated through targeting AKT1 and activating the PI3K-AKT pathway.

BACKGROUND: The ginseng endophyte Paenibacillus polymyxa Pp-7250 (Pp-7250) has multifaceted roles such as preventing ginseng diseases, promoting growth, increasing ginsenoside accumulation, and degrading pesticide residues, however, these effects still have room for improvements. Composite fungicides are an effective means to improve the biocontrol effect of fungicides, but the effect of Pp-7250 in combination with its symbiotic bacteria on ginseng needs to be further investigated, and its mechanism of action has not been elucidated. In this study, a series of experiments was conducted to elucidate the effect of Paenibacillus polymyxa and Bacillus cereus co-bacterial agent on the yield and quality of understory ginseng, and to investigate their mechanism of action.
RESULTS: The results indicated that P. polymyxa and B. cereus co-bacterial agent (PB) treatment improved ginseng yield, ginsenoside accumulation, disease prevention, and pesticide degradation. The mechanism is that PB treatment increased the abundance of beneficial microorganisms, including Rhodanobacter, Pseudolabrys, Gemmatimonas, Bacillus, Paenibacillus, Cortinarius, Russula, Paecilomyces, and Trechispora, and decreased the abundance of pathogenic microorganisms, including Ellin6067, Acidibacter, Fusarium, Tetracladium, Alternaria, and Ilyonectria in ginseng rhizosphere soil. PB co-bacterial agents enhanced the function of microbial metabolic pathways, biosynthesis of secondary metabolites, biosynthesis of antibiotics, biosynthesis of amino acids, carbon fixation pathways in prokaryotes, DNA replication, and terpenoid backbone biosynthesis, and decreased the function of microbial plant pathogens and animal pathogens.
CONCLUSIONS: The combination of P. polymyxa and B. cereus may be a potential biocontrol agent to promote the resistance of ginseng to disease and improve the yield, quality, and pesticide degradation.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Ginsenoside may be an ideal agent for UC treatment. However, its efficacy and safety are unknown. We aim to conduct a systematic evaluation to assess the effects and potential mechanisms of ginsenosides in animal models of UC.
METHODS: Six electronic databases will be searched (PubMed, Embase, Web of Science, China Knowledge Network (CNKI), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge). SYRCLE list will be used to assess the quality of literature, and STATA 15.1 for data analysis. Time-dose effects analysis will be used to reveal the time-dosage response relations between ginsenosides and UC.
RESULTS: Ultimately, fifteen studies involving 300 animals were included. Preliminary evidence was shown that ginsenosides could reduce Disease Activity Index (DAI) scores, weight loss, histological colitis score (HCS), spleen weight, Malondialdehyde (MDA), Myeloperoxidase (MPO) activity, interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and increase colon length (CL), myeloperoxidase (GSH), interleukin 4 (IL-4), interleukin 10 (IL-10), Zonula Occludens-1 (ZO-1) and occludin. Results of time-dose interval analysis indicated that ginsenosides at a dosage of 5-200 mg/kg with an intervention time of 7-28 days were relatively effective.
CONCLUSIONS: Preclinical evidence suggests that ginsenoside is a novel treatment for UC. And the mechanisms of ginsenosides in treating UC may involve anti-inflammatory, antioxidant, barrier protection, intestinal flora regulation, and immune regulation. Although, due to the high heterogeneity, further large-scale and high-quality preclinical studies are needed to examine the protection of ginsenosides against UC.

American ginseng (AG) has been reported to have anti-inflammatory effects in many diseases, but the key molecules and mechanisms are unclear. This study aims to evaluate the anti-inflammatory mechanism of AG and identify the key molecules by in vivo and in vitro models. Zebrafish was employed to assess the anti-inflammatory properties of AG and the compounds. Metabolomics was utilized to identify potential anti-inflammatory molecules in AG, while molecular dynamics simulations were conducted to forecast the interaction capabilities of these compounds with inflammatory targets. Additionally, macrophage cell was employed to investigate the anti-inflammatory mechanisms of the key molecules in AG by enzyme-linked immunosorbent assay and western blotting. Seven potential anti-inflammatory molecules were discovered in AG, with ginsenoside Rg1, ginsenoside Rs3 (G-Rs3), and oleanolic acid exhibiting the strongest affinity for signal transducer and activator of transcription 3. These compounds demonstrated inhibitory effects on macrophage migration in zebrafish models and the ability to regulate ROS levels in both zebrafish and macrophages. The cell experiments found that ginsenoside Rg1, ginsenoside Rs3, and oleanolic acid could promote macrophage M2/M1 polarization ratio and inhibit phosphorylation overexpression of signal transducer and activator of transcription 3. This study revealed the key anti-inflammatory molecules and mechanisms of AG, and provided new evidence of anti-inflammatory for the scientific use of AG.

BACKGROUND: Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in diabetic cardiomyopathy. Ginsenoside Rb1 (Rb1) is a major pharmacologically active component of ginseng to treat cardiovascular diseases. Whether Rb1 treat diabetes injured heart remains unknown. This study was to investigate the effect of Rb1 on diabetes injured cardiac muscle tissue and to further investigate its possible molecular pharmacology mechanisms.
METHODS: Male Sprague-Dawley rats were injected streptozotocin solution for 2 weeks, followed 6 weeks Rb1 or insulin treatment. The activity of SOD, CAT, Gpx, and the levels of MDA was measured; histological and ultrastructure analyses, RyR2 activity and phosphorylated RyR2(Ser2808) protein expression analyses; and Tunel assay were performed.
RESULTS: There was decreased activity of SOD, CAT, Gpx and increased levels of MDA in the diabetic group from control. Rb1 treatment increased activity of SOD, CAT, Gpx and decreased the levels of MDA as compared with diabetic rats. Neutralizing the RyR2 activity significantly decreased in diabetes from control, and increased in Rb1 treatment group from diabetic group. The expression of phosphorylation of RyR2 Ser2808 was increased in diabetic rats from control, and were attenuated with insulin and Rb1 treatment. Diabetes increased the apoptosis rate, and Rb1 treatment decreased the apoptosis rate. Rb1 and insulin ameliorated myocardial injury in diabetic rats.
CONCLUSIONS: These data indicate that Rb1 could be useful for mitigating oxidative damage, reduced phosphorylation of RyR2 Ser2808 and decreased the apoptosis rate of cardiomyocytes in diabetic cardiomyopathy.

Panax ginseng C.A. Mey., known for its medicinal and dietary supplement properties, primarily contains pharmacologically active ginsenosides. However, the regulatory mechanisms linking ginseng root development with ginsenoside biosynthesis are still unclear. Root meristem growth factors (RGFs) are crucial for regulating plant root growth. In our study, we identified five ginseng RGF peptide sequences from the ginseng genome and transcriptome libraries. We treated Arabidopsis and ginseng adventitious roots with exogenous Panax ginseng RGFs (PgRGFs) to assess their activities. Our results demonstrate that PgRGF1 influences gravitropic responses and reduces lateral root formation in Arabidopsis. PgRGF1 has been found to restrict the number and length of ginseng adventitious root branches in ginseng. Given the medicinal properties of ginseng, We determined the ginsenoside content and performed transcriptomic analysis of PgRGF1-treated ginseng adventitious roots. Specifically, the total ginsenoside content in ginseng adventitious roots decreased by 19.98 % and 63.71 % following treatments with 1 μM and 10 μM PgRGF1, respectively, compared to the control. The results revealed that PgRGF1 affects the accumulation of ginsenosides by regulating the expression of genes associated with auxin transportation and ginsenoside biosynthesis. These findings suggest that PgRGF1, as a peptide hormone regulator in ginseng, can modulate adventitious root growth and ginsenoside accumulation.

Ginsenosides, the primary bioactive ingredients derived from the root of Panax ginseng, are eagerly in demand for tumor patients as a complementary and alternative drug. Ginsenosides have increasingly become a \"hot topic\" in recent years due to their multifunctional role in treating colorectal cancer (CRC) and regulating tumor microenvironment (TME). Emerging experimental research on ginsenosides in the treatment and immune regulation of CRC has been published, while no review sums up its specific role in the CRC microenvironment. Therefore, this paper systematically introduces how ginsenosides affect the TME, specifically by enhancing immune response, inhibiting the activation of stromal cells, and altering the hallmarks of CRC cells. In addition, we discuss their impact on the physicochemical properties of the tumor microenvironment. Furthermore, we discuss the application of ginsenosides in clinical treatment as their efficacy in enhancing tumor patient immunity and prolonging survival. The future perspectives of ginsenoside as a complementary and alternative drug of CRC are also provided. This review hopes to open up a new horizon for the cancer treatment of Traditional Chinese Medicine monomers.

Ginseng (Panax ginseng C. A. Meyer) is an ancient and valuable Chinese herbal medicine, and ginsenoside, as the main active ingredient of ginseng, has received wide attention because of its various pharmacological active effects. Cytochrome P450 is the largest family of enzymes in plant metabolism and is involved in the biosynthesis of terpenoids, alkaloids, lipids, and other primary and secondary plant metabolites. It is significant to explore more PgCYP450 genes with unknown functions and reveal their roles in ginsenoside synthesis. In this study, based on the five PgCYP450 genes screened in the pre-laboratory, through the correlation analysis with the content of ginsenosides and the analysis of the interactions network of the key enzyme genes for ginsenoside synthesis, we screened out those highly correlated with ginsenosides, PgCYP309, as the target gene from among the five PgCYP450 genes. Methyl jasmonate-induced treatment of ginseng adventitious roots showed that the PgCYP309 gene responded to methyl jasmonate induction and was involved in the synthesis of ginsenosides. The PgCYP309 gene was cloned and the overexpression vector pBI121-PgCYP309 and the interference vector pART27-PgCYP309 were constructed. Transformation of ginseng adventitious roots by the Agrobacterium fermentum-mediated method and successful induction of transgenic ginseng hairy roots were achieved. The transformation rate of ginseng hairy roots with overexpression of the PgCYP309 gene was 22.7%, and the transformation rate of ginseng hairy roots with interference of the PgCYP309 gene was 40%. Analysis of ginseng saponin content and relative gene expression levels in positive ginseng hairy root asexual lines revealed a significant increase in PPD, PPT, and PPT-type monomeric saponins Re and Rg2. The relative expression levels of PgCYP309 and PgCYP716A53v2 genes were also significantly increased. PgCYP309 gene promotes the synthesis of ginsenosides, and it was preliminarily verified that PgCYP309 gene can promote the synthesis of dammarane-type ginsenosides.

BACKGROUND: Ginsenoside Rg3 is a component of ginseng that protects against myocardial ischemia/reperfusion (MI/R) injury. Ferroptosis is a new form of cell death characterized by oxidative damage to phospholipids. The purpose of this study was to examine the role and of ginsenoside Rg3 in MI/R and the mechanism.
METHODS: A mouse model of left anterior descending (LAD) ligation-induced myocardial ischemia/reperfusion (MI/R) injury and oxygen-glucose deprivation/reperfusion (OGD/R) were used as in vitro and in vivo models, respectively. Echocardiographic analysis, 2,3,5-triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (H&E) staining were used to assess the cardioprotective effects of ginsenoside Rg3. Western blotting, biochemical analysis, small interfering RNA analysis and molecular docking were performed to examine the underlying mechanism.
RESULTS: Ginsenoside Rg3 improved cardiac function and infarct size in mice with MI/R injury. Moreover, ginsenoside Rg3 increased the expression of the ferroptosis-related protein GPX4 and inhibited iron deposition in mice with MI/R injury. Ginsenoside Rg3 also activated the Nrf2 signaling pathway. Ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the Nrf2 signaling pathway. Notably, ginsenoside Rg3 regulated the keap1/Nrf2 signaling pathway to attenuate OGD/R-induced ferroptosis in H9C2 cells. Taken together, ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway.
CONCLUSIONS: Our findings demonstrated that ginsenoside Rg3 ameliorate MI/R-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway.