Astragalus mongholicus bunge and panax notoginseng formula (A&P) improves renal fibrosis in UUO mice via inhibiting the long non-coding RNA A330074K22Rik and downregulating ferroptosis signaling.

BACKGROUND: Chronic kidney disease (CKD) and its associated end-stage renal disease (ESRD) are significant health problems that pose a threat to human well-being. Renal fibrosis is a common feature and ultimate pathological outcome of various CKD leading to ESRD. The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a refined compound formulated by our research group, which has been clinically administered for over a decade and has demonstrated the ability to improve the inflammatory state of various acute or chronic kidney diseases. However, the underlying mechanism by which A&P ameliorates renal fibrosis remains unclear. METHODS: We established a mouse model by surgically ligating the unilateral ureter to induce renal injury in vivo. And we utilized renal in situ electroporation of a plasmid with low LncRNA A33 expression to establish the unilateral ureteral obstruction(UUO)mouse model. In vitro, we stimulated primary tubular epithelial cells(pTEC) injury using TGF-ß1, siRNA-A33, and pcDNA3.1-A33 plasmids were transfected into pTECs to respectively knockdown and overexpress LncRNA A33, and both in vitro and in vivo models were intervened with A&P. RESULTS: The results demonstrated that A&P effectively alleviated renal fibrosis in mice. Subsequent findings indicated high expression of LncRNA A33 in the kidneys of UUO mice and TGF-ß1-induced renal tubular cells. In situ, renal electroporation of a plasmid with reduced LncRNA A33 expression revealed that inhibiting LncRNA A33 significantly improved renal fibrosis in UUO mice. Moreover, A&P effectively suppressed LncRNA A33 expression both in vitro and in vivo. Subsequent downregulation of LncRNA A33 in renal tubular epithelial cells resulted in the downregulation of numerous fibrotic markers, a significant inhibition of LncRNA A33, and a notable reduction in downstream ferroptosis signaling. Cell experiments demonstrated that A&P improved renal fibrosis in UUO mice by inhibiting LncRNA A33 and downregulating ferroptosis signaling. CONCLUSION: Through the inhibition of LncRNA A33 and subsequent downregulation of ferroptosis signaling, A&P showed potential as a therapeutic approach for improving renal fibrosis in UUO mice, providing a potential treatment avenue for CKD.

A Versatile ß-Glycosidase from Petroclostridium xylanilyticum Prefers the Conversion of Ginsenoside Rb3 over Rb1, Rb2, and Rc to Rd by Its Specific Cleavage Activity toward 1,6-Glycosidic Linkages.

To convert ginsenosides Rb1, Rb2, Rb3, and Rc into Rd by a single enzyme, a putative ß-glycosidase (Pxbgl) from the xylan-degrading bacterium Petroclostridium xylanilyticum was identified and used. The kcat/Km value of Pxbgl for Rb3 was 18.18 ± 0.07 mM-1/s, which was significantly higher than those of Pxbgl for other ginsenosides. Pxbgl converted almost all Rb3 to Rd with a productivity of 5884 µM/h, which was 346-fold higher than that of only ß-xylosidase from Thermoascus aurantiacus. The productivity of Rd from the Panax ginseng root and Panax notoginseng leaf was 146 and 995 µM/h, respectively. Mutants N293 K and I447L from site-directed mutagenesis based on bioinformatics analysis showed an increase in specific activity of 29 and 7% toward Rb3, respectively. This is the first report of a ß-glycosidase that can simultaneously remove four different glycosyls at the C-20 position of natural PPD-type ginsenosides and produce Rd as the sole product from P. notoginseng leaf extracts with the highest productivity.

Screening of GLP-1r agonists from natural products using affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology: a case study of Panax ginseng.

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.

Effect of saponins in Panax notoginseng (Burkill) F. H. Chen on the steroid hormone levels in the chronic unpredictable mild stress model of depression in rats.

Recent research has indicated that Panax notoginseng saponins (PNS) extracted from the radix of Panax notoginseng (Burkill) F. H. Chen exert antidepressant effects. This study aimed to assess the antidepressive effects of ginsenoside Rg1 and PNS in a depression model induced by chronic unpredictable mild stress (CUMS). Over a period of three weeks, rats were administered ginsenoside Rg1 at a dose of 30 mg/kg and PNS at dosages ranging from 100 to 200 mg/kg body weight per day. To assess how ginsenoside Rg1 and PNS influence depression-like behaviours in rats, various assessments were conducted, including coat state evaluation, forced swim test, and elevated plus maze test. The levels of cortisol and testosterone in serum samples were analysed using the liquid chromatography-electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) method. LC-ESI-MS/MS method provides precise and accurate results. The lower limit of quantification values for cortisol and testosterone were determined as 100 and 2 pg/mL, respectively. Our data demonstrated that both ginsenoside Rg1 and PNS significantly reversed depression-like behaviour in rats by improving coat condition, reducing immobility time in the forced swim test, and increasing time spent in the open arms of the elevated plus maze test. Furthermore, ginsenoside Rg1 and PNS exhibited a regulatory effect on cortisol and testosterone levels in plasma. These findings suggest that ginsenoside Rg1 and PNS may be potential antidepressants in clinical treatment.

Overview of Panax ginseng and its active ingredients protective mechanism on cardiovascular diseases.

ETHNIC PHARMACOLOGICAL RELEVANCE: Panax ginseng is a traditional Chinese herbal medicine used to treat cardiovascular diseases (CVDs), and it is still widely used to improve the clinical symptoms of various CVDs. However, there is currently a lack of summary and analysis on the mechanism of Panax ginseng exerts its cardiovascular protective effects. This article provides a review of in vivo and in vitro pharmacological studies on Panax ginseng and its active ingredients in reducing CVDs damage. AIM OF THIS REVIEW: This review summarized the latest literature on Panax ginseng and its active ingredients in CVDs research, aiming to have a comprehensive and in-depth understanding of the cardiovascular protection mechanism of Panax ginseng, and to provide new ideas for the treatment of CVDs, as well as to optimize the clinical application of Panax ginseng. METHODS: Enrichment of pathways and biological terms using the traditional Chinese medicine molecular mechanism bioinformatics analysis tool (BATMAN-TCM). The literature search is based on electronic databases such as PubMed, ScienceDirect, Scopus, CNKI, with a search period of 2002-2023. The search terms include Panax ginseng, Panax ginseng ingredients, ginsenosides, ginseng polysaccharides, ginseng glycoproteins, ginseng volatile oil, CVDs, heart, and cardiac. RESULTS: 132 articles were ultimately included in the review. The ingredients in Panax ginseng that manifested cardiovascular protective effects are mainly ginsenosides (especially ginsenoside Rb1). Ginsenosides protected against CVDs such as ischemic reperfusion injury, atherosclerosis and heart failure mainly through improving energy metabolism, inhibiting hyper-autophagy, antioxidant, anti-inflammatory and promoting secretion of exosomes. CONCLUSION: Panax ginseng and its active ingredients have a particularly prominent effect on improving myocardial energy metabolism remodeling in protecting against CVDs. The AMPK and PPAR signaling pathways are the key targets through which Panax ginseng produces multiple mechanisms of cardiovascular protection. Extracellular vesicles and nanoparticles as carriers are potential delivery ways for optimizing the bioavailability of Panax ginseng and its active ingredients.

Widely Targeted Metabolomic Analysis Reveals the Improvement in Panax notoginseng Triterpenoids Triggered by Arbuscular Mycorrhizal Fungi via UPLC-ESI-MS/MS.

Panax notoginseng is a highly valued perennial medicinal herb in China and is widely used in clinical treatments. The main purpose of this study was to elucidate the changes in the composition of P. notoginseng saponins (PNSs), which are the main bioactive substances, triggered by arbuscular mycorrhizal fungi (AMF) via ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). A total of 202 putative terpenoid metabolites were detected, of which 150 triterpene glycosides were identified, accounting for 74.26% of the total. Correlation analysis, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of the metabolites revealed that the samples treated with AMF (group Ce) could be clearly separated from the CK samples. In total, 49 differential terpene metabolites were identified between the Ce and CK groups, of which 38 and 11 metabolites were upregulated and downregulated, respectively, and most of the upregulated differentially abundant metabolites were mainly triterpene glycosides. The relative abundances of the two major notoginsenosides (MNs), ginsenosides Rd and Re, and 13 rare notoginsenosides (RNs), significantly increased. The differential saponins, especially RNs, were more easily clustered into one branch and had a high positive correlation. It could be concluded that the biosynthesis and accumulation of some RNs share the same pathways as those triggered by AMF. This study provides a new way to obtain more notoginsenoside resources, particularly RNs, and sheds new light on the scientization and rationalization of the use of AMF agents in the ecological planting of medicinal plants.

[Isolation and identification of malonyl ginsenoside-Ra_1 and malonyl ginsenoside-Ra_2 from fresh roots of Panax 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-\[6-O-malonyl-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,20S-triol(1) and 3-O-\[6-O-malonyl-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1→2)-α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,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.

Effects of Panax species and their bioactive components on allergic airway diseases.

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.

Systematic exploration of therapeutic effects and key mechanisms of Panax ginseng using network-based approaches.

Background: Network pharmacology has emerged as a powerful tool to understand the therapeutic effects and mechanisms of natural products. However, there is a lack of comprehensive evaluations of network-based approaches for natural products on identifying therapeutic effects and key mechanisms. Purpose: We systematically explore the capabilities of network-based approaches on natural products, using Panax ginseng as a case study. P. ginseng is a widely used herb with a variety of therapeutic benefits, but its active ingredients and mechanisms of action on chronic diseases are not yet fully understood. Methods: Our study compiled and constructed a network focusing on P. ginseng by collecting and integrating data on ingredients, protein targets, and known indications. We then evaluated the performance of different network-based methods for summarizing known and unknown disease associations. The predicted results were validated in the hepatic stellate cell model. Results: We find that our multiscale interaction-based approach achieved an AUROC of 0.697 and an AUPR of 0.026, which outperforms other network-based approaches. As a case study, we further tested the ability of multiscale interactome-based approaches to identify active ingredients and their plausible mechanisms for breast cancer and liver cirrhosis. We also validated the beneficial effects of unreported and top-predicted ingredients, in cases of liver cirrhosis and gastrointestinal neoplasms. Conclusion: our study provides a promising framework to systematically explore the therapeutic effects and key mechanisms of natural products, and highlights the potential of network-based approaches in natural product research.

Effects of exogenous copper on microbial metabolic function and carbon use efficiency of Panax notoginseng planting soil.

Soil copper (Cu) pollution is a serious environmental risk in the Panax notoginseng planting area. However, the effect of Cu on soil microbial metabolism and nutrient cycling in this area remains unknown. Therefore, Biolog ECO-plate and enzyme stoichiometry methods were utilized in this study to investigate the impact of exogenous Cu (control: 0 mg·kg-1; Cu100: 100 mg·kg-1; Cu400: 400 mg·kg-1; and Cu600: 600 mg·kg-1) on the metabolic function of soil microbial and nutrient limitation in the P. notoginseng soil. The results indicated that Cu100 significantly increased soil organic carbon (SOC), total phosphorus (TP), soil C:N, microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) 9.89%, 15.65%, 17.91%, 61.87%, and 90.56% higher than the control, respectively. Moreover, the carbon source utilization ratio of carbohydrates, amino acids, and amphiphilic compounds of Cu100 also increased by 7.16%, 25.47%, and 84.68%, respectively, compared with the control. The activities of ß-1,4-glucosidase, cellobiohyrolase, leucine amino peptidase, ß-1,4-N-acetylglucosaminidase, and phosphatase significantly decreased with increasing Cu concentration. Soil enzyme stoichiometry showed that all treatments were limited by nitrogen (vector angle < 45°; 19.045-22.081). Cu600 led to the lowest carbon limitation (1.798) and highest carbon use efficiency (CUE:0.267). The PLS-SEM model also showed that MBC, MBN, MBP, and microbial diversity positively affected carbon and nitrogen limitation (0.654 and 0.424). Soil carbon, nitrogen, phosphorus, stoichiometric ratio, MBC, MBN, and MBP positively affected CUE (0.527 and 0.589). The microbial diversity index significantly negatively affected CUE (-1.490). Multiple linear stepwise regression analyses showed that CUE was mainly influenced by MBC, AP, C:P, and LAP. Thus, P. notoginseng soil can benefit soil microbial carbon and nitrogen limitations at low Cu concentrations. Clarifying the metabolic activity and nutritional status of microorganisms under Cu stress can provide some theoretical basis for realizing China's comprehensive and effective management and control policies for environmental risks from metals by 2035.

A ginseng polysaccharide protects intestinal barrier integrity in high-fat diet-fed obese mice.

A novel polysaccharide, GPH1, was extracted and isolated from ginseng. Structural analysis of GPH1 revealed a molecular weight of 7.321 × 105 Da and the presence of glucose and galactose components in a 30.2: 1 molar ratio. Results of methylation and NMR analyses indicated the GPH1 backbone consisted of →1)-α-Glc-(3→ and →1)-α-Glc-(6→. The anti-obesity activity of GPH1 was assessed by HFD-induced obesity mouse model. GPH1 was found to significantly reduced body weight, alleviated liver lipid accumulation and inflammatory damage. Meanwhile, GPH1 treatment increased the expression of tight junction proteins, including zonula occludens-1 (ZO-1) and claudin-1, while also regulating the intestinal microbiota of obese mice by promoting proliferation of beneficial bacteria with known anti-obesity effects, including s_Akkermansia muciniphila, s_Lactobacillus intestinalis, s_Lactobacillus reuteri, s_Streptococcus hyointestinalis, and s_Lactococcus garvieae. Our findings demonstrated that GPH1 is a practical natural dietary supplement with potential therapeutic effects on obesity.

Analyzing noncovalent interactions between notoginseng saponins and lysozyme by deposition scanning intensity fading MALDI-TOF mass spectrometry.

Analysis of noncovalent interactions between natural products and proteins is important for rapid screening of active ingredients and understanding their pharmacological activities. In this work, the intensity fading MALDI-TOF mass spectrometry (IF-MALDI-MS) method with improved reproducibility was implemented to investigate the binding interactions between saponins from Panax notoginseng and lysozyme. The benchmark IF-MALDI-MS experiment was established using N,N',N″-triacetylchitotriose-lysozyme as a model system. The reproducibility of ion intensities in IF-MALDI-MS was improved by scanning the whole sample deposition with a focused laser beam. The relative standard deviation (RSD) of deposition scanning IF-MALDI-MS is 5.7%. Similar decay trends of the relative intensities of notoginseng saponins against increasing amounts of lysozyme were observed for all six notoginseng saponins. The half-maximal fading concentration (FC50) was calculated to quantitatively characterize the binding affinity of each ligand based on the decay curve. According to the FC50 values obtained, the binding affinities of the six notoginseng saponins were evaluated in the following order: notoginsenoside S > notoginsenoside Fc > ginsenoside Rb1 > ginsenoside Rd > notoginsenoside Ft1 > ginsenoside Rg1. The binding order was in accordance with molecular docking studies, which showed hydrogen bonding might play a key role in stabilizing the binding interaction. Our results demonstrated that deposition scanning IF-MALDI-MS can provide valuable information on the noncovalent interactions between ligands and proteins.

Transcriptomic Analysis Under Drought and Salt Stress Provides Insight into Genes Putatively Involved in Ginsenoside Biosynthesis in Panax japonicus Meyer.

Panax japonicus Meyer, a perennial herb of the dicotyledonaceae family Araliaceae, is a rare folk traditional Chinese medicine, known as "the king of herbal medicine" in China. To understand the genes involved in secondary pathways under drought and salt stress, the transcriptomic analysis of P. japonicus is of vital importance. The transcriptome of underground rhizomes, stems, and leaves under drought and salt stress in P. japonicus were performed using the Illumina HiSeq platform. After de novo assembly of transcripts, expression profiling and identified differentially expressed genes (DEGs) were performed. Furthermore, putative functions of identified DEGs correlated with ginsenoside in P. japonicus were explored using Gene Ontology terms and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis. A total of 221,804 unigenes were obtained from the transcriptome of P. japonicus. The further analysis revealed that 10,839 unigenes were mapped to 91 KEGG pathways. Furthermore, a total of two metabolic pathways of P. japonicus in response to drought and salt stress related to triterpene saponin synthesis were screened. The sesquiterpene and triterpene metabolic pathways were annotated and finally putatively involved in ginsenoside content and correlation analysis of the expression of these genes were analyzed to identify four genes, ß-amyrin synthase, isoprene synthase, squalene epoxidase, and 1-deoxy-D-ketose-5-phosphate synthase, respectively. Our results paves the way for screening highly expressed genes and mining genes related to triterpenoid saponin synthesis. It also provides valuable references for the study of genes involved in ginsenoside biosynthesis and signal pathway of P. japonicus.

The use of Panax notoginseng saponins injections after intravenous thrombolysis in acute ischemic stroke: a systematic review and meta-analysis.

Background: As a bioactive metabolite preparation widely used in acute ischemic stroke (AIS), the efficacy and safety of Panax notoginseng saponins injections (PNSI) in patients with AIS after intravenous thrombolysis remain to be evaluated. Methods: This study included randomized controlled trials published before 26 April 2024 in 8 databases. AIS patients who received intravenous thrombolysis were included. The control group receiving conventional treatment and the treatment group receiving additional PNSI. Primary outcomes were selected as mortality, disability, and adverse events. Secondary outcomes were selected as all-cause mortality, improvement of neurological deficit, quality of life, and cerebral injury indicators. The revised Cochrane Risk of Bias tool was used to assess risk of bias. Risk ratio (RR) and mean differences (MD) were calculated for binary variables and continuous variables, respectively, based on a 95% confidence interval (CI). Results: A total of 20 trials involving 1,856 participants were included. None of them reported mortality or disability. There was no significant difference in the adverse events [RR: 1.04; 95% CI: 0.60 to 1.81] and hemorrhagic transformation [RR: 0.99; 95% CI: 0.36 to 2.70] between the two groups. Compared to the control group, the treatment group had a better effect in neurological improvement assessed by National Institutes of Health Stroke Scale [MD: -2.91; 95% CI: -4.76 to -1.06], a better effect in activities of daily living changes in Barthel Index [MD: 9.37; 95% CI: 1.86 to 16.88], and a lower serum neuron-specific enolase level [MD: -2.08; 95% CI: -2.67 to -1.49]. Conclusion: For AIS patients undergoing intravenous thrombolysis, the use of PNSI improved neurological deficits and enhanced activity of daily living in the short term without increasing the occurrence rate of adverse events. However, due to the moderate to very low certainty of evidence, it is advisable to conduct high-quality clinical trials to validate the findings of this study. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=466851, Identifier CRD42023466851.

Targeting MAPK14 in microglial cells: neuroimmune implications of Panax ginseng in post-stroke inflammation.

AIM: This study investigates the molecular mechanisms through which Panax ginseng and Panax notoginseng saponin (PNS) mitigate neuroinflammatory damage and promote neural repair postischemic stroke, utilizing bioinformatics, and experimental approaches. BACKGROUND: Cerebral infarction significantly contributes to disability worldwide, with chronic neuroinflammation worsening cognitive impairments and leading to neurodegenerative diseases. Addressing neuroimmune interactions is crucial for slowing disease progression and enhancing patient recovery, highlighting the need for advanced research in neuroimmune regulatory mechanisms and therapeutic strategies. OBJECTIVE: To elucidate the effects of the traditional Chinese medicine components Panax ginseng and PNS on neuroinflammatory damage following ischemic stroke, focusing on the molecular pathways involved in mitigating inflammation and facilitating neural repair. METHODS: The study employs single-cell sequencing and transcriptomic analysis to investigate gene expression changes associated with cerebral infarction. Gene set enrichment analysis and weighted gene co-expression network analysis are used to identify key molecular markers and core genes. Furthermore, pharmacological profiling, including functional assays, assesses the impact of Ginsenoside-Rc, a PNS derivative, on microglial cell viability, cytokine production, and reactive oxygen species (ROS) levels. RESULTS: Our analysis revealed that MAPK14 is a critical mediator in the neuroinflammatory response to ischemic stroke. Ginsenoside-Rc potentially targets and modulates MAPK14 activity to suppress inflammation. Experimental validation showed that Ginsenoside-Rc treatment, combined with MAPK14 silencing, significantly alters MAPK14 expression and mitigates neuroinflammatory damage, evidenced by reduced microglial cell death, inflammatory factor secretion, and ROS production. CONCLUSION: Ginsenoside-Rc's modulation of MAPK14 offers a promising therapeutic strategy for reducing neuroinflammation and potentially improving cognitive recovery post-ischemic stroke. This supports the therapeutic application of the traditional Chinese medicine Sanqi in ischemic stroke care, providing a theoretical and experimental foundation for its use. OTHERS: Future work will focus on extending these findings through clinical trials to evaluate the efficacy and safety of Ginsenoside-Rc in human subjects, aiming to translate these promising preclinical results into practical therapeutic interventions for ischemic stroke recovery.

Comparative Metabolome and Transcriptome Analyses Reveal Differential Enrichment of Metabolites with Age in Panax notoginseng Roots.

Panax notoginseng is a perennial plant well known for its versatile medicinal properties, including hepatoprotective, antioxidant, anti-inflammatory, anti-tumor, estrogen-like, and antidepressant characteristics. It has been reported that plant age affects the quality of P. notoginseng. This study aimed to explore the differential metabolome and transcriptome of 2-year (PN2) and 3-year-old (PN3) P. notoginseng plant root samples. Principal component analysis of metabolome and transcriptome data revealed major differences between the two groups (PN2 vs. PN3). A total of 1813 metabolites and 28,587 genes were detected in this study, of which 255 metabolites and 3141 genes were found to be differential (p < 0.05) between PN2 vs. PN3, respectively. Among differential metabolites and genes, 155 metabolites and 1217 genes were up-regulated, while 100 metabolites and 1924 genes were down-regulated. The KEGG pathway analysis revealed differentially enriched metabolites belonging to class lipids ("13S-hydroperoxy-9Z, 11E-octadecadionic acid", "9S-hydroxy-10E, 12Z-octadecadionic acid", "9S-oxo-10E, 12Z-octadecadionic acid", and "9,10,13-trihydroxy-11-octadecadionic acid"), nucleotides and derivatives (guanine and cytidine), and phenolic acids (chlorogenic acid) were found to be enriched (p < 0.05) in PN3 compared to PN2. Further, these differentially enriched metabolites were found to be significantly (p < 0.05) regulated via linoleic acid metabolism, nucleotide metabolism, plant hormone signal transduction, and arachidonic acid metabolism pathways. Furthermore, the transcriptome analysis showed the up-regulation of key genes MAT, DMAS, SDH, gallate 1-beta-glucosyltransferase, and beta-D-glucosidase in various plants' secondary metabolic pathways and SAUR, GID1, PP2C, ETR, CTR1, EBF1/2, and ERF1/2 genes observed in phytohormone signal transduction pathway that is involved in plant growth and development, and protection against the various stressors. This study concluded that the roots of a 3-year-old P. notoginseng plant have better metabolome and transcriptome profiles compared to a 2-year-old plant with importantly enriched metabolites and genes in pathways related to metabolism, plant hormone signal transduction, and various biological processes. These findings provide insights into the plant's dynamic biochemical and molecular changes during its growth that have several implications regarding its therapeutic use.

Protective effects of Panax ginseng as a medical food against chemical toxic agents: molecular and cellular mechanisms.

Humans are exposed to different types of toxic agents, which may directly induce organ malfunction or indirectly alter gene expression, leading to carcinogenic and teratogenic effects, and eventually death. Ginseng (Panax ginseng) is the most valuable of all medicinal herbs. Nevertheless, specific data on the antidotal mechanisms of this golden herb are currently unavailable. Based on the findings of in vitro, in vivo, and clinical studies, this review focused on the probable protective mechanisms of ginseng and its major components, such as protopanaxadiols, protopanaxatriols, and pentacyclic ginsenosides against various chemical toxic agents. Relevant articles from 2000 to 2023 were gathered from PubMed/Medline, Scopus, and Google Scholar. This literature review shows that P. ginseng and its main components have protective and antidotal effects against the deteriorative effects of pesticides, pharmaceutical agents, including acetaminophen, doxorubicin, isoproterenol, cyclosporine A, tacrolimus, and gentamicin, ethanol, and some chemical agents. These improvements occur through multi-functional mechanisms. They exhibit antioxidant activity, induce anti-inflammatory action, and block intrinsic and extrinsic apoptotic pathways. However, relevant clinical trials are necessary to validate the mentioned effects and translate the knowledge from basic science to human benefit, fulfilling the fundamental goal of all toxicologists.

Panax Notoginseng Saponins Regulate Angiogenic Cytokines Through the PI3K/AKT/mTOR Signaling Pathway to Promote Fracture Healing in Ovariectomized Rats.

Osteoporotic fractures seriously affect the quality of life of the elderly. Panax notoginseng saponins (PNS) have the potential function of preventing osteoporosis. The Phosphatidylinositol 3-kinase (PI3K)/protein kinase (AKT)/mammalian target of rapamycin (mTOR) pathway is involved in the regulation of osteoporosis and has been proven to be related to VEGF secretion and angiogenesis. Therefore, this study aimed to explore the effects of PNS on ovariectomized rats with osteoporotic fracture through the PI3K/AKT/mTOR pathway and angiogenesis-related factors. Female Sprague-Dawley rats were randomly divided into normal control, fracture model, ovariectomized fracture model, low-dose PNS (100 mg/kg/d), and high-dose PNS (200 mg/kg/d). The ovariectomized rat fracture model was established. In low and high dose groups, PNS was administered intraperitoneally. The vascularization of fracture ends was detected in vitro by micro-CT on the 7th, 14th, and 21st day after modeling, and the area and number of blood vessels in the unit field of vision of the callus healing plane were seen by hematoxylin-eosin staining. The expression levels of PI3K, AKT1, mTOR, hypoxia inducible factor-1; VEGF: vascular endothelial growth factor (HIF-1), VEGF, Ang-1, VEGFR2, and angiopoietin like 2 Gene (ANGPTL2) were determined using Western blotting. In the PNS treatment group, the area of cortical bone increased, the area of callus decreased, and the number and area of blood vessels increased significantly when compared with the ovariectomized fracture model group. PNS regulates the PI3K/AKT/mTOR signaling pathway and promotes the expression of vascular-related cytokines (VEGF, Ang-1, VEGFR2, and ANGPTL2) in osteoporotic fractures. PNS may regulate the expression of vascular-related factors through the PI3K/AKT/mTOR pathway and promote the healing of osteoporotic fractures in ovariectomized rats.

Genome-wide identification and integrated analysis of the FAR1/FHY3 gene family and genes expression analysis under methyl jasmonate treatment in Panax ginseng C. A. Mey.

Ginseng (Panax ginseng C. A. Mey.) is an important and valuable medicinal plant species used in traditional Chinese medicine, and its metabolite ginsenoside is the primary active ingredient. The FAR1/FHY3 gene family members play critical roles in plant growth and development as well as participate in a variety of physiological processes, including plant development and signaling of hormones. Studies have indicated that methyl jasmonate treatment of ginseng adventitious roots resulted in a significant increase in the content of protopanaxadiol ginsenosides. Therefore, it is highly significant to screen the FAR1/FHY3 gene family members in ginseng and preliminarily investigate their expression patterns in response to methyl jasmonic acid signaling. In this study, we screened and identified the FAR1/FHY3 family genes in the ginseng transcriptome databases. And then, we analyzed their gene structure and phylogeny, chromosomal localization and expression patterns, and promoter cis-acting elements, and made GO functional annotations on the members of this family. After that, we treated the ginseng adventitious roots with 200 mM methyl jasmonate and investigated the trend of the expression of four genes containing the largest number of methyl jasmonate cis-acting elements at different treatment times. All four genes were able to respond to methyl jasmonate, the most significant change was in the PgFAR40 gene. This study provides data support for subsequent studies of this family member in ginseng and provides experimental reference for subsequent validation of the function of this family member under methyl jasmonic acid signaling.

Temporal heterogeneity of the root microbiome in Panax ginseng soils across ecological compartments under mild soil disturbance.

Introduction: Knowledge on spatiotemporal heterogeneity of plant root microbiomes is lacking. The diversity of the root microbiome must be revealed for understanding plant-microbe interactions and the regulation of functionally crucial microbial taxa. Methods: We here investigated the dynamics of microbial group characteristics within each soil ecological compartment [rhizoplane (B), rhizosphere (J), and bulk soil (T)] across different cultivation years (year 4: F4 and year 5: F5) by using high-throughput sequencing (16S and ITS). Results: According to the species diversity, microbiome diversity and the ASV (amplified sequence variant) number in the rhizoplane ecotone increased significantly with an increase in the planting years. By contrast, the microbiome diversity of the rhizosphere soil remained relatively stable. PCoA and PERMANOVA analyses revealed that microbial taxa among different planting years and ecological compartments varied significantly. Planting years exerted the least effect on the rhizosphere microbiome, but their impact on fungi in the rhizoplane and bacteria in the bulk soil was the most significant. Discussion: Planting years influenced the microbial community composition in various ecological compartments of ginseng root soil. Potentially harmful fungi such as Cryptococcus (2.83%), Neonectria (0.89%), llyonectria (0.56%), Gibberella (0.41%), Piloderma (4.44%), and Plectosphaerella (3.88%) were enriched in F5B with an increase in planting years, whereas the abundance of potentially beneficial Mortierella increased. Correlation analysis indicated associations between bacterial taxa and soil pH/S-CAT, and between fungal taxa and soil moisture content/total potassium. Our study highlights the significance of changes in rhizoplane fungi and the stability of the rhizosphere microbial community in comprehending plant ecological sustainability.