Effects of saponins Rb1 and Re in American ginseng intervention on intestinal microbiota of aging model.

Aging brings about physiological dysfunction, disease, and eventual mortality. An increasing number of studies indicate that aging can easily lead to dysbiosis of the gut microbiota, which can further affect digestion, nerves, cognition, emotions, and more. Therefore, gut bacteria play an important role in regulating the physical functions of aging populations. While saponins, the primary components of American ginseng, are frequently utilized for treating common ailments in the elderly due to their potent antioxidant properties, there is a scarcity of comprehensive studies on aging organisms. This study focused on 18 month old aging mice and investigated the effects of single intervention and combined intervention of Rb1 and Re, the main components of Panax quinquefolium saponins, on the gut microbiota of aging mice. High throughput 16s RNA gene sequencing analysis was performed on the gut contents of the tested mice, and the results showed that Rb1 and Re had a significant impact on the gut microbiota. Rb1, Re, and Rb1 + Re can effectively enhance the diversity of gut microbiota, especially in the combined Rb1 + Re group, which can recover to the level of young mice. Re can promote the abundance of probiotics such as Lactobacillus, Lactobacillaceae, and Lactobacillus, and inhibit the abundance of harmful bacteria such as Enterobacteriaceae. This indicates that the intervention of Rb1, Re, and Rb1 + Re can maintain the homeostasis of gut microbiota, and the combined application of Rb1 + Re has a better effect. The relationship between aging, brain gut axis, and gut microbiota is very close. Saponins can improve the gut microbiota of aging individuals by maintaining the balance of gut microbiota and the normal function of the brain gut axis, enabling the body to achieve a gut microbiota homeostasis closer to that of young healthy mice.

Nano-Characterization, Composition Analysis, and Anti-Inflammatory Activity of American-Ginseng-Derived Vesicle-like Nanoparticles.

Medicinal plant-derived vesicle-like nanoparticles can carry chemical components and exert intercellular activity due to the encapsulation of nanostructures. American ginseng is well known as a traditional herb and is commonly used in clinical decoctions. However, the nano-characteristics and chemical composition of American-ginseng-derived vesicle-like nanoparticles (AGVNs) in decoctions are unclear. In this study, the gradient centrifugation method was used to extract and isolate AGVNs. A metabolomic method based on high-resolution mass spectrometry was established to analyze small molecules loaded in AGVNs. Zebrafish and RAW264.7 cells were employed to investigate the anti-inflammatory effects of AGVNs. The results showed that the particle size of AGVNs was generally 243.6 nm, and the zeta potential was -14.5 mV. AGVNs were found to contain 26 ginsenosides (14 protopanaxadiols, 11 protopanaxatriols, and 1 oleanolic acid). Ginsenoside Rb1 and malonyl-ginsenoside Rb1 tended to be enriched in AGVNs. Moreover, AGVNs were found to exert anti-inflammatory effects by reducing macrophage migration in zebrafish and regulating inflammatory factor (NO, TNF-α, IL-6, IL-10) secretion in RAW 264.7 cells. The characterization and analysis of AGVNs provide references and data that support the development of nanoscale anti-inflammatory substances from medicinal plants.

Identification and mechanistic exploration of key anti-inflammatory molecules in American ginseng: Impacts on signal transducer and activator of transcription 3 STAT3 phosphorylation and macrophage polarization.

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.

Lipid discovered in American ginseng alleviates doxorubicin-induced cardiotoxicity by inhibiting cardiomyocyte ferroptosis.

Doxorubicin (Dox)-induced cardiotoxicity (DIC) has limited its clinical application. It is crucial to discover more effective substances to treat DIC. In this study, a zebrafish model is used to evaluate the inhibition of DIC in the lipids in American ginseng (AGL) compared with the lipids in soybeans (SOL) and in egg yolks (YOL). A lipidomics approach based on Q Exactive LC-MS/MS is employed to monitor, identify, and analyze the lipid composition of three lipid samples. The H9c2 cell was used to investigate the key lipid in AGL for its effect mechanism in alleviating DIC. The results showed that AGL alleviated DIC on zebrafish by increasing the stroke volume, heart rate, and fractional shortening compared to SOL and YOL. A total of 216 differential lipids were identified among the three types of lipids using lipidomics. Besides, a fatty acid with 18 carbons and four double bonds, FA (18:4) was the dominant proportion in AGL and possessed the highest variable importance of projection (VIP) value. FA (18:4) also showed significant bioactivity to alleviate DIC in zebrafish. Furthermore, FA (18:4) reduced the ferric ions and reactive oxygen species (ROS) accumulation, increased GPX4 expression, and relieved mitochondrial damage to inhibit Dox-induced ferroptosis in H9c2 cells. Therefore, the composition characteristic and anti-DIC effect of AGL were revealed; FA (18,4) was identified for the first time to be a novel active component of AGL against DIC by inhibiting ferroptosis. These results provide a new understanding of AG-derived bioactive lipids and their potential benefits for heart health.

Effects of enzymatic hydrolysis technology on the physicochemical properties and biological activities of American ginseng beverages.

American ginseng (Panax quinquefolius L.) contains various biological macromolecules, such as polysaccharides, saponins, and proteins, which have various pharmacological activities, including antioxidant, anti-inflammatory, and hypoglycemic effects. Consequently, the utilization of novel processing technologies developed an American ginseng beverage to meet people's health needs and the preferences of young people. This study was the first to use American ginseng as a primary raw material, utilizing a three-step enzymatic hydrolysis approach with cellulase, pectinase, amylase, maltase, and flavor protease enzymes to prepare an American ginseng beverage. The basic nutritional and active ingredient contents of the product were determined. The antioxidant activity of enzymatic beverages was evaluated by calculating the free radical clearance rates of DPPH and ABTS, and the effect of enzymatic beverages on α-glucosidase activity was also tested. The anti-inflammatory activity of RAW264.7 cells induced by LPS was evaluated by measuring the production of NO, TNF-α, and IL-6 during the enzymatic hydrolysis process. The results indicated that the nutritional components of American ginseng beverage products met the beverage industry standards. Moreover, the application of enzymatic hydrolysis technology had improved the antioxidant and anti-inflammatory activities of American ginseng beverages. In addition, the enzymatic beverage of American ginseng exhibited certain hypoglycemic activity. Consequently, the established enzymatic hydrolysis technology provided a reference for the production of other beverage products.

Characterization of the structure, anti-inflammatory activity and molecular docking of a neutral polysaccharide separated from American ginseng berries.

AIM: American ginseng berries, grown in the aerial parts and harvested in August, are a potentially valuable material. The aim of the study was to analyze the specific polysaccharides in American ginseng berries, and to demonstrate the anti-inflammation effect through in vitro and in vivo experiments and molecular docking. METHODS: After deproteinization and dialysis, the extracted crude polysaccharide was separated and purified. The structure of the specific isolated polysaccharide was investigated by Fourier Transform infrared spectroscopy (FT-IR), GC-MS and nuclear magnetic resonance (NMR), and anti-inflammatory activity was evaluated using in vitro and in vivo models (Raw 264.7 cells and zebrafish). Molecular docking was used to analyze the binding capacity and interaction with cyclooxygenase-2 (COX-2). RESULTS: A novel neutral polysaccharide fraction (AGBP-A) was isolated from American ginseng berries. The structural analysis demonstrated that AGBP-A had a weight-average molecular weight (Mw) of 122,988 Da with a dispersity index (Mw/Mn) value of 1.59 and was composed of arabinose and galactose with a core structure containing →6)-Gal-(1→ residues as the backbone and a branching substitution at the C3 position. The side-chains comprised of α-L-Ara-(1→, α-L-Ara-(1→, →5)-α-L-Ara-(1→, ß-D-Gal-(1→. The results showed that it significantly decreased pro-inflammatory cytokines in the cell model. In a zebrafish model, AGBP-A reduced the massive recruitment of neutrophils to the caudal lateral line neuromast, suggesting the relief of inflammation. Molecular docking was used to analyze the combined capacity and interaction with COX-2. CONCLUSION: Our study indicated the potential efficacy of AGBP-A as a safe and valid natural anti-inflammatory component.

Beneficial effects of American ginseng (Panax quinquefolius L.) extract residue as a feed additive on production, health status, and gastrointestinal bacteria in sika deer (Cervus nippon).

American ginseng residue is an industrial by-product of ginseng saponin extraction, including polysaccharides and amino acids; however, it is often discarded into the natural environment, representing a waste of resources as well as an environmental issue. In this study, we examined the effects of adding American ginseng residue to the basal diet of sika deer. Twelve antler-bearing male sika deer were assigned randomly to groups fed a diet supplemented with 0% (CON), 1% (LGR), and 3% (HGR) American ginseng residue, respectively, (n = 4 per group) for 5 weeks. Supplementation with 3% American ginseng residue significantly increased antler production and feed utilization efficiency in antler-bearing sika deer (p < 0.05). There were no significant differences in serum biochemical indexes among the three groups, but serum immunoglobulin A and glutathione peroxidase levels were significantly increased in the LGR and HGR groups (p < 0.05). Supplementation with American ginseng residue affected rumen fermentation in sika deer, significantly increasing the rumen contents of acetic acid, propionic acid, and total volatile fatty acids, and decreasing rumen fluid pH (p < 0.05), but had no significant effect on microbial protein or ammoniacal nitrogen content. American ginseng residue also affected the rumen bacterial composition, with significant up-regulation of Bacteroidota abundance in the HGR group, significant increases in Fibrobacterota and Fibrobacter abundance in the LGR group, and a significant decrease in Oscillospiraceae_UCG-005. Supplementation with ginseng residue had no significant effect on volatile fatty acids in the feces of sika deer, but did affect the composition of fecal bacteria, with significant decreases in Desulfobacterota and Rikenellaceae_RC9_gut_group in the HGR group, and a significant increase in Ruminococcus in the LGR group (p < 0.05). In addition, the abundance of Paeniclostridium in the feces decreased linearly with increasing concentration of ginseng residue, with a significant difference among the groups (p < 0.05). This study comprehensively evaluated the effects of American ginseng residue as a potential feed additive on the production performance and gastrointestinal bacterial community in antler-bearing sika deer. The results indicated that ginseng residue was a suitable feed additive for improving production performance and health in sika deer.

Panaxynol improves crypt and mucosal architecture, suppresses colitis-enriched microbes, and alters the immune response to mitigate colitis.

Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol-a novel, potent, bioavailable compound found in American ginseng-can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. Fourteen-week-old C57BL/6 female mice were either given three rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or one round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage three times per week for the study duration. Consistent with our previous findings, panaxynol significantly (P < 0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (P < 0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16S Sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). In addition, panaxynol significantly (P < 0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into the mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.NEW & NOTEWORTHY In the current study, we report that panaxynol ameliorates chemically induced murine colitis by improving colonic crypt and mucosal architecture, suppressing colitis-enriched microbes, reducing macrophages, and promoting the differentiation of regulatory T-cells in the colonic lamina propria. This study suggests that this novel natural compound may serve as a safe and effective treatment option for colitis patients.

Occurrence and health risk of pesticide residues in Chinese herbal medicines from Shandong Province, China.

Pesticide residue was one of the stress factors affecting quality and safety of Chinese herbal medicines (CHMs). The present study was designed to investigate the occurrence and dietary exposure of 70 pesticide residues in 307 samples of CHMs, including 104 American ginseng, 100 Ganoderma lucidum (G. lucidum), and 103 Dendrobium officinale (D. officinale) in Shandong Province, China. The study revealed that a total of 29 pesticides were detected in the majority (92.5%) of samples, and the pesticide residues of 85 (27.7%) samples exceeded the maximum residue levels (MRLs). Particularly, the maximum concentration of chlorpyrifos was 23.8 mg kg-1, almost 50 times of the MRLs in food in GB 2763-2021, while there's no standard restrictions specified in CHMs in China. The chronic, acute, and cumulative risk assessment results indicated that risk exposure of the three types of CHMs were unlikely to pose a health risk to consumers. However, more attention should be paid to the multiple residues with the presence of four or more pesticides in one sample and high over-standard rate of pesticides. The pesticide users and the government should pay more attention to the pesticides used in CHMs and regularly monitor the presence of these compounds. The study recommended the MRLs of these pesticides in CHMs should be established and perfected by the relevant departments in China.

Increasing the Amounts of Bioactive Components in American Ginseng (Panax quinquefolium L.) Leaves Using Far-Infrared Irradiation.

Both the roots and leaves of American ginseng contain ginsenosides and polyphenols. The impact of thermal processing on enhancing the biological activities of the root by altering its component composition has been widely reported. However, the effects of far-infrared irradiation (FIR), an efficient heat treatment method, on the bioactive components of the leaves remain to be elucidated. In the present study, we investigated the effects of FIR heat treatment between 160 and 200 °C on the deglycosylation and dehydration rates of the bioactive components in American ginseng leaves. As the temperature was increased, the amounts of common ginsenosides decreased while those of rare ginsenosides increased. After FIR heat treatment of American ginseng leaves at an optimal 190 °C, the highest total polyphenolic content and kaempferol content were detected, the antioxidant activity was significantly enhanced, and the amounts of the rare ginsenosides F4, Rg6, Rh4, Rk3, Rk1, Rg3, and Rg5 were 41, 5, 37, 64, 222, 17, and 266 times higher than those in untreated leaves, respectively. Moreover, the radical scavenging rates for 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and the reducing power of the treated leaf extracts were 2.17, 1.86, and 1.77 times higher, respectively. Hence, FIR heat treatment at 190 °C is an efficient method for producing beneficial bioactive components from American ginseng leaves.

Phenotypic and Genotypic Variation of Cultivated Panax quinquefolius.

American ginseng (Panax quinquefolius) is widely used due to its medicinal properties. Ontario is a major producer of cultivated American ginseng, where seeds were originally collected from the wild without any subsequent scientific selection, and thus the crop is potentially very diverse. A collection of 162 American ginseng plants was harvested from a small area in a commercial garden and phenotyped for morphological traits, such as root grade, stem length, and fresh and dry weights of roots, leaves, stems, and seeds. All of the traits showed a range of values, and correlations were observed between root and stem weights, root dry weight and leaf dry weight, as well as root and leaf fresh weights. The plants were also genotyped using single nucleotide polymorphisms (SNPs) at the PW16 locus. SNP analysis revealed 22 groups based on sequence relatedness with some groups showing no SNPs and others being more diverse. The SNP groups correlated with significant differences in some traits, such as stem length and leaf weight. This study provides insights into the genetic and phenotypic diversity of cultivated American ginseng grown under similar environmental conditions, and the relationship between different phenotypes, as well as genotype and phenotype, will aid in future selection programs to develop American ginseng cultivars with desirable agronomic traits.

A soil fumigant increases American ginseng (Panax quinquefolius L.) survival and growth under continuous cropping by affecting soil microbiome assembly: a 4-year in situ field experiment.

IMPORTANCE: Numerous reports of soil fumigants and fungicides on annual crops exist; however, it is unclear whether the single application to perennial plants persistently improves plant growth and controls disease or whether it has a long-lasting impact on soil microbes. We found that soil fumigation enhances ginseng growth and suppresses root rot disease by reshaping the soil microbial community. Our findings benefit the agricultural development of ginseng and provide a theoretical basis for the prevention of ginseng diseases.

Biotransformation of American Ginseng Stems and Leaves by an Endophytic Fungus Umbelopsis sp. and Its Effect on Alzheimer's Disease Control.

BACKGROUND: Common ginsenosides can be transformed into rare ginsenosides through microbial fermentation, and some rare ginsenosides can prevent Alzheimer's disease (AD). This study aimed to transform common ginsenosides into rare ginsenosides through solid-state fermentation of American ginseng stems and leaves (AGSL) by an endophytic fungus and to explore whether fermented saponin extracts prevent AD. METHODS: The powders of AGSL were fermented in a solid state by endophytic fungus. Total saponins were extracted from fermentation products using the methanol extraction method. The types of saponins were analyzed by liquid chromatography mass spectrometry (LC/MS). The Aß42 concentration and ß-secretase activity were measured by ELISA for the prevention of AD. RESULTS: After AGSL was fermented by an endophytic fungus NSJG, the total saponin concentration of the fermented extract G-SL was higher than the unfermented CK-SL. Rare ginsenoside Rh1 was newly produced and the yield of compound K (561.79%), Rh2 (77.48%), and F2 (40.89%) was increased in G-SL. G-SL had a higher inhibition rate on Aß42 concentration (42.75%) and ß-secretase activity (42.22%) than CK-SL, possibly because the rare ginsenoside Rh1, Rh2, F2, and compound K included in it have a strong inhibitory effect on AD. CONCLUSION: The fermented saponin extracts of AGSL show more inhibition effects on AD and may be promising therapeutic drugs or nutrients for AD.

Comprehensive analysis of different types of ginsenosides in the different parts of American ginseng by targeted and nontargeted MS/MS scanning.

To comprehensively study the ginsenosides distribution in the various tissues of American ginseng, the qualitative and quantitative-targeted and nontargeted mass spectroscopic methods were established using the high-performance liquid chromatography coupled with Qtrap triple quadrupole mass spectrometry (HPLC-QtrapQQQ-MS). The total ginsenosides of the root, stem, and leaf of American ginseng were determined by a colorimetric method, and the contents showed the order from high to low root, stem, and leaf. Eighty-two kinds of ginsenosides were detected in the different parts of American ginseng by enhanced mass scan-information-dependent data acquisition (IDA)-enhanced product ion (EPI) scan mode, including 69 from the root, 62 from the stem, and 48 from the leaf. An HPLC-multiple reaction monitoring (MRM) method was established, and 28 representative ginsenosides were further quantified in the three parts. Nearly all ginsenosides had the highest contents in the root and the lowest content in the leaf. Three types of ginsenosides (protopanaxadiol [PPD]-, protopanaxatiol [PPT]-, and oleanolic acid [OA]-types) were analyzed by precursor ion-IDA-EPI and MRM-IDA-EPI scan modes. Root had the most abundant ginsenosides in PPD- and PPT-type ginsenosides. Meanwhile, the OA-type ginsenosides are significantly enriched in the stem and leaf of American ginseng. The results provided a supplement to the quality assessment of American ginseng. PRACTICAL APPLICATION: The distribution profile of ginsenosides in the parts of American ginseng is different. Except for the root, the stem, and leaf of American ginseng have the most abundant ginsenosides in oleanolic acid type. The results reported herein can help the manufacturers choose appropriate materials to extract the ginsenosides.

Effects of rotation and Bacillus on the changes of continuous cropping soil fungal communities in American ginseng.

The continuous cropping obstacle is the main factor in leading to difficulty in American ginseng replanting. The dormant microbiota in the soil may be the cause of American ginseng disease and eventually caused continuous cropping obstacles, but there are few studies on the dynamic changes of soil microenvironment after American ginseng planting. In this study, we tracked short-term variation in physicochemical properties, enzyme activities, and fungal communities over time-series in soils with continuous cropping obstacle under crop rotation and probiotic Bacillus treatments. Furthermore, we examined the relationships between the important fungal compositions and the soil properties. The results showed that sucrase, cellulase, urease and acid phosphatase activities were significantly increased, while catalase and dehydrogenase were decreased with treatments time. Rotation treatment significantly affected the diversity, dissimilarity degree and species distribution of soil fungal community with continuous cropping obstacle over a short-term. Moreover, beneficial fungal biomarkers such as Cladorrhinum, Oidiodendron, and Mariannaea were accumulated at 48 h under rotation treatments. Almost all fungal biomarkers were negatively correlated with hydrolases and positively correlated with oxidoreductases and acid phosphatase under crop rotation treatments. This study suggested that compared to probiotic Bacillus, crop rotation can significantly affect soil fungal community structure, especially the enrichment of specific potentially beneficial fungal species. Our findings provide a scientific basis for understanding the dynamic changes of fungal communities and soil properties with continuous cropping obstacle of American ginseng in initial stage of soil improvement.

A new ocotillol-type ginsenoside from American ginseng berry.

A new ocotillol-type ginsenoside, named pseudoginsenoside F12 (1), was isolated from American ginseng berry, whose structure was elucidated as 6-O-[α-L-2,3-epoxy-rhamnopyranosyl-(1-2)-ß-D-glucopyranosyl]-dammar-20S,24R-epoxy-3ß, 6α,12ß,25-tetraol. In addition, the known alkaloids ß-carboline-1-carboxylic acid (2) and anoectochine (3) were isolated for the first time from the Araliaceae family. The new compound 1 was evaluated for cytotoxicity against MDA-MB-231 breast cancer cell line.

Rhizosphere Microbiome and Phenolic Acid Exudation of the Healthy and Diseased American Ginseng Were Modulated by the Cropping History.

The infection of soil-borne diseases has the potential to modify root exudation and the rhizosphere microbiome. However, the extent to which these modifications occur in various monocropping histories remains inadequately explored. This study sampled healthy and diseased American ginseng (Panax quinquefolius L.) plants under 1-4 years of monocropping and analyzed the phenolic acids composition by HPLC, microbiome structure by high-throughput sequencing technique, and the abundance of pathogens by quantitative PCR. First, the fungal pathogens of Fusarium solani and Ilyonectria destructans in the rhizosphere soil were more abundant in the diseased plants than the healthy plants. The healthy American ginseng plants exudated more phenolic acid, especially p-coumaric acid, compared to the diseased plants after 1-2 years of monocropping, while this difference gradually diminished with the increase in monocropping years. The pathogen abundance was influenced by the exudation of phenolic acids, e.g., total phenolic acids (r = -0.455), p-coumaric acid (r = -0.465), and salicylic acid (r = -0.417), and the further in vitro test confirmed that increased concentration of p-coumaric acid inhibited the mycelial growth of the isolated pathogens for root rot. The healthy plants had a higher diversity of rhizosphere bacterial and fungal microbiome than the diseased plants only after a long period of monocropping. Our study has revealed that the cropping history of American ginseng has altered the effect of pathogens infection on rhizosphere microbiota and root exudation.

American Ginseng for the Treatment of Alzheimer's Disease: A Review.

Alzheimer's disease (AD) is a prevalent degenerative condition that is increasingly affecting populations globally. American ginseng (AG) has anti-AD bioactivity, and ginsenosides, as the main active components of AG, have shown strong anti-AD effects in both in vitro and in vivo studies. It has been reported that ginsenosides can inhibit amyloid ß-protein (Aß) production and deposition, tau phosphorylation, apoptosis and cytotoxicity, as well as possess anti-oxidant and anti-inflammatory properties, thus suppressing the progression of AD. In this review, we aim to provide a comprehensive overview of the pathogenesis of AD, the potential anti-AD effects of ginsenosides found in AG, and the underlying molecular mechanisms associated with these effects. Additionally, we will discuss the potential use of AG in the treatment of AD, and how ginsenosides in AG may exert more potent anti-AD effects in vivo may be a direction for further research.

Panaxynol alleviates colorectal cancer in a murine model via suppressing macrophages and inflammation.

Currently available colorectal cancer (CRC) therapies have limited efficacy and severe adverse effects that may be overcome with the alternative use of natural compounds. We previously reported that panaxynol (PA), a bioactive component in American ginseng, possesses anticancer properties in vitro and suppresses murine colitis through its proapoptotic and anti-inflammatory properties. Because colitis is a predisposing factor of CRC and inflammation is a major driver of CRC, we sought to evaluate the therapeutic potential of PA in CRC. Azoxymethane-dextran sodium sulfate (AOM/DSS) mice (C57BL/6) were administered 2.5 mg/kg PA or vehicle 3 times/wk via oral gavage over 12 wk. PA improved clinical symptoms (P ≤ 0.05) and reduced tumorigenesis (P ≤ 0.05). This improvement may be reflective of PA's restorative effect on intestinal barrier function; PA upregulated the expression of essential tight junction and mucin genes (P ≤ 0.05) and increased the abundance of mucin-producing goblet cells (P ≤ 0.05). Given that macrophages play a substantial role in the pathogenesis of CRC and that we previously demonstrated that PA targets macrophages in colitis, we next assessed macrophages. We show that PA reduces the relative abundance of colonic macrophages within the lamina propria (P ≤ 0.05), and this was consistent with a reduction in the expression of important markers of macrophages and inflammation (P ≤ 0.05). We further confirmed PA's inhibitory effects on macrophages in vitro under CRC conditions (P ≤ 0.05). These results suggest that PA is a promising therapeutic compound to treat CRC and improve clinical symptoms given its ability to inhibit macrophages and modulate the inflammatory environment in the colon.NEW & NOTEWORTHY We report that panaxynol (PA) reduces colorectal cancer (CRC) by improving the colonic and tumor environment. Specifically, we demonstrate that PA improves crypt morphology, upregulates crucial tight junction and mucin genes, and promotes the abundance of mucin-producing goblet cells. Furthermore, PA reduces macrophages and associated inflammation, important drivers of CRC, in the colonic environment. This present study provides novel insights into the potential of PA as a therapeutic agent to ameliorate CRC tumorigenesis.

Pharmacological Effects of Ginseng: Multiple Constituents and Multiple Actions on Humans.

Ginseng is a very commonly used natural product in the world, and its two main species are Asian ginseng and American ginseng. Ginseng is an adaptogenic botanical that reportedly protects the body against stress, stabilizes physiological processes, and restores homeostasis. Previously, different animal models and contemporary research methodologies have been used to reveal ginseng's biomedical activities in different body systems and the linked mechanisms of actions. However, human clinical observation data on ginseng effects have attracted more attention from the general public and medical community. In this paper, after an introduction of the phytochemistry of ginseng species, we review positive ginseng clinical studies, mainly conducted in developed countries, performed over the past 20 years. The reported effects of ginseng are presented in several sections, and conditions impacted by ginseng include diabetes; cardiovascular disorders; cognition, memory, and mood; the common cold and flu; cancer fatigue and well-being; quality of life and social functioning, etc. Administration of ginseng demonstrated a good safety record in humans. Although encouraging beneficial effects obtained from clinical data, using the study treatment regimen, the reported ginseng effects in general only ranged from mild to moderate. Nonetheless, these beneficial effects of ginseng could be a valuable add-on therapy for patients receiving standard drug treatments. Additionally, as a dietary supplement, ginseng possesses an important role in maintaining and promoting human health. We believe that the quality of future ginseng trials should be improved, particularly by providing detailed herbal phytochemistry and quality control information. With solid effectiveness data obtained from a well-designed, carefully executed ginseng clinical trial, this meritoriously herbal medicine will be widely used by consumers and patients.