-
Frontiers in Pharmacology 2024Ginsenosides, the primary bioactive ingredients derived from the root of Panax ginseng, are eagerly in demand for tumor patients as a complementary and alternative drug.... (Review)
Review
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.
PubMed: 38939839
DOI: 10.3389/fphar.2024.1408993 -
Acta Pharmacologica Sinica Jun 2024Reperfusion injury, which is distinct from ischaemic injury, occurs when blood flow is restored in previously ischaemic brain tissue, further compromising neurons and...
Reperfusion injury, which is distinct from ischaemic injury, occurs when blood flow is restored in previously ischaemic brain tissue, further compromising neurons and other cells and worsening the injury. There is currently a lack of pharmaceutical agents and therapeutic interventions that specifically mitigate cerebral ischaemia/reperfusion (I/R) injury. Ginsenoside Rg1 (Rg1), a protopanaxatriol-type saponin isolated from Panax ginseng C. A. Meyer, has been found to protect against cerebral I/R injury, but its intricate protective mechanisms remain to be elucidated. Numerous studies have shown that autophagy plays a crucial role in protecting brain tissue during the I/R process and is emerging as a promising therapeutic strategy for effective treatment. In this study, we investigated whether Rg1 protected against I/R damage in vitro and in vivo by regulating autophagy. Both MCAO and OGD/R models were established. SK-N-AS and SH-SY5Y cells were subjected to OGD followed by reperfusion with Rg1 (4-32 μM). MCAO mice were injected with Rg1 (30 mg·kg·d. i.p.) for 3 days before and on the day of surgery. Rg1 treatment significantly mitigated ischaemia/reperfusion injury both in vitro and in vivo. Furthermore, we demonstrated that the induction of autophagy contributed to I/R injury, which was effectively inhibited by Rg1 in both in vitro and in vivo models of cerebral I/R injury. Rg1 inhibited autophagy through multiple steps, including impeding autophagy initiation, inducing lysosomal dysfunction and inhibiting cathepsin enzyme activities. We revealed that mTOR activation was pivotal in mediating the inhibitory effect of Rg1 on autophagy. Treatment with Torin-1, an autophagy inducer and mTOR-specific inhibitor, significantly reversed the impact of Rg1 on autophagy, decreasing its protective efficacy against I/R injury both in vitro and in vivo. In conclusion, our results suggest that Rg1 may serve as a promising drug candidate against cerebral I/R injury by inhibiting autophagy through activation of mTOR signalling.
PubMed: 38937576
DOI: 10.1038/s41401-024-01334-4 -
Heliyon Jun 2024Ginsenoside Rd is a tetracyclic triterpenoid derivative, widely existing in , and other traditional Chinese medicines. Many studies have proved that ginsenoside Rd have...
Ginsenoside Rd is a tetracyclic triterpenoid derivative, widely existing in , and other traditional Chinese medicines. Many studies have proved that ginsenoside Rd have a variety of significant biological activities on certain types of cancer. However, the mechanism of ginsenoside Rd remains unclear in lung cancer. The findings of this study reveal that GS-Rd inhibits the proliferation of NSCLC cells, induces apoptosis, and suppresses migration and invasion. The results showed Ginsenoside Rd inhibited the cell proliferation (∼99.52 %) by S phase arrest in cell cycle and promoted the apoptosis (∼54.85 %) of NSCLC cells. It also inhibited the migration and invasion of cells (p < 0.001). The expression levels of related mitochondrial apoptosis proteins (Bax/Bcl-2/Cytochrome C) and matrix metalloproteinases (MMP-2/-9) were significantly changed. The results showed that ginsenoside Rd inhibited the proliferation of tumor cells by activating p53/bax-mediated mitochondrial apoptosis and the expression of key enzymes for cell apoptosis caspase-3/cleaved-caspase-3 were significantly increased. This research contributes to a better understanding of the anti-tumor effects and molecular mechanisms of GS-Rd, paving the way for its potential development and clinical application in NSCLC therapy.
PubMed: 38933967
DOI: 10.1016/j.heliyon.2024.e32483 -
Nutrients Jun 2024Sprout ginseng extract (ThinkGIN™) manufactured through a smart farm system has been shown to improve memory in preclinical studies. This study conducted a 12-week... (Randomized Controlled Trial)
Randomized Controlled Trial
Sprout ginseng extract (ThinkGIN™) manufactured through a smart farm system has been shown to improve memory in preclinical studies. This study conducted a 12-week randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of ThinkGIN™ for improving memory in subjective memory impairment (SMI). Subjects aged 55 to 75 years with SMI participated in this study. A total of 80 subjects who met the inclusion/exclusion criteria were assigned to the ThinkGIN™ group ( = 40, 450 mg ThinkGIN™/day) or a placebo group ( = 40). Efficacy and safety evaluations were conducted before intervention and at 12 weeks after intervention. As a result of 12 weeks of ThinkGIN™ intake, significant differences in SVLT, RCFT, MoCA-K, PSQI-K, and AChE were observed between the two groups. Safety evaluation (AEs, laboratory tests, vital signs, and electrocardiogram) revealed that ThinkGIN™ was safe with no clinically significant changes. Therefore, ThinkGIN™ has the potential to be used as a functional food to improve memory.
Topics: Humans; Panax; Double-Blind Method; Male; Plant Extracts; Middle Aged; Female; Aged; Memory Disorders; Treatment Outcome; Memory
PubMed: 38931306
DOI: 10.3390/nu16121952 -
Molecules (Basel, Switzerland) Jun 2024Ginseng (Panax ginseng C.A. Mey) is known for its rich saponin compounds and tonic effects. To better utilize the medicinal value of ginseng, this study investigated the...
Ginseng (Panax ginseng C.A. Mey) is known for its rich saponin compounds and tonic effects. To better utilize the medicinal value of ginseng, this study investigated the extraction process, components, free radical scavenging ability, and immunomodulatory activity of total saponins of ginseng fibrous roots. The response surface methodology was employed to optimize the extraction process of total saponins, and Q-Orbitrap high-resolution liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical constituents in the total saponins extract of ginseng fibrous roots (GRS). The results showed that the optimal extraction process was achieved with an ethanol concentration of 68%, a material-solvent ratio of 1:25 mL/g, and an extraction time of 20 min, yielding a total saponin content of 6.34% under these conditions. The extract contained four terpenoid compounds and four polyphenolic compounds. GRS exhibited considerable scavenging activity against DPPH and ABTS radicals, with IC values of 0.893 and 0.210 mg/mL, respectively. Moreover, GRS restored immune suppression in mice by increasing white blood cell, red blood cell, and neutrophil counts, and improving the lymphocyte. It also promoted immune system recovery, as evidenced by elevated serum levels of IL-2, IFN-γ, TNF-α, and IL-1β in mice. GRS is a natural compound with promising potential for developing antioxidants and immunomodulatory foods.
Topics: Panax; Saponins; Free Radical Scavengers; Plant Roots; Animals; Mice; Plant Extracts; Immunologic Factors; Immunomodulating Agents; Antioxidants
PubMed: 38930835
DOI: 10.3390/molecules29122770 -
Biomolecules Jun 2024Ginseng ( 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...
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 genes with unknown functions and reveal their roles in ginsenoside synthesis. In this study, based on the five 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, , as the target gene from among the five genes. Methyl jasmonate-induced treatment of ginseng adventitious roots showed that the gene responded to methyl jasmonate induction and was involved in the synthesis of ginsenosides. The gene was cloned and the overexpression vector pBI121-PgCYP309 and the interference vector pART27-PgCYP309 were constructed. Transformation of ginseng adventitious roots by the -mediated method and successful induction of transgenic ginseng hairy roots were achieved. The transformation rate of ginseng hairy roots with overexpression of the gene was 22.7%, and the transformation rate of ginseng hairy roots with interference of the 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 and genes were also significantly increased. gene promotes the synthesis of ginsenosides, and it was preliminarily verified that gene can promote the synthesis of dammarane-type ginsenosides.
Topics: Panax; Cytochrome P-450 Enzyme System; Ginsenosides; Gene Expression Regulation, Plant; Plant Roots; Plant Proteins; Oxylipins; Acetates; Cyclopentanes
PubMed: 38927118
DOI: 10.3390/biom14060715 -
Journal of Cardiovascular Pharmacology Apr 2024Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the...
Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.
PubMed: 38922585
DOI: 10.1097/FJC.0000000000001566 -
Frontiers in Microbiology 2024Knowledge on spatiotemporal heterogeneity of plant root microbiomes is lacking. The diversity of the root microbiome must be revealed for understanding plant-microbe...
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 (2.83%), (0.89%), (0.56%), (0.41%), (4.44%), and (3.88%) were enriched in F5B with an increase in planting years, whereas the abundance of potentially beneficial 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.
PubMed: 38919496
DOI: 10.3389/fmicb.2024.1340575 -
Journal of Agricultural and Food... Jun 2024In recent years, there has been a growing concern regarding health issues arising from exposure to nanoplastics (Nps) in the natural environment. The Nps bioaccumulate...
In recent years, there has been a growing concern regarding health issues arising from exposure to nanoplastics (Nps) in the natural environment. The Nps bioaccumulate within the body the circulatory system and accumulate in the liver, resulting in damage. Previous studies have demonstrated that maltol, derived from red ginseng ( C.A. Meyer) as a Maillard product, exhibits hepatoprotective effects by alleviating liver damage caused by carbon tetrachloride or cisplatin. In order to explore the specific mechanism of maltol in improving hepatotoxicity induced by Nps, mice exposed to 100 mg/kg Nps were given maltol at doses of 50 and 100 mg/kg, respectively. The results showed that Nps induced an increase in the levels of liver apoptotic factors BAX and cytochrome c, a decrease in the levels of the autophagy key gene LC3 II/I, and an increase in P62. It also caused oxidative stress by affecting the Nrf2/HO-1 pathway, and a decrease in GPX4 protein expression suggested the occurrence of ferroptosis. However, treatment with maltol significantly improved these changes. In addition, maltol (2, 4, and 8 μM) also protected human normal liver L02 cells from Np (400 μg/mL)-induced damage. Our data suggest that maltol could ameliorate Np-induced L02 cytotoxicity by reducing autophagy-dependent oxidative stress, exhibiting similar protective effects as . This study helps shed light on the specific molecular mechanism of Np-induced hepatotoxicity. For the first time, we studied the protective effect of maltol on Np-induced liver injury from multiple perspectives, expanding the possibility of treatment for diseases caused by environmental pollutants.
PubMed: 38915203
DOI: 10.1021/acs.jafc.4c02040 -
Drug Delivery and Translational Research Jun 2024(20 S)-Ginsenoside Rh2 is a natural saponin derived from Panax ginseng Meyer (P. ginseng), which showed significantly potent anticancer properties. However, its low...
(20 S)-Ginsenoside Rh2 is a natural saponin derived from Panax ginseng Meyer (P. ginseng), which showed significantly potent anticancer properties. However, its low water solubility and bioavailability strongly restrict its pharmaceutical applications. The aim of current research is to develop a modified (20 S)-Ginsenoside Rh2 formulation with high solubility, dissolution rate and bioavailability by combined computational and experimental methodology. The "PharmSD" model was employed to predict the optimal polymer for (20 S)-Ginsenoside Rh2 solid dispersion formulations. The solubility of (20 S)-Ginsenoside Rh2 in various polymers was assessed, and the optimal ternary solid dispersion was evaluated across different dissolution mediums. Characterization techniques included the Powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). Molecular dynamics simulations were employed to elucidate the formation mechanism of the solid dispersion and the interactions among active pharmaceutical ingredient (API) and excipient molecules. Cell and animal experiments were conducted to evaluate the in vivo performance of the modified formulation. The "PharmSD" solid dispersion model identified Gelucire 44/14 as the most effective polymer for enhancing the dissolution rate of Rh2. Subsequent experiment also confirmed that Gelucire 44/14 outperformed the other selected polymers. Moreover, the addition of the third component, sodium dodecyl sulfate (SDS), in the ternary solid dispersion formulation significantly amplified dissolution rates than the binary systems. Characterization experiments revealed that the API existed in an amorphous state and interacted via hydrogen bonding with SDS and Gelucire. Moreover, molecular modeling results provided additional evidence of hydrogen bonding interactions between the API and excipient molecules within the optimal ternary solid dispersion. Cell experiments demonstrated efflux ratio (EfR) of Rh2 ternary solid dispersion was lower than that of pure Rh2. In vivo experiments revealed that the modified formulation substantially improved the absorption of Rh2 in rats. Our research successfully developed an optimal ternary solid dispersion for Rh2 with high solubility, dissolution rate and bioavailability by integrated computational and experimental tools. The combination of Artificial Intelligence (AI) technology and molecular dynamics simulation is a wise way to support the future formulation development.
PubMed: 38914874
DOI: 10.1007/s13346-024-01628-4