Pityriasis Rosea-Like Eruption following anti-fatigue traditional herbs: Aconitum carmichaelii Debx and Panax Ginseng suspected.

Traditional herbs have a history of clinical use in anti-fatigue. However, several adverse effects of herbs have been identified. Pityriasis rosea-like eruption (PR-LE) is a rare cutaneous complication of herbs. To the best of our knowledge, there have been few reports of PR-LE following herbs. Here, we described a case of PR-LE that developed 6 days after taking anti-fatigue herbs. After the 17 days of stopping Aconitum carmichaelii Debx and Panax Ginseng, it notably faded. So, when anti-fatigue herbs being authorized for fatigue use, monitoring for potential adverse effects is necessary.

Ginseng supplementation and cardiovascular disease risk factors: a protocol for GRADE-assessed systematic review and dose-response meta-analysis.

INTRODUCTION: Heart diseases constitute a significant global public health concern. Cardiovascular diseases (CVDs) are characterised by disruptions in blood circulation and are notably prevalent among adults exposed to Westernised diets. Ginseng, a medicinal plant, has been recognised for its healing properties and has a history of use spanning thousands of years. This systematic review aims to evaluate the efficacy of ginseng in modifying risk factors for CVD, including lipid profiles, glycaemic control, anthropometric indices, inflammation indicators, blood pressure, oxidative stress, liver function tests, adipokines and heart rate among individuals aged 18 and above, encompassing both genders. METHODS AND ANALYSIS: We will conduct an electronic search for articles published from inception to September 2023 using a predefined search strategy in PubMed, Scopus, Web of Science, CENTRAL and EMBASE. Our search will focus exclusively on randomised controlled clinical trials involving both healthy and unhealthy participants. The process of reviewing articles, extracting pertinent information and assessing the quality of studies using the Cochrane risk of bias tool will be carried out independently by two reviewers. Any discrepancies will be resolved through discussion with a third party. If a sufficient number of eligible studies are identified, a meta-analysis will be conducted using these outcomes. ETHICS AND DISSEMINATION: This study serves as the procedural framework for a comprehensive examination and does not require ethical approval. Additionally, the study adhered to the guidelines outlined in the Declaration of Helsinki. Ethical approval for the study was obtained from the Ethics Committee of Golestan University of Medical Sciences (IR.GOUMS.REC.1402.298). PROSPERO REGISTRATION NUMBER: CRD42023465688.

[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.

[Identification and functional characterization of candidate genes involved in biosynthesis of ginsenoside Rg_1].

Panax ginseng is a perennial herb with the main active compounds of ginsenosides. Among the reported ginsenosides, ginsenoside Rg_1 not only has a wide range of medicinal functions and abundant content but also is one of the major ginsenoside for the quality evaluation of this herb in the Chinese Pharmacopoeia. The main biosynthesis pathway of ginsenoside Rg_1 in P. ginseng has been clarified, which lays a foundation for the comprehensive and in-depth analysis of the biosynthesis and regulatory mechanism of ginseno-side Rg_1. However, the biosynthesis of ginsenoside Rg_1 is associated with other complex processes involving a variety of regulatory genes and catalyzing enzyme genes, which remain to be studied comprehensively. With the transcriptome data of 344 root samples from 4-year-old P. ginseng plants and their corresponding ginsenoside Rg_1 content obtained in the previous study, this study screened out 217 differentially expressed genes(DEGs) with Rg_1 content changes by DEseq2 analysis in R language. Furthermore, the weighted gene co-expression network analysis(WGCNA) revealed 40 hub genes among the DEGs.Pearsoncorrelation analysis was further perforned to yield 20 candidate genes significantly correlated with ginsenoside Rg_1 content, and these genes were annotated to multiple metabolic processes including primary metabolism and secondary metabolism. Finally, the treatment of P. ginseng adventitious roots with methyl jasmonate indicated that 16 of these genes promoted the biosynthesis of ginsenoside Rg_1 in response to methyl jasmonate induction. Finally, one of the 16 genes was randomly selected to verify the function of the gene by genetic transformation and qRT-PCR and to confirm the rationality of the methodology of this study. The above results lay a foundation for studying the mechanism for regulation on the synthesis of ginsenoside Rg_1 and provide genetic resources for the industrial production of ginsenoside Rg_1.

[Simultaneous determination of maltol and seventeen saponins in red and black ginseng by UPLC-PDA wavelength switching method].

This study developed a UPLC-PDA wavelength switching method to simultaneously determine the content of maltol and seventeen saponins in red and black ginseng and compared the quality differences of two different processed products of red and black ginseng. A Waters HSS T3 column(2. 1 mm×100 mm, 1. 8 µm) at 30 ℃ was adopted, with the mobile phase of acetonitrile(A) and water containing 0. 1% phosphoric acid(B) under gradient elution, the flow rate of 0. 3 m L·min~(-1), and the injection volume of 2 µL.The wavelength switching was set at 273 nm within 0-11 min and 203 nm within 11-60 min. The content results of multiple batches of red and black ginseng samples were analyzed by the hierarchical cluster analysis(HCA) and principal component analysis(PCA) to evaluate the quality difference. The results showed that the 18 constituents exhibited good linear relationships within certain concentration ranges, with the correlation coefficients(r) greater than 0. 999 1. The relative standard deviations(RSDs) of precision,repeatability, and stability were all less than 5. 0%. The average recoveries ranged from 95. 93% to 104. 2%, with an RSD of 1. 8%-4. 2%. The content determination results showed that the quality of red and black ginseng samples was different, and the two types of processed products were intuitively distinguished by HCA and PCA. The method is accurate, reliable, and reproducible. It can be used to determine the content of maltol and seventeen saponins in red and black ginseng and provide basic information for the quality evaluation and comprehensive utilization of red and black ginseng.

Analysis of the Variation in Antioxidant Activity and Chemical Composition upon the Repeated Thermal Treatment of the By-Product of the Red Ginseng Manufacturing Process.

Steamed ginseng water (SGW) is a by-product of the repeated thermal processing of red ginseng, which is characterized by a high bioactive content, better skin care activity, and a large output. However, its value has been ignored, resulting in environmental pollution and resource waste. In this study, UHPLC-Q-Exactive-MS/MS liquid chromatography-mass spectrometry and multivariate statistical analysis were conducted to characterize the compositional features of the repeated thermal-treated SGW. The antioxidant activity (DPPH, ABTS, FRAP, and OH) and chemical composition (total sugars, total saponins, and reducing and non-reducing sugars) were comprehensively evaluated based on the entropy weighting method. Four comparison groups (groups 1 and 3, groups 1 and 5, groups 1 and 7, and groups 1 and 9) were screened for 37 important common difference markers using OPLS-DA analysis. The entropy weight method was used to analyze the weights of the indicators; the seventh SGW sample was reported to have a significant weight. The results of this study suggest that heat treatment time and frequency can be an important indicator value for the quality control of SGW cycling operations, which have great potential in antioxidant products.

Effects of a co-bacterial agent on the growth, disease control, and quality of ginseng based on rhizosphere microbial diversity.

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. CONCLUSION: 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.

Evaluation and comparison of liquid chromatography/high-resolution mass spectrometry platforms for the separation and characterization of ginsenosides from the leaves of Panax ginseng.

The measurement of data repeatability in small-molecule metabolites acquired within and among different liquid chromatography-mass spectrometry (LC-MS) platforms is crucial for data sharing or data transfer in natural products research. This work was designed to investigate and evaluate the separation and detection performance of three commercial high-resolution LC-MS platforms (e.g., Agilent 6550 QTOF, Waters Vion IM-QTOF, and Thermo Scientific Orbitrap Exploris 120) using 68 ginsenoside references and the extract of Panax ginseng leaf. The retention time (tR), measured on these three platforms (under the same chromatography condition), showed good stability in different concentration tests, and within/among different instruments for both intra-day and inter-day precision examinations. Correlation in tR of ginsenosides was also highly determined on these three platforms. In spite of the different mass analyzers involved, these three platforms gave the accurate mass determination ability, especially enhanced resolution gained because of the ion mobility (IM) separation facilitated by IM-quadrupole time-of-flight. The current study has systematically evaluated the separation and MS detection performance enabled by three high-resolution LC-MS platforms taking ginsenosides as the template, and the reported findings can benefit the researchers for the selection of analytical platforms and the purpose of data sharing or data transfer.

Pixel-Level Recognition of Trace Mycotoxins in Red Ginseng Based on Hyperspectral Imaging Combined with 1DCNN-Residual-BiLSTM-Attention Model.

Red ginseng is widely used in food and pharmaceuticals due to its significant nutritional value. However, during the processing and storage of red ginseng, it is susceptible to grow mold and produce mycotoxins, generating security issues. This study proposes a novel approach using hyperspectral imaging technology and a 1D-convolutional neural network-residual-bidirectional-long short-term memory attention mechanism (1DCNN-ResBiLSTM-Attention) for pixel-level mycotoxin recognition in red ginseng. The "Red Ginseng-Mycotoxin" (R-M) dataset is established, and optimal parameters for 1D-CNN, residual bidirectional long short-term memory (ResBiLSTM), and 1DCNN-ResBiLSTM-Attention models are determined. The models achieved testing accuracies of 98.75%, 99.03%, and 99.17%, respectively. To simulate real detection scenarios with potential interfering impurities during the sampling process, a "Red Ginseng-Mycotoxin-Interfering Impurities" (R-M-I) dataset was created. The testing accuracy of the 1DCNN-ResBiLSTM-Attention model reached 96.39%, and it successfully predicted pixel-wise classification for other unknown samples. This study introduces a novel method for real-time mycotoxin monitoring in traditional Chinese medicine, with important implications for the on-site quality control of herbal materials.

Free Radical Scavenging Effect and Immunomodulatory Activity of Total Saponins Extract of Ginseng Fibrous Roots.

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 IC50 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-1ß in mice. GRS is a natural compound with promising potential for developing antioxidants and immunomodulatory foods.

Efficacy and Safety of Panax ginseng Sprout Extract in Subjective Memory Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical 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 (n = 40, 450 mg ThinkGIN™/day) or a placebo group (n = 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.

20(R)-Panaxatriol enhances METTL3-mediated m6A modification of STUB1 to inhibit autophagy and exert antitumor effects in Triple-Negative Breast Cancer cells.

BACKGROUND: Aberrant activation of autophagy in triple-negative breast cancer (TNBC) has led researchers to investigate potential therapeutic strategies targeting this process. The regulation of autophagy is significantly influenced by METTL3. Our previous research has shown that the Panax ginseng-derived compound, 20(R)-panaxatriol (PT), has potential as an anti-tumor agent. However, it remains unclear whether PT can modulate autophagy through METTL3 to exert its anti-tumor effects. OBJECTIVE: Our objective is to investigate whether PT can regulate autophagy in TNBC cells and elucidate the molecular mechanisms. STUDY DESIGN: For in vitro experiments, we employed SUM-159-PT and MDA-MB-231 cells. While in vivo experiments involved BALB/c nude mice and NOD/SCID mice. METHODS: In vitro, TNBC cells were treated with PT, and cell lines with varying expression levels of METTL3 were established. We assessed the impact on tumor cell activity and autophagy by analyzing autophagic flux, Western Blot (WB), and methylation levels. In vivo, subcutaneous transplantation models were established in BALB/c nude and NOD/SCID mice to observe the effect of PT on TNBC growth. HE staining and immunofluorescence were employed to analyze histopathological changes in tumor tissues. MeRIP-seq and dual-luciferase reporter gene assays were used to identify key downstream targets. Additionally, the silencing of STIP1 Homology And U-Box Containing Protein 1 (STUB1) explored PT's effects. The mechanism of PT's action on STUB1 via METTL3 was elucidated through mRNA stability assays, mRNA alternative splicing analysis, and nuclear-cytoplasmic mRNA separation. RESULTS: In both in vivo and in vitro experiments, it was discovered that PT significantly upregulates the expression of METTL3, leading to autophagy inhibition and therapeutic effects in TNBC. Simultaneously, through MeRIP-seq analysis and dual-luciferase reporter gene assays, we have demonstrated that PT modulates STUB1 via METTL3, influencing autophagy in TNBC cells. Furthermore, intriguingly, PT extends the half-life of STUB1 mRNA by enhancing its methylation modification, thereby enhancing its stability. CONCLUSION: In summary, our research reveals that PT increases STUB1 m6A modification through a METTL3-mediated mechanism in TNBC cells, inhibiting autophagy and further accentuating its anti-tumor properties. Our study provides novel mechanistic insights into TNBC pathogenesis and potential drug targets for TNBC.

Study on the mechanism of quercetin in Sini Decoction Plus Ginseng Soup to inhibit liver cancer and HBV virus replication through CDK1.

BACKGROUND: To explore the anti-tumor and anti-virus key active ingredients of Sini Decoction Plus Ginseng Soup (SNRS) and their mechanisms. METHODS: The main ingredients of SNRS were analyzed by network pharmacology, and quercetin was identified as the key active ingredient. Then, we obtained the targets of quercetin by using Drugbank, PharmMapper, and SwissTargetPrediction databases. Then, the targets of HBV-related hepatocellular carcinoma (HBV-related HCC) were obtained by using Genecards database. In addition, using the gene expression profiles of HBV-related HCC patients in GEO database and the genes with the greatest survival difference in GEPIA 2 database identified the potential targets of quercetin. In addition, the mechanism of potential genes was studied through GO, KEGG analysis, and PPI network. Using AUC and survival analysis to evaluate the diagnostic and prognostic value of cyclin-dependent kinase 1 (CDK1) and CCNB1. Finally, the effects of quercetin on proliferation of Hep3B and HepG2215 cells and the level of CDK1 and CCNB1 were verified in vitro. ELISA was used to measure the expression levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) after the intervention by quercetin for 24 h and 48 h in HepG2215 cell. RESULTS: The first 10 key ingredients of SNRS were identified, and quercetin was the most key ingredient. The 101 potential quercetin targets were identified for the treatment of HBV-related HCC. GO and KEGG showed that 101 potential target enrichment in cancer and cell cycle regulation. By Venn analysis, CDK1 and CCNB1 were intersection targets, which could be used as potential targets for the action of quercetin on HBV-related HCC. Moreover, the expression of CDK1 and CCNB1 was highly expressed in the high-risk group, while the OS rate was low. The 1-year, 3-year and 5-year area under the curve (AUC) curves of CDK1 and CCNB1 were 0.724, 0.676, 0.622 and 0.745, 0.678, 0.634, respectively. Moreover, experimental results also showed that quercetin inhibited cell proliferation and reduced CDK1 expression in Hep3B and HepG2215 cells. The expressions of HBsAg and HBeAg in HepG2215 cell supernatant and cell gradually decreased with the increase of intervention time of quercetin and CDK1 inhibitor. CONCLUSIONS: Quercetin is a key ingredient of anti-HBV-related HCC activity and inhibits HBV replication in SNRS by inhibiting CDK1.

Functional Validation of the Cytochrome P450 Family PgCYP309 Gene in Panax ginseng.

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.

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.

Ginseng total saponin improves red blood cell oxidative stress injury by regulating tyrosine phosphorylation and glycolysis in red blood cells.

BACKGROUND: Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PURPOSE: This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. METHODS: The oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. RESULTS: GTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. CONCLUSIONS: This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.

The antiangiogenic effect of total saponins of Panax japonicus C.A. Meyer in rheumatoid arthritis is mediated by targeting the HIF-1α/VEGF/ANG-1 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese herbal medicine Panax japonicus C.A. Meyer has a long history in clinical treatment of rheumatoid arthritis (RA). Total saponins of Panax japonicus C.A. Meyer (TSPJs) were extracted from the root of Panax japonicus C.A. Meyer, and its anti-rheumatism mechanism is still unclear. AIM OF THE STUDY: To investigate whether TSPJs attenuated synovial angiogenesis in RA and explore the potential mechanisms. MATERIALS AND METHODS: Potential TSPJs targets involving gene function were predicted by network pharmacology related databases. Bioinformatics analysis and molecular docking technology were used to predict the mechanism of TSPJs in the treatment of RA. The predicted results were validated by cell experiments and a collagen-induced arthritis (CIA) mouse model. RESULTS: Bioinformatics analysis results showed that TSPJs may inhibit RA-related angiogenesis through the hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) pathways. In vitro, different doses of TSPJs showed a good inhibitory effect on the tube formation of EA.hy926 cells. The results of the cellular thermal shift assay indicated that TSPJs can bind to the HIF-1α, VEGFA, and angiopoietin-1 (ANG-1) proteins. In vivo, the administration of TSPJs alleviated the symptoms of CIA mice, including the arthritis index, hind paw thickness, and swollen joint count. The histological results demonstrated that TSPJs inhibited inflammation, angiogenesis, bone damage, and cartilage destruction. Furthermore, TSPJs decreased the number of vessels and the expression level of CD31. The mechanistic results revealed that TSPJs decreased the expression of HIF-1α, VEGFA, and ANG-1 in the serum or synovial tissues of CIA mice. CONCLUSION: These results suggest that TSPJs effectively inhibit angiogenesis in RA, and the mechanism may be related to inhibiting the HIF-1α/VEGF/ANG-1 axis.

Nanoplastic-Induced Liver Damage Was Alleviated by Maltol via Enhancing Autophagic Flow: An In Vivo and In Vitro Study.

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 via the circulatory system and accumulate in the liver, resulting in damage. Previous studies have demonstrated that maltol, derived from red ginseng (Panax 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 in vitro as in vivo. 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.

Biological network comparison identifies a novel synergistic mechanism of Ginseng Radix-Astragali Radix herb pair in cancer-related fatigue.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng Radix and Astragali Radix are commonly combined to tonify Qi and alleviate fatigue. Previous studies have employed biological networks to investigate the mechanisms of herb pairs in treating different diseases. However, these studies have only elucidated a single network for each herb pair, without emphasizing the superiority of the herb combination over individual herbs. AIM OF THE STUDY: This study proposes an approach of comparing biological networks to highlight the synergistic effect of the pair in treating cancer-related fatigue (CRF). METHODS: The compounds and targets of Ginseng Radix, Astragali Radix, and CRF diseases were collected and predicted using different databases. Subsequently, the overlapping targets between herbs and disease were imported into the STRING and DAVID tools to build protein-protein interaction (PPI) networks and analyze enriched KEGG pathways. The biological networks of Ginseng Radix and Astragali Radix were compared separately or together using the DyNet application. Molecular docking was used to verify the predicted results. Further, in vitro experiments were conducted to validate the synergistic pathways identified in in silico studies. RESULTS: In the PPI network comparison, the combination created 89 new interactions and an increased average degree (11.260) when compared to single herbs (10.296 and 9.394). The new interactions concentrated on HRAS, STAT3, JUN, and IL6. The topological analysis identified 20 core targets of the combination, including three Ginseng Radix-specific targets, three Astragali Radix-specific targets, and 14 shared targets. In KEGG enrichment analysis, the combination regulated additional signaling pathways (152) more than Ginseng Radix (146) and Astragali Radix (134) alone. The targets of the herb pair synergistically regulated cancer pathways, specifically hypoxia-inducible factor 1 (HIF-1) signaling pathway. In vitro experiments including enzyme-linked immunosorbent assay and Western blot demonstrated that two herbs combination could up-regulate HIF-1α signaling pathway at different combined concentrations compared to either single herb alone. CONCLUSION: The herb pair increased protein interactions and adjusted metabolic pathways more than single herbs. This study provides insights into the combination of Ginseng Radix and Astragali Radix in clinical practice.

Total saponins from Panax japonicus regulated the intestinal microbiota to alleviate lipid metabolism disorders in aging mice.

Total saponins from Panax japonicus (TSPJ) have many beneficial physiological activities, particularly in alleviating the damages of aging and abnormal lipid metabolism. This work used mice models to investigate if TSPJ reduced obesity and regulated metabolic functions via the intestinal microbiota, the disturbance of which has been shown to cause aging-related diseases. The results showed that TSPJ significantly reduced the weight and blood lipid level of aging mice. Further analyses showed that TSPJ significantly inhibited adipogenesis, changed the composition of the intestinal flora, and protected the integrity of the intestinal barrier. It was inferred from the accumulated experimental data that TSPJ helped to combat obesity in aging mice by regulating the intestinal microbiota and promoting microbial metabolism.