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ETHNOPHARMACOLOGICAL RELEVANCE: Mountain-cultivated Panax ginseng C.A.Mey. (MCG) with high market price and various properties was valuable special local product in Northeast of Asia. MCG has been historically used to mitigate heart failure (HF) for thousand years, HF is a clinical manifestation of deficiency of "heart-qi" in traditional Chinese medicine. However, there was little report focus on the activities of extracted residue of MCG. AIM OF THE STUDY: A novel glycopeptide (APMCG-1) was isolated from step ethanol precipitations of alkaline protease-assisted extract from MCG residue. MATERIALS AND METHODS: The molecular weight and subunit structure of APMCG-1 were determined by FT-IR, HPLC and GPC technologies, as well as the H9c2 cells, Tg (kdrl:EGFP) zebrafish were performed to evaluated the protective effect of APMCG-1. RESULTS: APMCG-1 was identified as a glycopeptide containing seven monosaccharides and seven amino acids via O-lined bonds. Further, in vitro, APMCG-1 significantly decreased reactive oxygen species production and lactate dehydrogenase contents in palmitic acid (PA)-induced H9c2 cells. APMCG-1 also attenuated endoplasmic reticulum stress and mitochondria-mediated apoptosis in H9c2 cells via the PI3K/AKT signaling pathway. More importantly, APMCG-1 reduced the blood glucose, lipid contents, the levels of heart injury, oxidative stress and inflammation of 5 days post fertilization Tg (kdrl:EGFP) zebrafish with type 2 diabetic symptoms in vivo. CONCLUSIONS: APMCG-1 protects PA-induced H9c2 cells while reducing cardiac dysfunction in zebrafish with type 2 diabetic symptoms. The present study provides a new insight into the development of natural glycopeptides as heart-related drug therapies.
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Diabetes Mellitus Tipo 2 , Glicopéptidos , Insuficiencia Cardíaca , Panax , Pez Cebra , Animales , Panax/química , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ratas , Línea Celular , Glicopéptidos/farmacología , Glicopéptidos/química , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Cardiotónicos/farmacología , Cardiotónicos/química , Cardiotónicos/aislamiento & purificación , Cardiotónicos/uso terapéutico , Miocitos Cardíacos/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacosRESUMEN
Panax ginseng C. A. Meyer (ginseng) is a medicinal plant widely used for promoting longevity. Recently, homogalacturonan (HG) domain-rich pectins purified from some plants have been reported to have anti-aging-related activities, leading us to explore the longevity-promoting activity of the HG pectins from ginseng. In this study, we discovered that two of low methyl-esterified ginseng HG pectins (named as WGPA-2-HG and WGPA-3-HG), whose degree of methyl-esterification (DM) was 16 % and 8 % respectively, promoted longevity in Caenorhabditis elegans. Results showed that WGPA-2-HG/WGPA-3-HG impaired insulin/insulin-like growth factor 1 (IGF-1) signalling (IIS) pathway, thereby increasing the nuclear accumulation of transcription factors SKN-1/Nrf2 and DAF-16/FOXO and enhancing the expression of relevant anti-aging genes. BLI and ITC analysis showed that the insulin-receptor binding, the first step to activate IIS pathway, was impeded by the engagement of WGPA-2-HG/WGPA-3-HG with insulin. By chemical modifications, we found that high methyl-esterification of WGPA-2-HG/WGPA-3-HG was detrimental for their longevity-promoting activity. These findings provided novel insight into the precise molecular mechanism for the longevity-promoting effect of ginseng pectins, and suggested a potential to utilize the ginseng HG pectins with appropriate DM values as natural nutrients for increasing human longevity.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Factor I del Crecimiento Similar a la Insulina , Insulina , Longevidad , Panax , Pectinas , Transducción de Señal , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/metabolismo , Panax/química , Factor I del Crecimiento Similar a la Insulina/metabolismo , Pectinas/farmacología , Pectinas/metabolismo , Pectinas/química , Longevidad/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Insulina/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , EsterificaciónRESUMEN
BACKGROUND: Previous clinical and basic studies have revealed that ginseng might have cardioprotective properties against anthracycline-induced cardiotoxicity (AIC). However, the underlying mechanism of ginseng action against AIC remains insufficiently understood. The aim of this study was to explore the related targets and pathways of ginseng against AIC using network pharmacology, molecular docking, cellular thermal shift assay (CETSA) and molecular dynamics (MD) simulations. RESULTS: Fourteen drug-disease common targets were identified. Enrichment analysis showed that the AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathway were potentially involved in the action of ginseng against AIC. Molecular docking demonstrated that the core components including Kaempferol, beta-Sitosterol, and Fumarine had notable binding activity with the three core targets CCNA2, STAT1, and ICAM1. Furthermore, the stable complex of STAT1 and Kaempferol with favorable affinity was further confirmed by CETSA and MD simulation. CONCLUSIONS: This study suggested that ginseng might exert their protective effects against AIC through the derived effector compounds beta-Sitosterol, Kaempferol and Fumarine by targeting CCNA2, STAT1, and ICAM1, and modulating AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathways.
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Antraciclinas , Cardiotoxicidad , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Farmacología en Red , Panax , Panax/química , Antraciclinas/efectos adversos , Antraciclinas/química , Antraciclinas/toxicidad , Humanos , Sitoesteroles/farmacología , Sitoesteroles/química , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT1/genética , Quempferoles/farmacología , Quempferoles/química , Transducción de Señal/efectos de los fármacosRESUMEN
Sepsis is a prevalent critical illness observed in emergency intensive care unit (ICU), characterized by life-threatening organ dysfunction caused by infection-induced inflammatory immune disorders in the body. The suppression of immune function plays a crucial role in the development and progression of sepsis. Traditional Chinese medicine theory of "acute deficiency syndrome" in sepsis shares similarities with the concept of "immunosuppression". According to this theory, ginseng is frequently utilized in clinical treatment of sepsis due to its ability to invigorate vitality and strengthen the body, playing a crucial role in tonifying deficiency and improving the overall health of patients. This paper provides a detailed discussion of the pathophysiological mechanisms of sepsis immune dysfunction and its correlation with "acute deficiency syndrome" in traditional Chinese medicine. It summarizes the current state of modern pharmacological research on ginseng's impact on the body's immune function, discusses relevant research progress and shortcomings regarding ginseng's therapeutic effects on immunosuppression in sepsis, and proposes future research directions.
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Panax , Sepsis , Humanos , Sepsis/tratamiento farmacológico , Sepsis/inmunología , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Ginseng, from the roots of Panax ginseng C. A. Meyer, is a widely used herbal medicine in Asian countries, known for its excellent therapeutic properties. The growth of P. ginseng is depend on specific and strict environments, with a preference for wetness but intolerance for flooding. Under excessive soil moisture, some irregular rust-like substances are deposited on the root epidermis, causing ginseng rusty symptoms (GRS). This condition leads to a significant reduce in yield and quality, resulting in substantial economic loses. However, there is less knowledge on the cause of GRS and there are no effective treatments available for its treatment once it occurs. Unsuitable environments lead to the generation of large amounts of reactive oxygen species (ROS). We investigated the key indicators associated with the stress response during different physiological stages of GRS development. We observed a significant change in ROS level, MDA contents, antioxidant enzymes activities, and non-enzymatic antioxidants contents prior to the GRS. Through the analysis of soil features with an abundance of moisture, we further determined the source of ROS. The levels of nitrate reductase (NR) and nitric oxide synthase (NOS) activities in the inter-root soil of ginseng with GRS were significantly elevated compared to those of healthy ginseng. These enzymes boost nitric oxide (NO) levels, which in turn showed a favorable correlation with the GRS. The activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase first rose and then decreased as GRS developed. Excess soil moisture causes a decrease in oxygen levels. This activated NR and NOS in the soil, resulting in a production of excess NO. The NO then diffused into the ginseng root and triggered a burst of ROS through NADPH located on the cell membrane. Additionally, Fe2+ in soil was oxidized to red Fe3+, and finally led to GRS. This conclusion was also verified by the Sodium Nitroprusside (SNP), a precursor compound producing NO. The presence of NO from NR and NOS in water-saturated soil is responsible for the generation of ROS. Among these, NO is the main component that contribute to the occurrence of GRS.
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Óxido Nítrico , Panax , Raíces de Plantas , Especies Reactivas de Oxígeno , Suelo , Panax/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Óxido Nítrico/metabolismo , Suelo/química , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico , Antioxidantes/metabolismo , Óxido Nítrico Sintasa/metabolismo , Nitrato-Reductasa/metabolismo , Enfermedades de las PlantasRESUMEN
The accumulation of secondary metabolites in Panax ginseng Meyer (P. ginseng) exhibits significant geographical variation, normally due to environmental factors. The current study aimed at elucidating the key environmental factors modulating the accumulation of secondary metabolites in P. ginseng. Plant and the associated soil samples were collected from ten geographical locations within the latitudinalrange of 27.09°N - 42.39°N and longitudinal range of 99.28°E - 128.19°E. 12 secondary metabolites in P. ginseng toots were measured. And the correlation between secondary metabolites with a series of soil properties and 7 climatic factors were investigated through Pearson's correlation, mantel test, random forest and pathway analysis. The results revealed that climatic factors were stronger drivers of ginseng secondary metabolite profile than soil nutrients. Specifically, temperature seasonality (TS) and soil available phosphorus (AP) were the most effective environments to have significantly and positively influence on the secondary metabolites of ginseng. This findings contribute to identifying optimal cultivation areas for P. ginseng, and hopefully establishing methods for interfering/shaping microclimate for cultivating high-quality P. ginseng.
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Ginsenósidos , Panax , Fósforo , Estaciones del Año , Suelo , Temperatura , Panax/metabolismo , Panax/crecimiento & desarrollo , Panax/química , Fósforo/análisis , Fósforo/metabolismo , Ginsenósidos/análisis , Ginsenósidos/metabolismo , Suelo/químicaRESUMEN
BACKGROUND: Rusted root rot is one of the most common root diseases in Panax ginseng, and Cylindrocarpon destructans is one of the main pathogenic fungus. The objective of this study was to screen and explore the extracts of biocontrol bacteria isolated from ginseng rhizosphere soil against Cylindrocarpon destructans. RESULTS: Bacterial strains Bacillus amyloliquefaciens YY8 and Enterobacteriacea YY115 were isolated and found to exhibit in vitro antifungal activity against C. destructans. A combination of crude protein extract from B. amyloliquefaciens YY8 and ethyl acetate extract from Enterobacteriacea YY115 in a 6:4 ratio exhibited the strongest antifungal activity against C. destructans. Measurements of electrical conductivity, protein content, and nucleic acid content in suspension cultures of C. destructans treated with a mixture extracts indicated that the extracts disrupted the cell membranes of rusted root rot mycelia, resulting in the leakage of electrolytes, proteins, and nucleic acids from the cells, and ultimately inhibiting the growth of C. destructans. The combined extracts suppressed the infection of ginseng roots discs by C. destructans effectively. CONCLUSION: The extracts obtained from the two bacterial strains effectively inhibited C. destructans in P. ginseng. It can provide scientific basis for the development of new biological control pesticides, reduce the use of chemical pesticides, and promote the sustainable development of agriculture.
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Bacillus amyloliquefaciens , Enterobacteriaceae , Panax , Enfermedades de las Plantas , Raíces de Plantas , Panax/microbiología , Panax/química , Bacillus amyloliquefaciens/metabolismo , Bacillus amyloliquefaciens/química , Bacillus amyloliquefaciens/fisiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Raíces de Plantas/microbiología , Enterobacteriaceae/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Microbiología del Suelo , Rizosfera , Acetatos/farmacología , Ascomicetos/efectos de los fármacos , Ascomicetos/química , Antifúngicos/farmacología , Antifúngicos/metabolismo , Agentes de Control Biológico/farmacologíaRESUMEN
Improving the cultivation mode and technology for traditional Chinese medicine has become important for its sustainable development. Monoculture enhances plant diseases, which decreases yield and quality. Intercropping is an effective measure to counterbalance that negative effect. In this study, we focused on Panax quinquefolium L. (ginseng) and four treatments were set up: the control without intercropping, P. quinquefolius + ryegrass (Lolium perenne L.), P. quinquefolius + red clover (Trifolium pratense L.), and P. quinquefolius + ryegrass + red clover. An LC-MS/MS system was used to detect the changes in the P. quinquefolius secondary metabolites, and high-throughput sequencing technology was used to determine the changes in the P. quinquefolius' rhizosphere soil microorganisms. Ginsenoside content, soil enzyme activities, and arbuscular mycorrhizal infection rate of P. quinquefolius were also measured using HPLC, ELISA kits, and microscopy, respectively. Co-intertia and Pearson's analysis were performed to explore the relationship between the metabolites and the P. quinquefolius microorganisms. Intercropping significantly increased the content of ginsenoside metabolites and recruited a large number of beneficial bacteria to the P. quinquefolius rhizosphere. The P. quinquefolius secondary metabolites were associated with the rhizosphere microbial community. For example, the dominant microorganisms, such as Acidobacteriota and Chloroflexi, played a key role in promoting the synthesis of ginsenoside Rd and (20R) ginsenoside Rg3 by P. quinquefolius. Intercropping led to changes in the P. quinquefolius secondary metabolites by driving and reshaping the rhizosphere microorganisms. These findings revealed the potential application of intercropping for improving the quality of P. quinquefolius.
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Ginsenósidos , Panax , Rizosfera , Panax/microbiología , Panax/metabolismo , Panax/fisiología , Panax/crecimiento & desarrollo , Ginsenósidos/metabolismo , Microbiología del Suelo , Micorrizas/fisiología , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Agricultura/métodos , Trifolium/microbiología , Trifolium/metabolismo , Trifolium/crecimiento & desarrollo , Trifolium/fisiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (P. ginseng) C.A. Meyer. Has been studied for decades for its various biological activities, especially in terms of immune-regulatory properties. Traditionally, it has been known that root, leaves, and fruits of P. ginseng were eaten for improving body's Qi and homeostasis. Also, these were used to protect body from various types of infectious diseases. However, molecular mechanisms of immunomodulatory activities of ginseng berries have not been systemically studied as often as other parts of the plant. AIM OF THE STUDY: The aim of this research is to discover the regulatory effects of P. ginseng berries, more importantly, their ginsenosides, on innate immune responses and to elucidate the molecular mechanism. MATERIALS AND METHODS: Ginseng berry concentrate (GBC) was orally injected into BALB/c mice for 30 days, and spleens were extracted for evaluation of immune-regulatory effects. Murine macrophage RAW264.7 cells were used for detailed molecular mechanism studies. Splenic natural killer (NK) cells were isolated using the magnetic-activated cell sorting (MACS) system, and the cytotoxic activity of isolated NK cells was measured using a lactate dehydrogenase (LDH) release assay. The splenic immune cell population was determined by flow-cytometry. NF-κB promoter activity was assessed by in vitro luciferase assay. Expression of inflammatory proteins and cytokines of the spleen and RAW264.7 cells were evaluated using western blotting and real-time PCR, respectively. RESULTS: The GBC enhanced cytotoxic activity of NK cells and the immune-regulation-related splenic cell population. Moreover, GBC promoted NF-κB promoter activity and stimulated the NF-κB signaling cascade. In spleen and RAW264.7 cells, expression of pro-inflammatory cytokines was increased upon GBC application, while expression of anti-inflammatory cytokines decreased. CONCLUSIONS: These results suggest that P. ginseng berry can stimulate innate immune responses and help maintain a balanced immune condition, mostly due to the action of its key ginsenoside Re, along with other protopanaxadiol- and protopanaxatriol-type ginsenosides. Such finding will provide a new insight into the field of well-being diet research as well as non-chemical immune modulator, by providing nature-derived and plant-based bioactive materials.
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Citocinas , Frutas , Ginsenósidos , Células Asesinas Naturales , Macrófagos , Ratones Endogámicos BALB C , FN-kappa B , Panax , Regulación hacia Arriba , Animales , Panax/química , Ginsenósidos/farmacología , FN-kappa B/metabolismo , Ratones , Células RAW 264.7 , Citocinas/metabolismo , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/inmunología , Regulación hacia Arriba/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/citología , Bazo/inmunología , Extractos Vegetales/farmacología , MasculinoRESUMEN
Steroid-resistant asthma (SRA), resisting glucocorticoids such as dexamethasone (DEX), is a bottleneck in the treatment of asthma. It is characterized by a predominantly neutrophilic inflammatory subtype and is prone to developing into severe refractory asthma and fatal asthma. Currently, there is a lack of universally effective treatments for SRA. Moreover, since cold stimulation does increase the risk of asthma development and exacerbate asthma symptoms, the treatment of cold-stimulated SRA (CSRA) will face greater challenges. To find effective new methods to ameliorate CSRA, this study established a CSRA mouse model of allergic airway inflammation mimicking human asthma for the first time and evaluated the alleviating effects of 80% ethanol extract of mountain-cultivated ginseng (MCG) based on multi-omics analysis. The results indicate that cold stimulation indeed exacerbated the SRA-related symptoms in mice; the DEX individual treatment did not show a satisfactory effect; while the combination treatment of DEX and MCG could dose-dependently significantly enhance the lung function; reduce neutrophil aggregation; decrease the levels of LPS, IFN-γ, IL-1ß, CXCL8, and IL-17; increase the level of IL-10; alleviate the inflammatory infiltration; and decrease the mucus secretion and the expression of MUC5AC. Moreover, the combination of DEX and high-dose (200 mg/kg) MCG could significantly increase the levels of tight junction proteins (TJs), regulate the disordered intestinal flora, increase the content of short-chain fatty acids (SCFAs), and regulate the abnormal gene profile and metabolic profile. Multi-omics integrated analysis showed that 7 gut microbes, 34 genes, 6 metabolites, and the involved 15 metabolic/signaling pathways were closely related to the pharmacological effects of combination therapy. In conclusion, integrated multi-omics profiling highlighted the benefits of MCG for CSRA mice by modulating the interactions of microbiota, genes, and metabolites. MCG shows great potential as a functional food in the adjuvant treatment of CSRA.
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Asma , Dexametasona , Panax , Extractos Vegetales , Animales , Asma/tratamiento farmacológico , Asma/microbiología , Asma/metabolismo , Panax/química , Ratones , Dexametasona/farmacología , Extractos Vegetales/farmacología , Frío , Modelos Animales de Enfermedad , Microbioma Gastrointestinal/efectos de los fármacos , Metabolómica/métodos , Microbiota/efectos de los fármacos , Ratones Endogámicos BALB C , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/microbiología , Pulmón/patología , Mucina 5AC/metabolismo , Mucina 5AC/genética , Citocinas/metabolismo , Resistencia a Medicamentos/genética , Femenino , MultiómicaRESUMEN
Diabetes mellitus (DM) is a chronic metabolic disease that predisposes to chronic damage and dysfunction of various organs, including leading to erectile dysfunction (ED) and asthenospermia. Literature suggests that ginseng plays an important role in the treatment and management of DM. Ginseng may have a therapeutic effect on the complications of DM-induced ED and asthenospermia. The study aimed to explore the mechanisms of ginseng in the treatment of DM-induced ED and asthenospermia following the Traditional Chinese Medicine (TCM) theory of "treating different diseases with the same treatment." This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of Ginseng for the treatment of DM-induced ED and asthenospermia. The chemical ingredients and targets of ginseng were acquired using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. The targets of DM, ED, and asthenospermia were extracted with the GeneCards and Online Mendelian Inheritance in Man databases. A protein-protein interaction network analysis was constructed. The Metascape platform was applied for analyzing the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways. AutoDock Vina was used to perform molecular docking. Network pharmacology revealed that the main active components of the target of action were kaempferol, beta-sitosterol, ginsenoside rh2, stigmasterol, and fumarine. Core targets of the protein-protein interaction network included TNF, IL-1ß, AKT1, PTGS2, BCL2, and JUN. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that they were mainly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, Lipid and atherosclerosis. The interactions of core active components and targets were analyzed by molecular docking. Ginseng may play a comprehensive therapeutic role in the treatment of DM-induced ED and asthenospermia through "multicomponent, multi-target, and multi-pathway" biological mechanisms such as inflammation and oxidative stress.
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Astenozoospermia , Disfunción Eréctil , Simulación del Acoplamiento Molecular , Farmacología en Red , Panax , Masculino , Humanos , Panax/química , Disfunción Eréctil/tratamiento farmacológico , Astenozoospermia/tratamiento farmacológico , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Mapas de Interacción de Proteínas , Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Sitoesteroles/farmacologíaRESUMEN
BACKGROUND: Panax ginseng C. A. Mey is a precious medicinal resource that could be used to treat a variety of diseases. Saponins are the most important bioactive components of, and rare ginsenosides (Rg3, Rh2, Rk1 and Rg5, etc.) refer to the chemical structure changes of primary ginsenosides through dehydration and desugarization reactions, to obtain triterpenoids that are easier to be absorbed by the human body and have higher activity. PURPOSE: At present, the research of P. ginseng. is widely focused on anticancer related aspects, and there are few studies on the antibacterial and skin protection effects of rare ginsenosides. This review summarizes the rare ginsenosides related to bacterial inhibition and skin protection and provides a new direction for P. ginseng research. METHODS: PubMed and Web of Science were searched for English-language studies on P. ginseng published between January 2002 and March 2024. Selected manuscripts were evaluated manually for additional relevant references. This review includes basic scientific articles and related studies such as prospective and retrospective cohort studies. CONCLUSION: This paper summarizes the latest research progress of several rare ginsenosides, discusses the antibacterial effect of rare ginsenosides, and finds that ginsenosides can effectively protect the skin and promote wound healing during use, so as to play an efficient antibacterial effect, and further explore the other medicinal value of ginseng. It is expected that this review will provide a wider understanding and new ideas for further research and development of P. ginseng drugs.
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Ginsenósidos , Panax , Ginsenósidos/farmacología , Ginsenósidos/química , Panax/química , Humanos , Antibacterianos/farmacología , Antibacterianos/química , AnimalesRESUMEN
Panax quinquefolius is a perennial plant with medicinal values. In this study, we assembled the complete mitochondrial genome (mitogenome) of P. quinquefolius using PMAT assembler. The total length of P. quinquefolius mitogenome is 573,154 bp. We annotated a total of 34 protein-coding genes (PCGs), 35 tRNA genes, and 6 rRNA genes in this mitogenome. The analysis of repetitive elements shows that there are 153 SSRs, 24 tandem repeats and 242 pairs of dispersed repeats this mitogenome. Also, we found 24 homologous sequences with a total length of 64,070 bp among its mitogenome and plastome, accounting for 41.05 % of the plastome, and 11.18 % of the mitogenome, showing a remarkable frequent sequence dialogue between plastome and mitogenomes. Besides, a total of 583 C to U RNA editing sites on 34 PCGs of high confidence were predicted by using Deepred-mt. We also inferred the phylogenetic relationships of P. quinquefolius and other angiosperms based on mitochondrial PCGs. Finally, we observed a shift from cis- to trans-splicing in P. quinquefolius for two mitochondrial introns, namely cox2i373 and nad1i728, and a pair of 48 bp short repetitive sequences may be associated with the breaking and rearrangement of the cox2i373 intron. The fragmentation of the cox2i373 intron was further confirmed by our PCR amplification experiments. In summary, our report on the P. quinquefolius mitogenome provides a new perspective on the intron evolution of the mitogenome.
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Genoma Mitocondrial , Intrones , Panax , Filogenia , Trans-Empalme , Panax/genética , Edición de ARN , Empalme del ARN , ARN de Transferencia/genéticaRESUMEN
INTRODUCTION: Ginseng berry (GB) has previously been demonstrated to improve systemic insulin resistance and regulate hepatic glucose metabolism and steatosis in mice with diet-induced obesity (DIO). OBJECTIVES: In this study, the role of GB in metabolism was assessed using metabolomics analysis on the total liver metabolites of DIO mice. METHODS: Metabolomic profiling was performed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF/MS) of liver tissue from mice on a 12-wk normal chow diet (NC), high-fat diet (HFD), and HFD supplemented with 0.1% GB (HFD + GB). The detected metabolites, its pathways, and functions were analyzed through partial least square discriminant analysis (PLS-DA), the small molecular pathway database (SMPDB), and MetaboAnalyst 5.0. RESULTS: The liver metabolite profiles of NC, HFD, and GB-fed mice (HFD + GB) were highly compartmentalized. Metabolites involved in major liver functions, such as mitochondrial function, gluconeogenesis/glycolysis, fatty acid metabolism, and primary bile acid biosynthesis, showed differences after GB intake. The metabolites that showed significant correlations with fasting blood glucose (FBG), insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were highly associated with mitochondrial membrane function, energy homeostasis, and glucose metabolism. Ginseng berry intake increased the levels of metabolites involved in mitochondrial membrane function, decreased the levels of metabolites related to glucose metabolism, and was highly correlated with metabolic phenotypes. CONCLUSION: This study demonstrated that long-term intake of GB changed the metabolite of hepatosteatotic livers in DIO mice, normalizing global liver metabolites involved in mitochondrial function and glucose metabolism and indicating the potential mechanism of GB in ameliorating hyperglycemia in DIO mice.
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Dieta Alta en Grasa , Glucosa , Hígado , Metabolómica , Obesidad , Panax , Animales , Panax/metabolismo , Panax/química , Ratones , Metabolómica/métodos , Hígado/metabolismo , Glucosa/metabolismo , Masculino , Obesidad/metabolismo , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Ratones Obesos , Resistencia a la Insulina , Frutas/metabolismo , Frutas/química , Metaboloma/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/efectos de los fármacosRESUMEN
As one of rare high-value ocotillol (OCT)-type ginsenosides, pseudoginsenoside Rt5 has been identified with significant pharmacological activities. UDP-glycosyltransferases (UGTs) play pivotal roles in catalyzing the transfer of a glycosyl moiety from a donor to an acceptor. In this study, the novel UGT, PjUGT10, was screened from the transcriptome database of Panax japonicus and identified with the enzymatic activity of transferring a glucosyl group on OCT to produce Rt5. The catalytic efficiency of PjUGT10 was further enhanced by employing site-directed mutation. Notably, the variant M7 exhibited a remarkable 6.16 × 103-fold increase in kcat/Km towards 20S,24R-ocotillol and a significant 2.02 × 103-fold increase to UDP-glucose, respectively. Moreover, molecular dynamics simulations illustrated a reduced distance between 20S,24R-ocotillol and the catalytic residue His15 or UDP-glucose, favoring conformation interactions between the enzyme and substrates. Subsequently, Rt5 was synthesized in an engineered Escherichia coli strain M7 coupled with a UDP-glucose synthetic system. This study not only shed light on the protein engineering that can enhance the catalytic activity of PjUGT10, but also established a whole-cell approach for the production of Rt5.
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Ginsenósidos , Glicosiltransferasas , Panax , Ingeniería de Proteínas , Panax/enzimología , Panax/genética , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Glicosiltransferasas/química , Ingeniería de Proteínas/métodos , Ginsenósidos/biosíntesis , Ginsenósidos/química , Ginsenósidos/metabolismo , Simulación de Dinámica Molecular , Especificidad por Sustrato , Escherichia coli/genéticaRESUMEN
Diabetes mellitus is a typical metabolic disease that has become a major threat to human health worldwide. Ginseng polypeptide (GP), a small molecule active substance isolated from ginseng, has shown positive hypoglycemic effects in preliminary studies. However, its mechanism in ameliorating multiorgan damage in db/db mice is unclear. In this study, we utilized network pharmacology, molecular docking, and animal experiments to explore the targets and biological mechanisms of GP to ameliorate multiorgan damage in T2DM. The results showed that GP improves T2DM by inhibiting inflammation and oxidative damage, thereby alleviating hyperglycemia, insulin resistance, and multiorgan damage in db/db mice. These effects are potentially mediated through the PI3K-Akt signaling pathway and the MAPK signaling pathway. This study establishes GP's efficacy in alleviating T2DM and provides a robust theoretical basis for the development of new drugs or functional foods for treating this disease.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Simulación del Acoplamiento Molecular , Farmacología en Red , Panax , Péptidos , Animales , Panax/química , Ratones , Hipoglucemiantes/química , Hipoglucemiantes/administración & dosificación , Masculino , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Péptidos/química , Péptidos/farmacología , Péptidos/administración & dosificación , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Extractos Vegetales/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Resistencia a la Insulina , Transducción de Señal/efectos de los fármacos , Glucemia/metabolismo , Glucemia/efectos de los fármacosRESUMEN
MicroRNA (miRNA) is a class of non-coding endogenous small-molecule, single-stranded RNAs, and it is involved in post-transcriptional gene expression regulation in plants and plays an important role in plant growth and development. Among them, miRNA156 regulates members of target SPL gene family and thus participates in plant growth and development, hormonal response and adversity stress. However, it has not been reported in ginseng. In this study, based on the previous analysis of the SPL gene family, the age-related and stably expressed SPL gene PgSPL24-09 was obtained in roots. The binding site of miRNA156 to this gene was analyzed using target gene prediction tools, and the interactions between miRNA156 and PgSPL24-09 gene were verified by dual luciferase reporter gene assay and RT-qPCR. At the same time, miRNA156 silencing vector and overexpression vector were constructed and transformed into ginseng adventitious roots and Arabidopsis thaliana to analyze the molecular mechanism of miRNA156-SPL module in regulating the growth of ginseng adventitious roots. This study provides a theoretical basis for the in-depth study of the molecular role of miRNAs in ginseng growth, and also lays the foundation for the study of the role of miRNA156-SPL module in regulating the growth and development of ginseng.
Asunto(s)
Regulación de la Expresión Génica de las Plantas , MicroARNs , Panax , Proteínas de Plantas , Raíces de Plantas , Factores de Transcripción , Panax/genética , Panax/metabolismo , Panax/crecimiento & desarrollo , MicroARNs/genética , MicroARNs/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Plantas Modificadas Genéticamente , ARN de Planta/genética , ARN de Planta/metabolismoRESUMEN
To meet societal needs, a large number of medicinal plants are cultivated artificially. However, issues such as diseases and continuous cropping obstacles (CCO) have severely impacted their quality and yield. Exploring and innovating the cultivation technology for medicinal plants is essential to meet their high demand and ensure sustainable development. The role of titanium dioxide nanoparticles (nano-TiO2) in medicinal plant cultivation remains unclear. To advance the application of nanotechnology in this field, a comprehensive exploration of its potential benefits is necessary. In this study, nano-TiO2 was applied to ginseng (Panax ginseng C.A. Meyer) to acquire a holistic comprehension of its impact on ginseng growth, rhizosphere, and ginseng-used soil. Our findings reveal that nano-TiO2 significantly enhances ginseng root activity and has notable effects on antioxidant enzyme systems. The two concentrations of nano-TiO2 markedly influenced the structure and composition of microbial communities in the rhizosphere and ginseng-used soil, including key microorganisms such as Chloroflexi and Acidobacteriota, which are closely involved in soil function. Furthermore, nano-TiO2 altered the competitive and cooperative relationships within microbial networks. Nano-TiO2 application significantly increased soil organic matter (SOM) content in rhizosphere and ginseng-used soils and affected the activities of several important soil enzymes. Environmental factors, such as EC, pH, and soil nutrients, were found to be the main factors influencing the microbial community. In conclusion, our findings illuminate the complex effects of nano-TiO2 on the "plant-microbial-soil" system in the context of ginseng cultivation. This work offers novel strategies for optimizing medicinal plant growth and development, as well as improving cultivated soil by using nanomaterials.
Asunto(s)
Microbiota , Panax , Plantas Medicinales , Microbiología del Suelo , Suelo , Titanio , Panax/crecimiento & desarrollo , Suelo/química , Microbiota/efectos de los fármacos , Rizosfera , Nanopartículas , Nanopartículas del MetalRESUMEN
GFRS is the conversion product of Panax ginseng Meyer berry after citric acid heat treatment, which is rich in rare ginsenosides. However, the anti-melanin role of GFRS in the regulation of skin pigmentation and its material basis remains unclear. To compare the anti-melanin activity before and after citric acid heat treatment, we determined the effects of GFS and GFRS on tyrosinase activity and melanin lever under α-MSH stimulation and found the potential anti-melanin effect of GFRS. Further, Western blot and immunofluorescence methods were used to reveal the mechanism by which GFRS detects anti-melanin activity by promoting autophagy flux levels. In zebrafish models, GFRS inhibited endogenous melanin and tyrosinase better than arbutin and promoted the accumulation of autophagy levels in vivo. To determine the material basis of the anti-melanin effect of GFRS, HPLC was used to isolate and prepare 12 ginsenosides from GFRS, and their activity evaluation and structure-activity relationship analysis were performed. The results showed that the inhibitory effect of GFRS on melanin was Rg3 > Rg5 > Rk1 > Rd. Molecular docking showed that their docking fraction with mushroom tyrosinase was significantly better than that of arbutin, but the presence of C-20 glycosylation decreased the anti-melanin activity of Rd. To maximize the content of Rg3, Rg5, and Rk1, we optimized the process by using citric acid heat treatment of ginsenoside Rd and found that citric acid heat treatment at 100°C almost completely transformed Rd and obtained a high content of active ingredients. In summary, our data demonstrated that GFRS exerted anti-melanin effects by inducing autophagy. It was further revealed that Rg3, Rg5, and Rk1, as effective active components, could be enriched by the improved process of converting ginsenoside Rd by citric acid heat treatment.
Asunto(s)
Autofagia , Ácido Cítrico , Ginsenósidos , Calor , Melaninas , Panax , Pez Cebra , Panax/química , Melaninas/metabolismo , Melaninas/antagonistas & inhibidores , Ginsenósidos/farmacología , Ginsenósidos/química , Ginsenósidos/aislamiento & purificación , Animales , Relación Estructura-Actividad , Autofagia/efectos de los fármacos , Ácido Cítrico/química , Ácido Cítrico/farmacología , Estructura Molecular , Frutas/química , Simulación del Acoplamiento Molecular , Relación Dosis-Respuesta a Droga , Monofenol Monooxigenasa/metabolismo , Monofenol Monooxigenasa/antagonistas & inhibidoresRESUMEN
Ginseng, a cornerstone of traditional herbal medicine in Asia, garnered significant attention for its therapeutic potential. Central to its pharmacological effects are ginsenosides, the primary active metabolites, many of which fall within the dammarane-type and share protopanaxadiol as a common precursor. Challenges in extracting protopanaxadiol and ginsenosides from ginseng arise due to their low concentrations in the roots. Emerging solutions involve leveraging microbial cell factories employing genetically engineered yeasts. Here, we optimized the fermentation conditions via the Design of Experiment, realizing 1.2 g/L protopanaxadiol in simple shake flask cultivations. Extrapolating the optimized setup to complex ginsenosides, like compound K, achieved 7.3-fold (0.22 g/L) titer improvements. Our adaptable fermentation conditions enable the production of high-value products, such as sustainable triterpenoids synthesis. Through synthetic biology, microbial engineering, and formulation studies, we pave the way for a scalable and sustainable production of bioactive compounds from ginseng.