RESUMEN
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
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
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
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
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.
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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
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.
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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.
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Fermentación , Ginsenósidos , Triterpenos , Ginsenósidos/biosíntesis , Ginsenósidos/metabolismo , Triterpenos/metabolismo , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/crecimiento & desarrollo , Panax/metabolismo , Panax/crecimiento & desarrollo , Panax/química , Ingeniería Metabólica , SapogeninasRESUMEN
The function of the Trihelix transcription factor is that it plays an important role in many abiotic stresses, especially in the signaling pathway of low temperature, drought, flood, saline, abscisic acid, methyl jasmonate, and other abiotic stresses. However, there are few studies on the Trihelix gene family of ginseng. In this study, 41 Trihelix gene family members were identified and screened from the ginseng genome database, and their physicochemical properties, cis-acting elements, subcellular localization, chromosomal assignment, and abiotic stress-induced expression patterns were analyzed by bioinformatics methods. The results showed that 85% of Trihelix family members of ginseng were located in the nucleus, and the main secondary structure of Trihelix protein was random coil and α helix. In the promoter region of Trihelix, cis-acting regulatory elements related to various abiotic stresses such as low temperature, hormone response, and growth and development were identified. Through the collinearity analysis of interspecific Trihelix transcription factors of model plants Arabidopsis thaliana and ginseng, 19 collinear gene pairs were found between A. thaliana and ginseng, and no collinear gene pairs existed on chromosomes 3, 6, and 12 only. qRT-PCR analysis showed that the expression of GWHGBEIJ010320.1 was significantly up-regulated under low temperature stress, a significant response to low temperature stress. This study lays a foundation for further research on the role of the Trihelix transcription factor of ginseng in abiotic stress, as well as the growth and development of ginseng.
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Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Panax , Filogenia , Proteínas de Plantas , Estrés Fisiológico , Factores de Transcripción , Panax/genética , Panax/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Estrés Fisiológico/genética , Regiones Promotoras Genéticas , Perfilación de la Expresión GénicaRESUMEN
Medicinal plant-derived vesicle-like nanoparticles can carry chemical components and exert intercellular activity due to the encapsulation of nanostructures. American ginseng is well known as a traditional herb and is commonly used in clinical decoctions. However, the nano-characteristics and chemical composition of American-ginseng-derived vesicle-like nanoparticles (AGVNs) in decoctions are unclear. In this study, the gradient centrifugation method was used to extract and isolate AGVNs. A metabolomic method based on high-resolution mass spectrometry was established to analyze small molecules loaded in AGVNs. Zebrafish and RAW264.7 cells were employed to investigate the anti-inflammatory effects of AGVNs. The results showed that the particle size of AGVNs was generally 243.6 nm, and the zeta potential was -14.5 mV. AGVNs were found to contain 26 ginsenosides (14 protopanaxadiols, 11 protopanaxatriols, and 1 oleanolic acid). Ginsenoside Rb1 and malonyl-ginsenoside Rb1 tended to be enriched in AGVNs. Moreover, AGVNs were found to exert anti-inflammatory effects by reducing macrophage migration in zebrafish and regulating inflammatory factor (NO, TNF-α, IL-6, IL-10) secretion in RAW 264.7 cells. The characterization and analysis of AGVNs provide references and data that support the development of nanoscale anti-inflammatory substances from medicinal plants.
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Antiinflamatorios , Nanopartículas , Panax , Pez Cebra , Animales , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/química , Células RAW 264.7 , Nanopartículas/química , Panax/química , Tamaño de la Partícula , Extractos Vegetales/farmacología , Extractos Vegetales/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ginsenósidos/farmacología , Ginsenósidos/químicaRESUMEN
Identifying the catalytic regioselectivity of enzymes remains a challenge. Compared to experimental trial-and-error approaches, computational methods like molecular dynamics simulations provide valuable insights into enzyme characteristics. However, the massive data generated by these simulations hinder the extraction of knowledge about enzyme catalytic mechanisms without adequate modeling techniques. Here, we propose a computational framework utilizing graph-based active learning from molecular dynamics to identify the regioselectivity of ginsenoside hydrolases (GHs), which selectively catalyze C6 or C20 positions to obtain rare deglycosylated bioactive compounds from Panax plants. Experimental results reveal that the dynamic-aware graph model can excellently distinguish GH regioselectivity with accuracy as high as 96-98% even when different enzyme-substrate systems exhibit similar dynamic behaviors. The active learning strategy equips our model to work robustly while reducing the reliance on dynamic data, indicating its capacity to mine sufficient knowledge from short multi-replica simulations. Moreover, the model's interpretability identified crucial residues and features associated with regioselectivity. Our findings contribute to the understanding of GH catalytic mechanisms and provide direct assistance for rational design to improve regioselectivity. We presented a general computational framework for modeling enzyme catalytic specificity from simulation data, paving the way for further integration of experimental and computational approaches in enzyme optimization and design.
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Ginsenósidos , Simulación de Dinámica Molecular , Ginsenósidos/química , Ginsenósidos/metabolismo , Especificidad por Sustrato , Hidrolasas/química , Hidrolasas/metabolismo , Panax/química , Panax/enzimologíaRESUMEN
The geographical origin of Panax ginseng significantly influences its nutritional value and chemical composition, which in turn affects its market price. Traditional methods for analyzing these differences are often time-consuming and require substantial quantities of reagents, rendering them inefficient. Therefore, hyperspectral imaging (HSI) in conjunction with X-ray technology were used for the swift and non-destructive traceability of Panax ginseng origin. Initially, outlier samples were effectively rejected by employing a combined isolated forest algorithm and density peak clustering (DPC) algorithm. Subsequently, random forest (RF) and support vector machine (SVM) classification models were constructed using hyperspectral spectral data. These models were further optimized through the application of 72 preprocessing methods and their combinations. Additionally, to enhance the model's performance, four variable screening algorithms were employed: SelectKBest, genetic algorithm (GA), least absolute shrinkage and selection operator (LASSO), and permutation feature importance (PFI). The optimized model, utilizing second derivative, auto scaling, permutation feature importance, and support vector machine (2nd Der-AS-PFI-SVM), achieved a prediction accuracy of 93.4 %, a Kappa value of 0.876, a Brier score of 0.030, an F1 score of 0.932, and an AUC of 0.994 on an independent prediction set. Moreover, the image data (including color information and texture information) extracted from color and X-ray images were used to construct classification models and evaluate their performance. Among them, the SVM model constructed using texture information from X -ray images performed the best, and it achieved a prediction accuracy of 63.0 % on the validation set, with a Brier score of 0.181, an F1 score of 0.518, and an AUC of 0.553. By implementing mid-level fusion and high-level data fusion based on the Stacking strategy, it was found that the model employing a high-level fusion of hyperspectral spectral information and X-ray images texture information significantly outperformed the model using only hyperspectral spectral information. This advanced model attained a prediction accuracy of 95.2 %, a Kappa value of 0.912, a Brier score of 0.027, an F1 score of 0.952, and an AUC of 0.997 on the independent prediction set. In summary, this study not only provides a novel technical path for fast and non-destructive traceability of Panax ginseng origin, but also demonstrates the great potential of the combined application of HSI and X-ray technology in the field of traceability of both medicinal and food products.
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Algoritmos , Imágenes Hiperespectrales , Panax , Máquina de Vectores de Soporte , Panax/clasificación , Panax/química , Imágenes Hiperespectrales/métodos , Luz , Rayos XRESUMEN
BACKGROUND: Ginseng Radix et Rhizoma (GS) is frequently used as an adjuvant therapy for patients with heart failure (HF). Metoprolol is widely used in patients with HF. However, there is no report on the combined effects of GS and metoprolol in patients with HF. OBJECTIVE: This study investigated the combined effects of GS and metoprolol in male C57BL/6J mice with HF and the underlying mechanisms. MATERIALS AND METHODS: We utilized a mouse myocardial HF model to measure the serum levels of creatine kinase (CK) and creatine kinase-MB form (CK-MB) using an automated biochemical analyzer. Lactate dehydrogenase (LDH) and cardiac troponin (cTnT) levels were determined using enzyme-linked immunosorbent assays. Autophagy of myocardial cells was evaluated using transmission electron microscopy, and changes in signal pathway proteins related to autophagy were analyzed by Western blotting. RESULTS: GS combined with metoprolol improved heart function, reduced heart damage, and decreased serum levels of CK, CK-MB, LDH, and cTnT. The combination of GS and metoprolol decreased autophagy in myocardial cells by reducing the levels of autophagy-related proteins (LC3, p62, Beclin1, and Atg5) and increasing the ratios of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. CONCLUSION: GS enhanced the anti-heart failure effect of metoprolol. Its mechanism of action might be related to the inhibition of autophagy mediated by the activation of the PI3K/Akt/mTOR pathway.
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Autofagia , Insuficiencia Cardíaca , Metoprolol , Ratones Endogámicos C57BL , Panax , Animales , Masculino , Autofagia/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/metabolismo , Metoprolol/farmacología , Ratones , Panax/química , Transducción de Señal/efectos de los fármacos , Enfermedad Crónica , Rizoma/química , Modelos Animales de Enfermedad , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Extractos Vegetales/farmacología , Creatina Quinasa/sangre , Sinergismo Farmacológico , Forma MB de la Creatina-Quinasa/sangreRESUMEN
Ginseng, a highly esteemed herbal medicine, has been utilized over 5000 years, predominantly in Far Eastern countries. Ginseng is categorized into garden ginseng (GG) and ginseng under forest (FG). However, in contrast to FG, excessive intake of GG may lead to potential adverse effects due to disruption of epithelial cell integrity, and the specific population groups that may be at higher risk. In this work, untargeted metabolomics were used to determine the heterogeneity between GG and FG, the data indicates that the content of Ethyl caffeate, Homoorientin, Citric acid and Quinic acid in GG were higher than in FG. Mass spectrometry imaging showed that ethyl caffeate and Homoorientin were concentrated on the brownish yellow exocarp of the primary root. Our experiments demonstrated that excessive exposure to ethyl caffeate and Homoorientin exacerbated the inflammatory response of HUVECs and reduced the expression of cell junctions. This suggest that the compounds causing adverse effects from excessive intake of GG are mainly concentrated in the yellow exocarp of the primary root of GG. These results suggest that untargeted metabolomics coupled with MALDI-MSI can visualize the spatial distribution of endogenous differential molecules of the same herb in different growth environments or developmental stages.
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Inflamación , Panax , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Panax/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Bosques , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Metabolómica/métodosRESUMEN
BACKGROUND: Vascular dementia (VaD) resulting from chronic cerebral hypoperfusion (CCH) induces cognitive impairment and white matter injury (WMI). We previously found that CCH induces dysfunction of the autophagy-lysosomal pathway (ALP) in white matter (WM) of rats. Enhancing oligodendrocyte autophagy to counteract ALP deficiency is beneficial for cognitive recovery. Pseudogenoside-F11 (PF11), a saponin extracted from Panax quinquefolium l., provides neuroprotective benefits in many animal models of cerebral ischemia and dementia. PURPOSE: To investigate how PF11 affects cognitive deterioration in rats with VaD induced by two vessel occlusion (2VO), and to determine if PF11 regulates ALP dysfunction in WM. METHODS: CCH-related VaD was induced in rats using the 2VO method. PF11 (6, 12, 24 mg/kg, intragastric administration) was given continuously for 4 weeks postoperatively. Behavioral tests related to cognitive function were performed on the 28th day following 2VO. Transmission electron microscopy, immunofluorescence, western blotting and Luxol fast blue staining were used to assess the WMI and the mechanism of action of PF11 in 2VO-induced VaD. RESULTS: PF11 (12 mg/kg) ameliorated 2VO-induced cognitive impairment. PF11 also alleviated WMI on the 28th day following 2VO, as characterized by reduction of neuronal axonal demyelination and axonal loss. Furthermore, PF11 prevented mature oligodendrocytes death by attenuating ALP deficiency in WM on the 14th day following 2VO, as manifested by enhancement of mechanistic target of rapamycin-mediated autophagy and lysosomal function, thereby reducing the aberrant accumulation of autophagy substrates and increasing the level of autophagosomes in WM. In addition, PF11 also prevented microglia and astrocytes from activating in WM on the 28th day following 2VO. CONCLUSION: PF11 significantly ameliorates cognitive impairment and WMI, and the mechanism is at least partly related to lessening ALP dysfunction in WM by enhancing autophagy and reducing lysosomal defects in oligodendrocytes.