RESUMEN

As a kind of tonic Chinese medicine with dual use in medicine and food, there is a large market demanding for Codonopsis pilosula. Taking one-year-old C. pilosula seedlings as materials, we conducted a field experiment to examine the effect of compound fertilizer (750 kg·hm-2), organic fertilizer (15 t·hm-2) and Streptomyces pactum Act12 agent (9 t·hm-2 Act12+10 t·hm-2 organic fertilizer) treatments on root morphology, secondary metabolite content and expression level of lobetyolin metabolic pathway gene of C. pilosula, to clarify the effects of three fertilizers on the root morphology and medicinal quality. Compared to the control (10 t·hm-2 organic fertilizer, conventional fertilization), three fertilization treatments could promote root growth and formation. All fertilization treatments promoted the accumulation of C. pilosula polysaccharides and secondary metabolites. Act12 agent significantly increased the content of lobetyolin, atractylenolideIII, and 5-hydroxymethylfurfural. The qRT-PCR analysis indicated that three fertilization treatments increased the expression level of lobetyolin metabolic pathway genes, with Act12 agent treatment showing the most significant effect. Pearson correlation analysis demonstrated that the expression level of CpHCT and CpFAD genes was significantly positively correlated with atractylenolide III content. In conclusion, three fertilization treatments could effectively improve the yield and quality of C. pilosula. Among the three treatments, Act12 agent performed better than that of compound fertilizer and organic fertilizer, which was an effective measure to increase the yield and quality of C. pilosula.

Asunto(s)

Codonopsis , Fertilizantes , Raíces de Plantas , Streptomyces , Codonopsis/crecimiento & desarrollo , Codonopsis/metabolismo , Streptomyces/crecimiento & desarrollo , Streptomyces/metabolismo , Streptomyces/genética , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Plantas Medicinales/crecimiento & desarrollo , Plantas Medicinales/metabolismo , Plantas Medicinales/química

RESUMEN

Codonopsis pilosula, an important medicinal and edible plant in traditional Chinese medicine, is used widely as a tonifying herb for various immunodeficiency diseases. A neutral polysaccharide (CPPs-D1N1) was purified from C. pilosula, composed of fructose and glucose in a molar ratio of 97.28:2.72, with an average molecular weight of 5.985 kDa. Structural analysis revealed a backbone composed of →1)-ß-D-Fruf-(2 â†’ units with some ß-D-Fruf-(2 â†’ linkages. In a murine immunosuppression model induced by cyclophosphamide injection, oral treatment with C. pilosula polysaccharide was administered, investigating changes in gut microbiota during therapy. The polysaccharide modulated serum immunoglobulins (Ig-G, Ig-M), cytokines (IL-2, IL-6, TNFα), and spleen and thymus indices in immunodeficient mice. Additionally, functional gene primer sequencing enrichment methods revealed alterations in abundance, diversity, and structure of butyrate-producing bacterial populations in the gut, with primary differential genera identified as Butyribacter, Rumanococcus, Dysosmobacter, and Ruseburia. This study provides in vivo evidence supporting the beneficial effects of C. pilosula polysaccharide oral therapy in improving gut microbiota, particularly butyrate-producing bacteria, during treatment of immunosuppressive diseases.

Asunto(s)

Codonopsis , Microbioma Gastrointestinal , Huésped Inmunocomprometido , Polisacáridos , Animales , Codonopsis/química , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Microbioma Gastrointestinal/efectos de los fármacos , Huésped Inmunocomprometido/efectos de los fármacos , Ácido Butírico/química , Ácido Butírico/farmacología , Bacterias/efectos de los fármacos , Intestinos/efectos de los fármacos , Intestinos/microbiología , Citocinas/metabolismo , Masculino

RESUMEN

The integrated plant-metabolite-soil regulation model of C. Pilosula growth and lobetyolin synthesis in response to continuous cropping lacks systematic investigation. In this study, we investigated the regulatory mechanisms of growth and lobetyolin synthesis in C. pilosula under continuous cropping stress based on high-performance liquid chromatography, transcriptome, and microbial sequencing on the root system and rhizosphere soil of C. pilosula from one year of cultivation and five years of continuous cropping. The findings of this study revealed that continuous cropping significantly inhibited the growth of C. pilosula and led to a notable decrease in the lobetyolin content. An effort was made to propose a potential pathway for lobetyolin biosynthesis in C. pilosula, which is closely linked to the expression of genes responsible for glucoside and unsaturated fatty acid chain synthesis. In addition, soil physicochemical properties and soil microorganisms had strong correlations with root growth and synthesis of lobetyolin, suggesting that soil physicochemical properties and microorganisms are the main factors triggering the succession disorder in C. pilosula. This study provides an in-depth interpretation of the regulatory mechanism of acetylenic glycoside synthesis and offers new insights into the triggering mechanism of C. pilosula succession disorder, which will guide future cultivation and industrial development.

Asunto(s)

Codonopsis , Raíces de Plantas , Plantas Medicinales , Suelo , Suelo/química , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/microbiología , Raíces de Plantas/química , Codonopsis/metabolismo , Codonopsis/crecimiento & desarrollo , Codonopsis/química , Plantas Medicinales/metabolismo , Plantas Medicinales/química , Plantas Medicinales/crecimiento & desarrollo , Plantas Medicinales/genética , Microbiología del Suelo , Poliinos/metabolismo , Rizosfera , Producción de Cultivos/métodos

RESUMEN

Codonopsis Radix (CR), a traditional tonic medicinal material in China, has been proven to possess a variety of bioactive functions. However, its chemical composition and in vivo metabolic pattern have not been fully elucidated. In this study, AB-8 macroporous resin column chromatography was employed for the enrichment of small molecular components in CR. Furthermore, a method combining ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry with Acquire X intelligent data acquisition technology software was developed for the preliminary screening and identification of the chemical composition of CR in vitro and their metabolites in vivo. As a result, a total of 116 components were preliminarily characterized in the CR extract, including 28 polyacetylenes, 33 organic acids, 4 amino acids, 23 alkaloids, 9 phenylpropanoids, 6 terpenoids, 2 nucleosides, and 11 others. Additionally, a total of 84 compounds, including 37 prototype components and 47 metabolites, were identified in the plasma, urine, and feces of rats after oral administration of CR. Specifically, 11, 24, 19, 32, and 25 constituents were identified in the heart, liver, spleen, lung, and kidney, respectively. Of note, the lung and spleen are the organs with the highest distribution of CR compounds. These findings will serve as valuable data for future research on the correlation between the chemical composition and pharmacological effects of CR.

Asunto(s)

Codonopsis , Medicamentos Herbarios Chinos , Animales , Ratas , Administración Oral , Alcaloides/análisis , Alcaloides/química , Cromatografía Líquida de Alta Presión/métodos , Codonopsis/química , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Heces/química , Espectrometría de Masas/métodos , Metaboloma , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/farmacocinética , Raíces de Plantas/química , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem/métodos , Distribución Tisular

RESUMEN

Codonopsis convolvulacea is a highly valued Chinese medicinal plant containing diverse bioactive compounds. While roots/tubers have been the main medicinal parts used in practice, leaves and stems may also harbor valuable phytochemicals. However, research comparing volatiles across tissues is lacking. This study performed metabolomic profiling of leaves, stems, and tubers of C. convolvulacea to elucidate tissue-specific accumulation patterns of volatile metabolites. Ultra-high performance liquid chromatography-tandem mass spectrometry identified 302 compounds, belonging to 14 classes. Multivariate analysis clearly differentiated the metabolic profiles of the three tissues. Numerous differentially accumulated metabolites (DAMs) were detected, especially terpenoids and esters. The leaves contained more terpenoids, ester, and alcohol. The stems accumulated higher levels of terpenoids, heterocyclics, and alkaloids with pharmaceutical potential. The tubers were enriched with carbohydrates like sugars and starch, befitting their storage role, but still retained reasonable amounts of valuable volatiles. The characterization of tissue-specific metabolic signatures provides a foundation for the selective utilization of C. convolvulacea parts. Key metabolites identified include niacinamide, p-cymene, tridecanal, benzeneacetic acid, benzene, and carveol. Leaves, stems, and tubers could be targeted for antioxidants, drug development, and tonics/nutraceuticals, respectively. The metabolomic insights can also guide breeding strategies to enhance the bioactive compound content in specific tissues. This study demonstrates the value of tissue-specific metabolite profiling for informing the phytochemical exploitation and genetic improvement of medicinal plants.

Asunto(s)

Codonopsis , Metabolómica , Fitoquímicos , Hojas de la Planta , Tallos de la Planta , Tubérculos de la Planta , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Tallos de la Planta/química , Tallos de la Planta/metabolismo , Metabolómica/métodos , Fitoquímicos/análisis , Fitoquímicos/metabolismo , Tubérculos de la Planta/química , Tubérculos de la Planta/metabolismo , Codonopsis/química , Codonopsis/metabolismo , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión , Metaboloma , Terpenos/metabolismo , Terpenos/análisis , Plantas Medicinales/metabolismo , Plantas Medicinales/química

RESUMEN

Age-related macular degeneration (AMD) is one of the leading causes of blindness. AMD is currently incurable; the best solution is to prevent its occurrence. To develop drugs for AMD, it is crucial to have a model system that mimics the symptoms and mechanisms in patients. It is most important to develop safer and more effective anti-AMD drug. In this study, the dose of A2E and the intensity of blue light were evaluated to establish an appropriate atrophic in vitro model of AMD and anti-AMD effect and therapeutic mechanism of Codonopsis lanceolata. The experimental groups included a control group an AMD group treated with A2E and blue light, a lutein group treated with 25 µM lutein after AMD induction, and three groups treated with different doses of C. lanceolata (10, 20, and 50 µg/mL) after AMD induction. Intrinsic apoptotic pathway (Bcl-2 family), anti-oxidative system (Keap1/Nrf2/HO-1 antioxidant response element), and anti-carbonyl effect (4-hydroxynonenal [4-HNE]) were evaluated using immunofluorescence, MTT, TUNEL, FACS, and western blotting analyses. A2E accumulation in the cytoplasm of ARPE-19 cells depending on the dose of A2E. Cell viability of ARPE-19 cells according to the dose of A2E and/or blue light intensity. The population of apoptotic or necrotic cells increased based on the A2E dose and blue light intensity. Codonopsis lanceolata dose-dependently prevented cell death which was induced by A2E and blue light. The antiapoptotic effect of that was caused by activating Keap1/Nrf2/HO-1 pathway, suppressing 4-HNE, and modulating Bcl-2 family proteins like increase of antiapoptotic proteins such as Bcl-2 and Bcl-XL and decrease of proapoptotic protein such as Bim. Based on these findings, 30 µM A2E and 20 mW/cm2 blue light on adult retinal pigment epithelium-19 cells was an appropriate condition for AMD model and C. lanceolata shows promise as an anti-AMD agent.

Asunto(s)

Apoptosis , Codonopsis , Degeneración Macular , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Codonopsis/química , Humanos , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/metabolismo , Degeneración Macular/patología , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Extractos Vegetales/farmacología , Antioxidantes/farmacología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Línea Celular , Aldehídos/farmacología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Luz/efectos adversos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo

RESUMEN

To address the low efficiency and high labor demands of manual Codonopsis pilosula cultivation, as well as the limitations of existing flat-type transplanting machines that create trenches of inconsistent depth hindering root growth and seedling emergence, a C. pilosula film-covered outcrop tilted transplanting machine was developed. Based on theoretical analysis of the prototype's key components and agronomic requirements for oblique C. pilosula transplanting, the structure and working parameters of the rotary tiller soil throwing device, soil lifting device, track-type soil conveying device, seedling throwing device, and film covering device were determined. The core components' working principles were analyzed, and the soil throwing process of the rotary tiller device was simulated using the discrete element method (DEM). A calculation domain was established, and the results showed that the average mass of the rotary tiller device was 49.44 kg, while the required soil lifting amount for the scraper-type soil lifting device was 21.84 kg, meeting the soil throwing requirements. Field experiments in 10 test areas demonstrated an average qualified rate of 89.50% for planting depth, 84.00% for planting posture, 90% for exposed plant spacing, 4.51 cm for plant spacing, and 8.67% coefficient of variation for planting spacing. These results meet industry standards for planting depth and planting spacing, confirming the machine's effectiveness in achieving high-quality tilted transplanting of C. pilosula seedlings.

Asunto(s)

Codonopsis , Suelo , Codonopsis/crecimiento & desarrollo , Suelo/química , Agricultura/métodos , Diseño de Equipo , Raíces de Plantas/crecimiento & desarrollo , Plantones/crecimiento & desarrollo

RESUMEN

Campanumoea javanica Bl. (CJ) traditionally used in Southwestern China, is now widely consumed as a health food across the nation. Due to its similar efficacy to Codonopsis Radix (CR) and their shared botanical family, CJ is often used as a substitute for CR. According to the Chinese Pharmacopoeia, Codonopsis pilosula var. modesta (Nannf.) L.T. Shen (CPM), Codonopsis pilosula (Franch.) Nannf. (CP), and Codonopsis tangshen Oliv. (CT) are the primary sources of CR. However, details on the differences in composition, effectiveness, and compositional between CJ and CR are still limited. Besides, there is little evidence to support the application of CJ as a drug. In this study, we employed widely targeted metabolomics, network pharmacology analysis, and molecular docking to explore the disparities in metabolite profiles between CJ and CR and to predict the pharmacological mechanisms of the dominant differential metabolites of CJ and their potential medicinal applications. The widely targeted metabolomics results indicated that 1,076, 1,102, 1,102, and 1,093 compounds, most phenolic acids, lipids, amino acids, and flavonoids, were characterized in CJ, CPM, CP, and CT, respectively. There were an average of 1061 shared compounds in CJ and CRs, with 95.07% similarity in metabolic profiles. Most of the metabolites in CJ were previously unreported. Twelve of the seventeen dominant metabolites found in CJ were directly associated with treating cancer and lactation, similar to the traditional medicinal efficacy. The molecular docking results showed that the dominant metabolites of CJ had good docking activity with the core targets PIK3R1, PIK3CA, ESR1, HSP90AA1, EGFR, and AKT1. This study provides a scientific basis for understanding the similarities and differences between CJ and CR at the metabolome level, offering a theoretical foundation for developing innovative medications from CJ. Additionally, it significantly enhances the metabolite databases for both CJ and CR.

Asunto(s)

Codonopsis , Metabolómica , Farmacología en Red , Codonopsis/química , Codonopsis/metabolismo , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Raíces de Plantas/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/metabolismo

RESUMEN

BACE1, a crucial enzyme in the amyloid-ß deposition theory of Alzheimer's disease (AD), is targeted by Codonopsis pilosula, a traditional tonic believed to impede AD onset. However, the specific active compounds responsible for its effects remain elusive. Our prior network pharmacology research identified C. pilosula polysaccharides (CPPS) and Lobetyolin may serve as potential inhibitors of AD by suppressing amyloidogenesis. Here, we recombinantly expressed BACE1 under varied conditions and assessed its activity using Fluorescence Resonance Energy Transfer technology. Through spectroscopy, molecular docking, and dynamics, we elucidated the interactions of CPPS, Lobetyolin, and BACE1. Optimal BACE1 expression occurred at 22 °C with 0.4 mM IPTG for 6 h, yielding a 72 kDa protein. Enzyme kinetics displayed a maximum rate of 4096 µmol/min and a Michaelis constant of 16 mg/mL for BACE1. Spectroscopic analysis revealed differing binding affinities of the compounds at various temperatures, peaking at 293 K. Lobetyolin exhibited superior binding to BACE1 compared to CPPS, driven by hydrophobic and electrostatic forces. Molecular docking and dynamics highlighted hydrophobic amino acids' role in BACE1 interactions with Lobetyolin and CPPS, with binding energy < -1.2 kcal/mol signifying strong affinities. Notably, Lobetyolin and CPPS showed higher BACE1 affinity than APP, with the Lobetyolin-BACE1 complex being the most stable.

Asunto(s)

Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Codonopsis , Simulación del Acoplamiento Molecular , Polisacáridos , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/genética , Ácido Aspártico Endopeptidasas/metabolismo , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/química , Humanos , Codonopsis/química , Polisacáridos/química , Polisacáridos/metabolismo , Cinética , Unión Proteica , Expresión Génica , Simulación de Dinámica Molecular , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/química

RESUMEN

Species of the genus Codonopsis (Campanulaceae) have a long history of application, acclaimed for its edible and therapeutic attributes. Scholarly inquiries into Codonopsis span botany, phytochemistry, quality assurance, pharmacodynamics, and toxicity, revealing a rich and comprehensive body of knowledge. This study synthesizes information from esteemed scientific databases like SciFinder, PubMed, China National Knowledge Infrastructure, and Chinese herbal classics to create a thorough scientific conceptual and theoretical framework for Codonopsis research. In this article, the phytochemical composition includes saccharides, polyacetylenes, polyenes, flavonoids, alkaloids, lignans, terpenoids, and organic acids was summarized. To date, over 350 monomeric compounds have been isolated and identified from Codonopsis, with recent studies primarily focusing on polysaccharides, aromatic derivatives, lignans, and polyacetylenes. Codonopsis exhibits broad pharmacological activities across various systems, including immune, blood, cardiovascular, central nervous, and digestive systems, with no significant toxicity or adverse effects reported. The existing research, focusing on various extracts and active parts without identifying specific active molecules, complicates the understanding of the mechanisms of action. There is an urgent need to advance research on the chemical composition and pharmacological effects to fully elucidate its pharmacodynamic properties and the basis of its material composition. Such efforts are crucial for the rational development, utilization, and clinical application of this herb.

Asunto(s)

Codonopsis , Codonopsis/química , Humanos , Fitoquímicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Lignanos/farmacología , Alcaloides/farmacología , Alcaloides/análisis

RESUMEN

In this work, the selenylation Codonopsis pilosula polysaccharide (Se-CPPS) were synthesized using an optimized microwave-assisted method. Then, physicochemical properties, including molecular weight, particle size, valence state of selenium, antioxidant capacity, release mechanism of selenium under gastrointestinal conditions, as well as their effects on HT-29 cell viability were comprehensively investigated. The results demonstrated that Se-CPPS with the highest selenium content (21.71 mg/g) was synthesized using 0.8% nitric acid concentration under microwave conditions of 90 min at 70 °C. FTIR and XPS analysis revealed that Se was bound to the polysaccharide chain in the form of O-Se-O and O-H···Se, with a valence state of either 0 or +4. In vitro investigations on antioxidant activity and selenium release capacity indicated that selenization not only enhanced the antioxidant activity of CPPS but also endowed Se-CPPS with robust selenium release capability in simulated gastric digestion. The effects of Se-CPPS on HT-29 cells was further investigated by CCK-8 method. The results showed that the selenide modification effectively reduced the toxicity of Na2SeO3 and enhanced the viability of CPPS. The findings of this study offer valuable methodological guidance for the synthesis of Se-polysaccharides with superior functional properties.

Asunto(s)

Antioxidantes , Supervivencia Celular , Codonopsis , Microondas , Polisacáridos , Selenio , Codonopsis/química , Humanos , Selenio/química , Polisacáridos/química , Polisacáridos/farmacología , Células HT29 , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Supervivencia Celular/efectos de los fármacos , Peso Molecular

RESUMEN

Codonopsis pilosula polysaccharides (CPP), the main active ingredient of Codonopsis pilosula, has gained significant attention as a liver-protective agent. Previous studies have demonstrated that CPP could alleviate gut microbiota dysbiosis in colitis or obese mice. However, the effects of CPP on mycotoxin-induced liver injury and gut microbiota dysbiosis are still poorly understood. In this study, we aimed to investigate the protective effects of CPP on sterigmatocystin (STC)-induced liver injury, as well as its regulatory effects on gut microbiota. Our results revealed that CPP intervention significantly alleviated STC-induced liver injury, as evidenced by decreased liver index, reduced liver histopathological changes, and modulation of related molecular markers. Additionally, we found that CPP could alleviate liver injury by reducing liver inflammation and oxidative stress, inhibiting hepatocyte apoptosis, and regulating lipid metabolism. Notably, we also observed that CPP could alleviate STC-induced gut microbiota dysbiosis by modulating the diversity and richness of gut microbiota, suggesting that gut microbiota modulation may also serve as a mechanism for CPP-mediated remission of liver injury. In summary, our study not only provided a new theoretical basis for understanding the hepatotoxicity of STC and the protective effects of CPP against STC-induced liver injury, but also provided new perspectives for the application of CPP in the fields of food, healthcare products, and medicine.

Asunto(s)

Enfermedad Hepática Inducida por Sustancias y Drogas , Codonopsis , Disbiosis , Microbioma Gastrointestinal , Polisacáridos , Esterigmatocistina , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Disbiosis/tratamiento farmacológico , Codonopsis/química , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Masculino , Esterigmatocistina/farmacología , Estrés Oxidativo/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología

RESUMEN

The majority of the immune cell population in the tumor microenvironment (TME) consists of tumor-associated macrophages (TAM), which are the main players in coordinating tumor-associated inflammation. TAM has a high plasticity and is divided into two main phenotypes, pro-inflammatory M1 type and anti-inflammatory M2 type, with tumor-suppressive and tumor-promoting functions, respectively. Considering the beneficial effects of M1 macrophages for anti-tumor and the high plasticity of macrophages, the conversion of M2 TAM to M1 TAM is feasible and positive for tumor treatment. This study sought to evaluate whether the glycopeptide derived from simulated digested Codonopsis pilosula extracts could regulate the polarization of M2-like TAM toward the M1 phenotype and the potential regulatory mechanisms. The results showed that after glycopeptide dCP1 treatment, the mRNA relative expression levels of some M2 phenotype marker genes in M2-like TAM in simulated TME were reduced, and the relative expression levels of M1 phenotype marker genes and inflammatory factor genes were increased. Analysis of RNA-Seq of M2-like TAM after glycopeptide dCP1 intervention showed that the gene sets such as glycolysis, which is associated with macrophage polarization in the M1 phenotype, were significantly up-regulated, whereas those of gene sets such as IL-6-JAK-STAT3 pathway, which is associated with polarization in the M2 phenotype, were significantly down-regulated. Moreover, PCA analysis and Pearson's correlation also indicated that M2-like TAM polarized toward the M1 phenotype at the transcriptional level after treatment with the glycopeptide dCP1. Lipid metabolomics was used to further explore the efficacy of the glycopeptide dCP1 in regulating the polarization of M2-like TAM to the M1 phenotype. It was found that the lipid metabolite profiles in dCP1-treated M2-like TAM showed M1 phenotype macrophage lipid metabolism profiles compared with blank M2-like TAM. Analysis of the key differential lipid metabolites revealed that the interconversion between phosphatidylcholine (PC) and diacylglycerol (DG) metabolites may be the central reaction of the glycopeptide dCP1 in regulating the conversion of M2-like TAM to the M1 phenotype. The above results suggest that the glycopeptide dCP1 has the efficacy to regulate the polarization of M2-like TAM to M1 phenotype in simulated TME.

Asunto(s)

Codonopsis , Fenotipo , Macrófagos Asociados a Tumores , Animales , Humanos , Ratones , Glicopéptidos/metabolismo , Glicopéptidos/farmacología , Activación de Macrófagos/efectos de los fármacos , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/inmunología , Microambiente Tumoral/efectos de los fármacos , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/efectos de los fármacos

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Codonopsis Radix, commonly known as Dangshen in Chinese, is frequently used to treat deficiencies of spleen and lung Qi, gastrointestinal discomfort, fatigue, asthmatic breathing, sallow complexion, lack of strength, shortness of breath, deficiencies of both Qi and blood, as well as impairments to both Qi and body fluids in suboptimal health status. AIM OF THE REVIEW: This review systematically expounds on the modern pharmacological studies related to the use of Codonopsis Radix in invigorating Qi and nourishing the body in recent years. The aim is to provide theoretical research and reference for the in-depth and systematic exploration and development of the applications of Codonopsis Radix in the fields of food and medicine. MATERIALS AND METHODS: This study employs "Codonopsis Radix," "Codonopsis," and "Dangshen" as keywords to gather pertinent information on Codonopsis Radix medicine through electronic searches of classical literature and databases such as PubMed, Elsevier, Google Scholar, Wiley, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Baidu Scholar. RESULTS: From previous studies, activities such as immune system modulation, gastrointestinal motility regulation, cardiac function revitalization, lung function improvement, blood circulation enhancement, aging process deceleration, learning and memory augmentation, fatigue resistance enhancement, and liver and kidney damage protection of Codonopsis Radix have been reported. Recognized as an important medicine and food homologous traditional Chinese herbal remedy for supplementing deficiencies, its mode of action is multi-elemental, multi-systemic, multi-organ, multi-mechanistic, and multi-targeted. Furthermore, the benefits of its tonic surpass its therapeutic value, establishing it as an extraordinary preventive and therapeutic medicine. CONCLUSIONS: With its long history of traditional applications and the revelations of contemporary pharmacological research, Codonopsis Radix exhibits great potential as both a therapeutic agent and a dietary supplement for further research in medicine, nutrition, and healthcare.

Asunto(s)

Codonopsis , Medicamentos Herbarios Chinos , Medicina Tradicional China , Codonopsis/química , Humanos , Medicina Tradicional China/métodos , Animales , Medicamentos Herbarios Chinos/farmacología , Raíces de Plantas/química

RESUMEN

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a nonspecific chronic inflammatory lung disease with no known cure. Codonopsis Radix (CR) has been shown to exhibit anti-inflammatory and antioxidant effects. Therefore, this study aimed to investigate the potential anti-inflammatory effects of different CR varieties on COPD mice. METHODS: Sixty male-specified pathogen-free grade C57BL/6J mice were randomly divided into 6 groups, 10 mice in each group. The COPD mice model was induced by cigarette smoke extract combined with lipopolysaccharide, and the mice in each group were given corresponding drugs. Lung function was assessed in all mice. Lung tissues were stained with hematoxylin-eosin, Masson, and periodic acid-Schiff stains, and serum levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α were detected using an ELISA. Further, serum and lung tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric assay. Network pharmacology and molecular docking were used to predict signaling pathways, which were validated by Western blot analysis. RESULTS: Compared with the COPD group, the mice in each dosing group of CR exhibited significant reductions in serum IL-8 and TNF-α levels, serum and lung tissue MDA levels, and pathological lung tissue damage, alongside elevations in lung function and SOD levels (p < 0.01). Western blot analysis also indicated significant downregulation of p-p65/p65 and p-IκB-α/IκB-α protein expression, alongside significant upregulation of Nrf2 protein expression in the lung tissues of mice treated with CR (p < 0.01). CONCLUSION: In summary, CR effectively enhances lung function, minimizes lung tissue damage, and inhibits inflammation and oxidative stress in mice with COPD. Additionally, these findings suggest that inhibition of the Nrf2/NF-κB axis may be a key mechanism of action of CR in the alleviation of COPD.

Asunto(s)

Codonopsis , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2 , FN-kappa B , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica , Transducción de Señal , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Codonopsis/química , Ratones , FN-kappa B/metabolismo , Antiinflamatorios/farmacología , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Modelos Animales de Enfermedad , Malondialdehído/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Interleucina-8/metabolismo , Superóxido Dismutasa/metabolismo , Simulación del Acoplamiento Molecular , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Lipopolisacáridos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Medicamentos Herbarios Chinos

RESUMEN

Codonopsis pilosula is a perennial herbaceous liana with medicinal value. It is critical to promote Codonopsis pilosula growth through effective and sustainable methods, and the use of plant growth-promoting bacteria (PGPB) is a promising candidate. In this study, we isolated a PGPB, Klebsiella michiganensis LDS17, that produced a highly active 1-aminocyclopropane-1-carboxylate deaminase from the Codonopsis pilosula rhizosphere. The strain exhibited multiple plant growth-promoting properties. The antagonistic activity of strain LDS17 against eight phytopathogenic fungi was investigated, and the results showed that strain LDS17 had obvious antagonistic effects on Rhizoctonia solani, Colletotrichum camelliae, Cytospora chrysosperma, and Phomopsis macrospore with growth inhibition rates of 54.22%, 49.41%, 48.89%, and 41.11%, respectively. Inoculation of strain LDS17 not only significantly increased the growth of Codonopsis pilosula seedlings but also increased the invertase and urease activities, the number of culturable bacteria, actinomycetes, and fungi, as well as the functional diversity of microbial communities in the rhizosphere soil of the seedlings. Heavy metal (HM) resistance tests showed that LDS17 is resistant to copper, zinc, and nickel. Whole-genome analysis of strain LDS17 revealed the genes involved in IAA production, siderophore synthesis, nitrogen fixation, P solubilization, and HM resistance. We further identified a gene (koyR) encoding a plant-responsive LuxR solo in the LDS17 genome. Klebsiella michiganensis LDS17 may therefore be useful in microbial fertilizers for Codonopsis pilosula. The identification of genes related to plant growth and HM resistance provides an important foundation for future analyses of the molecular mechanisms underlying the plant growth promotion and HM resistance of LDS17. IMPORTANCE: We comprehensively evaluated the plant growth-promoting characteristics and heavy metal (HM) resistance ability of the LDS17 strain, as well as the effects of strain LDS17 inoculation on the Codonopsis pilosula seedling growth and the soil qualities in the Codonopsis pilosula rhizosphere. We conducted whole-genome analysis and identified lots of genes and gene clusters contributing to plant-beneficial functions and HM resistance, which is critical for further elucidating the plant growth-promoting mechanism of strain LDS17 and expanding its application in the development of plant growth-promoting agents used in the environment under HM stress.

Asunto(s)

Codonopsis , Klebsiella , Rizosfera , Microbiología del Suelo , Klebsiella/genética , Klebsiella/enzimología , Klebsiella/efectos de los fármacos , Klebsiella/crecimiento & desarrollo , Codonopsis/genética , Codonopsis/crecimiento & desarrollo , Codonopsis/microbiología , Desarrollo de la Planta , Rhizoctonia/crecimiento & desarrollo , Rhizoctonia/genética , Rhizoctonia/efectos de los fármacos , Liasas de Carbono-Carbono/genética , Liasas de Carbono-Carbono/metabolismo , Raíces de Plantas/microbiología , Raíces de Plantas/crecimiento & desarrollo , Reguladores del Crecimiento de las Plantas/metabolismo , Enfermedades de las Plantas/microbiología , Suelo/química

RESUMEN

This study aims to reveal the effects of maltodextrin(MD) on the water adsorption and thermodynamic properties of Codonopsis Radix(DS) spray-dried powder by determining the moisture and energy changes of the powder in the process of moisture absorption. The static weighing method was used to obtain the isothermal water adsorption data of the spray-dried powder in 6 saturated salt solutions(KAc, MgCl_2·6H_2O, K_2CO_3, NaBr, NaCl, and KCl) at 3 temperatures(25, 35, and 45 ℃). Six models were used for fitting of the water adsorption process, and the most suitable model was selected based on the model performance. Furthermore, the corresponding net equivalent adsorption heat and differential entropy were calculated, and the adsorption entropy change was integrated. The linear relationship between net equivalent adsorption heat and differential entropy was drawn based on the entropy-enthalpy complementarity theory. The results showed that the water adsorption properties of DS and DS-MD spray-dried powder followed the type Ⅲ isotherm and was well fitted by the GAB model. The monolayer water content M_0 decreased with the increase in temperature. At the same temperature, the M_0 of DS spray-dried powder decreased after the addition of MD. The net equivalent adsorption heat and differential entropy of DS and DS-MD spray-dried powder decreased with the increase in water content, which presented a linear relationship. The addition of MD decreased the water activity corresponding to the lowest integral adsorption entropy of the powder, and the system became more stable. The results indicated that the spray-dried powder became more stable after the addition of MD.

Asunto(s)

Codonopsis , Polisacáridos , Agua , Adsorción , Polvos , Termodinámica

RESUMEN

BACKGROUND: Liver cancer, one of the most common types of cancer worldwide, accounts for millions of cases annually. With its multi-target and wide-ranging therapeutic effects, traditional Chinese medicine has emerged as a potential approach for treating various tumors. Codonopsis pilosula, a traditional herb, is known for its anti-inflammatory and antioxidant properties. In this study, we investigated the potential molecular mechanisms of Codonopsis pilosula in regulating the inhibition of CDK1 and the modulation of PDK1/ß-catenin, which are involved in hepatocellular carcinoma growth and metastasis. STUDY DESIGN/METHODS: Firstly, we screened the active chemical constituents of Codonopsis pilosula and identified their respective target proteins using the Herb database. Then, we applied the GeneCards database and transcriptome sequencing analysis to screen for critical genes associated with the occurrence and development of liver cancer. The intersection of the target proteins and disease-related genes was used to determine the potential targets of Codonopsis pilosula in hepatocellular carcinoma. Protein-protein interaction analysis and GO/KEGG analysis were subsequently performed to uncover the pathways through which Codonopsis pilosula acts on liver cancer. The Huh-7 cell line, exhibiting the highest sensitivity to Codonopsis pilosula polysaccharide solution (CPP) intervention, was chosen for subsequent studies. Cell viability was evaluated using the CCK-8 assay, colony formation assay was conducted to determine cell proliferation capacity, flow cytometry was used to analyze cell cycle, TUNEL staining was performed to assess cell apoptosis, scratch assay was carried out to evaluate cell migration ability, the expression of EMT-related proteins was detected and analyzed, and cell sphere formation assay was conducted to investigate cell stemness. Finally, a liver cancer animal model was established, and different doses of CPP were administered via gavage the next day. The expression levels of CDK1, PDK1, and ß-catenin in mouse liver tissues were detected and analyzed, immunohistochemistry staining was performed to assess the expression of tumor cell proliferation-related proteins Ki67 and PCNA in mouse xenografts, and TUNEL staining was carried out to evaluate cell apoptosis in mouse liver tissues. After intervention with CDK1 expression, the expression levels of CDK1, PDK1, and ß-catenin proteins and mRNA in each group of cells were detected using Western blot and RT-qPCR. RESULTS: Through network pharmacology analysis, transcriptome sequencing, and bioinformatics analysis, 35 target genes through which Codonopsis pilosula acts on liver cancer were identified. Among them, CDK1, with the highest degree in the PPI network, was considered an essential target protein for Codonopsis pilosula in treating liver cancer. In vitro cell experiments revealed that CPP could inhibit the expression of CDK1/PDK1/ß-catenin signaling axis factors, suppress cell proliferation, decrease cell migration ability, influence the EMT process, and reduce cell stemness by inhibiting CDK1 and affecting the PDK1/ß-catenin signaling axis. Similarly, in vivo experiments demonstrated that CPP could regulate the CDK1/PDK1/ß-catenin signaling axis, inhibit tumor growth, and induce cell apoptosis. CONCLUSION: Codonopsis pilosula may inhibit hepatocellular carcinoma growth by suppressing CDK1 and affecting the PDK1/ß-catenin signaling axis, limiting cell EMT and reducing cell stemness. These findings provide insights into the potential therapeutic role of Codonopsis pilosula in liver cancer.

Asunto(s)

Proteína Quinasa CDC2 , Carcinoma Hepatocelular , Codonopsis , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Animales , Humanos , Codonopsis/química , Línea Celular Tumoral , Proteína Quinasa CDC2/metabolismo , Ratones , Proliferación Celular/efectos de los fármacos , beta Catenina/metabolismo , Antineoplásicos Fitogénicos/farmacología , Ratones Desnudos , Ratones Endogámicos BALB C , Masculino , Movimiento Celular/efectos de los fármacos , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora , Ensayos Antitumor por Modelo de Xenoinjerto , Medicamentos Herbarios Chinos/farmacología

RESUMEN

Inulin-type fructan CP-A, a predominant polysaccharide in Codonopsis pilosula, demonstrates regulatory effects on immune activity and anti-inflammation. The efficacy of CP-A in treating ulcerative colitis (UC) is, however, not well-established. This study employed an in vitro lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) and an in vivo dextran sulfate sodium (DSS)-induced colitis mouse model to explore CP-A's protective effects against experimental colitis and its underlying mechanisms. We monitored the clinical symptoms in mice using various parameters: body weight, disease activity index (DAI), colon length, spleen weight, and histopathological scores. Additionally, molecular markers were assessed through enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting assays. Results showed that CP-A significantly reduced reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukins (IL-6, IL-1ß, IL-18) in LPS-induced cells while increasing IL-4 and IL-10 levels and enhancing the expression of Claudin-1, ZO-1, and occludin proteins in NCM460 cells. Correspondingly, in vivo findings revealed that CP-A administration markedly improved DAI, reduced colon shortening, and decreased the production of myeloperoxidase (MPO), malondialdehyde (MDA), ROS, IL-1ß, IL-18, and NOD-like receptor protein 3 (NLRP3) inflammasome-associated genes/proteins in UC mice. CP-A treatment also elevated glutathione (GSH) and superoxide dismutase (SOD) levels, stimulated autophagy (LC3B, P62, Beclin-1, and ATG5), and reinforced Claudin-1 and ZO-1 expression, thereby aiding in intestinal epithelial barrier repair in colitis mice. Notably, the inhibition of autophagy via chloroquine (CQ) diminished CP-A's protective impact against colitis in vivo. These findings elucidate that CP-A's therapeutic effect on experimental colitis possibly involves mitigating intestinal inflammation through autophagy-mediated NLRP3 inflammasome inactivation. Consequently, inulin-type fructan CP-A emerges as a promising drug candidate for UC treatment.

Asunto(s)

Codonopsis , Colitis Ulcerosa , Colitis , Ratones , Animales , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inulina/metabolismo , Inulina/farmacología , Inulina/uso terapéutico , Interleucina-18 , Codonopsis/metabolismo , Proteínas NLR/metabolismo , Fructanos/metabolismo , Fructanos/farmacología , Fructanos/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Lipopolisacáridos/farmacología , Claudina-1/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Autofagia , Sulfato de Dextran , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Colon/metabolismo , Colon/patología

RESUMEN

Codonopsis pilosula is a famous edible and medicinal plants, in which polysaccharides are recognized as one of the important active ingredients. A neutral polysaccharide (CPP-1) was purified from C. pilosula. The structure was characterized by HPSEC-MALLS-RID, UV, FT-IR, GC-MS, methylation analysis, and NMR. The results showed that CPP-1 was a homogeneous pure polysaccharide, mainly containing fructose and glucose, and a small amount of arabinose. Methylation analysis showed that CPP-1 composed of →1)-Fruf-(2→, Fruf-(1→ and Glcp-(1→ residues. Combined the NMR results the structure of CPP-1 was confirmed as α-D-Glcp-(1 â†’ [2)-ß-D-Fruf-(1 â†’ 2)-ß-D-Fruf-(1]26 â†’ 2)-ß-D-Fruf with the molecular weight of 4.890 × 103 Da. The model of AML12 hepatocyte fat damage was established in vitro. The results showed that CPP-1 could increase the activity of SOD and CAT antioxidant enzymes and reduce the content of MDA, thus protecting cells from oxidative damage. Subsequently, the liver protective effect of CPP-1 was studied in the mouse model of nonalcoholic fatty liver disease (NAFLD) induced by the high-fat diet. The results showed that CPP-1 significantly reduced the body weight, liver index, and body fat index of NAFLD mice, and significantly improved liver function. Therefore, CPP-1 should be a potential candidate for the treatment of NAFLD.

Asunto(s)

Codonopsis , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Codonopsis/química , Espectroscopía Infrarroja por Transformada de Fourier , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Polisacáridos/química , Antioxidantes/farmacología