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Microemulsion gel, as a promising transdermal nanoparticle delivery system, addresses the limitations of microemulsions and enhances their performance in drug delivery and release. This article aims to discuss the advantages of microemulsion gel, including improved drug bioavailability, reduced drug irritation, enhanced drug penetration and skin adhesion, and increased antimicrobial properties. It explores the methods for selecting microemulsion formulations and the general processes of microemulsion preparation, as well as commonly used oil phases, surfactants, and co-surfactants. Additionally, the biomedical applications of microemulsion gel in treating conditions, such as acne and psoriasis, are also discussed. Overall, this article elucidates the significant potential of microemulsion gel in topical drug delivery, providing insights into future development and clinical applications.
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Euphorbiae pekinensis Radix (EPR) is a traditional Chinese herb commonly used to treat edema, pleural effusion, and ascites. However, counterfeit and adulterated products often appear in the market because of the homonym phenomenon, similar appearance, and artificial forgery of Chinese herbs. This study comprehensively evaluated the quality of EPR using multiple methods. The DNA barcode technique was used to identify EPR, while the UPLC-Q-TOF-MS technique was utilized to analyze the chemical composition of EPR. A total of 15 tannin and phenolic acid components were identified. Furthermore, UPLC fingerprints of EPR and its common counterfeit products were established, and unsupervised and supervised pattern recognition models were developed using these fingerprints. The backpropagation artificial neural network and counter-propagation artificial neural network models accurately identified counterfeit and adulterated products, with a counterfeit ratio of more than 25%. Finally, the contents of the chemical markers 3,3'-di-O-methyl ellagic acid-4'-O-ß-D-glucopyranoside, ellagic acid, 3,3'-di-O-methyl ellagic acid-4'-O-ß-d-xylopyranoside, and 3,3'-di-O-methyl ellagic acid were determined to range from 0.05% to 0.11%, 1.95% to 8.52%, 0.27% to 0.86%, and 0.10% to 0.42%, respectively. This proposed strategy offers a general procedure for identifying Chinese herbs and distinguishing between counterfeit and adulterated products.
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Introduction: Scutellariae Radix (SR), derived from the root of Scutellaria baicalensis Georgi, is a traditional Chinese medicine (TCM) for clearing heat and cooling blood. It has been used as a traditional herbal medicine and is popular as a functional food in Asian countries today. Methods: In this study, UPLC-Q-TOF-MS was first employed to identify the chemical components in the ethanol extract of SR. Then, the extraction process was optimized using star point design-response surface methodology. Fingerprints of different batches and processed products were established, and chemical markers were screened through a combination of various artificial neural network models. Finally, network pharmacology and molecular simulation techniques were utilized for verification to determine the quality markers. Results: A total of 35 chemical components in SR were identified, and the optimal extraction process was determined as follows: ultrasonic extraction with 80% methanol at a ratio of 120:1 for 70 minutes, with a soaking time of 30 minutes. Through discriminant analysis using various artificial neural network models, the samples of SR could be classified into two categories based on their growth years: Kuqin (dried roots of older plants) and Ziqin (roots of younger plants). Moreover, the samples within each category could be further clustered according to their origins. The four different processed products of SR could also be distinguished separately. Finally, through the integration of network pharmacology and molecular simulation techniques, it was determined that baicalin, baicalein, wogonin, norwogonin, norwogonin-8-O-glucuronide, skullcapflavone II, hispidulin, 8, 8"-bibaicalein, and oroxylin A-7-O-beta-D-glucuronide could serve as quality markers for SR. Discussion: The primary factors affecting the quality of SR were its growth years. The geographic origin of SR was identified as a secondary factor affecting its quality. Processing also had a significant impact on its quality. The selected quality markers have laid the foundation for the quality control of SR, and this research strategy also provides a research paradigm for improving the quality of TCM.
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p-Sulfonatocalix[n]arenes (SCnA) have demonstrated great potential for drug encapsulation through host-guest complexation to improve solubility, stability, and bioavailability. In this study, the solubilization effect of SCnA (n = 4, 6, 8) on 95 active compounds derived from traditional Chinese medicine (TCM) was investigated. Based on the significant solubilization effect on alkaloids, SC6A/SC8A and 76 alkaloids were selected as the host and guest, respectively, to determine the binding constant by competitive fluorescence titration. LASSO regression was adopted to investigate the mechanism of the complex of SCnA with alkaloids. The binding constant of alkaloids-SC6A and alkaloids-SC8A was related to the alkaloid alkalinity. Also, the electronegativity, polarization, first ionization potential, hydrogen bond potential, the molecular size, and shape of alkaloids are critical properties to determine alkaloids-SC6A binding constant as well as electronegativity, polarization, hydrophobicity, and the molecular size and shape of alkaloids play an important role for the alkaloids-SC8A binding constant.
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Alcaloides , Medicina Tradicional Chinesa , Alcaloides/químicaRESUMO
Myrrh is widely used in clinical practice but accompanied by obvious toxicity. According to traditional Chinese medicines theory, processing with vinegar can effectively reduce its toxicity. However, the detoxification processing technology of Myrrh and the corresponding mechanism have been unclear. The objective of this study is to systematically analyze the variation in chemical composition of raw Myrrh and its processed products using UPLC-Q-TOF-MS/MS coupled with chemometrics. A total of 75 compounds including 56 sesquiterpenoids, 2 diterpenoids, 15 triterpenoids and 2 other types were identified. Raw Myrrh and its processed products were divided into two major groups, and 14 chemical markers were selected out by principal component analysis and partial least square discriminant analysis. Additionally, the exact content of 5 representative chemical markers was determined to be significantly reduced after vinegar-processing by UPLC-QQQ-MS/MS. Moreover, multivariate statistical analysis and the quantitative results comprehensively indicated that the optimized processing method was processing at a ratio of 200 : 5 (Myrrh:vinegar). This research provides not only a reliable foundation for the study of Myrrh, but also a scientific reference for clinical use of this herb.
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Commiphora , Medicamentos de Ervas Chinesas , Resinas Vegetais , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Espectrometria de Massa com Cromatografia Líquida , Ácido Acético , Medicamentos de Ervas Chinesas/química , Quimiometria , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal condition characterized by regurgitating stomach contents into the esophagus, causing mucosal damage or erosion. Clinical physical protection treatment mainly relies on the use of floating rafts. Bletilla striata (BS) is widely regarded as the first-choice drug for treating digestive tract injuries in Chinese Medicine. The rapid-floating gel-raft (B-R) was prepared via a one-step swelling method using natural BS polysaccharide and glyceryl monooleate. Panax notoginseng saponins (PNS) were loaded to further prepare P/B-R according to clinical experience. Possessing hydrophobic dense, stratified porous structure and stable rheological properties, an outperforming floating performance of P/B-R was proven compared with Gaviscon® (alginate-antacid formulation) in vitro. In vivo imaging results showed that P/B-R can retain and adhere to the gastric mucosa of rats for up to 90 min, protecting and repairing the mucosa. Besides physical protection in situ, the systemic effects of antioxidant and anti-inflammatory actions for treating GERD were achieved through the intestinal release of PNS. Acid-labile PNS was protected by P/B-R against gastric acid, attaining the desired release and permeability. A significantly effective mucosa injury protective effect of P/B-R was found in ethanol-induced gastric damage model on rats. Moreover, P/B-R exhibits excellent biosafety at the cellular level.
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Antiulcerosos , Refluxo Gastroesofágico , Ratos , Animais , Refluxo Gastroesofágico/tratamento farmacológico , AntiácidosRESUMO
BACKGROUND: Panax japonicus C.A. Meyer (Zhujieshen) is widely used in traditional medicine as a tonic hemostatic and anti-inflammatory agent in China, Japan, and Korea. Furthermore, it is used as an important substitute for ginseng roots by minority ethnic groups in China. The purpose of this review is to summarize the latest research on Zhujieshen in recent years, aiming at providing a systematic overview of the current knowledge, and perspectives for future research and exploitation. MAIN BODY: This review examines the research advances in botanical profile, phytochemicals, pharmacology, pharmacokinetics, and authentication of Zhujieshen. Various compounds have been reported as active components, mainly including saponins, volatile oils, and polysaccharides. Pharmacological investigations have demonstrated that Zhujieshen is an important herb with significant bioactivities, such as anti-inflammatory, hepato-protective, cardio-protective, neuro-protective, anti-tumor, anti-oxidant, anti-thrombotic and immunomodulatory activities. CONCLUSION: Currently, research on Zhujieshen is in the preliminary stages, and further research is required to understand the active compounds present and mechanisms of action. We hope that this comprehensive review of Zhujieshen will serve as a background for future research and exploitation.
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Metal ions are indispensable elements in living organisms and are associated with regulating various biological processes. An imbalance in metal ion content can lead to disorders in normal physiological functions of the human body and cause various diseases. Genetically encoded fluorescent protein sensors have the advantages of low biotoxicity, high specificity, and a long imaging time in vivo and have become a powerful tool to visualize or quantify the concentration level of biomolecules in vivo and in vitro, temporal and spatial distribution, and life activity process. This review analyzes the development status and current research hotspots in the field of genetically encoded fluorescent protein sensors by bibliometric analysis. Based on the results of bibliometric analysis, the research progress of genetically encoded fluorescent protein sensors for metal ion detection is reviewed, and the construction strategies, physicochemical properties, and applications of such sensors in biological imaging are summarized.
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Técnicas Biossensoriais , Corantes Fluorescentes , Humanos , Corantes Fluorescentes/química , Técnicas Biossensoriais/métodos , Metais/análise , Íons , BibliometriaRESUMO
In this study, nano-strategy for combined medication of active compounds from traditional Chinese medicine herbs was proposed to achieve the synergistic effects of inhibiting the doxorubicin (DOX) resistance, reducing the cardio-toxicity, and improving the treatment efficacy simultaneously. Dihydroartemisinin (DHA) and tetrandrine (TET) were co-delivered for the first time to treat DOX resistance of breast cancer with multi-pathway mechanism. Tumor micro-environment sensitivity prescription was adopted to enhance the reversal effect of DOX resistance nearly 50 times (resistance index, RI was 46.70) and uptake ability. The DHA-TET pH-sensitive liposomes (DHA-TET pH-sensitive LPs) had a good spherical structure and a uniform dispersion structure with particle size, polydispersity index (PDI), and zeta potential of 112.20 ± 4.80 nm, 0.20 ± 0.02, and - 8.63 ± 0.74 Mv, and was stable until 14 days under the storage environment of 4°C and for 6 months at room temperature environment. With the DOX resistance reversing ability increased, the inhibition effect of DHA-TET pH-sensitive LPs on both MCF-7/ADR cells and MCF-7 cells was significantly enhanced; meanwhile, the toxicity on cardiac cell (H9c2) was lowered. Ferroptosis induced by the DHA was investigated showing that the intracellular reactive oxygen species (ROS) and lipid peroxidation were increased to promote the synergistic effect through the due-loaded nano-carrier, providing a promising alternative for future clinical application.
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Lipopolissacarídeos , Lipossomos , Medicina Tradicional Chinesa , Doxorrubicina/farmacologia , Concentração de Íons de HidrogênioRESUMO
The utilization of rhizomes from the genus Atractylodes has been challenging due to their closely related origins. In this study, we developed an analytical strategy to differentiate Atractylodes lancea (A. lancea), Atractylodes chinensis (A. chinensis), Atractylodes japonica (A. japonica), and Atractylodes macrocephala (A. macrocephala), and compared their volatile compositions. Gas chromatography-mass spectrometry (GC/MS) was used to analyze the volatile profiles of essential oils extracted from 59â batches of samples. Chemometric methods enabled a better understanding of the differences in volatile oils between the four species and identified significant components affecting their classification and quality. A total of 50â volatile components were identified from the essential oils by GC/MS. Unsupervised and supervised chemometric analyses accurately distinguished A. lancea, A. chinensis, A. japonica, and A. macrocephala. Furthermore, five characteristic chemical markers, namely hinesol, ß-eudesmol, atractylon, atractylodin and atractylenolide I, were obtained, and their respective percentage contents in individual species and samples were determined. This study provides a valuable reference for the quality evaluation of medicinal plants with essential oils and holds significance for species differentiation and the rational clinical application of Atractylodes herbs.
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Atractylodes , Óleos Voláteis , Plantas Medicinais , Cromatografia Gasosa-Espectrometria de Massas , Plantas Medicinais/química , Atractylodes/química , Quimiometria , Óleos Voláteis/químicaRESUMO
Multifunctional drug delivery platforms represent ideal approaches to reliably targeting pharmacological agents of interest to the complex tumor microenvironment (TME), yet the complicated synthesis processes, high costs, and toxicities associated with these agents have hindered their clinical application to date. In this study, the properties of the TME are leveraged to develop a multifunctional pNAB/AS DNA microgel that is able to actively target tumors. This microgel is generated by a straightforward one-step free radical precipitation polymerization procedure, exhibiting extremely high drug encapsulation efficiency (â¼90%), and is responsive to three environmental stimuli including temperature, reduction, and an acidic pH while showing minimal drug leakage under physiological conditions. Through a synergistic combination of appropriate size and aptamer recognition, this microgel is able to reliably facilitate intratumoral drug accumulation and nuclear drug delivery. Critically, pNAB/AS-Dox treatment is associated with specific antitumor activity in vitro and in vivo while retaining a good biosafety profile and causing lower levels of off-target toxicity as compared to free drug treatment. Together, these findings emphasize the potential value of this multifunctional pNAB/AS DNA microgel as a platform amenable to targeted drug delivery to the TME, providing a foundation for further efforts to readily develop multifunctional drug delivery systems.
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Antineoplásicos , Microgéis , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , DNA , Concentração de Íons de Hidrogênio , Doxorrubicina/química , Microambiente TumoralRESUMO
Developing hemostatic agents with reliable biosafety and high efficiency has paramount clinical significance for saving lives. Herein, inspired from traditional Chinese medicine, a sponge (BC-S) with hierarchical porous structure is proposed for the treatment of bleeding. The BC-S is prepared by a simple self-assembly method employing Bletilla Striata polysaccharide and quaternary amine alkaloids (QA) from Bletilla Striata and Coptidis Rhizoma. The ideal cation donor encapsulated in the helical structure of BSP enlarges the inter-layer space of sponge by the action of electrostatic repulsion, forming wider channels which can accelerate the diversion speed of absorbed blood. Then, platelets and erythrocytes are trapped tightly in the reticular structure and extruded to deformation, activation. Subsequently, fibrin network forms and reinforces the internal multilayer mesh, blocks the outflow of blood. QA is released from the sponge skeleton mainly driven by a combination of surface erosion and potentially solution diffusion among pore to provide long-term antibacterial activity. Benefiting from the well-designed structure and the effective hemostatic mechanism, the BC-S displays more excellent hemostatic performance in different models in vivo and in vitro compared with typical gelatin hemostatic sponge. This work is expected to boost the development of emerging hemostatic agents.
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Hemostasia , Hemostáticos , Humanos , Porosidade , Hemostáticos/farmacologia , Hemorragia , Gelatina/farmacologia , Antibacterianos/farmacologiaRESUMO
Physalis Calyx seu Fructus (PCF) is a herb widely used in China for its function of clearing heat and detoxifying, benefitting the pharynx and reducing phlegm, both in health care and in tea drinking. However, the quality of its fruit and calyx is uneven and the storage period is short. Therefore, it is crucial to develop other parts of PCF with longer storage periods and obvious medicinal effects. Firstly, high-performance liquid chromatography was used to develop the fingerprint of different parts of PCF, and various chemometric analyses were conducted to screen out chemical markers. The calyxes of PCF were found to cluster together, distinct from the fruits, roots, stems and leaves. The active components of PCF were concentrated in the persistent calyxes, and flavonoids were mainly found in the persistent calyxes and leaves. Secondly, the extraction of persistent calyxes showed the strongest scavenging ability of DPPH and ABTS. Finally, the important chemical markers were verified by network pharmacological analysis and molecular docking. It provides a reference for the clinical application of PCF, and the obtained chemical markers offer a scientific basis for quality evaluation.
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Frutas , Physalis , Antioxidantes/farmacologia , Physalis/química , Simulação de Acoplamento Molecular , Quimiometria , Farmacologia em RedeRESUMO
Polygonati Rhizoma has been a famous traditional Chinese medicine (TCM) for two thousand years. It is increasingly being used not just as a traditional herbal medicine but also as a popular functional food. In this study, qualitative and quantitative analysis of PR from three different origins were initially performed using chemical fingerprint and chemometrics methods. Hierarchical cluster analysis (HCA) and Principal component analysis (PCA) were used to classify 60 PR samples from three different origins. The results revealed that the PR samples fell into three clusters related to the origins. In addition, pairwise comparison of varying PR and obtaining chemical markers between different species through the establishment of partial least squares discriminant analysis. Finally, chemical markers 9,13 and 17 were identified by LC/MS as disporopsin, 5,7-dihydroxy-3-(4'-hydroxybenzyl)-6,8-dimethylchroman-4-one and (3R)-5,7-dihydroxy-3-(4'-hydroxybenzyl)-6-methylchroman-4-one or isomer, respectively. In conclusion, these methods can be applied to identify and distinguish the quality of PR with other original plants and provide novel ideas for evaluating herbal products used in TCM.
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Quimiometria , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Medicina Tradicional Chinesa , Análise Discriminante , Análise de Componente Principal , Medicamentos de Ervas Chinesas/químicaRESUMO
Wedelolactone (WDL) is the major bioactive component in Ecliptae Herba. This present study investigated the effects of WDL on natural killer cell functions and possible underlying mechanisms. It was proved that wedelolactone enhanced the killing ability of NK92-MI by upregulating the expression of perforin and granzyme B through the JAK/STAT signaling pathway. Additionally, wedelolactone could induce the migration of NK-92MI cells by promoting CCR7 and CXCR4 expressions. However, the application of WDL is limited due to poor solubility and bioavailability. Accordingly, this study investigated the impact of polysaccharides from Ligustri Lucidi Fructus (LLFPs) on WDL. The biopharmaceutical properties and pharmacokinetic characteristics were determined to compare WDL individually and in combination with LLFPs. The results showed that LLFPs could benefit the biopharmaceutical properties of WDL. Specifically, stability, solubility, and permeability were increased by 1.19-1.82-fold, 3.22-fold, and 1.08-fold higher than those of WDL alone, respectively. Furthermore, the pharmacokinetic study revealed that LLFPs could remarkably improve AUC(0-t) (150.34 vs. 50.47 ng/mL ∗ h), t1/2 (40.78 vs. 2.81 h), and MRT(0-∞) (46.64 vs. 5.05 h) for WDL. In conclusion, WDL would be considered a potential immunopotentiator, and LLFPs could overcome the instability and insolubility, ultimately improving the bioavailability of this plant-derived phenolic coumestan.
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Ligustrum , Disponibilidade Biológica , Células Matadoras Naturais , Polissacarídeos/farmacologiaRESUMO
Berberine (BBR) is a quaternary ammonium alkaloid isolated from the Traditional Chinese Medicine Coptis chinensis. It possesses a plethora of pharmacological activities because its unique structure properties make it readily interact with macromolecules through π-π stacking and electrostatic interaction. Its anti-tumor effects are receiving more and more attention in recent years. Cytotoxicity and anti-proliferation are the important anti-tumor modes of BBR, which have been studied by many research groups. This study aims to review the structural modifications of BBR and its cytotoxic derivatives. Also, to study the corresponding structure-activity relationship. BBR showed potential activities toward tumor cells, however, its modest activity and poor physicochemical properties hindered its application in clinical. Structural modification is a common and effective approach to improve BBR's cytotoxic or anti-proliferative activities. The structural modifications of BBR, the cytotoxic or anti-proliferative activities of its derivatives, and the corresponding structure-activity relationship (SAR) were summarized in the review. The concluded SAR of BBR derivatives with their cytotoxic or anti-proliferative activities will provide great prospects for the future anti-tumor drug design with BBR as the lead compound.
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Antineoplásicos , Berberina , Berberina/farmacologia , Berberina/química , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/químicaRESUMO
MOTIVATION: Primer design is a routine practice for modern molecular biology labs. Bioinformatics tools like primer3 and primer-blast have standardized the primer design for a specific region. However, large-scale primer design, especially for genome-wide screening, is still a labor-intensive job for most wet-lab researchers using these pipelines. RESULTS: Here, we present the primerdiffer pipeline, which can be used to batch design primers that differentiate haplotypes on a large scale with precise false priming checking. This command-line interface (CLI) pipeline includes greedy primer search, local and global in silico PCR-based false priming checking, and automated best primer selection. The local CLI application provides flexibility to design primers with the user's own genome sequences and specific parameters. Some species-specific primers designed to genotype the hybrid introgression strains from Caenorhabditis briggsae and Caenorhabditis nigoni have been validated using single-worm PCR. This pipeline provides the first CLI-based large-scale primer design tool to differentiate haplotypes in any targeted region. AVAILABILITY AND IMPLEMENTATION: The open-source python modules are available at github (https://github.com/runsheng/primerdiffer, https://github.com/runsheng/primervcf) and Python package index (https://pypi.org/project/primerdiffer/, https://pypi.org/project/primervcf/).
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Biologia Computacional , Software , Haplótipos , Genótipo , Reação em Cadeia da PolimeraseRESUMO
Multidrug resistance (MDR) promotes tumor recurrence and metastasis and heavily reduces anticancer efficiency, which has become a primary reason for the failure of clinical chemotherapy. The mechanisms of MDR are so complex that conventional chemotherapy usually fails to achieve an ideal therapeutic effect and even accelerates the occurrence of MDR. In contrast, the combination of chemotherapy with dual-drug has significant advantages in tumor therapy. A novel dual-drug codelivery nanosystem, which combines dual-drug administration with nanotechnology, can overcome the application limitation of free drugs. Both the characteristics of nanoparticles and the synergistic effect of dual drugs contribute to circumventing various drug-resistant mechanisms in tumor cells. Therefore, developing dual-drug codelivery nanosystems with different multidrug-resistant mechanisms has an important reference value for reversing MDR and enhancing the clinical antitumor effect. In this review, the advantages, principles, and common codelivery nanocarriers in the application of dual-drug codelivery systems are summarized. The molecular mechanisms of MDR and the dual-drug codelivery nanosystems designed based on different mechanisms are mainly introduced. Meanwhile, the development prospects and challenges of codelivery nanosystems are also discussed, which provide guidelines to exploit optimized combined chemotherapy strategies in the future.
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Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Resistência a Múltiplos Medicamentos , Portadores de Fármacos , Antineoplásicos/farmacologiaRESUMO
Codonopsis pilosula (CP) possesses properties related to nourishing the spleen and stomach, and tonifying Qi of the stomach and mind in traditional Chinese medicine (TCM). Codonopsis pilosula polysaccharides (CPPS), which are the primary active components of CP, are thought to be in charge of their extensive use. Rutin, quercetin, luteoloside, and luteolin, are common and pharmacologically significant flavonoids with many pharmacological activities, but their oral bioavailability is limited by poor solubility and stability. In this study, high-performance gel permeation chromatography (HPGPC) estimated the molecular weight of CPPS to be 9.7 × 105 Da. Sugar analysis revealed that CPPS is composed of D-mannose, D-glucose, and D-xylose with a molar ratio of 5.8:1.9:1.0. Moreover, the antioxidant test showed that CPPS had good antioxidant activity. It is worth noting that CPPS integrated the four flavonoids to form a spongy compound that significantly increased the solubilities and stabilities of flavonoids. The bonding constants of the CPPS and flavonoid-derived inclusion complexes ranged from 60 L mol-1 to 2,030,816 L mol-1, which demonstrated the capacity of CPPS to interact with flavonoids intermolecularly to form a drug complex system, resulting in potentially enhanced biopharmaceutical properties of flavonoids. This finding could provide a reference point for further applications of polysaccharides from herbal medicines.