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1.
Carbohydr Polym ; 339: 122253, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823920

ABSTRACT

In vitro tumor models are essential for understanding tumor behavior and evaluating tumor biological properties. Hydrogels that can mimic the tumor extracellular matrix have become popular for creating 3D in vitro tumor models. However, designing biocompatible hydrogels with appropriate chemical and physical properties for constructing tumor models is still a challenge. In this study, we synthesized a series of ß-cyclodextrin (ß-CD)-crosslinked polyacrylamide hydrogels with different ß-CD densities and mechanical properties and evaluated their potential for use in 3D in vitro tumor model construction, including cell capture and spheroid formation. By utilizing a combination of ß-CD-methacrylate (CD-MA) and a small amount of N,N'-methylene bisacrylamide (BIS) as hydrogel crosslinkers and optimizing the CD-MA/BIS ratio, the hydrogels performed excellently for tumor cell 3D culture and spheroid formation. Notably, when we co-cultured L929 fibroblasts with HeLa tumor cells on the hydrogel surface, co-cultured spheroids were formed, showing that the hydrogel can mimic the complexity of the tumor extracellular matrix. This comprehensive investigation of the relationship between hydrogel mechanical properties and biocompatibility provides important insights for hydrogel-based in vitro tumor modeling and advances our understanding of the mechanisms underlying tumor growth and progression.


Subject(s)
Acrylic Resins , Hydrogels , Spheroids, Cellular , beta-Cyclodextrins , Spheroids, Cellular/drug effects , Humans , Acrylic Resins/chemistry , Acrylic Resins/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , beta-Cyclodextrins/chemistry , beta-Cyclodextrins/pharmacology , HeLa Cells , Animals , Mice , Cross-Linking Reagents/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Culture Techniques, Three Dimensional/methods , Methacrylates/chemistry , Coculture Techniques , Neoplasms/pathology
2.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6066-6075, 2022 Nov.
Article in Chinese | MEDLINE | ID: mdl-36471931

ABSTRACT

The present study aimed to explore the material basis of Rhei Radix et Rhizoma-Coptidis Rhizoma combination in alleviating "bitter-cold" properties based on the supramolecular chemistry of Chinese medicine.Dynamic light scattering and scanning/transmission electron microscopy were used to characterize the morphological characteristics of supramolecules in the decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma.The chemical composition of supramolecules, as well as the dissolution and release processes of supramolecules and the medicinal components of Coptidis Rhizoma decoction, was determined by the high-performance liquid chromatography-mass spectrometry.The differences in "bitter-cold" medicinal properties between Rhei Radix et Rhizoma decoction, Coptidis Rhizoma decoction, and co-decoction were analyzed by sensory evaluation, electronic tongue, mouse diarrhea model, and pathological indicators.The anthraquinones/tannins and alkaloids interacted to form supramolecules with a scale of about 400 nm when Rhei Radix et Rhizoma and Coptidis Rhizoma were decocted together, which delayed the dissolution and release of the active components represented by berberine. Compared with the consequence of single drug administration at 4 g·kg~(-1), the combination of the two drugs at 8 g·kg~(-1) significantly alleviated the "bitter-cold" properties.The effective components interacted to form supramolecules in the co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma, which affected the dissolution and release of the effective components of Chinese medicinal decoction, thereby alleviating the "bitter-cold" properties.The findings of this study provide a new idea for revealing the scientific compatibility of Rhei Radix et Rhizoma and Coptidis Rhizoma.


Subject(s)
Antineoplastic Agents , Drugs, Chinese Herbal , Mice , Animals , Drugs, Chinese Herbal/chemistry , Medicine, Chinese Traditional , Rhizome/chemistry , Anthraquinones/analysis , Chromatography, High Pressure Liquid/methods
3.
ACS Omega ; 7(48): 43510-43521, 2022 Dec 06.
Article in English | MEDLINE | ID: mdl-36506183

ABSTRACT

The carrier-free self-assembly of small molecules opens a new window for the development of nanomaterials. This study is dedicated to developing binary small-molecular self-assemblies derived from phytochemicals in traditional Chinese herbal medicine. Among them, Rhei Radix et Rhizoma and Coptidis Rhizoma are a common pair used in clinics for thousands of years. Here, we found that there were numerous spherical supramolecular nanoparticles (NPs) originated from Rhei Radix et Rhizoma and Coptidis Rhizoma decoction. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was used to analyze the composition of the supramolecules, and a total of 119 phytochemicals were identified (23 anthraquinones, 31 alkaloids, 24 organic acids, 8 tannins, and other components). Isothermal titration calorimetry (ITC) showed that the interaction between Rhei Radix et Rhizoma and Coptidis Rhizoma was a spontaneous exothermic reaction, indicating that their phytochemicals had the property of self-assembly and interacted to form supramolecules in the decocting process. Furthermore, scanning electron microscopy (SEM), UV, IR, NMR, and ITC were used to verify that rhein and coptisine could self-assemble into nanofibers (Rhe-Cop NFs), while emodin and coptisine could self-assemble into nanoparticles (Emo-Cop NPs). The formation mechanism analysis of the self-assemblies revealed that they were induced by electrostatic attraction, hydrogen bonding, and π-π stacking, forming nanospheres of about 50 nm and nanofibers. The current study not only provides an idea of discovering carrier-free self-assemblies from traditional herbal medicine decoction but also supplies a reference for the design of binary self-assembly of small molecules in the future.

4.
ACS Appl Mater Interfaces ; 14(38): 43035-43049, 2022 Sep 28.
Article in English | MEDLINE | ID: mdl-36124878

ABSTRACT

Antibacterial hydrogels have gradually become a powerful weapon to treat bacterially infected wounds and accelerate healing. In this paper, we designed a small-molecule self-healing antibacterial hydrogel containing 100% drug-loaded benzyl 3ß-amino-11-oxo-olean-12-en-30-oate (GN-Bn), which was governed by π-π stacking, hydrogen bonding, and van der Waals forces. Due to the carrier-free design concept, the problems of interbatch variability during sample preparation and carrier-related toxicity can be effectively avoided. Moreover, the GN-Bn hydrogel exhibited promising antibacterial activities against multidrug-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of the GN-Bn hydrogel was 1.5625 nmol/mL, which was lower than those against clinical agents such as norfloxacin, penicillin, and tetracycline. This is attributed to its unique antibacterial mechanism that aims at killing bacteria or preventing their growth by regulating arginine biosynthesis and metabolism through both transcriptomic (RNA-seq) analysis and quantitative polymerase chain reaction (qPCR) analysis. In addition, the GN-Bn hydrogel can also inhibit proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) to promote wound healing. Collectively, the GN-Bn hydrogel elicited dual therapeutic effects on an MRSA-infected full-thickness skin wound model through its antibacterial and anti-inflammatory activities, which is attributed to the fact that the GN-Bn hydrogel has multiple advantages including sufficient mechanical stability, biocompatibility, and unique antibacterial mechanisms, making it significantly accelerate MRSA-infected full-thickness skin wound healing as a wound dressing. In a word, the GN-Bn antibacterial hydrogel dressing with an anti-inflammatory and antibacterial bifunctional material holds great potential in clinical application.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Wound Infection , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Arginine/pharmacology , Bandages , Humans , Hydrogels/pharmacology , Interleukin-6 , Norfloxacin , Penicillins/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcus aureus , Tetracycline/pharmacology , Tumor Necrosis Factor-alpha/pharmacology , Wound Healing , Wound Infection/drug therapy
5.
Biomater Sci ; 9(18): 6282-6294, 2021 Sep 14.
Article in English | MEDLINE | ID: mdl-34378577

ABSTRACT

Photothermal therapy (PTT) is able to ablate tumors via hyperthermia, while immunotherapy could prevent tumor recurrence and metastasis by activating the host immune responses. Therefore, the combination of PTT and immunotherapy offers great advantages for the treatment of cancer. To achieve this goal, poly tannic acid (pTA) coated PLGA nanoparticles (PLGA-pTA NPs) were synthesized for combined photothermal-immunotherapy. pTA was a coordination complex formed by TA and Fe3+ and it could be easily coated on PLGA NPs within seconds with a coating rate of 5.89%. As a photothermal agent, PLGA-pTA revealed high photothermal conversion efficiency and excellent photo-stability upon 808 nm laser irradiation. It also exhibited strong photothermal cytotoxicity against 4T1 cells. Moreover, PLGA-pTA based PTT could effectively trigger DC maturation since it could induce the release of DAMPs. The result of animal experiments showed that PLGA-pTA plus laser irradiation raised the tumor temperature up to ca. 60 °C and effectively suppressed the growth of primary tumors. What's more, the progression of distant tumors as well as lung metastasis was also significantly inhibited due to the activation of anti-tumor responses by PLGA-pTA mediated PTT. When further combined with anti-PD-L1 antibody (a-PD-L1), the tumor growth and metastasis were almost completely inhibited. Our study provided a versatile platform to achieve combined photothermal-immunotherapy with enhanced therapeutic efficacy.


Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Animals , Cell Line, Tumor , Immunotherapy , Phototherapy , Tannins
6.
ACS Appl Mater Interfaces ; 13(28): 32729-32742, 2021 Jul 21.
Article in English | MEDLINE | ID: mdl-34247476

ABSTRACT

Aristolochic acid (AA) has been reported to cause a series of health problems, including aristolochic acid nephropathy and liver cancer. However, AA-containing herbs are highly safe in combination with berberine (Ber)-containing herbs in traditional medicine, suggesting the possible neutralizing effect of Ber on the toxicity of AA. In the present study, in vivo systematic toxicological experiments performed in zebrafish and mice showed that the supramolecule self-assembly formed by Ber and AA significantly reduced the toxicity of AA and attenuated AA-induced acute kidney injury. Ber and AA can self-assemble into linear heterogenous supramolecules (A-B) via electrostatic attraction and π-π stacking, with the hydrophobic groups outside and the hydrophilic groups inside during the drug combination practice. This self-assembly strategy may block the toxic site of AA and hinder its metabolism. Meanwhile, A-B linear supramolecules did not disrupt the homeostasis of gut microflora as AA did. RNA-sequence analysis, immunostaining, and western blot of the mice kidney also showed that A-B supramolecules almost abolished the acute nephrotoxicity of AA in the activation of the immune system and tumorigenesis-related pathways.


Subject(s)
Aristolochic Acids/toxicity , Berberine/therapeutic use , Drugs, Chinese Herbal/toxicity , Kidney Diseases/prevention & control , Macromolecular Substances/therapeutic use , Animals , Aristolochic Acids/chemistry , Berberine/chemistry , Drug Interactions , Drugs, Chinese Herbal/chemistry , Dysbiosis/prevention & control , Gastrointestinal Microbiome/drug effects , Gene Expression/drug effects , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Kidney Diseases/chemically induced , Kidney Diseases/pathology , Killer Cells, Natural/drug effects , Macromolecular Substances/chemistry , Macromolecular Substances/toxicity , Male , Mice, Inbred C57BL , Neutrophils/drug effects , Transcription Factor RelA/metabolism , Zebrafish , p38 Mitogen-Activated Protein Kinases/metabolism
7.
Curr Drug Deliv ; 18(7): 914-921, 2021.
Article in English | MEDLINE | ID: mdl-33234104

ABSTRACT

BACKGROUND: In the field of antibacterial, nanomaterials are favored by researchers because of their unique advantages. Medicinal plants, especially traditional Chinese medicine, are considered to be an important source of new chemicals with potential therapeutic effects, as well as an important source for the discovery of new antibiotics. MRSA is endangering people's lives as a kind of multidrug-resistant Staphylococcus aureus, which is resistant to tetracycline, amoxicillin, norfloxacin and other first-line antibiotics. It is a hotspot to find good anti-drug-resistant bacteriae, nature-originated nanomaterials with good biocompatibility. OBJECTIVE: We reported the formation of phytochemical nanoparticles (NPs) by the self-assembly of berberine (BBR) and 3,4,5-methoxycinnamic acid (3,4,5-TCA) from Chinese herb medicine, which had good antibacterial activity against MRSA. METHODS AND RESULTS: We found that NPs had good antibacterial activity against MRSA; especially, its antibacterial activity was better than first-line amoxicillin, norfloxacin and its self-assembling precursors on MRSA. When the concentration reached 0.1 µmol/mL, the inhibition rate of NPs reached 94.62%, which was higher than that of BBR and the other two antibiotics (p < 0.001). It was observed by Field-Emission Scanning Electron Microscopy (FESEM) that NPs could directly adhere to the bacterial surface, which might be an important aspect of the antibacterial activity of NPs. Meanwhile, we further analyzed that the self-assembly was formed by hydrogen bonds and π-π stacking through Ultraviolet-Visible (UV-vis), Fourier Transform Infrared Spectroscopy (FTIR), hydrogen Nuclear Magnetic Spectrum (1H NMR), and powder X-ray Diffraction (pXRD). NPs' morphology was observed by FESEM and TEM. The particle size and surface charge were characterized by Dynamic Light Scattering (DLS); and the surface charge was -31.6 mv, which proved that the synthesized NPs were stable. CONCLUSION: We successfully constructed a naturally self-assembled nanoparticle, originating from traditional Chinese medicine, which had a good antibacterial activity for MRSA. It is a promising way to obtain natural nanoparticles from medicinal plants and apply them to antibacterial therapy.


Subject(s)
Berberine , Metal Nanoparticles , Methicillin-Resistant Staphylococcus aureus , Nanoparticles , Anti-Bacterial Agents/pharmacology , Humans , Medicine, Chinese Traditional , Microbial Sensitivity Tests , Phytochemicals , Spectroscopy, Fourier Transform Infrared , Staphylococcus aureus
8.
Acta Pharm Sin B ; 10(9): 1784-1795, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33088696

ABSTRACT

The application of nanotechnology for antimicrobial delivery has capacity to improve antibacterial efficacy. Currently, the usage of various inorganic and organic carriers, such as metal ions, nano-silicon and surfactants, might increase the potential toxicity of nanoparticles and make their clinical transformation more difficult. Herein, a nano-delivery system was constructed by direct self-assembly of antibacterial phytochemicals (berberine and rhein) originated from traditional Chinese medicine Coptis chinensis Franch. and Rheum palmatum L., respectively. Combining X-ray single crystal diffraction, nuclear magnetic resonance and other spectra characterizations, the stacked structure of nanoparticles was profoundly demonstrated. Briefly, rhein acted as the layered backbone and berberine embedded in it. In vitro bacteriostasis experiment showed the minimum bactericidal concentration of nanoparticles was 0.1 µmol/mL, which was lower than that of berberine and rhein. The results of confocal laser scanning microscope, biofilm quantitive assay and scanning electron microscopy indicated that nanoparticles had strong inhibitory effects on Staphylococcus aureus biofilm. More importantly, transmission electron microscopy and mass spectra indicated the further bacteriostatic mechanism of nanoparticles. Meanwhile, the nanoparticles had well biocompatibility and safety. Current study will open up new prospect that the design of self-assemblies between active phytochemicals can be originated from traditional Chinese medicine combination.

9.
Front Pharmacol ; 11: 1210, 2020.
Article in English | MEDLINE | ID: mdl-32982718

ABSTRACT

Diarrhea-predominant irritable bowel syndrome (IBS-D) is one common chronic functional disease of the digestive system with limited treatments. The microbiota-gut-brain axis (MGBA) has a central function in the pathogeny of IBS-D, which includes the participation of many various factors, such as brain-gut peptides (BGPs), immune inflammation, and intestinal flora. Inspired by the drug combination in traditional Chinese medicine (TCM), our previous study discovered that berberine (BBR) and baicalin (BA) could form natural self-assemblies as BA-BBR nanoparticles (BA-BBR NPs) and showed synergistic effects against IBS-D. Here, we investigated the synergistic effects of BA-BBR NPs on IBS-D model mice induced by chronic restraint stress plus Senna alexandrina Mill decoction with the influence on MGBA. BA-BBR NPs showed the best therapeutic effect on improving visceral hypersensitivity and diarrhea on IBS-D model mice, compared with BBR, BA, and BA/BBR mixture. Furthermore, BA-BBR NPs significantly (P<0.05) reduced the levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal polypeptide (VIP) and choline acety transferase (CHAT) in colon tissues or of serum from BGPs; it lowered the expressions of the nuclear factor kappa-B (NF-κB) in colon tissues and changed the levels of basophil granulocyte (BASO) and leukomonocyte (LYMPH) in whole blood from immune inflammation; it altered the intestinal flora of Bacteroidia, Deferribacteres, Verrucomicrobia, Candidatus_Saccharibacteria, and Cyanobacteria from intestinal flora. In conclusion, BA-BBR NPs, after forming the natural self-assembly between BBR and BA, promoted the synergistic effect on IBS-D mice than the sum of BBR and BA effects, based to the formation of self-assemblies rather than the simple mixing. It further proved that synergistic effect of BA-BBR NPs on IBS-D mice might be related to BGPs, immune inflammation, and intestinal flora from three important interrelated components of MGBA. This study will provide a novel idea for the interpretation of TCM compatibility theory and provide the basis for BA-BBR NPs as a medicinal plant-derived natural and efficient nanomaterial for clinical use.

10.
Molecules ; 25(4)2020 Feb 20.
Article in English | MEDLINE | ID: mdl-32093264

ABSTRACT

Betulinic acid (BA) is a star member of the pentacyclic triterpenoid family, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, 21 BA-nitrogen heterocyclic derivatives were synthetized, in addition to four intermediates, 23 of which were first reported. Moreover, they were screened for in-vitro cytotoxicity against four tumor cell lines (Hela, HepG-2, BGC-823 and SK-SY5Y) by a standard methylthiazol tetrazolium (MTT) assay. The majority of these derivatives showed much stronger cytotoxic activity than BA. Remarkably, the most potent compound 7e (the half maximal inhibitory concentration (IC50) of which was 2.05 ± 0.66 µM) was 12-fold more toxic in vitro than BA-treated Hela. Furthermore, multiple fluorescent staining techniques and flow cytometry collectively revealed that compound 7e could induce the early apoptosis of Hela cells. Structure-activity relationships were also briefly discussed. The present study highlighted the importance of introducing nitrogen heterocyclic rings into betulinic acid in the discovery and development of novel antitumor agents.


Subject(s)
Antineoplastic Agents , Cytotoxins , Neoplasms/drug therapy , Triterpenes/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cytotoxins/chemical synthesis , Cytotoxins/chemistry , Cytotoxins/pharmacology , Drug Screening Assays, Antitumor , HeLa Cells , Hep G2 Cells , Humans , Neoplasms/metabolism , Neoplasms/pathology , Pentacyclic Triterpenes , Structure-Activity Relationship , Betulinic Acid
11.
Chin Herb Med ; 12(2): 188-194, 2020 Apr.
Article in English | MEDLINE | ID: mdl-36119796

ABSTRACT

Objective: There are some anthraquinones, anthraquinones and flavonones in Sennae Folium which exhibited significant acidity, such as sennoside A/B and sennoside C/D. The current strategies used in separating these components are mainly based on conventional column chromatography which is time consuming, laborious and costly. This study is aimed at exploring a method of precipitation extraction of acid components in Sennae Folium. Using alkaloid as a "hook", it is reasonable to use the principle of "acid-alkali complexation" to "fish" the acidic components in Sennae Folium. Methods: Isothermal titration calorimeter (ITC) was used to measure the extraction efficiency of different alkaloids. Then, alkaloid determined by ITC was mixed with extracting solution of Sennae Folium to form complex. High performance liquid chromatography coupled with mass spectrometry (HPLC-MS2) was used to investigate the ingredients "fished" by berberine (Ber). The mechanism of "fishing" process was explained by ITC, optical activity, fluorescence spectrometry and scanning electron microscope. Results: The ITC results proved that the choice of "hook" was particularly important in the process of "fishing". Among the hooks, the fishing efficiency of the isoquinoline alkaloids (Ber) was the highest, reaching 10.3%. Nine ingredients were detected and determined by HPLC-MS2, and the main components were sennoside A/B and sennoside C/D. Based on ITC test of Ber and sennoside A, the combination mechanism of the two ingredients was a chemical reaction with a nearly binding ratio (2:1). Fluorescence and optical properties of the active ingredients were changed after complexation. By scanning electron microscope, we found that two types of components had obviously self-assembled behavior during the formation process. Conclusion: Ber successfully "fished" the main acidic components, sennoside A/B and sennoside C/D, from Sennae Folium. Combined with different characterizations, the "fishing" process was determined as a chemical association reaction induced by electrostatic interaction or π-π stacking. Therefore, with special identification ability, the "fishing" process had the potential of practical application.

12.
ACS Appl Mater Interfaces ; 12(1): 227-237, 2020 Jan 08.
Article in English | MEDLINE | ID: mdl-31829617

ABSTRACT

S. aureus is resistant to various first-line antibiotics, and seeking multifarious strategies aimed at effective control of antibiotic-resistant behavior is urgently needed. Here, we report a two-component directed self-assembly mode: the phytochemicals berberine and cinnamic acid can directly self-assemble into nanoparticles (NPs) displaying good bacteriostastic activity. Compared with several first-line antibiotics, the obtained nanostructures have a better inhibitory effect on multidrug-resistant S. aureus (MRSA) and stronger ability for biofilm removal. These qualities are attributed to the fact that organic assemblies can first spontaneously adhere to the surface of the bacteria, infiltrate into the cell, and then lead to converging attack against MRSA; thereafter, multipath bactericidal mechanisms of NPs on MRSA are found by both transcriptomic analysis and quantitative Polymerase Chain Reaction analysis. Moreover, when combined with spectral data and single crystal X-ray diffraction, the NPs' self-assembly mechanism governed by hydrogen bonds and π-π stacking interactions is clearly elucidated. These non-covalent interactions induce the NPs' formation of butterfly-like one-dimensional self-assembled units and finally layered three-dimensional spatial configuration. In addition, biocompatibility tests show that the NPs are nonhemolytic with little toxicity in vitro and in vivo. This directed self-assembly mode can offer a new perspective toward the design of biocompatible antimicrobial nanomedicines for clinical translation.


Subject(s)
Anti-Bacterial Agents , Berberine , Cinnamates , Drug Resistance, Multiple, Bacterial/drug effects , Methicillin-Resistant Staphylococcus aureus/growth & development , Nanoparticles/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Berberine/chemistry , Berberine/pharmacology , Cinnamates/chemistry , Cinnamates/pharmacology , Dogs , Madin Darby Canine Kidney Cells , Rats , Zebrafish
13.
Phytomedicine ; 63: 153009, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31301540

ABSTRACT

BACKGROUND: Considering the limitations of conventional western treatment for community-acquired pneumonia (CAP) and the extensive exploration of Chinese herbal injections (CHIs), systematically and critically evaluating the efficacy of CHIs in the treatment of CAP is necessary. PURPOSE: This study constructed a network meta-analysis (NMA) to investigate the efficacy of CHIs (including the Reduning injection (RDN), Yanhuning injection (YHN), Xiyanping injection (XYP), and Tanreqing injection (TRQ)) combined with Western medicine (WM) and WM alone in CAP. METHODS: A literature review was conducted in several databases from inception to June 2018. The quality of the included studies was assessed by the Cochrane risk of bias tool and modified Jadad scale. Data were analyzed by STATA 13.0 and WinBUGS 14.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Clustering analysis was utilized to compare the effect of CHIs between two different outcomes. RESULTS: A total of 47 eligible randomized controlled trials involving 4713 patients and 4 CHIs were included. The results of the NMA showed that RDN, YHN, XYP and TRQ combined with WM significantly improved treatment performance compared to WM alone. YHN+WM had obvious superiorities in the clinical effective rate, time for the disappearance of cough and the level of C-reactive protein. TRQ+WM was the most advantageous in shortening the time for defervescence and the average hospitalization time. XYP+WM was shown to reduce the time for the disappearance of lung rales best. Sixteen articles reported adverse drug reactions/adverse drug events (ADRs/ADEs) in detail, and 17 articles reported that there were no obvious ADRs/ADEs. CONCLUSION: This NMA showed that using CHIs in combination with WM improved treatment performance and could be beneficial for patients with CAP compared to using WM alone. Thereinto, YHN+WM showed a preferable improvement on patients with CAP when unified considering the clinical effective rate and other outcomes. As for safety, more evidence is needed to support this hypothesis.


Subject(s)
Community-Acquired Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Pneumonia/drug therapy , Bayes Theorem , Cough/drug therapy , Diterpenes/administration & dosage , Diterpenes/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Humans , Injections , Length of Stay , Randomized Controlled Trials as Topic , Treatment Outcome
14.
ACS Nano ; 13(6): 6770-6781, 2019 06 25.
Article in English | MEDLINE | ID: mdl-31135129

ABSTRACT

The abuse of traditional antibiotics has caused a series of health problems including antimicrobial resistance, which threatens human health. Therefore, searching for broad sources of antimicrobial agents and developing multidimensional strategies to combat bacterial infections are urgent. Here, we reported two natural self-assembling modes between berberine (BBR) and flavonoid glycosides: nanoparticles (NPs) and nanofibers (NFs), which were both mainly governed by electrostatic and hydrophobic interactions. These two nanostructures exhibited different antibacterial properties from BBR. NPs showed significantly enhanced bacteriostatic activity, whereas NFs displayed a much weaker effect than BBR. The distinguishing properties can be attributed to the different spatial configurations and self-assembly processes of NPs and NFs. Flavonoid glycosides and BBR first formed a one-dimensional complex unit and subsequently self-assembled into three-dimensional nanostructures. With the hydrophilic glucuronic acid toward the outside, NPs exhibited stronger affinity to bacteria, thereby inducing the collapse of the bacteria population and the decrease in biofilm. In addition, in vitro hemolysis tests, cytotoxicity tests, and in vivo zebrafish toxicity evaluation showed that the obtained self-assemblies had good biocompatibility. This supramolecular self-assembly strategy can be applied to construct other nanoscale antibacterial drugs and thus provides weapons for the development of self-delivering drugs in bacterial infection treatment.


Subject(s)
Anti-Bacterial Agents/chemistry , Berberine/chemistry , Drugs, Chinese Herbal/chemistry , Nanoparticles/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Berberine/pharmacology , Berberine/toxicity , Dogs , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/toxicity , Hemolysis/drug effects , Madin Darby Canine Kidney Cells , Rats , Staphylococcus aureus/drug effects , Zebrafish
15.
Zhongguo Zhong Yao Za Zhi ; 42(20): 3969-3973, 2017 Oct.
Article in Chinese | MEDLINE | ID: mdl-29243435

ABSTRACT

It has been focused on that there will be precipitates when decoction of Scutellariat Radix mixed with Coptidis Rhizoma. Precipitation was derived from interaction between acidic and basic compounds. This study was based on the interaction between active ingredients after compatibility, strived to explore whether it was feasible to judge the qualities of different Scutellariat Radix by isothermal titration calorimetry (ITC), build a new method established to characterize the qualities of traditional Chinese medicine by taking a series of active ingredients as index. We selected Scutellariat Radix (including three batches of different Scutellariat Radix bought from market and immature Scutellariat Radix which usually was used as adulterant) in different batches as the samples. First, we used ITC to determine the binding heat of the reactions between berberine and the decoctions of different Scutellariat Radix. The test showed that the binding heat of berberine titrated Scutellariat Radix was Scutellariat Radix A (-317.20 µJ), Scutellariat Radix B (-292.83 µJ), Scutellariat Radix C (-208.95 µJ) and immature Scutellariat Radix (-21.53 µJ), respectively. We chose deionized water titrated by berberine (2.51 µJ) as control. The heat change of berberine titrated immature Scutellariat Radix was much less than berberine titrated Scutellariat Radix. Then we determined the absorbance of different decoctions of Scutellariat Radix by UV Spectrophotometry on the maximum absorption wavelength, and the result is: Scutellariat Radix A (0.372), Scutellariat Radix B (0.333), Scutellariat Radix C (0.272), immature Scutellariat Radix (0.124). The absorbance of immature Scutellariat Radix was also less than Scutellariat Radix. The result of ITC assay was corresponded to UV spectrophotometry test. In conclusion, ITC could be used to characterize the quality of Scutellariat Radix. The new method to characterize the qualities of traditional Chinese medicine by taking a kind of active ingredients as index building by ITC was simple, scientific and feasible.


Subject(s)
Calorimetry , Drugs, Chinese Herbal/standards , Scutellaria baicalensis/chemistry , Drugs, Chinese Herbal/chemistry , Medicine, Chinese Traditional , Plant Roots/chemistry , Quality Control , Rhizome
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