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1.
Molecules ; 28(21)2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37959658

ABSTRACT

Liver fibrosis refers to a complex inflammatory response caused by multiple factors, which is a known cause of liver cirrhosis and even liver cancer. As a valuable medicine food homology herb, saffron has been widely used in the world. Saffron is commonly used in liver-related diseases and has rich therapeutic and health benefits. The therapeutic effect is satisfactory, but its mechanism is still unclear. In order to clarify these problems, we planned to determine the pharmacological effects and mechanisms of saffron extract in preventing and treating liver fibrosis through network pharmacology analysis combined with in vivo validation experiments. Through UPLC-Q-Exactive-MS analysis, a total of fifty-six nutrients and active ingredients were identified, and nine of them were screened to predict their therapeutic targets for liver fibrosis. Then, network pharmacology analysis was applied to identify 321 targets for saffron extract to alleviate liver fibrosis. Functional and pathway enrichment analysis showed that the putative targets of saffron for the treatment of hepatic fibrosis are mainly involved in the calcium signaling pathway, the HIF-1 signaling pathway, endocrine resistance, the PI3K/Akt signaling pathway, lipid and atherosclerosis, and the cAMP signaling pathway. Based on the CCl4-induced liver fibrosis mice model, we experimentally confirmed that saffron extract can alleviate the severity and pathological changes during the progression of liver fibrosis. RT-PCR and Western blotting analysis confirmed that saffron treatment can prevent the CCl4-induced upregulation of HIF-1α, VEGFA, AKT, and PI3K, suggesting that saffron may regulate AKT/HIF-1α/VEGF and alleviate liver fibrosis.


Subject(s)
Crocus , Drugs, Chinese Herbal , Mice , Animals , Proto-Oncogene Proteins c-akt/metabolism , Vascular Endothelial Growth Factor A/metabolism , Crocus/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Coloring Agents/pharmacology , Drugs, Chinese Herbal/pharmacology
2.
Chin Med ; 18(1): 96, 2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37537605

ABSTRACT

Pulmonary fibrosis is a chronic progressive interstitial lung disease caused by a variety of etiologies. The disease can eventually lead to irreversible damage to the lung tissue structure, severely affecting respiratory function and posing a serious threat to human health. Currently, glucocorticoids and immunosuppressants are the main drugs used in the clinical treatment of pulmonary fibrosis, but their efficacy is limited and they can cause serious adverse effects. Traditional Chinese medicines have important research value and potential for clinical application in anti-pulmonary fibrosis. In recent years, more and more scientific researches have been conducted on the use of traditional Chinese medicine to improve or reduce pulmonary fibrosis, and some important breakthroughs have been made. This review paper systematically summarized the research progress of pharmacological mechanism of traditional Chinese medicines and their active compounds in improving or reducing pulmonary fibrosis. We conducted a systematic search in several main scientific databases, including PubMed, Web of Science, and Google Scholar, using keywords such as idiopathic pulmonary fibrosis, pulmonary fibrosis, interstitial pneumonia, natural products, herbal medicine, and therapeutic methods. Ultimately, 252 articles were included and systematically evaluated in this analysis. The anti-fibrotic mechanisms of these traditional Chinese medicine studies can be roughly categorized into 5 main aspects, including inhibition of epithelial-mesenchymal transition, anti-inflammatory and antioxidant effects, improvement of extracellular matrix deposition, mediation of apoptosis and autophagy, and inhibition of endoplasmic reticulum stress. The purpose of this article is to provide pharmaceutical researchers with information on the progress of scientific research on improving or reducing Pulmonary fibrosis with traditional Chinese medicine, and to provide reference for further pharmacological research.

3.
Cell ; 186(11): 2313-2328.e15, 2023 05 25.
Article in English | MEDLINE | ID: mdl-37146612

ABSTRACT

Hybrid potato breeding will transform the crop from a clonally propagated tetraploid to a seed-reproducing diploid. Historical accumulation of deleterious mutations in potato genomes has hindered the development of elite inbred lines and hybrids. Utilizing a whole-genome phylogeny of 92 Solanaceae and its sister clade species, we employ an evolutionary strategy to identify deleterious mutations. The deep phylogeny reveals the genome-wide landscape of highly constrained sites, comprising ∼2.4% of the genome. Based on a diploid potato diversity panel, we infer 367,499 deleterious variants, of which 50% occur at non-coding and 15% at synonymous sites. Counterintuitively, diploid lines with relatively high homozygous deleterious burden can be better starting material for inbred-line development, despite showing less vigorous growth. Inclusion of inferred deleterious mutations increases genomic-prediction accuracy for yield by 24.7%. Our study generates insights into the genome-wide incidence and properties of deleterious mutations and their far-reaching consequences for breeding.


Subject(s)
Plant Breeding , Solanum tuberosum , Diploidy , Mutation , Phylogeny , Solanum tuberosum/genetics
4.
Nat Genet ; 55(5): 852-860, 2023 05.
Article in English | MEDLINE | ID: mdl-37024581

ABSTRACT

Effective utilization of wild relatives is key to overcoming challenges in genetic improvement of cultivated tomato, which has a narrow genetic basis; however, current efforts to decipher high-quality genomes for tomato wild species are insufficient. Here, we report chromosome-scale tomato genomes from nine wild species and two cultivated accessions, representative of Solanum section Lycopersicon, the tomato clade. Together with two previously released genomes, we elucidate the phylogeny of Lycopersicon and construct a section-wide gene repertoire. We reveal the landscape of structural variants and provide entry to the genomic diversity among tomato wild relatives, enabling the discovery of a wild tomato gene with the potential to increase yields of modern cultivated tomatoes. Construction of a graph-based genome enables structural-variant-based genome-wide association studies, identifying numerous signals associated with tomato flavor-related traits and fruit metabolites. The tomato super-pangenome resources will expedite biological studies and breeding of this globally important crop.


Subject(s)
Solanum lycopersicum , Solanum , Solanum lycopersicum/genetics , Genome-Wide Association Study , Genome, Plant/genetics , Plant Breeding , Solanum/genetics , Genomics
5.
J Pharm Biomed Anal ; 227: 115277, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-36736110

ABSTRACT

The quality of traditional Chinese medicine (TCM) guarantees its clinical efficacy. Although advanced analytical techniques and methods can accurately determine the content of chemical components in TCM, it is difficult to accurately determine its clinical efficacy. In addition, the current analytical methods and technologies are complex and have difficulty meeting the requirements of a rapid, accurate and convenient determination of TCM quality. In this study, we first propose the concept of "indistinct" evaluation of the quality of TCM, that is, combining biological potency with character evaluation, quantifying the character evaluation, and preparing the safflower quality grade evaluation card based on the character analysis, which provides research ideas and methods for the rapid and accurate evaluation of the quality of TCM. We determined the biological potency of different batches of safflower based on the in vitro antiplatelet aggregation model and divided the safflower samples into two grades based on the biological potency. We further collected the color information of different grades of safflower samples, quantified the color information of different grades of safflower, drew a quality grade evaluation card for the rapid judgment of safflower quality grade and verified its accuracy by pharmacodynamic evaluation. To further analyze the differences in the material basis of different grades of safflower, the LC-MS method was used to simultaneously determine the contents of 19 chemical components, such as myricetin, in different grades of safflower samples to analyze the differences in the material basis of different grades of safflower. The result shows that the different grades of safflower exhibited significant differences in color. The pharmacodynamic results show that the quality evaluation card prepared based on color information can accurately evaluate quality, and the effect of first-class safflower is significantly better than that of second-class safflower. The chemical analysis results of different grades of safflower show that there are also significant differences between them, among which hypericin, 6-hydroxyapin-6-O-glucose-7-O-glucuronide, 6-hydroxykaempferol-3,6-O-diglucoside-7-O-glucuronic acid glycoside, 6-hydroxykaempferol-3,6,7-tri-O-glucoside and hydroxysafflower yellow A exhibit significant differences, which may be the main differentiating components of different grades of safflower. This study preliminarily confirmed that the "indistinct" evaluation of the quality of TCM based on character analysis is accurate and scientific, and the quality evaluation card prepared can accurately judge the quality of TCM, providing a reference for the rapid application of TCM character evaluation.


Subject(s)
Carthamus tinctorius , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Carthamus tinctorius/chemistry , Precision Medicine , Drugs, Chinese Herbal/chemistry , Chromatography, Liquid
6.
Adv Mater ; 35(3): e2207950, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36300600

ABSTRACT

Polymer-inorganic hybrid Janus nanoparticles (PI-JNPs) have attracted extensive attention due to their special structures and functions. However, achieving the synergistic enhancement of photochemical activity between polymer and inorganic moieties in PI-JNPs remains challenging. Herein, the construction of a novel Janus Au-porphyrin polymersome (J-AuPPS) heterostructure by a facile one-step photocatalytic synthesis is reported. The near-field enhancement (NFE) effect between porphyrin polymersome (PPS) and Au nanoparticles in J-AuPPS is achieved to enhance its near-infrared (NIR) light absorption and electric/thermal field intensity at their interface, which improves the energy transfer and energetic charge-carrier generation. Therefore, J-AuPPS shows a higher NIR-activated photothermal conversion efficiency (48.4%) and generates more singlet oxygen compared with non-Janus core-particle Au-PPS nanostructure (28.4%). As a result, J-AuPPS exhibits excellent dual-mode (photothermal/photodynamic) antibacterial and anti-biofilm performance, thereby significantly enhancing the in vivo therapeutic effect in an implant-associated-infection rat model. This work is believed to motivate the rational design of advanced hybrid JNPs with desirable NFE effect and further extend their biological applications.


Subject(s)
Metal Nanoparticles , Nanoparticles , Nanostructures , Rats , Animals , Gold/chemistry , Metal Nanoparticles/therapeutic use , Metal Nanoparticles/chemistry , Phototherapy , Polymers/chemistry
7.
J Sep Sci ; 46(2): e202200433, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36373183

ABSTRACT

Quality consistency of Glycyrrhiza formula granules is essential for guaranteeing clinical efficacy. However, a suitable method to accurately and conveniently evaluate the consistency of the clinical efficacy of Glycyrrhiza formula granules is currently not available. This study established a method for the simultaneous determination of 12 active components in Glycyrrhiza formula granules using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry. The rate of inhibition of cyclooxygenase-2 by different batches of Glycyrrhiza formula granules was determined. Near-infrared spectra were collected for different batches of Glycyrrhiza formula granules to detect their biological activity in the inhibition of cyclooxygenase-2. The quality consistency of the 11 batches of Glycyrrhiza formula granules was evaluated using principal component and correlation analyses. The results showed significant differences in the formula granules of Glycyrrhiza uralensis produced by the different manufacturers. Some differences were also observed among batches of formula granules produced by the same manufacturer. Correlation analysis of the chemical components and cyclooxygenase-2 activity showed that glycyrrhizic acid, liquiritin, and isoliquiritin were the main active components of Glycyrrhiza. Correlation analysis of the near-infrared spectra and cyclooxygenase-2 inhibition activity showed a high correlation between the active components and three characteristic bands: 3383-3995, 4227-4651, and 5315-5878 cm-1 . In this study, the main active anti-inflammatory components of Glycyrrhiza granules were screened. Thus, the near-infrared spectrum and characteristic active band of multi-index active components can be used to quickly detect the quality consistency of Glycyrrhiza formula granules, thereby improving the ability to control the quality and consistency of these granules.


Subject(s)
Drugs, Chinese Herbal , Glycyrrhiza uralensis , Glycyrrhiza , Drugs, Chinese Herbal/analysis , Cyclooxygenase 2 , Glycyrrhiza/chemistry , Glycyrrhiza uralensis/chemistry , Glycyrrhizic Acid/analysis , Chromatography, High Pressure Liquid/methods
8.
Phytomedicine ; 108: 154463, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36347177

ABSTRACT

BACKGROUND: Cardiovascular disease is one of the most concerning chronic diseases in the world. Many studies have shown that platelet overactivation is a very important factor in the occurrence and development of cardiovascular diseases. At present, the widely used antiplatelet drugs have some defects, such as drug resistance and adverse reactions. PURPOSE: The purpose of this article is to summarize the main mechanisms and pathways of platelet activation, the main targets of antiplatelet aggregation, and the antiplatelet aggregation components of natural drugs and their mechanisms of action to provide new research ideas for the development and application of antiplatelet drugs. STUDY DESIGN AND METHODS: In this review, we systematically searched the PubMed, Google Scholar, Web of Science, and CNKI databases and selected studies based on predefined eligibility criteria. We then assessed their quality and extracted data. RESULTS: ADP, AA, THR, AF, collagen, SDF-1α, and Ca2+ can induce platelet aggregation and trigger thrombosis. Natural drugs have a good inhibitory effect on platelet activation. More than 50 kinds of natural drugs and over 120 kinds of chemical compounds, including flavonoids, alkaloids, saponins, terpenoids, coumarins, and organic acids, have significantly inhibited platelet activation activity. The MAPK pathway, cGMP-PKG pathway, cAMP-PKA pathway, PI3K-AKT pathway, PTK pathway, PLC pathway, and AA pathway are the main mechanisms and pathways of platelet activation. CONCLUSION: Natural drugs and their active ingredients have shown good activity and application prospects in anti-platelet aggregation. We hope that this review provides new research ideas for the development and application of antiplatelet drugs.


Subject(s)
Cardiovascular Diseases , Platelet Aggregation Inhibitors , Humans , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Phosphatidylinositol 3-Kinases/metabolism , Platelet Activation , Platelet Aggregation , Blood Platelets , Cardiovascular Diseases/metabolism
10.
Comput Biol Med ; 149: 106001, 2022 10.
Article in English | MEDLINE | ID: mdl-36055159

ABSTRACT

Insomnia is a very common disease worldwide. It seriously affects the quality of human life and even endangers health. Traditional Chinese medicine (TCM) has unique advantages in the intervention and treatment of insomnia. However, its underlying mechanism has yet to be elucidated. This study was performed to explore the potential biomarkers and mechanisms of insomnia, and treatment TCM and classical prescriptions. The gene microarray data of insomnia is downloaded and preprocessed. Differentially expressed genes (DEGs) and GO and KEGG enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed. Small molecule drugs for curing insomnia were identified using cMap and CTD databases. We searched the TCM corresponding to small molecule drugs and the classic prescriptions corresponding to TCM by the TCMSP database. We constructed a network of "ingredient-TCM-classic prescriptions". The molecular docking was performed to validate the screening results. We obtained a total of 124 DEGs, including 78 up-regulated genes, 46 down-regulated genes, 10 Hub genes and 3 key modules. A total of 125 significant GO entries and 15 significant KEGG were enriched (P < 0.05). The main biological processes involve neuronal apoptosis, autophagy, cell growth and apoptosis, etc. These signaling pathways may be involved in molecular regulatory mechanisms of insomnia, such as autophagy regulation, Alzheimer's disease, pathways to neurodegenerative diseases and neurotrophic factor signaling pathways. We identified 10 traditional Chinese medicines and 2 classical prescriptions of potential value. In addition, the molecular docking results indicated that small molecule ligands were nicely bound to the Hub gene, and the binding affinity ranged from -7.6 to -9.7 kcal/mol. This study provides a foundation for the clinical treatment of insomnia, explains the molecular mechanisms, and efficiently develops TCM and classical prescriptions.


Subject(s)
Computational Biology , Sleep Initiation and Maintenance Disorders , Biomarkers , Computational Biology/methods , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Humans , Ligands , Molecular Docking Simulation , Nerve Growth Factors , Prescriptions , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/genetics
11.
Nature ; 606(7914): 535-541, 2022 06.
Article in English | MEDLINE | ID: mdl-35676481

ABSTRACT

Potato (Solanum tuberosum L.) is the world's most important non-cereal food crop, and the vast majority of commercially grown cultivars are highly heterozygous tetraploids. Advances in diploid hybrid breeding based on true seeds have the potential to revolutionize future potato breeding and production1-4. So far, relatively few studies have examined the genome evolution and diversity of wild and cultivated landrace potatoes, which limits the application of their diversity in potato breeding. Here we assemble 44 high-quality diploid potato genomes from 24 wild and 20 cultivated accessions that are representative of Solanum section Petota, the tuber-bearing clade, as well as 2 genomes from the neighbouring section, Etuberosum. Extensive discordance of phylogenomic relationships suggests the complexity of potato evolution. We find that the potato genome substantially expanded its repertoire of disease-resistance genes when compared with closely related seed-propagated solanaceous crops, indicative of the effect of tuber-based propagation strategies on the evolution of the potato genome. We discover a transcription factor that determines tuber identity and interacts with the mobile tuberization inductive signal SP6A. We also identify 561,433 high-confidence structural variants and construct a map of large inversions, which provides insights for improving inbred lines and precluding potential linkage drag, as exemplified by a 5.8-Mb inversion that is associated with carotenoid content in tubers. This study will accelerate hybrid potato breeding and enrich our understanding of the evolution and biology of potato as a global staple food crop.


Subject(s)
Crops, Agricultural , Evolution, Molecular , Genome, Plant , Solanum tuberosum , Crops, Agricultural/genetics , Genome, Plant/genetics , Plant Breeding , Plant Tubers/genetics , Solanum tuberosum/genetics
12.
J Ethnopharmacol ; 290: 115114, 2022 May 23.
Article in English | MEDLINE | ID: mdl-35181489

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (THSWD) is based on the "First Recipe of Gynecology." It is widely used in various blood stasis and deficiency syndromes, mainly in gynecological blood stasis, irregular menstruation, and dysmenorrhea. THSWD has great demand in traditional Chinese medicine (TCM), gynecology, orthopedics, and internal medicine. According to classical records, three medicinal materials, namely Rehmanniae radix, Angelica sinensis, and Carthamus tinctorius, used in THSWD need to be "washed with yellow rice wine." In the study of TCM prescriptions, the processing methods of medicinal materials not only needed to follow traditional records but also should consider modern technical conditions. Many medicinal materials in the repertoire of classical prescriptions involve yellow rice wine processing. Determining the processing method for medicinal materials is a key and difficult problem in the research and development of classical prescriptions. AIM OF THE STUDY: With THSWD as the representative, this study analyzed differences between no processing method, the modern processing method of "stir-frying the materials with yellow rice wine," and the traditional processing method of "washing with yellow rice wine." We focused on three aspects: composition, efficacy, and endogenous metabolism. This study aimed to provide a reference for research on the processing methods of medicinal materials used in classical prescriptions. MATERIALS AND METHODS: UPLC-Q-Orbitrap HRMS was used to quickly identify and classify the main chemical compounds of THSWD. A model of primary dysmenorrhea (PD) was established using estradiol benzoate combined with oxytocin. The latent period and writhing time; the levels of serum PGF2α, PGE2, ET-1, and ß-EP; and the pathological sections of the uterus were observed to determine their pharmacodynamic differences. GC-TOF/MS was used to analyze the differences in serum metabolites in rats. RESULTS: A total of 54 active compounds were identified, and the results showed that catalpol and rehmapicroside disappeared following yellow rice wine processing. Compared with materials processed by the traditional method, the relative contents of 15 components, such as 5-hydroxymethylfurfural and digitalis C, increased in materials processed by the modern method. However, the relative contents of 16 components, such as hydroxysafflor yellow A, verbascoside, and ferulic acid, decreased in the modern processing method. The modern and classic processing methods acted on PD through different metabolic pathways. THSWD obtained by classical processing methods mainly treated PD through anti-inflammatory and estrogen metabolism pathways, whereas THSWD obtained by modern processing methods mainly treated PD through anti-inflammatory metabolic pathways. CONCLUSION: The study revealed the differences in different yellow rice wine processing methods in terms of chemical composition of the THSWD obtained, as well as the mechanisms of action for the treatment of PD. This study provides a reference for the clinical application of THSWD and development of classical prescription preparations.


Subject(s)
Chemistry, Pharmaceutical/methods , Drugs, Chinese Herbal/chemistry , Oryza/chemistry , Wine , Angelica sinensis , Carthamus tinctorius , Chalcone/analogs & derivatives , Chalcone/chemistry , Humans , Quinones/chemistry , Rehmannia
13.
J Ethnopharmacol ; 285: 114838, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-34788645

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. AIM OF THE STUDY: To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. MATERIALS AND METHODS: Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. RESULTS: Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1ß, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. CONCLUSION: These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases.


Subject(s)
Acute Lung Injury , Antiviral Agents/pharmacology , Bronchoalveolar Lavage Fluid , COVID-19 , Drugs, Chinese Herbal/pharmacology , Lung , Acute Lung Injury/drug therapy , Acute Lung Injury/immunology , Acute Lung Injury/pathology , Animals , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/virology , COVID-19/complications , COVID-19/immunology , COVID-19/virology , Capsules , Chemokine CXCL2/analysis , Coix , Forsythia , Interleukin-1beta/analysis , Interleukin-6/analysis , Lonicera , Lung/drug effects , Lung/metabolism , Lung/pathology , Lung/virology , Mice , Mortality , Morus , Peptide Fragments/analysis , Prunus armeniaca , Respiration/drug effects , SARS-CoV-2 , Treatment Outcome , Tumor Necrosis Factor-alpha/analysis
14.
Chin J Integr Med ; 26(9): 648-655, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32676976

ABSTRACT

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS: Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).


Subject(s)
Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/administration & dosage , Interferon-alpha/administration & dosage , Lopinavir/administration & dosage , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Administration, Inhalation , Adult , COVID-19 , China , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Integrative Medicine , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Risk Assessment , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/mortality , Severity of Illness Index , Survival Rate
15.
Front Pharmacol ; 11: 746, 2020.
Article in English | MEDLINE | ID: mdl-32523531

ABSTRACT

As chemical analysis for quality control (QC) of traditional Chinese medicine (TCM) formula is difficult to guarantee the effectiveness, a bioassay method that combines QC with evaluation of therapeutic effects has been developed to assess the TCM quality. Here, we chose a thirteen-component TCM formula, Lianhua Qingwen capsule (LHQW), as a representative sample, to explore the pivotal biomarkers for a bioassay and to investigate close association between QC and pharmacological actions. Initially, our results showed that chemical fingerprinting could not effectively distinguish batches of LHQW. Pharmacological experiments indicated that LHQW could treat influenza A virus (H1N1) infection in the H1N1 mouse model, as claimed in clinical trials, by improving pathologic alterations and bodyweight loss, and decreasing virus replication, lung lesions and inflammation. Furthermore, by using serum metabolomics analysis, we identified two important metabolites, prostaglandin F2α and arachidonic acid, and their metabolic pathway, arachidonic acid metabolism, as vital indicators of LHQW in treatment of influenza. Subsequently, macrophages transcriptomics highlighted the prominent role of cyclooxygenase-2 (COX-2) as the major rate-limiting enzyme in the arachidonic acid metabolism pathway. Finally, COX-2 was validated by in vivo gene expression and in vitro enzymatic activity with 43 batches of LHQW as a viable pharmacological biomarker for the establishment of bioassay-based QC. Our study provides systematic methodology in the pharmacological biomarker exploration for establishing the bioassay-based QC of LHQW or other TCM formulas relating to their pharmacological activities and mechanism.

16.
Nat Commun ; 11(1): 1724, 2020 04 07.
Article in English | MEDLINE | ID: mdl-32265490

ABSTRACT

Vesicular photothermal therapy agents (PTAs) are highly desirable in photothermal therapy (PTT) for their excellent light-harvesting ability and versatile hollow compartments. However, up to now, the reported vesicular PTAs are generally self-assembled from small molecules like liposomes, and polymer vesicles have seldom been used as PTAs due to the unsatisfactory photothermal conversion efficiency resulting from the irregular packing of chromophores in the vesicle membranes. Here we report a nano-sized polymer vesicle from hyperbranched polyporphyrins with favorable photothermal stability and extraordinarily high photothermal efficiency (44.1%), showing great potential in imaging-guided PTT for tumors through in vitro and in vivo experiments. These excellent properties are attributed to the in situ supramolecular polymerization of porphyrin units inside the vesicle membrane into well-organized 1D monofilaments driven by π-π stacking. We believe the supramolecular polymerization-enhanced self-assembly process reported here will shed a new light on the design of supramolecular materials with new structures and functions.


Subject(s)
Cell Survival/drug effects , Hyperthermia, Induced/methods , Nanoparticles/chemistry , Phototherapy/methods , Polymers/chemistry , Porphyrins/chemistry , Animals , Circular Dichroism , Female , Humans , Hydrophobic and Hydrophilic Interactions , MCF-7 Cells , Membranes, Artificial , Mice , Mice, Nude , Microscopy, Electron, Scanning , Molecular Dynamics Simulation , NIH 3T3 Cells , Nanoparticles/therapeutic use , Nanoparticles/ultrastructure , Polymerization , Polymers/chemical synthesis , Polymers/pharmacokinetics , Polymers/therapeutic use , Porphyrins/chemical synthesis , Porphyrins/pharmacokinetics , Porphyrins/therapeutic use , Rats , Spectrometry, Fluorescence , Temperature , Transplantation, Heterologous
17.
Anal Bioanal Chem ; 411(27): 7187-7196, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31620825

ABSTRACT

Surface-enhanced Raman spectroscopy (SERS) has the potential to detect pesticide residues in agricultural products. However, some systemic pesticides, such as chlorpyrifos, can enter the plant tissue, and not just stay on the surface. Consequently, many SERS studies halted at practical application because of its complexity. In this work, SERS technology was used to detect chlorpyrifos residues in tea products at the semiquantitative level. A simple pretreatment method effectively avoided interference of other fluorescent substances, and all major peaks could be distinguished on the basis of a novel substrate. A principal component analysis algorithm was applied to form a regression model, and a nanogram detection limit was obtained. Furthermore, chlorpyrifos residues in the same tea products were also measured by gas chromatography-mass spectrometry, and the results show a small range of errors. From the comparative study of the two detection methods, the results suggest the great promise of SERS technology for rapid inspection of agricultural products.


Subject(s)
Chlorpyrifos/analysis , Pesticide Residues/analysis , Spectrum Analysis, Raman/methods , Tea/chemistry , Gas Chromatography-Mass Spectrometry , Limit of Detection , Pesticides/analysis
18.
Zhongguo Zhong Yao Za Zhi ; 43(18): 3756-3763, 2018 Sep.
Article in Chinese | MEDLINE | ID: mdl-30384543

ABSTRACT

To investigate the hepatoprotective effect of Schisandrae Chinensis Fructus (SCF) on CCl4-induced liver injury, observe its effect on serum metabolites, explore its scientific connotation in liver preservation and find the biomarkers for hepatoprotective effect of SCF. Liver injury model was established by using CCl4. The pathological sections of liver tissues were observed and the contents of alanine transaminase (ALT) and aspartate transaminase (AST) in serum were determined. The metabolic skills were adopted based on ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC-Q-TOF-MS), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) for screening and identification of biomarkers related to liver injury. The results showed the metabolites in blank group, model group and administration group could be easily distinguished, 50 differential compounds were identified and 7 possible metabolic pathways of liver protection were enriched. In this experiment, the hepatoprotective effect of SCF was verified, and the related metabolic pathways such as amino acid metabolism, vitamin metabolism and glycerophospholipid metabolism were discussed.


Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Drugs, Chinese Herbal/chemistry , Metabolomics , Schisandra/chemistry , Animals , Biomarkers , Chromatography, High Pressure Liquid , Fruit/chemistry , Liver/drug effects , Liver/metabolism , Principal Component Analysis , Tandem Mass Spectrometry
19.
Sci Rep ; 8(1): 5695, 2018 04 09.
Article in English | MEDLINE | ID: mdl-29632384

ABSTRACT

Experiential quality assessment(EQA) is an important sensory analysis for judging herbal quality grades. Because of the high empirical utility of expert experience, the consistency, science and inheritance of such experience are continuously in dispute. To explore the scientific evidence for this subjective method, we designed a Delphi expert investigation coupled with chemical analysis to evaluate the quality of Schisandrae Chinensis Fructus (SCF). Initially, 13 experts were invited to independently evaluate the grades of 11 batches of SCF. After screening the consistency and repeatability of the evaluation results, typical samples of all quality levels were identified. Seven significant physical characters were detected; colour and size were found to be the key parameters for identifying SCF quality. Based on this correlation, a decision tree model was ultimately established and converted to a quality evaluation card. Over 80% consistency in a novice test demonstrated the technical advantages and application characteristics of the model. Further correlation analysis revealed that EQA quality grades of SCF were positively correlated to the content of polysaccharides and polyphenols, while negatively correlated to the content of lignans. Biological activities were also approving it. In summary, our study proves that subjective EQA is consistency, repeatability and could be inherited.


Subject(s)
Lignans/analysis , Polyphenols/analysis , Polysaccharides/analysis , Schisandra/chemistry , Chromatography, High Pressure Liquid , Decision Trees , Delphi Technique , Drugs, Chinese Herbal/chemistry , Humans , Phenotype , Quality Control
20.
Zhongguo Zhong Yao Za Zhi ; 42(3): 600-606, 2017 Feb.
Article in Chinese | MEDLINE | ID: mdl-28952271

ABSTRACT

A typical clinical case of taking Dictamni Cortex(Baixianpi) powder was analyzed to study liver damage caused by Dictamni Cortex. Liver damage was diagnosed according to the integrated evidence chain method recommended by the Guideline for Diagnosis and Treatment of Herb-Induced Liver Injury. By analyzing clinical history and biochemistry and imaging examinations, underlying diseases, such as viral hepatitis, autoimmune liver disease and alcoholic liver disease, were excluded. Through the investigation of medication history, we made it clear that the patient only took Dictamni Cortex powder during the period, and thus suspected that the liver injury was induced by Dictamni Cortex. Furthermore, the quality of the drug was tested, and the results showed it was consistent with the quality standard of Chinese Pharmacopoeia. DNA barcoding showed that the drug was 100% similar with Dictamnus dasycarpus. Moreover, exogenous harmful substances and chemical drug additions were tested, and the results showed that the content of heavy metal, pesticide residues and microbial toxin were consistent with the required standards, and no chemical drug additions were found in Agilent Fake TCM-Drugs database. In summary, we confirmed that the clinical case of drug-induced liver injury was induced by D. dasycarpus with the dose of 15 g•d⁻¹, which exceeded the prescribed amount of Chinese Pharmacopoeia. According to the Guideline for Diagnosis and Treatment of Herb-Induced Liver Injury, the case of drug-induced liver injury induced by D. dasycarpus was confirmed, which provided a direct and reliable evidence for the study of risk of liver injury induced by D. dasycarpus and its relevant preparations.


Subject(s)
Chemical and Drug Induced Liver Injury , Dictamnus/adverse effects , Drugs, Chinese Herbal/adverse effects , Humans
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