Research Progress of Natural Product Photosensitizers in Photodynamic Therapy.

Photodynamic therapy is a noninvasive cancer treatment that utilizes photosensitizers to generate reactive oxygen species upon light exposure, leading to tumor cell apoptosis. Although photosensitizers have shown efficacy in clinical practice, they are associated with certain disadvantages, such as a certain degree of toxicity and limited availability. Recent studies have shown that natural product photosensitizers offer promising options due to their low toxicity and potential therapeutic effects. In this review, we provide a summary and evaluation of the current clinical photosensitizers that are commonly used and delve into the anticancer potential of natural product photosensitizers like psoralens, quinonoids, chlorophyll derivatives, curcumin, chrysophanol, doxorubicin, tetracyclines, Leguminosae extracts, and Lonicera japonica extract. The emphasis is on their phototoxicity, pharmacological benefits, and effectiveness against different types of diseases. Novel and more effective natural product photosensitizers for future clinical application are yet to be explored in further research. In conclusion, natural product photosensitizers have potential in photodynamic therapy and represent a promising area of research for cancer treatment.

Network pharmacology integrated with molecular docking technology to reveal the potential mechanism of Shuganfang against drug-induced liver injury.

This study aimed to investigate the active composition and mechanism of the Shuganfang (SGF) in treating drug-induced liver injury (DILI) using network pharmacology and molecular docking. The potential active ingredients and targets of SGF were obtained from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. DILI-related targets were queried from various databases including GEO, GeneCards, OMIM, NCBI, and DisGeNET. The STRING database was used to establish a protein-protein interaction (PPI) network. DAVID was utilized for conducting gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The data visualization and analysis of herb-ingredient-target and disease-pathway-target-ingredient networks were conducted using Cytoscape software (version 3.7.2). PyMoL and AutoDock software was used to select the best binding target for molecular docking. A total of 177 active ingredients,126 targets and 10112 disease targets were obtained, including 122 intersection targets. The identified potential active ingredients consisted of quercetin, kaempferol, luteolin, tanshinone IIa, nobiletin, isorhamnetin, beta-sitosterol and naringenin. The core targets implicated in the study were IL6, estrogen receptor 1 (ESR1), hypoxia-inducible factor alpha subunit 1 (HIF1A), MYC and vascular endothelial growth factor A (VEGFA). KEGG analysis revealed that the treatment of DILI with SGF mainly acted through apoptosis, the PI3K-Akt signaling pathway, and the tumor necrosis factor (TNF) signaling pathway. Furthermore, the binding affinities between the potential ingredients and the core targets were subsequently confirmed through molecular docking experiments. The findings indicated that the docking outcomes remained consistent and demonstrated a favorable capacity for binding. SGF exerts a therapeutic effect on DILI through multiple active ingredients, multiple targets and multiple pathways. Our findings contribute to a positive investigation and establish a theoretical basis for further extensive exploration of SGF as a potential treatment for DILI in future research.

Core outcomes were rarely reported overall in systematic reviews on acupuncture for osteoarthritis: a cross-sectional meta-epidemiological study.

OBJECTIVE: To identify a comprehensive list of outcomes and explore the reporting rate of core outcome sets (COS) and related factors in systematic reviews (SRs) of acupuncture for osteoarthritis (OA). STUDY DESIGN AND SETTING: Databases were searched for the relative SRs. Descriptive statistics were calculated as frequencies and percentages. Binary logistic regression was used to explore the factors affecting the reporting rate of COS. RESULTS: We included 59 SRs. Outcome measures reported in the SRs were classified into 11 domains and 67 unique outcomes. No SR completely reported COS. In COS released in 2016, 75% of outcomes (6/8) were only reported by ⩽5% SRs. In COS released in 2019, the reporting rate was very low (from 0% to 17%) for 73.3% of outcomes (11/15). SRs published in the most recent 5 years had a significantly greater possibility of reporting COS (odds ratio (OR) = 4.74, 95% confidence interval (CI) = 1.33 to 16.88, p = 0.016). CONCLUSION: Core outcomes were rarely reported in systematic reviews of acupuncture for OA, with considerable heterogeneity in the use of outcomes. The publication of COS in the COMET (Core Outcome Measures in Effectiveness Trials) database may help promote the reporting of COS. We encourage systematic reviewers to use relevant COS.

[Intestinal absorption characteristics of root tuber of Cynanchum auriculatum extract in normal and functional dyspepsia model rats via everted intestine sac model].

The study investigated the difference of intestinal absorption characteristics of root tuber of Cynanchum auriculatum extract between normal and functional dyspepsia(FD) model rats with everted intestine sac model.The content of syringic acid, scopoletin, caudatin, baishouwu benzophenone, qingyangshengenin and deacyhmetaplexigenin in the C.auriculatum extract in different intestinal segments was detected by UPLC-MS/MS.The cumulative absorption amount(Q) and absorption rate constant(K_a) of the six chemical constituents were calculated.The results showed that the six components could be absorbed into the intestinal sac and were unsaturated, which indicated that the absorption mechanism of scopoletin was active transport in the intestine, while that of the other five components were passive diffusion.For normal group, the syringic acid and baishouwu benzophenone in ileum, qingyangshengenin and deacyhmetaplexigenin in ileum and duodenum, and caudatin in colon were well absorbed and scopoletin at low, medium and high concentrations was found excellent absorption in jejunum, ileum, and colon, respectively.Whereas the best absorption site of each component was ileum in model group.The absorption characteristics of each component between normal group and model group were complex at different concentrations, showing inconsistent tendency of absorption, which suggested that the components of root tuber of C.auriculatum extract were selectively absorbed in small intestine, and the absorption characteristics of the six components could be changed under FD status.This study provided theoretical basis for the clinical drug application and development of root tuber of C.auriculatum.

A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice.

The Coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented public health crisis worldwide. Although several vaccines are available, the global supply of vaccines, particularly within developing countries, is inadequate, and this necessitates a need for the development of less expensive, accessible vaccine options. To this end, here, we used the Escherichia coli expression system to produce a recombinant fusion protein comprising the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; residues 319-541) and the fragment A domain of Cross-Reacting Material 197 (CRM197); hereafter, CRMA-RBD. We show that this CRMA-RBD fusion protein has excellent physicochemical properties and strong reactivity with COVID-19 convalescent sera and representative neutralizing antibodies (nAbs). Furthermore, compared with the use of a traditional aluminum adjuvant, we find that combining the CRMA-RBD protein with a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH-002C-Ac) leads to stronger humoral immune responses in mice, with 4-log neutralizing antibody titers. Overall, our study highlights the value of this E. coli-expressed fusion protein as an alternative vaccine candidate strategy against COVID-19.

Mechanisms underlying the therapeutic effects of Qingfeiyin in treating acute lung injury based on GEO datasets, network pharmacology and molecular docking.

BACKGROUND: Qingfeiyin (QFY) is a common Chinese herbal formula for the treatment of acute lung injury (ALI). However, its mechanisms of action are unclear. In this study, we systematically explored the effects and mechanism of action of QFY in ALI using network pharmacology and molecular docking. METHODS: Active compounds and targets of QFY were obtained from TCMSP and TCMID. ALI-related targets were retrieved from GEO datasets combined with GeneCards, OMIM, and TTD databases. A protein-protein interaction (PPI) network was built to screen the core targets. DAVID was used for GO and KEGG pathway enrichment analyses. The tissue and organ distribution of targets was evaluated. Interactions between potential targets and active compounds were assessed by molecular docking. A molecular dynamics simulation was conducted for the optimal core protein-compound complexes obtained by molecular docking. RESULTS: In total, 128 active compounds and 121 targets of QFY were identified. A topological analysis of the PPI network revealed 13 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of QFY are mediated by genes related to inflammation, apoptosis, and oxidative stress as well as the MAPK and PI3K-Akt signaling pathways. Molecular docking and molecular dynamics simulations revealed good binding ability between the active compounds and screened targets. CONCLUSIONS: This study successfully predict the effective components and potential targets and pathways involved in the treatment of ALI for QFY. We provided a novel strategy for future research of molecular mechanisms of QFY in ALI treatment. Moreover, the potential active ingredients provide a reliable source for drug screening for ALI.

[Differences in intestinal absorption characteristics of Cynanchum auriculatum extract based on in situ intestinal circulation perfusion model in two states].

The present study aimed to investigate the intestinal absorption characteristics of six components(syringic acid, scopoletin, baishouwu benzophenone, caudatin, qingyangshengenin, and deacylmetaplexigenin) in Cynanchum auriculatum extract. In situ intestinal circulation perfusion model was employed to investigate the differences in intestinal absorption characteristics of C. auriculatum extract under the influence of different intestinal segments, different drug concentrations, and bile in the normal and functional dyspepsia(FD) states. The results showed that the absorption of baishouwu benzophenone decreased with the increase in the concentration of C. auriculatum extract(P<0.01), while the absorption of syringic acid and other components increased in a dose-independent manner, suggesting that baishouwu benzophenone might follow active absorption, while other components might not be on a single absorption pattern. The main absorption sites of each component in the normal state were different from those in the FD state. The cumulative absorption conversion rates in the FD state were generally lower than those in the normal state, and bile inhibited the absorption of other components except for scopoletin in both states(P<0.05). As revealed, the small intestine showed selectivity to the absorption of drugs, and the pathological state(such as FD) and bile both affected the absorption of the main components, which provides a theoretical basis for the development of new drugs and further development of C. auriculatum.

[Excretion of Cynanchum auriculatum extract in urine and feces of normal and functional dyspepsia rats].

In the present study, the excretion of four active components(qingyangshengenin, deacylmetaplexigenin, baishouwu benzophenone, and scopoletin) in Cynanchum auriculatum extract in the urine and feces of normal and functional dyspepsia(FD) rats was investigated. Rats were divided into a normal group and an FD model group. The FD model was induced by oral administration of ice hydrochloric acid combined with irregular feeding. The C. auriculatum extract was administered orally at a dose of 1 g·kg~(-1). The rat urine and feces were collected at 4, 8, 12, 24, 36, 48, 60, 72, and 84 h for UPLC-ESI-MS/MS analysis. The differences in excretion of the four components were compared between normal and FD rats. The results showed that except for the baishouwu benzophenone in the feces, the components such as qingyangshengenin in the urine and feces did not reach the plateau value within 84 h. Qingyangshengenin was mainly excreted through defecation, and the cumulative excretion rates in the normal state and FD were 0.32% and 0.66%, respectively. Deacylmetaplexigenin was mainly excreted through urination, and the cumulative excretion rates in the normal state and FD were 6.70% and 7.56%, respectively. Baishouwu benzophenone was mainly excreted through defecation in the normal state, but mainly excreted through urination in the FD state, with cumulative excretion rates of 0.41% and 0.52%, respectively. Scopoletin was mainly excreted through urination, with cumulative excretion rates of 0.83% and 2.13% in the normal state and FD, respectively. In general, the components were mainly excreted in the urine in the FD state. Compared with the normal group, the FD group showed decreased cumulative excretion rates of qingyangshengenin, baishouwu benzophenone, and scopoletin in the urine(P<0.05). Therefore, FD had a certain influence on the excretion of the main components of C. auriculatum extract, and the excretion of each component through urination and defecation was low, suggesting that there might be a wide range of metabolic pathways after oral administration and components were mainly excreted in the form of metabolites. This experiment provides a reference for the new drug development and clinical application of C. auriculatum.

[Simultaneous determination of four components of Shuganning Injection in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study].

This study aims to reveal the pharmacokinetics of Shuganning Injection in normal rats. In this experiment,ultra-high performance liquid chromatography-electrospray-tandem mass spectrometry( UPLC-ESI-MS/MS) was used to establish an analytical method for simultaneous determination of chlorogenic acid,gardenioside,oroxylin A and baicalin in rat plasma. Then,the non-compartmental model( NCA) in Phoenix WinN onL in 6. 4 software was used to fit pharmacokinetic parameters. The methodological validation showed that the linear relationship of the components in rat plasma samples were good( r>0. 995). The recovery rate and matrix effect of plasma samples with low,middle and high concentration were 79. 14%-101. 4%. The intra-day and inter-day precision,accuracy and stability meet the requirements of biological sample analysis. The half-life( t1/2) of chlorogenic acid,gardenioside,oroxylin A did not change significantly and the area under blood concentration-time curve( AUC0-t) is proportional to the dose,which suggested that three components showed a linear kinetic characteristics,but baicalin showed nonlinear kinetic characteristics. Moreover,the retention time of each component in rats was short. The established UPLC-MS/MS quantitative analysis method is rapid,sensitive and accurate,which can be used for the determination of chlorogenic acid,gardenioside,oroxylin A and baicalin in rat plasma and pharmacokinetic study of Shuganning Injection.

[Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress].

Gingseng is commonly used in traditional Chinese medicine community for the treatment of depression-like disorders. Ginsenosides is considered to be the major active components of ginseng. Previous studies have demonstrated that ginsenosides produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether ginsenosides could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticosterone level, glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in rats exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated rats. Daily intragastric administration of ginsenosides (12.5, 25, 50 mg x kg(-1)) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. However, there was no significant difference in MR mRNA level among groups. The results suggest that the antidepressant-like action of ginsenosides is likely mediated by modulating the function of hypothalamic- pituitary -adrenal axis and increasing the expression of BDNF in brain tissues.