Mechanism of polygonum capitatum intervention in pulmonary nodule based on network pharmacology and molecular docking technology.

The present study utilizes network pharmacology and molecular docking methodologies to investigate the mechanism of action behind the intervention of Polygonum capitatum Buch.-Ham.ex D. Don (THL) in treating pulmonary nodules (PN). This research aims to provide a theoretical foundation for broadening the clinical application of THL. Active components of THL were identified and screened through an extensive literature review and the PharmMapper database, followed by an analysis of their target interactions. Relevant targets associated with PN were selected using databases such as OMIM and GeneCards, with an intersection of the two sets being determined. STRING11.5 facilitated the acquisition of protein-protein interaction data, which was then imported into Cytoscape 3.7.2 to establish a protein interaction network topology. This enabled the identification of pivotal targets affected by THL intervention in PN. The study further employed the Metascape database to conduct GO and KEGG bioinformatics enrichment analyses, which illuminated core pathways involved in THL's therapeutic effects on PN. A comprehensive component-target-pathway diagram was constructed utilizing Cytoscape 3.7.2 software, with molecular docking validations carried out via Maestro software. A total of 49 active THL ingredients were discerned, implicating 67 PN-relevant targets. Subsequent software analysis pinpointed 10 key targets, including ALB, EGFR, and SRC. Molecular docking studies indicated strong binding affinities for most protein-compound pairs, with 44 out of 60 docking results exhibiting binding energies below -5 kcal/mol. Enrichment analysis highlights that key targets are mainly involved in pathways such as cancer, lipid metabolism and atherosclerosis, estrogen signaling, IL-17 signaling, complement and coagulation cascades, and chemical carcinogenesis through receptor activation. Through comprehensive network pharmacological approaches, this research delineates the synergy of THL's multiple components, targets, and pathways in mitigating PN. It posits that primary active ingredients of THL - quercetin, salidroside, and oleanolic acid - may exert effects on targets like ALB, EGFR, SRC, potentially modulating pathways associated with cancer, lipid and atherosclerosis, and IL-17 signaling in the context of PN intervention.

Study on the mechanism of inhibition of Escherichia coli by Polygonum capitatum based on network pharmacology and molecular docking technology: A review.

This study aims to analyze the effective components of Polygonum capitatum (PC) inhibiting Escherichia coli based on network pharmacology methods and predict its molecular mechanism of action. PC compounds and targets were collected from the TCMSP database, Swiss Target Prediction, and the literature. E coli targets were searched using the GeneCards database. The targets of E coli and the targets of the active ingredients of PC were taken as intersections to obtain the intersecting targets. The resulting overlapping targets were uploaded to the STRING database to construct the protein interaction network diagram of E coli target inhibition. The key targets for the inhibitory effect of PC on E coli were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by uploading key targets into the DAVID database. The results showed that there were 50 targets for PC to inhibit E coli. Among them, there are 5 core targets, mainly including AKT1, TNF, EGFR, JUN, and ESR1. A total of 196 gene ontology functional analysis results and 126 Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results were obtained. These include cellular response to cadmium-ion, cellular response to reactive oxygen species, pathways in cancer, prostate cancer, and PI3K-Akt signaling pathway. Molecular docking results indicate that Lutedin, Hirsutin, Flazin, and Ellagic acid in PC have high affinity for the target genes AKT1, TNF, MAPK3 and EGFR. PC exerts its inhibitory effect on E coli through multi-targets and multi-pathways, which provides a new basis for the new use of PC as an old medicine.

Mechanism of Polygonum capitatum intervention in pulmonary fibrosis based on network pharmacology and molecular docking technology: A review.

Pulmonary fibrosis (PF) is a serious interstitial disease that includes diffuse collagen deposition of lung tissue. Polygonum capitatum Buch.-Ham. ex D. Don (THL) is a traditional vaccine that has antibacterial and anti-inflammatory effects. In this research, to investigate the mechanism of action of THL in the intervention of pulmonary fibrosis by network pharmacology and molecular docking related research methods, in order to provide a theoretical basis for expanding the scope of THL medication. A total of 49 active ingredients were analyzed and screened in Cephalus cephalusis, including 35 pulmonary fibrosis targets, and 10 key targets such as ALB, EGFR were screened after software analysis. The molecular docking results showed that there were 44 binding energies less than -3 kcal·mol-1 in the 60 docking results, indicating that most proteins had strong binding energies with compounds. The key targets of KEGG enrichment analysis were mainly enriched in 20 core action pathways, such as hemostasis-related pathway, regulation of kinase activity. This study shows that based on network pharmacology, the multicomponent-multitarget-multipathway effect of THL intervention in pulmonary fibrosis is discussed.

Vitamin D can ameliorate premature ovarian failure by inhibiting neutrophil extracellular traps: A review.

The etiology of premature ovarian failure (POF) is mainly related to inflammatory diseases, autoimmune diseases, and tumor radiotherapy and chemotherapy; however, its specific pathogenesis has not been clarified. Vitamin D (VD), a fat-soluble vitamin, is an essential steroid hormone in the human body. Neutrophil extracellular traps (NETs) are meshwork structures that are formed when neutrophils are stimulated by inflammation and other factors and are closely associated with autoimmune and inflammatory diseases. Notably, VD inhibits NET formation and intervenes in the development of POF in terms of inflammatory and immune responses, oxidative stress, and tissue fibrosis. Therefore, this study aimed to theorize the relationship between NETs, VD, and POF and provide new ideas and targets for the pathogenesis and clinical treatment of POF.

Ankylosing spondylitis disease activity and serum vitamin D levels: A systematic review and meta-analysis.

BACKGROUND: To prove that serum vitamin D (VD) levels are strongly associated with ankylosing spondylitis (AS) disease activity, the association between serum VD levels and key monitoring indicators of AS disease activity has been analyzed, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). METHODS: Studies published in PubMed, Cochrane Library, EMBASE, and China National Knowledge Infrastructure by August 30, 2022 were searched, and 6 studies finally met the selection criteria. Serum 25-hydroxyvitamin D (25(OH)D), ESR, CRP levels, and correlation coefficients between serum VD and BASDAI, ESR, CRP in AS, and control in these studies were extracted for the meta-analysis. RESULTS: When compared to controls, patients with AS had considerably lower blood 25(OH)D levels (MD = -7.53 ng/mL, 95% CI, -9.78 to -5.28, P < .001) and significantly higher ESR and CRP levels (ESR: MD = 11.75 mm/h, 95% CI, 4.20 to 19.31, P = .002; CRP: MD = 15.36 mg/L, 95% CI, 4.95 to 25.77, P = .004). Additionally, a negative correlation was discovered between serum VD levels and BASDAI, ESR, and CRP (Fisher' Z = -0.34, -0.38, -0.35, respectively). CONCLUSION: The findings of our meta-analysis demonstrated a negative correlation between serum VD levels and the main monitoring indices of disease activity in patients with AS and verified that the differences in the continent and ethnicity may be one of the major contributors to this finding.

1H-NMR-based metabolic profiling of rat urine to assess the toxicity-attenuating effect of the sweat-soaking method on Radix Wikstroemia indica.

Radix Wikstroemia indica (L.) C.A. Mey. (RWI) is a toxic medicinal species primarily present in the Miao area of China. The toxicity of RWI is effectively reduced whilst maintaining the therapeutic effect when processed using the 'sweat-soaking method', which is a common method of Traditional Chinese Medicine preparation. However, there is a lack of scientific and medical evidence to explain the potential mechanisms by which the toxicity of RWI is reduced after preparation using this method, and the endogenous systemic metabolic effect of RWI remains uncertain. The aim of the present study was to explore the endogetnous metabolic alterations caused by RWI and to examine the possibility of reducing the toxicity of RWI using the sweat-soaking method using proton nuclear magnetic resonance (NMR) metabolomic analysis in rats. Principal Component Analysis, Partial Least Squares-Discriminant Analysis (PLS-DA) and Orthogonal PLS-DA were used to assess individual proton NMR spectra. A total of 34 metabolic products were altered after delivering raw RWI, and 32 endogenous metabolites were induced by processed RWI. The metabolic pathways that lead to a significant impact on energy and carbohydrate, amino acid, organic acids and lipid metabolism following raw and processed RWI use were identified. The mitochondria of hepatic and renal tubules of rats were injured in the raw RWI group, whereas the processed product reduced or interfered with energy substrate, carbohydrate and amino acid metabolism, whilst reducing the levels of metabolic markers of hepatotoxicity and nephrotoxicity, without causing damage to the mitochondria. Our previous study showed that the median lethal dose (LD50) value of raw RWI was 4.05 g/kg in rats after oral administration; however, the LD50 value of the processed RWI could not be measured. The maximum tolerated dose and minimum lethal dose were 20 and 30 g/kg for the processed RWI, respectively, corresponding to 109 and 164 times the clinical daily dose (0.029 g/kg). Thus, the sweat-soaking method reduced the toxicity of RWI. Moreover, after processing, the toxic component YH-10 was converted into a YH-10 + OH compound, reducing the content of the toxic YH-10 by 48%, whilst also reducing the contents of the toxic components YH-12 and YH-15 by 44 and 65%, respectively. In conclusion, the present study showed that the sweat-soaking method reduced the toxicity of RWI, as evidenced by the reduction of the levels of metabolic markers and the activity of metabolic pathways, thus providing a basis for processing of RWI for clinical use.

Advanced Studies on Rhizoma Dioscoreae Collettii.

Rhizoma Dioscoreae Collettii, is known as Huang Dioscorea collettii, Rhizoma Coptidis Brevisepalae or yellow ginger. It is neutral in nature and bitter in taste which is described to Gan (Liver) meridian, Wei (Stomach) meridian and Pangguang (Bladder) meridian. It was often used in the treatment of chyloid stranguria, gonorrhea, leucorrhagia, rheumatism arthralgia pain, joints disable, and lumbar knee pain syndrome in clinical.

Total Flavonoids in Caragana (TFC) Promotes Angiogenesis and Enhances Cerebral Perfusion in a Rat Model of Ischemic Stroke.

Previous studies have demonstrated that total flavonoid extracts from Caragana sinica (TFC) exert multiple therapeutic effects, promote blood flow, and exhibit anti-inflammatory and antioxidant properties. The present study aimed to investigate whether TFC promotes angiogenesis and exerts neuroprotective effects in a rat model of transient middle cerebral artery occlusion (tMCAO). Male Wistar rats were subjected to tMCAO for 1.5 h, followed by 24 h of reperfusion. TFC (15, 30, 60 mg/kg) was administered for 14 days. Evaluations of neurological function were performed following reperfusion, and infarct volumes were assessed in brain slices stained with 2,3,5-triphenyltetrazolium chloride (TTC). Our results indicated that TFC significantly attenuated cerebral infarct volume and neurological deficits following tMCAO. Laser Doppler, micro-PET/CT, and MRI analyses further demonstrated that TFC reduced infarct volume and enhanced cerebral blood flow in a dose-dependent manner, with the most significant effects occurring at a concentration of 60 mg/kg. Significant up-regulation of CD31, VEGF, Ang-1, HIF-1α, delta-like 4 (Dll4), and Notch1 expression was also observed in the experimental groups, relative to that in the vehicle group. In summary, the results of the present study indicate that TFC (15, 30, 60 mg/kg) attenuates neurological deficits, reduces infarct volume, and promotes angiogenesis following MCAO in a concentration-dependent manner, likely via increases in the expression of CD31, VEGF, Ang-1, HIF-1α, Dll4, and Notch1. Further studies are required to determine the clinical usefulness and potential mechanisms of TFC in patients with cerebral focal ischemic stroke.

Evidence and evolution of magnetic polaron in HgCr2Se4 investigated by electron spin resonance.

The evidence and evolution of magnetic polarons (MPs) in HgCr2Se4 have been studied by electron spin resonance (ESR), magnetism and conductivity measurements in a temperature range of 5-300 K. A single paramagnetic resonance line is observed in the high-temperature range while multiple resonance lines appear in the low-temperature range. As temperature decreases, the peak-to-peak linewidth ΔH pp shows a minimum at T min ≈ 210 K, with the activation energy fitted by small polaron hopping model consistent with the bottleneck mechanism, providing an evidence for existence of small MPs above T min. The analysis of the temperature dependence of ΔH pp, double integrated intensity I, and g factor of ESR signals, combined with the temperature dependence of magnetization and conductivity, reveals an evolution process from small MPs at zone I (T > T min) to correlated MPs at zone II (T c < T * ⩽ T ⩽ T min) in the paramagnetic regime. Three critical temperatures, T min (≈210 K), T th (≈175 K), and T * (≈121 K), which determine the evolution characteristics of MPs, are distinguished. The magnetic correlation length ξ of Cr3+-Se2--Cr3+ should account for the evolution of MPs.

Astragalosides increase the cardiac diastolic function and regulate the "Calcium sensing receptor-protein kinase C-protein phosphatase 1" pathway in rats with heart failure.

This study was designed to investigate the effects of astragalosides on cardiac diastolic function, and an emphasis was placed on the variation of the upstream molecular regulators of phospholamban. Chronic heart failure (CHF) rats were induced by ligaturing the left anterior coronary artery, and rats in the therapeutic groups were treated with either a 50 mg/kg dose of captopril, 10 mg/kg dose of astragalosides or 20 mg/kg dose of astragalosides. Four weeks after treatment, the ratio of the early and atrial peak filling velocities (E/A) and maximal slope diastolic pressure decrement (-dp/dt) both decreased in CHF rats (by 30.3% and 25.5%, respectively) and significantly increased in 20 mg/kg astragalosides and captopril-treated rats. The protein phosphatase-1 activity was lower in the 20 mg/kg astragalosides group than in the CHF group (0.22 vs 0.44, P < 0.01), and the inhibitor-1 levels in the astragalosides and captopril-treated groups were increased. Chronic heart failure increased expression of protein kinase C-α and calcium-sensing receptor, and these changes were attenuated by astragalosides therapy. Astragalosides restored the diastolic dysfunction of chronic heart failure rats, possibly by downregulation of calcium-sensing receptor and protein kinase C-α, which in turn augmented inhibitor-1 expression, reduced protein phosphatase-1 activity and increased phospholamban phosphorylation.

Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study.

BACKGROUND: Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. PURPOSE: Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. METHODS: The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RESULTS: RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10 + OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. CONCLUSION: A Q-marker database of processed RWI by "sweat soaking method" was established according to the results and relationship of "effect-toxicity-chemicals", which provided a scientific evidence for processing methods, mechanism and the clinical application of RWI, also provided experimental results to explore the application of Q-marker in CHM.

Real-Space Observation of Nonvolatile Zero-Field Biskyrmion Lattice Generation in MnNiGa Magnet.

Magnetic skyrmions, particular those without the support of external magnetic fields over a wide temperature region, are promising as alternative spintronic units to overcome the fundamental size limitation of conventional magnetic bits. In this study, we use in situ Lorentz microscope to directly demonstrate the generation and sustainability of robust biskyrmion lattice at zero magnetic field over a wide temperature range of 16-338 K in MnNiGa alloy. This procedure includes a simple field-cooling manipulation from 360 K (higher than Curie temperature TC ∼ 350 K), where topological transition easily occurs by adapting the short-range magnetic clusters under a certain magnetic field. The biskyrmion phase is favored upon cooling below TC. Once they are generated, the robust high-density biskyrmions persist even after removing the external magnetic field due to the topological protection and the increased energy barrier.

A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan.

Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images. With the aid of chromatographic separation and mass spectrometry, we achieved the rapid and reliable screening of active compounds from the Chinese herbal medicine Tong-Mai-Yang-Xin-Wan (TMYX) for treating EMT. Five fractions were found to exert anti-EMT activity and were further identified by liquid chromatography coupled with tandem mass spectrometry. Glycyrrhizic acid, glyasperin A, and licorisoflavan A were found to inhibit EMT. The proposed approach was successfully applied to screen active compounds from TMYX on TGF-ß1-stimulated HK-2 cells and may offer a new means for identifying lead compounds for treating EMT from registered Chinese herbal medicines.

Naringin administration inhibits platelet aggregation and release by reducing blood cholesterol levels and the cytosolic free calcium concentration in hyperlipidemic rabbits.

This study investigated the effects of naringin on platelet aggregation and release in hyperlipidemic rabbits, and the underlying mechanisms. The safety of naringin was also investigated. The rabbits were orally administered 60, 30 or 15 mg/kg of naringin once a day for 14 days after being fed a high fat/cholesterol diet for four weeks. Following the two weeks of drug administration, the degree of platelet aggregation induced by arachidonic acid, adenosine diphosphate and collagen was significantly reduced by naringin at certain doses compared with those in the rabbits of the model group (P<0.01). The levels of P-selectin and platelet factor 4 (PF4) also decreased following treatment with naringin compared with those of the model group. Certain doses of naringin significantly reduced the total cholesterol (TC) levels and elevated the ratio of high-density lipoprotein cholesterol to TC compared with those in the model group, and significantly decreased the cytosolic free calcium concentration ([Ca2+]i). No significant difference in the coagulation function was observed between the control and drug-treatment groups. These results indicate that naringin improved platelet aggregation and inhibited the excessive release of P-selectin and PF4 in hyperlipidemic rabbits. This study suggests that the antiplatelet effect of naringin may be due to its ability to regulate the levels of blood cholesterol and [Ca2+]i in platelets. Naringin also did not cause bleeding in the hyperlipidemic rabbits.

Lactones from Ligusticum chuanxiong Hort. reduces atherosclerotic lesions in apoE-deficient mice via inhibiting over expression of NF-kB-dependent adhesion molecules.

The present study aims to investigate the anti-atherosclerotic effects of lactones extracted from Ligusticum chuanxiong Hort (LLC) in apoE-deficient mice (ApoE(-/-) mice) and proclaim its underlying mechanisms. Expression of endothelial adhesion molecules and NF-κB around the atherosclerotic lesions was detected by immunohistochemistry (IHC). To further validate the mechanism, effect of LLC on the secretion of ICAM-1 and VCAM-1 of human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor α (TNF-α) was measured by ELISA. And the activation of NF-κB was detected by western blot. Mice treated with LLC showed significant reduction in lesion sizes of thoracic segments of the aorta (p<0.01). Meanwhile, LLC treatments lead to decreases of serum TG, TC and LDL-C contents, respectively. LLC also decreased the expression of CD31, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-kappa B (NF-κB) in the atherosclerotic plaque. Moreover, LLC at 3.125-25 µg/mL can dose-dependently attenuate the expression of ICAM-1 and VCAM-1 in TNF-α stimulated HUVECs. Western blot result indicated LLC inhibited activation of NF-κB. These results suggested that LLC could ameliorate atherosclerosis in ApoE(-/-) mice. The mechanism of action of LLC on anti-atherosclerotic effect may be attributed to the suppression of the production of NF-κB-dependent adhesion molecules.