Monomer Components Research Articles

Ground-State Orbital Analysis Predicts S1 Charge Transfer in Donor-Acceptor Materials.

Donor-acceptor (D-A) materials can exhibit a wide range of unique photophysical properties with applications in next-generation optoelectronics. Electronic structure calculations of D-A dimers are often employed to predict the properties of D-A materials. One of the most important D-A dimer quantities is the degree of charge transfer (DCT) in the S1 state, which correlates with properties such as fluorescence lifetimes and intersystem crossing rates in D-A materials. While predictive metrics of the S1 DCT generally require an excited-state quantum chemistry calculation, presented here is a novel metric that predicts S1 DCT solely with ground-state orbital analysis. This metric quantifies the similarity of the orbitals between a dimer complex and its monomer components. A linear relationship is found between this similarity metric and the S1 DCT, calculated using a data set of 31 D-A dimers. Best practices for integrating this novel orbital structure-function relationship into high-throughput screening methods are discussed.

Research progress on separation and characterization of bioflavonoids from Coreopsis tinctoria Nutt

Coreopsis tinctoria Nutt (C. tinctoria) or a common name ‘Snow chrysanthemum’ because of its growing condition at high altitude，is one of the popular medicinal-food plants, mainly grows in the northwest area of China. Because of its rich nutrients, particularly polyphenols (majorly flavonoids), and volatile oils among others, C. tinctoria has become a research hotspot in recent years. In addition, the flavonoids of C. tinctoria, especially the flavanomarein, marein, okanin and other bioactive phytochemicals, have effective biological activity. They possess good antioxidant and anti-inflammatory effects, also have significant effects on lowering blood pressure, hypoglycemia and reducing levels of triglycerides and cholesterol. However, at present, studies on the bioactivity of C. tinctoria are mainly focused on crude extracts or total flavonoids. The study of monomer components is largely limited to the isolation and purification process, which is difficult for a systematic study because of the chemical-physical nature of marein, flavanomarein and other compounds in C. tinctoria. Therefore, to have an updated isolation of C. tinctoria bioactive components, this paper reviewed the current research status of the separation and purification methods of flavonoids from C. tinctoria, by analyzing and comparing the technical characteristics of these methods, and providing prospects on the development and application of the separation and purification methods of C. tinctoria.

APPLICATION OF HIGH PERFORMANCE POLYMERS IN PROSTHETIC RESTORATION ON IMPLANTS

For prosthetic hybrid restorations on implants, different combinations of materials are used, from metal alloys, titanium, ceramics, polymers or composites. The aim of this paper is to summarize the char- acteristics and advantages of certain polymers in the production of hybrid restorations, as well as to present the protocol for treating patients with this type of restoration. Polymers based on poly-ether-ether-ketone have gained great popularity and success in the field of implant-prosthetic therapy. Among them, the most famous high-performance polymers developed by Bredent (Bredent group, Senden Germany) are BioHPP (containing 20% ceramic fillers) and breCAM.HIPC (highly cross-linked polymer composite material). Both polymers are machinable and are used to make temporary and permanent resaturations in prosthetics. They are biocompatible and non-allergenic, do not contain metal, oxide and monomer components, and also do not discolor the gingiva. They are characterized by excellent workability and elasticity, which is greater than zirconium ceramics and metal alloys, different shades of color is characteristics for breCAM. HIPC, unlike BioHPP, which is monolithic and monochromatic. Due to their characteristics, these high-per- formance polymers can be exceptional “allies” for the restorations on implants.

Investigation of the active ingredients of Shuangshen Ningxin Fomula and the mechanism underlying their protective effects against myocardial ischemia-reperfusion injury by mass spectrometric imaging

BackgroundTraditional Chinese medicine, particularly Shuangshen Ningxin Capsule (SSNX), has been studied intensely. SSNX includes total ginseng saponins (from Panax ginseng Meyer), total phenolic acids from Salvia miltiorrhiza Bunge, and total alkaloids from Corydalis yanhusuo W. T. Wang. It has been suggested to protect against myocardial ischemia by a mechanism that has not been fully elucidated. MethodsThe composition and content of SSNX were determined by UHPLC-Q-TOFQ-TOF / MS. Then, a rat model of myocardial ischemia-reperfusion injury was established, and the protective effect of SSNX was measured. The protective mechanism was investigated using spatial metabolomics. ResultsWe found that SSNX significantly improved left ventricular function and ameliorated pathological damages in rats with myocardial ischemia-reperfusion injury. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), the protective mechanism of SSNX was examined by comparing the monomer components of drugs targeted in myocardial tissue with the distribution of myocardial energy metabolism-related molecules and phospholipids. Interestingly, some lipids display inconsistent content distribution in the myocardial ischemia risk and non-risk zones. These discrepancies reflect the degree of myocardial injury in different regions. ConclusionThese findings suggest that SSNX protects against myocardial ischemia-reperfusion injury by correcting abnormal myocardial energy metabolism, changing the levels and distribution patterns of phospholipids, and stabilizing the structure of the myocardial cell membrane. MALDI-TOF MS can detect the spatial distribution of small molecule metabolites in the myocardium and can be used in pharmacological research.

Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2

Osteoarthritis (OA) is associated with ferroptosis, a newly discovered form of programmed cell death associated with lipid peroxidation. Curcumin, the main monomer component in turmeric rhizomes, possesses antioxidant and anti-ferroptosis properties, but its effect on ferroptosis in chondrocytes of OA is unknown. This study aimed to investigate the protective effect and potential mechanism of curcumin on chondrocytes induced by erastin, a ferroptosis inducer. CCK-8 assays were used to assess cell viability in mouse primary chondrocytes treated with 3.33 μM erastin alone or in combination with different doses of curcumin. Various parameters were detected, including LDH, SOD, GSH-PX, MDA, ROS and Fe2+ contents. The ferroptosis-related proteins, such as SLC7A11, GPX4, TFR1, ACSL4, and FTH1, were examined using immunofluorescence and western blotting. Nrf2 was knocked down using siRNA to explore the molecular mechanism through which curcumin protects chondrocytes from erastin-induced ferroptosis. In a mouse model of knee ferroptosis induced by intracavity injection of 10 μL erastin (5 mg/mL), HE staining, Safranin O-Fast Green staining, and immunohistochemistry were employed to evaluate articular cartilage injury. The results demonstrated that erastin significantly suppressed the expression of SOD, GSH-PX, SLC7A11, GPX4, and FTH1 while upregulating the levels of LDH, MDA, ROS, ACSL4, and TFR1 in chondrocytes. Moreover, erastin-induced chondrocyte ferroptosis, lipid ROS, and Fe2+ production were reversed by curcumin. Additionally, curcumin significantly upregulated the expression level of the Nrf2 gene and protein. Silencing Nrf2 reversed the protective effect of curcumin on erastin-induced chondrocyte ferroptosis. In animal experiments, silencing Nrf2 counteracted the impact and damage of curcumin on erastin-induced ferroptosis of cartilage tissue in vivo, leading to significant inhibition of OA progression. Taken together, these findings suggest that curcumin can inhibit chondrocyte ferroptosis by activating the Nrf2 signaling pathway, providing further insight into the regulatory mechanism of curcumin in OA and supporting its potential therapeutic use in OA treatment.

The Effect of an Extract of Sappanwood, Protosappanin A and Protosappanin B on Osteogenesis in Periodontitis.

Sappanwood is widely used in the prevention and treatment in diseases due to its ability to seal blood vessels, dissipate stasis, and relieve pain. Important monomer components of sappanwood, Protosappanin A (PA) and Protosappanin B (PB) have anti-tumour and antimicrobial medicinal properties. This study investigated the anti-inflammatory and osteogenic differentiation effects of a crude extract of Sappanwood (ESP), PA and PB against periodontitis in periodontal ligament stem cells (PDLSCs). Oil Red O staining was used to assess the ability of adipocytes to differentiate. Alizarin Red staining was used to assess the capacity to differentiate into osteoblasts. Third-passage PDLSCs were grown in either basic medium alone or basic media with varying doses of ESP (0.0625 mg/mL, 0.03125 mg/mL and 0.125 mg/mL), PA and PB (2.5 µM, 5 µM, 10 µM). The CCK-8 assay was used to measure cell proliferation. Real Time PCR (RT-qPCR) and Enzyme-Linked Immunosorbnent Assay (ELISA) assay were used to measure gene expression. The capacity to differentiate into osteoblasts was evaluated using Alizarin Red staining, and Alkaline Phosphatase (ALP) staining and activity. The development of lipid droplets and mineralized nodules was examined using Oil Red O staining and Alizarin Red staining. Flow cytometry revealed that PDLSCs were CD29 (98.23%) and CD44 (98.81%) positive, but CD34 (0.16%) and CD45 (0.09%) negative. CCK-8 assay showed that ESP at three concentrations (0.03125 mg/mL, 0.0625 mg/mL and 0.125 mg/mL) and 2.5 µM, 5 µM and 10 µM PA and PB had no cytotoxicity at 5 and 7 days (p < 0.05). qRT-PCR and ELISA assay indicated that ESP, PA and PB downregulated the inflammatory cytokines IL-8, IL-6, IL-1β, IL-10 and IL-4 and elevated the mRNA expression of osteogenesis cytokines RUNX2 , OSX and OCN in PDLSCs (p < 0.05). Alizarin red staining, and ALP staining and activity showed that ESP, PA and PB increased mineralized nodules and the ALP content of in PDLSCs (p < 0.05). ESP, PA and PB can reduce the inflammatory response and amplify the osteogenic differentiation of PDLSCs. Therefore, ESP, PA and PB may have potential pharmacological effects in controlling the progression of periodontitis and promoting periodontal tissue regeneration.

Predicting the mass spectrum of polymerizing linoleates using weighted random graph modeling

Biopolymers and biopolymer networks that form via autoxidation, like in drying of oil paint or fat degradation in food components, contain a large variety of monomeric building blocks. While the monomer variety complicates the modeling itself, obtaining experimental validation of infinite polymer networks is inherently difficult as well. A new model is developed, where an automated reaction network generation (ARNG) procedure is used to automatically generate the monomer components, structures and masses, and their reactions. This methodology is combined with random graph (RG) modeling to predict global polymer properties: distributions of numbers of monomer units and molar masses, gel point and gel fraction. This computational framework is applied to two model systems for linseed oil paint binder: the polymerization of ethyl linoleate (EL) and methyl linoleate (ML). A novel method was constructed to deal with the variability of monomer masses that complicates inferring molar mass from monomer number distribution. By modeling the polymer as a weighted random graph where the nodes contain information about the monomer masses in the system, the total weight of the finite connected components is computed. The predicted mass spectrum of finite connected components is used for validation with experimental data. A size exclusion chromatography (SEC) trace of ML is employed, which after calibration using the proposed framework, proves consistency between model and SEC data. The model provides a practical approach to both characterize complex biopolymers as polymers in terms of molar mass distribution and gel point, while preserving the information down to the level of monomeric units.

Stoichiometric effect on the structural transformation and spatial variation of polyamide reverse osmosis membranes: A molecular dynamics study

Reverse osmosis based on polyamide membranes is currently the leading technology for desalination and water purification. However, the spatial variation of polyamide architecture, especially regarding stoichiometric criteria at the real reaction interface during membrane fabrication, is poorly understood. Here we conducted equilibrium molecular dynamic simulations, mimicking the practical construction of polyamide matrices using a variety of monomer component stoichiometries, to investigate resulting differences in both the morphological transformation and mass transport through the polymer network. Our simulations indicated that an equal stoichiometry of the reactive functional groups predominantly resulted in favorable polyamide matrix qualities such as a high crosslinking density, uniform pore size distribution, and adequate layer compactness. Despite the thickness-dependent water diffusion across the active layer, an analysis of polyamide membrane density revealed depth heterogeneity, particularly for membranes constructed under unequal concentrations. Consequently, uncontrollable defects are likely to be created, as evidenced by the partial penetration of Na+ across such membranes. In addition, the residual functional groups in the polyamide matrices (–COOH and –NH2) influenced the transport behavior of ions near the membrane surface. Overall, our simulations provide a visual platform for understanding the stoichiometry-induced relationship between membrane structure and performance, which may guide the future design of defect-free and scaling-resistant reverse osmosis membranes.

Fatty acid metabolism disorders and potential therapeutic traditional Chinese medicines in cardiovascular diseases.

Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid metabolism are crucial contributors in the development of cardiovascular diseases. The abnormal cardiac fatty acid metabolism usually leads to energy deficit, oxidative stress, excessive apoptosis, and inflammation. Targeting fatty acid metabolism has been regarded as a novel approach to the treatment of cardiovascular diseases. However, there are currently no specific drugs that regulate fatty acid metabolism to treat cardiovascular diseases. Many traditional Chinese medicines have been widely used to treat cardiovascular diseases in clinics. And modern studies have shown that they exert a cardioprotective effect by regulating the expression of key proteins involved in fatty acid metabolism, such as peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase 1. Hence, we systematically reviewed the relationship between fatty acid metabolism disorders and four types of cardiovascular diseases including heart failure, coronary artery disease, cardiac hypertrophy, and diabetic cardiomyopathy. In addition, 18 extracts and eight monomer components from traditional Chinese medicines showed cardioprotective effects by restoring cardiac fatty acid metabolism. This work aims to provide a reference for the finding of novel cardioprotective agents targeting fatty acid metabolism.

Investigation of the mechanism of action of simiao pill against gout using network pharmacology and experimental validation

BackgroundGout is a chronic disease of deposition of monosodium urate crystals, characterised by hyperuricaemia and gouty arthritis, plaguing the whole world. Simiao Pill (SMP), a classic herbal formula, has been extensively used to treat arthritic symptoms in clinical practice in China for centuries. The action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of gout. However, the pharmacological mechanisms of SMP still remain vague to date. Hypothesis/PurposeIn this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypouricemic mechanisms of SMP. Study designAt first, we collected putative targets of SMP based on Traditional Chinese Medicine Systems Pharmacology Database databases, and relevant targets of gout were summarised by four searching database, including Disgenet, therapeutic target database, Online Mendelian Inheritance in Man, and Gene Cards. The putative targets of SMP and known therapeutic targets of gout built an interaction network, so the networks of compound targets and disease-targets were obtained soon. Then, the protein–protein interactions analysis and molecular docking verification were established. Finally, the key genes were used to find the biological pathway and explain the therapeutic mechanism by genome ontology and kyoto encyclopaedia of genes and genomes analysis. ResultsIn our study, 30 hypouricemic components and 600 hypouricemic targets of SMP were filtrated based on an online network database. Then the component-target interaction network was constructed, 10 key components and 15 key targets were further obtained. Docking studies indicated that the bio-active compounds could stably bind the pockets of target proteins. Go enrichment and and kyoto encyclopaedia of Genes and genomes pathway analysis indicated that SMP had a strong integration with gout and hyperuricemia, which might significantly contribute to multiple therapeutic effect. ConclusionsIn summary, this study used systems pharmacology to demonstrate the main components and mechanism of SMP in treating gout. Moreover, the work provided a scientific basis for the further effect research of SMP and its monomer components, but also provided a new therapeutic strategy in gout.

A network pharmacology approach to decipher the total flavonoid extract of Dracocephalum Moldavica L. in the treatment of cerebral ischemia- reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is a major injury that seriously endangers human health and is characterized by high mortality and high disability. The total flavonoid extract of Dracocephalum moldavica L.(TFDM) in the treatment of CIRI has been proved by clinical practice. But the mechanism for the treatment of CIRI by TFDM has not been systematically revealed. The active compounds contained in TFDM were screened by literature mining and pharmacokinetic parameters, and the targets related to CIRI were collected by searching Drugbank, Genecards and OMIM databases. Cytoscape software was used to construct the protein interaction network of TFDM for the prevention and treatment of CIRI. Geneontology and signal pathway enrichment were analyzed. The key target pathway network of TFDM compounds was constructed and verified by pharmacological experiment in vitro. 21 active components were screened, 158 potential drug targets for the prevention and treatment of CIRI were obtained, 53 main targets were further screened in the protein-protein interaction network, and 106 signal pathways, 76 biological processes, 26 cell components and 50 molecular functions were enriched (P<0.05). Through the compound-target-pathway network, the key compounds that play a role in the prevention and treatment of CIRI, such as acacetin, apigenin and other flavonoids, as well as the corresponding key targets and key signal pathways, such as AKT1, SRC and EGFR were obtained. TFDM significantly decreased LDH, MDA levels and increased the NO activity levels in CIRI. Further studies have shown that TFDM increases the number of SRC proteins, and TFDM also increases p-AKT/ AKT. Molecular docking results showed that acacetin-7-O (- 6''-acetyl) -glucopyranoside, acacetin7-O-β-D-glucopyranoside, apigenin-7-O-β-D-galactoside respectively had good affinity for SRC protein. Acacetin-7-O (- 6''-acetyl) -glucopyranoside,acacetin-7-O-β-D-glucuronide, acacetin7-O-β-D-glucopyranoside had good affinity for AKT1 protein, respectively. Our research showed that TFDM had the characteristics of multi-component, multi-target and multi-channel in the treatment of CIRI. The potential mechanism may be associated with the following signaling pathways:1) the signaling pathways of VEGF/SRC, which promote angiogenesis, 2) the signaling pathways of PI3K/AKT, which inhibit apoptosis, and 3) acacetin-7-O (- 6''-acetyl) -glucopyranoside is expected to be used as a candidate monomer component for natural drugs for further development.

Comparison of two different integrated method of pharmacokinetics by the integrated pharmacokinetic research of fangji huangqi decoction

Traditional Chinese medicine (TCM) is characterized by its multiple components. The utilization of mathematical statistical methods to integrate the pharmacokinetics of monomer components can provide a comprehensive understanding of the holistic pharmacokinetic process of TCM. Two distinct integrated methods, namely the correlation coefficient method and the AUC-based weight coefficient method, were employed in this study to elucidate and compare their differences in the integrated pharmacokinetic research of Fangji Huangqi decoction (FHD). FHD is commonly used in clinical practice to treat the nephrotic syndrome. Firstly, one-dose FHD was given to doxorubicin-induced nephropathy (DN) rats, and the prototype compounds of FHD and their metabolites in plasma were qualitatively and semi-quantitatively analyzed by UHPLC-MS/MS. Secondly, the efficacy of FHD was quantitatively characterized by the relative distance method based on metabolomics. The correlation coefficients were obtained by analyzing the correlation between efficacy (relative distance values) and the content of compound, and they were subsequently used for the model integration (correlation coefficient method). Thirdly, the effective compounds of FHD treating DN were screened by integrating network pharmacology and molecular docking, and they were used for another integrated pharmacokinetic model by AUD-based weight coefficient method. Finally, the 2 integrated methods and the 2 integrated pharmacokinetic models were compared. In this study, 30 prototype compounds and 41 metabolites of FHD in plasma were identified, and the pharmacokinetic curve of 18 prototype compounds were built. The efficacy of FHD in the treatment of DN has been relatively quantitation. The 2 established integrated pharmacokinetic models of FHD indicated that the correlation coefficient method was the optimal approach for conducting the integrated pharmacokinetic research on the TCM with unknown effective compounds, whereas the AUC-based coefficient method was suitable for the TCM with the clear effective compounds. The integrated pharmacokinetic models indicated that FHD had high bioavailability and an absorption peak at about 6 h after administration, indicating that the 6 h after administration was the critical period of FHD treating DN. This research would be helpful for the pharmacological and pharmacokinetic research of FHD, and provide a method reference for the integrated pharmacokinetic research of TCM.

Gandouling inhibits hepatic fibrosis in Wilson's disease through Wnt-1/β-catenin signaling pathway.

Wilson's disease (WD) hepatic fibrosis is the result of chronic liver injury induced by Cu2+ deposition in the liver. Gandouling (GDL) is a hospital preparation of the First Affiliated Hospital of Anhui University of Chinese Medicine. Previous studies have found that GDL can play an anti-inflammatory, anti-oxidation, and promote Cu2+ excretion, which has a clear anti-WD effect. We found that Wnt-1 was significantly up-regulated in the liver tissue of toxic-milk (TX) mouse in the WD gene mutant model, and the monomer components of GDL could combine well with Wnt-1. Therefore, in this work, we used RT-qPCR, Western blot, immunofluorescence, network pharmacology, molecular docking, and related methods to study the effects of GDL on hepatic stellate cell (HSC) activation and Wnt-1/β-catenin pathway in TX mice to clarify the effect of GDL on WD hepatic fibrosis. GDL could alleviate hepatic fibrosis, improve liver function, and inhibit the activation of HSC in TX mice. Network pharmacology predicted that the Wnt-1/β-catenin was the target of GDL, and molecular dynamics further revealed that GDL has a good binding ability with Wnt-1 and inhibits the Wnt/β-catenin signaling pathway through Wnt-1. Furthermore, we found that GDL blocked the Wnt-1/β-catenin signaling pathway in the liver of TX mice in vivo. In vitro, serum containing GDL blocked the Cu2+ ion-induced Wnt-1/β-catenin signaling pathway in LX-2cells. Therefore, GDL blocked the Wnt-1/β-catenin signaling pathway, inhibited HSC activation, and improved WD hepatic fibrosis by binding to Wnt-1. GDL improves hepatic fibrosis in WD model mice by blocking the Wnt-1/β-catenin signaling pathway, and Wnt-1 may be a new target for the diagnosis and treatment of WD. This reveals a new mechanism of GDL against WD, and promotes the clinical promotion of GDL.

Reversible Light-Induced Dimerization of Secondary Face Azobenzene-Functionalized β-Cyclodextrin Derivatives.

β-cyclodextrin (βCyD) derivatives equipped with aromatic appendages at the secondary face exhibit tailorable self-assembling capabilities. The aromatic modules can participate in inclusion phenomena and/or aromatic-aromatic interactions. Supramolecular species can thus form that, at their turn, can engage in further co-assembling with third components in a highly regulated manner; the design of nonviral gene delivery systems is an illustrative example. Endowing such systems with stimuli responsiveness while keeping diastereomeric purity and a low synthetic effort is a highly wanted advancement. Here, we show that an azobenzene moiety can be "clicked" to a single secondary O-2 position of βCyD affording 1,2,3-triazole-linked βCyD-azobenzene derivatives that undergo reversible light-controlled self-organization into dimers where the monomer components face their secondary rims. Their photoswitching and supramolecular properties have been thoroughly characterized by UV-vis absorption, induced circular dichroism, nuclear magnetic resonance, and computational techniques. As model processes, the formation of inclusion complexes between a water-soluble triazolylazobenzene derivative and βCyD as well as the assembly of native βCyD/βCyD-azobenzene derivative heterodimers have been investigated in parallel. The stability of the host-guest supramolecules has been challenged against the competitor guest adamantylamine and the decrease of the medium polarity using methanol-water mixtures. The collective data support that the E-configured βCyD-azobenzene derivatives, in aqueous solution, form dimers stabilized by the interplay of aromatic-aromatic and aromatic-βCyD cavity interactions after partial reciprocal inclusion. Photoswitching to the Z-isomer disrupts the dimers into monomeric species, offering opportunity for the spatiotemporal control of the organizational status by light.

The Effects of Cross-Linking Agents on the Mechanical Properties of Poly (Methyl Methacrylate) Resin.

Cross-linking agents are incorporated into denture base materials to improve their mechanical properties. This study investigated the effects of various cross-linking agents, with different cross-linking chain lengths and flexibilities, on the flexural strength, impact strength, and surface hardness of polymethyl methacrylate (PMMA). The cross-linking agents used were ethylene glycol dimethacrylate (EGDMA), tetraethylene glycol dimethacrylate (TEGDMA), tetraethylene glycol diacrylate (TEGDA), and polyethylene glycol dimethacrylate (PEGDMA). These agents were added to the methyl methacrylate (MMA) monomer component in concentrations of 5%, 10%, 15%, and 20% by volume and 10% by molecular weight. A total of 630 specimens, comprising 21 groups, were fabricated. Flexural strength and elastic modulus were assessed using a 3-point bending test, impact strength was measured via the Charpy type test, and surface Vickers hardness was determined. Statistical analyses were performed using the Kolmogorov-Smirnov Test, Kruskal-Wallis Test, Mann-Whitney U Test, and ANOVA with post hoc Tamhane test (p ≤ 0.05). No significant increase in flexural strength, elastic modulus, or impact strength was observed in the cross-linking groups compared to conventional PMMA. However, surface hardness values notably decreased with the addition of 5% to 20% PEGDMA. The incorporation of cross-linking agents in concentrations ranging from 5% to 15% led to an improvement in the mechanical properties of PMMA.

An optimal combination of five main monomer components in Wuzi Yanzong Pill that prevents neural tube defects and reduces apoptosis and oxidative stress

Ethnopharmacological relevanceWuzi Yanzong Pill (WYP) is a classic traditional Chinese medicine (TCM) formula that is used for reproductive system diseases. Previous studies showed that WYP had a preventive effect on the development of neural tube defects (NTDs) induced by all-trans retinoic acid (atRA) in mice. Aim of the studyThis study aimed to determine the optimal combination of main monomer components in WYP on preventing NTDs and to understand the underlying mechanism. Materials and methodsAn optimal combination was made from five representative components in WYP including hyperoside, acteoside, schizandrol A, kaempferide and ellagic acid by orthogonal design method. In a mouse model of NTDs induced by intraperitoneal injection of atRA, pathological changes of neural tube tissues were observed by Hematoxylin & Eosin (HE) staining, neural tube epithelial cells apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), protein changes related to apoptosis, anti-apoptosis, and antioxidant factors were detected with Western blot. Potential targets and mechanisms of monomer compatibility group (MCG) acting on NTDs were analyzed by bioinformatics. ResultsTreatment with different combinations of WYP bioactive ingredients resulted in varying decreases in the incidence of NTDs in mice embryos. The combination of MCG15 (200 mg/kg of hyperoside, 100 mg/kg of acteoside, 10 mg/kg of schizandrol A, 100 mg/kg of kaempferide and 1 mg/kg of ellagic acid) showed the most significant reduction in NTD incidence. Mechanistically, MCG15 inhibited apoptosis and oxidative stress, as evidenced by reduced TUNEL-positive cells, downregulation of caspase-9, cleaved caspase-3, Bad, and Bax, and upregulation of Bcl-2, as well as decreased MDA and increased SOD, CAT, GSH, HO-1, and GPX1 levels. Bioinformatics analysis showed that MCG15 acted on the PI3K/Akt signaling pathway, which was confirmed by Western blot analysis showing increased expression of p-PI3K, p-Akt/Akt, and Nrf2 related indicators. ConclusionWe have identified an optimal combination of five bioactive components in WYP (MCG15) that prevented NTDs in mice embryos induced by atRA by activating the PI3K/Akt signaling pathway and inhibiting apoptosis and oxidative stress.

Lycorine protects against septic myocardial injury by activating AMPK-related pathways.

Cardiac dysfunction is a common complication in patients with sepsis triggering high morbidity and mortality. Lycorine (LYC), the main effective monomer component extracted from Lycoris bulbs, possesses antiviral, anti-inflammatory, analgesic, liver protection properties. In this study, the effect of LYC pre- and post-treatment as well as the underlying mechanism were evaluated in the cecal ligation and puncture (CLP) model of Balb/c mice. The survival rate, anal temperature, sepsis score, blood biochemical/routine indicators, cardiac function, sepsis-related pathophysiological processes, and AMPK signaling in septic mice were observed by echocardiography, histological staining, western blot, qPCR, and etc. LYC pretreatment attenuated myocardial injury in septic mice by improving survival rate, sepsis score, blood biochemical/routine indicators, cardiac function and structure, inhibiting inflammation and oxidative stress, improving mitochondrial function, modulating endoplasmic reticulum stress, and activating AMPK pathway. In particular, AMPK deficiency and AMPK inhibitor (Compound C) partially reversed the protective effects of LYC in septic mice. In addition, LYC posttreatment also has slight protective phenotypes on septic myocardial injury, but the effect is not as ideal as pretreatment. Taken together, these findings suggest that LYC may be a potential drug for the treatment of sepsis.

The mechanism of Leonuri Herba in improving polycystic ovary syndrome was analyzed based on network pharmacology and molecular docking.

Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting women. Chinese herbs have been considered as an alternative treatment for PCOS, and Yi-mu-cao (Leonuri Herba) is one of the most commonly used herbs to treat PCOS, which can relieve symptoms of PCOS patients. But the mechanism of its treatment remains unclear. Method: The main active ingredients and potential targets of Leonuri Herba were obtained by TCMSP and Swiss Target Forecast, and the related targets of PCOS were obtained by searching DrugBank, GeneCard and DisGeNet databases. The Protein-Protein Interaction (PPI) network was constructed using STRING database. GO and KEGG were used to detect the enrichment pathways of key targets. Cytoscape software was used to construct the component-target-pathway network, analyze the PPI network core, and verify the reliability of target binding by molecular docking technology. Result: 8 components and 116 targets of Leonuri Herba on PCOS were screened. Common targets mainly involve the Lipid and atherosclerosis, Endocrine resistance, AGE-RAGE signaling in diabetic complications and other signaling pathways. It is suggested that it can form multi-target and multi-pathway regulatory network through quercetin, kaempferol and other active substances to regulate endocrine disorders and reduce inflammatory response, so as to systematically improve PCOS. Molecular docking experiments showed that the active constituents of Leonurus had good binding activity with potential targets of PCOS. Conclusion: In summary, this study elucidates the potential effect of Leonuri Herba on PCOS, which is helpful to provide reference for clinical practice. This is also conducive to the secondary development of motherwort and its monomer components, and precision medicine for PCOS.

Interaction between Chinese medicine and digoxin: Clinical and research update.

Background: Digoxin is one of the most widely and commonly used cardiac drug, which plays an irreplaceable role in treating heart failure and arrhythmia. The 2010 Edition of Pharmacopoeia of the People's Republic of China stipulates that the effective range of digoxin plasma concentration is 0.5-2.0ng/mL and it is toxic at plasma concentration >2ng/mL. Its effective plasma drug concentration is close to the toxic concentration, and large individual differences in the effects of the drug have been observed. It is often used in combination with other drugs, but drug interactions have a great impact on the plasma concentration of digoxin and lead to adverse reactions (ADRs), such as poisoning. Most of the reported drug interactions are with Western drugs. However, there are many combinations of traditional Chinese medicine (TCM) and Western drugs, TCM interacting with digoxin comprises monomer components, single medicines, and Chinese patent medicines. Aim of the study: We aimed i) to provide an overview of the TCM formulations affecting the pharmacology of digoxin and their mechanisms of action and ii) to provide a theoretical reference for the safe and rational use of digoxin in combination with TCM in clinical practice and to avoid ADRs. Methods: A literature search of electronic databases, including PubMed, MEDLINE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WANFANG Data, was performed to search for articles published between 1 January 1960, and 1 August 2022. Search terms used included "digoxin," "traditional Chinese medicine," "Chinese patent medicine," and "adverse reactions" and their combinations. Results: A total of 49 articles were obtained, including clinical reports, pharmacological experiments and in vitro experiments. The mechanisms of action affecting the pharmacology of digoxin are complex. TCM formulations may affect the pharmacology of digoxin in vivo by influencing gastrointestinal motility or gastric juice pH, regulating P-glycoprotein levels, exerting cumulative pharmacological effects, and enhancing the sensitivity of the heart to digoxin. Although studies have shown that some TCM formulations interact with digoxin, they may be influenced by the complexity of the composition and the pharmacological effects of the TCM, the sensitivity of digoxin concentration determination methods, etc. The results of existing studies are controversial and further in-depth studies are required. Conclusion: Combinations of digoxin and TCM formulations are commonly used. This article serves as a reference to understand the interactions between TCM formulations and digoxin to avoid the occurrence of ADRs and improve the efficacy and safety of digoxin.

Effect of P-Glycoprotein on the Blood-Brain Barrier Transport of the Major Active Constituents of Salvia miltiorrhiza Based on the MDCK-MDR1 Cell Model.

Salvia miltiorrhiza Bunge (S. miltiorrhiza) is a traditional Chinese medicine that has been widely used in the treatment of various central nervous system (CNS) diseases. However, the mechanism of active components of S. miltiorrhiza crossing the blood-brain barrier (BBB) stays unclear. The purpose of this study was to clarify the mechanism of four ingredients of S. miltiorrhiza, i.e., cryptotanshinone (CTS), dihydrotanshinone I (DTS I), tanshinone IIA (TS IIA), and protocatechuic acid (PCTA) crossing the BBB using the in vitro model. The bidirectional transport of detectable components was tested using the MDCK-MDR1 monolayers. High performance liquid chromatography coupled to triple-quadrupole mass spectrometry (HPLC-QQQ/MS) was used to detect the content changes of S. miltiorrhiza monomer components transported through the BBB. Papp of CTS, DTS I, and TS IIA in the absorption direction were lower than 1.0 × 10-6 cm/s, suggesting that these components were poorly absorbed, while PCTA was moderately absorbed through the BBB. The efflux ratio (ER) of CTS, DTS I, TS IIA, and PCTA were 1.65, 0.92, 4.27, and 1.48, respectively. After treatment with P-gp inhibitor tariquidar, the efflux ratio (ER) of CTS, DTS I, and TS IIA significantly decreased from 1.65 to 1.27, 0.92 to 0.36, and 4.27 to 0.86 (P < 0.05), respectively, while the efflux ratio of PCTA decreased without significance from 1.48 to 0.80. This indicated that the transport of CTS, DTS I, and TS IIA might be related to P-gp. TS IIA and CTS were verified as the substrates of P-gp among the four components since the ER of TS IIA and CTS is greater than 1.5. For PCTA and DTS I, their transport mechanism may be related to other transport proteins or passive transport. The results were confirmed by molecular docking in our current work. In this study, an in vitro BBB model was established and applied to the trans-BBB study of active components in S. miltiorrhiza for the first time, which may provide a basis for further research on the mechanisms of other TCMs in treating CNS diseases and is of great significance in promoting the rational and effective use of TCMs.