Chemical Basis Research Articles

Identification of in vitro-in vivo components of Caoguo using accelerated solvent extraction combined with gas chromatography-mass spectrometry integrated with network pharmacology on indigestion

BackgroundCaoguo (Tsaoko Fructus), a traditional Chinese medicine, is widely used as medicine and dietary spices. Volatile components are among its important bioactive constituents used to treatment of abdominal distension and pain, but the mechanism is not clear up to now. The purpose of this study was to develop a simple, sensitive, and accurate method to analyze and identify components of Caoguo in vitro and in vivo, and further investigate the therapeutic mechanism of Caoguo on indigestion using network pharmacology.MethodsCaoguo were extracted by accelerated solvent extraction (ASE) and n-hexane:ethyl acetate (1:1, v/v) was selected as the extraction solvent. Gas chromatography-mass spectrometry (GC-MS) was adopted to analyze and identify the volatile components in vitro and in vivo. Network pharmacology including protein-protein network construction, Gene Ontology (GO) enrichment and pathway enrichment analysis and component-target-pathway network construction was applied.ResultsBy comparing the retention times and mass spectrometry data, as well as retrieving the reference literature, a total of 169 components were tentatively identified in Caoguo extract and 43 components were identified in rats plasma samples for the first time. The results of network pharmacology analysis indicated that the potential mechanism was mainly associated with regulation of lipolysis in adipocytes and serotonergic synapse signaling pathway, which might be responsible for the effect of indigestion.ConclusionsCaoguo was first extracted by ASE and the volatile chemical components in vivo were first identified by GC-MS. Coupled with network pharmacology analysis, a network of component-target-pathway was constructed to reveal the possible mechanism of Caoguo in treatment of indigestion. This study provided a new reference method for the extraction and analysis of Caoguo, laid a chemical basis for in-depth studies on pharmacodynamics and pharmacology, and revealed an updated understanding of the therapeutic effects of Caoguo on indigestion.

Comparison of Nutritional Compositions and Essential Oil Profiles of Different Parts of a Dill and Two Fennel Cultivars.

Fennel and dill are widely used as food additives owing to their various biological activities, such as antioxidants, antimicrobials, food-preservatives, and seasoning capacities. Herein, the nutritional composition and essential oil (EO) chemical profiles of fruits, umbels, stalks, and roots from one dill and two fennel cultivars were evaluated. The fruits had the highest content of crude protein (≥15%), crude fat (≥8%), and phosphorus (≥0.5%), and exhibited the highest total energy (≥20 MJ/kg) and EO yield (≥2%). Moreover, estragole (86.56% in Fdf), anethole (71.17% in Fhf), fenchone (16.74% in Fhf), limonene (50.19% in Agf), and carvone (42.41% in Agf) were the main components of the EOs generated from the fruits. The chemical profiles of EOs in the roots were significantly different from those of the aerial parts of the fennel and dill; thus, the roots and aerial parts could be distinguished based on myristicin (Variable Importance in Projection (VIP) = 1.90399) and apiol (VIP = 1.85922). The EO components of the aerial parts varied remarkably, and the chemical markers for differentiating these three cultivars were anethole (VIP = 1.36571), estragole (VIP = 1.30292), and carvone (VIP = 1.11947). Overall, our results provide a noteworthy chemical basis for further development of fennel and dill, especially as food additives.

Cryo-EM structures of human PRMT5:MEP50 complex reveal chemical basis for designing high-specificity inhibitors

Cryo-EM structures of human PRMT5:MEP50 complex reveal chemical basis for designing high-specificity inhibitors

Sulfate and Molybdate Incorporation at the Calcite-Water Interface: Insights from Ab Initio Molecular Dynamics.

Sulfur and molybdenum trace impurities in speleothems (stalagmites and stalactites) can provide long and continuous records of volcanic activity, which are important for past climatic and environmental reconstructions. However, the chemistry governing the incorporation of the trace element-bearing species into the calcium carbonate phases forming speleothems is not well understood. Our previous work has shown that substitution of tetrahedral oxyanions [XO4]2– (X = S and Mo) replacing [CO3]2– in CaCO3 bulk phases (except perhaps for vaterite) is thermodynamically unfavorable with respect to the formation of competing phases, due to the larger size and different shape of the [XO4]2– tetrahedral anions in comparison with the flat [CO3]2– anions, which implied that most of the incorporation would happen at the surface rather than at the bulk of the mineral. Here, we present an ab initio molecular dynamics study, exploring the incorporation of these impurities at the mineral–water interface. We show that the oxyanion substitution at the aqueous calcite (10.4) surface is clearly favored over bulk incorporation, due to the lower structural strain on the calcium carbonate solid. Incorporation at surface step sites is even more favorable for both oxyanions, thanks to the additional interface space afforded by the surface line defect to accommodate the tetrahedral anion. Differences between sulfate and molybdate substitutions can be mostly explained by the size of the anions. The molybdate oxyanion is more difficult to incorporate in the calcite bulk than the smaller sulfate oxyanion. However, when molybdate is substituted at the surface, the elastic cost is avoided because the oxyanion protrudes out of the surface and gains stability via the interaction with water at the interface, which in balance results in more favorable surface substitution for molybdate than for sulfate. The detailed molecular-level insights provided by our calculations will be useful to understand the chemical basis of S- and Mo-based speleothem records.

Synthesis of 2-(Cyanomethyl)benzoic Esters via Carbon-Carbon Bond Cleavage of Indanones.

A novel synthesis of 2-(cyanomethyl)benzoic esters from indanone derivatives has been established. This reaction proceeds via a deprotonation of alcohols with a chemical base, followed by a nucleophilic addition to indanones and Beckmann fragmentation. In addition, this reaction could also work under electrochemical conditions, and no external chemical bases were needed. This mild method offers a novel strategy for the late-stage functionalization of various natural alcohols.

Drug-Induced Photosensitivity-From Light and Chemistry to Biological Reactions and Clinical Symptoms.

Photosensitivity is one of the most common cutaneous adverse drug reactions. There are two types of drug-induced photosensitivity: photoallergy and phototoxicity. Currently, the number of photosensitization cases is constantly increasing due to excessive exposure to sunlight, the aesthetic value of a tan, and the increasing number of photosensitizing substances in food, dietary supplements, and pharmaceutical and cosmetic products. The risk of photosensitivity reactions relates to several hundred externally and systemically administered drugs, including nonsteroidal anti-inflammatory, cardiovascular, psychotropic, antimicrobial, antihyperlipidemic, and antineoplastic drugs. Photosensitivity reactions often lead to hospitalization, additional treatment, medical management, decrease in patient’s comfort, and the limitations of drug usage. Mechanisms of drug-induced photosensitivity are complex and are observed at a cellular, molecular, and biochemical level. Photoexcitation and photoconversion of drugs trigger multidirectional biological reactions, including oxidative stress, inflammation, and changes in melanin synthesis. These effects contribute to the appearance of the following symptoms: erythema, swelling, blisters, exudation, peeling, burning, itching, and hyperpigmentation of the skin. This article reviews in detail the chemical and biological basis of drug-induced photosensitivity. The following factors are considered: the chemical properties, the influence of individual ranges of sunlight, the presence of melanin biopolymers, and the defense mechanisms of particular types of tested cells.

Systematic screening and structural characterization of dipeptides using offline 2D LC-LTQ-Orbitrap MS: A case study of Cordyceps sinensis

Cordyceps sinensis (C. sinensis) is a widely used and highly valuable traditional Chinese medicine. Several dipeptides have been detected in C. sinensis, but current scientific knowledge of its chemical makeup remains limited. In this study, an improved approach that integrates offline two-dimensional liquid chromatography (2D LC) separation, precursor ion list, library screening, and diagnostic ion filtering was established to systematically screen and characterize dipeptides in C. sinensis. Offline 2D LC integrating hydrophilic interaction LC and reverse phase separations was established to eliminate interference and identify the target dipeptides. A library containing the potential 400 dipeptides was created, and a precursor ion list with all theoretical precursor ions was adopted to trigger the MS/MS scan with high sensitivity. To identify dipeptides, the type and connection sequence of amino acids were determined according to the product ions. Ile and Leu residues were differentiated for the first time according to the characteristic ion at m/z 69.07. Ultimately, 170 dipeptides were identified or tentatively characterized from C. sinensis, and most are reported for the first time in this species herein. In addition, the identified dipeptides were also applied for discrimination among the three Cordyceps species, and 11 markers were identified. The obtained results provide a deeper understanding of the chemical basis of C. sinensis.

Identifiability Analysis of Degradation Model Parameters from Transient CO2 Release in Low-Temperature PEM Fuel Cell under Various AST Protocols

The detrimental effects of the catalyst degradation on the overall envisaged lifetime of low-temperature proton-exchange membrane fuel cells (LT-PEMFCs) represent a significant challenge towards further lowering platinum loadings and simultaneously achieving a long cycle life. The elaborated physically based modeling of the degradation processes is thus an invaluable step in elucidating causal interaction between fuel cell design, its operating conditions, and degradation phenomena. However, many parameters need to be determined based on experimental data to ensure plausible simulation results of the catalyst degradation models, which proves to be challenging with the in situ measurements. To fill this knowledge gap, this paper demonstrates the application of a mechanistically based PEMFC modeling framework, comprising real-time capable fuel cell performance, and platinum and carbon support degradation models, to model transient CO2 release rates in the LT-PEMFCs with the consistent calibration of reaction rate parameters under multiple different accelerated stress tests at once. The results confirm the credibility of the physical and chemical modeling basis of the proposed modeling framework, as well as its prediction and extrapolation capabilities. This is confirmed by an increase of only 29% of root mean square deviations values when using a model calibrated on all three data sets at once in comparison to a model calibrated on only one data set. Furthermore, the unique identifiability and interconnection of individual model calibration parameters are determined via Fisher information matrix analysis. This analysis enables optimal reduction of the set of calibration parameters, which results in the speed up of both the calibration process and the general simulation time while retaining the full extrapolation capabilities of the framework.

Aggregation and Degradation of Dispersants and Oil by Microbial Exopolymers (ADDOMEx): Toward a Synthesis of Processes and Pathways of Marine Oil Snow Formation in Determining the Fate of Hydrocarbons

Microbes (bacteria, phytoplankton) in the ocean are responsible for the copious production of exopolymeric substances (EPS) that include transparent exopolymeric particles. These materials act as a matrix to form marine snow. After the Deepwater Horizon oil spill, marine oil snow (MOS) formed in massive quantities and influenced the fate and transport of oil in the ocean. The processes and pathways of MOS formation require further elucidation to be better understood, in particular we need to better understand how dispersants affect aggregation and degradation of oil. Toward that end, recent work has characterized EPS as a function of microbial community and environmental conditions. We present a conceptual model that incorporates recent findings in our understanding of the driving forces of MOS sedimentation and flocculent accumulation (MOSSFA) including factors that influence the scavenging of oil into MOS and the routes that promote decomposition of the oil post MOS formation. In particular, the model incorporates advances in our understanding of processes that control interactions between oil, dispersant, and EPS in producing either MOS that can sink or dispersed gels promoting microbial degradation of oil compounds. A critical element is the role of protein to carbohydrate ratios (P/C ratios) of EPS in the aggregation process of colloid and particle formation. The P/C ratio of EPS provides a chemical basis for the “stickiness” factor that is used in analytical or numerical simulations of the aggregation process. This factor also provides a relative measure for the strength of attachment of EPS to particle surfaces. Results from recent laboratory experiments demonstrate (i) the rapid formation of microbial assemblages, including their EPS, on oil droplets that is enhanced in the presence of Corexit-dispersed oil, and (ii) the subsequent rapid oil oxidation and microbial degradation in water. These findings, combined with the conceptual model, further improve our understanding of the fate of the sinking MOS (e.g., subsequent sedimentation and preservation/degradation) and expand our ability to predict the behavior and transport of spilled oil in the ocean, and the potential effects of Corexit application, specifically with respect to MOS processes (i.e., formation, fate, and half-lives) and Marine Oil Snow Sedimentation and Flocculent Accumulation.

Biological activity of sod - podzolic sandsand soil with meloriative application of hydrogels

Biological activity of the soil is an indicator characterizing the number of organisms living in the soil, and quantitatively evaluating the results of their vital activity. High biological activity is a factor in increasing soil fertility and its phytosanitary state, achieved by creating optimal living conditions for soil microorganisms: providing nutrients, especially organic matter, moisture, heat and soil aeration. In this paper, we assess the effect of hydrogels of different chemical bases on the microbiological activity of sod-podzolic sandy loam soil. The effect of hydrogels on the microbiological activity of sod-podzolic soil was studied in a microfield experiment in a special installation (“dry place”) under conditions of soil drought and field conditions (Menkovsky branch of the FSBIU API, Gatchinsky district, Leningrad region). The experience was laid with two types of hydrogels (potassium and sodium base) with a single dose (40 g/m2). In the experiment, the indicators of soil biological activity were compared in the following variants: soil - control with the addition of 90 kg ha-1 NPK in the form of an azofoska, hydrogel introduced to a depth of 10–12 cm + N90 P90 K90, hydrogel introduced to a depth of 20–22 cm + N90P90K90. Samples of sod-podzolic sandy loam soil were taken from depths (10–12 cm and 20–22 cm) at the beginning and at the end of the growing season. In the course of the studies, it was found that when the hydrogel is introduced, both in the upper root-inhabited soil layer and in the 20–22 cm layer, favorable conditions are created for the microbiological activity of sod-podzolic sandy loam soil. It has been established that the chemical basis of the hydrogel does not inhibit the activity of the microbial community.

Analysis of Additional Methods of purification of Mixtures while Conducting Differential Lysis under Sexual Crimes

The article is focused on the problem of studying mixed biological traces during the research of the growing number and severity of sexual crimes. The presence of blood and epithelial cells with a small amount of sperm on things removed at the crime scene and smears from the victim’s body, complicates the molecular and genetic examination and the likelihood of obtaining a quality DNA profile from the sperm of the rapist. Therefore, the author has defined chemical basis of the standard method of differential lysis and the correlation of the components of the mixture of epithelial cells and sperm, which can help to get mixed and pure DNA profiles while amplify using the sets AmpFlSTR® Identifiler® PCR Amplification Kit, GlobalFiler STR PCR Amp Afication ™ PCR Amplification Kit. The author has analyzed literature data on the developed and perspective methods and additional stages of the differential lysis technique for purification of the mixture and aimed at sorting and reducing the number of epithelial cells. Chemical methods of mixture purification have been studied, including additional washing and incubation of the mortar, use of DNases, SDS lysis buffer and magnetic sorting with the use of antibodies (MOSPD3 and RH-20), and physical methods such as laser microdissection, acoustic lysis, hydrodynamic effect in small Reynolds numbers, microchips with additional integration of Cialyl Lewis oligosaccharide sequence and DEPArray technology. The main advantages and disadvantages of the procedures, the possibility of combining with other types, the impact on subsequent stages of molecular and genetic examination and the possibility of automating the research process have been provided for the methods. For the methods, the author has studied the probability of contamination during the procedure and the possibility of using for obsolete traces of sperm, where the destruction of sperm structure occurred. The author has indicated the possibility of automation of physical systems for forensic examination of molecular and genetic analysis by integrating the stages of sample preparation, cell counting and DNA isolation on a single device, which will reduce the time of the analysis of research objects in the future. The analysis of the literature data showed an improvement in the quality of DNA profiles while using the above methods, so it has been offered to use the presented methods for testing in expert practice.

Chemical aspects of polymer recycling

Since recycling of polymers is a preferred means of reducing unwanted wastes and land-filling activity, and recovering monomers or other materials of economic value, tertiary methods of recycling (chemical recycling) have been critically reviewed, giving special attention, in each case, to the chemical basis of the particular recycling pathway and its potential applicability. Recycling issues of each of the widely used commodity polymers – polyesters, polyamides, polyurethanes, epoxies, poly(vinyl chloride), polystyrene, and polyolefins – have been discussed individually, giving attention to both conventional and unconventional methods of perceived high potential, such as enzymatic degradation, ionic liquids mediation, microwave irradiation, and treatment in super critical liquids as well as super fluids. In addition, novel emerging methods undergoing greater study at present, such as cross-alkane metathesis (CAM), tandem hydrogenolysis/aromatization, vitrimer-based recycling, and dynamic covalent bonding are also highlighted.

Effects of four organic amendments on soil physiochemical properties and yield of maize (Zea mays) and cowpea (Vigna unguiculata) intercrop in Awka, southeastern Nigeria

Effects of four organic amendments on some soil physical and chemical properties were investigated in Awka, Anambra State in southeastern Nigeria. Over the years, use of synthetic materials in crop production has been a common practice globally. The attendant detrimental effects of the chemicals used in the formulation of these synthetics on animal and human health as well as the environment has made researchers to look out for a better agronomic practice that would not only improve productivity but at the same time sustain a healthy environment. Sole maize, sole cowpea and maize-cowpea intercrop (study area conventional practices) were planted using four soil organic amendments viz: cassava peel (CP), poultry manure (PM), pig waste (PW) and rice husk (RH) at the rate of 20 t ha–1 with the fifth as the control. The treatments were laid out in a 3 × 5 factorial in randomized complete block design and replicated four times. Data on the treatments’ effects on the selected soil physical properties (bulk density, total porosity, soil moisture) and chemical properties (soil pH, available phosphorus, cation exchange capacity (CEC), organic carbon, exchangeable bases and exchangeable acidity) were subjected to factorial analysis of variance using GenStat 2006 Edition. Results indicated that for sole maize, the amendments had significant effect onexchangeable Al3+and Na+; organic carbon, soil pH, available phosphorus and CEC but had no significant effect on Ca2+, H+, Mg2+ and K+ as compared to the control. For sole cowpea, compared to the plots with no amendment (control), all the chemical parameters analyzed differed significantly except organic carbon. Whereas, for maize-cowpea intercrop the treatments had no significant effect on Al3+, Na+, K+ and available phosphorus but differed significantly in exchangeable H+, Ca2+, Mg2+, organic carbon, soil pH, and CEC. There was a decrease in bulk density following the amendment. For sole maize, sole cowpea and maizecowpea intercrop; bulk density, total porosity and moisture content of the amended plots were significantly (p< 0.05) influenced. Organic amendments also significantly improved the growth and yield of maize and cowpea in both the sole and intercrop systems. Generally, poultry manure resulted in higher plant height,number of leaves and leaf area for maize; vine length, number of branches for cowpea as compared with other amendments. Hence, poultry manure was the most effective organic amendment in improving the soil physical and chemical properties as well as the growth and yield of cowpea and maize.
 Key words: Growth, maize-cowpea intercrop, soil physical and chemical properties, soil organic amendments

Integrating Constituents Absorbed into Blood, Network Pharmacology, and Quantitative Analysis to Reveal the Active Components in Rubus chingii var. suavissimus that Regulate Lipid Metabolism Disorder.

Rubus chingii var. suavissimus (S. K. Lee) L. T. Lu (RS)—a sweet plant also known as Tiancha distributed in the south of China where it is used as a beverage—recently gained extensive attention as adjuvant therapy of diabetes and hypertension. Although pharmacological studies indicate that RS has beneficial effects in regulating lipid metabolism disorder characteristics, the active chemicals responsible for this effect remains unclear. The present study aims to predict the effective substances of RS on regulating lipid metabolism disorder through the analysis of the chemical profile of RS, the absorbed prototype components in rat plasma, and network pharmacology. Also, a UPLC method able to quantify the screened potential effective chemicals of RS products was established. First, a total of 69 components—including diterpene, triterpenoids, flavonoids, polyphenols, and lignans—were systematically characterized in RS. Of those, 50 compounds were detected in the plasma of rats administered with RS extract. Through network pharmacology, 9 potential effective components, 71 target genes, and 20 pathways were predicted to be involved in RS-mediated regulation of lipid metabolism disorder. The quantitative analysis suggested that the contents of potential effective components varied among samples from different marketplaces. In conclusion, the presented results provide a chemical basis for further research of Rubus chingii var. suavissimus.

Difference Analysis of Ecological Vulnerability and Zoning Changes of National Energy and Chemical Bases Using FAHP Method.

Ecological vulnerability zoning research is an important basis for taking targeted regional ecological environment restoration and governance measures. This study analyzes the ecological vulnerability pattern and trend in the National Energy and Chemical Base (NECB) in the typical region of the Loess Plateau using GIS (Geographic Information System) data and the fuzzy analytic hierarchy process (FAHP) approach. Based on the human activity–natural environment factor index system, 13 factors representing human activities, socioeconomics, meteorology, soil and topography are selected to build an ecological vulnerability index (EVI) system in the NECB region, which aims at identifying the regional features of eco-environment and major environmental problems in the Loess Plateau. By calculating ecological vulnerability zoning, a model of ecological vulnerability trend change is constructed to quantitatively study the overall temporal and spatial variation of ecological vulnerability. The results indicate that the medium and heavy levels of ecological vulnerability index were mostly distributed in the areas with developed energy and chemical industries, and the slight and light levels were distributed in the southern area and developed agricultural regions. A comprehensive ecological vulnerability index had a score of 2.3207 in 2015 and 2.441 in 2000, indicating that the ecological security gradually improved. Nevertheless, highly intense human activities accelerated the degradation of regional eco-environment in recent years.

The Use of Chinese Yang/Qi-Invigorating Tonic Botanical Drugs/Herbal Formulations in Ameliorating Chronic Kidney Disease by Enhancing Mitochondrial Function.

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality. Mitochondrial dysfunction has been implicated as a key factor in the development of CKD. According to traditional Chinese medicine (TCM) theory, many Chinese Yang/Qi-invigorating botanical drugs/herbal formulations have been shown to produce promising outcomes in the clinical management of CKD. Experimental studies have indicated that the health-promoting action of Yang/Qi invigoration in TCM is related to the up-regulation of mitochondrial energy generation and antioxidant status. Objective: In this review, we aim to test whether Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations can provide medical benefits in CKD and its complications. And we also explore the possible involvement of mitochondrial-associated signaling pathway underlying the beneficial effects of Yang/Qi invigoration in TCM. Methods: A systematic search of “PubMed”, “China National Knowledge Infrastructure (CNKI)” and “Google Scholar” was carried out to collect all the available articles in English or Chinese related to Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their effects on mitochondrial function and chronic kidney disease. Result and Discussion: The relationship between the progression of CKD and mitochondrial function is discussed. The effects of Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their active ingredients, including phytosterols/triterpenes, flavonoids, and dibenzocyclooctadiene lignans, on CKD and related alterations in mitochondrial signaling pathways are also presented in this review. In the future, exploration of the possible beneficial effects and clinical studies of more Yang- and Qi-invigorating botanical drugs/herbal formulations in the prevention and/or/treatment of CKD and the molecular mechanisms relating to the enhancement of mitochondrial functions warrants further investigation. Conclusion: Given the critical role of mitochondrial function in safeguarding renal functional integrity, the enhancement of mitochondrial energy metabolism and antioxidant status in kidney tissue is likely involved in renal protection. Future studies on the biochemical and chemical basis underlying the effects of Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations from a mitochondrial perspective will hopefully provide novel insights into the rational development of new drugs for the prevention and/or treatment of CKD.

Integration of non-targeted metabolomics and E-tongue evaluation reveals the chemical variation and taste characteristics of five typical dark teas

The chemical profile and taste quality of various dark teas vary considerably due to the huge differences in tea cultivar, processing technology, and production region. Herein, we integrated liquid chromatography-mass spectrometry and electronic tongue to reveal variations in chemical profile and taste quality of five typical dark teas, namely Pu-erh tea (PET), Fuzhuan tea (FZT), Qingzhuan tea (QZT), Kangzhuan tea (KZT), and Liubao tea (LBT), and elucidate chemical basis for their taste quality. The chemical phenotypes of dark teas were classified into FZT, PET, and QZT-KZT-LBT, whereas their taste phenotypes were classified into FZT, PET-QZT, and KZT-LBT. Totally, 49 compounds were identified as differential metabolites, with higher contents of catechins and flavonoid glycosides in FZT, and higher contents of catechin derivatives, flavonoids, and alkaloids in PET. PET had the strongest bitterness and aftertaste-bitterness, while FZT showed the strongest astringency, aftertaste-astringency, and saltiness among five typical dark teas. The bitterness and aftertaste-bitterness of dark teas were negatively associated with polyphenols, flavonoids, and polysaccharides, but positively associated with theabrownins; their aftertaste-astringency was positively related to polyphenols and flavonoids, but negatively related to theabrownins. This study will guide dark tea taste quality control and lay a foundation for comparing their health benefits.

Unveiling Potential Active Constituents and Pharmacological Mechanisms of Pudilanxiaoyan Oral Liquid for Anti-Coronavirus Pneumonia Using Network Pharmacology

AbstractThe outbreak of novel coronavirus pneumonia (COVID-19), defined as a worldwide pandemic, has been a public health emergency of international concern. Pudilanxiaoyan oral liquid (PDL), an effective drug of Traditional Chinese Medicine (TCM), is considered to be an effective and alternative means for clinical prevention of COVID-19. The purpose of this study was to identify potential active constituents of PDL, and explore its underlying anti-COVID-19 mechanism using network pharmacology. Integration of target prediction (SwissTargetPrediction and STITCH database) was used to elucidate the active components of PDL. Protein–protein interaction network analyses, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, network construction, and molecular docking were applied to analyze the prospective mechanisms of the predicted target genes. Our results showed that the key active ingredients in PDL were luteolin, apigenin, esculetin, chrysin, baicalein, oroxylin A, baicalin, wogonin, cymaroside, and gallic acid. A majority of the predicted targets were mainly involved in the pathways related to viral infection, lung injury, and inflammatory responses. An in vitro study further inferred that inhibiting the activity of nuclear factor (NF)-кB signaling pathway was a key mechanism by which PDL exerted anti-COVID-19 effects. This study not only provides chemical basis and pharmacology of PDL but also the rationale for strategies to exploring future TCM for COVID-19 therapy.

Chemical Profile Assessment and Potential Bioactive Component Screening of a Chinese Patent Herbal Drug Yi-Shen-Hua-Shi Granule

Yi-Shen-Hua-Shi (YSHS) Granule is a well-known patented herbal drug for treating chronic glomerulonephritis (CGN) in China. Its chemical compositions and anti-CGN components are not fully understood. This study aimed to establish the chemical profile and to identify the anti-CGN components of YSHS Granule. For these purposes, a HPLC-Q-TOF-MS/MS method was developed. A total of 105 peaks were detected in the mass spectrum of the Granule. Of these, 99 compounds were tentatively identified as terpenoids, flavonoids, coumarins, alkaloids, phenols, and other types of compounds, and 15 were further identified with reference substances. To screen bioactive compounds, a cell membrane immobilized chromatography (CMIC) method was used. Lipopolysaccharide (LPS)-challenged rat glomerular mesangial cells (HBZY-1) were incubated with YSHS Granule (100 μg/mL), and the binding components to the cell membrane were extracted and analyzed using the established HPLC-Q-TOF-MS/MS method. Seven potential bioactive components that bound to HBZY-1 cell membranes were detected and identified as calycosin-7- O-β-D-glucoside, 6-gingerol, naringin, ginsenoside Re, poncirin, liquiritigenin, and isoliquiritigenin. The outcomes of the present study provide a chemical basis for clinical use of the Granule in managing CGN, and provide quality control markers for the Granule’s production and use.

Direct Alkylation of Deoxyguanosine by Azaserine Leads to O6-Carboxymethyldeoxyguanosine.

The O6-alkylguanosine adduct O6-carboxymethyldeoxyguanosine (O6-CMdG) has been detected at elevated levels in blood and tissue samples from colorectal cancer patients and from healthy volunteers after consuming red meat. The diazo compound l-azaserine leads to the formation of O6-CMdG as well as the corresponding methyl adduct O6-methyldeoxyguanosine (O6-MedG) in cells and is therefore in wide use as a chemical probe in cellular studies concerning DNA damage and mutation. However, there remain knowledge gaps concerning the chemical basis of DNA adduct formation by l-azaserine. To characterize O6-CMdG formation by l-azaserine, we carried out a combination of chemical and enzymatic stability and reactivity studies supported by liquid chromatography tandem mass spectrometry for the simultaneous quantification of O6-CMdG and O6-MedG. We found that l-azaserine is stable under physiological and alkaline conditions as well as in active biological matrices but undergoes acid-catalyzed hydrolysis. We show, for the first time, that l-azaserine reacts directly with guanosine (dG) and oligonucleotides to form an O6-serine-CMdG (O6-Ser-CMdG) adduct. Moreover, by characterizing the reaction of dG with l-azaserine, we demonstrate that O6-Ser-CMdG forms as an intermediate that spontaneously decomposes to form O6-CMdG. Finally, we quantified levels of O6-CMdG and O6-MedG in a human cell line exposed to l-azaserine and found maximal adduct levels after 48 h. The findings of this work elucidate the chemical basis of how l-azaserine reacts with deoxyguanosine and support its use as a chemical probe for N-nitroso compound exposure in carcinogenesis research, particularly concerning the identification of pathways and factors that promote adduct formation.