Natural sources,refined extraction,biosynthesis,metabolism,and bioactivities of dietary polymethoxyflavones(PMFs)

Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different PMFs,such as nobiletin,sinensetin,tangeretin,and casticin,have been isolated from these natural sources.PMFs have received increasing attention due to their multiple bioactivities,such as antioxidant,anti-inflammatory,anti-cancer,metabolic regulatory,immunoregulatory,neuroprotective,and skin protective effects.These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota.In order to provide a comprehensive and updated review of PMFs,their natural sources,refined extraction,biosynthesis,metabolism,and bioactivities are summarised and discussed,with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases.Overall,PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.

Methodological survey of using Bayesian Network for predicting pharmacology-based bioactivities of Chinese medicines:a scoping review

Background:It seems to be numerous unclear black-box mechanisms of Chinese Medicines(CMs)with multiple bioactivities in the real-world clinical practice.Meanwhile,prior prediction is necessary before the implementation of pharmacodynamics-pharmacokinetics-based researches.With emergent ML techniques for TCM domain,Bayesian Network(BN)has shown its potentials for CM-bioactivity prediction and syndromes identification in Traditional Chinese Medicine(TCM),benefited from many advantages,such as flexibility in addressing,data-driven and probability-based inference under complex uncertainty.Although BN has been extensively used in TCM,the scarcity of researches on refining methodological features of BN-modelling for optimization poses a significant challenge.Our goal is to present methodological overview of BN-modelling for CM-bioactivities prediction towards pharmacology,which tends to acquire a sequence of intimations for boosting in-depth and optimized CM-BN collaboration based on detected gaps.Methods:We performed systematic search of 13 databases from their inception to November 10th 2022 regardless of language written,which excluded unindexed journals and clinical trial registries,using the 3 keywords(CM,Pharmacology,BN).And full-text original researches with the given subject were under consideration.Afterwards,selection of eligible studies,data refinement and inspection were totally conducted by 6 review authors.Results:A total of 7 studies involving 17 BN models were included for synthesis and refinement,based on existing literatures and databases with 2 modelling functions:regression and tagging.There were 3 prediction patterns:property-bioactivity,efficacy-bioactivity and constituent-bioactivity inference,covering 8 feature-utilized efficacies,5 feature-utilized properties and 10 feature-utilized constituents.Thereafter,without an independent validation dataset,established BNs were mostly utilized to predict the root-node probabilities of unknown data.Indeed,incomplete report on modelling samples,directed acyclic graphs,conditional probability tables and algorithms hindered us from gathering information.Conclusion:A spot of studies were found in this work.And current evidence suggested that some breakthroughs should be achieved in CM-BN integration in the future.At last,to our knowledge,we preliminarily proposed certain recommendations and elicited implications for future work.

Studies on Acaricidal Bioactivities of Artemisia annua L.Extracts Against Tetranychus cinnabarinus Bois.(Acari:Tetranychidae)

The aim of this study was to determine the best extraction technique, the most suitable solvent, the optimal plant parts, and the acaricidal activities of Artemisia annua L. The petroleum ether （30-60℃）, petroleum ether （60-90℃）, ethanol, acetone, and water parallel and sequenced extracts were obtained from the leaves, stems and roots of different period of A. annua L. in April, May, June, July and September respectively. And then the acaricidal bioactivities against Tetranychus cinnabarinus of all extracts were determined by the slide-capillary method in the laboratory. The results indicated that the acaricidal bioactivities elevated as the development of A. annua plant at the concentration of 5 mg mL-L The general tendency exhibited the sequence of July 〉 June 〉 May 〉 April, but September decreased comparing to July. However, the most effective extracts in five months were all acetone parallel extract of A. annua leaf, and the corrected mortalities treated after 48 h ranged from 74 to 100%. The median lethal concentrations （LC50） against T. cinnabarinus of acetone parallel extracts ofA. annua leaves in September, July, June, May and April were 0.5986, 0.4341, 0.8376, 0.9443 and 1.3817 mg mL^-1, respectively, treated after 48 h. The 13 groups were isolated from acetone extracts ofA. annua leaves in July by column chromatography, both the 1 lth and 12th groups exhibited strong bioactivities. The median lethal concentrations of the 1 lth and 12th groups against T. cinnabarinus were 0.3683 and 0.1586 mg mL^-1, respectively. The acetone parallel extract ofA. annua leaf in July was the most toxic to T. cinnabarinus and the corrected mortality was 100% after 48 h. The acetone parallel extract of the 1 lth and 12th groupswere the most active components, acted as the emphases in further study.

Identification and Bioactivities of Secondary Metabolites Derived from Endophytic Fungi Isolated from Ethnomedicinal Plants of Tujia in Hubei Province:A Review

Tujia is a national minority,inhabiting in the mountainous Wuling area in China.Since 1978,Tujia medicine has been studied,summarized and developed,leading to numerous achievements by Chinese researchers,such as the publishing of approximately 30 monographs of Tujia medicine.These publications are focused on summarizing and improving the theory of Tujia medicine and developing clinical therapies from this system of medicine.The shortage of natural medicinal plants used in Tujia medicine has created the need to discover new resources to replace them and protect endangered natural plant species.Endophytic fungi are one of the conservation options,are considered a source of new bioactive natural products,and are a renewable and inexhaustible source of new drugs and agrochemicals.This review summarizes 260 compounds from endophytic fungi that have been previously isolated from the medicinal plants of Tujia.These compounds include steroids,terpenoids,meroterpenoids,polyketides,alkaloids,peptides,aliphatic compounds,aromatic compounds,and heterocyclic compounds.

Research Progress of the Antiviral Bioactivities of Natural Flavonoids

Flavonoids are now considered as an indispensable component in a variety of nutraceutical and pharmaceutical applications.Most recent researches have focused on the health aspects of flavonoids for humans.Especially,different flavonoids have been investigated for their potential antiviral activities,and several natural flavonoids exhibited significant antiviral properties both in vitro and in vivo.This review provides a survey of the literature regarding the evidence for antiviral bioactivities of natural flavonoids,highlights the cellular and molecular mechanisms of natural flavonoids on viruses,and presents the details of most reported flavonoids.Meanwhile,future perspectives on therapeutic applications of flavonoids against viral infections were discussed.

Chemical constituents from the aerial parts of Euphorbia sikkimensis and their bioactivities

Phytochemical investigation of the aerial parts of Euphorbia sikkimensis led to the isolation of one new diterpenoids,named sikkimenoid E(1),together with thirteen other known compounds(2-14).Their structures were established by means of spectroscopic methods.Compound 2 was identified to be a trinortriterpenoid,and derived for the first time from a natural source.In this paper we reveal for the first time its comprehensive spectral data and NMR spectral assignment.Compound 4 showed anti-angiogenic activity with an IC_(50) value of 5.66μM in a zebrafish model,and compounds 5 and 6 exhibited cytotoxicity toward A549 cell line with IC_(50) values of 12.12 and 6.45μM,respectively.

Synthesis, Crystal Structure and Bioactivities of 1-(4-Chlorophenyl)-3-[5-(pyrid-4-yl)-1,3,4-thiadiazol-2-yl]urea

The title compound 1-（4-chlorophenyl）-3-[5-（pyrid-4-yl）-1,3,4-thiadiazol-2-yl]urea （C14H10CIN5OS, Mr = 331.79） has been synthesized by the reaction of 2-amino-5-（pyrid-4-yl）- 1,3,4-thiadiazole with 4-chlorobenzoyl azide, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to triclinic system, space group PI with a = 5.8550（8）, b = 7.5668（10）, c = 16.416（2）A, α= 78.364（2）, β= 81.204（2）, γ= 84.749（2）°, V= 702.58（16）A^3, Z= 2, Dc = 1.568 g/cm^3, p = 0.429 mm ^-1, F（000） = 340, the final R = 0.0442 and wR = 0.1092 for 2001 observed reflections （1 〉 2σ（I））. X-ray diffraction analysis reveals that the title molecule is nearly planar. In the crystal structure, the molecules are linked by strong intermolecular N-H…N hydrogen bonds together with weak nonclassical intennolccular （C-H…Y, Y = N, O and CI） hydrogen bonds and stacked through π-π interactions. The preliminary bioassay shows that the title compound exhibits good fungicidal activities against Rhizoctonia solani, Botrytis cinerea and Dothiorella gregaria.

Microwave-assisted Syntheses,Structures and Bioactivities of α-Aminophosphonates Containing Pyrazole and 2-Hydroxybenzyl Units

Using 3-amino-4-cyanopyrazole, salicylaldehyde and dialkylphosphite as materials, a series of a-aminophosphonates containing pyrazole and 2-hydroxybenzyl units were synthesized under microwave irradiation without solvents and catalysts. The structures of the compounds were verified by IR, 1H NMR, J3C NMR and elemental analysis. The crystal structure of diisobutyl {a-[3- （4-cyano-lH-pyrazol）amino）]-N-（2-hydroxylbenzyl）}phosphonate （4d, C19H27N404P） was deter- mined by single-crystal X-ray diffraction. Compound 4d crystallizes in the orthorhombic system, space group Pbcn with a = 17.329（4）, b = 20.091（5）, c = 12.433（3）/k, V = 4328.7（17） A3, M,. = 406.42, Dc = 1.247 g/cm3, Z = 8, F（000） = 1728,μ = 0.158 mm-1, MoKa radiation （2 = 0.71073 A）, the final R = 0.064 and wR = 0.0169 for observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals that two planes lie in 4d, and the dihedral angle is 85.76°. Intermolecular O（1）-H（1B）-O（2）, N（1）-H（1）-N（4）, N（3）-H（3）.-.N（2） and N（3）-H（3）...O（1） hydrogen bonds are found in the structure. All the compounds were evaluated for their antiviral and antitumor activities respectively. Among them, 4d and 4e showed moderate anti-TMV activities at 500 gg/mL, and 4e possessed excellent antitumor activity against PC3 cells at 10 gmol/L.

Synthesis, X-ray Crystallographic Analysis and Bioactivities of α-Aminophosphonates Featuring Pyrazole and Fluorine Moieties

A series of novel -aminophosphonates containing pyrazole and fluorine moieties was designed and synthesized through ultrasonic-assisted condensation and solvent-free addition reactions. Their structures were verified by IR, ^1H NMR, ^13C NMR and elemental analysis. The crystal structure of diethyl[（4-cyano-1H-pyrazol-3-ylamino）（3,5-difluorophenyl）methyl]phosphonate（4a, C15H17F2N4O3P） was determined by single-crystal X-ray diffraction. Compound 4a crystallizes in the triclinic system, space group P1 with a = 8.381（3）, b = 10.103（5）, c = 11.268（3） A, α= 83.772（19）, β= 74.726（19）, γ= 70.964（18）, V = 869.9（6） 3, Mr = 370.30, Dc = 1.414 g/cm^3, Z = 2, F（000） = 384, = 0.200 mm^-1, MoKa radiation（ = 0.71073 ）, the final R = 0.0487 and w R = 0.0823 for 1582 observed reflections with I 〉 2（I）. X-ray diffraction analysis reveals that there are two planes in 4a, and the dihedral angle is 71.51°. Two intermolecular hydrogen bonds and a face-to-face … stacking interaction are observed in the crystal structure. The compounds were evaluated for their antifungal, antiviral and antitumor activities, respectively. Among them, 4b, 4c, 4g and 4h exhibit good activities on Sclerotium rolfsii Sacc at 200 μg/m L, while 4b, 4c, 4f and 4g possess good anti-TMV activities at 500 μg/m L. Unfortunately, all of the compounds showed weak antitumor activities.

Two Cu(Ⅱ) Complexes with Hydrolyzed Nicotinamide Ligand: Crystal Structures and Bioactivities

Two Cu(Ⅱ) complexes of [Cu(2,6-DPC)(Hnta)(H2O)]·H2O(2,6-DPC = 2,6-pyridinedicarboxylic-carboxylate, Hnta = nicotinic acid) and [Cu2(2,4-D)4(Hnta)2](2,4-D = 2,4-dichlorophenoxyacetic-carboxylate) were synthesized and successfully obtained as single crystals in this paper. The supramolecular structures of the complexes from zero to three dimensions and the weak intermolecular force in the crystal were analyzed. The single-crystal structures of the complexes were further analyzed by Hirshfeld surface analysis. The competition capacity of the complexes about calf thymus DNA(ct-DNA) was also analyzed by fluorescence spectroscopy. The ability of complexes to cleave the plasmid DNA(pBR322-DNA) was determined by gel electrophoresis assay. And at last, the complexes’ cytotoxic activities were reviewed for four kinds of cancer cell lines(HeLa, MCF-7, HepG, SKOV-3), showing that the coordination polymer has anti-tumor activity and cytotoxicity.

Chemistry and bioactivities of natural steroidal alkaloids

Steroidal alkaloids possess the basic steroidal skeleton with a nitrogen atom in rings or side chains incorporated as an integral part of the molecule.They have demonstrated a wide range of biological activities,and some of them have even been developed as therapeutic drugs,such as abiraterone acetate(Zytiga®),a blockbuster drug,which has been used for the treatment of prostate cancer.Structurally diverse natural steroidal alkaloids present a wide spectrum of biological activities,which are attractive for natural product chemistry and medicinal chemistry communities.This review comprehensively covers the structural classification,isolation and various biological activities of 697 natural steroidal alkaloids discovered from 1926 to October 2021,with 363 references being cited.

Novel Phosphonoacetic Acid Derivatives.Synthesis of N-(Ethoxycarbonylmethylphosphonyl)-α-Amino Esters and-α-Amino Phosphonic Acid Esters and Their Bioactivities

A series of novel phosphonoacetic acid derivatives, N-(ethoxycarbonylmethy-ethoxyphosphonyl)-α-amino acid esters and α-amino phosphonates, were synthesized via the reaction of the corresponding phosphonyl chloride with amino acid ester hydrochlorides or amino phosphonates in the presence of a base. The preliminary bioassay shows that some compounds show significant anti-viral activity against tobacco mosaic virus (TMV)

Isolation,Purification and Bioactivities of Polysaccharides from Irpex lacteus

Irpex lacteus has been widely used for treating chronic glomerulonephritis as a traditional Chinese medicine.Seven water-soluble polysaccharide fractions（ILN I,ILN II,ILN III,ILA I,ILA II,ILB I and ILB II） were isolated and purified from Irpex lacteus by hot-water extraction,deproteinization,decolorization,dicthy laminoethyl（DEAE）-cellulose ion exchange and sephadex G100 chromatographies,respectively.The average molecular weights and monosaccharide composition of these polysaccharide fractions greatly differed from each other.The antitumor and antinephritis activities of the seven polysaccharide fractions were evaluated.It was found that ILN III displayed significant inhibition effects on both humar hepatocellular liver carcinoma（HepG2） and hentietta lacks（HeLa） tumor cells with IC 50 values of 60.95 and 99.95 μg/mL,respectively.ILA I exhibited significant inhibition effects on murine mesangial cells（HBZT-1） with an IC 50 value of 185.06 μg/mL.The inhibition effects of other polysaccharide fractions on these three cells were significantly different.These results suggest that the polysaccharide fractions isolated from Irpex lacteus have potential antitumor and antinephritis activities.

Bioactivities of Culture Supernatants from Retroviral Packaging Cells Carrying the Mouse Fas Ligand Gene

The bioactivities of culture supernatants from retroviral packaging cells carrying the mouse Fas ligand (mFasL) gene was investigated. FasLcDNA was cloned into PLXIN with an internal ribosome entry site to link two cistrons through gene recombination technology, PLXIN and the recombinant vector PLFIN were separately transfected into PA317 retrovirus packing cell line by lipofectamine 2000, and the resistant clones were selected with G418 selective medium. The integration of genome DNA was assayed by genomic DNA PCR. NIH3T3 cells were transduced by the culture supernatants from PA317 carrying the mFasLcDNA gene, and were selected with G418 selective medium, so as to select the PLFIN-PA317 clone capable of producing higher titer of supernatants. The levels of mFasL protein on NIH3T3 cells membrane were assayed by flow cytometry (FCM). The biological activity of mFasL on NIH3T3 cells membrane was investigated by the inducing apoptosis of Fas + Yac-1 cells co-cultured with NIH3T3 cells expressing Fas ligand. To explore the direct mFasL cytotoxicity of culture supernatants from retroviral packaging cells carrying the mFasL gene, the culture supernatants from PLFIN-PA317 and PLXIN-PA317 were separately co-cultured with Yac-1 cells in parallel. The recombinant PLFIN was successfully constructed. The highest titer of supernatants from twelve resistant clones was 8.5×10 5 colony-forming-unit (CFU)/ml. The NIH3T3 cells transfected by above supernatants had a higher level of mFasL (53.81±6.9 %), and significantly induced the apoptosis of Fas + Yac-1 cells (56.78±4.5 %), as both were cocultured for 5 h at 1∶1 ratio, whereas it is 7.08±3.4 % in control group (P<0.01). Supernatant from PLFIN-PA317 could also directly induce the apoptosis of Yac-1 within 5 h of incubation. Thus, the culture supernatants from PLFIN-PA317 possessed both infectivity and cytotoxicity of mFasL.

Mannich Base Derivatives of 1,2-Benzisothiazolin-3-one: Syntheses, Crystal Structures and Bioactivities

Twelve Mannich base derivatives of 1,2-benzisothiazolin-3-one were synthesized by the reaction of 1,2-benzisothiazol-3（2H）-one （BIT） with different amines and formaldehyde. All the compounds were characterized by elemental analysis, IR spectroscopy, MS and 1H NMR. The crystal structure for 2,2＇-methylenebis（benzo[d]isothiazol-3（2H）-one） （3） has been determined by X-ray single-crystal structure analysis. Compound 3 （C15HIoN202S2） crystallizes in the monoclinic system, space group C2/c with a = 25.052（8）, b = 4.510（1）, c = 11.948（4） A, β = 100.992（4）°, V= 1325.2（7） A3, Mr = 314.37, Dc = 1.576 Mg.m-3, p = 0.25 mm-1, F（000） = 648, Z = 4, R = 0.034 and wR = 0.087. The preliminary biological test indicated that the compounds （2b, 2c） showed growth inhibitory activity against the gram-positive and gram-negative bacteria.

Syntheses and Bioactivities of 4-Ar-2-oxo-glutaric Acids

Fourteen novel compounds were synthesized and characterized by using NMR and ESI-MS methods. The bioactivities of the four novel 4-Ar-2-oxo-glutaric acids were studied by using the LC-MS method. The experimental results show that 3-nitrobenzyl-2-oxo-glutaric acid is a mild inhibitor for the hydroxylation reaction catalyzed by PHD2. The decarboxylated peak for 3-fluorobenzyl-2-oxo-glutaric acid was observed by using the negative LC-MS method, indicating that it can be used as a mild cosubstrate to replace 2-OG, but this is possible only in the presence of the prime peptide CODD 19 mer.

Steroids and dihydroisocoumarin glycosides from Xylaria sp.by the one strain many compounds strategy and their bioactivities

The fungus Xylaria sp.KYJ-15 was isolated from Illigera celebica.Based on the one strain many compounds(OSMAC)strategy,the strain was fermented on potato and rice solid media,respectively.As a result,two novel steroids,xylarsteroids A(1)and B(2),which are the first examples of C28-steroid with an unusualβ-andγ-lactone ring,respectively,along with two new dihydroisocoumarin glycosides,xylarglycosides A(3)and B(4),were identified.Their structures were elucidated by spectroscopic methods,X-ray diffraction and electronic circular dichroism(ECD)experiments.All isolated compounds were evaluated for cytotoxicity,DPPH radical scavenging activity,acetylcholinesterase inhibitory and antimicrobial effect.Compound 1 exhibited potent AChE inhibitory activity with an IC50 value of 2.61±0.05μmol·L^(−1).Theβ-lactone ring unit of 1 is critical for its AChE inhibitory activity.The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking.In addition,both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration(MIC)of 2μg·mL^(−1).Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2μg·mL^(−1),respectively,which also exhibited DPPH radical scavenging activity comparable to the positive control with IC50 values of 9.2±0.03 and 13.3±0.01μmol·L^(−1),respectively.

Betalains protect various body organs through antioxidant and anti-inflammatory pathways

Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-inflammatory properties,which are highly imperative.Further in-vivo studies reported that betalains protect various body organs,leading to health enhancement.Body organs,including the heart,liver,kidney,lung,etc.,are important for a healthy life.However,these organs can be affected or damaged by various stress factors,toxicants,and harmful substances.Recent studies have claimed that betalains could protect all vital organs of the body through antioxidant and anti-inflammatory mechanisms.This review article described the in-vivo antioxidant and anti-inflammatory activities of betalains in various cell-line or animal models.A comprehensive discussion has been provided on the mechanism of action of betalains in protecting various body organs,including cardio-protective effect,hepato-protective ability,renal protection capacity,repro-protective ability,neuro-protective effect,lung protection,and gut protection ability.Finally,future research directions and conclusions have been outlined.

A review of isolation methods, structure features and bioactivities of polysaccharides from Dendrobium species

Dendrobium,orchid,is a traditional Chinese herb medicine applied extensively as tonic and precious food for thousands of years recorded in ancient Chinese medical book"Shen Nong’s Materia Medica".It’s well known that bioactivities are usually related to the ingredients’basis.Based on the previous research,Dendrobium species contain amino acid,sesquiterpenoids,alkaloids and polysaccharides.As the bioactive substances,carbohydrate shows extensive activities in antitumor,antiglycation,immune-enhancing,antivirus,antioxidant,antitumor and etc.Therefore,as the main biologically active substance,the exact structures and latent activities of polysaccharides from Dendrobium species are widely focused on.In this review,we focus on the advancements of extraction methods and diversity of structures and bioactivities of polysaccharides obtained from Dendrobium species.

Valorization of Camellia oleifera oil processing byproducts to value-added chemicals and biobased materials: A critical review

The C.oleifera oil processing industry generates large amounts of solid wastes,including C.oleifera shell(COS)and C.oleifera cake(COC).Distinct from generally acknowledged lignocellulosic biomass(corn stover,bamboo,birch,etc.),Camellia wastes contain diverse bioactive substances in addition to the abundant lignocellulosic components,and thus,the biorefinery utilization of C.oleifera processing byproducts involves complicated processing technologies.This reviewfirst summarizes various technologies for extracting and converting the main components in C.oleifera oil processing byproducts into value-added chemicals and biobased materials,as well as their potential applications.Microwave,ultrasound,and Soxhlet extractions are compared for the extraction of functional bioactive components(tannin,flavonoid,saponin,etc.),while solvothermal conversion and pyrolysis are discussed for the conversion of lignocellulosic components into value-added chemicals.The application areas of these chemicals according to their properties are introduced in detail,including utilizing antioxidant and anti-in-flammatory properties of the bioactive substances for the specific application,as well as drop-in chemicals for the substitution of unrenewable fossil fuel-derived products.In addition to chemical production,biochar fabricated from COS and its applications in thefields of adsorption,supercapacitor,soil remediation and wood composites are comprehensively reviewed and discussed.Finally,based on the compositions and structural characteristics of C.oleifera byproducts,the development of full-component valorization strategies and the expansion of the appli-cationfields are proposed.