A NEW AND EFFICIENT SYNTHESIS OF 3-IODO DERIVATIVES OF FLAVONES, THIOFLAVONES AND THIOCHROMONES

The title compounds are prepared in good yields by iodination of the corresponding flavones, thioflavones and thiochromones respectively using I_2-CAN(ceric ammonium nitrate) system. The compounds thus prepared are potentially useful precursors for the synthesis of C-3 linked binuclear compounds.

Antioxidations and Their Correlations with Total Flavones and Anthocyanin Contents in Different Black Rice Varieties

The antioxidations and their correlations with total flavones and anthocyanin contents in different black rice varieties were studied. The results indicated that the great differences in total antioxidant capacity （TAC）, scavenging free radical capacity （SFRC）, total flavones and anthocyanin contents existed among 242 black rice varieties. Comparisons of TAC, SFRC, total flavones and anthocyanin contents of different black rice types showed that the differences between black rice and white rice, indica one and japonica one, and nonglutinous one and glutinous one were significant at 0.01 levels, respectively. This showed that the TAC, SFRC, total flavones and anthocyanin contents of japonica type were higher than those of indica one, and nonglutinous type were higher than glutinous one. According to the fast clustering procedure, 242 black rice varieties could be clustered into 10 clusters, 184 indica rice varieties into 10 clusters, and 58 japonica rice varieties into 6 clusters. Most significant （P〈0.01） correlations existed between TAC and total flavones and anthocyanin contents, and between SFRC and total flavones and anthocyanin contents of black rice, respectively. This showed that the antioxidation of black rice was closely correlated with its active compositions of flavones and anthocyanin.

ANTAGONISM OF TOTAL FLAVONES OF GYNOSTEMMA PENTAPHYLLUM (THUNB) MAK TO ANIMAL EXPERIMENTAL ARRHYTHMIA

The action of total flavones of Gynostemma pentaphyllum (Thunb) Mak (TFG) 60 mg/kg i.v. could prevent arrhythmias induced by drugs and myocardial ischemia were investigated. In anesthetized rats and guinea pigs. The results showed that in TFG group the duration of ventricular tachycardia (VT) induced by aconitine in rats was shortened (P<0 01) and the incidence of ventricular fibrillation (VF) and the mortality were decreased (P<0 01) respectively. The arrhythmias induced by i.v. BaCl 2 4 mg/kg in rats were immediately recovered to a normal sinus rhythm and VT induced by i.v. CaCl 2 130 mg/kg in rats was decreased by TFG i.v. TFG i.v. elevated the doses of i.v. strophanthin G to induce ectopic beats (EB), VT, VF and cardiac arrest (CA) in guinea pigs by 89%, 58%, 27%, and 28% (P<0 01) respectively. The incidence of VF induced by coronary artery ligation in rats was decreased (P<0 01), duration of EB, duraton of VT and VF decreased to 45%, 42% and 0% of the NS group respectively. The results suggest that TFG in dosage of 60 mg/kg might be useful for the prevention of VT and VF.

In Vitro Anti-viral Activities and Structureactivity Relationship Studies of Flavones and Dihydroflavone Derivatives as Influenza Virus Potential Neuraminidase Inhibitors

From the bioassay tests, 14 neuraminidase inhibitors （NIs） flavones and dihydroflavones derivatives from natural plants displayed different degree of inhibitory activities. Further- more, compounds No. 8 and 14 showed good inhibitory activity against influenza A virus with IC50 = 835.4 and 860.6 μg/mL. Then, to investigate interactions between NIs and neuraminidase （NA）, molecular docking was performed. Docking results indicated that Arg118, Asp151, Arg292 and Arg371 were the key residues in the active pocket of 2ht8. Main influencing factors of interactions between NIs and NA were hydrogen bond and electrostatic, then hydrophobic factor. Moreover, experimental activities of NIs were consistent with total scores of the docking. In order to understand the chemical-biological interactions governing their activities toward NA, QSAR models of 14 NIs were developed. The obtained HQSAR （hologram quantitative structure activity relationship）, PLS （partial least squares） and SRA （stepwise regression analysis） models were robust and had good exterior predictive capabilities. Moreover, squared multiple correlation coefficients （R2） and squared cross-validated correlation coefficients （Q2） of HQSAR and PLS models based on descriptors by Gaussian and Sarchitect were 0.832 and 0.721, 0.925 and 0.688, 0.892 and 0.692, respectively. R2 and SE （standard error） of SRA model based on descriptors by Gaussian were 0.922 and 0.072. Therefore, these models may be further used to design and evaluate the bioactivity of new compounds.

Development of mild and efficient method for synthesis of substituted flavones using oxalic acid catalyst

Oxalic acid has been used as a catalyst for intramolecular cyclisation of 2-hydroxychalcones to form flavones in good yields. The efficiency of the catalyst was proved with a variety of substrates ranging from electron-deficient to electron-rich aryl aldehydes and 2-hydroxychalcone.

Immunoregulatory Effects of Sanguis Draconis Flavones on Mouse Spleen Lymphocytes

[Objectives] This study aimed to study the effects of Sanguis Draconis flavones( SDF) on the immune regulation of mouse spleen lymphocytes. [Methods]A total of 60 BALB/c male mice were evenly and randomly divided into normal control group,model group,positive group,and high,middle and low-dose SDF groups. The mice in the model group were injected intraperitoneally with cyclophosphamide to establish mouse immunosuppressive model. The mice in the other groups were intragastrically administered at the respective doses,and the body weight was weighed once a week during the administration period. After 30 d of administration,the thymus and spleen indexes,the spleen lymphocyte proliferation ability,the NK cell activity,and the IL-2,IL-4 and INF-γ contents in the culture supernatant were measured. [Results]SDF could significantly increase the thymus and spleen indexes and improve the spleen lymphocyte proliferation ability and NK cell activity of the mice,as well as increasing the IL-2 and INF-γ contents and reducing the IL-4 content in spleen lymphocyte suspension culture. [Conclusions] SDF have good immunoregulatory effect.

Protective Effect of GRK2 and Effect of Sanguis Draconis Flavones on Focal Cerebral Ischemia-Reperfusion Injury in Rats

[Objectives] To explore the protective effect of Sanguis Draconis flavones (SDF) on rat focal cerebral ischemia-reperfusion injury (CIRI) models established by middle cerebral artery occlusion (MCAO).[Methods] A total of 60 healthy adult male Sprague-Dawley rats were selected. They were evenly and randomly divided into sham group, model group, edaravone group (12 mg/kg) and SDF group (360 mg/kg), and administered intragastrically and intraperitoneally. The middle cerebral artery of each rat was blocked by suture-occluded method to establish a CIRI model. After ischemia for 2 h and reperfusion for 48 h, the pathological injury on the ischemic side was observed by HE staining;the neuron and myelin sheath structure was observed by transmission electron microscopy;the expression of G protein-coupled receptor kinase 2 (GRK2) was preserved by immunohistochemistry;and the transfer of GRK2 was detected by western-blot.[Results] After 48 h of CIRI, the nuclei of the penumbral cortical neurons shrank, the chromatin was unevenly distributed, the nuclear membrane was dissolved and the mitochondria in the cytoplasm were swollen and vacuolated. The myelin layer was disordered. With this change, the distribution of GRK2 subcellular cells in the penumbra of the injured lateral cortex transferred from the cytoplasm to the membrane. SDF can effectively restore neuronal and myelin sheath structural damage and reduce the functional (membrane coupling) expression of GRK2.[Conclusions] GRK2 may be an effective target for SDF to protect the impaired blood-brain barrier (BBB) in CIRI.

Research Progress of Total Flavones in Marchantia convoluta

According to the literature retrieval,the composition,detection method,preparation method and product development of total flavones in Marchantia convoluta were reviewed and prospected. This paper will provide a theoretical basis for further study and product development of total flavones in M. convoluta.

Separation and Purification Process of Total Flavones from Litchi Pericarp by Macroporous Absorption Resin

[ Objective] This study aimed to optimize the conditions for purification of total flavones from litchi pericarp by macroporous absorption resin. E Method] The flavones adsorption rates and desorption rates of macroporous absorption resins （AB-8, HPD-600, D101 ） were compared, and the technological parameters of D101 during the purification process were investigated. E Result] D101 macroporous absorption resin was ap- propriate for the purification of total flavonoids from litchi pericarp. The optimal technological conditions were selected .. the pH of sample solution was 5.0; concentration of sample solution was 4 mg/ml, with a volume of 2.5BV; 80% ethanol was used as elution solution, with a volume of 2.0BV. [ Condusion] The content of total flavones achieved 83% after separation by D101 macoporous absorption resin.

Structure of Flavones and Flavonols. Part II: Role of Position on the O-H Bond Dissociation Enthalpy

The enthalpies of bond dissociations of the hydroxyl groups, the energy of the highest occupied molecular orbitals and the corresponding radicals spin densities of all possible ten isomeric mono-hydroxyl flavones are calculated by means of 3-parameter Becke, Lee, Yang and Parr functional. The structural factors affecting these descriptors of radical-scavenging activity are outlined. The results obtained show that the hydroxyl groups in ring A and C are more involved in the process of a radical-capturing than recently believed.

The neuroprotective efets of total flavones of Dracoce phalum moldavica L.on Parkinson's disease model in mouse

It was found that the extract of total flavones from Dracoce phalum moldavica L.(TFD)could exert neuroprotective effect on moase Parkinson's disease(PD)model,but the underlying mechanisms remained unclear.The aim of this study was to detect the mechanisms of TFD neuroprotective effect on PD mice.The PD model was established by injection with MPTP to mice.Using behavioral experiment and ELISA test as well as immunohistochemistry and Western blot analysis,the following parameters were examined:①the falling latency and climbing time,②the content of serum MDA as well as activities of SOD and GSH-Px,③the count of dopaminergic neurons with expression of TH in the substantia nigra of model mice,and④the expression levels of TH,caspase-3,Bcl-2 and Bax in the midbrain tissue.

A 180-Day Subchronic Oral Toxicity Study of Total Flavones of <i>E. leptorrhizum</i>Stearn in Rats

A subchronic oral toxicity was conducted to evaluate the safety of total flavones of E. leptorrhizum Stearn in Sprague-Dawley rats. The test article was administered once daily by gavage in male and female rats at dose levels of 24, 48, and 96 mg/kg body weight/day for 180 days. 90 and 180 days after administration, ten and tweedy animals (each half of male and female) of each group were tested. 28 days after withdrawal, five male and female rats were tested. There were no significant toxicological changes shown in daily clinical signs, body weight, food consumption, hematology parameters, blood biochemistry, organ weights and histopathological examination except leukocyte differential count. It was concluded that the no-observed-effect level (NOEL) for total flavones of E. leptorrhizum Stearn was >96 mg/kg in SD rats.

A Study on the Whitening Efficacy of Flavones in Lotus Leaf

Taking lotus flavones as the research object, cytotoxicity was evaluated by MTT test, inhibitory effects onthe activity of tyrosinase was studied, and DPPH scavenging experiments were carried out. Lotus flavoneswere used in a formula of skin cream and facial whitening effects were examined. Results shows that lotusflavones are exhibited no cytotoxicity at a concentration equal or less than 1%, and it can decrease the activityof tyrosinase at a concentration between 0.02%~0.30%. Lotus flavones can scavenge DPPH radical. The skincream containing lotus flavones declines facial melanin content. Lotus flavones have good biological safety andare suitable in cosmetics as whitening agents.

Flavones Isolated from Codonopsis xundianensis

Genus Codonopsis comprises more than 40 species in China. The roots of these plants have been used as traditional Chinese medicines or folk love herbs. Codonopsis xundianensis Wang ZT et Xu GJ grows in Yunnan Province and its roots are often used as a tonic. In this paper, we report the isolation and structural elucidation of chrysoeriol (1), tricin (2), wogonin (3) and luteolin (4) from the roots of Codonopsis xundianensis. Compounds 1-3 were found in Codonopsis for the first time.

Synthesis of A New Group of Flavones Containing Crown Ether Moiety

Flavones are main components of natural occurring flavonoils. It is well documented in the literatures that flavones are known to exhibit a wide variety of biological and pharmaceutical activities. Many of them have been used therapentically for the treatments of symptoms of chronic venous insufficiency, of varicose veins, of conditions and of diabetic retinopathy, etc.. Some flavones have

Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies

OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins,flavones, and alkaloids on experimental animals with autoimmune diseases(AIDs).METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO(CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, Pub Med,Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases;consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines.RESULTS: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin(IL)-1β[standardized mean difference(SMD) =-1.94, 95%confidence interval(CI)(-2.99,-0.90), P = 0.0003], IL-6 [SMD =-1.65, 95% CI(-2.33,-0.97,) P < 0.000 01],IL-17 [SMD =-2.41, 95% CI(-3.61,-1.20), P <0.0001], tumor necrosis factor(TNF)-α [SMD =-1.84, 95%CI(-2.61,-1.06), P < 0.0001], and interferon(IFN)-γ[SMD =-1.54, 95% CI(-2.43,-0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI(0.15,2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI(1.39,2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD =-0.63, 95% CI(-1.82, 0.57), P = 0.30].CONCLUTIONS: Substances containing saponins,flavones, and alkaloids regulated the changes of immunerelated cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.

Immunological Effects of Total Flavones from Leaves of Choerospondias axillaris on Mice

ObjectiveTo investigate the effect of total flavones from the leaves of Choerospondias axillaris (TFLCA) on the immune function of normal mice and to provide the experimental basis for the reasonable application of C. axillaris.MethodsThe carbon clearance method, cutaneous delayed hypersensitivity reaction method, serum hemolysin method, and index of immune organs were used to study the effect of TFLCA on the immune function of mice.ResultsTFLCA could enhance the phagocytic function of mononuclear macrophage and the cutaneous delayed hypersensitivity reaction of mice, and increase the content of hemolysin antibody and the thymus index in mice.ConclusionTFLCA could improve the celiac macrophage activity and specific immunity of mice, and TFLCA, consisting with the total flavones of Choerospondiatis Fructus (TFCF), has the effect on the immune function of mice. So both TFLCA and TFCF have the regulatory effects on the immune function of mice.

The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis

Background:Polymethoxylatedflavones(PMFs)are compounds present in citrus peels and other Rutaceae plants,which exhibit diverse biological activities,including robust antitumor and antioxidant effects.However,the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown.In the present study,we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs.Methods:MTT Cell viability assay and colony formation assay were used to investigate the effect of PMFs combined with PTX in reversing HCT8/T cell resistance ex vivo;the mRNA and protein levels of the target were detected by SDS-PAGE(sodium dodecyl sulfate-polyacrylamide gel electrophoresis),quantitative real-timefluorescence polymerase chain reaction(qRT-PCR)and Western blot protein immunoblotting(WB);An HCT8/T cell xenograft model was established to investigate the MDR reversal activity of PMFs in vivo;The extracellular acidification rate(ECAR)and the oxygen consumption rate(OCR)were detected to assess the cellular oxygen consumption rate and glycolytic process.Results:HCT8/T cells demonstrated significant resistance to PTX,up-regulating the expression levels of ABCB1 mRNA,P-gp,LC3-I,and LC3-II protein,and increasing intracellular reactive oxygen species(ROS)content.PMFs mainly contain two active ingredients,nobiletin,and tangeretin,which were able to reverse drug resistance in HCT8/T cells in a concentration-dependent manner.PMFs exhibited high tolerance in the HCT8/T nude mouse model while increasing the sensitivity of PTX-resistant cells and suppressing tumor growth significantly.PMFs combined with PTX reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)in HCT8/T cells.Additionally,PMFs reduced intracellular ROS content,down-regulated the expression levels of autophagy-related proteins LC3-I,LC3-II,Beclin1,and ATG7,and significantly reduced the number of autophagosomes in HCT8/T cells.Conclusions:The present study demonstrated that PMFs could potentially reverse PTX resistance in colon cancer by regulating the aerobic glycolysis-ROS-autophagy signaling axis,which indicated that PMFs would be potential potentiators for future chemotherapeutic agents in colon cancer.

Recent advances in the diversification of chromones and flavones by direct C-H bond activation or functionalization

Chromone and flavone are both central backbones of natural products and clinical medicines.Synthesis of diversely functionalized chromones and flavones constitutes significant research contents of the modern synthetic science because abundant molecular libraries of such types are crucial in providing candidate compounds for the discovery of new pharmaceuticals and functional materials.The direct C—H bond activation or functionalization on these heterocyclic backbones provides highly powerful tools for the rapid accesses to densely functionalized chromone and flavone derivatives.Considering the importance of the functionalized chromone and flavone compounds as well as the notable advances in the synthesis of such products by direct C—H activation or functionalization,we review herein the research advances in the C—H bond activation and functionalization reactions of chro mone and flavones,in hope of showing the current states and promise of the research domain.