Total Flavones Research Articles

SUN-004 THE REGULATION OF THE GUT-KIDNEY AXIS IN VIVO BY TOTAL FLAVONE OF ABELMOSCHUS MANIHOT, A NATURAL EXTRACT, CONTRIBUTES TO THE AMELIORATION OF ADENINE-INDUCED RENAL FAILURE

Targeting gut microbiota dysbiosis and uremic toxins accumulation is important for the amelioration of renal dysfunction in chronic renal failure (CRF). Total flavone of abelmoschus manihot (TFA), a natural extract, has been applied extensively for treatment of the CRF patients in China. However, its therapeutic mechanisms remained elusive. Therefore, in this study, using an adenine-induced renal failure (RF) rat model, we examined the effects of TFA on the gut-kidney axis in vivo, compared with lubiprostone (LUB), then to clarify the potential mechanisms. Rats were randomly divided into 4 groups, the Sham-operated group, the Vehicle-given group, the TFA-treated group and the LUB-treated group. TFA, LUB and saline were daily administrated for 4 weeks after induction of RF by adenine gavage with unilateral ureteral obstruction (UUO). Renal injurious and dysfunctional indicators, tubulointerstitial fibrosis (TIF), fecal microbiota, gut-derived uremic toxins, colon histological characteristics and tight junction proteins expressions, as well as the key protein expression levels of TLR4/NF-κB/NLRP3 inflammasome pathways in the colon and the kidneys were examined, respectively. In the RF model rats, in addition to renal lesions and uremic toxins accumulation, the abundance of Lactobacillus in the gut was decreased, while that of C. perfringens in the gut was increased; There appeared the ulcers in the colon, accompanied with the low-expression of ZO-1 and claudin-1; Besides, TLR4/NF-κB/NLRP3 inflammasome pathways in the colon and the kidneys were activated, respectively. After the treatment of TFA or LUB, renal dysfunction and TIF in the RF model rats were significantly improved. Furthermore, the disordered Lactobacillus, Enterococcus, E. coli and C. perfringens in the gut, the damaged intestinal environment and the accumulative indoxyl sulfate and p-cresyl sulfate in serum were all ameliorated. More notably, TFA synchronously inhibited TLR4/NF-κB/NLRP3 inflammasome pathways activity in the colon and the kidneys, whereas, LUB only suppressed TLR4/NF-κB/NLRP3 inflammasome pathway activity in the colon. TFA, as a natural regulator in vivo, regulates the gut-kidney axis and ameliorates renal dysfunction in the RF model rats by modulating gut microbiota, reducing uremic toxins and inhibiting TLR4/NF-κB/NLRP3 inflammasome pathways activity in the colon and the kidneys, which is different from LUB. These findings may provide the first evidence for the gut-kidney axis, as the unusual target of TFA treatment in CRF.

Total flavone of Abelmoschus manihot ameliorates Crohn's disease by regulating the NF‑κB and MAPK signaling pathways.

Crohn's disease (CD) is a chronic relapsing form of inflammatory bowel disease, and its pathogenesis remains unknown. Total flavone of Abelmoschus manihot L. Medic (TFA), has been used as anti‑inflammatory and myocardial ischemia protective drug. The present study aimed to explore the effects of TFA on CD and its underlying mechanism. We reported that TFA comprises eight flavone glycosides, including quercetin‑3‑O‑robinobioside, gossypetin‑3‑O‑glucoside, quercetin‑3'‑O‑glucoside, isoquercetin, hyperoside, myricetin, gossypetin and quercetin. In vivo, TFA promoted the survival of 2,4,6‑trinitrobenzene sulfonic acid (TNBS)‑induced colitis in mice, decreased weight loss and increased colon length in a dose‑dependent manner. Additionally, TFA notably ameliorated the inflammatory response in mice with TNBS‑induced colitis as determined by histopathological analysis. In addition, the administration of TFA in mice with TNBS‑induced colitis led to a significant decrease in the levels of cytokines in the sera and colon tissues; a significant decrease myeloperoxidase activity in the colon tissues was also observed. These findings may be associated with the suppression of the nuclear factor‑κB (NF‑κB) and mitogen‑activated protein kinase (MAPK) signaling pathways. In vitro, TFA significantly downregulated the expression of cytokines in lipopolysaccharide (LPS)‑induced RAW264.7 cells. In addition, TFA suppressed LPS‑induced activation of the NF‑κB and MAPK signaling pathways in RAW264.7 cells. Our findings indicated that TFA could suppress the inflammatory response in mice with TNBS‑induced colitis via inhibition of the NF‑κB and MAPK signaling pathways. The results of the present study may improve understanding of the function of TFA and provide a novel theoretical basis for the treatment of CD.

Molecular mechanisms of insulin resistance and interventional effects of Chinese herbal medicine

It is considered that insulin resistance(IR)and its signaling pathway disorder are one of pathogenesis that causes insulin target-organs/issues lesions and their slow progression. The clinical diagnosis index of IR is the homeostatic model of insulin resistance(HOMA-IR)based on fasting blood-glucose and fasting serum insulin. Furthermore, the emerging IR biomarkers including adiponectin may be the references for clinical diagnosis. The influence factors of IR are obesity, chronic microinflammation and a lack of exercise. The major signaling pathways of IR include insulin receptor substrate 1(IRS1)/phosphatidylinositiol-3-kinase(PI3 K)/serine-threonine kinase(Akt)pathway, mitogen-activated protein kinase(MAPK)pathway and Smad3 pathway. In clinics, insulin sensibility and IR could be increased and improved via promoting insulin secretion and enhancing insulin signaling activation. At present, insulin sensitizers treating IR not only have the classic thiazolidinediones and its ramifications but also have the newly discovered metformin and vitamin D. In addition, it is reported that some extracts from single Chinese herbal medicine(CHM)and Chinese herbal compound prescription such as total flavone from the flowers of Abelmoschl manihot, berberine, astragalus polysaccharides and Huang-qi decoction also have the beneficial effects in ameliorating IR. In the field of chronic kidney disease, targeting a common insulin target-organs/issues lesion, the early renal damage in diabetic mellitus, the intervention studies regarding to regulating podocyte IR signaling pathways by CHM will be one of the significant directions in the future.

De novo characterization of the Goji berry (Lycium barbarium L.) fruit transcriptome and analysis of candidate genes involved in sugar metabolism under different CO2 concentrations.

Goji berry (Lycium barbarum L.) is one of the important economic crops due to its exceptional nutritional value and medicinal benefits. Although reduced sugar levels in goji berry exposed to long-term elevated carbon dioxide (CO2) have been documented, the underlying molecular mechanisms remain unknown. The objective of this study was to explore the transcriptome of goji berry fruit under ambient and elevated CO2 concentrations and further to screen the differentially expressed genes (DEGs) for functions related to sugar metabolism. Fruit samples from goji berry exposed to ambient (400 μmol mol-1) and elevated (700 μmol mol-1) levels of CO2 for 120 days were analyzed for total sugar, carotenoid and flavone analysis. In this study, a reduction in total sugar and carotenoid levels in the fruits grown under elevated CO2 levels were observed. Fruit samples were also used to construct cDNA libraries using a HiSeqTM2500 platform. Consequently, 81,100 unigenes were assembled, of which 35,111 (43.3%) were annotated using various databases. Through DEGs analysis, it was found that 55 genes were upregulated and 18 were down-regulated in response to elevated CO2 treatment. Genes involved in the sugar metabolism and the related pathways were identified by Gene Ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Furthermore, three genes, LBGAE (Lycium barbarum UDP-glucuronate 4-epimerase), LBGALA (Lycium barbarum alpha-galactosidase) and LBMS (Lycium barbarum malate synthase), associated with sugar metabolism were identified and discussed with respect to the reduction in the total sugar levels along with the enzymes acid invertase (AI), sucrose synthase (SS) and sucrose phosphate synthase (SPS) of the sucrose metabolism. This study can provide gene sources for elucidating the molecular mechanisms of sugar metabolism in the fruit of goji berry under elevated CO2.

Effects and mechanism of total phenols of Magnolia officinalis combined with Maijunan Tablets on blood pressure of spontaneous hypertensive rats

ObjectiveMaijunan (MJA) Tablets is a protected variety of traditional Chinese medicine (TCM) consisted of Pueraria lobata, hydrochlorothiazide (HTCZ), Uncaria rhynchophylla (366:1:980) and excipient. In the present work, MJA was consisted of the total flavones of P. lobata, HCTZ and total alkaloids of U. rhynchophylla (40:11:75). The combination of MJA and the total phenols of Magnolia officinalis (M-MJA) was consisted of the total flavones of P. lobata, the total phenols of M. officinalis, HCTZ and the total alkaloids of U. rhynchophylla (40:40:11:75). The aim of this work was to examine the effect and mechanism of M-MJA on the blood pressure of spontaneous hypertensive rats (SHRs). MethodsAdult male SHRs were randomly divided into control group, MJA group (180 mg/kg·d), and the M-MJA group (218 mg/kg·d) (n = 5). SHRs were orally administered with M-MJA and MJA respectively once a day for 8 weeks, the blood pressure of SHRs was measured every two weeks, and the biochemical indicators related to blood pressures were detected at the last dosing. ResultsAfter oral administration of M-MJA to SHRs once a day for 8 weeks, the systolic and diastolic blood pressures of SHRs were deceased significantly. M-MJA affected renin-angiotensin-aldosterone system by decreasing the levels of Ren, Ang II and ALD, affected the endothelial function by decreasing the levels of ET-1 and 20-HETE, and increasing the level of eNOS, affected the oxidative stress by increasing the protein expression of Nrf2 and the activities of HO-1 and GSH-Px, and decreasing the protein expression of CYP2E1 and CYP4A, as well as the content of MDA. ConclusionThese results indicated that M-MJA could regulate the renin-angiotensin-aldosterone system, improve endothelial function, and inhibit CYP4A activity to reduce the production of 20-HETE, alleviate the oxidative stress disorder of the visceral organs, and eventually exert antihypertensive effect. Additionally, the anti-oxidant ability, regulating the renin-angiotensin-aldosterone system and improving endothelial function of M-MJA are more powerful than that of MJA, suggesting that M-MJA may have a better anti-hypertensive effect than MJA.

Effects of dodder total flavone on polycystic ovary syndrome rat models induced by DHEA combined HCG.

AimsExplore the effects of dodder total flavone on polycystic ovary syndrome (PCOS) rat models induced by dehydroepiandrosterone (DHEA) combined human chorionic gonadotropin (HCG).MethodsExcept the blank group, the rest of the rats were injected with DHEA 6 mg/100 g on the back of the neck and 1.5 IU HCG each day, for 21 consecutive days. On the 16th day of modeling, vaginal smear was performed to select the model rats, which were randomly divided into model group, dacin-35 group, large, middle and small dose dodder total flavonoids groups, and given the medicine for three weeks. At the end of the last administration, take samples, so as to calculate the ovaries and uterus indexes, measure serum LH/FSH ratio, P, PRL and INS levels, fixed the uterus and pancreas in 10% formalin solution and stained with HE to observe the morphological changes of the organs. And measure the expression of TNF-α and IGF-l proteins in ovaries by immunohistochemistry.ResultsCompared with the blank group, ovarian and uterine indexes, serum LH/FSH ratio, serum PRL and INS levels, ovary TNF-α and IGF-l protein expression were significantly increased, and significant pathological changes were observed in the uterine and pancreatic tissues in model group (P < 0.01). While the serum P level decreased significantly (P < 0.01), Compared with the model group, the ovarian and uterine indexes, serum LH/FSH ratio, serum P, PRL and INS levels, ovary TNF-α protein expression were significantly decreased in large, middle and small dose dodder total flavonoids groups (P < 0.01); The expression of IGF-1 protein was decreased and uterus pathological changes were improved in different extents (P < 0.01 or P < 0.05), pancreas pathological changes were improved significantly (P < 0.01).ConclusionPCOS rat models was successfully replicated. Dodder total flavone can protect PCOS rats induced by DHEA combined HCG by different action pathways.

Identification of Bioactive Compounds and Analysis of Inhibitory Potential of the Digestive Enzymes fromSyzygiumsp. Extracts

Diabetes and obesity represent major public health problems worldwide. High cost of medicines and drug treatments propose the research for less expensive alternatives, such as enzymatic inhibitors present in medicinal plants from natural sources. An example of such medicinal plant is the jambolanSyzygiumsp., which is referred to be hypoglycemic and efficient in weight loss. With this in mind, we identified the bioactive compounds fromSyzygiumsp. commercial teas and evaluated the inhibitory potential and the antioxidant activity of digestive enzymes from a simulated gastric fluid.Syzygiumsp. samples showed low percentages of enzymatic inhibition at 1 : 200 dilution. Antioxidant activity was significant, although it was not expressive of the contents of total phenolic compounds, tannins, flavonoids, flavones, and alkaloids. Maldi-Tof spectroscopy suggested the presence of luteolin inSyzygiumsp. samples. Molecular docking predicted that luteolin binds at theα-amylase catalytic site in a similar manner as acarbose, the carbohydrate inhibitor from the enzyme crystallographic structure. The phytochemical content and biological activity were distinct among samples from commercial teas. Thus, additional studies should be conducted to elucidate efficacy and safety ofSyzygiumsp. extracts, especiallyin vivoexperiments.Syzygiumsp. might be in the near future recommended as a medicinal plant in low cost diabetes and obesity treatments.

Analysis of antioxidant compounds and antioxidant activities from three materials of Lonicera

The buds and leaves of 3 varieties (lines) of Lonicera were used as the materials to measure the contents of total phenols, flavone, anthocyanin, luteoloside and chlorogenic acid, at the same time, to analysis and compare the capacity of flower buds of scavenging DPPH, O2·−, ·OH to the leaves. The results showed that the contents of total phenolics in the leaves of 3 varieties (lines) were the highest, and the content of anthocyanins was the lowest. The content of total phenols, flavone, anthocyanin, luteoloside in leaves were higher than that of in flower buds; The capacity of flower buds and leaves of scavenging DPPH and O2·− was higher than the capacity of scavenging ·OH. “Cuilei 109” buds and leaves had the highest antioxidant compounds and antioxidant activities.

Pollen Typhae Total Flavone Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway.

To test the hypothesis that the inhibition of endoplasmic reticulum (ER) stress-induced apoptosis in oxidized low-density lipoproteins (ox-LDL)-induced human aortic-vascular smooth muscle cells (HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein homologous protein (CHOP) signaling pathway by Pollen Typhae total flavone (PTF). Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups, including a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an HPTF group (70 μg/mL high ox-LDL+500 μg/mL PTF), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), and a LPTF group (70 μg/mL high ox-LDL+100 μg/mL PTF) in the first part; and a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), a shRNA group (transducted with PERK shRNA lentiviral particles), a scramble shRNA group (transducted with control shRNA lentiviral particles), an MPTF+ox-LDL+shRNA group (250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group (70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot, and their mRNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test cell viability, and the level of apoptosis was monitored by flow cytometry. The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis, which was attenuated in PTF treatment groups and shRNA groups. Moreover, the ox-LDL group had increased protein and mRNA levels of binding immunoglobulin protein and ER-associated apoptosis proteins, such as PERK, eIF2α, ATF4 and CHOP, which were attenuated in PTF treatment groups and shRNA groups. The apoptosis induced by ox-LDL had a strong relation to ER stress. The protective effect of PTF on ER stressinduced apoptosis was associated with inhibition of the PERK-eIF2α-ATF4-CHOP pathway, which might be a potential therapeutic strategy for enhancing the stability of atherosclerotic plaques.

Enrichment of total flavones and licochalcone A from licorice residues and its hypoglycemic activity

Industrial processing of glycyrrhizic leads to a lot of residues which are usually threw away randomly or used as feed. Therefore, the purpose of this study was to study licorice residues as a source of bioactive compounds with potentially applications. In this study, the enrichment and purification of total flavones from the licorice residues was achieved by using macroporous resins. The performances and separation characteristics of four selected macroporous resins with different chemical and physical properties were investigated. HPD-100 resin was the most effective, the content of total flavones increased from 50.94% in the original extract to 82.98% in the 80% ethanol fraction (a 1.63-fold increase). Further purification treatment by polyamide resin, licochalcone A with a purity of 80.28% was obtained in a 45% ethanol fraction, and a higher purity (>85%) of licochalcone A can be obtained by single crystallization operation. And hypoglycemic effect of the total flavones from licorice residues on high fat diet and STZ induced diabetic c57 mice was preliminary investigated. The results showed: the fasting blood glucose of mice in the low and medium dose total flavones group decreased significantly. The proposed technique is uncomplicated, easily managed, cost-effective, and environmentally friendly and is proper for both large-scale licorice residues application and waste management.

The role of total flavone of Camellia on cerebrovascular vasopasm after subarachnoid hemorrhage in rats

Background: This study was undertaken to explore the role of total flavones of Camellia (TFC) on the cerebrovascular dysfunction in rats after experimental subarachnoid hemorrhage (SAH). Materials and Methods: The contraction and dilation of cerebral basilar artery (BA), nitric oxide (NO) level, and nitric oxide synthase (NOS) activity in rat serum and the expression of endothelial NOS (eNOS) in cerebral vessels were measured. Furthermore, the effect of potassium channel blockers, endothelium removal, L-NG-nitroarginine methyl ester (L-NAME), or prostacyclin I2 (PG I2) production inhibitor on the response of isolated BA derived from normal rats was also evaluated to explore the underlying mechanism of vasodilation induced by total flavones. Results: The contraction of rat BA to U46619 markedly increased and the vasodilation to acetylcholine remarkably reduced after SAH. Interestingly, these vascular dysfunctions were profoundly ameliorated by pretreatment of TFC. Moreover, total flavones could induce a concentration-dependent relaxation in isolated BA from normal rats, which was obviously eliminated by co-application of potassium channel blockers, ChTx and Apamin, application of L-NAME, or endothelial removal. In addition, total flavones pretreatment obviously improved the expression of eNOS in BA, serum NO level, and NOS activity at 48 h after SAH. Conclusion: These findings revealed that TFC has protective effect on cerebrovascular dysfunction after SAH and demonstrated that the protection could be due to its upregulation of eNOS expression and activation of potassium channel.

Extraction of diverse polyphenols in relation with storage periods of Citrus paradisi CV. Shamber through HPLC-DAD technique using different solvent.

In this article, Citrus paradisi, (Shamber) an exceptional source of Vitamins A and C and full of nutrients, selected for extraction of diverse polyphenols including dietary flavonoids and essential flavonoids by HPLC-DAD technique using various solvents. These essential targeted compounds also analyze after keeping different storage periods and compare with fresh fruits for better efficacy of these compounds. The highest number of phenolic compounds including gallic acid, chlorogenic acid sinapic acid, ferulic acid, myricetin, quercetin, and kaempferol extracted in methanol solvent leading to the new compounds of tetra-O-methylscutellar and heptamethoxy flavone. The essential flavonoids determined by polyethersulfone filter and insoluble precipitation separated by the dimethyl sulfoxide. The results showed that the methanolic extraction exhibited higher essential flavonoids including nobiletin, sinensetin, tangeritin, and tetra-O-methylscutellarein and heptamethoxy flavone. The RP-HPLC analysis exposed the maximum number of nutritional flavonoids like naringin, hesperidin, total flavones, glycosyl. Moreover, it observed that dietary flavonoids and phenolic compounds of stored fruits were unaffected in 30days of storage periods while minor variations were pragmatic during 60-90days storage. The investigation revealed that C. paradisi proves to be the valuable resource of different phenolic compounds and flavonoids which are effective against various oxidative stresses in the human body.

LANNEA BARTERI ENGL. (ANACARDIACEAE) PLANT USED IN THE TREATMENT OF URINARY TRACT INFECTIONS IN IVORY COAST: BIOLOGICAL AND CHEMICAL STUDIES OF THE AQUEOUS EXTRACT

Objective: This research aims to evaluate the antibacterial activity and determine the chemical composition of the aqueous extract of the bark of Lannea barteri Engl. (DA) used in the traditional treatment of urinary tract infections in the Ivory Coast.Methods: The material is composed of DA, the bacterial strains of Pseudomonas aeruginosa and Acinetobacter baumannii, isolated from the urine of patients from different hospitals and subsequently stored. The qualitative analysis was performed using color-based detection tests and thin layer chromatography (TLC) reactions and the quantification of total phenols, flavonoids, flavone aglycones and anthocyanins using the method of Folin Ciocalteu. The method of diffusion on Mueller Hinton (MH) agar medium has been used for sensitivity tests. Results: The phytochemical screening of DA has revealed the presence of polyphenols, terpenes, and derivatives, coumarins, tannins, flavonoids, and alkaloids. Furthermore, the quantification of some polyphenols such as flavonoids, flavone aglycones, and anthocyanins was determined. The total polyphenols found was 0.757±0.003 mg/g MS representing respectively; 0.230±0.01 for flavonoids; 0.028±0.02 for flavone aglycones and 0.016±0.02 mg/g MS for anthocyanins. DA is bactericidal against Pseudomonas aeruginosa and Acinetobacter baumannii, which are mainly responsible for urinary tract infections.Conclusion: The bark of Lannea barteri Engl. (DA) is rich in flavonoids, flavone aglycones, and anthocyanins which are probably responsible for its antibacterial properties on Pseudomonas aeruginosa and Acinetobacter baumannii. This research thereby supports the use of this plant in the treatment of urinary tract infections.

Effects of PI3K/Akt-eNOS signaling pathway on total flavones in Clematis filamentosa post-conditioning alleviated of myocardial ischemia-reperfusion injury in rats

The aim of this paper was to study the effect of total flavones of Clematis filamentosa Dunn(TFCD) post-conditioning against myocardial ischemia-reperfusion injury (MIRI) and the role of PI3K/Akt-eNOS signaling pathway. Forty male SD rats were divided randomly into five groups: Sham group, model group (I/R), TFCD post-conditioning group (TFCD), TFCD post-condition-ing+LY294002 (a PI3K/Akt signaling pathway inhibitor) group (TFCD+LY), and LY294002 group (LY). At the end of reperfusion, hemodynamic parameters were recorded, morphology changes of myocardial tissue were evaluated by using HE staining, and myocardial infarct size were observed, blood samples were obtained to determine plasma activation of lactate dehydrogenase (LDH), creatine kinase (CK) nitric oxide (NO), endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), maleic dialdehyde (MDA) and glutathione peroxidase (GSH-Px). The expressions of Akt, p-Akt, eNOS and p-eNOS proteins were assessed by using Western blot, and eNOS and inducible nitric oxide synthase (iNOS) mRNA was measured by RT-PCR. The results showed that, compared with the model group, TFCD post-conditioning remarkably improved hemodynamics function and myocardial structure, reduced myocardial infarct size and enhanced the contents of NO, eNOS, SOD and GSH-Px, and decreased the contents of LDH, CK and MDA, increased the levels of phosphorylation of Akt and eNOS protein expression, eNOS and iNOS mRNA expression significantly(P＜0.05 or P＜0.01). These effects were inhibited by LY294002, a blocker of PI3K/Akt signaling pathway. The above experiments indicated that TFCD post-conditioning could significantly reduce MIRI in rats, the mechanism of which may be associated with increasing antioxidation, scavenging oxygen free radicals, regulating NO generation and activating PI3K/Akt-eNOS signaling pathway.

The protective mechanism underlying total flavones of Dracocephalum (TFD) effects on rat cerebral ischemia reperfusion injury

ABSTRACTPreviously, total flavones of Dracocephalum (TFD), derived from Dracocephalum, were found to exert protective effects in cerebral ischemia reperfusion injury (CIRI) in middle cerebral artery occlusion (MCAO) rat model. However, the mechanisms underlying these observed effects of TFD on MCAO-induced rats still remain to be determined. Therefore, the aim of this study was to examine whether TFD alleviated MCAO through mechanisms involving anti-inflammatory and anti-apoptotic using MCAO rats. The following parameters were measured: (1) percentage (%) area of brain infarction; (2) serum levels of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and (3) expression protein levels of caspase-3 and AMP-activated protein kinase (AMPK). Results showed that MCAO significantly increased the % area of brain infarction, while TFD administration in these animals markedly reduced % area of brain infarction. A significant elevation on serum levels of TNF-α and IL-6 was noted with MCAO which was markedly reduced by TFD. In addition, MCAO produced a significant rise in protein expression levels of caspase-3 and AMPK. In contrast, TFD markedly lowered protein expression levels of caspase-3 and AMPK. Data suggest that the protective effects of TFD in MCAO model animals may involve inhibition of inflammatory mediator release associated with apoptosis through down regulation of AMPK signaling pathway.

The protective mechanism underlying total flavones of Dracocephalum (TFD) effects on rat cerebral ischemia reperfusion injury

ABSTRACTPreviously, total flavones of Dracocephalum (TFD), derived from Dracocephalum, were found to exert protective effects in cerebral ischemia reperfusion injury (CIRI) in middle cerebral artery occlusion (MCAO) rat model. However, the mechanisms underlying these observed effects of TFD on MCAO-induced rats still remain to be determined. Therefore, the aim of this study was to examine whether TFD alleviated MCAO through mechanisms involving anti-inflammatory and anti-apoptotic using MCAO rats. The following parameters were measured: (1) percentage (%) area of brain infarction; (2) serum levels of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and (3) expression protein levels of caspase-3 and AMP-activated protein kinase (AMPK). Results showed that MCAO significantly increased the % area of brain infarction, while TFD administration in these animals markedly reduced % area of brain infarction. A significant elevation on serum levels of TNF-α and IL-6 was noted with MCAO which was markedly reduced by TFD. In addition, MCAO produced a significant rise in protein expression levels of caspase-3 and AMPK. In contrast, TFD markedly lowered protein expression levels of caspase-3 and AMPK. Data suggest that the protective effects of TFD in MCAO model animals may involve inhibition of inflammatory mediator release associated with apoptosis through down regulation of AMPK signaling pathway.

Estimation of daily intake of flavonoids and major food sources in middle-aged Australian men and women

Flavonoid consumption has reported health benefits such as reducing cardiovascular disease risk factors, improving endothelial function, and delaying age-related cognitive decline. However, there are little dietary intake data for Australians, which limit our ability to make dietary recommendations to increase intakes to a level where health benefits are seen. The aim of this cross-sectional study was to determine the intake of flavonoids, flavonoid classes, and flavonoid subclasses of 1183 Australians aged 39 to 65 years using a validated 215-item food frequency questionnaire. Based on limited global flavonoid intake data, flavanols are the major dietary flavonoid and are found predominantly in tea and cocoa. As Australians are large tea drinkers, we anticipated that flavanols would be the major flavonoid in the Australian diet. The flavonoid content of foods was determined using a combination of the United States Department of Agriculture Databases and the Phenol-Explorer Database. One-way analysis of variance was undertaken to examine differences between flavonoid intake between men and women. Total flavonoid intake was 626 ± 579 mg/d. Men and women consumed 566 ± 559 mg and 660 ± 588 mg of total flavonoids per day, respectively. Thearubigin accounted for 58% of the flavonoid intake. Women consumed more total flavonoids, thearubigins (both P < .01), anthocyanidins (P < .0001), flavan-3-ols, flavones, and flavonols (all P < .05) than men, whereas men consumed more flavanones than women (P = .01). There was no difference between sexes for the consumption of isoflavones. The data indicated that flavan-3-ols, predominantly thearubigin from tea, were the main flavonoid consumed by Australians. This information contributes to population flavonoid intakes, which should be considered when exploring flavonoid and health relationships.

Total flavones of fermentation broth by co-culture of Coprinus comatus and Morchella esculenta induces an anti-inflammatory effect on LPS-stimulated RAW264.7 macrophages cells via the MAPK signaling pathway

The inflammatory cellular model of RAW264.7 cells induced by lipopolysaccharide (LPS) has always been used to investigate the effect of anti-inflammatory agents in vitro. In the present study, the anti-inflammatory activity of total flavones extracted from the fermentation broth of the co-culture of Coprinus comatus and Morchella esculenta (MCF-F), and its potential molecular mechanism in LPS-challenged RAW264.7 macrophage cells were investigated. The data revealed that MCF-F exhibited anti-inflammatory activity in LPS-stimulated RAW264.7 cells. At the same time, MCF-F was less cytotoxic under a concentration of 16 μg/ml in RAW264.7 cells. The anti-inflammatory activity of MCF-F was detected using the Griess method and ELISA assay, and the results well-corroborated with the observed decrease in expression in pro-inflammatory mediators, including nitric oxide, tumor necrosis factor-α and inteleukin-1β (IL-1β). In addition, the expression of inducible NO synthase (iNOS) and cyclooxygenase2 (COX-2) were confirmed by RT-PCR and western blot, and it was found that both mRNA and protein levels were downregulated after MCF-F treatment. The data also revealed that MCF-F downregulated the phosphorylation of JNK, ERK and P38 MAPK. Collectively, these results lead to the conclusion that MCF-F exerts an anti-inflammatory effect against LPS-challenged RAW264.7 cells via the MAPK pathway.

Microwave Irradiation Enhances the Germination Rate of Tartary Buckwheat and Content of Some Compounds in Its Sprouts

Tartary buckwheat (Fagopyrum tataricum) seeds were irradiated with microwaves at various power levels of 200, 400, 600 and 800 W for 10 or 30 s. The irradiated grains were germinated for 3, 5, and 7 days and harvested. The germination rate of the tartary buckwheat seeds and contents of some compounds in the sprouts were investigated. The results showed that the exposure to 600 W microwaves for 10 s resulted in the highest final germination rate after 7 days of germination, which was 2 times that of the control. The exposure of seeds to 800 W for 30 s showed the lowest germination rate (approximately 10%), which decreased by 87% compared with the control (p<0.05). The exposure at 600 W for 30 s stimulated the total flavones content, reduced the sugar and soluble protein contents, and increased the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The highest free amino acid content (11 mg/g) was observed in 5-day sprouts exposed to 800 W for 10 s. Moreover, the microwave treatment had a positive effect on the catalase (CAT) and superoxide dismutase (SOD) activity.

Transcriptomics and metabonomics of the anti-aging properties of total flavones of Epimedium in relation to lipid metabolism

Ethnopharmacological relevanceTotal flavones of Epimedium (TFE) is the main active ingredient in Herba Epimedii, which is a well-known Chinese herbal medicine that is widely used to treat certain age-related diseases in oriental countries. Aim of the studyThe aim of this work was to investigate the anti-aging properties of TFE related to lipid metabolism. Materials and methodsBoth transcriptomics and metabonomics were applied in this work to investigate the anti-aging properties of TFE. Microarray and LC–MS analysis were conducted on liver samples of three groups of rats, including young (4 months), old (24 months), and old rats administrated TFE. ResultsTranscriptomics analysis highlighted 287 transcripts related to the anti-aging effect of TFE, in which the expression ratio of 18 genes regulating lipid metabolism, including HMGCS1 and NR1H3, returned to normal levels after TFE treatment. In addition, 24 aging-related metabolites were discovered in a metabonomics study, and 15 of these were structurally identified, including palmitic amide, linoleamide, and oleamide. Bioinformatics and integral data analysis on the results of the transcriptomics and metabonomics suggest the involvement of 12 key metabolic pathways, half of which are highly related to lipid metabolism. ConclusionsThis study demonstrates that the role played by TFE in the lipid metabolism of aging rats is multifaceted and multi-layered.