Improvement effects and mechanism of total flavonoids of Bidens pilosa on lipopolysaccharide-induced neuroin-flammation in mice / 中国药房

OBJECTIVE To investigate the effect and mechanism of total flavonoids of Bidens pilosa L. （TFB） on lipopolysaccharide （LPS）-induced neuroinflammation in mice. METHODS Fifty C57BL/6 mice were randomly divided into normal control group， LPS group and TFB low-dose， medium-dose and high-dose groups， with 10 mice in each group. TFB low-dose， medium-dose and high-dose groups were given TFB solution intragastrically at 60， 120 and 240 mg/kg， and the normal control group and LPS group were given corresponding volume of normal saline， once a day， for consecutive 21 d. From the 15th day of administration， except for the normal control group， other groups were given LPS （400 μg/kg） intraperitoneally for 7 consecutive days to establish neuroinflammatory model. Brain tissues were taken under anesthesia 4 h after the final administration. The morphological changes of neuronal cells in mice were observed； the contents of nitric oxide （NO）， tumor necrosis factor α （TNF- α）， interleukin-1β （IL-1β）， IL-6 and IL-10 were measured， and the expressions of inflammatory pathway-related proteins [inducible NO synthase （iNOS）， cyclooxygenase-2 （COX-2）， myeloid differentiation factor 88 （Myd88） and protein kinase C （PKC）] were measured in the brain tissues of mice. RESULTS Compared with the normal control group， the neuronal arrangement in the hippocampal region of the brain tissue of mice in the LPS group was sparsely disorganized， with a large number of neuronal fixations and shrunken nuclei； the contents of TNF-α， IL-1β， IL-6 and NO in the brain tissue were significantly increased， the contents of IL-10 were significantly decreased， and the relative expressions of iNOS， COX-2， Myd88 and PKC proteins were significantly increased （P＜0.05）. Compared with the LPS group， the neuronal pathological changes in the brain tissue of mice in the TFB low-dose， medium-dose and high-dose groups were 202014810） significantly improved， and the changes of the above indices in the brain tissue were significantly reversed （P＜0.05） CONCLUSIONS TFB has an inhibitory effect on E-mail：pangxjun@163.com neuroinflammation， and its mechanism of action may be related to down-regulation of the expressions of inflammatory pathway-related proteins iNOS， COX-2， Myd88 and PKC， and reduction of inflammatory factors release.

Study on the pharmacodynamics and mechanism of Blumea balsamifera total flavonoids against acute myocardial infarction model rats / 中国药房

OBJECTIVE To study pharmacodynamics and potential mechanism of Blumea balsamifera total flavonoids against acute myocardial infarction （AMI） model rats. METHODS AMI model of SD rats was established by ligating anterior descending branch of left coronary artery. Fifty model rats were randomly divided into model group （0.8% carboxymethyl cellulose solution）， positive control group （Compound danshen tablet， 300 mg/kg）， B. balsamifera total flavonoids low-dose， medium-dose and high- dose groups （3， 10， 30 mg/kg）， with 10 rats in each group. Other 10 rats were included in sham operation group （0.8% carboxymethyl cellulose solution）. After 1 day of surgery， they were given relevant medicine 3 mL/kg intragastrically， once a day， for 4 consecutive weeks. The changes of S-T segment were recorded before and after operation， after weekly intragastric administration. The hemodynamic indexes of rats were all determined， i.e. systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， left ventricular end diastolic blood pressure （LVEDP）， maximal left ventricular pressure rising rate （+LVdp/dtmax）， maximal left ventricular pressure decreasing rate （－LVdp/ dtmax）. The levels of serum myocardial enzymes [lactate dehydrogenase （LDH）， creatine kinase isoenzyme-MB （CK-MB）] and inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β] were determined. The myocardial infarction rate of rats and the phosphorylation levels of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） proteins in myocardial tissue were determined. RESULTS Compared with model group， S-T segments of electrocardiogram were all decreased significantly in administration groups （P＜0.05）. SBP， DBP， MAP， LVSP， +LVdp/dtmax， －LVdp/dtmax， and ratio of p-PI3KTyr607/ PI3K， p-AktThr308/Akt， p-Aktser473/Akt were increased significantly in B. balsamifera total flavonoids medium-dose and high-dose groups （P＜0.05）. The levels of LVEDP， serum myocardial enzymes and inflammatory factors， myocardial infarction rate were all decreased significantly （P＜0.05）. CONCLUSIONS balsamifera total flavonoids can improve cardiac function of AMI model rats， the mechanism of which may be associated with inhibiting the expression of inflammatory factor and activating PI3K/Akt signaling pathway.

Inhibition of total flavonoids from Abelmoschus Manihot on cytochrome P450 / 中国药科大学学报

@#To investigate the influential mechanism of total flavonoids from Abelmoschus Manihot (HKZ) on cytochrome P450 (CYP450) isoforms in human liver microsomes and to verify its effect on the most significantly inhibited subtype CYP2C9 in rats.The inhibitory effects of HKZ on human CYP3A4, CYP2C9, CYP2C19, CYP2E1, CYP1A2 and CYP2D6 were evaluated through the cocktail method using ultra-performance liquid chromatography tandem mass spectrometry, then its inhibitory mechanism was investigated and kinetic parameters of enzyme inhibition were calculated By comparing the pharmacokinetic behaviors of tolbutamide after single or multiple administration of 200 mg/kg HKZ and equal dose of CMC-Na in rats, the effects of HKZ on CYP2C11 enzyme (CYP2C9 isoenzyme) was estimated.The results indicated the significant inhibitory effect of HKZ on CYP2C9 and CYP2E1 with IC50 of 3.22 and 8.64 μg/mL, respectively. Also, it showed certain inhibitory ability on other isoforms with IC50 of 20-30 μg/mL.As demonstrated, HKZ may not be a time-dependent inhibitor which competitively inhibited CYP2E1 and CYP2C9 with Ki of 3.84 and 6.33 μg/mL.In contrast, it showed noncompetitive inhibition on CYP3A4 mediated testosterone-6β-hydroxylation and midazolam-4-hydroxylation reaction with Ki of 7.37 and 3.32 μg/mL.It was also a noncompetitive inhibitor of CYP1A2, CYP2D6 and CYPC219 with Ki values of 8.66, 11.49 and 21.94 μg/mL. HKZ did not change the pharmacokinetic parameters of CYP2C11 probe substrate tolbutamide in rat, but it affected the AUC0-t, cmax of 4-hydroxytolubutamide (P < 0.05). Therefore, drug-drug interaction mediated by CYP450 should be considered in clinical study.

Effect and Mechanism of Cuscutae Semen Total Flavonoids Combined with Tripterygium wilfordii Polyglycoside Tablets on Ovarian Germline Stem Cells of Physiological Mice by Notch Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Cuscutae Semen total flavonoids combined with Tripterygium wilfordii polyglycoside tablets （TWPT） on ovarian germline stem cells of female physiological mice through neurogenic locus notch homolog （Notch） signaling pathway. MethodSixty female Kunming mice （5 weeks old） were randomly divided into normal group， Tripterygium wilfordii polyglycoside tablets low-， high-dose groups （13.65 mg·kg-1·d-1 and 27.3 mg·kg-1·d-1， 1 and 2 times clinical equivalent dose）， Cuscutae Semen total flavonoids low- and high-dose groups （150 mg·kg-1·d-1 and 300 mg·kg-1·d-1）， and combination group （13.65 mg·kg-1·d-1 TWPT and 150 mg·kg-1·d-1 Cuscutae Semen total flavonoids）， with 10 in each group. After 3 weeks of continuous administration， the uterus/brain and ovarian/brain indexes were calculated， and the pathological changes of ovarian tissue were observed under light microscope. The content of estradiol in serum was determined by enzyme linked immunosorbent assay （ELISA）. Immunofluorescence assay was performed to observe the expressions of germline stem cell markers in ovarian epithelium， including mouse vasa homologue （Mvh）， octamer-binding transcription factor 4 （Oct4）， tyrosine-protein kinase receptor （c-kit）， Nanog， Notch signaling pathway molecules， neurogenic locus notch homolog protein 1 （Notch1）， hes family BHLH transcription factor 1（Hes1）， and jagged canonical Notch ligand 1 （JAG1）. ResultCompared with the normal group， low and high doses of TWPT had no significant effect on the uterus/brain and ovary/brain indexes and the uterus and ovary morphologies of mice， while only the number of atretic follicles was increased （P<0.01）. The expressions of ovarian germline stem cell markers and Notch signaling pathway molecules had a decreasing trend in TWPT low-dose group， while the expressions of Mvh， c-kit， and Nanog were down-regulated （P<0.05， P<0.01） and the expressions of Notch1 and Hes1 were also reduced （P<0.01） in TWPT high-dose group. However， the above indexes were increased in Cuscutae Semen total flavonoids low-dose group （P<0.05， P<0.01）. Compared with the low does of TWPT group， the combination group had a decrease in the increased number of atretic follicles （P<0.01）， an improvement in the down-regulated expressions of Mvh and Nanog （P<0.01）， and an increase in the expressions of Notch1 and Hes1 （P<0.05， P<0.01）. ConclusionOvarian germline stem cells are the source target of the reproductive toxicity of TWPT. Cuscutae Semen total flavonoids participate in the regulation of the germline stem cell pathways to alleviate the reproductive toxicity caused by TWPT， and its mechanism of action may be related to the Notch signaling pathway.

Quality difference of wild Lysimachiae Herba in the source areas of Sichuan, Chongqing and Guizhou / 国际中医中药杂志

Objective:To determine the contents of quercetin, kaempferol, total flavonoids and extracts in 52 samples of Lysimachiae Herba collected from different origins; To analyze the quality differences of Lysimachiae Herba among different producing areas. Methods:The quercetin and kaempferol contents of the Lysimachiae Herba from Guizhou Province, Sichuan Province and Chongqing were determined by HPLC, and the total flavonoids were determined by Symergy HTX microplate reader. Results:The total content of quercetin and kaempferol in 52 samples was among 0.146 2-2.517 0 mg/g, with an average content of 0.872 6 mg/g, among which the average content of Sichuan was 1.073 2 mg/g, that of Guizhou was 0.705 4 mg/g, and that of Chongqing was 0.865 1 mg/g. Among them, 20 samples reached the standard of the Chinese Pharmacopoeia. The average content of the samples that met the standard was 1.439 7 mg/g. The compliance rate of samples collected in Guizhou, Sichuan and Chongqing reached 12.5%, 62.5%, and 38.8% respectively. The total flavonoid content of 52 samples was among 0.994 2- 3.866 4 mg/g, and 52 samples were in conformity with the ethanol hot extract standard of the Chinese Pharmacopoeia. Conclusions:The total contents of quercetin and kaempferol from different sources in Sichuan, Guizhou and Chongqing are quite different, and the total contents of quercetin and kaempferol collected from the same district and county are also quite different, and the compliance rate is low. There are great differences in total flavonoids in different producing areas and different populations of Lysimachiae Herba samples collected in the field.

Effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/PPARγ pathway in arrhythmic rats / 中国中药杂志

This paper aimed to investigate the effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/peroxisome proliferator-activated receptor γ(PPARγ) pathway in arrhythmic rats. SD rats were randomly divided into a control group, a model group, a low-dose(20 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a medium-dose(40 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a high-dose(80 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a propranolol hydrochloride(2 mg·kg~(-1)) group, with 12 rats in each group. Except the control group, rats in other groups were prepared as models of arrhythmia by sublingual injection of 1 mL·kg~(-1) of 0.002% aconitine. After grouping and intervention with drugs, the arrhythmia, myocardial cells apoptosis, myocardial tissue glutathione peroxidase(GSH-Px), catalase(CAT), malondialdehyde(MDA), serum interleukin-6(IL-6), prostaglandin E2(PGE2) levels, myocardial tissue apoptosis, and Wnt/β-catenin/PPARγ pathway-related protein expression of rats in each group were measured. As compared with the control group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA levels in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels increased significantly in the model group, whereas the GSH-Px and CAT levels, and Bcl-2 and PPARγ protein expression levels in myocardial tissues reduced significantly. As compared with the model group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA leve in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels reduced in the drug intervention groups, whereas the GSH-Px and CAT levels and Bcl-2 and PPARγ protein expression levels in myocardial tissues increased. The groups of total flavonoids of buckwheat flower and leaf were in a dose-dependent manner. There was no significant difference in the levels of each index in rats between the propranolol hydrochloride group and the high-dose group of total flavonoids of buckwheat flower and leaf. The total flavonoids of buckwheat flower and leaf inhibit the activation of Wnt/β-catenin pathway, up-regulate the expression of PPARγ, reduce oxidative stress and inflammatory damage in myocardial tissues of arrhythmic rats, reduce myocardial cell apoptosis, and improve the symptoms of arrhythmia in rats.

Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway / 中国中药杂志

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

Mechanism of total flavonoids of Rhododendra simsii in alleviating ischemic brain injury / 中国中药杂志

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.

Crystallization transformation of amorphous extracts of traditional Chinese medicine and its effect on dissolution behavior — Taking total flavonoids from Pueraria lobata as an example / 中国药科大学学报

@#In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.

Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition / 中国中药杂志

To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. The experimental results showed that VFD and DS basically kept the original color of MFOEU. The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. Considering the color of MFOEU, the suitable drying methods were DS and VFD. Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas.

Physiochemical and nutritional evaluation of whole kumquat fruits powder and its protective effect on thyroid hormones and blood sugar levels in diabetic rats / Avaliação físico-química e nutricional de frutas inteiras de kumquat em pó e seu efeito protetor sobre os hormônios da tireoide e os níveis de açúcar no sangue em ratos diabéticos

The present study was conducted to evaluate the chemical composition, antioxidant activity and hypoglycemic effects of whole kumquat (Ku) powder in diabetic rats fed a high-fat-high-cholesterol (HFHC) diet. The antioxidant activities were evaluated using stable 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical scavenging method, 2,2'-azinobis (3-ethyl benzo thiazoline-6-sulphonic acid) radical cation (ABTS) and Ferric reducing antioxidant power (FRAP). Total phenolic content was (51.85 mg GAE/g) and total flavonoid content was (0.24 mg Cateachin Equivalent, CE/g). DPPH and ABTS values were 3.32 and 3.98 mg Trolox equivalent (TE)/g where FRAP value was 3.00 mM Fe²+/kg dry material. A total of 90 albino rats were used in the present study. Rats group were as follows: normal diet; normal treated (2, 4, and 6% Ku.), diabetic rats (non-treated), diabetic + HFHC diet (non-treated), HFHC (non-treated), Diabetic (treated), HFHC (treated) and Diabetic + HFHC (treated). The diets were followed for 8 weeks. Blood samples were collected at the end of the experiment. Serum glucose was recorded and thyroid hormones (T4, Thyroxine and T3, Triiodothyronine) were conducted. Diet supplemented with Kumquat at different concentrations have a hypoglycemic effect and improve the thyroid hormones of both diabetic rats and HFHC diabetic rats.

O presente estudo foi conduzido para avaliar a composição química, a atividade antioxidante e os efeitos hipoglicêmicos do pó de kumquat (Ku) em ratos diabéticos alimentados com uma dieta rica em gordura e colesterol (HFHC). As atividades antioxidantes foram avaliadas usando o método de eliminação de radicais livres de 1,1-difenil 2-picrilhidrazil (DPPH), 2,2'-azinobis (ácido 3-etilbenzotiazolina-6-sulfônico) radical cátion (ABTS) e antioxidante redutor férrico potência (FRAP). O conteúdo fenólico total foi (51,85 mg GAE / g) e o conteúdo total de flavonoides foi (0,24 mg Cateachin Equivalent, CE / g). Os valores de DPPH e ABTS foram 3,32 e 3,98 mg equivalente de Trolox (TE) / g, em que o valor de FRAP foi de 3,00 mM Fe²+ / kg de material seco. Um total de 90 ratos albinos foi usado no presente estudo. O grupo dos ratos foi o seguinte: dieta normal: tratados normais (2, 4 e 6% Ku.), ratos diabéticos (não tratados), diabéticos + dieta HFHC (não tratados), HFHC (não tratados), diabéticos (tratados), HFHC (tratados) e diabéticos + HFHC (tratados). As dietas foram seguidas por 8 semanas. Amostras de sangue foram coletadas ao final do experimento. A glicose sérica foi registrada e os hormônios tireoidianos (T4, Tiroxina e T3, Triiodotironina) foram conduzidos. A dieta suplementada com kumquat em diferentes concentrações tem um efeito hipoglicêmico e melhora os hormônios tireoidianos tanto de ratos diabéticos quanto de ratos diabéticos com HFHC.

Physiochemical and nutritional evaluation of whole kumquat fruits powder and its protective effect on thyroid hormones and blood sugar levels in diabetic rats

Abstract The present study was conducted to evaluate the chemical composition, antioxidant activity and hypoglycemic effects of whole kumquat (Ku) powder in diabetic rats fed a high-fat-high-cholesterol (HFHC) diet. The antioxidant activities were evaluated using stable 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical scavenging method, 2,2´-azinobis (3-ethyl benzo thiazoline-6-sulphonic acid) radical cation (ABTS) and Ferric reducing antioxidant power (FRAP). Total phenolic content was (51.85 mg GAE/g) and total flavonoid content was (0.24 mg Cateachin Equivalent, CE/g). DPPH and ABTS values were 3.32 and 3.98 mg Trolox equivalent (TE)/g where FRAP value was 3.00 mM Fe2+/kg dry material. A total of 90 albino rats were used in the present study. Rats group were as follows: normal diet; normal treated (2, 4, and 6% Ku.), diabetic rats (non-treated), diabetic + HFHC diet (non-treated), HFHC (non-treated), Diabetic (treated), HFHC (treated) and Diabetic + HFHC (treated). The diets were followed for 8 weeks. Blood samples were collected at the end of the experiment. Serum glucose was recorded and thyroid hormones (T4, Thyroxine and T3, Triiodothyronine) were conducted. Diet supplemented with Kumquat at different concentrations have a hypoglycemic effect and improve the thyroid hormones of both diabetic rats and HFHC diabetic rats.

Resumo O presente estudo foi conduzido para avaliar a composição química, a atividade antioxidante e os efeitos hipoglicêmicos do pó de kumquat (Ku) em ratos diabéticos alimentados com uma dieta rica em gordura e colesterol (HFHC). As atividades antioxidantes foram avaliadas usando o método de eliminação de radicais livres de 1,1-difenil 2-picrilhidrazil (DPPH), 2,2-azinobis (ácido 3-etilbenzotiazolina-6-sulfônico) radical cátion (ABTS) e antioxidante redutor férrico potência (FRAP). O conteúdo fenólico total foi (51,85 mg GAE / g) e o conteúdo total de flavonoides foi (0,24 mg Cateachin Equivalent, CE / g). Os valores de DPPH e ABTS foram 3,32 e 3,98 mg equivalente de Trolox (TE) / g, em que o valor de FRAP foi de 3,00 mM Fe2 + / kg de material seco. Um total de 90 ratos albinos foi usado no presente estudo. O grupo dos ratos foi o seguinte: dieta normal: tratados normais (2, 4 e 6% Ku.), ratos diabéticos (não tratados), diabéticos + dieta HFHC (não tratados), HFHC (não tratados), diabéticos (tratados), HFHC (tratados) e diabéticos + HFHC (tratados). As dietas foram seguidas por 8 semanas. Amostras de sangue foram coletadas ao final do experimento. A glicose sérica foi registrada e os hormônios tireoidianos (T4, Tiroxina e T3, Triiodotironina) foram conduzidos. A dieta suplementada com kumquat em diferentes concentrações tem um efeito hipoglicêmico e melhora os hormônios tireoidianos tanto de ratos diabéticos quanto de ratos diabéticos com HFHC.

Physiochemical and nutritional evaluation of whole kumquat fruits powder and its protective effect on thyroid hormones and blood sugar levels in diabetic rats / Avaliação físico-química e nutricional de frutas inteiras de kumquat em pó e seu efeito protetor sobre os hormônios da tireoide e os níveis de açúcar no sangue em ratos diabéticos

Abstract The present study was conducted to evaluate the chemical composition, antioxidant activity and hypoglycemic effects of whole kumquat (Ku) powder in diabetic rats fed a high-fat-high-cholesterol (HFHC) diet. The antioxidant activities were evaluated using stable 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical scavenging method, 2,2´-azinobis (3-ethyl benzo thiazoline-6-sulphonic acid) radical cation (ABTS) and Ferric reducing antioxidant power (FRAP). Total phenolic content was (51.85 mg GAE/g) and total flavonoid content was (0.24 mg Cateachin Equivalent, CE/g). DPPH and ABTS values were 3.32 and 3.98 mg Trolox equivalent (TE)/g where FRAP value was 3.00 mM Fe2+/kg dry material. A total of 90 albino rats were used in the present study. Rats group were as follows: normal diet; normal treated (2, 4, and 6% Ku.), diabetic rats (non-treated), diabetic + HFHC diet (non-treated), HFHC (non-treated), Diabetic (treated), HFHC (treated) and Diabetic + HFHC (treated). The diets were followed for 8 weeks. Blood samples were collected at the end of the experiment. Serum glucose was recorded and thyroid hormones (T4, Thyroxine and T3, Triiodothyronine) were conducted. Diet supplemented with Kumquat at different concentrations have a hypoglycemic effect and improve the thyroid hormones of both diabetic rats and HFHC diabetic rats.

Resumo O presente estudo foi conduzido para avaliar a composição química, a atividade antioxidante e os efeitos hipoglicêmicos do pó de kumquat (Ku) em ratos diabéticos alimentados com uma dieta rica em gordura e colesterol (HFHC). As atividades antioxidantes foram avaliadas usando o método de eliminação de radicais livres de 1,1-difenil 2-picrilhidrazil (DPPH), 2,2'-azinobis (ácido 3-etilbenzotiazolina-6-sulfônico) radical cátion (ABTS) e antioxidante redutor férrico potência (FRAP). O conteúdo fenólico total foi (51,85 mg GAE / g) e o conteúdo total de flavonoides foi (0,24 mg Cateachin Equivalent, CE / g). Os valores de DPPH e ABTS foram 3,32 e 3,98 mg equivalente de Trolox (TE) / g, em que o valor de FRAP foi de 3,00 mM Fe2 + / kg de material seco. Um total de 90 ratos albinos foi usado ​​no presente estudo. O grupo dos ratos foi o seguinte: dieta normal: tratados normais (2, 4 e 6% Ku.), ratos diabéticos (não tratados), diabéticos + dieta HFHC (não tratados), HFHC (não tratados), diabéticos (tratados), HFHC (tratados) e diabéticos + HFHC (tratados). As dietas foram seguidas por 8 semanas. Amostras de sangue foram coletadas ao final do experimento. A glicose sérica foi registrada e os hormônios tireoidianos (T4, Tiroxina e T3, Triiodotironina) foram conduzidos. A dieta suplementada com kumquat em diferentes concentrações tem um efeito hipoglicêmico e melhora os hormônios tireoidianos tanto de ratos diabéticos quanto de ratos diabéticos com HFHC.

Screening of active ingredients for estrogenic effect of total flavonoids from Cuscutae Semen / 中国药房

OBJECTIVE To screen the active ingredient with estrogenic effect from total flavonoids of Cuscutae Semen. METHODS The estrogenic effect of total flavonoids from 10 batches of Cuscutae Semen was evaluated with mouse uterus coefficient and endometrial thickness as evaluation indexes， establish its fingerprint and calibrate the common peak. Common peak and spectrum-effect relationship of the above two indicators were analyzed by bivariate relationship analysis and grey correlation analysis to screen active components with estrogenic effect. UPLC-Q-TOF-MS technology was used to characterize the active components. RESULTS The estrogenic effect of total flavonoids from 10 batches of Cuscutae Semen was good. Twenty-eight and thirty-three common peaks of total flavonoids in Cuscutae Semen were obtained in the positive and negative ion modes respectively. The constituents represented by peaks 7，10，12-16，26 in positive ion mode and peaks 2，5，8，9，12，16，19，22-26 in negative ion mode were highly correlated with the estrogenic effect of total flavonoids from Cuscutae Semen. Further identification showed that the active substances with estrogenic effect from the total flavonoids of Cuscutae Semen were 5，7，3′， 4′-tetramethoxyflavone， 6- O-（trans） p-coumarin-furanfructose-（2→1）-glucopyranoside， rutin， kaempferol-3，7-diglucoside， apigenin-7-O-glucoside， hyperoside， baicalin， quercitin， quercetin， apigenin， kaempferol， isorhamnetin， rhododendron， isoquercetin， kaempferol-3-furan arabinoside， 2，6-octadecanediacetylic acid. CONCLUSIONS A total of 16 chemical components with estrogenic effect are screened from total flavonoids of Cuscutae Semen in the study， which can provide reference for the development of phytoestrogens.

Quality evaluation of total flavonoids of Lamiophlomis rotata from different producing areas / 中国药房

OBJECTIVE To evaluate the quality of total flavonoids of Lamiophlomis rotata from different producing areas. METHODS Total flavonoids of S1-S15 batches of L. rotata from different producing areas were extracted by percolation and purified by polyamide column. The content of total flavonoids was determined by UV spectrophotometry， and its purity was calculated. HPLC fingerprint chromatograms and control fingerprint of total flavonoids from 15 batches of L. rotata were established with Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 version）. Their similarities were analyzed. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were used to evaluate the quality of total flavonoids from 15 batches of L. rotata， and the main components which affected the quality of total flavonoids were analyzed. RESULTS The purities of total flavonoids from 15 batches of L. rotata were 55.82%-94.12%， with an average value of 77.72%； a total of five common peaks were identified in the fingerprint， and No. 3 peak was luteolin； the similarities between the fingerprint of each batch of samples and the control fingerprint were 0.925-1.000. By cluster analysis， S1 and S3-S9 were clustered into the first class， which were samples from Qinghai Province and Tibet Autonomous Region. S14 and S15 were clustered into the second class， which were samples from Yunnan Province. S10-S13 were clustered into the third class， which were all samples from Sichuan Province. S2 was clustered into the fourth class. The principal component analysis showed that the qualities of samples from the first and fourth classes were better； peaks 2， 3 and 5 were identified as the main components that caused the differences among different batches of samples by orthogonal partial least squares-discriminant analysis. CONCLUSIONS The qualities of total flavonoids of L. rotata from Qinghai Province and Tibet Autonomous Region are better.

Comprehensive evaluation of the quality of Eriobotrya japonica leaves from different producing areas based on entropy weight TOPSIS method / 中国药房

OBJECTIVE To comprehensively evaluate the quality of Eriobotrya japonica leaves from different producing areas. METHODS The contents of alcohol-soluble extracts were determined by hot-dipping method using 30 batches of E. japonica leaves from different producing areas as samples. The contents of total flavonoids and total triterpene acids were determined by ultraviolet spectrophotometry. The contents of five kinds of triterpenic acids （euscaphic acid，crataegolic acid，corosolic acid，oleanolic acid and ursolic acid） were determined by HPLC. The quality of E. japonica leaves from different producing areas was comprehensively evaluated by using entropy weight technique for order preference by similarity to an ideal solution （TOPSIS）. The bivariate correlation analysis of E. japonica leaves was conducted by SPSS 22.0 software in terms of weight， comprehensive evaluation value， the content of alcohol-soluble extract， the contents of total flavonoids， total triterpene acids and five triterpenic acids. RESULTS The contents of alcohol-soluble extract in 30 batches of E. japonica leaves were （24.56±0.08）%-（34.85±0.13）%； the contents of total flavonoids were （4.69±0.11）-（14.23±0.27） mg/g； the contents of total triterpene acid were （27.58±0.59）- （63.95±1.27） mg/g； the contents of euscaphic acid， crataegolic acid， corosolic acid， oleanolic acid and ursolic acid were （0.728± 0.011）-（6.064±0.063）， （0.526±0.013）-（3.245±0.022）， （1.222±0.025）-（8.807±0.094）， （0.856±0.021）-（2.931±0.075）， （4.704±0.087）-（11.806±0.283） mg/g， respectively. The analysis result of entropy weight TOPSIS method showed that the top three samples with comprehensive evaluation values （No.Kjcx-5） were S14 （Huotian Town， Yunxiao County， Zhangzhou，Fujian）， S19 （Qinnan District， Qinzhou， Guangxi） and S29 （Guoyang County， Bozhou， Anhui）. Comprehensive evaluation 0596-2559522。E-mail：jxrcwxp@163.com of E. japonica leaves was positively correlated with the contents of five kinds of triterpenic acids， such as euscaphic acid， crataegolic acid， corosolic acid， oleanolic acid and ursolic acid （P＜0.01）. The weight of E. japonica leaves was positively correlated with the comprehensive evaluation value （P＜0.01）. CONCLUSIONS The qualities of E. japonica leaves from different producing areas are very different. Among them， the qualities of E. japonica leaves from Huotian Town， Yunxiao County， Zhangzhou of Fujian， Qinzhou Qinnan District of Guangxi， and Bozhou Guoyang County of Anhui are relatively better. The weight of E. japonica leaves is positively correlated with their quality.

Total flavonoids of Dracocephalum moldavica L. inhibit oxidative stress against H9c2 cell ischemia-reperfusion injury via VEGF-B/AMPK pathway / 药学学报

Total flavonoids of Dracocephalum moldavica L. (TFDM) is an effective component extracted and isolated from the traditional Uighur medicinal herb Cymbidium fragrans. Cymbidium fragrans has the effects of tonifying the heart and brain, promoting blood circulation and resolving blood stasis, and has been widely used in the treatment of cardiovascular and cerebrovascular diseases for a long time. The purpose of this study was to determine the effect of total flavonoids from Cymbidium fragrans on hypoxia/re-oxygenation (H/R) injury in H9c2 (rat cardiomyocytes) cells and its mechanism. A model (H/R) of hypoxia/re-oxygenation injury in H9c2 cells was established using hypoxia and glucose deprivation for 9 h combined with re-oxygenation and rehydration for 2 h to simulate myocardial ischemia-reperfusion injury. The effects of total flavonoids from Cymbidium fragrans on cell viability, markers of myocardial cell damage, oxidative stress levels, and reactive oxygen radical (ROS) content were investigated, Western blot was used to detect the expression of vascular endothelial growth factor B (VEGF-B) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway related proteins. The results showed that the total flavonoids of Cymbidium fragrans significantly increased the viability of myocardial cells after H/R injury, and decreased the content of lactate dehydrogenase (LDH) and creatine kinase isozyme (CK-MB) in the cell supernatant. It significantly reduced malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and decreased intracellular ROS and nitric oxide (NO) content. Western blot analysis showed that the total flavonoids of Cymbidium fragrans decreased Bax levels in H9c2 cells damaged by H/R and increased Bcl-2 expression. Total flavones of Cymbidium fragrans upregulate VEGF-B/AMPK pathway related proteins VEGF-B, vascular endothelial growth factor receptor 1 (VEGFR-1), neuropilin 1 (NRP-1), peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α), phosphorylated adenosine monophosphate activated protein (p-AMPK) and phospho mechanistic target of rapamycin (p-MTOR) levels. The above research results indicate that the total flavonoids of Cymbidium can significantly reduce the H/R injury of myocardial cells, which may be related to the upregulation of VEGF-B/AMPK pathway and inhibition of oxidative stress response.

Improvement effect and mechanism of total flavonoids from Alpinia zerumbet on gastric mucosa injury induced by absolute ethanol / 中国药房

OBJECTIVE To explore the improvement effect and potential mechanism of total flavonoids from Alpinia zerumbet on gastric mucosa injury induced by absolute ethanol through microRNA-146a-5p （miR-146a-5p）. METHODS Using human gastric mucosa GES-1 cells as objects， the acute gastric ulcer model was established by absolute ethanol； based on the investigation of the effects of different concentrations of total flavonoids from A. zerumbet on cell activity and the selection of action concentration， the relative expression level of miR-146a-5p in GES-1 cells was detected， the protein expressions of tumor necrosis factor （TNF） receptor-associated factor 6（TRAF6）， nuclear factor-κB p65 （NF-κB p65） and TNF-α were detected， and the levels of interleukin- 1β （IL-1β）， IL-6 and prostaglandin E2 （PGE2） in cell supernatant were determined. The targeting relationship between miR-146a- 5p and TRAF6 was verified； the effects of overexpressed miR-146a-5p and TRAF6 knockdown on the levels of IL-1β， IL-6 and PEG2 in supernatant of model cells as well as the effects of miR-146a-5p knockdown on anti-gastric ulcer effect of total flavonoids from A. zerumbet were observed. RESULTS Compared with the blank group， the relative expression of miR-146a-5p in cells and the level of PGE2 in cell supernatant were decreased significantly in the model group （P＜0.01）， while the protein expressions of TRAF6， NF-κB p65 and TNF-α in cells and the levels of IL-1β and IL-6 in cell supernatant were increased significantly （P＜ 0.01）. Compared with the model group， the relative expression of miR-146a-5p in cells and the level of PGE2 in cell supernatant were increased significantly in model+A. zerumbet total flavonoids （60 mg/L） group （P＜0.01）， while the protein expressions of TRAF6， NF-κB p65 and TNF-α in cells and 82260767） the levels of IL-1β and IL-6 in cell supernatant were decreased significantly （P＜0.05 or P＜0.01）. There was a targeted relationship and a negative correlation between miR-146a-5p E-mail：3113836821@qq.com and TRAF6. After overexpression of miR-146a-5p or TRAF6 knockdown， the levels of IL-1β and IL-6 were decreased significantly in cell supernatant， while the level of PGE2 was increased significantly （P＜0.05）. After miR-146a-5p knockdown， the levels of IL-1β and IL-6 in cell supernatant and the protein expression of TRAF6 in cells administered with total flavonoids of A. zerumbet were increased significantly， while the level of PGE2 was decreased significantly （P＜0.05）. CONCLUSIONS Total flavonoids of A. zerumbet can improve the gastric mucosa injury induced by absolute ethanol. The mechanism may be related to up-regulating the expression of miR-146a-5p， inhibiting the expression of TRAF6， and further inhibiting the secretion of related inflammatory factors.

Fingerprint establishment of Scutellaria barbata standard decoction and chemical pattern recognition of anti- oxidant components / 中国药房

OBJECTIVE To determi ne the contents of total fla vonoids i n Scutellaria barbata standard decoction ，evaluate in vitro antioxidant activity ，establish the fingerprint and conduct chemical pattern recognition analysis. METHODS The contents of total flavonoids in S. barbata standard decoction （calculated by scutellarein ）were determined by ultraviet-visible spectrophotometry. In vitro antioxidant activity of S. barbata standard decoction was investigated by free radical scavenging tests of 1，1-diphenyl- 2-trinitrophenylhydrazine（DPPH）and 2，2′-azino-bis（3-ethylbenzothiazoline-6-sulfonic acid ）ammonium salt （ABTS）；HPLC method was adopted. Using scutellarin as reference ，the fingerprints of 16 batches of S. barbata standard decoction were drawn and evaluated by Similarity Evaluation System of TCM Chromatogram Fingerprint （2004 A edition ），and the common peaks were determined；Pearson correlation analysis was carried out by using SPSS 24.0 software to screen substances with in vitro antioxidant activity. Taking them as variables ，cluster analysis and principal component analysis were carried out by using SPSS 24.0 and SIMCA 14.1 software. RESULTS The linear range of total flavonoids were 2.106-21.06 μg/mL（R2＝0.999 3）；RSDs of precision ， reproducibility and stability tests （120 min）were all lower than 2％；the recovery was 100.62％（RSD＝0.55％，n＝6）；the contents of total flavonoids were 0.634-1.053 mg/mL. Median inhibitory concentration （IC50） of DPPH radical scavenging experiment ranged 1.120-3.602 mg/mL，and IC 50 of ABTS radical scavenging e xperiment range d 0.684-1.327 mg/mL. The results of correlation analysis showed that the content of total flavonoids Δ 基金项目 ：河北省高校省级重点学科建设项目 （No.冀教 in S. barbata standard decoction was negatively correlated 高〔2013〕4号）；承德医学院自然科学研究计划项目（No.201824） ＊讲师，硕士。研究方向：中药质量控制 。电话：0314-2291186。 with the IC 50 of DPPH free radical and ABTS free radical E-mail：duyilongww@sina.com scavenging experiment ，and the correlation coefficients were # 通信作者 ：教授，硕士。研究方向 ：中药质量控制 。电话： －0.976 and －0.940 respectively（P＜0.01）. There were 18 0314-2291186。E-mail：phf2301@163.com common peaks in the fin gerprints of 16 batches of S. barbata 中国药房 2022年第33卷第4期 China Pharmacy 2022Vol. 33 No. 4 ·425· standard decoction ；the s imilarities were 0.964-0.997. A total of 4 common peaks were identified ，such as scutellarin （peak 8）， scutellarein（peak 14），luteolin（peak 15），apigenin（peak 17）.In the HPLC fingerprints of S. barbata standard decoction ，the peak areas of peak 3-4，8-9，12-15 and 17 were significantly negatively correlated with the IC 50 of DPPH free radical and ABTS free radical scavenging experiment （P＜0.05）. The results of cluster analysis showed that 16 batches of S. barbata standard decoction could be clustered into two categories ，of which S 2，S7-S8 and S 14-S16 were clustered into one category ，S1，S3-S6 and S 9-S13 were clustered into one category. By principal component analysis ，16 batches of S. barbata standard decoction were divided into two categories ，of which S 2，S4，S7 and S 14-S16 were clustered into one category ，and S 1，S3，S5-S6 and S 8-S13 were clustered into one. The comprehensive scores were high in the samples of S 4，S13，S15. CONCLUSIONS Established HPLC fingerprint and chemical pattern recognition analysis method can be used to evaluate the quality of S. barbata standard decoction ； peak 3-4，8-9，12-15 and 17 and total flavonoids are the potential material basis for S. barbata standard decoction to scavenge DPPH free radical and ABTS free radical.

Improvement effects of total flavonoids of Psidium guajava leaves on myocardial hypertrophy in hypertensive model rats / 中国药房

OBJECTIVE To study the imp rovement effects of total flavonoids of Psidium guajava leaves on myocardial hypertrophy in hypertensive model rats. METHODS Ten rats were randomly selected from 60 healthy SD rats as the normal group ； other 50 rats established hypertensive model ，and 44 rats with successful modeling were randomly divided into model group ， anisomycin group [p38 mitogen-activated protein kinase （p38 MAPK）activator，1 mg/kg]，total flavonoids of P. guajava leaves+ anisomycin group （200 mg/kg total flavonoids+ 1 mg/kg anisomycin ）and total flavonoids of P. guajava leaves group （200 mg/kg） by random volume mass ranking method ，with 11 rats in each group. Rats in normal group and model group were given 3％ hydroxymethylcellulose sodium solution ，and other groups were given relevant solution intragastrically ，once a day ，for consecutive 6 weeks. Blood pressure （systolic blood pressure ，diastolic blood pressure ，mean arterial pressure ），cardiac index and left ventricular index were measured. The levels of tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β）and IL- 6 in myocardial tissue were detected. The pathomorphological changes of myocardial tissue were observed. The expression of p 38 MAPK， phosphorylated p 38 MAPK （p-p38 MAPK），extracellular regulated protein kinase 1/2 （ERK1/2），phosphorylated ERK 1/2 （p-ERK1/2），c-Jun N-terminal kinase （JNK）and phosphorylated JNK （p-JNK）in myocardial tissue were detected. RESULTS Compared with normal group ，the systolic blood pressure ，diastolic blood pressure ，mean arterial pressure ，cardiac index ，left ventricular index as well as the levels of TNF-α，IL-1β and IL-6 and protein expression of p-p 38 MAPK，p-ERK1/2 and p-JNK in myocardial tissue were increased significantly in anisomycin group and model group （P＜0.05）；it was also found that hypertrophy of cardiomyocytes ，disorder of myocardial fibers ，looseness，edema and proliferation of connective tissue between myocardial fibers，increased infiltration of inflammatory cells ，etc. Compared with anisomycin group and model group ，the le vels of above indexes in total flavonoids of P. guajava leaves+ anisomycin group and total flavonoids of P. guajava leaves group were decreased significantly （P＜0.05）； cardiomyocytes were 163.com slightly larger and arranged reasonably ；the degree of myocardial hypertrophy，looseness，edema and proliferation of connective tissue were relieved ，and the improvement effect of total flavonoids of P. guajava leaves group was more significant （P＜0.05）. CONCLUSIONS The total flavonoids of P. guajava leaves can reduce blood pressure and improve myocardial hypertrophy in hypertensive model rats. Its mechanism may be related to the inhibition of p38 MAPK signal pathway activity and the expression of inflammatory factors.