Application of partial least squares algorithm to explore bioactive components of crude and stir-baked hawthorn for invigorating spleen and promoting digestion / 中国中药杂志

This study was aimed at identifying the bioactive components of the crude and stir-baked hawthorn for invigorating spleen and promoting digestion, respectively, to clarify the processing mechanism of hawthorn by applying the partial least squares(PLS) algorithm to build the spectrum-effect relationship model. Firstly, different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions were prepared, respectively. Then, the contents of 24 chemical components were determined by ultra-high performance liquid chromatography-mass spectrometry. The effects of different polar fractions of crude hawthorn and stir-baked hawthorn aqueous extracts and combinations of different fractions were evaluated by measuring the gastric emptying rate and small intestinal propulsion rate. Finally, the PLS algorithm was used to establish the spectrum-effect relationship model. The results showed that there were significant differences in the contents of 24 chemical components for different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions, and the gastric emptying rate and small intestinal propulsion rate of model rats were improved by administration of different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions. The bioactive components of crude hawthorn identified by PLS models were vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, neochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, malic acid, quinic acid and fumaric acid, while neochlorogenic acid, cryptochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, quinic acid and fumaric acid were the bioactive components of stir-baked hawthorn. This study provided data support and scientific basis for identifying the bioactive components of crude and stir-baked hawthorn, and clarifying the processing mechanism of hawthorn.

Effects of Zhibitai capsule combined with pitavastatin calcium tablets on coronary heart disease complicated with diabetes mellitus / 中国基层医药

Objective:To investigate the effects of Zhibitai capsule combined with pitavastatin calcium tablets on blood lipids, blood glucose, and glycated hemoglobin in patients with coronary heart disease complicated by diabetes mellitus. Methods:A total of 100 patients with coronary heart disease and diabetes mellitus who received treatment in The Third Affiliated Hospital of Jinzhou Medical University from January 2017 to June 2020 were included in this study. They were divided into a control group ( n = 50) and an observation group ( n = 50) according to different treatment methods. Both groups were given conventional treatment such as pitavastatin calcium tablets. The control group was given pitavastatin calcium tablets based on conventional treatment. The observation group was given Zhibitai capsule combined with pitavastatin calcium tablets based on conventional treatment. After 6 months of treatment, serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and glycated hemoglobin were compared between the two groups. Results:After treatment, serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, glycated hemoglobin in the observation group were (4.26 ± 0.67) mmol/L, (1.85 ± 0.38) mmol/L, (3.16 ± 0.27) mmol/L, (8.29 ± 1.07) mmol/L, and (8.20 ± 0.77)%, respectively, and they were (4.50 ± 0.39) mmol/L, (1.99 ± 0.19) mmol/L, (3.28 ± 0.27) mmol/L, (8.80 ± 0.66) mmol/L, (8.54 ± 0.74)%, respectively in the control group. After treatment, these indices in each group were decreased compared with those before treatment (control group: t = 19.56, 14.60, 10.66, 8.60, 10.18; observation group: t = 15.04, 14.68, 11.36, 12.36, 12.89, all P < 0.05). After treatment, these indices in the observation group were significantly lower than those in the control group ( t = -2.12, -2.23, 2.26, -2.84, -2.44, all P < 0.05). After treatment, the level of high-density lipoprotein cholesterol in the observation and control groups was (1.16 ± 0.18) mmol/L and (1.09 ± 0.13) mmol/L, respectively. After treatment, the level of high-density lipoprotein cholesterol in each group was increased compared with that before treatment (control group: t = -11.10, observation group: t = -11.07, P < 0.05). After treatment, the level of high-density lipoprotein cholesterol in the observation group was significantly higher than that in the control group ( t = 2.11, P < 0.05). Conclusion:Zhibitai capsule combined with pitavastatin calcium tablets can greatly improve the level of blood lipids and blood glucose in patients with coronary heart disease complicated by diabetes mellitus.

Effects of hawthorn flavonoids on atherosclerotic and hyperlipidemia / 中国临床药理学与治疗学

AIM: To investigate the preventive and therapeutic effects of Hawthorn flavone on hyperlipidemia and atherosclerosis rats. METHODS: The atherosclerosis model was established by high fat diet plus vitamin D2. The blood lipid levels, heart index, atherosclerosis index (AI1, AI2) and coronary heart index were measured in each group. The histopathological changes of aorta were observed by oil red O staining, HE staining and Masson staining. ELISA experiments were used to detect IL-6, ICAM-1, MCP-1 and VCAM-1 protein level. RESULTS: Compared with normal group, total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), heart index, atherosclerosis index (AI1, AI2) and coronary index in atherosclerosis model group were significantly increased (P<0.01), while high density lipoprotein cholesterol (HDL-C) was significantly decreased (P<0.01). The pathological score of aorta and the degree of fibrosis were significantly increased (P<0.01). Compared with model group, TC, TG, LDL-C, heart index, atherosclerosis index (AI1, AI2) and coronary heart index were significantly decreased (P<0.01), and high-density lipoprotein cholesterol (HDL-C) was significantly increased (P<0.01) in medium, high dose hawthorn flavonoids and atorvastatin groups. The pathological score of aorta significantly decreased and the degree of fibrosis significantly improved (P<0.01). The variation trend of blood lipid levels in hyperlipidemia rats is basically consistent with atherosclerotic rats. Meanwhile, compared with model group, the medium, high dose hawthorn flavonoids and atorvastatin groups could significantly inhibit the expression levels of IL-6, MCP-1, ICAM-1 and VCAM-1 adhesion molecules (P<0.01). CONCLUSION: The hawthorn flavone can inhibit the formation of aortic endothelial atherosclerotic plaque, reduce the degree of fibrosis and inflammation of atherosclerotic plaque in rats, and achieve the purpose of anti-atherosclerosis. Meanwhile, the hawthorn flavone has the effect of regulating blood lipid.

Comparative analysis of chemical constituents in hawthorn leaves from different sources / 药学学报

We identified and analyzed the components and chemical constituents of hawthorn leaves of Crataegus pinnatifida Bge. (wild) and C. pinnatifida Bge. var major N. E. Br (cultivated) by using ultra high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MSE) combined with UNIFI data analysis platform and multivariate statistics. Fifty-eight chemical compounds were identified, including organic acids, flavonoids, triterpenoic acids, monoterpenes and sesquiterpenoids; among them, terpenoid content was the most abundant. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to identify the differential components of hawthorn leaves from two sources. The results show that there are differences in the chemical compositions of the two sources, including 24 flavonoids and terpenoids (including monoterpenoids, sesquiterpenoids and triterpenoid acids). The types of flavonoids (such as rutin, vitexin-2''-O-rhamnoside, isovitexin-2''-O-rhamnoside, hyperoside, quercetin-3-O-β-D-glucoside) and terpenoids (crataegolic acid, corosolic acid and ursolic acid) in C. pinnatifida were more varied than those found in C. pinnatifida Bge. var major N. E. Br, and their contents were relatively higher. This study provides a comprehensively analysis of the different chemical components of hawthorn leaves from two sources listed in the Chinese Pharmacopoeia, and provides a basis for the selection of raw materials and the potential development and utilization of hawthorn leaves.

Terpenoids from leaves of Chinese hawthorn / 中国中药杂志

Fifteen compounds were isolated from the 70% EtOH extract of leaves of Chinese hawthorn(Crataegus pinnatifida var. major) by various purification steps, and their structures were determined as 2α,3α,12β,19α,-tetrahydroxyursan-13β,28-olide(1),euscaphic acid(2), tormentic acid(3), ursolic acid(4), pomolic acid(5), corosolic acid(6), maslinic acid(7), linalyl rutinoside(8),(Z)-3-hexenyl β-D-glucoside(9),(3S, 6S)-cis-linalool-3,7-oxide-β-D-glucopyranoside(10), pisumionoside(11), icariside B6(12), byzantionoside B(13),(6R,7E,9R)-9-Hydroxy-4,7-megastigmadien-3-one 9-O-β-D-glucopyranoside(14) and(6S,7E,9R)-6,9-dihydroxy-4,7-megastigmadien-3-one 9-O-β-D-glucopyranoside(15) mainly based on the mass spectrum(MS) and nuclear magnetic resonance(NMR) spectroscopic techniques, of which compound 1 was a new pentacyclic triterpene, and compounds 2, 5, 6, 8, 10, 13 and 15 were isolated form this plant for the first time.

Effects of hawthorn and melanoidins on the in-vitro growth of Bifidobacterium and E.coli / 药学实践杂志

Objective Effect of hawthorn and melanoidins on the in-vitro growth of Bifidobacterium and E.coli. Methods According to methods of the Chinese pharmacopoeia (2015),the charred hawthorn was prepared. The melanoidins in charred hawthorn were separated and purified by the macroporous resin extraction process. Ultraviolet spectrophotometry was used to detect melanoidins. The gas chromatography was used to detect the effects of hawthorn, charred hawthorn and melanoidins on the content of the acetic acid in Bifidobacterium and E.coli during growth, stable and decay period. Results In the early stage, the effects of hawthorn and charred hawthorn on bacteria were greater than melanoidins. In the middle and late stage, melanoidins inhibited the growth and metabolism of E.coli by changing the generation of acetic acid, and contributed to that of Bifidobacterium and also promoted the generation of acetic acid and regulate the intestinal flora. Conclusion Hawthorn, charred hawthorn and melanoidins all promote digestion by promoting the growth and metabolism of intestinal flora. Among them, charred hawthorn has a better effect on intestinal flora.

Experimental study on inhibitory effect of hawthorn leaves flavonoids on human glioblastoma U87 cells / 中国药理学通报

Aim To explore the inhibitory effect of hawthorn leaves flavonoids (HLF) on human glioblastoma U87 cells. Methods U87 cells were cultured in vitro. The concentration of HLF was 25, 50, 100 mg . L¹ as drug concentration. The effects of HLF on the proliferation, migration, invasion and adhesion of U87 cells were detected by CCK-8 assay, scratch assay, Transwell assay and adhesion assay, and clone forming ability was detected by cell clonogenic assay. Results HLF inhibited the proliferation, migration, invasion and adhesion of U87 cells in a concentration-dependent manner, and the difference was statistically significant compared with control group (P < 0. 05). When HLF reached 50 mg . L¹ the inhibition of tumor growth was the most significant. Conclusion HLF has a certain inhibitory effect on glioma U87 cells.

Hawthorn Extract Alleviates Atherosclerosis through Regulating Inflammation and Apoptosis Related Factors: An Experimental Study / 中国结合医学杂志

OBJECTIVE@#To determine the effects of hawthorn extract on serum lipid levels, pathological changes in aortic atherosclerosis plaque, inflammatory factors, and apoptosis-related protein and mRNA expression in apolipoprotein E gene knockout (ApoE) mice.@*METHODS@#Thirty-six ApoE mice were fed with a high-fat diet starting at the age of 8 weeks. Mice were randomly divided into 3 groups by a random number table including model group, hawthorn extract group, and simvastatin group, 12 mice in each group. Twelve 8-week-old C57BL/6 mice were fed a basic diet and served as control. The mice in the control and model groups were administered 0.2 mL saline daily, the mice in the hawthorn extract and simvastatin groups were administered with 50 mg/kg hawthorn extract or 5 mg/kg simvastatin daily for 16 weeks. After 16 weeks, plasma lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by an enzymatic assay. Aortic atherosclerotic lesions were observed by light microscopy, scanning and transmission electron microscopy, respectively. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β), adiponectin (APN), and hypersensitive C-reactive protein (hs-CRP) were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expressions of Bax and Bcl-2 in the aorta were assessed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively.@*RESULTS@#Compared to the control group, the plasma levels of TC, TG and LDL-C were significantly increased and HDL-C were significantly decreased in the model group (P<0.01). Compared to the model group, treatment with hawthorn extract significantly decreased the plasma levels of TC, TG, and LDL-C and increased the plasma level of HDL-C in ApoE mice (P<0.01). The levels of MCP-1, IL-1ß, and hs-CRP in the model group were significantly increased and APN was significantly decreased compared with the control group (P<0.01). Compared to the model group, treatment with hawthorn extract decreased the levels of MCP-1, IL-1ß, and hs-CRP and increased the APN level (P<0.01). Compared to the control group, the protein and mRNA expression of Bax in the model group were significantly increased and the expression of Bcl-2 was significantly decreased (P<0.01). Hawthorn extract also reduced the protein and mRNA expression of Bax and increased the Bcl-2 expression in the aorta (P<0.01).@*CONCLUSION@#Hawthorn extract has anti-atherosclerosis and stabilizing unstable plaque effects. The mechanism may be related to the inflflammation and apoptosis signaling pathways.

Influence of Hawthorn (Crataegus oxyacantha) Leaves Extract Administration on Myocardial Infarction Induced by Isoproterenol in Rats

Aims: To investigate the influence of ethanolic hawthorn leaves extract (EHLE) oral administration (200 mg / kg body weight /day) on isoproterenol (ISO) induced- myocardial infarction (MI) in rats and its bioactive constituents. Methods: Healthy adult male albino rats (Sprague-Dawely strain) were divided into five groups (10 rats /group); MI was induced in rats by ISO at a dose of {85 mg/kg body weight/day subcutaneously (S.C.,)} on two consecutive days with a 24 hours interval. Results: Pre-and post-treatment with EHLE significantly (p≤0.05) lowered the elevated serum cardiac enzyme marker activities namely, creatine kinase (CK), creatine kinase MB (CK- MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and specific MI markers level of galectin-3(Gal-3), cardiac troponin I (cTnI). Also, significantly (p≤0.05) ameliorated oxidant/ antioxidant status by decreasing oxidative stress biomarkers [tissue nitric oxide (NO), serum and tissue malondialdehyde (MDA)], and increasing antioxidant status [glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH)] in ISO-injected rats. Microscopic examination of heart tissues confirmed these results. Conclusion: Our results demonstrated that EHLE has a cardioprotective effect against ISO-induced MI in rats due to its high antioxidant properties, inhibition of lipid peroxidation and restoration of cardiac enzyme activities.

Calcium mobilizing effect of hawthorn leaf procyanidins in vascular endothelial cells / 中国中药杂志

The hawthorn leaves have the effect of activating blood, removing blood stasis, regulating qi through the veins, dissolving turbidity and lowering lipid. Procyanidinis is one of its main active components and plays an important role in regulating vasoactivity. Previous studies showed that the regulating effect of procyanidins was related to its regulation on nitric oxide secretion from vascular endothelial cells, and this effect was dependent on the extracellular calcium concentration, suggesting that the changes in intracellular calcium ion concentration in endothelial cells may play a key role in this process. However, the research on this issue is still insufficient so far. This study is aimed to observe the effect of hawthorn leaf oligomeric procyanidins (HLP) on calcium mobilization of vascular endothelial cells, and investigate the underlying mechanism. Human umbilical vein endothelial cells (HUVEC) were cultured and labeled with Fura-2. HUVEC were treated with HLP at concentrations of 6.25, 12.5, 25 and 50 mg·L⁻¹, and the intracellular calcium concentrations were measured with a living cell microscope for 30 min. HLP increased the intracellular calcium concentration of HUVEC in a concentration dependent manner; and the intracellular calcium concentrations in 25 and 50 mg·L⁻¹ HLP groups were significantly higher than that in the normal group. With the use of calcium-free incubation buffer, addition of calcium chelating agent EGTA in incubation buffer, or use of inhibitors for sodium calcium exchanger, the effect of HLP was significantly inhibited. On the other hand, the effect of HLP could also be weakened by inhibiting the calcium release from the intracellular storage. In conclusion, these results suggest that HLP can elicit calcium mobilization in vascular endothelial cells, which may be one of the mechanisms for its vascular modulatory activity; and this calcium mobilizing effect may be achieved through promoting both extracellular calcium influx and intracellular calcium release, additionally the former may be related to activating the reverse transport of Na⁺-Ca²⁺ exchangers on the cell membrane.

Key physical parameters of hawthorn leaf granules by stepwise regression analysis method / 中国中药杂志

The purpose of this study was to investigate the effect of key physical properties of hawthorn leaf granule on its dissolution behavior. Hawthorn leaves extract was utilized as a model drug. The extract was mixed with microcrystalline cellulose or starch with the same ratio by using different methods. Appropriate amount of lubricant and disintegrating agent was added into part of the mixed powder, and then the granules were prepared by using extrusion granulation and high shear granulation. The granules dissolution behavior was evaluated by using equilibrium dissolution quantity and dissolution rate constant of the hypericin as the indicators. Then the effect of physical properties on dissolution behavior was analyzed through the stepwise regression analysis method. The equilibrium dissolution quantity of hypericin and adsorption heat constant in hawthorn leaves were positively correlated with the monolayer adsorption capacity and negatively correlated with the moisture absorption rate constant. The dissolution rate constants were decreased with the increase of Hausner rate, monolayer adsorption capacity and adsorption heat constant, and were increased with the increase of Carr index and specific surface area. Adsorption heat constant, monolayer adsorption capacity, moisture absorption rate constant, Carr index and specific surface area were the key physical properties of hawthorn leaf granule to affect its dissolution behavior.

Effect of Hawthorn Jiangzhi powder on blood lipids in patients with hyperlipidemia: a pathological analysis of 484 cases / 中国中西医结合急救杂志

Objective To observe the effect of Hawthorn Jiangzhi powder on blood lipids in hyperlipidemia patients.Methods Four hundreds and eighty-four patients with hyperlipidemia were selected from Department of Cardiology in Huanghuai University Affiliated Hospital from January 2011 to June 2016,and they were divided into observation group and control group by random number table,each group 242 cases.The observation group took orally Hawthorn Jiangzhi powder (including ingredients:hawthorn 6 g,salvia miltiorrhiza 18 g,black soybean 16 g,hoelen 6 g,ganoderma lucidum 9 g,kudzuvine root 6 g,Chinese yam 6 g,fructus amomum 9 g,coix seed 16 g,cassia seed 6 g) once 6-9 g powder,twice a day,once in the morning and another in the evening;the control group was given simvastatin,20 mg each day during taking dinner;the therapeutic period lasted 2 months in both groups.The differences in serum lipid and serum inflammatory factor levels were compared before and after treatment in the two groups;the changes of lymphocyte subsets of the two groups were observed and compared with the changes of the subset results of 100 normal healthy subjects aged 35-80 years old in the same period in our hospital,and the total efficiency,the situations of adverse reactions and liver and kidney functions of two groups were observed.Results In the observation group and the control group,before treatment the levels of CD4+,CD8+,CD4+/CD8+ were lower than those of healthy control group,but after treatment the levels of CD4+,CD8+ and CD4+/CD8+ were higher than those before treatment,and the changes of the observation group were more significant than those of the control group(CD4+:0.47±0.11 vs.0.40±0.10,CD8+:0.28 ± 0.10 vs.0.26 ± 0.08,CD4+/CD8+:1.67 ± 0.79 vs.1.53 ± 0.45);After treatment,the levels of hypersensitive C-reactive protein (hs-CRP),interleukin-6 (IL-6),von Willebrand factor (vWF) and homocysteine (Hcy) in the two groups were significantly lower than those before treatment,and the levels of hs-CRP,IL-6 and vWF in the observation group were obviously lower than those in the control group [hs-CRP (mg/L):5.1 ± 1.8 vs.5.8 ± 1.7,IL-6 (ng/L):2.9 ± 1.6 vs.3.7 ± 1.8,vWF:(126.8 ± 12.8)％ vs.(156.5 ± 11.3)％,all P ＜ 0.05].After treatment,Hcy in the observation group was lower than that in the control group,but there was no significant difference between the two groups (μμmol/L:5.2 ± 1.8 vs.5.4 ± 2.6,P ＞ 0.05).In the observation group after treatment at each time point,the levels of total cholesterol (TC),triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) were lower than those before treatment,while the levels of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein cholesterol/total cholesterol (HDL/TC) were higher than those before treatment;after treatment in the control group,the levels of TC,TG and LDL-C were decreased,and the levels of HDL-C and HDL/TC were obviously increased compared with those before treatment;The levels of TC,TG and LDL-C in the observation group after treatment for 2 months were significantly lower than those in the control group [TC (mmol/L):1.26 ± 0.57 vs.2.26 ± 0.56;TG (mmol/L):3.45 ± 0.78 vs.5.45 ± 0.75,LDL-C (mmol/L):2.40±0.65 vs.2.72±0.85;all P ＜ 0.05),and HDL/TC was obviously increased (1.19±0.15 vs.0.62±0.35,P ＜ 0.01).The total therapeutic effective rate of the observation group was significantly higher than that of the control group [90.1％ (218/242) vs.73.4％ (178/242),P ＜ 0.01].Adverse reactions and changes of liver and kidney functions during the period of treatment in the two groups were minimal.Conclusions Hawthorn Jiangzhi powder can effectively reduce the blood lipids and serum inflammation cytokines in patients with hyperlipidemia,improve blood rheological situation,reduce serum levels of inflammatory factors,inhibit the formation and development of atherosclerosis and enhance the immune function obviously in patients with high lipid abnormalities.

Effects of hawthorn leaf polymeric procyanidins on calcium mobilization in human umbilical vein endothelial cells / 中国病理生理杂志

AIM:To observe the effects of hawthorn leaf polymeric procyanidins ( PPC) on calcium mobiliza-tion of vascular endothelial cells , and to study the underlying mechanism .METHODS: Free calcium in cultured human umbilical vein endothelial cells (HUVECs) was labeled with Fura-2.HUVECs were treated with ATP, a positive control drug, and PPC at concentrations of 12.5, 25 and 50 mg/L..The intracellular calcium concentrations were measured with a living cell microscope for 30 min.RESULTS:PPC concentration-dependently increased the intracellular calcium concen-tration of HUVECs .The intracellular calcium concentrations in 25 and 50 mg/L PPC groups were significantly higher than that in normal group (P<0.01).The dynamic manner of calcium concentration elevations elicited by PPC was a slow in -crease which happened after a latency time of several minutes , lasted for several minutes , and reached a plateau finally . This manner was quite different from that elicited by ATP , a typical SOC operator , hinting different mechanisms between them .Inhibiting the intracellular calcium release did not influence the effects of PPC;however , deleting extracellular calci-um, inhibiting the reverse mode of Na +-Ca2+exchange, or deleting extracellular sodium , restrained or even abolished the effects of PPC.CONCLUSION:PPC elicits calcium mobilization in vascular endothelial cells , which may be one of the mechanisms of the vascular modulatory activity of hawthorn procyanidins .This effect may be achieved through inducing the influx of sodium and then activating the reverse mode of Na +-Ca2+exchange.

Effects of hawthorn proanthocyanidins and vitamin C on kidney protection in insulin-resistance rats / 中草药

Objective To explore the effects of hawthorn proanthocyanidins (HPC) and vitamin C (VC) on kidney protection in insulin-resistance (IR) rats. Methods The IR rats were induced by high-fat diet in order to establish the model of nephropathy in type II diabetic rats, and the high-fat feeding were continued for 2 weeks after the IR rats were made. The contents of fasting blood glucose, serum insulin, glucose and microabuminuria (mAlb) in urine were tested. Fifty IR model rats were divided into model, HPC (56 mg/kg), VC (180 mg/kg), combined application of HPC (56 mg/kg) and VC (180 mg/kg), and rosiglitazone (2 mg/kg) groups. Another 10 normal rats were selected randomly to be control group. After continuous ig administration for 20 weeks in each group, these indexs, such as the levels of fasting blood glucose (FBG), serum insulin (SI), glucose in urine (24 h), creatinine (Cr), urea nitrongen (UN), uric acid (UA), were all detected. The excretion of urinary total protein (UTP), microabuminuria (mAlb), N-acetyl-β-D-glucosaminidase (NAG) were also measured. Moreover, the histopathological microstructure of kidney was observed by light microscope. Results After modeling, the levels of FBG, SI and glucose in urine increased significantly (P < 0.01) in comparation with the control group, so does the levels of UN, Cr, UA (P < 0.01) and the excretion rates of UTP, mAlb, NAG (P < 0.01). However, all these indexs were decreased significantly (P < 0.01) after the combined use of HPC and VC, which were more notable than that in HPC and VC group (P < 0.01) and equivalent to that in rosiglitazone group. Conclusion The combined application of HPC and VC can improve the renal function of IR rats and have protective effects on kidney injury.

Quantitative and morphological analysis of five heavy metal elements Cu, As, Cd, Hg, and Pb in hawthorn pill / 中草药

Objective: To study Cu, As, Cd, Hg, and Pb in 52 batches of of hawthorn pill samples from four different production enterprises in China. Methods: The residues of five heavy metal elements were determined with microwave digestion-inductively coupled plasma mass spectrometry (ICP-MS). The valence of As and Hg in the contaminated samples was analyzed with HPLC-ICP-MS. The heavy metal pollution in hawthorn pill was evaluated with the single and comprehensive pollution index method. Results: The method had good linear correlation (r ≥ 0.999 4).The detection limit ranges of five heavy metal elements were from 0.4 to 5.6 μg/kg. The recovery values ranged from 92.54% to 102.79%. The relative standard deviations for all elements were less than 3.5%. Green Standards of Foreign Trading Medicinal Plants & Preparations was used as the standard to evaluate the pollution status of Cu, As, Cd, Hg, and Pb in hawthorn pill. The results showed that the residues of Cu, Cd, and Pb were all bellow the limit of the standard, however, the As of some samples (S30, S37) from the production enterprise in Jilin exceeded the limit, Hg in all samples exceeded the limit. The As and Hg mainly existed in the form of arsenous acid (3), arsenic acid (5) and bivalent mercury. After the evaluation, there were 32 batches of safety level samples, two batches of warning level samples (S17, S25) from the production enterprise in Tianjin, which was occupied 7.41% of their samples, one batch of mild level polluted sample (S38), one batch of moderate level polluted sample (S40), and 16 batches of high level polluted samples (S28—S37, S39, S41—S45) from the production enterprise in Jilin, all samples from that enterprise were contaminated. Conclusion: The heavy metal pollution levels of hawthorn pill sold in china shows distinct difference since the different production enterprises, which should attach great importance to it. The study provides a reference for further research on safety of Chinese medicine.

Research on equilibrium solubility and apparent oil/water partition coefficient of flavonoids components in hawthorn leaves by similarity analysis / 中草药

Objective To study the equilibrium solubility and oil/water partition coefficient of Hawthorn leaves flavonoids (HLF) components, and compare their similarity, to lay the foundation for the characterization of the overall water soluble and fat soluble HLF components. Methods Taking HLF components as model drug, rutin, quercetin, and hyperin as representative components. The HPLC method was used to determine the equilibrium solubility and apparent oil/water distribution coefficient (Papp) of the components at different pH values and water. The similarity was evaluated by the vector cosine method (cosines) and Grubbs method (Grubbs). Chromatographic conditions: The chromatographic column was Zorbax Eclipse Plus C18 column (250 mm × 4.6 mm, 5 μm), and the flow phase was acetonitrile (A) - 0.4% phosphate solution (B). The gradient elution program was 0—10 min (80% B), 10—11 min (80%—60% B), 11—20 min (60% B), 20—21 min (60%—80% B), and 21—25 min (80% B); The detection wavelength was 360 nm; The volume flow was 0.8 mL/min; The column temperature was 40 ℃. Results The equilibrium solubility and Papp of rutin, quercetin, hyperin were similar in different pH buffer solution and water. The solubility value of lutin, quercetin, and hyperoside in thebuffer solution of different pH were 0.998, 0.988, and 0.987, respectively. The cosine value of the apparent oil-water distribution coefficient was 0.976, 0.981, and 0.978, respectively. The cosine value was greater than 0.9. The Grubbs value of equilibrium solubility of lutin, quercetin and hyperoside were 1.057, 1.083, 1.124, 1.117, 1.022, 1.030, 1.082, and 1.112, respectively. The Grubbs values of the apparent oil-water distribution coefficient were 1.125, 1.107, 1.079, 1.034, 1.041, 1.037, 1.129, and 1.128. The results of Grubbs were less than G critical value of 1.153, and the similarity was good. Conclusion The similarity analysis reflects that the degree of dispersion of components objectively, which could increase the science of components evaluation and provide the basis for the formulation design of components of traditional Chinese medicine.

Effects of Hawthorn Leaf Procyanidins on Over Expressions of ICAM-1 and E-selectin in Human Umbilical Vein Endothelial Cells Induced by TNF-α / 中国中医药信息杂志

Objective To observe the effects of hawthorn leaf procyanidins (HLP) on over expressions of ICAM-1 and E-selectin in human umbilical vein endothelial cells (HUVEC) induced by TNF-α,and clarify the mechanism of HLP's anti-inflammation effect. Methods HUVEC were cultured in vitro. MTT assay was used to detect cell viabilities. The expressions of ICAM-1 and E-selectin in HUVEC were detected by flowcytometry. Results Up to 200 mg/L, HLP showed no significant decrease in cell viabilities; the expression levels of ICAM-1 and E-selectin in the model group significantly increased, compared with that in the normal group; 10, 20, 30, 40, 50 mg/L HLP inhibited the expression elevations of ICAM-1 and E-selectin in concentration-dependent manner; and there were statistical significances in 40, 50 mg/L HLP groups, compared with the model group. Conclusion HLP can inhibit the over expressions of ICAM-1 and E-selectin of vascular endothelial cells induced by TNF-α, which possibly underlies HLP's anti-inflammation effect.

Effects of total flavone of hawthorn leaf on expression of p38MAPK signaling pathway and inflam-mation factors in rats brain with chronic cerebral ischemia / 中华行为医学与脑科学杂志

Objective To investigate the therapeutic effect and mechanism of total flavone of haw-thorn leaf ( TFHL) on p38MAPK signaling pathway and inflammation factors in rats brain with chronic cere-bral ischemia.Methods SPF class healthy male SD rats were randomly divided into sham group, model group,TFHL group and Ginkgo leaf group( 12 rats in each group) .Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model.Morris water maze method was used to evaluate learn-ing and memory abilities of rats.Immunohistochemistry and Western blot methods were used to measure the expression of caspase-3 and p38MAPK proteins.ELISA method was used to measure the amounts of TNF-αand IL-1βin hippocampal tissue.Results Compared with the model group,TFHL treatment (36 d) can im-prove learning and memory capabilities of vascular dementia rats,shorten the escape latency ( TFHL group(10.01±2.85) s vs Model group (19.54±6.12) s, P<0.05) and the course of searching platform(TFHL group(2.6044±0.3219)m vs model group(3.3502±0.6231)m, P<0.05),increase the numbers of crossing the platform (TFHL group(5.17±2.12) times vs Model group (3.96±1.34) time,s P<0.05) and the platform quadrant swimming distance percentage (TFHL group(48.22±7.39)%vs model group (33.42±5.32) %, P<0.01).The number of caspase-3 positive cells in the hippocampus significantly reduced (TFHL group(1.677 ±0.164) vs Model group (2.387±0.171), P<0.05),the expression level of P38MAPK protein (TFHL group (0.0161±0.0003) vs Model group (0.0254±0.0018), P<0.05),TNF-α(TFHL group(19.61±3.61) ng/10 mg vs Model group (27.82±6.57) ng/10 mg, P<0.01)and IL-1β(TFHL group(24.41±2.56) ng/10 mg vs Model group (29.43±5.26) ng/10 mg, P<0.05) were significantly decreased.Conclusion TFHL plays a protective role in nerve function of the chronic cerebral ischemia rats.The mechanism of its antia-poptosis might be associated with the activation of P 38MAPK signaling pathway,inflammation and the apoptosis of neurons in the brain.

Simultaneous determination of oleanolic acid and ursolic acid in Hawthorn extract by HPLC / 药学实践杂志

Objective To establish a HPLC method for simultaneous determination of oleanolic acid and ursolic acid and provide the basis for quality control of Hawthorn extract .Methods Chromatographic separation was performed on Agilent Zorbax SB C18 column(250 mm × 4 .6 mm ,5 μm) with mobile phase of methanol (A)-0 .06 mol/L ammonium acetate solution (B) (85∶15 ,V/V ) under isocratic elution for 30 min .The flow rate was set at 0 .8 ml/min and the detection was set at the wavelength of 210 nm .Results Oleanolic acid and ursolic acid showed good linearity (r> 0 .999 5) in the ranges of 0 .496-2.480 g and 0 .498-9 .960 g ,respectively .Repeatability ,precision ,recovery and stability were conform to the method valida-tion requirements of China Pharmacopoeia .Conclusion The method could provide the basis for the quality control of Hawthorn extract and its preparation .

Advance in study on hawthorn resource for prevention and treatment of type 2 diabetes and its complications / 中草药

Hawthorn, also known as dried Crataegus pinnatifida, is a kind of woody plants widely distributed in China. Hawthorn resources including berries, leaves, flowers, and barks, which enrich the bioactive substances, such as flavonoids, triterpenes, sterols, organic acid, sugar, and so on. A lot of studies have found the role of hawthorn for preventing and treating type 2 diabetes and its complications. Till now, hawthorn resources have been used as medicine in clinic. In order to take better advantage of hawthorn resources and explore new diabetic drugs, we review here the recent advances in study on the pharmacological effects of hawthorn resources, i.e. reducing blood glucose, lipid, insulin resistance, oxidant stress, inflammations, and relative vascular complications.