Optimal Formula of Angelica sinensis Ameliorates Memory Deficits in ß-amyloid Protein-induced Alzheimer's Disease Rat Model.

OBJECTIVE: Angelica (A.) sinensis is used as a traditional medical herb for the treatment of neurodegeneration, aging, and inflammation in Asia. A. sinensis optimal formula (AOF) is the best combination in A. sinensis that has been screened to rescue the cognitive ability in ß-amyloid peptide (Aß25-35)-treated Alzheimer's disease (AD) rats. The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms. METHODS: Male Wistar rats were infused with Aß25-35 for AD model induction or saline (negative control). Five groups of AD rats were fed on AOF at 20, 40, or 80 mL/kg every day, donepezil at 0.9 mg/kg every day (positive control), or an equal volume of water (AD model) intragastrically once a day for 4 weeks, while the negative control rats were fed on water. The Morris water maze test was used to evaluate the cognitive function of the rats. The Aß accumulation, cholinergic levels, and antioxidative ability were detected by ELISA. Additionally, the candidate mechanism was determined by gene sequencing and quantitative real-time polymerase chain reaction. RESULTS: The results showed that AOF administration significantly ameliorated Aß25-35-induced memory impairment. AOF decreased the levels of amyloid-ß precursor protein and Aß in the hippocampus, rescued the cholinergic levels, increased the activity of superoxide dismutase, and decreased the malondialdehyde level. In addition, AOF inhibited the expression of IL1b, Mpo, and Prkcg in the hippocampus. CONCLUSION: These experimental findings illustrate that AOF prevents the decrease in cognitive function and Aß deposits in Aß25-35-treated rats via modulating neuroinflammation and oxidative stress, thus highlighting a potential therapeutic avenue to promote the co-administration of formulas that act on different nodes to maximize beneficial effects and minimize negative side effects.

[Effect of Angelica sinensis radix on colonic morphology and mucus secretion of experimental XuexuBianmi model mice].

OBJECTIVE: To study the effects of Angelicaesinensis radix (Danggui) decoction on the therapeutic action and the colonic morphology and mucus secretion in XuexuBianmi model mice. METHODS: Sixty Kunming mice, maleandfemaleinhalf, were randomly divided into six groups according to gender and weight (n=10):normal control group, XuexuBianmi model group, positive control group, and high-dose, middle-dose and low-dose Danggui groups. Except the normal control group, the mice in the rest groups were orally administrated with diphenoxylate (DPN) and subcutaneously injected with acetylphenyhydrazine (APH) and intraperitoneally injected with cyclophosphamide (CPA) to copy XuexuBianmi model. Fromthe 14th day, the mice in Danggui groups were orally administered with different doses of Danggui decoction (16.67、8.33、4.17 g/kg), the mice in positive control group were orally administered with Changtongshu granule (5 g/kg), the mice in XuexuBianmi model group were administered with normal saline (NS) at the same volume (10 ml/kg), once a day for consecutive 28 days. The general status were observed, the first black defecation time (FBDT), the water content in stool and in colon in mice of all groups were tested. And the colon tissue was stained with hematoxylin-eosin (HE) and AB-PAS to observe the changes of colonic morphology and the mucus secretion. RESULTS: Compared with the normal control group, there appeared the XuexuBianmi syndromes in model group as follows, the defecation time (FBDT) was significantly prolonged, the water contentinstool and in colon were decreased (P<0.01), the colonic mucosa and gland were atrophied, mucous membrane layer was thinned (P<0.01), mucus secretion was decreased. Compared with the XuexuBianmimodel group, the Xuexu and Bianmi syndromes were improved, the FBDT was significantly shortened (P<0.05, P<0.01), the water content of colon was increased in the three groups of Danggui decoction (P<0.05, P<0.01). The water content of the stool was obviouslyincreased in groups of 16.67and 8.33kg.dDanggui decoction (P<0.05). The atrophy of colon mucosa and gland was improved, the mucus secretion was increased, and the colon lubrication function was improved in the three groups in different doses of Danggui decoction. CONCLUSIONS: Dangguican improve the mucosal atrophy, and increase the secretion of colonic mucus, then the stool is softened and promoted to discharge.

[Social network analysis of traditional Chinese medicine on treatment of constipation].

The methods of literature metrology and data mining were used to study the research topics and social network analysis of traditional Chinese medicine for constipation. The major Chinese databases were searched to include the research studies of traditional Chinese medicine for constipation. BICOMS analysis software was used to extract and collect the main information and produce co-occurrence Matrix; gCLUTO software was used for cluster analysis. Data analysis was conducted by using SPSS 19.0 software. The results showed that the number of studies on traditional Chinese medicine for constipation was constantly increased, with two literature volume peaks respectively in 2003 and 2006. Related studies have been published in 31 provinces, autonomous regions and municipalities have published, but the studies in developed areas were more than those in developing areas. There was little cooperation between research institutions and the authors, especially the cooperation between different areas. At present, the research field of Chinese medicine for constipation is divided into five research topics. In terms of specific traditional Chinese medicine, angelica sinensis is in the core position. The results showed regional imbalance in the number of studies on Chinese medicine treatment for constipation, as well as little cooperation between researchers and research institutions. The research topics mainly focused on the evaluation of clinical efficacy, but the research on optimizing the prescriptions was still not enough, so the future researchers shall pay more attention to the studies of constipation prescriptions with Angelica sinensis as the core herb.

[Therapeutic effects of Dunhuang Liaofengxushouruo decoction on chronic heart failure in rats].

OBJECTIVE: To observe the therapeutic effects and mechanism of Dunhuang Liaofengxushouruo decoction (LXD) (Traditional Chinese Medicine) on chronic heart failure(CHF) in rats. METHODS: Forty-eight male Wistar rats were randomly divided into normal group(n=8):model group, captopril group and LXD(Traditional Chinese Medicine) high, medium and low dose group. Except the normal group, the rats were intravenous injected with adriamycin 2.5 mg/kg in one day for 6 weeks, the captopril rats were intragastric administrated by captopril 25 mg/kg, LXD high, medium and low dose groups were intragastric administrated by LXD of 80, 40, 20 g/kg for 6 consecutive weeks. The rats breathing, coat color, activity, body weight(BW) and time of exhaustive swimming were measured; Heart rate, mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of left ventricular pressure (+dp/dtmax or -dp/dtmax)of each rat were examined by Power Lab. The levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured; The rats were sacrificed and hearts removed for separation of left and right ventricle, the antioxidant activity and ventricular mass index were measured, left ventricular myocardium was administrated by 4% paraformaldehyde, HE staining, morphological changes were observed under microscope. RESULTS: Body weight of each group decreased, and time of exhaustive swimming decreased after modeling (P<0.01). At 28 days after administration, BW in high and middle dose of LXD groups were increased and the swimming time of rats in LXD high dose group was increased (P<0.05).At 42 days, BW in all of LXD groups were increased and the exhaustive swimming time of high and middle dose of LXD were prolonged (P<0.05), MAP was decreased and LVSP, +dp/dtmax or -dp/dtmax were increased in LXD high and middle groups. The LVEDP was decreased in high dose of LXD group(P<0.05,P<0.01). The levels of creatine kinase (CK) and aspartate aminotransferase (AST) in middle and low dose of LXD groups were decreased(P<0.05,P<0.01), and the serum levels of IL-6, TNF-α and malondialdehyde (MDA) in serum in LXD high and middle dose groups were lower. The activities of superoxide dismutase (SOD) in serum were increased in all of LXD groups, and the LVMI and RVMI were decreased in high and middle dose of LXD groups(P<0.05,P<0.01). The pathological results showed that myocardial fiber arrangement and myocardial interstitial edema phenomenon were obviously improved in high dose of LXD group and CMD decreased. CONCLUSIONS: Therapeutic effect of LXD on CHF by doxorubicin-induced in rats is confirmed, the mechanisms are associated with improved hemodynamics and myocardial tissue.

[Establishment and effect observation on three kinds of Ti-Xu with constipation rat models].

OBJECTIVE: To establish three types constipation models with the syndrome of Xue-Xu, Yin-Xu and Yang-Xu in rats, and to compare the difference of colonic motility, colonic water metabolism, colonic mucus secretion and the level of aquaporin-2 (AQP2). METHODS: Forty Sprague Dawley rats, male and female in half, were randomly divided into four groups:normal control group(N), Xue-Xu with constipation group(XC), Yin-Xu with constipation group(YC) and Yang-Xu with constipation group(YAC). Bloodletting and loperamide were used to induce the Xue-Xu with constipation in rats, thyroxin and loperamide were used to induce the Yin-Xu with constipation in rats, ice-water stimulation and loperamide were used to induce the Yang-Xu with constipation in rats. Bloodletting was coducted once a week,drug was ad-ministrated orally to rats once a day for continuous 42 days. Rats'state, body weights, stool character, transfer time between mouth and anal, small intestinal propulsion rate were measured. The colon tissues of rats were stained with alcian blue-periodic acid schiff (AB-PAS) to analyze the changes of mucus secretion. The aquaporin-2 expressions in proximal and distal colon of rats were measured by immunohistochemical method. RESULTS: Compared to normal control group, weight-increasing speed of the rats were reduced in three models. The order of indepen-dent movement change was YC, XC and YAC. Solid stool appeared at 30 d, fecal scores were increased. Transfer time between mouth and anal was significantly extended, small intestinal propulsion rate were significantly decreased(P < 0.05, P < 0.01). Water content in stool were significantly decreased in three type models(P < 0.05, P < 0.01), the content of water in colon were decreased in XC and YAC group (P < 0.05, P < 0.01). The colonic gland and goblet cells were narrowed in some extent, the mucus excretion were decreased. The levels of aquaporin-2 expressions in proximal and distal colon of rats were increased(P < 0.05, P < 0.01), increasing order of AQP2 expression in proximal colon was YAC, YC and XC, increasing order of AQP2 expression in distal colon was YAC, XC and YC. CONCLUSIONS: Long term stimulation of complex factors could induce Ti-Xu with constipation animal model, and there were some differences in colonic motility, water metabolism, colonic mucus secretion and AQP2 in rats.

[Protective Effects of Angelica sinensis Volatile Oil on Atherosclerosis in Hyperlipidemia Mice].

Objective: To study the protective effects of Angelica sinensis volatile oil on atherosclerosis in hyperlipidemia mice. Methods: 60 mice were randomly divided into normal control group, model group, fluvastatin group, and high-, medium- and low-dose groups of Angelica sinensis volatile oil. Normal control group were fed with normal diet, the other groups were fed with high fat diet, and treated orally Vitamin D3 (100 million IU/kg) daily for 42 d. At the 14th day after modeling, fluvastatin group were orally administrated fluvastatin (6.7 mg /kg), and high-, medium- and low-doses of Angelica sinensis volatile oil groups were orally administrated Angelica sinensis volatile oil (40, 20, 10 mg /kg) for 28 d, and the normal control group and model group were administrated equal volume normal saline. The activity state, body weight and the levels of TC, TG, HDL-C and LDL-C in serum were measured. The atherosclerosis indexes (AI1, AI2), coronary heart index (R-CHR) were calculated. After the mice were killed, the heart, liver and abdominal aortas were taken. The mass of the heart and liver were measured, and the organ indexes were calculated; the tissues were fixed by formalin, embedded in paraffin, sliced, HE stained, and the histopathology changes were observed by microscope. Results: Compared with normal control group, the body weight of mice in the model group were decreased (P＜0.01), and the heart, liver indexes were significantly increased (P＜0.05), the levels TC, TG, LDL-C and HDL-C in serum and AI1, AI2 and R-CHR were significantly increased after modeling 42 d (P < 0.01). Compared with the model group, the mice body weight were significantly increased, and the heart, liver index were significantly decreased (P＜0.05) in the high-, middle-dose group of Angelica sinensis volatile oil groups; the TC, TG and LDL-C levels were significantly decreased in low-dose group (P＜0.05 or P＜0.01); AI1 and R-CHR were significantly decreased (P＜0.05 or P＜0.01) in all Angelica sinensis volatile oil groups, but the AI2 in the high-dose group of Angelica sinensis volatile oil was significantly decreased (P＜0.05). The histopathology results showed that Angelica sinensis volatile oil could relieve the fatty degeneration of hepatic cells and the injury of thoracic aortic intimae, and myocardial fibrosis, which could inhibit the formation of atherosclerotic plaque. Conclusion: The certain protective effects of Angelica sinensis volatile oil are determinated on atherosclerosis in hyperlipidemia mice.

[Effects of extraction of Angelicae sinensis and Astragalus mongholicus on the peritoneal structure, functions and TGF-ß1 expression in the chronic peritoneal failure rats].

OBJECTIVE: To study the effects of extraction of Angelicae sinensis and Astragalus mongholicus (EAA) on the peritoneal structure, functions and transforming growth factor-ß1(TGF-ß1) expression in the chronic peritoneal failure rats. METHODS: Fifty SD rats were randomly divided into normal control group, model control group, positive control group, high-dose and low-dose EAA group(n=10). The modeling rats were established by intraperitoneal injection(ip) 4.25% high-glucose peritoneal dialysate 100 ml/kg, lasted 40 d, and ip lipopolysaccharides (LPS) 5 mg/kg at 8thd, 10thd and 12thd. At the same time, the rats were treated with the corresponding drugs. The body weight and general states, the levels of ultrafiltration volume, the parameters of peritoneal transport function, the changes of peritoneal morphology and the TGF-ß1 expression in parietal peritoneum of rats were observed. RESULTS: EAA could increase the levels of ultrafiltration volume and improve the parameters of peritoneal transport function. The peritoneal thickness were decreased, and the TGF-ß1 expression in parietal peritoneum were also lowered significantly. CONCLUSIONS: EAA has some protective effects on the peritoneal structure and functions, and can inhibit TGF-ß1 expression.

Gentiopicroside prevents interleukin-1 beta induced inflammation response in rat articular chondrocyte.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, Gentiana macrophylla Pall have been prescribed for the treatment of pain and inflammatory conditions. In addition, it is a common Tibetan medicinal herb used for the treatment of tonsillitis, urticaria, and rheumatoid arthritis (RA), while the flowers of G. macrophylla Pall have been traditionally treated as an anti-inflammatory agent to clear heat in Mongolian medicine. The secoiridoid glycosides and their derivatives are the primary active components of G. macrophylla and have been demonstrated to be effective as anti-inflammatory agents. MATERIALS AND METHODS: Solvent extraction and D101 macroporous resin columns were employed to concentratethe gentiopicroside. Gentiopicroside cytotoxicity was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the toxicity of gentiopicroside in chondrocytes was reconfirmed using Hoechst staining. Western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were utilized to explore the protective effects and mechanisms of gentiopicroside prevents interleukin-1 beta induced inflammation response in rat articular chondrocyte. RESULTS: The MTT assay demonstrated that 50, 500, and 1,500 µg/mL of gentiopicroside exhibited no significant toxicity to chondrocytes (P>0.05) after 24h. Using immunohistochemistry, ELISA, RT-PCR, Western blot method to explore the protective effect and mechanism of gentiopicroside on chondrocytes induced by IL-1ß. The results showed some pathways of IL-1ß signal transduction were inhibited by gentiopicroside in rat chondrocytes: p38, ERK and JNK. Meanwhile, gentiopicroside showed inhibition in the IL-1ß-induced release of MMPs while increasing Collagen type II expression. CONCLUSIONS: The current study demonstrated that gentiopicroside exhibited a potent protective effect on IL-1ß induced inflammation response in rat articular chondrocyte. Thus, gentiopicroside could be a potential therapeutic strategy for treatment of OA.

[Therapeutic effects of ethanol extracts of Angelica sinensis and Astragalus mongholicus in diabetic gastroparesis rats].

OBJECTIVE: To observe therapeutic effects of the ethanol extract of Angelica sinensis and Astragalus mongholicus (1:2) in diabetic gastroparesis (DG) rats. METHODS: Diabetic rats were induced by intraperitoneal injection of alloxan (200 mg/kg). DG was based on gastrointestinal motility index and the character of stool in diabetic rats. The metformin and cisapride mixed solution (containing met-formin 175 mg/kg and cisapride 3.5 mg/kg)was intragastric administrated in the positive control group, the ethanol extract of Angelica sinensis and Astragalus mongholicus was intragastric treated in the high dose (10. 5 g/kg) and low dose(5. 2 g/kg) group rats, 1/d for 42 consecutive days. The body weight, fasting blood glucose (FBG) value and 24 h intake and drinking amount were detected at interval of 14 days. The gastrointestinal propulsion index, motilin (MOT), glucagon (GLG) and gastrin (GAS) contents in the blood were detected after the last administration. And then the gastric antrum smooth muscle cells and interstitial cells of Cajal were observed in microscope. RESULTS: The general state and stool had been improved,and the body weight and 24 h intake were significantly increased, and 24 h drinking in the high and low dose groups at 28 d of administration were reduced. At the 42th day,the body weight and 24 h in- take were increased, 24 h drinking water and FBG were reduced, and the MOT, GAS and GLG contents were decreased in the high dose group. Gastric mucosa and gastric smooth muscle tissue morphology were significantly improved. CONCLUSION: The therapeutic effect of ethanol extracts of Angelica sinensis and Astragalus mongholicus was obvious in DG rats. Its mechanism of action was associated with FBG, MOT and GAS levels decreasing.