[Effect of Kanli Granule on Myocardial Mechanics in Pressure Overload Induced Diastolic Heart Failure Rats].

OBJECTIVE: To observe the effect of Kanli Granule (KG) on myocardial mechanics in pressure overload induced diastolic heart failure (DHF) rats. METHODS: Totally 60 male Wistar rats were divided into the sham-operation group, the model group, the KG group, and the Valsartan group according to random digit table, 15 in each group. The pressure overload induced DHF model was established in all groups except the sham-operation group using abdominal aortic constriction surgery. Totally 7 rats died after modeling (with the mortality of 10. 67%) , and the rest 53 finished the following test. Rats in the KG group were administered with KG extract (calculated as 6. 75 g crude drug/kg) by gastrogavage. Rats in the Valsartan group were administered with Valsartan (7.2 µg/g) by gastrogavage. Equal volume of double distilled water was administered to rats in the model group and the sham-operation group by gastrogavage. All rats were intervened for 32 weeks. The response of isolated heart papillary muscle tonus to isoprenaline (ISO) and adenylate cyclase (Forskolin) was respectively observed. The enhancement phenomenon after resting development force (DF) of isolated heart papillary muscle tonus, and changes of DF in different Ca²âº concentrations were observed. RESULTS: (1) In the ISO response test: Compared with the sham-operation group, the amplifications of DF, ±df/dt, -df/dt were obviously elevated in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously lowered in the KG group (P < 0.01), and the amplification of ±df/dt was also reduced in the Valsartan group (P < 0.01). (2) In the Forskolin response test: Compared with the sham-operation group, the amplifications of DF and ±df/dt obviously increased in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously reduced in the KG group (P < 0.01), and the amplification of DF was also reduced in the Valsartan group (P < 0.05). (3) In post-resting DF enhancement test: Compared with the sham-operation group, the amplification of DF showed gradually decreasing tendency along with prolonged resting time in the model group, and they were obviously lowered at all time points (P < 0.05). Compared with the model group, the amplification of DF was gradually increasing along with prolonged resting time in the KG group. The amplification of DF at post-resting 240 s was obviously larger in the KG group than in the model group (P < 0.05). The amplification of post-resting DF still showed gradually decreasing tendency along with prolonged resting time in the Valsartan group, with increased amplifications of DF at post-resting 60 s and 120 s (P < 0. 05) (4) The amplifications of DF in different Ca²âº concentrations: Compared with the sham-operation group, the amplifications of DF were significantly elevated in different Ca²âº concentrations (1.75, 3.5, 7.0 mmol/L ) (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in amplification of DF in different Ca²âº concentrations in the KG group (P > 0.05). The amplifications of DF in different Ca²âº concentrations were significantly reduced in the Valsartan group (P < 0.05). CONCLUSIONS: The ISO response and the Forskolin response were enhanced in isolated heart papillary muscle tonus of pressure overload induced DHF rats; enhanced post-resting DF was reduced; DF in different supra-physiologic levels of Ca²âº was still enhanced. KG could significantly improve excessive enhancement of pressure overload induced DHF rats in ISO response and Forskolin response, and improve enhancement of post-resting myocardium.

Curcumin induces apoptosis in human gastric carcinoma AGS cells and colon carcinoma HT-29 cells through mitochondrial dysfunction and endoplasmic reticulum stress.

In the present study, we investigate the effect of curcumin, a major active component isolated from rhizomes of Curcuma longa, on the cytotoxicity of three human carcinoma cell lines (AGS, HT-29 and MGC803) in gastrointestinal tract and a normal gastric epithelial cell line GES-1, and the mechanism of curcumin-induced apoptosis. The results indicated that curcumin inhibited the gastrointestinal carcinoma cell growth in a dose-dependent manner and cytotoxicity was more towards the gastric carcinoma cell AGS and colon carcinoma cell HT-29 compared to normal gastric cell GES-1, and increased externalization of phosphatidylserine residue was observed by Annexin V/PI staining in the two cell lines. Treatment of AGS and HT-29 cells with curcumin enhanced the cleavage of procaspase-3, -7, -8 and -9. Meanwhile, curcumin induced endoplasmic reticulum (ER) stress and mitochondrial dysfunction as evidenced by up-regulation of CCAAT/enhancer binding protein homologous protein (CHOP), phosphorylation of JNK and down-regulation of SERCA2ATPase, release of cytochrome c, decrease of Bcl-2 and reduction of mitochondrial membrane potential in both AGS and HT-29 cells. Overexpression of bax, total JNK, phospho-FADD and total FADD were also observed in curcumin-treated HT-29 cells. Moreover, curcumin decreased cytosolic and ER Ca(2+), but increased mitochondrial Ca(2+) in the two cell lines. 2-Aminoethoxydiphenyl borate, an antagonist of inositol 1, 4, 5-triphosphate receptor, partly blocked curcumin-induced cytosolic Ca(2+) decrease in AGS and HT-29 cells. Additionally, carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca(2+) uptake, reversed curcumin-triggered AGS and HT-29 cells growth inhibition. siRNA to CHOP markedly reduced curcumin-induced apoptosis. These results suggest that curcumin can impact on ER stress and mitochondria functional pathways in AGS and HT-29 cells, death receptor pathway was also involved in curcumin-treated HT-29 cells, thus identifying specific well-defined molecular mechanisms that may be targeted by therapeutic strategies.

α-asarone from Acorus gramineus alleviates epilepsy by modulating A-type GABA receptors.

Alpha (α)-asarone is a major effective compound isolated from the Chinese medicinal herb Acorus gramineus, which is widely used in clinical practice as an antiepileptic drug; however, its mechanism of action remains unclear. In this study, we have characterized the action of α-asarone on the excitability of rat hippocampal neurons in culture and on the epileptic activity induced by pentylenetetrazole or kainate injection in vivo. Under cell-attached configuration, the firing rate of spontaneous spiking was inhibited by application of α-asarone, which was maintained in the Mg(2+)-free solution. Under whole-cell configuration, α-asarone induced inward currents in a concentration-dependent manner with an EC(50) of 248 ± 33 µM, which was inhibited by a GABA(A) receptor blocker picotoxin and a competitive GABA(A) receptor antagonist bicuculline but not a specific glycine receptor inhibitor strychnine. Measurement of tonic GABA currents and miniature spontaneous inhibitory postsynaptic currents indicated that α-asarone enhanced tonic GABAergic inhibition while left phasic GABAergic inhibition unaffected. In both pentylenetetrazole and kainate seizure models, α-asarone suppressed epileptic activity of mice by prolonging the latency to clonic and tonic seizures and reducing the mortality as well as the susceptibility to seizure in vivo presumably dependent on the activation of GABA(A) receptors. In summary, our results suggest that α-asarone inhibits the activity of hippocampal neurons and produces antiepileptic effect in central nervous system through enhancing tonic GABAergic inhibition.

Subunit-specific inhibition of glycine receptors by curcumol.

Emerging evidence has suggested that inhibitory glycine receptors (GlyRs) are an important molecular target in the treatment of numerous neurological disorders. Rhizoma curcumae is a medicinal plant with positive neurological effects. In this study, we showed that curcumol, a major bioactive component of R. curcumae, reversibly and concentration-dependently inhibited the glycine-activated current (IGly) in cultured rat hippocampal neurons. The inhibitory effect was neither voltage- nor agonist concentration-dependent. Moreover, curcumol selectively inhibited homomeric α2-containing, but not α1- or α3-containing, GlyRs. The addition of ß subunit conferred the curcumol sensitivity of α3-containing, but not α1-containing, GlyRs. Site-directed mutagenesis analysis revealed that a threonine at position 59 of the α2 subunit is critical for the susceptibility of GlyRs to curcumol-mediated inhibition. Furthermore, paralleling a decline of α2 subunit expression during spinal cord development, the degree of IGly inhibition by curcumol decreased with prolonged culture of rat spinal dorsal horn neurons. Taken together, our results suggest that the GlyRs are novel molecular targets of curcumol, which may underlie its pharmaceutical effects in the central nervous system.

Effect of jatrorrhizine on delayed gastrointestinal transit in rat postoperative ileus.

OBJECTIVES: Postoperative ileus is major cause of postoperative complication and prolonged hospitalization. Jatrorrhizine, which is a protoberberine alkaloid isolated from the medicinal plants Berberis aristata and Coptis chinensis, has been found to increase contractility of gastric antral and ileum smooth muscles of rat gastrointestinal tract. We have investigated whether jatrorrhizine could offset gastrointestinal transit in rat with postoperative ileus. METHODS: Postoperative ileus was induced by laparotomy with intestinal manipulation under anaesthesia. Gastrointestinal transit was evaluated by measurement of gastric emptying, geometric centre and the migration of Evans blue. KEY FINDINGS: Postoperative ileus significantly delayed gastric emptying and intestinal transit. Jatrorrhizine dose-dependently (0.1, 0.3 and 1 mg/kg) offset delayed gastric emptying and intestinal transit (geometric centre and the migration of Evans blue) in postoperative ileus. Pretreatment of animals with atropine inhibited the action of jatrorrhizine on gastric emptying and intestinal transit, but pretreatment of animals with SB204070 did not influence the effect of jatrorrhizine on gastric emptying and intestinal transit in postoperative ileus. CONCLUSIONS: Jatrorrhizine offset postoperative ileus-induced delayed gastric emptying and intestinal transit in rats, an action mediated via the cholinergic pathway, but not involving activation of 5-HT(4) receptors.

[Effects of sinensetin on proliferation and apoptosis of human gastric cancer AGS cells].

OBJECTIVE: To study the effects and mechanisms of sinensetin on proliferation and apoptosis of human AGS gastric cancer cells. METHOD: MTT assay was used to detect the growth inhibition rates of human AGS gastric cancer cells treated with sinsesectin in different concentrations and times. The cell cycle distribution was measured by flow cytometry. The apoptosis was examined by Annexin-FITC/PI staining and DNA fragment analysis. The apoptosis morphology was observed by inverted fluorescence microscope after Hoechst 33342 staining. The protein expressions of p21 and p53 were detected by western blot. RESULT: MTT assay showed that sinensetin inhibited the growth of AGS gastric cancer cells in a dose- and time-dependent manner. Sinensetin blocked AGS cells in G2/ M and increased the apoptosis rates of AGS cells in a dose-dependent manner. DNA ladder was observed in cells treated with 60 micromol x L(-1) sinensetin for 48 h. The typical apoptotic morphological changes including cell nucleus shrinkage, chromatin condensation and apoptotic bodies were observed when treated with different dose of sinensetin. Western blot showed that sinensetin increased expressions of p53 and p21 in a dose-dependent manner. CONCLUSION: Sinensetin could inhibit human AGS gastric cancer cells proliferation and induce cell cycle block in G2/M phase and apoptosis. The up regulation of p53 and p21 protein might be one of the mechanisms.

Traditional Chinese formula, lubricating gut pill, stimulates cAMP-dependent CI(−) secretion across rat distal colonic mucosa.

AIM OF THE STUDY: Lubricating gut pill (LGP), a traditional Chinese formula, had been conformed to improve the loperamide-induced rat constipation by stimulation of Cl(-) secretion, but its mechanism has not been fully explored. Thus, the purpose of this study was to identify the action sites of LGP-stimulated Cl(-) secretion across rat distal colonic mucosa. MATERIALS AND METHODS: Rat distal colonic mucosa was mounted in Ussing chambers and short circuit current (I(SC)), apical Cl(-) current and basolateral K(+) current were recorded. Intracellular cyclic adenosine monophosphate (cAMP) content and protein kinase A (PKA) activity were determined with ELISA kit and the non-radioactive PepTag test, respectively. RESULTS: LGP at 800µg/ml elicited a sustained increase in Cl(-) secretory response, which was inhibited by CFTR(inh)172, a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor. Permeabilizing apical membrane with nystatin revealed that LGP-stimulated basolateral K(+) current was significantly inhibited by KCNQ1 K(+) channel inhibitor chromanol 293B. LGP-stimulated I(SC) was markedly reduced by pretreatment with cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2amine (MDL-12,330A) and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), but not with inhibitors of Ca(2+)-dependent signaling pathway. Treatment of tissue with LGP resulted in an increase in intracellular cAMP level and the activation in protein kinase A. The E-prostanoid(4) (EP)(4) receptor antagonist L-161,982 completely eliminated LGP-induced response. CONCLUSIONS: The results showed that LGP enhances Cl(-) and fluid secretion via prostanoid receptor signaling and also cAMP and protein kinase A pathway, subsequently triggering the activation of apical Cl(-) channels mostly CFTR and basolateral cAMP-dependent K(+) channel.

[Effects of Coptis chinensis and Evodia rutaecarpa water extract on DMH-induced precancerous lesion of colon].

OBJECTIVE: To investigate the effects of Coptis chinensis and Evodia rutaecarpa water extract on precancerous lesion of colon induced by DMH and proliferation and apoptosis changes of colon mucosa crypts. METHOD: Precancerous lesion of colon was induced by DMH. The changes of proliferation and apoptosis of colon mucosa crypts were detected by morphological analysis. The numbers of aberrant crypt foci (ACF) were measured by feulgen staining. RESULT: C. chinensis and E. rutaecarpa water extract could significantly inhibit the formation of ACF in model animals. The proliferative crypts were increased obviously in middle and distal colon, and decreased by C. chinensis and E. rutaecarpa water extract. The apoptosis crypts were increased in distal colon but not middle colon. C. chinensis and E. rutaecarpa water extract could promote apoptosis of both middle and distal colon. CONCLUSION: C. chinensis and E. rutaecarpa water extract could significantly inhibit the formation of ACF in model animals. These results indicated that C. chinensis and E. rutaecarpa water extract maybe have an inhibitory and clinically therapeutic effect on colon cancer, which were partly resulted from inhibiting proliferation and promoting apoptosis of crypts in middle and distal colon.

Traditional Chinese formula, lubricating gut pill, improves loperamide-induced rat constipation involved in enhance of Cl- secretion across distal colonic epithelium.

AIM OF THE STUDY: Lubricating gut pill (LGP), a traditional Chinese formula, was widely used for the treatment of chronic constipation, especially in the elderly, in China. However, it is unclear whether LGP-induced laxative and/or lubricating effect is involved in water and electrolytes transport in distal colonic epithelium. MATERIALS AND METHODS: The present study was designed to evaluate the effect of LGP on Cl(-) secretion across rat distal colonic epithelium mounted in Ussing chambers, and on a rat constipation model induced by loperamide, respectively. RESULTS: Application of LGP in the apical side elicited a sustained increase in short circuit current (I(SC)) response in a concentration-dependent manner. Evidence that LGP-stimulated I(SC) was due to Cl(-) secretion is based on inhibition of current by (a) a Na(+)-K(+)-2Cl(-) cotransporter inhibitor bumetanide, (b) removal of Cl(-) ions in bath solution, and (c) the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel blocker DPC, suggesting that a apical cAMP-dependent Cl(-) channel was activated. LGP-stimulated I(SC) was also strongly inhibited by pretreatment with clotrimazole, indicating that the basolateral K(+) channel was also involved in maintaining this cAMP-dependent Cl(-) secretion. Pretreatment of tissues with indomethacin, but not atropine, tetrodotoxin or hexamethonium, inhibited LGP-induced response. In a rat constipation model, oral administration with LGP was significantly restored number of fecal pellets, water content and mucus secretion compared with loperamide-treated group alone. CONCLUSIONS: LGP enhances Cl(-) secretion that is mostly mediated through the release of cyclooxygenase metabolites, by which provided an osmotic force for the subsequent laxative action observed in the rat constipation model.

[Tongxie Yaofang inhibits the contraction of colonic smooth muscle isolated from rats through a mechanism related to calcium mobilization].

OBJECTIVE: To study the relationship between the inhibitory effects of Tongxie Yaofang, a compound traditional Chinese herbal medicine, on the contraction of the colonic smooth muscle isolated from rats and calcium mobilization. METHODS: By measuring the tension of the isolated colonic smooth muscle strips, the inhibitory effects of Tongxie Yaofang on the contraction induced by acetylcholine (ACh), KCl and exhausting Ca(2+) of internal calcium store were assessed respectively. RESULTS: Tongxie Yaofang could concentration-dependently inhibit the contraction of isolated rat colonic smooth muscle strips induced by KCl and exhausting the Ca(2+) of internal calcium store. Tongxie Yaofang could also inhibit the tension of the second contractile phase induced by ACh (P<0.01, vs control), but had no influence on the first contractile phase. CONCLUSION: Tongxie Yaofang can inhibit the contraction of isolated rat colonic smooth muscle strips mainly by preventing the influx of extracellular Ca(2+), which may be associated with blocking voltage-dependent channel, store-operated channel and receptor-operated channel, but not by preventing the release of internal Ca(2+) from calcium store.

Effects of Puerariae radix extract on the increasing intestinal permeability in rat with alcohol-induced liver injury.

AIM OF THE STUDY: Puerariae radix, as an edible plant, has been used for centuries in China to treat alcohol-related problems, including alcoholic liver disease (ALD). However, the mechanisms of Puerariae radix on the liver-protective effect have not been fully explored. Because an increased intestinal permeability is a major factor for ALD, the present study investigates whether Puerariae radix extract (PRE) inhibits ALD through prevention of alterations in intestinal permeability. MATERIALS AND METHODS: We used an animal model of chronic alcohol-induced liver injury that is associated with increased intestinal permeability. Male Wistar rats were given increasing alcohol doses from 2 g/kg/d to 8 g/kg/d and alcohol plus PRE via intragastric feeding for 10 weeks. Chronic alcohol exposure caused an elevation in serum alanine aminotransferase (ALT) as well as aspartate aminotransferase (AST) levels and a decrease in superoxide dismutase (SOD) activity, and hepatic damages including steatosis, inflammation, and necrosis, determined by serum enzymatic analysis and morphological analysis, respectively. The damage to small intestine induced by chronic alcohol treatment was examined by intestinal histological, immunohistochemical analysis, and permeability assays. RESULTS: Alcohol-induced hepatic pathological changes, elevations in ALT and AST, and a decrease in SOD activity were significantly inhibited in PRE treated animals. The inhibitory effect of PRE on alcohol-induced liver injury was associated with suppression of alcohol induced the increase of intestinal permeability. CONCLUSIONS: The results showed that this beneficial effect of PRE on ALD could be partly explained by improving intestinal barrier dysfunction induced by alcohol.

[Effects of extracts and active components of Rhizoma Coptidis on contraction of circular smooth muscle isolated from guinea pig gastric antrum].

OBJECTIVE: To identify the influence of extracts and active components of Rhizoma Coptidis on gastric smooth muscle contractility of guinea pigs, and to explore the potential pharmacological mechanism of Rhizoma Coptidis in "invigorating the stomach" and "impairing the stomach". METHODS: Observing the effects of the water extract and the alkaloids from Rhizoma Coptidis (at doses ranging from 0.3 to 1,000 microg/L) and other active components such as berberine, palmatine and jatrorrhizine (at doses ranging from 0.3 to 1,000 micromol/L) on the spontaneous and electrical field stimulation (EFS)-induced contractions of antral circular smooth muscle strips from guinea pig stomach via a force transducer in vitro. RESULTS: The water extract or the alkaloids from Rhizoma Coptidis could improve the spontaneous contraction at the low doses, but inhibit the spontaneous contraction at the high doses. Berberine, palmatine and jatrorrhizine also showed the similar effects. Moreover, the water extract and the alkaloids of Rhizoma Coptidis, as well as berberine, palmatine and jatrorrhizine could increase the EFS-induced contraction. Among the three monomers, jatrorrhizine exhibited the most potent effect on EFS-induced contraction. CONCLUSION: The effects of Rhizoma Coptidis in "invigorating the stomach" or "impairing the stomach" may be related to its effect on gastric smooth muscle contractility. Berberine, palmatine and jatrorrhizine are all effective components of Rhizoma Coptidis affecting the contraction of gastric smooth muscle, among which jatrorrhizine is the most potent agent in promoting the contraction while berberine is the most potent one for inhibiting the contraction.

[Effects of Astragalus membranaccus on cardiac function and SERCA2a gene expression in myocardial tissues of rats with chronic heart failure].

OBJECTIVE: To investigate the effects of Astragalus membranaccus (As) on cardiac function and SERCA2a gene expression in left ventricular tissues of rats with chronic heart failure. METHODS: Heart failure was induced by clipping the abdominal aorta 60 male SD rats were divided into four groups: sham-operated (Sham), aortic stenosis (Model), Model + As (20 g/kg) and Model + Captopril (0.05 g/kg). The drugs were administered orally from the 13th week after surgery. Rats were examined after 12 weeks' treatment with drugs. The parameters of hemodynamics including LVSP, LVEDP, and +/- LVdp/dt(max) were measured. SERCA2a mRNA and protein expressions in left ventricular tissues were determined by half-quantitative RT-PCR and Western blot normalized to abundance of GAPDH mRNA and portein, respectively. RESULTS: LVSP and LVEDP were obviously enhanced (P < 0.01 or P < 0.001) in model rats in vivo. Both Captopril and As prevented the increase of LVSP (P < 0.05 or P < 0.01) and LVEDP (P < 0.05 or P < 0.01). RT-PCR and Western blot results demonstrated that SERCA2a gene expression was downregulated (P < 0.05) significantly in model group compared with sham group. As upregulated SERCA2a gene expression (P < 0.05), whereas Captopril had no effect on that. CONCLUSION: As can ameliorate abnormity of cardiac function, especially diastoilc function in rats with pressure overload-induced heart failure, and that may be partly related to its up-regulation of SERCA2a gene expressions in left ventricular tissues.

[Inhibitory effect on activated renin-angiotensin system by astragaloside IV in rats with pressure-overload induced cardiac hypertrophy].

OBJECTIVE: To investigate the effect of astragaloside IV (As IV) on the activation of rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy. METHOD: Left ventricle hypertrophy was induced by abdominal aorta banding between bilateral renal aortas for 12 weeks. Rats were given astragaloside IV 1.0 mg x kg(-1) and 3.3 mg x kg(-1) for 12 weeks, respectively. After treatment, the left ventricular mass index (LVMI)was calculated by morphometry methods. Plasma and cardiac tissue angiotensin II, and plasma aldosterone were measured by ELISA method. Gene expressions of ACE, AT1 and AT2 in cardiac tissue were detected by real time PCR. Protein expressions of AT1 and AT2 in cardiac tissue were detected by Western blot. RESULT: Compared with model rats, LVMI was decreased by astragaloside IV treatment. Biochemical results indicated that the contents of angiotensin II in plasma and cardiac tissue as well as aldosterone in plasma were all increased in abdominal aorta banding rats comparing with sham-operated rats, then, decreased by astragaloside IV treatment. Gene expressions of cardiac ACE was downregulated by astragaloside IV, however, gene and protein expressions of cardiac AT2 were upregulated by astragaloside IV. Both elevated gene and protein expressions of AT1 were not attenuated by astragaloside IV. CONCLUSION: Excessive activated rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy is inhibited by astragaloside IV treatment.

[Effect of astragalus on calcium accumulation and SERCA2a gene expression in myocardial tissues in rats with pressure overload-induced left ventricular hypertrophy].

OBJECTIVE: To investigate the effect of astragalus (As) on calcium accumulation and SERCA2a gene expression in left ventricular tissues in rats with pressure overload-induced cardiac hypertrophy. METHOD: cardiac hypertrophy was induced by clipping the abdominal aorta in rats. Male SD rats were allocated to six groups: sham-operrated (Sham), aortic stenosis (Model), model +As-L (5 g x kg(-1) x d(-1)), model+As-M (10 g x kg(-1) x d(-1)), model+As-H (20 g x kg(-1) x d(-1)) and model + captopril (0.05 mg x kg(-1) x d(-1), a positive control). The drugs were administered orally from the 13 th week after surgery. Rats were examined after 12 week treatment with drugs. The cardiac hypertrophy was evaluated by left ventricular mass index (LVMI, left ventricular weight/ body weight). The calcium content in left ventricular tissue was measured by atomic absorption spectrometry. SERCA2a mRNA and protein expressions in left ventricular tissues were determined by half-quantitative RT-PCR and Western blot normalized to abundance of GAPDH mRNA and protein, respectively. RESULT: The increase of LVMI was dose-dependently lessened by As (P < 0.01, P < 0.001). The effect of As-H was similar to that of Captopril. As markedly attenuated calcium accumulation in myocardial tissure (P < 0.01). RT-PCR and Western blot results demonstrated that SERCA2a gene expressions were downregulated (P < 0.05) significantly in model group compared with sham group. As-H upregulated SERCA2a gene expressions (P < 0.05), whereas Captopril had no effect on that. CONCLUSION: The inhibition of As on left ventricular hypertrophy induced by pressure overload in rats may partly contribute to its attenuation of calcium accumulation and up-regulation of SERCA2a gene expressions in left ventricular tissues.

[Effect of jinfu kang to experimental precancerous colon lesions and urinary metabolites in rat].

OBJECTIVE: : To profile urinary metabolite variations from 1, 2-dimethylhydrazine (DMH)-induced precancerous colon rats, Jinfu Kang treated rats and healthy controls. METHOD: We used ethyl chloroformate derivatization and gas chromatography-mass spectrometry (GC-MS) based metabonomic method to analyze rat urines. RESULT: The time-dependent variations of metabolite profile showed a progressive deviation of the metabolism in the model group from the initial pattern over time and a systemic recovery of the metabolism in the treatment group, which is consistent with the histological results. The in-depth analysis indicated that the disorder of tricarboxylic acid cycle (TCA), tryptophan metabolism, polyamine metabolism and gut flora structure were associated with DMH intervention. CONCLUSION: Metabolic study revealed that Jinfu Kang can effectively reverse metabolic departures in DMH-induced precancerous colon rat, which is consistent with pathological results.

In vitro and in vivo evaluation of the anti-asthmatic activities of fractions from Pheretima.

Pheretima (family Megascolecidae) has been documented as a potent agent for the treatment of cough and breathing difficulty in traditional Chinese medicine for nearly 2000 years. The water extract of Pheretima was separated into three fractions of the ethanolic precipitate, the alkaline fraction and the acidic fraction. Among the three fractions, the acidic fraction showed the most potent spasmolytic effects on histamine-induced contractions in isolated guinea pig tracheal rings, and the most inhibitory activities on increase of short circuit current induced by carbachol in isolated rat tracheal epitheliums with the IC50 values of 0.15 and 0.08 mg/ml, respectively. Further in vivo studies also displayed that the acidic fraction could protect experimental asthma model induced by the combination of histamine and acetylcholine chloride in guinea pigs to prolong the latent periods of asthma (P < 0.05) and significantly decrease the cough frequency caused by ammonia water in mice (P < 0.001).

Gastroprotective effect of fructus evodiae water extract on ethanol-induced gastric lesions in rats.

Fructus Evodiae is a widely used herbal medicine with anti-inflammatory and analgetic activities in China. The present study was designed to investigate the effect of Fructus Evodiae water extract (FE) on ethanol-induced gastric lesions in rats. Three hours before ethanol challenge, animals were intraperitoneally treated with FE (424.8 mg/kg, 141.6 mg/kg, and 47.6 mg/kg). Subsequently, we employed ex-vivo chamber technique to examine the effect of FE on gastric transmucosal potential difference (PD) changes. NO(x) (nitrate and nitrite) in gastric perfusate and gastric lesion index of whole glandular stomach were determined by intubation. The results showed that FE dose-dependently accelerated the recovery of PD reduction by ethanol, and increased NO(x) production in gastric perfusate. FE also inhibited gastric lesion formation in a dose-dependent manner. These results suggested that FE prevented ethanol-induced gastric mucosal lesions by strengthening the mucosal barrier integrity and increasing gastric mucosal nitric oxide (NO) synthesis.

Gastroprotective effect of a traditional Chinese herbal drug "Baishouwu" on experimental gastric lesions in rats.

"Baishouwu" is an appellative name of dried root tubers from three Asclepiadaceae plants: Cynanchum auriculatum Royle ex Wight, Cynanchum bungei Decne and Cynoctonum wilfordii Maxim. In order to establish the pharmacological basis for the ethnomedicinal use of Baishouwu in gastric disorders, this study examined the effects of ethanol extracts and fractions from root tubers of Cynanchum auriculatum, Cynanchum bungei and Cynoctonum wilfordii on ethanol-, indomethacin-induced gastric lesions and histamine-induced gastric acid secretion in rats. Plant materials were collected from various areas of China. Oral administration of ethanol extract and chloroform fraction of Cynoctonum wilfordii collected from Changbai Cordillera at doses of 150 and 68 mg/kg, respectively, significantly inhibited the development of ethanol- and indomethacin-induced gastric lesions and also caused significant decrease of gastric acid secretion after histamine-induced gastric lesion. Oral administrations of ethanol extract and chloroform fraction of Cynanchum auriculatum collected from Binhai at the doses of 300 and 69 mg/kg, respectively, significantly inhibited ethanol- and indomethacin-induced gastric lesions. This study demonstrates the gastroprotective property of Baishouwu for the first time.

[Study on the proportion & mechanism of reliving asthma of drug partnership comprising herbal Ephedrae sinica & Pheretima aspergilum].

OBJECTIVE: To study the proportion and mechanism of relieving asthma of drug partnership comprising herbal Ephedrae & Pheretima. METHOD: To study relaxant effect on 10 micromol x L(-1) carbachol (CCh) and 10 micromol x L(-1) histamine (His) precontracted isolated tracheal rings and lowering effect on short-circuit current (Isc) increase induced by 10 micromol x L(-1) CCh with 3 proportions of 1:1, 1:3, 1:9 extract. RESULT: 1:3 proportions dose-dependently relaxed CCh-precontracted isolated tracheal rings, IC50 of 1:1, 1:3 is 7.5, 15 mg x mL(-1) respectively, 1:9 could not produce 50% inhibition effect on CCh-evoked contraction; 3 proportions also dose-dependently relaxed His-precontracted isolated tracheal rings, IC50 of 1:9, 1:3 and 1:1 is 0.19, 0.61, 1.8 mg x mL(-1) respectively. On the other hand,the orders potency of the decrease effect on CCh-evoked short circuit current increase is 1:3 > 1:1 > 1:9. The difference is not significant (P < 0.05). CONCLUSION: Herbal Ephedrae & Pheretima had tracheal muscle relaxant and epithelium ion secretion inhibition effect, its mechanism of relieving asthma involved anti-CCh and anti-His effect 1:3 was the most appropriate dosage ratio in the anti-asthmatic drug partnership.