Zhuo Qu

Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat

Aging is associated with Alzheimers disease (AD), cardiovascular disease and cancer. Oxidative stress is considered as a major factor that accelerates the aging process. d-galactose (d-gal), a reducing sugar, induces oxidative stress resulting in alteration in mitochondrial dynamics and apoptosis of neurons. To understand the ability of tetrahydropalmatine (THP) to ameliorate memory impairment caused by aging, we investigated the effect of THP on d-gal induced memory impairment in rats. Subcutaneous injection of d-gal (100mg/kg/d) for 8weeks caused memory loss as detected by the Morris water maze and morphologic abnormalities of neurons in the hippocampus regions and cortex of rat brain. THP treatment ameliorated d-gal induced memory impairment associated with the decrease of malondialdehyde (MDA) and nitric oxide (NO) contents, as well as the increase of glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. THP treatment was also found to reverse the abnormality of acetylcholine (ACh) levels and acetylcholinesterase (AChE) activities. In addition, treatment with THP could decrease the expression of nuclear factor κ (NF-κB) and glial fibrillary acidic protein (GFAP) which prevented the neuroinflammation and memory impairment in the d-gal treated rats. Taken together, these results clearly demonstrated that subcutaneous injection of d-gal produced memory deficits, meanwhile THP could protect neuron from d-gal insults and improve cognition. This study provided an experimental basis for clinical application of THP in AD therapy.

Pharmacokinetic study on costunolide and dehydrocostuslactone after oral administration of traditional medicine Aucklandia lappa Decne. by LC/MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE Radix Aucklandiae (RA), a well known traditional Chinese medicine, is widely used for treating various problems in digestive system. A selective and sensitive high-performance liquid chromatography coupled with mass spectrometry method was first developed and validated for simultaneous quantification of costunolide and dehydrocostuslactone in rat plasma with diazepam as internal standard after oral administration of RA extraction. MATERIALS AND METHODS Plasma samples were extracted via solid-phase extraction and detected by multiple-reaction monitoring mode under positive electrospray. Chromatographic separation was accomplished on an Agilent C18 column (2.1 mm × 150 mm, 5 µm), with 0.1% formic acid and acetonitrile (1:1) as the mobile phase at a flow rate of 0.5 mL/min. RESULTS The quantification was performed using the transitions of m/z 233/187 for costunolide, m/z 231/185 for dehydrocostuslactone and m/z 285/193 for diazepam, respectively. Calibration curves were linear over the concentration range of 0.7-769.7 ng/mL for costunolide and 0.9-956.0 ng/mL for dehydrocostuslactone. The intra-day and inter-day precisions (RSD%) for two compounds was less than 8.76% and 9.70% and the accuracy (RE%) range from 6.14% to 5.35%. The time to reach the maximum plasma concentration (Tmax) was 10.46 h for costunolide, 12.39 h dehydrocostuslactone. The elimination half-time (t1/2) of costunolide and dehydrocostuslactone was 5.54 ± 0.81 and 4.32 ± 0.71 (h). The AUC of costunolide and dehydrocostuslactone was 308.83 and 7884.51 respectively (ngh/mL). CONCLUSIONS It was the first report for the study of pharmacokinetic profile of costunolide and dehydrocostuslactone in rat plasma after oral administration of RA extract. These results provided a meaningful basis for better understanding the absorption of traditional medicine, RA, and provide useful scientific data for clinical application.

Gastrointestinal effect of methanol extract of Radix Aucklandiae and selected active substances on the transit activity of rat isolated intestinal strips

Abstract Context: Radix Aucklandiae, the dry rhizome of Aucklandia lappa Decne (Asteraceae), enjoyed traditional popularity for its antidiarrheal effects. Although there are many investigations on its chemical constituents and pharmacologic actions, few studies explaining its activity and mechanism in gastrointestinal disorders are available. Objective: In this paper, we focused on the effects of the methanol extract of R. Aucklandiae (RA ext) on gastrointestinal tract, so as to assess some of the possible mechanisms involved in the clinical treatment. Materials and methods: In vivo, in neostigmine-induced mice and normal mice, after intragastric administration, RA ext (100, 200, 300, and 400 mg/kg) was studied on gastrointestinal transit including gastric emptying and small intestinal motility. Meanwhile, in vitro, the effect of it (0.1, 0.2, 0.3, and 0.4 mg/mL) on the isolated tissue preparations of rat jejunum was also investigated, as well as costunolide and dehydrocostuslactone which were the main constituents. Results: In vivo, the gastric emptying increased and intestinal transit decreased after the administration of RA ext in normal mice. However, RA ext inhibited the gastric emptying and the intestinal transit throughout the concentrations in neostigmine-induced mice. In vitro, RA ext caused inhibitory effect on the spontaneous contraction of rat-isolated jejunum in a dose-dependent manner ranging from 0.1 to 0.4 mg/mL, and it also relaxed the acetylcholine chloride (Ach, 10−5 M), 5-hydroxytryptamine (5-HT, 200 μM)-induced, and K+ (60 mM)-induced contractions. RA ext shifted the Ca2+ concentration–response curves to right, similar to that caused by verapamil (0.025 mM). The Ca2+ concentration–response curves were shifted by costunolide (CO) (5.4, 8.1, and 10.8 μg/mL), dehydrocostuslactone (DE) (4.6, 6.9, and 9.2 μg/mL), costunolide–dehydrocostuslactone (CO–DE) (5.4–4.6, 8.1–6.9, and 10.8–9.2 μg/mL) to the right, similar to that caused by verapamil (0.01 mM). Discussion and conclusion: These results indicate that RA ext played a spasmolytic role in gastrointestinal motility, which is probably mediated through the inhibition of muscarinic receptors, 5-HT receptors, and calcium influx. The presence of cholinergic and calcium antagonist constituents may be the compatibility of CO and DE. All these results provide a pharmacological basis for its clinical use in the gastrointestinal tract.

Ferulic acid ameliorates memory impairment in d-galactose-induced aging mouse model.

Abstract Ferulic acid (FA) acts as a powerful antioxidant against various age-related diseases. To investigate the effect and underlying mechanism of FA against d-galactose(d-gal)-induced memory deficit, mice were injected with d-gal to induce memory impairment and simultaneously treated with FA and donepezil. The behavioral results revealed that chronic FA treatment reversed d-gal-induced memory impairment. Further, FA treatment inhibited d-gal-induced AChE activity and oxidative stress via increase of superoxide dismutase activity and reduced glutathione content, as well as decrease of malondialdehyde and nitric oxide levels. We also observed that FA significantly inhibits inflammation in the brain through reduction of NF-κB and IL-1β by enzyme-linked immunosorbent assay. Additionally, FA treatment significantly reduces the caspase-3 level in the hippocampus of d-gal-treated mice. Hematoxylin and eosin and Nissl staining showed that FA prevents neurodegeneration induced by d-gal. These findings showed that FA inhibits d-gal-induced AChE activity, oxidative stress, neuroinflammation and neurodegeneration, and consequently ameliorates memory impairment.

Bidirectional effects of methanol extract of Wei-Chang-An pill on gastrointestinal transit and the spasmolytic activity on isolated rat jejunum

ETHNOPHARMACOLOGICAL RELEVANCE Wei-Chang-An pill (WCA pill), a traditional Chinese medicine, has been used for treating various gastrointestinal diseases for several decades. Despite the popular medicinal use of WCA pill, less data was available to its activity and mechanism in gastrointestinal disorders. To examine the effects of the methanol extract of WCA pill (ME) on gastrointestinal tract so as to assess some of the possible mechanisms involved in the clinical treatment. MATERIALS AND METHODS ME was studied on gastrointestinal transit in vivo including gastric emptying and small intestinal motility in normal and neostigmine-induced mice, as well as on the isolated tissue preparations of rat jejunum in vitro. RESULTS In vivo, the gastric emptying decreased and intestinal transit increased after administration of ME in normal mice. However, administration of ME accelerated the intestinal transit ranging from 0.01 to 0.8 mg/mL and reduced it at the concentration of 1.6 and 3.2 mg/mL, while the gastric emptying was inhibited throughout the concentrations in neostigmine-induced mice. in vitro, ME caused inhibitory effect on the spontaneous contraction of rat-isolated jejunum in dose-dependent manner ranging from 0.01 to 6 mg/mL and also relaxed the acetylcholine chloride (Ach, 10(-6) M)-induced and K+ (60 mM)-induced contractions. ME shifted the Ca2+ concentration-response curves to right, similar to that caused by verapamil (0.025 mM). CONCLUSIONS These results indicated that ME might play a bidirectional role in gastrointestinal transit modulation and the effects on isolated tissue are probably mediated through calcium influx and muscarinic receptors, which provides pharmacological basis for the clinical use of WCA pill in gastrointestinal tract disorders.

Effects of drying processes on starch-related physicochemical properties, bioactive components and antioxidant properties of yam flours

The effects of five different drying processes, air drying (AD), sulphur fumigation drying (SFD), hot air drying (HAD), freeze drying (FD) and microwave drying (MWD) for yams in terms of starch-related properties and antioxidant activity were studied. From the results of scanning electron microscopy (SEM), polarized optical microscopy (POM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR), the MWD sample was found to contain gelatinized starch granules. The FD yam had more slow digestible (SDS) and resistant starches (RS) compared with those processed with other modern drying methods. The bioactive components and the reducing power of the dried yams, were lower than those of fresh yam. When five dried samples were compared by principal component analysis, the HAD and SFD samples were observed to have the highest comprehensive principal component values. Based on our results, HAD would be a better method for yam drying than the more traditional SFD.

Antidiabetic effect of ligustilide-rich total lactones derived from Shunaoxin dropping pills on mice with type 2 diabetes induced by a high-fat diet and streptozotocin

Shunaoxin dropping pill, a well-known Traditional Chinese Medicine formula, has been used to treat cerebrovascular diseases in China since 2005. It is composed of two herbs named Chuanxiong (Ligusticum chuanxiong Hort, Umbelliferae) and Danggui (Angelica sinensis radix, Umbelliferae). It has been reported that these two herbs have anti-diabetic activities. Phenolic acids and lactones are the main active components in Chuanxiong and Danggui. Ferulic acid and ligustilide are the representative compounds of phenolic acids and lactones, respectively. Previous study has documented the hypoglycemic activity of ferulic acid. However, the anti-diabetic activities of total lactones from Chuanxiong and Danggui or ligustilide have not been well studied. Therefore, the present study was designed to demonstrate the antihyperglycemic and antihyperlipidemic activities of ligustilide-rich total lactones (LT) from Shunaoxin dropping pills in vivo, thereby elucidating its probable antidiabetic mechanism. The present results showed that after 3 weeks of treating with LT, the blood glucose levels were significantly reduced in diabetic mice, and the oral glucose tolerance test showed that LT could improve glucose tolerance. The serum insulin concentration was also dramatically reduced. In addition, there was a marked decline in the serum levels of TG, TC, and LDL-C in mice treated with LT. In addition, the serum level of HDL-C was enhanced to a certain degree in diabetic mice treated with LT. In the histopathological examination of the mouse pancreas, LT showed significant protection of the pancreas in diabetic mice. The results provide a sound rationale for future clinical trials of the oral administration of LT for the primary prevention of diabetes mellitus.

Antihypertensive and cardioprotective effects of Cerebralcare granule® on spontaneously hypertensive rats from the perspective of the gaseous triumvirate NO-CO-H2S system.

Cerebralcare granule(®) (CG) has been reported to have hypotensive effect. However, several pathways involved in the mechanism of hypotension are still unclear. This study was designed to verify the antihypertensive effect of CG and to characterize its mechanism of action, especially from the perspective of gasotrasmmiter NO/cGMP, CO/HO and H2S/CSE systems. By using the widely used in vitro model of rat isolated thoracic aortic rings, the vasorelaxant effect of CG were studied. Furthermore, we assessed the chronic hypotensive effect of CG on spontaneously hypertensive rats (SHRs) and further to explore the potential mechanisms of its antihypertensive activity. Data in the present study demonstrated that oral treatment with CG could induce a potent antihypertensive effect. CG could reduce the intima-media thickness (IMT) of thoracic aorta significantly and increase the serum NO and H2S levels. In addition, the present results indicated that CG played a critical protective role against pressure overload-induced cardiac hypertrophy. CG not only inhibited the development of cardiac hypertrophy but also improved ventricular function. In vitro, the results showed that CG induced relaxation in rat aortic rings through an endothelium-dependent pathway mediated by NO/cGMP, CO/HO and H2S/CSE systems. Taken together, the present study demonstrated that CG could induce a potent antihypertensive effect that was partly due to the improvement of endothelial function. Also CG played a critical protective role against pressure overload-induced cardiac hypertrophy. In addition, CG could induce relaxation in rat aortic rings.

Antihypertensive and vasorelaxant effects of Rhizoma corydalis and its active component tetrahydropalmatine via NO/cGMP pathway and calcium channel blockade in isolated rat thoracic aorta

Rhizoma corydalis has been used for the treatment of a variety of cardiovascular diseases in China. Tetrahydropalmatine (THP), one of the main active ingredients isolated from Rhizoma corydalis, is reported to have potent analgesic effects and it has been used in Chinese clinical practice for many years. The main roles of the extract of Rhizoma corydalis and THP are their analgesic effect and protective effect towards the cardio-cerebral vascular system. Although there is a lot of research about the cardiovascular protective effects of Rhizoma corydalis and THP, their vasorelaxant effects on thoracic aorta have not been well studied. Therefore, the aim of the present study was designed to observe the acute antihypertensive effect of a 70% ethanol extract of Rhizoma corydalis (RC) and THP as well as investigating the possible mechanisms of vasodilatation induced by RC and THP on isolated rat aorta. The in vivo acute antihypertensive activity was measured on spontaneously hypertensive rats. Measurements (systolic blood pressure and diastolic blood pressure) were recorded before and after RC and THP treatments at 0, 1, 2, 4 and 6 h by a tail cuff method. Isolated rat thoracic aorta were used in vitro, including endothelium-intact and endothelium-denuded aortic rings. Specific inhibitors including L-NAME, ODQ, INDO, TEA, Gli and atropine were used, which were added 20 min before the NA contracted rat thoracic aorta, and then RC and THP were added to induce vasodilatation. The results demonstrated that RC and THP induced vasodilatation in an endothelium dependent and endothelium independent manner. The endothelium dependent pathway was the result of activation of the NO/cGMP signaling pathway. The endothelium independent pathways were involved in the blockade of VDCCs and inhibition of Ca2+ mobilization from intracellular stores, as well as the stimulation of the muscarinic receptor. In addition, the KATP channel was activated in the vasorelaxant mechanism of THP.

Study on the mechanisms of the bronchodilator effects of Folium Eriobotryae and the selected active ingredient on isolated guinea pig tracheal strips.

Abstract Context: Folium Eriobotryae (FE), the dry leaf of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae), has been widely used to treat respiratory disorders. Objective: To examine the bronchodilatory activity of FE and the potential mechanisms involved. Materials and methods: The effects of ethyl acetate fraction of FE (EFE) (0.05–0.3 mg/mL) on the isolated tracheal strips, and ursolic acid (UA) (5–30 μg/mL) that was the main constituent of EFE, were tested in vitro. Meanwhile, acetylcholine (Ach) and histamine (His)-induced bronchospasm were conducted in vivo in guinea pig. Furthermore, mechanisms of relaxant effects of EFE and UA were evaluated in the absence and presence of specific inhibitors. Results: With in vitro studies, the contractile response evoked by Ach or His (EC50 = 0.21 and 0.16 mg/mL) was decreased by EFE, and UA caused a concentration-dependent relaxation precontracted by His (EC50 = 23.2 μg/mL). With in vivo studies, EFE strongly prolonged preconvulsive time similar to isoprenalin. The bronchodilator effects of EFE could be blocked by propranolol (1 μM), NG-nitro-l-arginine methyl ester (l-NAME) (100 μM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 μM). EFE also inhibited the contraction in Ca2+-free medium and produced rightward parallel displacement of CaCl2 curves. In addition, the relaxant effects of UA could only be blocked by l-NAME and ODQ. Discussion and conclusion: These results suggest that bronchodilator activities of EFE were related to activation of β-adrenoceptor and NO/cGMP pathway. Blockage of Ca2+ channels and inhibition of IP3R-mediated internal Ca2+ release were also involved. Additionally, UA produced relaxant effects by the NO/cGMP pathway.