Changyu Li

Beta-asarone, a major component of Acorus tatarinowii Schott, attenuates focal cerebral ischemia induced by middle cerebral artery occlusion in rats

BackgroundIschemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. β-Asarone, which has significant pharmacological effects on the central nervous system (CNS), was used in the prevention of cerebral ischemia in this paper.MethodsThe right middle cerebral artery occlusion model was used in the study. The effects of β-Asarone on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+-K+-ATPase activity and glutathione S transferase activity in a rat model were studied respectively.Resultsβ-Asarone significantly improved the neurological outcome after cerebral ischemia and reperfusion in terms of neurobehavioral function in rats. Meanwhile, supplementation of β-Asarone significantly boosted the defense mechanism against cerebral ischemia via increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may help the brain recover from ischemic injury.ConclusionsThese experimental results suggest that complement β-Asarone is protective against cerebral ischemia in specific way. The administration of β-Asarone could reduce focal cerebral ischemic/reperfusion injury. The Mechanism of β-Asarone in protection of cerebral ischemia was via increasing antioxidants activity related to lesion pathogenesis.

Protective effect of gan mai da zao decoction in unpredictable chronic mild stress-induced behavioral and biochemical alterations.

Aim: Growing evidence indicates that the glutamatergic system, especially the abnormalities of glutamate and N-methyl-D-aspartate (NMDA) receptors contribute to the pathophysiology and possibly the pathogenesis of major depressive disorders. This study is to evaluate the effect of gan mai da zao (GMDZ) decoction on glutamate and NMDA receptor in unpredictable chronic mild stress (UCMS) rats. Materials and methods: Sucrose preference test and open field test were used to estimate the depressive-like behaviors of UCMS rats. Glutamate levels and NMDA receptor subunits (NR1, NR2A and NR2B) in the frontal cortex and hippocampus were determined by HPLC-FLD and by western-blot respectively. Results: 32 days UCMS induced depressive-like behaviors, increased glutamate concentration and decreased NMDA receptor subunits NR2A and NR2B in the frontal cortex and hippocampus of rats. However, NR1 expression remained constant in stressed rats compared with normal. The GMDZ decoction alleviated the depressive-like behavior, decreased glutamate level, and increased expression of NMDA receptor subunit NR2A and NR2B in the frontal cortex and hippocampus of stressed rats. Conclusions: These results suggest that GMDZ treatment reversed chronic unpredictable stress-induced depressive-like behaviors in UCMS rats, possibly via reducing glutamate levels and increasing the NMDA receptor subunits NR2A and NR2B in frontal cortex and hippocampus.

Metabolomics Study of Type 2 Diabetes Mellitus and the AntiDiabetic Effect of Berberine in Zucker Diabetic Fatty Rats Using Uplc‐ESI‐Hdms

The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti‐diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra‐performance liquid chromatography/electrospray ionization synapt high‐definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as ‘differentiating metabolites’ with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near‐normal state. These results suggested that the anti‐diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5′‐monophosphate‐activated protein kinase. Our work not only provides a better understanding of the anti‐diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright

Vanadium-Enriched Cordyceps sinensis, a Contemporary Treatment Approach to Both Diabetes and Depression in Rats.

This article studies a contemporary treatment approach toward both diabetes and depression management by vanadium-enriched Cordyceps sinensis (VECS). Streptozotocin-induced hyperglycemic rats were used in the study. After the rats were administered with VECS, a significant reduction in blood glucose levels was seen (P < .05) and the levels of serum insulin increased significantly (P < .05). At the same time, the study revealed a significant decrease in immobility with a corresponding increase in the swimming and climbing behavior in hyperglycemic rats following VECS treatment. The results described herein demonstrate that VECS is a contemporary treatment approach that advocates an aggressive stance toward both diabetes and depression management.

Shenqiwan Ameliorates Renal Fibrosis in Rats by Inhibiting TGF-β1/Smads Signaling Pathway

Epithelial-mesenchymal transition (EMT) refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF). Traditional Chinese Medicine Shenqiwan (SQW) is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-β1/Smads signaling pathway. A rat model of adenine (150 mg/kg) was established and intragastrically treated with various concentrations of SQW at dose of 1.5 g/kg, 3 g/kg, and 6 g/kg. Control group and model group were given the same volume of saline. Meanwhile, the positive control group was treated with Enalapril (4 mg/kg). Animals were sacrificed on 21st day after administration. The results showed that SQW could significantly relieve renal pathological damage caused by adenine, increase gene and protein expression of E-cadherin, and decrease the expression of Vimentin in kidney samples. In addition, SQW efficiently inhibited the mRNA and protein expression of p-Smad2/3 by upregulating Smad7. These results suggest that SQW could slow down the progression of renal fibrosis, possibly by inhibiting TGF-β1/Smads signaling pathway.

Urinary Metabolomic Profiling in Zucker Diabetic Fatty Rats with Type 2 Diabetes Mellitus Treated with Glimepiride, Metformin, and Their Combination.

Type 2 diabetes mellitus (T2DM) is a high incidence metabolic disease. Glimepiride, metformin, and their combination are the most commonly used therapeutics for T2DM in the clinic, but little is known about the metabolic responses of these therapies. In this study, ultrahigh-pressure liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-QTOF-MS)-based metabolomics was applied to detect changes in the urinary metabolomic profile of Zucker diabetic fatty (ZDF) rats in response to these treatments. Additionally, standard biochemical parameters (e.g., fasting plasma glucose, glycosylated hemoglobin, oral glucose tolerance, urinary glucose, triglyceride, total cholesterol, and insulin) and liver histopathology were monitored and observed. Six metabolites, including 3-galactosyl lactose, citric acid, sphingosine, phytosphingosine, ribothymidine, and succinoadenosine, were found significantly reverted to the normal level after these therapies. The present study is the first to present citric acid and sphinganine as the potential markers of T2DM, which could be used as indicators to observe the anti-diabetic effects of glimepiride, metformin, and their combination treatments.

Neuroprotective Effects and Mechanism of β-Asarone against Aβ1–42-Induced Injury in Astrocytes

Emerging evidence suggests that activated astrocytes play important roles in AD, and β-asarone, a major component of Acorus tatarinowii Schott, was shown to be a potential therapeutic candidate for AD. While our previous study found that β-asarone could improve the cognitive function of rats hippocampally injected with Aβ, the effects of β-asarone on astrocytes remain unclear, and this study aimed to investigate these effects. A rat model of Aβ1–42 (10 μg) was established, and the rats were intragastrically treated with β-asarone at doses of 10, 20, and 30 mg/kg or donepezil at a dose of 0.75 mg/kg. The sham and model groups were intragastrically injected with an equal volume of saline. Animals were sacrificed on the 28th day after administration of the drugs. In addition, a cellular model of Aβ1–42 (1.1 μM, 6 h) was established, and cells were treated with β-asarone at doses of 0, 2.06, 6.17, 18.5, 55.6, and 166.7 μg/mL. β-Asarone improved cognitive impairment, alleviated Aβ deposition and hippocampal damage, and inhibited GFAP, AQP4, IL-1β, and TNF-α expression. These results suggested that β-asarone could alleviate the symptoms of AD by protecting astrocytes, possibly by inhibiting TNF-α and IL-1β secretion and then downregulating AQP4 expression.

Metabolomics Study of the Hepatoprotective Effect of Phellinus Igniarius in Chronic Ethanol-Induced Liver Injury Mice using UPLC-Q/TOF-MS combined with Ingenuity Pathway Analysis

BACKGROUND Phellinus igniarius (L.) Quèl as a potential medicinal mushroom possesses multiple biological activities including hepatoprotection, but the hepatoprotective mechanism is not clear. PURPOSE To elucidate the hepatoprotective effect and potential target of P. igniarius. METHODS The male C57BL/6 mice were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as control diet with or without P. igniarius decoction (PID) in the dosage of 0.65 g/kg and 2.6 g/kg. The levels of serum biomarkers were detected by an automatic biochemistry analyser. The histopathological changes of liver were observed by hematoxylin and eosin (H&E) staining. Ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was applied for investigating the dynamic changes of serum metabolites in chronic ethanol-induced liver injury mice and after treatment with PID. Ingenuity pathway analysis (IPA) was employed to identify the potential target of PID. RESULTS PID could significantly reduce the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG) and total bile acid (TBA) in serum and improved hepatic steatosis and inflammation. In terms of metabolism, a total of 36 serum differential metabolites were identified, and PID intervention regulated 24 of them, involving the key metabolic pathways such as the biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis, glycerophospholipid metabolism, fatty acids biosynthesis, ether lipid metabolism and arachidonic acid metabolism. On the mechanism, IPA showed that farnesol X receptor (FXR) was the major potential target for PID, and PID could improve chronic alcohol intake induced by the inhibition of mRNA expression of FXR in the liver and the activation of mRNA expression of FXR in the intestine in mice. CONCLUSION The present study for the first time systematically illustrated the hepatoprotective effect of P. igniarius and preliminarily explored its potential target FXR. P. igniarius might be exploited as a promising therapeutic option for alcoholic liver injury.

Transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin‑treated Sprague‑Dawley rats with type 2 diabetes mellitus

The main actions of metformin are as follows: To reduce hyperglycemia via the suppression of gluconeogenesis, improve glucose uptake and insulin sensitivity, and stimulate activation of adenosine monophosphate-activated protein kinase during the treatment of diabetes mellitus. It is well known that metformin acts via complex mechanisms, including multitarget and multipathway mechanisms; however, the multi-targeted antidiabetic genes of metformin remain obscure. The present study aimed to perform transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin-treated Sprague-Dawley rats with type 2 diabetes mellitus. The type 2 diabetes rat model was established using streptozotocin. Fasting blood glucose, hemoglobin A1c, serum insulin and biological parameters were subsequently measured. Differentially expressed genes (DEGs) and proteins were identified in the rat livers by expression profile analysis and isobaric tags for relative and absolute quantitation (iTRAQ). A 1.5-fold alteration in gene expression, as determined using chip-based expression profile analysis, and a 1.2-fold alteration in protein expression, as determined using iTRAQ, were considered physiologically significant benchmarks, which were used to identify DEGS in metformin-treated rats with type 2 diabetes mellitus. The DEGs were verified using quantitative polymerase chain reaction (qPCR) and western blot analysis. Numerous hepatic genes involved in various metabolic pathways were affected by metformin; in particular, genes associated with lipid metabolism were markedly affected. Expression profile analysis and iTRAQ analysis suggested that carboxylesterase 1C subunit (Ces1C) and cholesterol 7α-hydroxylyase (Cyp7a1) may serve as important DEGs, which were validated by qPCR and western blot analysis. Ces1C and Cyp7a1 are the main enzymes in cholesterol metabolism, yet the result of western blotting was not consistent with qPCR. The present study demonstrated that metformin may affect the expression of numerous hepatic genes involved in metabolic pathways, particularly the lipid and cholesterol metabolic pathways. Ces1C and Cyp7a1 may be considered novel therapeutic target genes in the liver, which are involved in the antidiabetic effects of metformin.

Identification of Potential Therapeutic Targets in the Liver of Pioglitazone-Treated Type 2 Diabetes Sprague-Dawley Rats via Expression Profile Chip and iTRAQ Assay

The aim of the present study was to identify key antidiabetic nodes in the livers of pioglitazone-treated type 2 diabetes mellitus Sprague-Dawley rats by transcriptomic and proteomic analysis. Rats were randomly divided into the control, the diabetes model, and the pioglitazone-treated groups. After treatment with pioglitazone for 11 weeks, the effects on fasting blood glucose, body weight, and blood biochemistry parameters were evaluated. Microarray and iTRAQ analysis were used to determine the differentially expressed genes/proteins in rat livers. 1.5-fold changes in gene expression and 1.2-fold changes in protein were set as the screening criteria. After treatment with pioglitazone for 11 weeks, fasting blood glucose in pioglitazone-treated rats was significantly lower than that in the model group. There was a tendency for pioglitazone to reduce TC, TG, TP, ALB, BUN, and HDL-c levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) were applied to analyze differentially expressed genes/proteins. Furthermore, Western blotting and RT-qPCR were used to validate the results of microarray and iTRAQ. In conclusion, Cyp7a1, Cp, and RT1-EC2 are differentially expressed genes/proteins since they showed a similar trend in rats in the model group and the pioglitazone-treated group.