Wutou decoction ameliorates experimental rheumatoid arthritis via regulating NF-kB and Nrf2: Integrating efficacy-oriented compatibility of traditional Chinese medicine

BackgroundThousands of years of clinical application of Wutou decoction (WTD) support its reliable efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying molecular mechanism remains unclear, and the synergistic involvement of assistant herbs in WTD in enhancing the sovereign herb in treating RA is unknown.PurposeThis study aimed to investigate the efficacy-oriented compatibility of five herbs in WTD and the underlying mechanisms.MethodsThe anti-arthritic effects of WTD and the compatibilities of the five herbs in WTD were studied in vivo with adjuvant-induced arthritis (AIA) rat model and in vitro with LPS-induced RAW264.7 macrophage. Network pharmacology analysis was conducted to identify the dominant pathways involved in the anti-arthritis mechanisms of WTD and how the five herbs work synergistically. The results were further verified by in vivo and in vitro experiments.ResultsOur data revealed that the five herbs in WTD exert synergistic anti-arthritic effects on RA. Moreover, Radix Aconite (AC) is the principal anti-inflammatory component in WTD according to the extent of therapeutic effects exerted on the AIA rats. In vivo and in vitro experiments demonstrated that WTD inhibited NF-κB phosphorylation and simultaneously increased the expression of Nrf2, which were the major pathways identified by the network pharmacology analysis. The major assistant component, Herba Ephedrae (EP), evidently inhibited NF-κB mediated inflammatory response. The other assistant component, Radix Astragali (AS), considerably enhanced the expression of Nrf2 when used alone or in combination with AC. These combinations improved the anti-arthritis effects on the AIA rats better than that of AC alone. Nevertheless, WTD always achieved the best effects than any combinations both in vivo and in vitro.ConclusionThe ministerial herbs EP and AS intensify the anti-arthritic effects of AC by regulating the NF-κB-mediated inflammatory pathway and the Nrf2-mediated anti-oxidation pathway which are the major pathways of WTD for alleviating the symptoms of RA.     

Anti-aging function and molecular mechanism of Radix Astragali and Radix Astragali preparata via network pharmacology and PI3K/Akt signaling pathway

BackgroundRadix Astragali (RA) consists of the dried root of Astragalus membranaceus Bunge and is one of the most frequently used dietetic Chinese herbs to treat inflammation and neurodegenerative disease among other conditions. Radix Astragali preparata (RAP) is a medicinal form of RA. RA and RAP have been used as anti-aging agent, however, the mechanisms underlying their effects are still unclear.PurposeConsidering the wide application of RA and RAP in clinical practice, it is necessary to identify the better product between the two and elucidate the molecular mechanism responsible for their anti-aging effects.Study DesignIn this study, network pharmacology integrated with molecular biology techniques were employed to explore the possible mechanism of RA and RAP against aging.MethodsAging animal models were constructed by exposure to D-galactose (D-gal), and the anti-aging effect of RA and RAP were determined based on behavior tests and histomorphological observation. Network pharmacology was performed to construct the “compound-target-pathway” network. Gene and protein expression of possible targets were validated and analyzed using qRT-PCR and Western blotting.ResultsTreatment by RA and RAP could alleviate the symptoms of aging such as a decrease in body weight and organ indices, behavioral impairment, increased oxidative stress, weaken histopathological evaluation. The effect of RAP was more pronounced than that of RA in preventing aging process in a mouse model. The anti-aging effect of RA and RAP is associated with the balance of oxidative stress and activation of PI3K/Akt signaling pathway.ConclusionUsing an integrated strategy of network pharmacology and molecular biology we attempted to elucidate the mechanisms of action of RA and RAP.     

Uncovering the mechanism of Astragali Radix against nephrotic syndrome by intergrating lipidomics and network pharmacology

BackgroundAstragali Radix (AR), a common Traditional Chinese Medicine (TCM), is commonly used for treating nephrotic syndrome (NS) in China. At present, the research on the efficacy of AR against NS is relative clearly, but there are fewer researches on the mechanism.PurposeThe aim of this study was to evaluate the potential beneficial effects of AR in an adriamycin-induced nephropathy rat model, as well as investigate the possible mechanisms of action and potential lipid biomarkers.MethodsIn this work, a rat model of NS was established by two injections of ADR (3.5 + 1 mg/kg) into the tail vein. The potential metabolites and targets involved in the anti-NS effects of AR were predicted by lipidomics coupled with the network pharmacology approach, and the crucial metabolite and protein were further validated by western blotting and ELISA.ResultsThe results showed that 22 metabolites such as l-carnitine, LysoPC (20:3), and SM (d18:1/16:0) were associated with renal injury. Moreover, SMPD1, CPT1A and LCAT were predicted as lipids linked targets of AR against NS, whilst glycerophospholipid, sphingolipid and fatty acids metabolism were involved as key pathways of AR against NS. Besides, AR could play a critical role in NS by improving oxidative stress, inhibiting apoptosis and reducing inflammation. Interestingly, our results indicated that key metabolite l-carnitine and target CPT1 were one of the important metabolites and targets for AR to exert anti-NS effects.ConclusionIn summary, this study offered a new understanding of the protection mechanism of AR against NS by network pharmacology and lipidomic method.     

A novel biotransformation of astragalosides to astragaloside IV with the deacetylation of fungal endophyte Penicillium canescens

Under the deacetylation of fungal endophyte Penicillium canescens, which was isolated from pigeon pea, a novel and highly efficient biotransformation method of astragalosides to astragaloside IV in Radix Astragali was investigated. After single factor tests of the biotransformation procedure, the optimum biotransformation conditions were confirmed as the liquid solid ratio 20:1, the biotransformation temperature 30 °C, time 36 h and pH 7, respectively. Final content of astragaloside IV in Radix Astragali reached 7.66 ± 0.44 mg/g, which was 5.51-fold to that of untreated one and contents of astragaloside I and astragaloside II significantly decreased. The immobilized Ca-alginate gel beads with P. canescens could be reused at least for 13 runs. This is the first report that fungal endophyte was applied for the biotransformation of astragalosides to astragaloside IV in Radix Astragali and this novel high-efficiency biotransformation method will be an alternative to enhance the content of astragaloside IV in Radix Astragali in commercial process.     

复方薏苡仁方对小鼠肠道菌群及 微环境的调节作用研究

目的观察复方薏苡仁方调节小鼠肠道菌群功能及胃肠运动的效果,并考察复方薏苡仁方对小鼠盲肠内容物pH及肠黏膜结构等肠道内环境的影响。方法参照《保健食品检验与评价技术规范》(2003版)的规定进行调节肠道菌群实验和小肠墨汁推进试验,检测小鼠盲肠内容物pH,并对肠道黏膜结构进行病理形态学观察。结果 (1)与给样前相比,复方薏苡仁方中、高剂量组肠杆菌数和低、高剂量组肠球菌数均明显减少(P0.05),中、高剂量组乳杆菌数和双歧杆菌数均明显或显著增加(P0.05或P0.01),且高剂量组乳杆菌数和中、高剂量组双歧杆菌数明显高于阳性对照组(P0.05);(2)复方薏苡仁方各剂量组小鼠盲肠内容物pH值均显著降低(P0.01),且均低于阳性对照组,其中低、高剂量组差异有统计学意义(P0.05或P0.01);(3)与正常对照组相比,复方薏苡仁方低、中、高剂量组小鼠十二指肠、空肠、回肠绒毛长度/隐窝深度比值(A/V)均明显或显著增加(P0.05或P0.01),且中、高剂量组十二指肠、空肠及回肠A/V比值明显或显著高于阳性对照组(P0.05或P0.01);(4)与模型对照组相比,复方薏苡仁方各剂量组小鼠小肠推进率均显著增加(P0.01),且均高于阳性对照组(P0.01)。结论复方薏苡仁方对调节肠道菌群及改善肠道微环境具有一定的促进作用。     

Moderate physical exercise attenuates the alterations of feeding behaviour induced by social stress in female rats

Epidemiological studies have demonstrated that stress‐related disorders, such as the increase on the caloric intake, are twice as common in women as in men, but surprisingly, very few studies have been tested this subject on female experimental animals. Additionally, it has been proposed that regular physical exercise can improve the deleterious effects of stress. Therefore, the present longitudinal study, performed in female rats, aimed to test the influence of chronic stress (ST) imposed by social isolation on the animals’ caloric intake and to assess the effect of regular physical exercise of low intensity on this behaviour. In 4 groups of Wistars rats (control sedentary, n = 6; control exercised, n = 6; ST sedentary, n = 6; ST exercised, n = 6), body weight, food intake, abdominal fat weight, adrenal weight, corticosterone metabolites in faeces and plasma insulin levels were measured during the experimental protocol and/or at its end. The results showed that social isolation was not able to modify the amount of abdominal fat and the body weight; however, it promoted significant increases in the corticosterone metabolites and in the amount of caloric intake, which were attenuated in exercised rats. Additionally, exercised groups presented lower levels of fasting insulin than sedentary groups. Therefore, the present study demonstrated that regular physical exercise of low intensity attenuates the corticosterone metabolites and overeating behaviour triggered by social stress. Copyright © 2013 John Wiley & Sons, Ltd.     

Discrimination of geographical origin and adulteration of radix astragali using fourier transform infrared spectroscopy and chemometric methods

Introduction – Radix Astragali, one of most widely used and important traditional Chinese medicines, is cultivated in different geographical regions. Because of varying growing conditions, the qualities of Radix Astragali vary, which can give rise to differences in clinical therapy. Detecting adulteration is a routine requirement in pharmaceutical practice. Objective – To develop a simple and accurate approach to discriminate the geographical origin and potential adulteration of Radix Astragali, derived from the root of Astragalus membranaceus (Fischer) Bunge var. mongholicus (Bunge) Hsiao, using Fourier transform infrared (FT‐IR) spectroscopy and chemometric methods. Methodology – To obtain characteristic IR spectra for accurate discrimination, a one‐solvent extraction method was utilised following a novel evaluation method for selecting appropriate solvents. Samples of Radix Astragali from different geographical origins were discriminated using FT‐IR spectroscopy and discriminant partial least squares (DPLS) methods. FT‐IR spectroscopy combined with Mahalanobis distance was employed to detect adulteration of Radix Astragali. Results – In comparison with other solvents, butanone was more effective at extracting samples. Radix Astragali samples were accurately assigned to their corresponding geographical origins by using FT‐IR spectroscopy and DPLS method. Most adulterated samples were detected accurately by application of FT‐IR spectroscopy combined with Mahalanobis distance. Conclusion – FT‐IR spectroscopy combined with chemometric method was developed and demonstrated to be a useful tool to discriminate geographical origin and adulteration of Radix Astragali. Copyright © 2010 John Wiley & Sons, Ltd.     

黄芪含药血清对NK细胞活性及KLRK1表达的影响

目的：探讨黄芪含药血清对自然杀伤（NK）细胞活性及杀伤细胞凝集素样受体K1（KLRK1）表达的影响。方法：SD大鼠灌胃不同剂量的黄芪水煎剂制备黄芪含药血清。NK92MI细胞与不同剂量黄芪含药血清及对照血清孵育12h后,采用乳酸脱氢酶释放测定法检测NK细胞对靶细胞YAC-1的杀伤活性,采用qPCR和western blot检测KLRK1 mRNA和蛋白表达。结果：不同浓度黄芪含药血清刺激12h后NK细胞杀伤活性明显增强,KLRK1表达显著升高。结论：黄芪含药血清能活化NK细胞,其机制可能与其激活KLRK1有关。     

Systems pharmacology approach uncovers the therapeutic mechanism of medicarpin against scopolamine-induced memory loss

BackgroundMedicarpin is a natural pterocarpan-type phytoalexin widely distributed in many traditional Chinese medicines, such as Astragali Radix. A previous study showed that Astragali Radix demonstrated promising protective effects in neurons. However, there is no reported study on the neuroprotective function and the underlying mechanism of Medicarpin.PurposeThis study aimed to demonstrate the neuroprotective effect of Medicarpin on Alzheimer's disease (AD) and explore the therapeutic mechanisms.MethodFirst, we carried out animal behavioral tests and biochemical analysis to assess the anti-AD potential of Medicarpin for ameliorating spatial learning and memory and modulating cholinergic metabolism in scopolamine-induced amnesic mice. Subsequently, network proximity prediction was used to measure the network distance between the Medicarpin target network and AD-related endophenotype module. We identified Medicarpin-regulated AD pathological processes and highlighted the key disease targets via network analysis. Finally, experimental approaches including Nissl staining and Western blotting were conducted to validate our network-based findings.ResultIn this study, we first observed that Medicarpin can ameliorate cognitive and memory dysfunction and significantly modulate cholinergic metabolism in scopolamine-induced amnesic mice. We then proposed an endophenotype network-based framework to comprehensively explore the AD therapeutic mechanisms of Medicarpin by integrating 25 AD-related endophenotype modules, gold-standard AD seed genes, an experimentally validated drug-target network of Medicarpin, and a global human protein-protein interactome. In silico prediction revealed that the effect of Medicarpin is highly relevant to neuronal apoptosis and synaptic plasticity, which was validated by experimental assays. Network analysis and Western blotting further identified two key targets, GSK-3β and MAPK14 (p38), in the AD-related protein regulatory network, which play key roles in the regulation of neuronal apoptosis and synaptic plasticity by Medicarpin.ConclusionsThis study presented a powerful endophenotype network-based strategy to explore the mechanisms of action (MOAs) of new AD therapeutics, and first identified Medicarpin as a potential anti-AD candidate by targeting multiple pathways.     

Effects of supplementing different chromium histidinate complexes on glucose and lipid metabolism and related protein expressions in rats fed a high-fat diet

BackgroundThe objective of this study was to investigate the effects of different chromium histidinate (CrHis) complexes added to the diet of rats fed a high-fat diet (HFD) on body weight changes, glucose and lipid metabolism parameters, and changes in biomarkers such as PPAR-γ, IRS-1, GLUTs, and NF-κB proteins.MethodsForty-two Sprague–Dawley rats were divided equally into six groups and fed either a control, an HFD, or an HFD supplemented with either CrHis1, CrHis2, CrHis3, or a combination of the CrHis complexes as CrHisM.ResultsFeeding an HFD to rats increased body weights, HOMA-IR values, fasting serum glucose, insulin, leptin, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, and MDA concentrations as well as AST activities, and decreased serum and brain serotonin concentrations compared with rats fed a control diet (P < 0.0001). The levels of the PPAR-γ, IRS-1, and GLUTs in the liver and brain decreased, while NF-κB level increased, with feeding an HFD (P < 0.05). Although all the CrHis supplements reversed the negative effects of feeding an HFD (P < 0.05), the CrHis1 complex was most effective in changing the protein levels, while CrHisM was most effective in influencing certain parameters such as body weight and serum metabolites.ConclusionThe results of the present work suggest that the CrHis1 complex is most potent for alleviating the negative effects of feeding an HFD. The efficacy of CrHisM is likely due to the presence of the CrHis1 complex.     

中药水提物对白念珠菌生物膜抑制作用的研究

目的研究中药水提物对体外白念珠菌生物膜的影响。方法体外构建白念珠菌生物膜,微量稀释法测定中药提取物对白念珠菌浮游菌最低抑菌浓度（M IC）,XTT减低法评价中药提取物对白念珠菌生物膜SM IC（SM IC80,SM IC50）及对白念珠菌黏附能力的影响。结果野菊花、土槿皮和决明子SM IC80为125 mg/m l,其余中药SM IC80为250或500 mg/m l;地肤子SM IC50为7.81 mg/m l,川芎、苏梗、藿香和决明子SM IC50为15.63 mg/m l,其他中药SM IC50在62.5~250 mg/m l。10味中药在100 mg/m l时均能显著抑制白念珠菌细胞的黏附,10 mg/m l时地肤子、苏梗和苦参对黏附仍具抑制作用。结论该10味中药水提物对体外白念珠菌生物膜有较强抑制效应。     

GABAA receptors in nucleus accumbens shell mediate the hyperphagia and weight gain following haloperidol treatment in rats

AimsWeight gain is a common outcome of antipsychotics therapy in schizophrenic patients. However, the underlying neuronal mechanisms are unclear. The present study was undertaken to investigate the role of GABA_A receptors within the framework of nucleus accumbens shell (AcbSh) in haloperidol-induced hyperphagia and body weight gain in sated rats.Main methodsIn acute studies, GABA_A receptor agonists muscimol, diazepam or antagonist bicuculline were administered by AcbSh route, alone or in combination with haloperidol (intraperitoneal/ip). Immediately after these treatments, preweighed food was offered to the animals at commencement of dark phase. Cumulative food intake was measured at 2 and 6 h post-injection time-points. Furthermore, effects of subacute haloperidol treatment, alone or in combination with muscimol, diazepam or bicuculline, on food intake and body weight were investigated.Key findingsWhile acute treatment with haloperidol, muscimol or diazepam dose dependently stimulated the food intake, bicuculline suppressed the same. Prior administration of muscimol (20 ng/rat, intra-AcbSh) and diazepam (5 µg/rat, intra-AcbSh) significantly potentiated, whereas bicuculline (40 ng/rat, intra-AcbSh) negated the hyperphagic effect of acute haloperidol (0.005 or 0.01 mg/kg/rat, ip). Subacute administration of haloperidol (0.01 mg/kg/rat/day, ip) for 15 days produced increase in food intake and body weight. Although, concomitant administration of muscimol (20 ng/rat/day, intra-AcbSh) or diazepam (5 μg/rat/day, intra-AcbSh) markedly enhanced, bicuculline (40 ng/rat/day, intra-AcbSh) prevented the subacute haloperidol-induced hyperphagia and weight gain.SignificanceThe results of present study suggest that increased food intake and body weight following haloperidol treatment in rats, may be mediated via AcbSh GABA_A receptors.     

Network pharmacology combined with metabolomics approach to investigate the protective role and detoxification mechanism of Yunnan Baiyao formulation

BackgroundYunnan Baiyao (YNBY) is a traditional Chinese medicine formulae, which has the functions of hemostasis, activating blood circulation and removing blood stasis, anti-inflammation, etc. Although the presence of Caowu (CW, Aconiti Kusnezoffii Radix), the detoxification mechanism of YNBY is still unclear.PurposeIn current study, network pharmacology, toxicological methods and metabolomics technique were applied to explore YNBY in attenuating toxicity of CW.MethodsPrediction of targets and pathways of CW were carried out by commonly used network pharmacological method. Simultaneously, SD rats were orally administrated with CW, processed CW (ZCW), YNBY, and YNBY which lack of CW (QCW) for 15 days. Tissue samples were observed with histopathology. Urine samples were analyzed with ultra-performance liquid chromatography-mass spectrometry to screen differential metabolites and related metabolic pathways associated with toxicity of CW. Furthermore, by comparing the changes of the metabolite contents, focused the attenuated metabolic pathway. Finally, the network pharmacological and experimental data were integrated to investigate detoxification mechanism of YNBY.ResultsA total of 44 potential toxicity biomarkers were identified and 14 related pathways were involved in the toxicity of CW. Furthermore, 5 core toxicity biomarkers (2-keto-6-acetamidocaproate, γ-glutamylleucine, prostaglandin E₃, 4-hydroxy-5-(3’-hydroxyphenyl)-valeric acid-3’-O-sulphate, and 3,4-dihydroxy- phenylglycol O-sulfate) were regulated to normal condition in YNBY group. Lysine degradation was locked as the core metabolic pathway of detoxification of YNBY. Integrating the predicted results of network pharmacology, ACHE, SLC6A3, SLC6A4 might be the target of protective role of other herbs in YNBY.ConclusionNetwork pharmacology combined with metabolomics exhibited a powerful mean to investigate the herbal toxicity and probed into the detoxification mechanism of formulae, which contributes to its safety evaluation.     

沙苑子酚类提取物的抗氧化能力研究

为有效开发利用沙苑子,探究其抗氧化特性为深加工提供理论依据和经验参数,本文主要从沙苑子酚类提取物的总还原能力,对超氧阴离子自由基和羟基自由基的清除能力,及对Fe2+诱导的脂质过氧化的抑制作用等四个方面进行了研究并比较了三种不同沙苑子酚类提取物的抗氧化性能。结果表明沙苑子酚类提取物均具有一定的抗氧化能力,在实验浓度范围内呈现一定的量效关系。     

LIG抗炎,解热活性的研究

本文研究了当归提取物LIG的抗炎,解热活性.研究发现LIG(2.5,5,10 mg/kg)对角叉菜和右旋糖苷诱导的足肿胀的抑制率分别为22.2%,49.4%,76.5%和20.8%,44.2%,75.3%(P＜0.001);对棉球肉芽肿的抑制率为29.2%,44.9%,58.8%(P＜O.001);对小鼠白细胞迁移的抑制率为20.7%,35.6%,48.2%(P＜0.001).此外,LIG可降低啤酒酵母导致的高热(P＜0.001).并且,LIG的抗炎,解热作用均成剂量依赖性.以上结果显示LIG具有非常强的抗炎,解热活性.     

Altered gut microbiota and metabolites profile are associated with reduced bone metabolism in ethanol‐induced osteoporosis

ObjectiveChronic heavy drinking causes ethanol‐induced osteoporosis (EIO). The present study aimed to explore the role of GM in EIO.Material and MethodsA rat EIO model was established by chronic ethanol intake. Taking the antibiotic application as the matched group of dysbacteriosis, an integrated 16S rRNA sequencing and liquid chromatography–tandem mass spectrometry‐based metabolomics in serum and faeces were applied to explore the association of differential metabolic phenotypes and screen out the candidate metabolites detrimental to ossification. The colon organoids were used to track the source of 5‐HT and the effect of 5‐HT on bone formation was examined in vitro . ResultsCompared with antibiotics application, ethanol‐gavaged decreased the BMD in rats. We found that both ethanol and antibiotic intake affected the composition of GM, but ethanol intake increased the ratio of Firmicutes to Bacteroidetes. Elevated serotonin was proved to be positively correlated with the changes of the composition of GM and faecal metabolites and inhibited the proliferation and mineralization of osteogenesis‐related cells. However, the direct secretory promotion of serotonin was absent in the colon organoids exposed to ethanol.ConclusionThis study demonstrated that ethanol consumption led to osteoporosis and intestinal‐specific dysbacteriosis. Conjoint analysis of the genetic profiles of GM and metabolic phenotypes in serum and faeces allowed us to understand the endogenous metabolite, 5‐HT, as detrimental regulators in the gut‐bone axis to impair bone formation.

A rat ethanol‐induced osteoporosis model was established by long‐term ethanol intake. Taking the antibiotic application as the matched group of dysbacteriosis, an integrated 16S rRNA sequencing and liquid chromatography–tandem mass spectrometry‐based metabolomics in serum and faeces were applied to explore the association of differential metabolic phenotypes and screen out the candidate metabolites detrimental to ossification. The colon organoids were used to track the source of 5‐HT and the effect of 5‐HT on bone formation was examined in vitro .     

Amelioration of hyperglycaemia and hyperlipidaemia by adjusting the interplay between gut microbiota and bile acid metabolism: Radix Scutellariae as a case

BackgroundOur previous clinical research showed that the interaction between gut microbiota and bile acids (BAs) in patients with type 2 diabetes mellitus (T2DM) changed significantly. We hypothesized that T2DM could be improved by adjusting this interaction mediated by farnesoid X receptor (FXR). T2DM belongs to the category of “xiaoke” in traditional Chinese medicine. Radix scutellariae has the effects of clearing away heat and eliminating dampness, curing jaundice and quenching thirst and is widely used alone or in combination with other medicines for the treatment of T2DM in China and throughout Asia. Additionally, the interaction between Radix scutellariae and gut microbiota may influence its efficacy in the treatment of T2DM.PurposeThis study chose Radix scutellariae to validate that T2DM could improve by adjusting the interaction between gut microbiota and bile acid metabolism.Study design and methodsRadix scutellariae water extract (WESB) was administered to a T2DM rat model established by a high-fat diet combined with streptozotocin. The body weight and blood glucose and insulin levels were measured. The levels of serum lipids, creatinine, uric acid, albumin and total bile acid were also detected. Changes in the pathology and histology of the pancreas, liver and kidney were observed by haematoxylin-eosin staining. The 16S rRNAs of gut microbiota were sequenced, and the faecal and serum BAs were determined by liquid chromatography tandem mass spectrometry. The expression levels of BA metabolism-associated proteins in the liver and intestine were evaluated by immunoblot analysis.ResultsThe results showed that WESB improved hyperglycaemia, hyperlipaemia, and liver and kidney damage in T2DM rats. In addition, the abundances of key gut microbiota and the concentrations of certain secondary BAs in faeces and serum were restored. Moreover, there was a significant correlation between the restored gut microbiota and BAs, which might be related to the activation of liver cholesterol 7α-hydroxylase (CYP7A1) and the inhibition of FXR expression in the intestine rather than the liver.ConclusionsThis study provided new ideas for the prevention or treatment of clinical diabetes and its complications by adjusting the interaction between gut microbiota and bile acid metabolism.     

Exploring the protective effects of Danqi Tongmai tablet on acute myocardial ischemia rats by comprehensive metabolomics profiling

BackgroundDanqi Tongmai tablet (DQTM), a combination of salvianolic acids (SA) and panax notoginsenosides (PNS), is now in phase II clinical trial developed for the treatment of cardiovascular diseases. However, the mechanisms of its protective effects through regulating endogenous metabolites remain unclear.PurposeThe purpose of this study was to explore the protective effects of DQTM on acute myocardial ischemia rats by comprehensive metabolomics profiling.Study designThe rats were divided into three groups: sham-operating, acute myocardial ischemia (AMI) and DQTM groups. The plasma and heart were collected and profiled by LC-MS based metabolomics and lipidomics. Based on the identified differential metabolites, the pathway analysis results were obtained and further validated using the network pharmacology approach.MethodsThe AMI model was induced by ligating the left anterior descending coronary artery. The metabolomics and lipidomics profiling were based on two established LC–QTOF/MS analysis methods. The raw data were processed using XCMS Online, then the differential metabolites with nonparametric t-test p value less than 0.05 were selected and identified using HMDB and METLIN. The pathway analysis was conducted using MetaboAnalyst and validated with the predicted network results obtained by BATMAN-TCM.ResultsThe metabolomics and lipidomics profiles of plasma and heart in response to AMI and DQTM were significantly different. The AMI operation had a serious influence on metabolites in heart ischemia region, while DQTM had a greater impact on lipids in heart non-ischemia region. A total of 151 differential metabolites were identified, including mainly amino acids and fatty acids. Multiple metabolic pathways were disturbed after AMI and could be restored by DQTM, of which arachidonic acid metabolism was further validated with the predicted results of network pharmacology.ConclusionThe protective effects of DQTM on acute myocardial ischemia rats could be achieved through the regulation of multiple metabolic pathways.     

Topiramate Reduces Energy and Fat Gains in Lean (Fa/?) and Obese (fa/fa) Zucker Rats

Objective: This study examined the effects of topiramate (TPM), a novel neurotherapeutic agent reported to reduce body weight in humans, on the components of energy balance in female Zucker rats. Research Methods and Procedures: A 2 × 3 factorial experiment was performed in which two cohorts of Zucker rats differing in their phenotype (phenotype: lean, Fa/?; obese, fa/fa) were each divided into three groups defined by the dose of TPM administered (dose: TPM 0, vehicle; TPM 15, 15 mg/kg; TPM 60, 60 mg/kg). Results: The reduction in body weight gain induced by TPM in both lean and obese rats reflected a decrease in total body energy gain, which was more evident in obese than in lean rats. Whereas TPM administration did not influence the intake of digestible energy in lean rats, it induced a reduction in food intake in obese animals. In lean, but not in obese rats, apparent energy expenditure (as calculated by the difference between energy intake and energy gain) was higher in rats treated with TPM than in animals administered the vehicle. The low dose of TPM decreased fat gain (with emphasis on subcutaneous fat) without affecting protein gain, whereas the high dose of the drug induced a reduction in both fat and protein gains. The effects of TPM on muscle and fat depot weights were representative of the global effects of TPM on whole body fat and protein gains. The calculated energetic efficiency (energy gain/energy intake) was decreased in both lean and obese rats after TPM treatment. TPM dose independently reduced hyperinsulinemia of obese rats, but it did not alter insulinemia of lean animals. Discussion: The present results provide sound evidence for the ability of TPM to reduce fat and energy gains through reducing energetic efficiency in both lean and obese Zucker rats.