ABSTRACT
Objective:To explore the possible mechanism of Chloriti Lapis in the treatment of epilepsy by the metabonomics of brain tissue in pentylenetetrazol （PTZ）-kindled epileptic rats treated with Chloriti Lapis. Method:The epileptic animal model in rats was established by PTZ kindling， and the rats were divided into the control group， model group， carbamazepine group and Chloriti Lapis group. The brain tissue samples were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）， and the experimental results were statistically analyzed by partial least squares-discriminant analysis （PLS-DA） and SPSS 18.0. Result:The metabolic fingerprints and metabolic profiles of the rat brain tissue were established， which showed that the metabolic profiles of each group had changed significantly and could be separated well among the groups. Moreover， the Chloriti Lapis group had a tendency to be closer to the control group than the carbamazepine group. Seven differential metabolites were screened， including phosphatidylserine （PS） （18∶0/18∶0）， <italic>L</italic>-glutamic acid， docosahexaenoyl ethanolamide， arachidonic acid， glucosylsphingosine， cholestane-3，7，12，24，25-pentol and lysophosphatidylcholine （LysoPC） （P-18∶0）. Except for docosahexaenoyl ethanolamide and LysoPC （P-18∶0）， Chloriti Lapis had significant intervening and regulating effects on the other five differential metabolites. There were 12 possible metabolic pathways that affected the metabolic disorder of PTZ-kindled rats， and 3 important metabolic pathways （pathway impact>0.1）， namely， <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism， alanine， aspartate and glutamate metabolism， and arachidonic acid metabolism， among which <italic>D-</italic>glutamine and <italic>D-</italic>glutamate metabolism was the most important metabolic pathways. Conclusion:From this point of view， Chloriti Lapis has a clear intervention effect on PTZ-kindled epileptic rats， which may be related to the intervention of the above differential metabolite contents and related metabolic pathways. It can reduce the toxic effect of excitatory neurotransmitters on neurons in brain tissue and inhibit the development of inflammation in brain tissue， so as to maintain the biological function of brain cells and slow down the occurrence of epilepsy.
ABSTRACT
To study the effect of mineral Chloriti Lapis on pulmonary metabolites and metabolic pathways in lung tissues of rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). The AECOPD rat model of phlegm heat syndrome was replicated by the method of smoking combined with Klebsiella pneumoniae infection. Except for using UPLC-Q-TOF-MS analysis, SPSS 18.0, SIMCA 13.0 and other software were also used for statistical analysis. Through literature search and online database comparison, the differential metabolites were identified, and the possible metabolic pathways were analyzed. After 15 days of administration, PLS-DA analysis was carried out on lung tissue samples of rats in each group. The results showed that the metabolic profiles of lung tissues of rats in each group could be well separated, which indicated that Chloriti Lapis and aminophylline had significant intervention effect on the lung metabolic profile of rats with AECOPD. Moreover, the metabolic profile of Chloriti Lapis group was closer to that of control group, and the intervention effect was better than that of aminophylline group. As a result, 15 potential differential metabolites were identified: phytosphingosine, sphinganine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], lysoPC(18∶0), stearic acid, lysoPC(15∶0), arachidonic acid, docosapentaenoic acid, linoleic acid and palmitic acid. Among them, Chloriti Lapis could significantly improve the levels of 10 differential metabolites of phytosphingosine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], stearic acid, lysoPC(15∶0), and palmitic acid(P<0.05). The intervention effect of Chloriti Lapis group was better than that of aminophylline group. Analysis of metabolic pathways showed that there were 8 possible metabolic pathways that could be affected, and three of the most important metabolic pathways(pathway impact>0.1) were involved: linoleic acid metabolism, arachidonic acid metabolism, and sphingolipid metabolism. Chloriti Lapis had obvious intervention effects on lung tissue-related metabolites and metabolic pathways in rats with AECOPD, and the effect was better than that of aminophyllinne.
Subject(s)
Animals , Rats , Lung , Medicine, Chinese Traditional , Metabolomics , Minerals , Pulmonary Disease, Chronic ObstructiveABSTRACT
The effects of Chloriti Lapis on metal elements in plasma and lung tissue of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) rats were studied. The rat AECOPD model with phlegm heat syndrome was established by smoking combined with Klebsiella pneumoniae infection. After the rats were treated by Chloriti Lapis,the contents of metal elements in plasma and lung tissue were determined by inductively coupled plasma-optical emission spectroscopy( ICP-OES) and inductively coupled plasma mass spectrometry( ICP-MS). The changes in the contents of metal elements were analyzed by SPSS 18. 0. Further,the correlations of differential metal elements( including Cu/Zn ratio) with differential metabolites in plasma,lung tissue and urine of AECOPD rats treated with Chloriti Lapis were analyzed. The results showed that Chloriti Lapis significantly up-regulated the contents of Fe,Al,Mn,Cu,Zn,Sn( P<0. 05),V,Co( P< 0. 01) and Cu/Zn ratio( P< 0. 05),and significantly down-regulated the contents of Ti( P< 0. 05)and Pb( P<0. 05) in the model rat plasma. It significantly increased the content of Be( P<0. 05) and decreased the contents of Mg,Ti and Al( P<0. 01) in model rat lung tissue. The element profiles of normal group,model group and Chloriti Lapis group can be well separated. Chloriti Lapis group and other groups were clustered into two categories. The taurine in plasma and phytosphingosine in lung tissue had the strongest correlations with differential metal elements. The Fe,Al,Mg,Be,Ti,V,Mn,Cu,Zn,Sn,and Co in Chloriti Lapis may directly or indirectly participate in the intervention of AECOPD rats. This group of metal elements may be the material basis of Chloriti Lapis acting on AECOPD rats,and reduce the Cu/Zn value in vivo. It was further confirmed that Chloriti Lapis could interfere with the metabolic pathways of taurine and hypotaurine in plasma and urine as well as the sphingolipid metabolism pathway in lung tissue of AECOPD rats. In addition,this study confirmed that long-term smoking can cause high-concentration Cd accumulation in the lung and damage the lung tissue.
Subject(s)
Animals , Rats , Lung , Medicine, Chinese Traditional , Minerals , Pulmonary Disease, Chronic Obstructive , Spectrum Analysis , Trace Elements/analysisABSTRACT
Objective:To investigate the effect of Chloriti Lapis on metal elements in brain tissue and plasma of epileptic rats kindled by pentylenetetrazol （PTZ）， and to explore the possible material basis of Chloriti Lapis. Method:PTZ kindling method was used to establish epileptic rat model. Inductively coupled plasma mass spectrometry （ICP-MS） and inductively coupled plasma optical emission spectrometer （ICP-OES） were used to determine the contents of metal elements in brain tissue and plasma of the blank group， model group， carbamazepine group （0.1 g·kg<sup>-1</sup>） and Chloriti Lapis group （2 g·kg<sup>-1</sup>）. The data were statistically analyzed by SPSS 18.0 software. Result:Compared with the blank group， the contents of Sr， Sb and Ba in brain tissue of rats in the model group were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the contents of Zn， Fe， Cu， K， Li， Co， Sn and Pb were significantly decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the contents of Zn， Fe， K， Li， Co， As and Pb in brain tissue of rats in the Chloriti Lapis group were obviously increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the contents of Sr and Sb were significantly decreased （<italic>P</italic><0.01）. These results showed that Chloriti Lapis had positive effect on the regulation of the content of metal elements in rat brain tissue to normal level， the intervention effect was clear， and the overall effect was better than that of carbamazepine group. The determination of 21 metal elements in plasma showed that compared with the blank group， the levels of K， Sr and Cd in the model group were significantly increased （<italic>P</italic><0.05）， and the contents of Li， Al， Ti and Cr were significantly decreased （<italic>P</italic><0.05）. Compared with the model group， the contents of Ca， K， Li， Al and V in the Chloriti Lapis group were obviously increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， and the contents of Fe， Ti， Sr and Cd were significantly decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）. The correlation analysis of metal elements among the groups showed that there were 17 pairs of elements had positively correlation in the brain tissue of rats， 2 pairs of elements had significant negative correlation. In the plasma of rats， 8 pairs of elements had significant positive correlation and 6 pairs of elements had significant negative correlation. Conclusion:The metal element groups represented by Zn， Fe， K， Li， Co， As， Pb， Sr， Sb， Ca， Al， V， Ti and Cd may be the effective material basis for Chloriti Lapis to interfere PTZ-kindled epileptic model rats， which may be related to the influence of these metal element groups on the release of neurotransmitters and the electrical balance of neurons， the regulation of abnormal synchronous discharge induced by Na<sup>+</sup>， K<sup>+</sup>， Ca<sup>2+</sup> channel disorders and intervention of metabolism pathways in brain tissue related to epilepsy. It can make the excitatory and inhibitory activities restrain each other， and finally reach the normal physiological state of neurons and cells. The intervention effect of Chloriti Lapis group was better than that of carbamazepine group.
ABSTRACT
To establish a fingerprint spectrum for Atractylodis Macrocephalae Rhizoma stir-fried with wheat bran based on UFLC/Q-TOF-MS, and make a principal component analysis (PCA) with Markview software, in order to compare the changes of components between raw and processed Atractylodis Macrocephalae Rhizoma with raw wheat bran as the blank. The results showed that the changed in components raw Atractylodis Macrocephalae Rhizoma and Atractylodis Macrocephalae Rhizoma stir-fried with wheat bran were apparently observed by PCA. Six compounds were identified to have significant changes in mass fraction before and after being stir-fried, namely atractylenolide-I, atractylenolide-II, atractylenolide-III, atractylentrid, atractylon and an unknown compound. Among them, atractylenolide-I and atractylenolide-II generated from dehydration and dehydrogenation of atractylenolide-III may be the material base of Atractylodis Macrocephalae Rhizoma stir-fried with wheat bran for strengthening spleen.