1.Optimal processing technology of Zhangbang vinegar-processed Olibanum with multi-indicator-response surface methodology and anticoagulant effect evaluation.
Xiao-Lin XIAO ; Gan-Ming YAN ; Qian-Feng GONG ; Huan YU ; Dan-Yang YANG ; Xiao-Ying WU ; Ying-Hui ZHU ; Xin-Lin PENG
China Journal of Chinese Materia Medica 2023;48(16):4402-4412
This study first optimized the processing technology for Zhangbang vinegar-processed Olibanum and investigated its in vitro anticoagulant activity. A multi-index-response surface methodology was used, with yield, powder yield, and the relative percentage of the content of six non-volatile components [11-keto-boswellic acid(KBA), 3-acetyl-11-keto-boswellic acid(AKBA), β-elemonic acid, α-boswellic acid(α-BA), β-boswellic acid(β-BA), and α-acetyl-boswellic acid(α-BA)] and three volatile components(octyl acetate, incensole, and incensole acetate) as evaluation indicators. Analytical hierarchy process(AHP) combined with coefficient of variation method was used to calculate the weight of each indicator and calculate the comprehensive score(OD). Furthermore, response surface methodology was used to investigate the effects of frying temperature(A), burning time(B), rice vinegar dosage(C), and steaming time(D) on the processing technology of vinegar-processed Olibanum. Vinegar-steamed Olibanum was prepared according to the optimal processing technology for in vitro anticoagulant experiments. The results showed that the weights of octyl acetate, incensole, incensole acetate, KBA, AKBA, β-elemonic acid, α-BA, β-BA, α-ABA, yield, and powder yield were 0.358 2, 0.104 5, 0.146 4, 0.032 9, 0.123 7, 0.044 4, 0.022 1, 0.042 2, 0.110 1, 0.012 2, and 0.0032, respectively. The optimal processing technology for Zhangbang vinegar-processed Olibanum was as follows. Olibanum(50 g) with a particle size of 1-5 mm was continuously stir-fried at a low heat of 150-180 ℃ until in a gel-like state, ignited for burning for 15 s, sprayed with 7.5 g of rice vinegar(15%), and steamed for 3 min without fire. Subsequently, the cover was removed, and the product was continuously stir-fried at 150-180 ℃ until in a soft lump shape, removed, cooled, and crushed. The results of the in vitro anticoagulant experiments showed that compared with the blank group, both Olibanum and vinegar-processed Olibanum significantly prolonged the activated partial thromboplastin time(APTT), thrombin time(TT), and prothrombin time(PT) of rat platelet-poor plasma(PPP), and the effect of vinegar-processed Olibanum was significantly better than that of Olibanum(P<0.05). The optimized processing technology for Zhangbang vinegar-processed Olibanum is stable, feasible, and beneficial for the further development and utilization of Olibanum slices. At the same time, using the content of volatile and non-volatile components, yield, and powder yield as indicators, and verifying through pharmacological experiments, the obtained results are more reasonable and credible, and have positive guiding significance for the clinical application of characteristic processed Olibanum products.
Rats
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Animals
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Frankincense
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Acetic Acid
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Powders
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Triterpenes
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Anticoagulants/pharmacology*
;
Technology
2.Toxicity comparison of raw and vinegar-processed Bupleuri Radix based on ~1H-NMR metabolomics.
Hui-Min SUN ; Ting ZHANG ; Zhen-Yu LI ; Xue-Mei QIN
China Journal of Chinese Materia Medica 2022;47(19):5224-5234
This study compared the toxicity of raw Bupleuri Radix(BR) and vinegar-processed Bupleuri Radix(VPBR) based on proton nuclear magnetic resonance(~1H-NMR), and explored the mechanism of toxicity. Thirty-two male Sprague-Dawley(SD) rats were randomly divided into four groups: a control group(distilled water), a raw BR group(15 g·kg~(-1)·d~(-1)), a rice VPBR(R-VPBR) group(15 g·kg~(-1)·d~(-1)), and a shanxi VPBR(S-VPBR) group(15 g·kg~(-1)·d~(-1)). After administration for 30 d, pathological sections were treated and observed, and biochemical indexes related to liver and renal function were determined. The serum, liver, and kidney of rats were collected and analyzed by ~1H-NMR. The principal component analysis(PCA) and orthogonal partial least squares-discrimination analysis(OPLS-DA) were performed. The results showed that, as compared with the control group, alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) in the raw BR group were increased significantly, while ALT and ALP in the R-VPBR and S-VPBR groups were significantly decreased(P<0.05), which indicated that BR showed certain hepatotoxicity, and vinegar processing reduced its hepatotoxicity. No significant difference of blood urea nitrogen(BUN) and creatinine(CREA), the biochemical indexes related to renal function, was observed in the control group and administration groups, indicating that BR had less effect on the renal function. The results of multivariate statistical analysis showed that the biomarkers of BR affecting liver metabolism were methionine, glutamine, and glutamic acid, and affecting kidney metabolism were taurine, ornithine, and inosine. These biomarkers were mainly involved in amino acid metabolism, energy metabolism, lipid metabolism, and taurine metabolism. VPBR alleviated the effect on the biomarkers, and S-VPBR had smaller effect than R-VPBR. Combining the results of biochemical indexes and metabolomics analysis, both raw BR and VPBR showed toxic effect on rats, whereas vinegar processing reduced its toxicity. S-VPBR has smaller effect on kidney and liver metabolism than R-VPBR, which indicates that the vinegar used for processing has certain effect on the toxicity of BR.
Male
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Rats
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Animals
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Acetic Acid/chemistry*
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Drugs, Chinese Herbal/chemistry*
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Proton Magnetic Resonance Spectroscopy
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Rats, Sprague-Dawley
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Metabolomics/methods*
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Liver
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Chemical and Drug Induced Liver Injury/pathology*
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Taurine/pharmacology*
3.Comparative of functional components, antioxidant and α-glucosidase inhibition activities between Choerospondias axillaris fruit peel vinegar and apple vinegar.
Tong JIANG ; Xin-Lin LYU ; Xiang-Wei LI ; Zi-Yang LI ; Dan YANG ; Zi-Long ZHANG ; Jing-Jing ZHU ; Zhi-Min WANG ; Zhi-Gao LIU ; Ji-Yan LIU
China Journal of Chinese Materia Medica 2020;45(5):1180-1187
Based on the idea of plant metabolomics, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to compare the chemical composition between 6 batches of fruit vinegar brewed from Choerospondias axillaris fruit peel and 6 batches of apple vinegar purchased from 3 companies. Antioxidant and α-glucosidase inhibition activities were also tested in vitro. A total of 43 compounds were identified by reference substance, liquid chromatography-mass spectrometry(LC-MS/MS) fragmentation information or literature data. A total of 40 compounds were identified in the C. axillaris fruit peel vinegar. A total of 16 compounds were identified in apple vinegar. There were 13 common ingredients including organic acids and esters such as citric acid, 2-isopropyl malic acid, and triethyl citrate. The results of partial leastsquares-discriminant analysis(PLS-DA) indicated that they had 33 significantly different compounds such as proanthocyanidin oligomer, quercetin-3-O-rhamnoside and heptadecanoic acid. The proanthocyanidins and flavonoid glycosides in C. axillaris peel vinegar were more abundant than apple vinegar, so it had better health function than ordinary fruit vinegar. The results showed that C. axillaris fruit peel vinegar had stronger antioxidant and α-glucosidase inhibition activities in vitro. The vinegar brewed from waste C. axillaris fruit peel had more chemical ingredients than the apple vinegar. C. axillaris fruit peel vinegar had better biological activity and health function, so it had good development prospect. This study provided the scientific evidence for exploiting the C. axillaris fruit peel into high value-added products. It also provided ideas for the comprehensive development and utilization of similar Chinese medicine waste.
Acetic Acid/pharmacology*
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Anacardiaceae/chemistry*
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Antioxidants
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Chromatography, High Pressure Liquid
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Fruit/chemistry*
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Glycoside Hydrolase Inhibitors/pharmacology*
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Malus/chemistry*
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Plant Extracts
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Tandem Mass Spectrometry
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alpha-Glucosidases
4.UFLC-Q-TOF-MS fingerprints of rhizome of Curcuma phaeocaulis and its vinegar processed products and inhibitory effect on thrombosis.
Shen SONG ; Li-Yun GU ; Jin-Guo XU ; Xiao-Bing CUI ; Sha-Li DU ; Wei-Dong LI
China Journal of Chinese Materia Medica 2019;44(12):2511-2518
Both raw and vinegar products of the rhizome of Curcuma phaeocaulis are common drugs for promoting blood circulation and removing blood stasis in traditional Chinese medicine,which could be reflected in the inhibition of tail thrombosis in mice. As the traditional processing theory instructs,vinegar tastes sour and bitter,but can activate blood circulation and remove stasis after being infiltrated into the rhizome of C. phaeocaulis as an excipient. In this study,under the help of the ultrafast liquid chromatography-quadrupole time-offlight mass spectrometry( UFLC-Q-TOF-MS),the spectrum-effect relationship between the inhibition of tail thrombosis in mice and the rhizome of C. phaeocaulis both before and after the vinegar processing,were established to explore the functional changes of blood circulation and stasis after vinegar process. Based on the peak area from the fingerprint of UFLC-Q-TOF-MS of the alcohol extracts from the raw and vinegar-processed rhizome of C. phaeocaulis and their efficacy for inhibiting tail thrombosis,the correlation between the chromatography of UFLC-Q-TOF-MS and the inhibition of tail thrombosis in mice were analyzed by orthogonal partial least squares discriminant analysis( OPLS-DA) method. The results,produced by Simca-P software,showed that effective components consisted of eight peaks 16,24( aromadendrene oxide),3,11,22( dehydro-α-curcumene),19[( R)-(-)-α-curcumene],23 and 10 from the fingerprint,making great contribution to distinguish C. phaeocaulis raw products and the corresponding vinegar processed products. Therefore,from the perspective of inhibiting the formation of tail thrombosis in mice,the marker components could be found through the spectrum-effect relationship to distinguish C.phaeocaulis raw and vinegar products. This study provided new basis to explain the difference between the raw and the processed products of traditional Chinese medicine in the functional change of promoting blood circulation and removing blood stasis.
Acetic Acid
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Animals
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Chromatography, High Pressure Liquid
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Curcuma
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chemistry
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Drugs, Chinese Herbal
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chemistry
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pharmacology
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Mass Spectrometry
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Mice
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Rhizome
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chemistry
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Thrombosis
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drug therapy
5.Soft coral Cespitularia stolonifera: New cytotoxic ceramides and gastroprotective activity.
Abdelsamed I ELSHAMY ; Walaa A EL-KASHAK ; Heba M I ABDALLAH ; Abdelrazik H FARRAG ; Mahmoud I NASSAR
Chinese Journal of Natural Medicines (English Ed.) 2017;15(2):105-114
In the present study, a new ceramide, namely 2S, 3R-4E, 8E-2-(heptadecanoylamino)-heptadeca-4, 8-diene-1, 3-diol (1), along with four known steroids, including 24-methylcholesta-5, 24(28)-diene-3β-ol (2), 24-methylcholesta-5, 24(28)-diene-3β-acetate (3), 4-methyl-24-methylcholesta-22-ene-3-ol (4), and cholesterol, was isolated and characterized from CHCl/MeOH extract of Cespitularia stolonifera. A new acetate derivative of compound 1, termed 2S, 3R-4E, 8E-2-(heptadecanoylamino)-heptadeca-4, 8-diene-1, 3-diacetate (1a), was also prepared in the present study. All the structures were established on the basis of modern spectroscopic techniques, including FT-IR, 1D, 2D-NMR, HRESI-MS, and GC-MS, in addition of chemical methods. (-)-Alloaromadendren, ledane, (1)-alloaromadendren oxide, isoaromadendrene epoxide and (-)-caryophellen oxide were identified from the n-hexane fraction using GC-MS. The extract and the two ceramides (1) and (1a) exhibited significant cytotoxic activity against lung cancer A549 cells, while the extract and the two steroids (2) and (3) exhibited significant cytotoxic activity against breast cancer MCF-7 cells. The CHCl/MeOH extract exhibited significant antiulcer activity in both ethanol and acetic acid induced ulcer models in rats, as evidenced by histopathological, histochemical, and biochemical examinations.
A549 Cells
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Acetic Acid
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Animals
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Anthozoa
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chemistry
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Anti-Ulcer Agents
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chemistry
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isolation & purification
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pharmacology
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therapeutic use
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Antineoplastic Agents
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chemistry
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isolation & purification
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pharmacology
;
therapeutic use
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Biological Products
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chemistry
;
isolation & purification
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pharmacology
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therapeutic use
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Breast Neoplasms
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drug therapy
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Ceramides
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chemistry
;
isolation & purification
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pharmacology
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therapeutic use
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Disease Models, Animal
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Ethanol
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Female
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Humans
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Lung Neoplasms
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drug therapy
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MCF-7 Cells
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Magnetic Resonance Spectroscopy
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methods
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Rats
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Spectroscopy, Fourier Transform Infrared
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methods
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Steroids
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chemistry
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isolation & purification
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pharmacology
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therapeutic use
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Ulcer
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chemically induced
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drug therapy
6.Anti-inflammatory and analgesic effects of Bi-yuan-ling granules.
Xiao-Bing CHEN ; Han-Wen SU ; Huan-Xiang LIU ; Xian YIN ; Feng HE ; Yong-Shen REN ; Kang DAI ; Mei-Xian XIANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(3):456-462
Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.
Acetic Acid
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Acute Lung Injury
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chemically induced
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drug therapy
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pathology
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Analgesics
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pharmacology
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Animals
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Anti-Inflammatory Agents
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pharmacology
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Carrageenan
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administration & dosage
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Chlorogenic Acid
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pharmacology
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Dinoprostone
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antagonists & inhibitors
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biosynthesis
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Disease Models, Animal
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Dosage Forms
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal
;
pharmacology
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Ear
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pathology
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Edema
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chemically induced
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drug therapy
;
pathology
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Flavonoids
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pharmacology
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Lipopolysaccharides
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administration & dosage
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Male
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Mice
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Mice, Inbred Strains
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Pain
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chemically induced
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drug therapy
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physiopathology
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Rats
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Rats, Sprague-Dawley
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Xylenes
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administration & dosage
7.Advances in the progress of anti-bacterial biofilms properties of acetic acid.
Xinxin GAO ; Zhenghua JIN ; Xinxin CHEN ; Jia'ao YU
Chinese Journal of Burns 2016;32(6):382-384
Bacterial biofilms are considered to be the hindrance in the treatment of chronic wound, because of their tolerance toward antibiotics and other antimicrobial agents. They also have strong ability to escape from the host immune attack. Acetic acid, as a kind of organic weak acid, can disturb the biofilms by freely diffusing through the bacterial biofilms and bacterial cell membrane structure. Then the acid dissociates to release the hydrogen ions, leading to the disorder of the acid-base imbalance, change of protein conformation, and the degradation of the DNA within the membranes. This paper reviews the literature on the characteristics and treatment strategies of the bacterial biofilms and the acetic acid intervention on them, so as to demonstrate the roles acetic acid may play in the treatment of chronic wound, and thus provide a convincing treatment strategy for this kind of disease.
Acetic Acid
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pharmacology
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Anti-Bacterial Agents
;
pharmacology
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Biofilms
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drug effects
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Humans
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Wound Healing
8.Advances in functional genomics studies underlying acetic acid tolerance of Saccharomyces cerevisiae.
Xinqing ZHAO ; Mingming ZHANG ; Guihong XU ; Jianren XU ; Fengwu BAI
Chinese Journal of Biotechnology 2014;30(3):368-380
Industrial microorganisms are subject to various stress conditions, including products and substrates inhibitions. Therefore, improvement of stress tolerance is of great importance for industrial microbial production. Acetic acid is one of the major inhibitors in the cellulosic hydrolysates, which affects seriously on cell growth and metabolism of Saccharomyces cerevisiae. Studies on the molecular mechanisms underlying adaptive response and tolerance of acetic acid of S. cerevisiae benefit breeding of robust strains of industrial yeast for more efficient production. In recent years, more insights into the molecular mechanisms underlying acetic acid tolerance have been revealed through analysis of global gene expression and metabolomics analysis, as well as phenomics analysis by single gene deletion libraries. Novel genes related to response to acetic acid and improvement of acetic acid tolerance have been identified, and novel strains with improved acetic acid tolerance were constructed by modifying key genes. Metal ions including potassium and zinc play important roles in acetic acid tolerance in S. cerevisiae, and the effect of zinc was first discovered in our previous studies on flocculating yeast. Genes involved in cell wall remodeling, membrane transport, energy metabolism, amino acid biosynthesis and transport, as well as global transcription regulation were discussed. Exploration and modification of the molecular mechanisms of yeast acetic acid tolerance will be done further on levels such as post-translational modifications and synthetic biology and engineering; and the knowledge obtained will pave the way for breeding robust strains for more efficient bioconversion of cellulosic materials to produce biofuels and bio-based chemicals.
Acetic Acid
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pharmacology
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Genomics
;
Industrial Microbiology
;
Saccharomyces cerevisiae
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drug effects
;
genetics
9.Protective effect of ginger volatile oil against acetic acid-induced colitis in rats: a light microscopic evaluation.
Amir RASHIDIAN ; Saeed MEHRZADI ; Ali Reza GHANNADI ; Parvin MAHZOONI ; Samira SADR ; Mohsen MINAIYAN ; E-mail: MINAIYAN@PHARM.MUI.AC.IR.
Journal of Integrative Medicine 2014;12(2):115-120
OBJECTIVEUlcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. In the present study, the effect of ginger (rhizome of Zingiber officinale Roscoe) volatile oil on a rat model of colitis was evaluated.
METHODSVolatile oil of ginger with doses of 100, 200, and 400 mg/kg, prednisolone (4 mg/kg), or vehicle were administered orally to groups of male Wistar rats (n = 6) for 5 d. Animals were randomly divided into 6 groups, each group consisting of 6 rats. Colitis was induced by intracolonic instillation of 2 mL of 4% (v/v) acetic acid solution. All rats were sacrificed 24 h later and the tissue injuries were assessed macroscopically and histopathologically.
RESULTSGinger volatile oil with all doses reduced colon weight/length ratio (P < 0.01) and the effects were similar to the reference drugs. Higher oral doses of volatile oil (200 and 400 mg/kg) reduced ulcer severity (P < 0.05 and P < 0.01), ulcer area (P < 0.01) and ulcer index (P < 0.01). On the other hand, evaluation of microscopic scores showed that the dose of 400 mg/kg of volatile oil was effective to reduce inflammation severity (P < 0.01) and inflammation extent (P < 0.05) compared to the control group.
CONCLUSIONIt is concluded that ginger volatile oil could effectively reduce symptoms of experimental colitis in a dose-dependent manner.
Acetic Acid ; pharmacology ; Animals ; Colitis ; chemically induced ; pathology ; prevention & control ; Dose-Response Relationship, Drug ; Ginger ; chemistry ; Male ; Microscopy ; Oils, Volatile ; isolation & purification ; therapeutic use ; Plant Extracts ; isolation & purification ; therapeutic use ; Plant Oils ; isolation & purification ; therapeutic use ; Rats ; Rats, Wistar ; Rhizome ; chemistry
10.Effect of Fagopyrum cymosum (Trev.) Meisn alcohol extract on defecation and isolated colon of diarrhea-IBS rats and its mechanism.
Li-Na LIU ; Jing YAN ; Zhi-Guang SUN
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(12):1469-1475
OBJECTIVETo explore the intervention of Fagopyrum cymosum (Trev.) Meisn alcohol extract (FAE) on defecation function and motor functions of isolated colons of diarrhea-predominant irritable bowel syndrome (D-IBS) rats and to study its underlying mechanism.
METHODSThe D-IBS rat model was established by neonatal pups maternal separation (NMS) combined with intracolonic infusion of acetic acid (AA). Adult IBS rats were randomly divided into the pre-intervention control group (n = 10, with no gastrogavage), the normal saline control group (n = 10, administered with normal saline by gastrogavage), the pre-treatment model group (n = 8,with no gastrogavage),the normal saline model group (n = 8, administered with normal saline by gastrogavage), the low dose FAE group (n = 8, administered with 6 g/kg FAE by gastrogavage), the high dose FAE group (n = 8, administered with 24 g/kg FAE by gastrogavage), and the Pinaverium Bromide group (n = 8, administered with 0.02 g/kg Pinaverium Bromide by gastrogavage). All medication was performed once daily for 2 weeks. The abdominal withdrawal reflex (AWR) was employed to evaluate the visceral hypersensitivity; their loose and watery stool grade was assessed by Bristol scores for stool consistency; and their fresh feces weight was calculated. In vitro effect of different concentrations of FAE and Pinaverium Bromide (0.02 μg/mL) on spontaneous contraction and spasmodic contraction induced by acetylcholine (Ach) in rats' isolated colon were observed and the influence on the intestinal calcium channel was evaluated.
RESULTSCompared with the pre-intervention control group, the pain pressure threshold and the maximum tolerance pressure decreased significantly in the pre-intervention model group (P < 0.05), and the loose and watery stool grade and fresh feces weight increased drastically (P < 0.01). Compared with the normal saline control group, the pain pressure threshold and the maximum tolerance pressure decreased significantly in the normal saline model group (P < 0.05), and the loose and watery stool grade and fresh feces weight increased markedly (P < 0.01). Compared with the normal saline model group, the pain pressure threshold of 24 g/kg FAE and Pinaverium Bromide group significantly increased (P < 0.05). The loose and watery stool grade and fresh feces weight decreased obviously in the low dose FAE group, the high dose FAE group, and the Pinaverium Bromide group (P < 0.05). FAE (30, 100, 300, 1,000, and 3,000 μg/mL) and Pinaverium Bromide could significantly inhibit spontaneous contraction of isolated intestines (P < 0.05, P < 0.01), and FAE (30, 100, and 300 x 10(-6) g/mL) could remarkably inhibit their spasmodic contraction and contractile tension induced by Ach and Ca2+ respectively (P < 0.05, P < 0.01) in a concentration-dependent manner. Pinaverium Bromide also could significantly inhibit Ach and Ca2+ induced contraction.
CONCLUSIONEffective components of FAE improved the defecation function and inhibited enterospasm induced intestinal hyperactivity in IBS model rats via antagonizing calcium channel competitively and inhibiting colonic motility dose-dependently.
Acetic Acid ; Animals ; Defecation ; drug effects ; Diarrhea ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fagopyrum ; Irritable Bowel Syndrome ; drug therapy ; Rats

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