Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents

Objective

To assess the hepatoprotective effect of Solanum xanthocarpum (S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.

Methods

Ethanolic (50%) fruit extract of S. xanthocarpum (100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid (I) 7.5 mg/kg, rifampicin (R) 10 mg/kg and pyrazinamide (P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), total bilirubin (TBL), albumin (ALB), total protein (TP), lactate dehydroginase (LDH), and serum cholesterol (CHL). Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.

Results

The results demonstrated that treatment with S. xanthocarpum significantly (P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, S. xanthocarpum significantly (up to P<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpum attenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.

Conclusions

The results of this study strongly indicate the protective effect of S. xanthocarpum against liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.     

试验性抗结核治疗鉴别肠结核与克罗恩病的临床与内镜分析

目的探讨试验性抗结核治疗鉴别诊断肠结核与克罗恩病的评估标准及合适的判断时间点。方法回顾分析接受试验性抗结核治疗且最后得以确诊的28例肠结核（ITB）和11例克罗恩病（CD）患者在治疗过程中临床表现及肠镜下的改变。结果2组患者基线时较特异的临床特征包括活动性肺结核、PPD强阳性、肛瘘或肛周脓肿等差异均无统计学意义。抗结核治疗后2组临床症状均有改善,但3个月后ITB组无好转率为0,CD组为27．3％（P=0．004）。抗结核治疗3个月及6个月,ITB组活动性溃疡消失率＋明显好转率分别为90．9％（20／22）＋9．1％（2／22）及100％（28／28）＋0;结节样病变消失率＋明显好转率为58．8％（10／17）＋41．2％（7／17）及76．5％（13／17）＋23．5％（4／17）。而CD组在各时点活动性溃疡、结节样病变均无明显好转（P均〈0．01）。结论ITB和CD的鉴别因缺乏特异性指标,部分鉴别困难的病例仍需采用试验性抗结核治疗。试验性抗结核治疗后3个月,回结肠镜复查见活动性溃疡及结节样病变消失或明显好转,伴临床症状痊愈或明显好转可评定为试验治疗有效。     

高危人群抗结核药物性肝损害分析

目的：探讨高危人群抗结核药物性肝损害的特点。方法：选取我院结核科抗结核治疗94例存在高危因素人群病人,统计两组在抗结核治疗中出现药物性肝损害的时间及临床症状,肝损发生率及引起肝损的原因。结果：对照组（未干预）肝损发生率、程度和合并黄疸的例数、均较实验组（干预）升高,出现肝损与时间之间两组存在显著性差异,而ALT120～200U/L的例数较对照组降低。两组资料显示引起药物性肝损的原因中以利福平为主,出现药物性肝损的时间高峰为4周以内,而引起肝损的3种药物的构成比差异无显著性（P〉0.05）。结论：对于老年人、长期饮酒者、HBV感染者、营养不良、免疫功能低下者这些高危因素人群抗结核治疗时给予干预方案,可以减少肝损发生。     

Antimicrobial activity of pomegranate fruit constituents against drug-resistant Mycobacterium tuberculosis and β-lactamase producing Klebsiella pneumoniae

Abstract

Context: The global surge in multi-drug resistant bacteria and the imminence of tuberculosis pandemic necessitate alternative therapeutic approaches to augment the existing medications. Pomegranate, the fruit of Punica granatum Linn. (Punicaceae), widely recognized for potency against a broad spectrum of bacterial pathogens, deserves further investigation in this respect.

Objective: This study determines the therapeutic potential of pomegranate juice, extracts of non-edible peel prepared with methanol/water, and its four polyphenolic constituents, namely caffeic acid, ellagic acid, epigallocatechin-3-gallate (EGCG) and quercetin, against drug-resistant clinical isolates.

Materials and methods: Phenotypic characterisation of Mycobacterium tuberculosis, extended-spectrum β-lactamase (ESBL) and KPC-type carbapenemase producing Klebsiella pneumoniae was performed by biochemical and molecular methods. Resistance profiles of M. tuberculosis and K. pneumoniae were determined using LJ proportion and Kirby–Bauer methods, respectively. Pomegranate fruit extracts, and the compounds, were evaluated at a dose range of 1024–0.5?µg/mL, and 512–0.25?µg/mL, respectively, to determine minimum inhibitory (MIC) and bactericidal concentrations (MBC) against the drug-resistant isolates by the broth micro-dilution method.

Results: The peel extracts exhibited greater antimycobacterial activity (MIC 64–1024?μg/mL) than the potable juice (MIC 256?-?>?1024?μg/mL). EGCG and quercetin exhibited higher antitubercular (MIC 32–256?μg/mL) and antibacterial (MIC 64–56?μg/mL) potencies than caffeic acid and ellagic acid (MIC 64–512?μg/mL).

Discussion and conclusion: The pomegranate fruit peel and pure constituents were active against a broad panel of M. tuberculosis and β-lactamase producing K. pneumoniae isolates. EGCG and quercetin need further investigation for prospective application against respiratory infections.     

Antitubercular Activity of Compounds Isolated from Pelargonium sidoides.

Abstract

The recent increase in the incidence of tuberculosis with the emergence of multidrug-resistant (MDR) cases has lead to the search for new drugs that are effective against MDR strains of Mycobacterium tuberculosis. and can augment the potential of existing drugs against tuberculosis. Pelargonium sidoides. DC (Geraniaceae) is highly valued by traditional healers for its curative properties and is well-known to treat coughs, diarrhea, and tuberculosis. The butanol root extract was found have bioactive inhibitory activity against M. tuberculosis. at a concentration of 2.5 × 10³ µg/mL. Phytochemical analysis of the active fraction from the root of P. sidoides. led to the isolation and identification of six compounds: coumarins (umckalin, scopoletin, 6,8-dihydroxy-5.7-dimethoxy-2H.-benzopyran-2-one, and 6,8-dihydroxy-7-methoxy-2H.-benzopyran-2-one) and flavonoids (catechin and epigallocatechin, which is reported for the first time from P. sidoides.). The isolated compounds were evaluated for antitubercular activity with M. smegmatis. and M. tuberculosis.. Intracellular activity of these compounds was also investigated using THP-1 human macrophages infected with M. tuberculosis.. The isolated compounds did not show activity inhibitory against M. tuberculosis., intracellularly and extracellularly, at the highest concentration tested in the current study. Epigallocatechin and scopoletin showed good inhibitory activity against M. smegmatis., exhibiting a minimum inhibitory concentration (MIC) of 7.8 µg/mL. Catechin and umckalin exhibited MIC values of 31.25 and 62.5 µg/mL, respectively.     

Identification of 1-[4-Benzyloxyphenyl)-but-3-enyl]-1H-azoles as New Class of Antitubercular and Antimicrobial Agents

相似文献   

Antitubercular activity of Arctium lappa and Tussilago farfara extracts and constituents

Ethnopharmacological relevance

Arctium lappa and Tussilago farfara (Asteraceae) are two plant species used traditionally as antitubercular remedies. The aim of this study was (i) to screen Arctium lappa and Tussilago farfara extracts for activity against Mycobacterium tuberculosis and (ii) to isolate and identify the compound(s) responsible for this reputed anti-TB effect.

Materials and methods

The activity of extracts and isolated compounds was determined against Mycobacterium tuberculosis H₃₇R_v using a high throughput spot culture growth inhibition (HT-SPOTi) assay.

Results

The n-hexane extracts of both plants, the ethyl acetate extract of Tussilago farfara and the dichloromethane phase derived from the methanol extract of Arctium lappa displayed antitubercular activity (MIC 62.5 μg/mL). Further chemical investigation of Arctium lappa led to the isolation of n-nonacosane (1), taraxasterol acetate (2), taraxasterol (3), a (1:1) mixture of β sitosterol/stigmasterol (4), isololiolide (5), melitensin (6), trans-caffeic acid (7), kaempferol (8), quercetin (9), kaempferol-3-O-glucoside (10). Compounds isolated from Tussilago farfara were identified as a (1:1) mixture of β sitosterol/stigmasterol (4), trans-caffeic acid (7), kaempferol (8), quercetin (9), kaempferol-3-O-glucoside (10), loliolide (11), a (4:1) mixture of p-coumaric acid/4-hydroxybenzoic acid (12), p-coumaric acid (13). All compounds were identified following analyses of their physicochemical and spectroscopic data (MS, ¹H and ¹³C-NMR) and by comparison with published data. This is the first report of the isolation of n-nonacosane (1), isololiolide (5), melitensin (6) and kaempferol-3-O-glucoside (10) from Arctium lappa, and of loliolide (11) from Tussilago farfara. Amongst the isolated compounds, the best activity was observed for p-coumaric acid (13) (MIC 31.3 μg/mL or 190.9 μM) alone and in mixture with 4-hydroxybenzoic acid (12) (MIC 62.5 μg/mL).

Conclusions

The above results provide for the first time some scientific evidence to support, to some extent, the ethno-medicinal use of Arctium lappa and Tussilago farfara as traditional antitubercular remedies.     

New series of isoniazid hydrazones linked with electron-withdrawing substituents

A series of new isoniazid hydrazones was synthesized by two procedures. In the first isoniazid was activated with diethoxymethyl acetate and condensed with the appropriate anilines. Alternatively, substituted anilines were activated by diethoxymethyl acetate and subsequently condensed with isoniazid. NMR study confirmed that both synthetic approaches gave the same tautomer. All compounds were screened for in vitro antimycobacterial activity. Most of them exhibited the same activity against Mycobacterium tuberculosis (MIC 1 μmol L⁻¹) as isoniazid (INH), better activity against Mycobacterium kansasii 325/80 (MIC 0.125–0.250 μmol L⁻¹), high value of selectivity index (SI) and IC₅₀ between 0.0218 and 0.326 mmol L⁻¹. Compound 2o with the best SI was used as a model compound for the stability test and was found to be stable at neutral pH, but under acidic conditions it slowly hydrolysed.     

焦磷酸测序技术检测结核分枝杆菌四种药物耐药性

目的 利用焦磷酸测序技术检测结核分枝杆菌对利福平、异烟肼、氧氟沙星、阿米卡星的耐药性,并对其临床应用进行评价.方法 收集上海市肺科医院2008-2009年临床确诊的肺结核患者的痰标本培养阳性结核分枝杆菌89株.所有菌株按<结核病诊断实验室检验规程>进行分枝杆菌培养、菌种鉴定.另外10株已知药敏结果的结核分枝杆菌来自上海市肺科医院菌株库.利用焦磷酸测序技术,以10株已知药敏结果和经直接测序已知耐药基因突变情况的结核分枝杆菌为试验菌株,探索焦磷酸测序检测结核分枝杆菌rpoB、katG、gyrA、rrs耐药基因的最佳模式,并用该条件检测89株结核分枝杆菌临床分离株,检测结果与Bactec 960药敏法进行比较.结果 rpoB、gyrA基因检测宜采用焦磷酸测序序列分析模式,katG、rrs基因检测宜采用焦磷酸测序单核苷酸多态性模式.以Bactec 960药敏法测定结果为判断标准,则焦磷酸测序法检测89株结核分枝杆菌临床分离株对利福平、异烟肼、氧氟沙星、阿米卡星耐药性的敏感度分别为98.0%、64.1%、79.5%、78.3%,特异度分别为97.5%、100.0%、90.0%、100.0%,准确性分别为97.8%、77.5%、85.4%、94.4%,该法检测利福平、氧氟沙星、阿米卡星的检测结果与Bactec 960药敏检测结果一致性较好,Kappa值均≥0.7.结论 焦磷酸测序技术检测结核分枝杆菌对利福平、异烟肼、氧氟沙星、阿米卡星耐药性具有快速、准确、高通量的优点,是一种可对结核分枝杆菌多种药物耐药性进行快速检测的方法.

Abstract：

Objective To develop an assay to determine Mycobacterium tuberculosis resistance to rifampin, isoniazid, ofloxacin and amikacin by pyrosequencing and evaluate the value of this method in clinical application. Methods Eighty-nine clinical isolates of Mycobacterium tuberculosis from tuberculosis patients were collected from Shanghai Pulmonary Hospital during 2008 to 2009. All strains were isolated from decontaminated sputum, cultured on Lowenstein-Jensen media and identified by traditional biochemical tests with standard methods. Ten Mycobacterium tuberculosis were selected from the strain bank of Shanghai Pulmonary Hospital. The optimal conditions of detection of rpoB, katG, gyrA and rrs gene by pyroseuencing were determined, using the 10 Mycobacterium tuberculosis strains whose drug susceptibility of Bactec 960 and sequence of rpoB, katG, gyrA, rrs gene were known. Then the drug susceptibility of 89 Mycobacterium tuberculosis clinical isolate strains were detected by pyrosequencing using this conditions and the results were compared with that of the Bactec 960 methods. Results The pyrosequencing program of sequence analysis was suitable for the detection of the mutations of rpoB and gyrA genes, and the program of single nucleotide polymorphism was suitable for katG and rrs genes. Among the 89 Mycobacterium tuberculosis clinical isolates,when using the drug susceptibility of Bactec 960 as the standard, the sensitivity of rifampin, isoniazid,ofloxacin and amikacin is 98.0%, 64. 1%, 79.5%, 78. 3% respectively, the specificity is 97.5%,100. 0%, 90. 0%, 100. 0% respectively, the accuracy is 97.8%, 77. 5%, 85.4%, 94. 4% respectively,tested by pyrosequencing. The results of the detection of resistance to rifampin, isoniazid, ofloxacin and amikacin in Mycobacterium tuberculosis using pyrosequencing technique were almost the same with that of Bactec 960, and Kappa ≥0. 7 in each detection. Conclusion Pyrosequencing is thus a rapid, accurate and high throughput method for detecting Mycobacterium tuberculosis resistance to these four drugs.     

护肝片在防治抗结核药物所致肝损伤的临床应用

目的探讨护肝片在防治抗结核药物所致肝损伤中的应用前景及疗效。方法对比分析治疗组与对照组之间在抗结核治疗中肝损害发生率、损害程度、发生时间,并进行差异显著性分析。结果 535例病例中,肝损害发生率为6.92%,治疗组ALT升高9例,发生率为3.37%,升高幅度在50~120U之间,损害多发生在治疗的2~4周,之后逐渐减少,HBsAg阳性病人发生率高,损害程度轻。对照组发生ALT升高28例,发生率为10.48%,升幅在75~180U之间,损害多发生于开始治疗4周左右,HBsAg阳性病人肝损害多为中重度损害,两组肝损害比较差异有统计学意义（χ2=9.34,P〈0.01）。结论潜在的肝损害人群中,以HBsAg阳性人群和老年人群最为危险,在抗结核治疗中应全程加服护肝片,并密切注意肝功能的变化。