Terminalia chebula supplementation attenuates cisplatin-induced nephrotoxicity in Wistar rats through modulation of apoptotic pathway

In the present study, we have evaluated the nephroprotective effect of hydroalcoholic extract of Terminalia chebula in cisplatin-induced nephrotoxicity model. Standardised extract was orally administered to Wistar rats for 10 days at different doses. On day 7, 8 mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. T. chebula, in a dose-dependent manner significantly inhibited the elevation of serum creatinine, blood urea nitrogen and oxidant stress markers. The immunohistochemical analysis revealed the increased levels of apoptotic markers and cytokines in cisplatin group were significantly lowered by T. chebula extract. The cisplatin-treated rats kidney showed diffused tubular necrosis and infilteration of inflammatory cells which was reversed in the treatment group. Chemical characterisation of extract by HPLC revealed the presence of corilagin, chebulinic, chebulagic, chebulic, gallic and ellagic acid. The findings of this study discovered that T. chebula ameliorated oxidative and histological damage caused by cisplatin.     

Comparative analysis of oil composition and antibacterial activity of aerial parts of Terminalia arjuna (Roxb.)

Abstract

Volatile oil composition of leaves and fruits of Terminalia arjuna (Roxb.) was reported for the first time. Oils were extracted by microwave assisted hydrodistillation where yield of both oils were found to be 0.20% and their GC-MS analyses led to the identification of 65 and 48 constituents, respectively. Major constituents of leaves were carvacrol (11.17%), thymol (6.52%), α-terpinyl acetate (5.92%) and anethole (5.13%) while that of fruits were (E)-isoeugenol (11.48%), furfural (8.25%), p-vinylguaiacol (6.8%) and p-ethylguaiacol (5.72%) that demonstrated a significant difference between composition of its aerial parts, however, 33 constituents were identical that showed similarity characteristics in quality of these oils. Both leaf and fruit oils were found active against pathogenic and drug-resistant microbes: E. coli, Methicillin-resistant S. aureus, P. aeruginosa, Total-drug-resistant P. aeruginosa and K. pneumoniae with MIC values of 0.32, 0.32, 0.64, 0.64, 2.56?mg/mL and 0.16, 0.16, 0.32, 0.64, 1.28?mg/mL, respectively.     

Combined chromatographic strategy based on macroporous resin,high‐speed counter‐current chromatography and preparative HPLC for systematic separation of seven antioxidants from the fruit of Terminalia billerica

In the present study, combined chromatographic strategy based on macroporous resin, high‐speed counter‐current chromatography and preparative high‐performance liquid chromatography for systematic separation of antioxidants from crude samples guided by high‐performance liquid chromatography with 1,1‐diphenyl‐2‐picrylhydrazyl has been successfully established. Based on this strategy, seven antioxidants including isorugosin A, _β‐1,2,3,6‐tetragalloyl‐D ‐glucose, chebulinic acid, 1,2,3,4,6‐penta‐O‐galloyl‐_β‐D‐glucose, chebulagic acid, ethyl gallate, and gallic acid were obtained from the fruit of Terminalia billerica. First, high‐performance liquid chromatography with 1,1‐diphenyl‐2‐picrylhydrazyl experiment showed the presence of seven main antioxidants in the crude extract of the fruit of Terminalia billerica. Then, a macroporous resin column chromatography method was developed for the enrichment of these seven antioxidants. Finally, an efficient method based on high‐speed counter‐current chromatography and preparative high‐performance liquid chromatography was developed for the separation of these antioxidants. In the selection of solvent systems, it was found that acetic acid could be a good regulator for modifying the partition coefficient values of tannins. The present study provides a reference for systematic separation of antioxidants from crude samples. Considering the general existence of antioxidants in crude samples, this combined chromatographic strategy might lead to broader application prospects.     

基于液相色谱信息的西青果化学成分抑制α-葡萄糖苷酶活性数学模型的构建

中药提取物是一个组成复杂、机理不明晰的混合物体系,其对靶标的作用是其中所有化合物的综合影响,如何表征和评价其生物活性值得深入研究。本文采用羟丙基葡聚糖凝胶色谱柱分离西青果乙醇提取物,得到29组成分连续变化的样品,采集样品的色谱信息(254 nm波长下)与活性信息,运用逐步回归法建立成分的峰面积(Vi,自变量)与活性(以对酶的抑制率(W)表示,因变量)之间的数学方程,确定对活性影响显著的成分。结果表明,29组样品包含55个峰,这些峰对应成分的峰面积(Vi,i=1,2,…,55)与W之间存在数学关系:W=V7×(-0.034±0.013)+V18×(-0.155±0.051)+V29×(-0.142±0.028)+V4×(0.079±0.020)+V11×(0.074±0.028)+V36×(-0.117±0.053)+85.669±4.476,复相关系数R=0.854,显著度=0.037,稳健性良好,对活性影响最显著的物质为第18、29、36、4、11和7号峰对应的化合物。该方法同样适用于不同中药资源的成分与多种不同活性等方面的研究,对于中药的研发具有重要意义。     

Phytochemical Profiling and Quality Control of Terminalia sericea Burch. ex DC. Using HPTLC Metabolomics

Terminalia sericea is used throughout Africa for the treatment of a variety of conditions and has been identified as a potential commercial plant. The study was aimed at establishing a high-performance thin layer chromatography (HPTLC) chemical fingerprint for T. sericea root bark as a reference for quality control and exploring chemical variation within the species using HPTLC metabo3lomics. Forty-two root bark samples were collected from ten populations in South Africa and extracted with dichloromethane: methanol (1:1). An HPTLC method was optimized to resolve the major compounds from other sample components. Dichloromethane: ethyl acetate: methanol: formic acid (90:10:30:1) was used as the developing solvent and the plates were visualized using 10% sulfuric acid in methanol as derivatizing agent. The concentrations of three major bioactive compounds, sericic acid, sericoside and resveratrol-3-O-β-rutinoside, in the extracts were determined using a validated ultra-performance liquid chromatography-photodiode array (UPLC-PDA) detection method. The rTLC software (written in the R-programming language) was used to select the most informative retardation factor (Rf) ranges from the images of the analysed sample extracts. Further chemometric models, including principal component analysis (PCA) and hierarchical cluster analysis (HCA), were constructed using the web-based high throughput metabolomic software. The rTLC chemometric models were compared with the models previously obtained from ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). A characteristic fingerprint containing clear bands for the three bioactive compounds was established. All three bioactive compounds were present in all the samples, although their corresponding band intensities varied. The intensities correlated with the UPLC-PDA results, in that samples containing a high concentration of a particular compound, displayed a more intense band. Chemometric analysis using HCA revealed two chemotypes, and the subsequent construction of a loadings plot indicated that sericic acid and sericoside were responsible for the chemotypic variation; with sericoside concentrated in Chemotype 1, while sericic acid was more abundant in Chemotype 2. A characteristic chemical fingerprint with clearly distinguishable features was established for T. sericea root bark that can be used for species authentication, and to select samples with high concentrations of a particular marker compound(s). Different chemotypes, potentially differing in their therapeutic potency towards a particular target, could be distinguished. The models revealed the three analytes as biomarkers, corresponding to results reported for UPLC-MS profiling and thereby indicating that HPTLC is a suitable technique for the quality control of T. sericea root bark.     

诃子抗嗜水气单胞菌活性组分分离及其对鲫鱼的毒性试验

研究以抑菌圈直径大小作为评价指标,利用提取分离技术对诃子进行抗嗜水气单胞茵活性成分分离追踪,并对诃子的抗菌活性单体进行安全评价．结果显示,诃子的抗嗜水气单胞茵的活性部位为乙酸乙酯萃取部位,其浓度为4mg·L^-1时,抑茵圈直径为18mm．活性部位经多次柱层析分离,得到一白色针状晶体．抑菌试验结果显示,最小抑菌浓度（MIC）和最小杀菌浓度（MBC）分别为2．8mg-L^-1和5．6mg·L^-1．急性毒性实验结果显示,活性单体对鲫鱼的96h半致死浓度为220．7mg·L^-1,其安全浓度为85．2mg·L^-1,但其化学结构还有待于进一步研究．     

Hepatitis C Virus NS3/4A Inhibition and Host Immunomodulation by Tannins from Terminalia chebula: A Structural Perspective

Terminalia chebula Retz. forms a key component of traditional folk medicine and is also reported to possess antihepatitis C virus (HCV) and immunomodulatory activities. However, information on the intermolecular interactions of phytochemicals from this plant with HCV and human proteins are yet to be established. Thus, by this current study, we investigated the HCV NS3/4A inhibitory and host immune-modulatory activity of phytocompounds from T. chebula through in silico strategies involving network pharmacology and structural bioinformatics techniques. To start with, the phytochemical dataset of T. chebula was curated from biological databases and the published literature. Further, the target ability of the phytocompounds was predicted using BindingDB for both HCV NS3/4A and other probable host targets involved in the immune system. Further, the identified targets were docked to the phytochemical dataset using AutoDock Vina executed through the POAP pipeline. The resultant docked complexes with significant binding energy were subjected to 50 ns molecular dynamics (MD) simulation in order to infer the stability of complex formation. During network pharmacology analysis, the gene set pathway enrichment of host targets was performed using the STRING and Reactome pathway databases. Further, the biological network among compounds, proteins, and pathways was constructed using Cytoscape 3.6.1. Furthermore, the druglikeness, side effects, and toxicity of the phytocompounds were also predicted using the MolSoft, ADVERpred, and PreADMET methods, respectively. Out of 41 selected compounds, 10 were predicted to target HCV NS3/4A and also to possess druglike and nontoxic properties. Among these 10 molecules, Chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose exhibited potent HCV NS3/4A inhibitory activity, as these scored a lowest binding energy (BE) of −8.6 kcal/mol and −7.7 kcal/mol with 11 and 20 intermolecular interactions with active site residues, respectively. These findings are highly comparable with Asunaprevir (known inhibitor of HCV NS3/4A), which scored a BE of −7.4 kcal/mol with 20 key intermolecular interactions. MD studies also strongly suggest that chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose as promising leads, as these molecules showed stable binding during 50 ns of production run. Further, the gene set enrichment and network analysis of 18 protein targets prioritized 10 compounds and were predicted to potentially modulate the host immune system, hemostasis, cytokine levels, interleukins signaling pathways, and platelet aggregation. On overall analysis, this present study predicts that tannins from T. chebula have a potential HCV NS3/4A inhibitory and host immune-modulatory activity. However, further experimental studies are required to confirm the efficacies.     

Flavonoid Glycosides from Terminalia catappa L.

Under the inhibition of Cu⁺²‐induced LDL oxidation‐guided fractionation, two new flavone glycosides with galloyl substitution were isolated from the dried fallen leaves of Terminalia catappa L. Their structures were established as apigenin 6‐C‐(2″‐O‐galloyl)‐β‐D‐glucopyranoside ( 1 ) and apigenin 8‐C‐(2″‐O‐galloyl)‐β‐D‐glucopyranoside ( 2 ), together with four known flavone glycosides, isovitexin, vitexin, isoorientin, and rutin, on the basis of spectroscopic method. Compounds 1 and 2 showed significant antioxidative effects. Their IC₅₀ were 2.1 and 4.5 μM, respectively.     

诃子与川楝子配伍后挥发油化学成分分析

采用水蒸气蒸馏法将诃子与川楝子按1∶1的质量比配伍后提取挥发油,并用GC-M S联机技术对其化学成分进行研究,分离出249个组分,鉴定了其中的13个,主要成分有单[2-乙基己基]邻苯二甲酸、2,2′-亚甲基叔丁基对甲酚,乙基（2E）-3-[4-甲氧基苯基]-2-丙烯、7-甲基-Z-十四烯-1-醇酯。