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Antidiabetic activity of Terminalia catappa Linn fruits.

In view of alleged antidiabetic potential, effect of the petroleum ether, methanol, and aqueous extracts of Terminalia catappa Linn (combretaceae) fruit, on fasting blood sugar levels and serum biochemical analysis in alloxan-induced diabetic rats were investigated. All the three extracts of Terminalia catappa produced a significant antidiabetic activity at dose levels 1/5 of their lethal doses. Concurrent histological studies of the pancreas of these animals showed comparable regeneration by methanolic and aqueous extracts which were earlier, necrosed by alloxan.

Alloxan↗

Terminalia arjuna reverses impaired endothelial function in chronic smokers.

BACKGROUND: Smoking, largely through increased oxidative stress, causes endothelial dysfunction which is an early key event in atherosclerosis. Smoking cessation and antioxidant vitamin therapy are shown to have beneficial role by restoring altered endothelial physiology. The present study was aimed to determine whether Terminalia arjuna, an Indian medicinal plant with potent antioxidant constituents, would improve endothelial dysfunction in smokers. METHODS AND RESULTS: Eighteen healthy male smokers (age 28.16+/-9.45 years) and equal number of age-matched non-smoker controls participated in the study. The baseline brachial artery reactivity studies were performed using high frequency ultrasound according to standard protocol under identical conditions to determine endothelium-dependent, flow-mediated dilation and endothelium-independent nitroglycerine-mediated dilation. The two groups were matched regarding age, body mass index, blood pressure, serum cholesterol, mean resting vessel diameters and post-occlusion flow velocities (all p=NS). While flow-mediated dilation was significantly impaired amongst smokers compared to controls (4.71+/-2.22 v. 11.75+/-5.94%, p <0.005), the nitroglycerine-mediated dilation was similar in the two groups (20.35+/-3.89 v. 19.68+/-3.74%, p=NS). Subsequently the smokers were given Terminalia arjuna (500 mg q8h) or matching placebo randomly in a double blind cross-over design for two weeks each, followed by repetition of brachial artery reactivity studies to determine various parameters including flow-mediated dilation after each period. There was no significant difference as regards vessel diameter and flow velocities between the two therapies. However, the flow-mediated dilation showed significant improvement from baseline values after Terrminalia arjuna therapy but not with placebo (9.31+/-3.74 v. 5.17+/-2.42%, p <0.005). CONCLUSIONS: Smokers have impaired endothelium-dependent but normal endothelium-independent vasodilation as determined by brachial artery reactivity studies. Further, Terrminalia arjuna therapy for two weeks leads to significant regression of this endothelial abnormality amongst smokers.

Adolescent↗

Effect of Terminalia arjuna stem bark on antioxidant status in liver and kidney of alloxan diabetic rats.

Free radicals and associated oxidative stress induced by alloxan are implicated in eliciting pathological changes in diabetes mellitus. Terminalia arjuna bark, an indigenous plant used in ayurvedic medicine in India, primarily as a cardiotonic is also used in treating diabetes, anemia, tumors and hypertension. The present study examined the effect of ethanolic extract (250 and 500 mg/kg body weight) of Terminalia arjuna stem bark in alloxan induced diabetic rats and its lipid peroxidation, enzymatic and nonenzymatic activity was investigated in the liver and kidney tissues. The extract produced significant (P<0.05) reduction in lipid peroxidation (LPO). The effect of oral T. arjuna at the dose of 500 mg/kg body weight was more than the 250 mg/kg body weight. The extract also causes a significant (P<0.05) increase in superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase glutathione reductase and glucose-6-phosphate dehydrogenase, reduced glutathione, vitamin A, vitamin C, vitamin E, total sulfhydryl groups (TSH) and non protein sulfhydryl groups (NPSH) in liver and kidney of alloxan induced diabetic rats, which clearly shows, the antioxidant property of T. arjuna bark. The result indicates that the extract exhibit the antioxidant activity through correction of oxidative stress and validates the traditional use of this plant in diabetic animals.

Alloxan↗

Isolation and structure determination of terminalin A toxic condensed tannin from Terminalia oblongata.

Terminalia oblongata (yellow wood) is a small deciduous tree growing over an area of central Queensland that supports a large proportion of this state's cattle population. Cattle and sheep that consume yellow wood leaves are poisoned and die. Severe losses of these animals can occur, and this problem is considered the main cause of economic loss to the cattle industry in the area apart from drought. A new toxic condensed tannin, terminalin was isolated from Terminalia oblongata. Its structure was deduced following NMR, IR, UV, MS analyses and in the knowledge that these data show good correlations to those obtained from the related punicalagin molecule which is present in the plant. Terminalin has a high toxicity (20 mg/kg) to white Quackenbush male mice and produces a vascular renal necrosis with slight liver necrosis, unlike punicalagin, which produces liver lesions but not kidney lesions. Similar results were obtained with sheep. A most interesting aspect is that there are two different specific toxins in the plant.

Animals↗

Terminalia arjuna.

Terminalia arjuna is a deciduous tree found throughout India growing to a height of 60-90 feet. The thick, white-to-pinkish-gray bark has been used in India's native Ayurvedic medicine for over three centuries, primarily as a cardiac tonic. Clinical evaluation of this botanical medicine indicates it can be of benefit in the treatment of coronary artery disease, heart failure, and possibly hypercholesterolemia. It has also been found to be antibacterial and antimutagenic. Terminalia's active constituents include tannins, triterpenoid saponins (arjunic acid, arjunolic acid, arjungenin, arjunglycosides), flavonoids (arjunone, arjunolone, luteolin), gallic acid, ellagic acid, oligomeric proanthocyanidins (OPCs), phytosterols, calcium, magnesium, zinc, and copper.

Animals↗

Antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree-bark powder: a randomised placebo-controlled trial.

OBJECTIVE: To evaluate the antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree bark (a popular cardiotonic substance in Indian pharmacopoeia) and to compare it with a known antioxidant, vitamin E, we performed a randomized controlled trial. METHODS: One hundred and five successive patients with coronary heart disease (CHD) presenting to our centre were recruited and using a Latin-square design divided into 3 groups of 35 each. The groups were matched for age, lifestyle and dietary variables, clinical diagnosis and drug treatment status. None of the patients was on lipid-lowering drugs. Supplemental vitamins were stopped for one month before study began and American Heart Association Step II dietary advice was given to all. At baseline, total cholesterol, triglycerides, HDL and LDL cholesterol and lipid peroxide estimated as thiobarbituric acid reactive substances (TBARS) were determined. Group I received placebo capsules; Group II vitamin E capsules 400 units/day; and Group III received finely pulverized T. arjuna tree bark-powder (500 mg) in capsules daily. Lipids and lipid peroxide levels were determined at 30 days follow-up. RESULTS: Response rate in various groups varied from 86% to 91%. No significant changes in total, HDL, LDL cholesterol and triglycerides levels were seen in Groups I and II (paired t-test p > 0.05). In Group III there was a significant decrease in total cholesterol (-9.7 +/- 12.7%), and LDL cholesterol (-15.8 +/- 25.6%) (paired t-test p < 0.01). Lipid peroxide levels decreased significantly in both the treatment groups (p < 0.01). This decrease was more in vitamin E group (-36.4 +/- 17.7%) as compared to the T. arjuna group (-29.3 +/- 18.9%). CONCLUSIONS: Terminalia arjuna tree bark powder has significant antioxidant action that is comparable to vitamin E. In addition, it also has a significant hypocholesterolaemic effect.

Anticholesteremic Agents↗

Susceptibility of Helicobacter pylori and Candida spp. to the east African plant Terminalia spinosa.

Trees of the genus Terminalia have long been used in the traditional medicine of Kenya (East Africa). In an ethnopharmacological approach, extracts of the stem bark of Terminalia spinosa were investigated for antibacterial and antifungal activity. The extracts were active against Helicobacter pylori, with the following minimum inhibitory concentrations (MIC): MIC50 of 125 mg/l, MIC90 of 250 mg/l, and MIC-range of 62.5-500 mg/l. Yeasts of the genus Candida showed a similar susceptibility. The results indicate that the plant if a source of antimicrobial compounds with therapeutic potential.

Bacteria↗

Targeting EGFR in cancer using Terminalia arjuna: An integrated In Silico, molecular dynamics, experimental validation, and network pharmacology study.

The Epidermal Growth Factor Receptor (EGFR) plays a pivotal role in 20-60% of cancer cases, including glioblastoma, lung adenocarcinoma, and head and neck squamous cell carcinoma, as reported in The Cancer Genome Atlas (TCGA) dataset. The present study employed an integrated in silico and experimental workflow to evaluate EGFR-targeted compounds from Terminalia arjuna. Drug-likeness and ADMET screening were performed, followed by molecular docking and 1000&#x202f;ns molecular dynamics simulations. In vitro validation was conducted using cancer cell-based assays and network pharmacology to explore the molecular mechanisms associated with the identified compound. Screening shortlisted eight compounds from T. arjuna. Molecular docking identified Arjunaside C (-8.2&#x202f;kcal/mol), Arjunapthanoloside (-7.7&#x202f;kcal/mol), and Beta-sitosterol (-7.4&#x202f;kcal/mol) as potential EGFR inhibitors compared to Erlotinib (-6.6&#x202f;kcal/mol). Arjunapthanoloside formed more H-bonds and exhibited most stable interactions with EGFR. MD simulations at 1000&#x202f;ns revealed lower RMSD, RMSF, SASA, and Rg values for the Arjunapthanoloside-EGFR complex, indicating enhanced stability. Direct binding validation was limited by the unavailability of purified Arjunapthanoloside; therefore, Arjuna extract was evaluated, which demonstrated potent cytotoxicity with an IC&#x2085;&#x2080; of 9&#x202f;&#xb5;g/mL in H357 oral cancer cells. Flow cytometry confirmed apoptosis-mediated cell death by increased early- and late-apoptotic cell populations. Network pharmacology analysis further identified additional targets (MMP3, MMP7, MMP9, and HRAS) that are directly involved in various cancers. Overall, the findings provide new insights into the therapeutic potential of Arjunapthanoloside as a stable compound that interacts with EGFR from T. arjuna, highlighting its significance in EGFR-targeted anticancer research.

ErbB Receptors↗

Determination of hydrolyzable tannins in the fruit of Terminalia chebula Retz. by high-performance liquid chromatography and capillary electrophoresis.

A RP-HPLC method for determining fourteen components (gallic acid, chebulic acid, 1,6-di-O-galloyl-D-glucose, punicalagin, 3,4,6-tri-O-galloyl-D-glucose, casuarinin, chebulanin, corilagin, neochebulinic acid, terchebulin, ellagic acid, chebulagic acid, chebulinic acid, and 1,2,3,4,6-penta-O-galloyl-D-glucose) in the fruit of Terminalia chebula Retz. is described. The separation was achieved within 80 min using a binary gradient with mobile phases consisting of a pH 2.7 phosphoric acid solution and an 80% CH3CN solution. Capillary electrophoretic analyses were also attempted, and it was found that CZE (25 mM Na2B4O7, 5 mM NaH2PO4, pH 7.0) was an efficient method for the separation of gallotannins, while an MEKC method (25 mM Na2B4O7, 5 mM NaH2PO4, 20 mM SDS, pH 7.0, and 10% acetonitrile) provided a better separation for most of the tannins examined. The HPLC and CE methods developed were both successfully applied to the assay of tannins in commercial samples of Chebulae Fructus.

Calibration↗

Preparative isolation of hydrolysable tannins chebulagic acid and chebulinic acid from Terminalia chebula by high-speed counter-current chromatography.

As a chromatographic column, the high-speed counter-current chromatography system was equipped with a preparative HPLC series, enabling the successful isolation of hydrolysable tannins from the fruits of Terminalia chebula, a traditional Chinese medicine. The two-phase solvent system was composed of n-hexane-ethyl acetate-methanol-water (1:20:1:20 v/v). As a result, 33.2 mg chebulagic and 15.8 mg chebulinic acids were obtained in one step from 300 mg of crude extract. Their purities were determined by HPLC to be 95.3 and 96.1%, respectively. The chemical structures were identified by their MS and 1H NMR spectra.

Benzopyrans↗

Quantitative determination of oleane derivatives in Terminalia arjuna by high performance thin layer chromatography.

A simple, precise and rapid high performance thin layer chromatographic method has been developed for the simultaneous quantitative determination of five oleane derivatives, namely, arjunic acid, arjunolic acid, arjungenin, arjunetin and arjunglucoside I from stem bark extract of Terminalia arjuna. The isolation and separation of these compounds was carried out on 60F254 layers eluted with chloroform:methanol (90:10), and the analytes were visualised through colour development with vanillin in concentrated sulphuric acid:ethanol. Scanning and quantification of the spots at 640 nm showed good recoveries in the range 96.40-101.7%.

Calibration↗

Inhibitory effect against polymerase and ribonuclease activities of HIV-reverse transcriptase of the aqueous leaf extract of Terminalia triflora.

Dichloromethane, methanol and aqueous extracts from the leaves of Terminalia triflora were investigated for their inhibitory effect on polymerase and ribonuclease activities of HIV reverse transcriptase.The most potent activity was found in the aqueous extract, which inhibited both polymerase and ribonuclease activities of the enzyme with an IC50 of 1.6 micro g/mL and 1.8 micro g/mL respectively. The antiinfective activity of the extract was demonstrated in HLT4LacZ-IIIB cell culture with an IC50 of 1.0 micro g/mL. The extract was submitted to a purification process by extractive and chromatographic methods. The activity remained in the hydrophillic fraction. Tannins present in this active purified fraction, as determined by TLC and HPLC methods, could account for the anti HIV-RT activity found in the aqueous extract.

Anti-HIV Agents↗

Arjunetin from Terminalia arjuna as an insect feeding-deterrent and growth inhibitor.

Crude ethanolic extract of the stem bark of Terminalia arjuna (Combretaceae) and its three compounds namely arjunic acid, arjungenin and arjunetin were evaluated for antifeedant, growth inhibitory and oviposition-deterrent activities against a lepidopterous insect Spilarctia obliqua. The compound arjunetin showed highest growth inhibitory and feeding-deterrent properties with a growth inhibition (GI(50)) and feeding-inhibition (FD(50)) of 188.5 and 287.1 micro g/g diet respectively. Oviposition bioassays indicated no oviposition-deterrence in any of the compounds tested. The structure-activity relationship study indicated the importance of a glycosidation linkage in arjunetin.

Animals↗

Two ellagitannins from the leaves of Terminalia triflora with inhibitory activity on HIV-1 reverse transcriptase.

The bioassay- guided fractionation of the aqueous extract of Terminalia triflora leaves afforded punicalin and 2-O-galloylpunicalin, isolated for the first time from this species. These compounds showed inhibitory activity on HIV-1 reverse transcriptase in a dose-dependent manner. Punicalin showed an IC(50) of 0.11 microg/ml (0.14 microM) and 2-O-galloylpunicalin an IC(50) of 0.10 microg/ml (0.11 microM).

Dose-Response Relationship, Drug↗

Cytoprotective effect on oxidative stress and inhibitory effect on cellular aging of Terminalia chebula fruit.

The ethanol extract from the fruit of Terminalia chebula (Combretaceae) exhibited significant inhibitory activity on oxidative stress and the age-dependent shortening of the telomeric DNA length. In the peroxidation model using t-BuOOH, the T. chebula extract showed a notable cytoprotective effect on the HEK-N/F cells with 60.5 +/- 3.8% at a concentration of 50 microg/ml. In addition, the T. chebula extract exhibited a significant cytoprotective effect against UVB-induced oxidative damage. The life-span of the HEK-N/F cells was elongated by 40% as a result of the continuous administration of 3 microg/ml of the T. chebula extract compared to that of the control. These observations were attributed to the inhibitory effect of the T. chebula extract on the age-dependent shortening of the telomere, length as shown by the Southern blots of the terminal restriction fragments (TRFs) of DNA extracted from subculture passages.

DNA↗

Acceleration of lipid degradation by sericoside of Terminalia sericea roots in Fully differentiated 3T3-L1 cells.

Sericoside is a traditional herbal saponin from Terminalia sericea (Family Combretaceae). The influence of sericoside on lipolysis was studied in fully differentiated 3T3-L1 cells, and glycerol release into the cytosol and residual triglyceride were measured. The addition of sericoside stimulated glycerol release into the cytosol from deposited triglyceride in a dose- and time-dependent manner. These data suggested that sericoside has a strong lipolytic activity.

3T3-L1 Cells↗

Influence of Terminalia chebula on dermal wound healing in rats.

The effects of topical administration of an alcohol extract of the leaves of an evergreen plant, Terminalia chebula, on the healing of rat dermal wounds, in vivo, was assessed. T. chebula treated wounds healed much faster as indicated by improved rates of contraction and a decreased period of epithelialization. Biochemical studies revealed a significant increase in total protein, DNA and collagen contents in the granulation tissues of treated wounds. The levels of hexosamine and uronic acid in these tissues, also increased upto day 8 post-wounding. Reduced lipid peroxide levels in treated wounds, as well as ESR measurement of antioxidant activity by DPPH radical quenching, suggested that T. chebula possessed antioxidant activities. The tensile strength of tissues from extract-treated incision wounds increased by about 40%. In addition, T. chebula possessed antimicrobial activity and was active largely against Staphylococcus aureus and Klebsiella. These results strongly document the beneficial effects of T. chebula in the acceleration of the healing process.

Administration, Topical↗

Isolation of chebulic acid from Terminalia chebula Retz. and its antioxidant effect in isolated rat hepatocytes.

A hepatoprotective compound was isolated from the ethanolic extract of the fruits of Terminalia chebula Retz. by consecutive solvent partitioning, followed by silica gel and Sephadex LH-20 column chromatographies. The purified compound was identified as a mixture of chebulic acid and its minor isomer, neochebulic acid, with a ratio of 2:1 by spectroscopic analysis including 1D and 2D NMR and MS spectroscopy. To our knowledge, this is the first report on the protection of rat hepatocytes against oxidative toxicity by chebulic acid obtained from T. chebula Retz. This compound exhibited in vitro a free radical-scavenging activity and ferric-reducing antioxidant activity. Also, the specific ESR spectrum for the (*)OOH radical signals consisting of three-line ESR spectra was within the field of 0.27 mT, whereas 2.5 and 0.25 mg/ml of chebulic acid significantly reduced the signal intensity of the ESR spectra to 0.06 mT and 0.11 mT, respectively. Using isolated rat hepatocyte experiment, we demonstrated that the treatment of hepatocytes with chebulic acid significantly reduced the tert-butyl hydroperoxide (t-BHP)-induced cell cytotoxicity, intracellular reactive oxygen species level, and the ratio of GSSH, oxidized form of glutathione (GSH) to the over total GSH (GSH + GSSG) (4.42%) as compared to that with t-BHP alone (8.33%).

Animals↗