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Ethnopharmacological Relevance: Diabetic ulcers (DUs) are commonly seen in the lower limbs, especially the feet. Long-term hyperglycaemia in diabetic patients may cause peripheral microvascular damage, which affects local blood flow reconstruction when the skin is ruptured. This results in delayed or even non-healing of skin wounds. Chebulae Fructus Immaturus (CFI) is a traditional Chinese medicine. According to traditional Chinese medicine theory, CFI belongs to the lung channel and large intestine channel. Clinical data confirm a significant clinical effect of CFI in the treatment of skin diseases. CFI can be safely used to treat wounds due to its natural active ingredients., Aim of the Study: This study utilised HPLC-ESI-QTOF-MS/MS combined with network pharmacology to investigate the mechanism of Chebulae Fructus Immaturus extract (CFIE) in the treatment of DU. Moreover, the efficacy of CFIE on DU was verified in vitro and in vivo by constructing cell models and mouse models., Materials and Methods: The main ingredients of CFIE were identified by HPLC-ESI-QTOF-MS/MS. The targets of these ingredients were predicted by database analysis and intersected with the DU targets. Gene ontology (GO) was used for functional enrichment of differential genes, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for enrichment of signalling pathways related to the differential genes. The network pharmacology findings were validated in vivo and in vitro, and the affinity of key targets and active components was assessed using molecular docking., Results: Twenty-nine compounds of CFIE were identified by HPLC-ESI-QTOF-MS/MS, and their potential targets were predicted. Among these, 41 targets were associated with DU. KEGG enrichment analysis showed that the PI3K/AKT and HIF-1α signalling pathways were significantly enriched, which may be related to the promotion of wound angiogenesis. In vitro cell experiments showed that CFIE promoted the proliferation, migration and angiogenesis of HUVECs, and also affected the expression of pathway-related proteins. In vivo experiments showed that CFIE increased the expression of pathway-related proteins in wound tissue and promoted the formation of blood vessels., Conclusions: In summary, this study systematically demonstrated the possible therapeutic effects and mechanisms of CFIE on DU through network pharmacology analysis and experimental verification. The results revealed that CFIE can accelerate the angiogenesis of diabetic wounds through the PI3K/AKT and HIF-1α signalling pathways, ultimately promoting the healing of diabetic wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Occurrence of obesity and its associated metabolic disorders continues to escalate. The present study evaluates the anti-obesity effects of ethanolic fruit extract of Terminalia chebula (EETC) on high fat diet induced obese mice. The bioactive compounds present in the EETC is evaluated by Fourier-transform infrared (FT-IR), Gas chromatography-mass spectrometry (GC-MS), and Liquid chromatography-mass spectrometry (LC-MS) analysis. The effects of EETC on energy intake, glucose tolerance, and various biochemical parameters were analyzed using laboratory mice. Relative gene expression of Fatty acid synthase (FAS), Peroxisome proliferator-activated receptors α (PPARα), Carnitine palmitoyltransferase-1 (CPT-1), Tumor necrosis factor alpha (TNF-α) as well as Interleukin 6 (IL-6) were analyzed in liver and adipose tissues. The findings reveal the hypolipidemic and anti-obesity potential of EETC on high fat fed obese mice. EETC exerts its anti-obesity effects by suppressing lipogenesis through reduction in lipogenic enzyme (FAS) expression, increased fatty acid oxidation via PPARα and CPT-1 and by triggering the anti-inflammatory responses. To our knowledge, this is the first report of the effect of EETC on PPARα and CPT-1 in in vivo., (© 2021 Wiley-VCH GmbH.)

Background: After cardiovascular illness, cancer is the one of the main and second cause of death in the worldwide. Despite significant advances in this field, low survival, drug resistance, and side effects of chemotherapy remain an unsolved problem. Due to the high mortality rate among cancer patients, finding the new substance to treatment with low side effects is important. Previous studies have been informed that positive effects of herbal medicines on cancer patients, which are very efficient in the treatment of cancer., Methods: In this study, the antitumor effect of ethanolic Terminalia catappa leaf extract (TCE) on MCF-7, MDA-231, and A549 cell lines was examined. For this reason, the effects of TCE on cell migration, gene expression, and growth were investigated by scratch, test, real-time PCR (qPCR) qPCR, and MTT tests respectively., Results: As a reported by the MTT outcomes, TCE significantly decreased the viability of A549, MCF-7, and MDA-231 cells (P < 0.05).  Moreover, genes expression patterns that are related to proliferation (miR-21, miR-34a), migration (MMP-13, Vimentin), and apoptosis (Cas-3, Cas-8, Cas-9, Bcl-2, Bax) also have changed significantly after treatment with TCE. Also, in the A549 cell line, Bax (p value: 0.029), Cas-9 (p value: 0.00023), miR-34a (p value: 0.031), Bcl-2 (p value: 0.0076), MMP-13 (p value: 0.041), Cas-3 (p value: 0.00051) and in MCF-7 cell line Bax (p value: 0.0004), Cas-3 (p value: 0.0003), Cas-9(p value: 0.037), miR-34a (p value: 0.005), Bcl-2(pvalue:0.0007), mir-21(p value:0.016), MMP-13(p value: 0.011) and in MDA-231 cell line Bax(p value<0.0001), Cas-3(p value: 0.003), Cas-9(p value: 0.0004). mir-34a (p value:0.0019), Bcl-2(p value:0.0023), MMP-13(p value: 0.032) have significantly changed compare to control group., Conclusion: The outcomes of this research determined that T. Catappa might be a potential source of antitumor compounds and could be a candidate for further research., .

Ethnopharmacological Relevance: Terminalia chebula Retz. (T.chebula) is an important medicinal plant in Tibetan medicine and Ayurveda. T.chebula is known as the "King of Tibetan Medicine", due to its widespread clinical pharmacological activity such as anti-inflammatory, antioxidative, antidiabetic as well as anticancer in lots of in vivo and in vitro models. In this study, we use transgenic and/or RNAi Caenorhabditis elegans (C.elegans) model to simulation the AD pathological features induced by Aβ, to detect the effect of TWE on improving Aβ-induced toxicity and the corresponding molecular mechanism., Aim of Study: The study aimed to tested the activities and its possible mechanism of T.chebula to against Aβ 1-42 induced toxicity and Aβ 1-42 aggregation., Materials and Methods: Using transgenic C.elegans strain CL2006 and CL4176 as models respond to paralytic induced by Aβ toxicity. The transcription factors DAF-16 and SKN-1 were analyzed used a fluorescence microscope in transgenic strains (DAF-16:GFP, SKN-1:GFP). The function of DAF-16 and SKN-1 was further investigated using loss-of-function strains by feeding RNA interference (RNAi) bacteria. To evaluate the aggregation level of Aβ in the transgenic C.elegans, Thioflavin S (ThS) staining and WB visualized the levels of Aβ monomers and oligomers., Results: TWE treatment can significantly improve the paralysis of transgenic C.elegans caused by Aβ aggregation (up to 14%). The Aβ aggregates in transgenic C.elegans are significantly inhibited under TWE exposure (up to 70%). TWE increases the nuclear localization of the key transcription factor DAF-16 and HSF-1, which in turn leads to the expression of downstream Hsp-16.2 protein and exerts its inhibitory effect on Aβ aggregation. Meanwhile, paralysis improved has not observed in SKN-1 mutation and/or RNAi C.elegans., Conclusion: Our results indicate that TWE can protect C.elegans against the Aβ 1-42 -induced toxicity, inhibition Aβ 1-42 aggregation and delaying Aβ-induced paralysis. The neuroprotective effect of TWE involves the activation of DAF-16/HSF-1/Hsp-16.2 pathway., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Objective: Rheumatoid Arthritis (RA) is an autoimmune disease characterized by failure of spontaneous resolution of inflammation with lifetime perseverance, becoming principal cause of inactivity. Many conventional therapies are in use but the side effects associated with them are equally problematic. Therefore, an urge to explore advanced therapeutic approaches with least adverse events has seeded the idea of discovering newer herbal drugs and their respective constituents in management of RA. The current research explores anti-arthritic activity of Terminalia catappa fruits hydroalcoholic extract in CFA induced Wistar rats., Methods: The fruits were obtained, washed, dried and processed to obtain hydroalcoholic powdered extract which was dissolved in water and given orally to the rats. Wistar rats of either sex were used in the study. The animals were injected with 0.1 ml of complete freund's adjuvant (CFA) in footpad of left hind paw. The treatment was initiated from day 0 by oral dosing of Terminalia catappa fruit extract in doses of 40 mg/kg and 80 mg/kg followed by CFA administration to day 21 and behavioral, hematological parameters besides histopathological screening were assessed simultaneously., Results: The arthritic symptoms were observed to gradually decrease in treatment groups when compared against disease control groups. The parameters like body weight and pain latency were increased whereas paw volume and arthritic score were found to significantly decrease in treatment groups as compared to disease control group. The hematological parameters were also modified and were studied in treatment groups. The histopathological estimation depicted extent of damage in joint tissue of diseased rat comparable to normal, standard and combination therapy group., Conclusion: The fruits possess anti-arthritic properties and significantly reduced paw volume, arthritic score and increased pain threshold and body weight gain besides theory hematological effects like increase in Hb and RBC and decrease in WBC, platelets and ESR levels simultaneously. The histopathological estimation confirmed decreased deterioration of joint tissue in treatment groups as compared to disease control group hence proving to be an emerging therapeutic option in management of RA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective and Background: Diabetic retinopathy is amongst the most common microvascular complications associated with diabetes. Controlling blood glucose level alone cannot manage diabetes associated complications. Thus, mechanisms that additionally prevent diabetes associated complications are the need of the hour, driving the researchers towards herbal therapies. Terminalia catappa is renowned for its anti-inflammatory, antioxidant, anti-hyperglycemic and anti-angiogenic activity. The current study explores the effect of Terminalia catappa fruit extract on streptozotocin-induced diabetic retinopathy in rats., Methods: Streptozotocin-induced chronic diabetic rat model was utilized in the study. The hydroalcoholic fruit extract of T. catappa in 20mg/kg, 30mg/kg and 40mg/kg dose and standard anti-diabetic drug, glibenclamide (10mg/kg) was given orally. Retinopathy was evaluated by monitoring lenticular, fundus images and measuring arteriole and venule tortuosity index. Oxidative, angiogenic and inflammatory biomarkers were assessed at the 12th week in the retinal homogenate. Histopathological changes in the retina were also examined. Data was analyzed using one-way Repeated Measure ANOVA followed by the Mann-Whitney test., Results: The hydro-alcoholic fruit extract of T. catappa significantly decreased blood glucose (p<0.001) in a dose-dependent manner in diabetic rats. Cataract lens was observed in all experimental groups and became clear (grade 0) with 40mg/kg and with 40mg/kg along with glibenclamide at the eighth and sixth week, respectively. The hydro-alcoholic fruit extract in all three doses significantly reduced (p<0.01) arteriole and venule tortuosity in diabetic rats. T. catappa in all three doses in diabetic rats showed a modulatory effect in oxidative, angiogenic and inflammatory biomarkers., Conclusion: T. catappa reverses diabetes-induced retinopathy by anti-hyperglycemic, anti-oxidant, anti-angiogenic and anti-inflammatory actions, and thus has a potential to be used in diabetes-induced retinopathy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Terminalia chebula (TC) is a deciduous tree of which extracts have demonstrated efficacy for treatment of photodamage, skin aging, and wound healing. However, molecular and cellular mechanisms underlying these benefits remain unclear., Objective: To profile dermal expression responses to a standardized tannin-enriched TC fruit extract (Synastol ® TC)., Materials and Methods: Microarrays were used to evaluate gene expression in three-dimensional reconstituted human skin cultures., Results: Genome-wide expression responses to TC were the opposite to those observed in cells exposed to oxidative stress, solar-simulated UV radiation, and wounding, with increased expression of genes associated with water homeostasis, skin barrier establishment, blood vessel development, and circadian rhythms. TC also increased expression of extracellular matrix components, such as collagens (COL1A1, COL1A2) and proteoglycans (PRELP, OGN), and in separate assays, we showed that TC inhibits MMP enzymes (MMP-1, MMP-2, MMP-3, MMP-9, MMP-12) and microbial activity (S. aureus, P. acnes). Unexpectedly, mRNA and protein levels of late keratinocyte (KC) differentiation markers (FLG, LOR) were increased by TC, and expression responses in skin cultures broadly resembled those that occur with KC differentiation. Consistent with these results, TC increased expression of transcription factors regulating KC differentiation (FOS, GHRL3, PPARG) and we noted enrichment of AP-1 binding sites in regions upstream of TC-increased genes., Conclusion: These results demonstrate that functionally important TC extract responses occur in the epidermis and are therefore not restricted to the dermal layer. Our findings thus suggest mechanisms by which TC may strengthen full-thickness skin architecture for treatment of skin aging and/or chronic wounds.

Background: Hyperuricemia is an independent risk factor in chronic kidney disease (CKD). Allopurinol and febuxostat are prescription medicines used to treat hyperuricemia but suffer side-effects. Earlier clinical study has shown that an aqueous extract of Terminalia bellerica (TBE), significantly reduced uric acid levels with no serious adverse effects in hyperuricemic subjects. The objective of this study is to determine the efficacy and tolerability of TB in reducing uric acid and creatinine levels in CKD subjects., Methods: 59-subjects were randomized to three groups-40 mg-once-daily febuxostat, 500 mg-twice-daily and 1000 mg-twice-daily of TBE. Serum uric acid, creatinine levels and estimated-glometular-filtration-rate were measured at baseline, 4, 8, 12, 16, 20, 24-weeks. Biomarkers of oxidative-stress, endothelial function, systemic inflammation, and platelet-aggregation were evaluated at baseline, 4, 8, 12, 24-weeks. Adverse drug reactions were recorded. Statistical analysis evaluated using GraphPadPrism4., Results: 55-subjects completed 24-week study. Starting at 4-weeks, all treatment groups showed a significant decrease in serum uric acid levels from baseline (p ≤ 0.0001). At 24-weeks, febuxostat, T.bellerica 500 mg-twice-daily, and T.bellerica 1000 mg-twice-daily doses decreased mean-percentage serum uric acid by 63.70 ± 4.62, 19.84 ± 6.43 and 33.88% ± 4.95% respectively (p ≤ 0.0001). Significant decrease in serum creatinine with all the groups starting at 16-weeks was seen (p ≤ 0.005-p ≤ 0.0001). At 24-weeks, the mean-percentage change in creatinine levels was 23.71 ± 12.50, 11.70 ± 9.0, and 24.42 ± 8.14, respectively with febuxostat, T.bellerica 500 mg-twice-daily and T.bellerica 1000 mg-twice-daily. Statistically significant (p ≤ 0.05) increase in estimated glomerular filtration rate-(eGFR) was seen at 20 (p ≤ 0.05) and 24-weeks (p ≤ 0.01) for both febuxostat vs T.bellerica 500 mg-twice-daily and T.bellerica 1000 mg-twice-daily vs T.bellerica 500 mg-twice-daily. There was no statistically significant difference between febuxostat and T.bellerica 1000 mg-twice-daily, with an increase of eGFR of 41.38 and 40.39 ml/min/1.73m 2 respectively, with the inference that T.bellerica at 1000 mg-twice-daily dose is as good as febuxostat 40 mg-once-daily. Positive improvements were made by all the groups in endothelial function and the related biomarkers and high-sensitivity C-reactive protein. None of the products showed effect on platelet aggregation., Conclusion: In this 24-week study Febuxostat 40 mg, T. bellerica 500 mg-twice-daily and 1000 mg-twice-daily, significantly decreased the serum uric acid and creatinine levels, increased eGFR in CKD subjects. T. bellerica 500 mg-twice-daily and 1000 mg-twice-daily were one-third and more than half as effective at 24-weeks, respectively. T. bellerica extract may be considered a natural alternative for reducing serum uric acid levels., Trial Registration: This study was registered with the Clinical Trials Registry - India (CTRI) with the registration number: CTRI/2019/11/022093 [Registered on: 21/11/2019] Trial Registered Retrospectively.

Arjunic acid (AA) is one of the major active component of Terminalia arjuna known for its health benefits. In the present study, we evaluated cardioprotective potential of Terminalia arjuna extract (TAE) and AA against cobalt chloride (CoCl 2 )-induced hypoxia damage and apoptosis in rat cardiomyocytes. TAE (50 μg/ml) and AA (8 μg/ml) significantly (p < 0.001) protected H9c2 cells as evidenced by cell viability assays against CoCl 2 (1.2 mM)-induced cytotoxicity. TAE and AA pretreatments protected the cells from oxidative damage by decreasing the generation of free radicals (ROS, hydroperoxide, and nitrite levels). TAE and AA pretreatments retained mitochondrial membrane potential by alleviating the rate of lipid peroxidation induced by CoCl 2 treatment. TAE and AA pretreatments elevated antioxidant status including phase II antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and total glutathione levels against CoCl 2 -induced oxidative stress. Further immunoblotting studies confirmed anti-apoptotic effects of TAE and AA by alleviating the phosphorylation of JNK and c-jun and also by regulating protein expression levels of Bcl2, Bax, caspase 3, heat shock protein-70, and inducible nitric oxide synthase. Overall, our results suggest that both the extract and the active component exhibit antioxidant and anti-apoptotic defense against CoCl 2 -induced hypoxic injury.

Ethnopharmacological Relevance: Folk knowledge transmitted between generations allows traditional populations to maintain the use of medicinal plants for the treatment of several diseases. In this context, the species Terminalia fagifolia Mart., native to Brazil, is used for the treatment of chronic and infectious diseases. Plants rich in secondary metabolites, such as this species and their derivatives, may represent therapeutic alternatives for the treatment of diseases that reduce the quality of life of people., Aim of the Study: The aim of this study was to evaluate the antifungal and anti-inflammatory potential of aqueous fraction from ethanolic extract of T. fagifolia, with in silico study of the major compound of the fraction., Material and Methods: The phytochemical study of the aqueous fraction was performed by HPLC, LC/MS and NMR. The antifungal activity was evaluated against yeasts, by determination of the minimum inhibitory concentration and minimum fungicidal concentration. The effect on Candida albicans was analyzed by AFM. The antibiofilm potential against biofilms of C. albicans was also tested. The anti-inflammatory potential of the aqueous fraction was evaluated in vivo by the carrageenan-induced paw edema and peritonitis. A microglial model of LPS-induced neuroinflammation was also studied. Further insights on the activation mechanism were studied using quantum chemistry computer simulations. Toxicity was evaluated in the Galleria mellonella and human erythrocytes models., Results: Eschweilenol C was identified as the major constituent of the aqueous fraction of the ethanolic extract of T. fagifolia. The aqueous fraction was active against all Candida strains used (sensitive and resistant to Fluconazole) with MICs ranging from 1000 to 0.4 μg/mL. By AFM it was possible to observe morphological alterations in treated Candida cells. The fraction significantly (p < 0.05) inhibited paw edema and decreased levels of malondialdehyde induced by carrageenan. In a microglial cell model, aqueous fraction demonstrated the ability to inhibit NF-κB after induction with lipopolysaccharide. The theoretical studies showed structural similarity between eschweilenol C and indomethacin and an excellent antioxidant potential. The aqueous fraction did not present toxicity in the studied models., Conclusion: The results indicate that the aqueous fraction of T. fagifolia has potential for biomedical applications with low toxicity. This finding can be attributed to the predominance of eschweilenol C in the aqueous fraction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: The present study was conducted to compare the efficacy of all Punica granatum, Terminalia chebula , and Vitis vinifera on salivary Streptococcus mutans levels in children and also to evaluate their substantivity at an interval of 15 days that is at day 1, days 16, and 31., Materials and Methods: This study was designed for a randomized clinical double-blinded study where 80 children of 8-15 years of age were living in a residential premise. Subjects were randomly divided into 4 groups of 20 each to whom mouthrinses were given. The criteria for assessing the efficacy was done by collecting the saliva sample for pH, buffering capacity, plaque index, and Streptococcus mutans microbiologic assay. These values were assessed at the baseline, days 16, and 31. Children were asked to discontinue mouthrinse from days 16 to 31. The supervisor was trained to administer the mouthrinses properly., Results: The data were coded and analysis was done using the SPSS version 20. The level of significance was set at p < 0.05. The pH and buffering capacity showed that values were almost the same among all four groups at various time intervals which showed statistically nonsignificant results. Punica granatum showed a maximum reduction in S. mutans count followed by T. chebula and V. vinifera , although they were statistically nonsignificant. The Vitis vinifera group had successfully reduced more plaque score at day 16 (0.04) followed by T. chebula (0.09) and P. granatum (0.12)., Conclusion: This in vivo study implied that V. vinifera had shown the lowest plaque reduction owing to its antioxidant and phytochemical properties. And P. granatum showed the maximum substantivity., Clinical Significance: Mouthrinses helped in reducing plaque deposition, caries activity, and helped in oral hygiene maintenance. Hereby, we can conclude that nutraceutical mouthrinses are safe in children and produced superior results than the chemical mouthrinses.

Ethnopharmacological Relevance: Terminalia arjuna Roxb. (Combretaceae) is traditionally used in Ayurveda medicine and holds ethnomedicinal importance for treatment of gastrointestinal disorders. In view of its anti-inflammatory, antidiarrheal and antioxidant potential, it could be beneficial for the treatment of inflammatory bowel disease (IBD), which is associated with interaction between genetic, environmental factors and intestinal microbiome leading to dysregulated immune responses. This study evaluates the effect of hydroalcoholic extract of Terminalia arjuna bark (TAHA) in trinitrobenzenesulfonic acid (TNBS) model of rat colitis which resembles human IBD., Materials and Methods: TAHA (500, 250, 125 mg/kg) was administered orally for 28 days in TNBS induced rats. Response to treatment was assessed by comparing observations in diseased and treated groups using disease activity index (DAI); macroscopic/histological damage; determining oxidative stress indicators: myeloperoxidase, malondialdehyde, nitric oxide, catalase, superoxide dismutase, and reduced glutathione; gene expression of pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α and chemokine: MCP-1. Furthermore, the role of TAHA in altering the gut microbiota profile in rat feces and plasma zinc was also studied., Results: TAHA treatment in colitic rats directed decreased DAI scores, macroscopic and histologic damage. It also reduced myeloperoxidase, malondialdehyde and nitric oxide level. Whereas, prevented depletion of plasma catalase, superoxide dismutase and glutathione level. In addition, TAHA treatment down-regulated the gene expression of pro-inflammatory mediators and displayed altered beneficial effect on fecal microbiota. Furthermore, enhanced plasma zinc level supported the beneficial effect of TAHA in colitic rats. The dose of TAHA that produced most significant beneficial effect was 500 mg/kg., Conclusion: TAHA administration relieved the disease activity in TNBS induced colitis by reducing expression of pro-inflammatory cytokines and chemokine, decreasing oxidative stress, and improving plasma zinc level and structure of gut microbiota., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To establish a method to analyze the commonalities and characteristics of the aqueous extracts from three Uighur medicines., Methods: In this study, a combination method of three-stage infrared spectroscopy and ultra-performance liquid chromatography-time of flight-mass spectra (UPLC-TOF-MS) method was used to analyze the commonalities and characteristics of the aqueous extracts from Hezi (Fructus Chebulae), Maohezi (Terminalia Belliricae Fructus) and Xiqingguo (Chebulae Fructus Immaturus)., Results: In Fourier transform-infrared spectroscopy spectra, all three samples showed the characteristic absorption peaks of tannins similarly. According to UPLC-TOF-MS data analysis, the difference of the position and intensity of the peaks at 1713- 1707 cm－1 in the three samples were related to the difference in the relative content of tannin and pentacyclic triterpenoids. In second derivative infrared spectroscopy spectra, further analysis of the differences in the infrared spectra of the three samples was performed by increasing the apparent resolution. In combination with UPLC-TOF-MS data, some features infrared absorption peaks were assigned. The absorption peaks at 1032-1030 cm－1 assigned to the stretching vibration of C-O-C (ether bond) groups of tannins; 1164-1163, 1063-1062, 1009- 1005, 904 cm－1 attributed to the stretching vibration of C-O (ether bond) and C-O-C groups of glycosidic compounds. 1385-1383 cm－1 attributed to the bending vibration of C-H (alkyl hydrogen) of methoxyl group of pentacyclic triterpenoids. Peak 835 cm－1 was assigned to the characteristic absorption peak of bending vibration of = C-H groups of pentacyclic triterpenoids. The two dimensional correlation infrared spectroscopy could further quickly distinguish three samples through the dynamic structural information of their chemical components and discrepancy of auto-peaks and cross- peaks intuitively in the range of 1720-419 cm－1., Conclusion: By comparing the intensity of the infrared characteristic absorption peaks, the main chemical components were assigned, which significantly enriched and perfected the data analysis of the infrared spectra of three Uighur Medicines. It provided a rationale for the identification of medicinal materials with complex and similar chemical components using the three-stage infrared spectroscopy and UPLC-TOF-MS.

Ethnopharmacological Relevance: Terminalia argentea Mart. (Combretaceae), known mainly as "capitão", is a native tree, not endemic, that occurs in the Amazon, Caatinga, Cerrado and Atlantic Forest in Brazil. Leaf infusion is popularly mentioned by riverine communities that inhabit the microregion of Northern Araguaia (Mato Grosso, Brazil) for the treatment of gastric ulcer, bronchitis and haemorrhage. Considering the wide medicinal use, lack of studies that evaluate the safety of use and the scarcity of phytochemical studies of T. argentea leaves, this work was carried out with the objective of evaluating the toxicity of the hydroethanolic extract of the leaves of T. argentea Mart. (HETa) in experimental models in vivo and in vitro, as well as to advance the phytochemical analysis of HETa., Materials and Methods: HETa was prepared by macerating the leaf powder in hydroethanolic solution. Phytochemical characterisation was carried out by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and mass spectrometry through direct flow infusion coupled with electrospray ionization and ion-trap analyzer (DFI-ESI-IT-MS analyses) The contents of phenols, flavonoids and phytosterols were analysed by colorimetric methods. Cytotoxicity was assessed by the Alamar blue assay on Chinese hamster ovary epithelial cells (CHO-K1) and human gastric adenocarcinoma cells (AGS). In vitro genotoxicity of HETa (10, 30 or 100 μg/mL) was assessed by micronucleus (MN) and comet tests using CHO-K1 cells. The acute toxicity assessment was performed by oral administration of HETa in single dose Swiss mice (males and females) up to 2000 mg/kg and sub-chronic toxicity by daily oral administration of HETa (50, 200 and 800 mg/kg) in Wistar rats for 30 days. The parameters related to the clinical and toxicological observations were determined every 6 days and at the end of the treatment the blood was collected for biochemical and haematological analysis, and some organs were removed for macroscopic and histopathological analysis., Results: Preliminary phytochemistry and TLC analysis of HETa revealed the presence of phenolic compounds (18.8%), flavonoids (10.8%), saponins, tannins and phytosterols (19%). The HPLC data revealed the presence of gallic acid, rutin, ellagic acid, catechin, quercetin and kaempferol. In the analysis by DFI-ESI-IT-MS, the presence of gallic acid, rutin, ellagic acid and quercetin was confirmed and identified caffeic acid, quinic acid, galloylmucic acid, quercetin xyloside, quercetin rhamnoside, quercetin glucoside, caffeoyl ellagic acid, quercetin galloyl xyloside, terminalin, quercetin galloyl glucose, corilagin, quercetin digalloyl xyloside, quercetin digalloyl glucoside, punicalin and punicalagin. HETa showed no cytotoxic effect on CHO-K1 and AGS cells. In the MN assay, HETa increased the number of MNs and nuclear buds (NBUDs) in binucleate cells at the three concentrations tested and the nucleoplasmic bridges (NPBs) number at 30 μg/mL. In the comet test, HETa (10 and 100 μg/mL) alone showed a genotoxic effect on CHO-K1 cells. In pre-treatment, HETa at all concentrations tested prevented DNA damage induced by H 2 O 2 . In co-treatment with H 2 O 2 , HETa showed genotoxic effects at the three concentrations, and post-treatment DNA damage in exposed CHO-K1 cells to H 2 O 2 was repaired in 22.5% with 10 μg/mL HETa. In the acute toxicity test, the HETa did not cause death in the mice, being verified only by piloerection and reversible in 2 h in males and in 4 days in females. No macroscopic changes were observed in the analysed organs. In the sub-chronic toxicity test, the HETa did not cause death in the rats after 30 days and the few changes were: absolute (10 3 /mm 3 ) and relative (%) values of basophils increased by 477.8% and 423% (p < 0.001), respectively, with 50 mg/kg; reduction in feed intake (23.6%, p < 0.01) only on day 18; total cholesterol concentration (13.1%, p < 0.05) and relative heart weight (13.2% %, p < 0.05) at a dose of 800 mg/kg. These effects were not dose-dependent nor followed by clinical signs and symptoms of intoxication, nor of macroscopic and histopathological changes in the organs of animals treated with HETa., Conclusions: The results demonstrated that HETa had no cytotoxic in vitro effects for CHO-K1 and AGS cells. In in vitro genotoxicity assays, the HETa induced different responses, according to concentration and experimental condition. In the MN test the HETa presented genotoxic potential by increasing the number of MNs, NBUDs and NPBs. In the comet assay, HETa was genotoxic by itself and in the co-treatment protocol with H 2 O 2 . In pre-treatment or post-treatment protocols with H 2 O 2 , HETa presented an antigenotoxic effect by preventing or repairing, respectively, the genotoxicity induced by H 2 O 2 . In the in vivo models, HETa was shown to be relatively safe after acute administration in mice [no-observed-adverse effect level (NOAEL) of 2000 mg/kg] and sub-chronic in rats (NOAEL of 800 mg/kg), confirming the riverine information that it is non-toxic in the dosage used. Phytochemical analysis of HETa revealed the presence of phenolic compounds, flavonoids, saponins, tannins and phytosterols. Among the flavonoids and tannins, we highlight gallic acid, rutin, ellagic acid, quercetin, caffeic acid, quinic acid, corilagin, punicalin and punicalagin. Thus, it can be stated that HETa has a good safety margin for therapeutic use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Terminalia laxiflora Engl. & Diels, (Sudanese Arabic name: Darout الدروت) and Terminalia brownii Fresen (Sudanese Arabic name: Alshaf ألشاف) (Combretaceae) are used in Sudanese traditional folk medicine and in other African countries for treatment of infectious diseases, TB and its symptoms, such as cough, bronchitis and chest pain., Aim of Study: Because of the frequent use of T. laxiflora and T. brownii in African traditional medicine and due to the absence of studies regarding their antimycobacterial potential there was a need to screen extracts of T. laxiflora and T. brownii for their growth inhibitory potential and to study the chemical composition and compounds in growth inhibitory extracts., Materials and Methods: The plant species were collected in Sudan (Blue Nile Forest, Ed Damazin Forestry areas) and selected according to their uses in traditional medicine for the treatment of bacterial infections, including TB. Eighty extracts and fractions of the stem bark, stem wood, roots, leaves and fruits of T. laxiflora and T. brownii and nine pure compounds present in the active extracts were screened against Mycobacterium smegmatis ATCC 14468 using agar diffusion and microplate dilution methods. Inhibition zones and MIC values were estimated and compared to rifampicin. HPLC-UV/DAD, GC/MS and UHPLC/Q-TOF MS were employed to identify the compounds in the growth inhibitory extracts., Results: The roots of T. laxiflora and T. brownii gave the best antimycobacterial effects (IZ 22-27 mm) against Mycobacterium smegmatis. The lowest MIC of 625 µg/ml was observed for an acetone extract of the root of T. laxiflora followed by methanol and ethyl acetate extracts, both giving MIC values of 1250 µg/ml. Sephadex LH-20 column chromatography purification of T. brownii roots resulted in low MIC values of 62.5 µg/ml and 125 µg/ml for acetone and ethanol fractions, respectively, compared to 5000 µg/ml for the crude methanol extract. Methyl (S)-flavogallonate is suggested to be the main active compound in the Sephadex LH- 20 acetone fraction, while ellagic acid xyloside and methyl ellagic acid xyloside are suggested to give good antimycobacterial activity in the Sephadex LH-20 ethanol fraction. RP-18 TLC purifications of an ethyl acetate extract of T. laxiflora roots resulted in the enrichment of punicalagin in one of the fractions (Fr5). This fraction gave a five times smaller MIC (500 µg/ml) than the crude ethyl acetate extract (2500 µg/ml) and this improved activity is suggested to be mostly due to punicalagin. 1,18-octadec-9-ene-dioate, stigmast-4-en-3-one, 5α-stigmastan-3,6-dione, triacontanol, sitostenone and β-sitosterol were found in antimycobacterial hexane extracts of the stem bark of both studied species. Of these compounds, 1,18-octadec-9-ene-dioate, stigmast-4-en-3-one, 5α-stigmastan-3,6-dione, triacontanol, sitostenone have not been previously identified in T. brownii and T. laxiflora. Moreover, both plant species contained friedelin, betulinic acid, β-amyrine and two unknown oleanane-type triterpenoids. Of the listed compounds, friedelin, triacontanol and sitostenone gave a MIC of 250 µg/ml against M. smegmatis, whereas stigmasterol and β-sitosterol gave MIC values of 500 µg/ml., Conclusions: Our results show that T. laxiflora and T. brownii contain antimycobacterial compounds of diverse polarities and support the traditional uses of various parts of T. laxiflora and T.brownii as decoctions for treatment of tuberculosis. Further investigations are warranted to explore additional (new) antimycobacterial compounds in the active extracts of T. laxiflora and T. brownii., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: This article investigates the anxiolytic activity of Terminalia chebula tannin-rich extract against picrotoxin (PTX; GABA antagonist)-induced anxiety in mice model., Methods: Anxiolytic activity was studied by elevated plus maze (EPM), open field test (OFT), light/dark box test (LDT) and Vogel's conflict test (VCT). Electroencephalogram (EEG) was performed to know the changes in brain activity instigated by GABA antagonist. 5-hydroxytryptamine (5-HT), dopamine and norepinephrine levels in brain tissues were estimated by HPLC. The mRNA (CREB, BDNF, GABA, and 5-HT 1A ) and protein expression (CREB, p-CREB, BDNF, ERK ½, p-ERK ½, GABA A Rα1, 5-HT 1A and GAPDH) levels in brain tissue were determined by RT-PCR and Western blot analysis, respectively., Key Findings: Terminalia chebula tannin-rich extract (TCHE) supplementation increased locomotion in mice towards open arm (EPM), time spent in illuminated area (LDT), rearing frequency (OFT) and number of shocks (VCT) compared to PTX (P < 0.05). Furthermore, TCHE down-regulated serum cortisol levels and showed increased levels of 5-HT, DA and NE. Gene expressions such as BDNF, CREB, GABA A and 5-HT 1A were up-regulated by TCHE treatment compared to PTX., Conclusions: Terminalia chebula tannin-rich extract showed significant anxiolytic activity against picrotoxin and could be used as natural therapy in neurodegenerative disorders., (© 2018 Royal Pharmaceutical Society.)

Context: Chatuphalatika (CTPT), is a Thai herbal formulation mixture of Phyllanthus emblica Linn. (Euphorbiaceae), Terminalia belerica Linn. (Combretaceae), T. chebula and the fruit of T. arjuna (Roxb.) Wight & Arn. CTPT is considered to exert anti-inflammatory and antihyperuricemic effects, but there have been no reports to demonstrate these pharmacological effects in a quantitative manner., Objectives: To investigate the antioxidative, anti-inflammatory and antihyperuricemic effects of CTPT., Materials and Methods: Antioxidant activities of CTPT extracts were measured in vitro by DPPH, ABTS and FRAP assays, and anti-inflammatory effect by measuring inflammatory mediator production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages. The mechanism of the hypouricemic effect was investigated using oxonate-induced hyperuricemic ddY mice treated with oral administrations of CTPT at 250, 500 and 1000 mg/kg., Results: Antioxidant activities of CTPT measured by ABTS and FRAP assays were 1.35 g TEAC/g extract and 10.3 mmol/100 g extract, respectively. IC 50 for the inhibition of DPPH radical was 13.8 µg/mL. CTPT (10 µg/mL) significantly downregulated the mRNA expression of TNF-α and iNOS in RAW 264.7 cells. Lineweaver-Burk analysis of the enzyme kinetics showed that CTPT inhibited xanthine oxidase (XOD) activity in a noncompetitive manner with the K i of 576.9 µg/mL. Oral administration of CTPT (1000 mg/kg) significantly suppressed uric acid production by inhibiting hepatic XOD activity, and decreased plasma uric acid levels in hyperuricemic mice by approximately 40% (p < 0.05)., Conclusions: This study demonstrated for the first time the antioxidative, anti-inflammatory and antihyperuricemic effects of CTPT in vivo and in vitro, suggesting a possibility of using CTPT for the treatment of hyperuricemia in gout.

Excessive oxidative stress plays a critical role in the progression of various diseases. Recently, we showed that Terminalia bellirica (Gaertn.) Roxb. extract (TBE) inhibits inflammatory response and reactive oxygen species (ROS) production in THP-1 macrophages. However, molecular mechanisms underlying anti-inflammatory and antioxidant activities of TBE and its major polyphenolic compounds gallic acid (GA) and ellagic acid (EA) remain unclear. We found that TBE and GA attenuated LPS-induced inflammatory mediator expression, ROS production, and activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF- κ B) in RAW 264 macrophages. Furthermore, TBE and GA increased antioxidant enzyme expression along with upstream mediators nuclear factor erythroid-2-related factor 2 (Nrf2), Akt, and AMP-activated protein kinase (AMPK). Importantly, knockdown of Nrf2 by siRNA and specific inhibition of Akt and AMPK significantly reduced antioxidant enzyme expression induced by TBE and GA. Finally, in vivo effects on histopathology and gene expression were assessed in tissues collected after intraperitoneal injection of LPS with or without TBE treatment. TBE enhanced antioxidant enzyme expression and improved acute kidney injury in LPS-shock model mice. In conclusion, TBE and GA exert protective effects against inflammation and oxidative stress by suppressing MAPK/NF- κ B pathway and by activating Akt/AMPK/Nrf2 pathway. These results suggest that TBE and GA might be effective for the treatment of inflammation-related diseases.

Background: Dental caries is a multifactorial disease in which microorganisms play an important role. Recently, herbs have been tried as mouthrinses to combat the side effects of chemical mouthrinses. The anticaries efficacy of Sodium fluoride, Tulsi leaf, and Black myrobalans fruit extracts on Streptococcus mutans (S. mutans) have been reported in the literature, but no comparative study has been done yet., Aim: This study aims to observe the change in the pH of saliva and to assess the efficacy of the herbal rinses-Tulsi and Black myrobalans on S. mutans count while comparing it with Sodium fluoride mouthrinse., Methods: Herbal ethanolic extracts of Tulsi (4%) and Black myrobalans (2.5%) were prepared as mouthrinses and compared with sodium fluoride mouthrinse (0.05%). Sixty high caries risk patients were selected and allocated randomly into three groups [n = 20], categorized as Group A-Sodium fluoride mouthrinse, Group B-Tulsi mouthrinse, and Group C-Black myrobalans mouthrinse. They were instructed to rinse their mouth with their assigned mouthrinses for 7 days. Salivary samples were collected and sent to the laboratory at baseline, 1 h postrinsing and after 7 th day of rinsing for determining the salivary pH and S. mutans count. The increase in pH and reduction of S. mutans were determined. The values obtained were tabulated and statistically analyzed., Results: There was a significant increase in the salivary pH and reduction in S. mutans count after rinsing in all the three groups. Increase in salivary pH was more in the Sodium fluoride mouthrinse when compared to the experimental herbal groups (Group B and Group C). While S. mutans counts reduced more with Tulsi mouthrinse at 1 h postrinsing and after the 7 th day of rinsing more reduction was seen in Black myrobalans mouthrinse group., Conclusion: The results of the study suggest that herbal mouthrinses could be tried as an adjunctive anticaries agent against dental caries causing microorganisms., Competing Interests: None

Objective: The aim of the present study was to evaluate anti-inflammatory activity of methanolic extract of Terminalia coriacea., Materials and Methods: A methanolic extract of T. coriacea leaves was studied in albino Wistar rats with carrageenan-induced paw edema, an acute model, and cotton pellet-induced granuloma, a chronic model, at 3 oral test doses (125, 250, and 500 mg/kg). Aspirin 100 mg/kg was used as a positive control. Paw volume and wet and dry weights of cotton pellets were determined. The data were analyzed by one-way ANOVA followed by Dunnett's multiple comparison test., Results: The test extract at doses of 125 and 250 mg/kg decreased paw volume and wet and dry weights of cotton pellets. The highest test dose (500 mg/kg) displayed a response comparable to that of the standard drug (p < 0.01) on paw volume. The extract produced similar (p < 0.05) decrease in wet weight of the cotton pellet at 125 and 250 mg/kg, whereas the effect of 500 mg/kg of the extract was comparable to that of aspirin 100 mg/kg (p < 0.01). The extract of T. coriacea at 500 mg/kg induced the most significant (p < 0.01) effect on wet weight of granulomatous tissue., Conclusion: The methanolic extract of T. coriacea leaves successfully decreased paw edema as well as dry and wet weights of granulomatous tissue in both acute and chronic inflammatory models thus confirming the anti- edematogenic, antitransudative, and antiproliferative properties of T. coriacea., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: The aqueous extract of Terminalia arjuna (TA) bark (TA AqE ) has been shown to have a direct inotropic effect on ventricular myocytes. Active constituents of TA AqE contain various flavonoids and proanthocyanidins, some of which are known to have antioxidant activities. Whether TA AqE affords a cardioprotective action against oxidative stress (OS) remains unclear., Purpose: Increased OS is one of the major mechanisms underlying cardiotoxicity induced by doxorubicin (DOX), a commonly-used anticancer agent. The aim of the present study was to investigate potential cardioprotective effect of TA AqE against DOX-induced OS and cardiac dysfunction., Methods: OS and cytotoxicity were induced by 1 µM DOX for 24 h in H9c2 cells, a cardiac tissue-derived cell line, and left ventricular (LV) dysfunction was induced by intrapleural injection of DOX (accumulative 20 mg/kg body weight) to mice. Cellular oxidative levels and morphology were assessed using microscopy and oxidative-sensitive fluorescent dyes with and without co-treatment with TA AqE . LV function was monitored weekly with echocardiography., Results: TA AqE reduced OS and preserved mitochondria and cell growth of H9c2 cells against DOX treatment. TA AqE (in drinking water) attenuated the decreased LV function and altered myocardial structure caused by DOX treatment., Conclusion: TA AqE exerts a protective action against cardiotoxicity caused by DOX in part via suppression of OS. Thus, TA AqE is a promising cardiotonic in adjuvant cancer chemotherapy., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Context: Terminalia chebula Retz (Combretaceae) and Musa balbisiana Colla (Musaceae) have a traditional reputation as a male contraceptive., Objective: To determine the hypo-testicular activity of aqueous extracts of Terminalia chebula (fruit) and Musa balbisiana (seed) separately, and in composite manner at the ratio of 1:1 named as 'Contracept-TM' compared to cyproterone acetate (CPA), for developing a polyherbal contraceptive., Materials and Methods: The separate extract of above said plants or 'Contracept-TM' at the dose of 40 mg/100 g body weight of rat/day or CPA at 2 mg/100 g body weight of rat/day was administered for 28 days. Spermiological, androgenic and oxidative stress sensors, LD 50 and ED 50 /100 g body weight values were measured., Results: Treatment of individual, 'Contracept-TM' or CPA resulted significant decrease in the count of spermatogonia A (36.36-49.09%), pre-leptotene spermatocyte (19.11-55.30%), mid-pachytene spermatocyte (28.65-47.28%) and step 7 spermatid (29.65-51.59%). Activities of testicular Δ 5 , 3β (21.25-48.02%),17β-hydroxysteroid dehydrogenases (29.75-55.08%), catalase (19.06-43.29%) and peroxidase (30.76-62.82%), levels of testosterone (28.15-63.44%), testicular cholesterol (19.61-49.33%), conjugated diene (29.69-84.99%) and thiobarbituric acid reactive substances (41.25-86.73%) were elevated compare to the control. The ED 50 and LD 50 values were 40 mg and 5.8 g (T. chebula), 48 mg and 6.3 g (M. bulbisiana), 40 mg and 6.0 g ('Contracept-TM'), respectively., Discussion and Conclusion: The said spermiological and androgenic sensors' levels were decreased significantly by 'Contracept-TM' than its constitutional individual plant extract and it may be comparable to standard anti-testicular drug like CPA. So, it may be concluded that above polyherbal formulation is potent for inducing hypo-testicular activity.

Context: Terminalia muelleri Benth. (Combretaceae), is rich with phenolics that have antioxidant and cytotoxic activities. No screening studies were published before on T. muelleri., Objective: The study focused on isolation and identification of secondary metabolites from aqueous methanol leaf extract of T. muelleri and evaluation of its biological activities., Materials and Methods: The n-butanol extract was chromatographed on polyamide 6, and eluted with H 2 O/MeOH mixtures of decreasing polarity, then separated by different chromatographic tools that yielded 10 phenolic compounds. The antioxidant activity of the extract was evaluated by investigating its total phenolic and flavonoid content and DPPH scavenging effectiveness. The extract and the two acylated flavones were evaluated for their anticancer activity towards MCF-7 and PC3 cancer cell lines. Molecular docking study of the acylated flavones was performed against topoisomerase enzyme., Results and Discussion: Two acylated flavonoids, apigenin-8-C-(2″-O-galloyl) glucoside 1 and luteolin-8-C-(2″-O-galloyl) glucoside 2, were isolated and identified for the second time in nature, with eight tannins (3-10), from the leaves of T. muelleri. The extract and compound 10 showed the most significant antioxidant activity (IC 50  = 3.55 and 6.34 μg/mL), respectively. The total extract and compound 2 demonstrated cytotoxic effect against MCF-7 with IC 50  = 29.7 and 45.2 μg/mL respectively, while compound 1 showed cytotoxic effect against PC3 (IC 50  = 40.8 μg/mL). The docking study of compounds 1 and 2 confirmed unique binding mode in the active site of human DNA topoisomerase enzyme., Conclusions: Terminalia muelleri is a promising medicinal plant as it possesses high antioxidant activity and moderate cytotoxic activity against MCF-7.

The present study was conducted to explore the efficacy and safety of a herbal combination in the treatment of women with hyperlipidemic type 2 diabetes. The herbal combination capsule (600 mg) contained Terminalia chebula fruit extract (200 mg), Commiphora mukul (200 mg), and Commiphora myrrha oleo-gum-resin (200 mg), and the placebo capsule contained 600 mg toast powder. The patients in one group took the herbal combination and those in the other group took placebo capsules 3 times a day for 3 months. In the herbal combination-treated patients, the fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol levels were decreased and hidh-density lipoprotein cholesterol levels was increased significantly at the endpoint compared with the placebo and baseline. Other blood parameters such as glycosylated hemoglobin, triglyceride, blood urea nitrogen, creatinine, SGOT, and SGPT levels were not significantly changed after 3 months in both groups. In conclusion, the herbal combination improves glycemic control and lipid profile in women with hyperlipidemic type 2 diabetes without any adverse events.

In this study, we report the in vitro anti-HIV1 activity of acetone and methanol extracts of fruit of Terminalia paniculata. Cytotoxicity tests were conducted on TZM-bl cells and peripheral blood mononuclear cells (PBMC), the CC 50 values of both the extracts were ≥260 μg/mL. Using TZM-bl cells, the extracts were tested for their ability to inhibit replication of two primary isolates HIV-1 (X4, Subtype D) and HIV-1 (R5, Subtype C). The activity against HIV-1 primary isolate (R5, Subtype C) was confirmed using activated PBMC and by quantification of HIV-1 p24 antigen. Both the extracts showed anti-HIV1 activity in a dose-dependent manner. The EC 50 values of the acetone and methanol extracts of T. paniculata were ≤10.3 μg/mL. The enzymatic assays were performed to determine the mechanism of action which indicated that the anti-HIV1 activity might be due to inhibition of reverse transcriptase (≥77.7% inhibition) and protease (≥69.9% inhibition) enzymes.

Background: Quinolinic acid (QA) is a product of tryptophan degradation and its pathologic accumulation has been found to induce neuroinflammatory and demyelinating diseases such as multiple sclerosis via excessive free radicals generation. Recent studies showed that Terminalia chebula has several pharmacological effects such as antioxidant, anti-inflammatory and neuroprotective properties. The aim of this study was evaluation of the protective effect of T. chebula alcoholic extract (TCAE) on oxidative PC12 and OLN-93 cells death induced by QA., Methods: The cells were pretreated with TCAE (6.25-50μg/mL) for 2h and then subjected to QA (8mM) for 24h. Cell viability and the parameters of redox status including the levels of intracellular reactive oxygen species (ROS), lipid peroxidation and oxidative DNA damage were measured using 2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT), 2,7-dicholorofluorecin diacetate (DCF-DA), thiobarbituric acid and comet assays, respectively., Results: Based on Folin-Ciocalteu method, the total phenolic compounds in TCAE were estimated about 1.18%. TCAE at concentration ranges of 6.25-50μg/mL had no toxic effect on cell viability (p>0.05). Treatment with TCAE significantly increased cell viability following QA insult at concentrations above 25μg/mL (p<0.01). Cytoprotective potential of TCAE also ameliorated ROS accumulation, lipid peroxidation and DNA damage induced by QA., Conclusion: These data suggest that TCAE exhibits neuroprotection and oligoprotection potential by means of alleviating oxidative stress parameters., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Periodontal diseases are one of the major health problems and among the most important preventable global infectious diseases. Porphyromonas gingivalis is an anaerobic Gram-negative bacterium which has been strongly implicated in the etiology of periodontitis. Additionally, matrix metalloproteinases-9 (MMP-9) is an important factor contributing to periodontal tissue destruction by a variety of mechanisms. The purpose of this study was to evaluate the selected Sudanese medicinal plants against P. gingivalis bacteria and their inhibitory activities on MMP-9., Methods: Sixty two methanolic and 50% ethanolic extracts from 24 plants species were tested for antibacterial activity against P. gingivalis using microplate dilution assay method to determine the minimum inhibitory concentration (MIC). The inhibitory activity of seven methanol extracts selected from the 62 extracts against MMP-9 was determined by Colorimetric Drug Discovery Kit. In search of bioactive lead compounds, Combretum hartmannianum bark which was found to be within the most active plant extracts was subjected to various chromatographic (medium pressure liquid chromatography, column chromatography on a Sephadex LH-20, preparative high performance liquid chromatography) and spectroscopic methods (liquid chromatography-mass spectrometry, Nuclear Magnetic Resonance (NMR)) to isolate and characterize flavogalonic acid dilactone and terchebulin as bioactive compounds., Results: About 80% of the crude extracts provided a MIC value ≤4 mg/ml against bacteria. The extracts which revealed the highest potency were: methanolic extracts of Terminalia laxiflora (wood; MIC = 0.25 mg/ml) followed by Acacia totrtilis (bark), Ambrosia maritima (aerial part), Argemone mexicana (seed), C. hartmannianum (bark), Terminalia brownii (wood) and 50% ethanolic extract of T. brownii (bark) with MIC values of 0.5 mg/ml. T. laxiflora (wood) and C. hartmannianum (bark) which belong to combretaceae family showed an inhibitory activity over 50% at the concentration of 10 μg/ml against MMP-9. Additionally, MMP-9 was significantly inhibited by terchebulin with IC 50 value of 6.7 μM., Conclusions: To the best of our knowledge, flavogalonic acid dilactone and terchebulin were isolated from C. hartmannianium bark for the first time in this study. Because of terchebulin and some crude extracts acting on P. gingivalis bacteria and MMP-9 enzyme that would make them promising natural preference for preventing and treating periodontal diseases.

Triphala is a combination of three herbs amla, bahera and haritaki, it is widely available in the form churna and is a valued formula since ancient times. The aim of this research was to develop reproducible batches of triphala tablets and evaluation of the optimized batch. Direct compression was the method of choice. The tablets were prepared using different directly compressible excipients MicroceLac, Ludipress, Ludiflash. High Performance Liquid Chromatography (HPLC) method was employed for authentification of the herbs using gallic acid as the marker. The tablets were evaluated as per the pharmacopoeial tests. The tablets each weighing 600 mg were successfully formulated fulfilling the limits of evaluation.

Aedes aegypti Linn is one of the most important mosquito species. The vectors are responsible for causing deadly diseases like dengue and dengue hemorrhagic fever. Several chemical pesticides used to control these dengue vectors caused severe toxic significances on human health and other non-target beneficial insects. Therefore the current investigation has been made to access the bio-efficacy of the crude seed extracts of T. chebula against the dengue vector Ae. aegypti. The GC-MS analysis of crude seed extracts of T. chebula identified nine chemical compounds with major peak area in the 1,2,3-Benzenetriol (61.96%), followed by Tridecanoic acid (09.55%). Ae. aegypti larvae showed dose dependent mortality rate was observed between the treatments. Prominent protection rate at greater concentrations of 100ppm and moderate protection at 75 and 50ppm was observed in the repellent assay. Lethal concentration (LC 50 and LC 90 ) of fourth instar larvae of Ae. aegypti was observed in 138 and 220ppm concentration respectively. Similarly, the seed extracts showed 100% adulticidal activity at the concentration of 400ppm at 30min of exposure time. Phytochemicals present in the seed extracts of T. chebula significantly affects the major portions of the midgut tissues of Ae. aegypti at the concentration of 100ppm. The toxicological evaluation of seed extracts also proved non-toxic towards the A. bouvieri and Tx. splendens aquatic predatory insects. Hence, the present result suggest that bio-rational plant derived T. chebula could be incorporated in the dengue vector control and have no adverse effects on non-target beneficial insects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Aqueous bark extract of Terminalia arjuna (TA) has been in use as an ethnomedicine for cardiovascular ailments in the Indian subcontinent for centuries. Studies using hemodynamic, ROS scavenging and anti-inflammatory parameters in animal models have shown its anti-atherogenic, hypotensive, inotropic, anti-inflammatory effects. However, details analysis on its effects on established molecular and cell biological markers are a prerequisite for its wider acceptance to the medical community., Aims of the Study: To test the efficacy of TA extract in ameliorating cardiac hypertrophy induced by ISO in rats., Methods: Cardiac hypertrophy was induced by ISO (5mg/kg/day s.c. for 14 days) in rats and a standardized aqueous extract of TA stem bark was orally administered by gavage. Total RNA and protein were isolated from control, ISO, ISO plus TA and TA treated rat hearts and analyzed for the transcripts for the markers of hypertrophy, signaling kinases, transcription factors and total protein profile., Results: TA extract reversed the induction of fetal genes like β-myosin heavy chain, skeletal α-actin and brain natriuretic peptide in hypertrophic rat hearts. While ISO slightly increased the level of phospho-ERK, TA repressed it to about one third of the base line level. Survival kinase Akt, ER stress marker Grp78 and epigenetic regulator HDAC5 were augmented by ISO and TA restored them by various extents. ISO administration moderately increased the transcription factor NFκB binding activity, while coadministration of TA further increased it. AP-1 binding activity was largely unchanged by ISO treatment but it was upregulated when administered along with TA. MEF2D binding activity was increased by ISO and TA restored it to the baseline level. Global proteomic analysis revealed that TA treatment restored a subset of proteins up- and down-regulated in the hypertrophied hearts. Amongst those restored by TA were purinergic receptor X, myosin light chain 3, tropomyosin, and kininogen; suggesting a nodal role of TA in modulating cardiac function., Conclusions: This study for the first time reveals that TA partially or completely restores the marker mRNAs, signaling kinases, transcription factors and total protein profile in rat heart, thereby demonstrating its efficacy in preventing ISO-induced cardiac hypertrophy., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: The fruit of the Terminalia chebula tree has been widely used for the treatment of various disorders. Its anti-diabetic, anti-mutagenic, anti-oxidant, anti-bacterial, anti-fungal, and anti-viral effects have been studied. Dental plaque bacteria (DPB) are intimately associated with gingivitis and periodontitis. In the quest for materials that will prove useful in the treatment and prevention of periodontal disease, we investigated the preventive effects of an ethanol extract of Terminalia chebula (EETC) on DPB-induced inflammation and bone resorption., Methods: The anti-bacterial effect of EETC was analyzed using the disc diffusion method. The anti-inflammatory effect of EETC was determined by molecular biological analysis of the DPB-mediated culture cells. Prevention of osteoclastic bone resorption by EETC was explored using osteoclast formation and pit formation assays., Results: EETC suppressed the growth of oral bacteria and reduced the induction of inflammatory cytokines and proteases, abolishing the expression of PGE2 and COX-2 and inhibiting matrix damage. By stimulating the DPB-derived lipopolysaccharides, EETC inhibited both osteoclast formation in osteoclast precursors and RANKL expression in osteoblasts, thereby contributing to the prevention of bone resorption., Conclusions: EETC may be a beneficial supplement to help prevent DPB-mediated periodontal disease.

Context: Schizophrenia is a heterogenous neurological disorder, which has been hypothetically linked to oxidative imbalance and associated behavioral perturbations. Preliminary evidence from animal models predictive of human psychosis suggests that Terminalia ivorensis A. Chev. (Combretaceae) has antipsychotic-like activity in mice., Objective: This study investigates the neuroprotective property of the ethanol stem bark extracts of T. ivorensis (EETI) in reversal treatment of ketamine-induced schizophrenia-like behaviors and oxidative alteration in adult male Swiss albino mice., Materials and Methods: Animals were divided into six treatment groups (n = 5). Animals received distilled water or ketamine (20 mg/kg) once daily intraperitoneally (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with EETI (125, 250 or 500 mg/kg), risperidone (RIS) or vehicle orally once daily. Behaviors related to positive (locomotor activity) and cognitive (Y maze) symptoms of schizophrenia were assessed. Glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, including malondialdehyde (MDA) concentration were measured in mice whole brains., Result: The LD 50 of EETI was 2236.06 mg/kg, p.o. body weight. EETI (125, 250 or 500 mg/kg, p.o.) demonstrated significant (p < 0.05) inhibition of ketamine-induced hyperlocomotion and cognitive dysfunction. The extract decreased MDA concentration (39.0, 62.6 and 67.5%) in a dose-dependent manner. Moreover, EETI significantly (p < 0.05) reversed the depletion of GSH, and increased activities of SOD and CAT in brain tissues., Discussion and Conclusion: These findings suggest that EETI probably exert its antipsychotic-like activity, via a neuroprotective compensatory mechanism of action, and as such, could be relevant in the management of schizophrenia.

Background: Medicinal plants have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, venous insufficiency and arrhythmia since centuries. A recent increase in the popularity of alternative medicine and natural products has revived interest in traditional remedies that have been used for the treatment of cardiovascular diseases., Aim: The purpose of this review is to provide updated, comprehensive and categorized information on the history and traditional uses of some herbal medicines that affect the cardiovascular system in order to explore their therapeutic potential and evaluate future research opportunities., Methods: Systematic literature searches were carried out and the available information on various medicinal plants traditionally used for cardiovascular disorders was collected via electronic search (using Pubmed, SciFinder, Scirus, GoogleScholar, JCCC@INSTIRC and Web of Science) and a library search for articles published in peer-reviewed journals. No restrictions regarding the language of publication were imposed., Results: This article highlights the cardiovascular effects of four potent traditional botanicals viz. Garlic (Allium sativum), Guggul (Commiphora wightii), Hawthorn (Crataegus oxyacantha) and Arjuna (Terminalia arjuna). Although these plants have been used in the treatment of heart disease for hundreds of years, current research methods show us they can be utilized effectively in the treatment of cardiovascular diseases including ischemic heart disease, congestive heart failure, arrhythmias and hypertension., Conclusion: Although the mechanisms of action are not very clear, there is enough evidence of their efficacy in various cardiovascular disorders. However, for bringing more objectivity and also to confirm traditional claims, more systematic, well-designed animal and randomized clinical studies with sufficient sample sizes are necessary. Multidisciplinary research is still required to exploit the vast potential of these plants. Potential synergistic and adverse side effects of herb-drug interactions also need to be studied. These approaches will help in establishing them as remedies for cardiovascular diseases and including them in the mainstream of healthcare system., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Ethnopharmacological Relevance: Terminalia arjuna (Roxb. ex DC.) Wight & Arn. (T. arjuna) has been widely used in the traditional ayurvedic system of medicine as a cardioprotectant and for acute and chronic renal diseases supporting its ethnopharmacological use., Aim of the Study: The present study aimed at evaluating the diuretic action of an alcoholic extract of T. arjuna and its possible use as a prophylactic to prevent vascular leakage during acute mountain sickness at high altitude., Materials and Methods: Rats were exposed to hypobaric hypoxia simulated to an altitude of 27,000 ft. in a decompression chamber for 12h. T. arjuna bark extract was administered at a single dose of 150 mg/kg (p.o.) to male Sprague Dawley rats (200 ± 20 g) 30 min prior to exposure. Total urine volume was measured during exposure to hypobaric hypoxia. The animals were then investigated for cerebral vascular leakage and serum concentration of sodium, potassium, renin, angiotensin-II, aldosterone and atrial natriuretic peptide (ANP)., Results: T. arjuna ameliorated acute hypobaric hypoxia induced decrease in glomerular filtration rate (p<0.5), increased total urine output (p<0.5) and prevented cerebral vascular leakage in hypoxic rats. T. arjuna treated animals also showed decrease in serum levels of renin (p<0.001) and angiotensin-II (p<0.5) as compared to placebo treated animals. Administration of T. arjuna attenuated acute hypobaric hypoxia induced oxidative stress, improved aldosterone levels and altered electrolyte balance in animals through ANP dependent mechanism., Conclusion: Results of the present study indicate towards diuretic potential of hydro-alcoholic extract of T. arjuna bark and provide evidence for its novel application as a prophylactic to attenuate acute hypobaric hypoxia induced cerebral vascular leakage through ANP mediated modulation of renin-angiotensin-aldosterone system., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10-30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome.

Plants of the genus Terminalia are amongst the most widely used plants for traditional medicinal purposes worldwide. Many species are used for their antibacterial, antifungal, antiprotozoal, antiviral, antidiarrhoeal, analgesic, antimalarial, antioxidant, antiinflammatory and anticancer activities. Wound healing and cardiovascular effects have also been credited to some species. Many Terminalia species have multiple beneficial effects for multiple diseases and ailments. Indeed, the Indian species Terminalia chebula is known as the king of plants in Ayurveda due to its broad range of medicinal uses. However, apart from the reported ethnopharmacological uses of many Terminalia species, surprisingly few studies have rigorously examined this important genus for their medical properties/mechanisms and phytochemistry. This is likely due to the high tannin content common to many Terminalia species and the perception that these tannins may be responsible for much of their beneficial properties. As the complexities of tannins make them poor candidates for drug design, most interest in Terminalia species has been for their pharmacognostic and nutraceutical value and they have often been overlooked as potentials for drug discovery. However, recent reports have identified many other interesting phytochemicals and demonstrated that these may be responsible for several of the reported bioactivities of the Terminalia species used in traditional medicinal systems. The last decade has seen a large increase in the number of studies into the use of Terminalia species as therapeutic agents. Several species used in Ayurvedic medicine (Terminalia arjuna, Terminalia bellerica, Terminalia catappa, T. chebula) in particular have received much recent attention. Similarly, recent reports have also highlighted the medicinal potential of species from Africa, Australia and the Americas. The aim of this report is to summarise the recent research into the medicinal properties, phytochemistry and therapeutic mechanisms of Terminalia species and thus to highlight and direct future areas of research into the medicinal activities of this important genus.

Context: Hyperlipidemia is known to be a major risk factor for the development of cardiovascular diseases (CVDs) which include atherosclerosis, coronary heart disease, and stroke. Although there are a large number of anti-hyperlipidemic drugs available, unfortunately, they all have side effects., Objective: Terminalia chebula Retz. (Combretaceae) is a plant used to treat cardiac disorders in the traditional Ayurveda medicine in India. The objective of this study was to assess the anti-hyperlipidemic properties of a methanol (MeOH) bark extract of T. chebula., Materials and Methods: Acute toxicity studies were performed according to the Organisation for Economic Cooperation and Development (OECD) guideline no. 423 using various doses (5, 50, 300, and 2000 mg/kg) of T. chebula bark. Anti-hyperlipidemic effect of MeOH bark extract of T. chebula at doses of 200, 400, and 600 mg/kg and fasting glucose levels after treatment with MeOH bark extract of T. chebula at doses of 200, 400, and 600 mg/kg were analyzed using commercially available kits., Results: Acute toxicity studies did not show any morbidity and mortality at various doses. The MeOH extract of T. chebula bark at doses of 200, 400, and 600 mg/kg significantly lowered serum cholesterol and triglyceride levels. Moreover, the extract of T. chebula and the positive control atorvastatin-treated groups of animals showed a significant increase in the serum high-density lipoprotein (HDL) cholesterol levels in diet-induced hypercholesterolemic animals., Conclusion: The overall results confirm that the bark extract of T. chebula possesses significant anti-hyperlipidemic activity.

Aim: The aim of the present study was to evaluate the efficacy of triphala mouth rinse (aqueous) in the reduction of plaque and gingivitis among children., Methods: The study was a randomized, double-blinded, controlled trial, with a total of 60 school children (n = 30 in each group; triphala and chlorhexidine groups). Plaque and gingival indices were used to evaluate baseline and follow-up plaque and gingivitis., Results: A total of 57 children completed the study. Both chlorhexidine and triphala groups showed significantly lower mean gingival and plaque index scores at follow up than baseline (P < 0.001). There was no significant difference in the percentage change in the mean gingival index between the two groups (P = 0.826). The percentage change in the mean plaque index was significantly higher in the chlorhexidine group compared to the triphala group (P = 0.048)., Conclusion: The effectiveness of triphala in the reduction of plaque and gingivitis was comparable to chlorhexidine, and can be used for short-term purposes without potential side-effects. It is a cost-effective alternative in reducing plaque and gingivitis., (© 2014 Wiley Publishing Asia Pty Ltd.)

Background: The aim of this study was to evaluate the efficacy of ethanol extract of Terminalia chebula in the treatment of hot water-induced burn wounds and to compare the results with silver sulfadiazine (SSD) in rats., Methods: Five groups of ten rats were burned with hot water. Animals were administrated with topical cream at control, normal saline, 5%, 10% T. chebula extracts and standard SSD creams. Several parameters were assessed, including wound area, visual inspection of wound, bacteriology assessment, percentage of wound contraction and histopathological examination., Results: The average area of wound on 10th day was 11.2 ± 3.3, 11 ± 3.2, 8.5 ± 2.3, 9.5 ± 4.2 and 5.1 ± 2.2 cm(2) for SSD1%, base cream, normal saline, herbal extract 5% and 10%, respectively. T. chebula 10% cream exhibited lower wound size than SSD1% and control groups at 10th day post burn injury. On day 15, the percentage of wound contraction in T. chebula was 5% and 10% more than 18% and 53% in comparison to SSD1% group, respectively. Histopathological results exhibited well-formed horizontally oriented collagen fibers for appropriate tension. Strength of scar on burned tissue was better in T. chebula 5% and 10% as compared with control and SSD groups., Conclusions: The results of this study showed that T. chebula extract was capable of accelerating wound healing in rats by wound contraction, and had beneficial effects more than SSD 1% cream in the management of burn injury.

The present study evaluated the cardioprotective effects of Terminalia arjuna on classical and immuno-inflammatory markers in coronary artery disease (CAD) as an adjuvant therapy. One hundred sixteen patients with stable CAD were administered placebo/T. arjuna (500 mg twice a day) along with medications in a randomized, double-blind clinical trial. To understand the specificity and efficacy of T. arjuna, we evaluated its effect through microarray and in silico analysis in few representative samples. Data was further validated via real-time PCR (n = 50) each at baseline, 3 months, and 6 months, respectively. rIL-18 cytokine was used to induce inflammation in vitro to compare its effects with atorvastatin. T. arjuna significantly down-regulated TG, VLDL-C, and immuno-inflammatory markers in stable CAD versus placebo-treated subjects. Microarray and pathway analysis of a few samples from T. arjuna/placebo-treated groups and real-time PCR validation further confirmed our observations. Our data demonstrate the anti-inflammatory and immunomodulatory effects of T. arjuna that may attenuate ongoing inflammation and immune imbalance in medicated CAD subjects.

Background: The prevalence and severity of obesity and associated co-morbidities are rapidly increasing across the world. Natural products-based drug intervention has been proposed as one of the crucial strategies for management of obesity ailments. This study was designed to investigate the anti-obesity activities of ethanolic extract of Terminalia paniculata bark (TPEE) on high fat diet-induced obese rats., Methods: LC-MS/MS analysis was done for ethanolic extract of T. paniculata bark. Male Sprague-Dawley (SD) rats were randomly divided into six groups of six each, normal diet fed (NC), high fat diet-fed (HFD), HFD+ orlistat (standard drug control) administered, and remaining three groups were fed with HFD + TPEE in different doses (100,150 and 200 mg/kg b. wt). For induction of obesity rats were initially fed with HFD for 9 weeks, then, (TPEE) was supplemented along with HFD for 42 days. Changes in body weight, body composition, blood glucose, insulin, tissue and serum lipid profiles, atherogenic index, liver markers, and expression of adipogenesis-related genes such as leptin, adiponectin, FAS, PPARgamma, AMPK-1alpha and SREBP-1c, were studied in experimental rats. Also, histopathological examination of adipose tissue was carried out., Results: Supplementation of TPEE reduced significantly (P < 0.05) body weight, total fat, fat percentage, atherogenic index, blood glucose, insulin, lipid profiles and liver markers in HFD-fed groups, in a dose-dependent manner. The expression of adipogenesis-related genes such as Leptin, FAS, PPARgamma, and SREBP-1c were down regulated while Adiponectin and AMPK-1alpha were up regulated in TPEE + HFD-fed rats. Furthermore, histopathological examination of adipose tissue revealed the alleviating effect of TPEE which is evident by reduced size of adipocytes., Conclusions: Together, the biochemical, histological and molecular studies unambiguously demonstrate the potential anti adipogenic and anti obesity activities of TPEE promoting it as a formidable candidate to develop anti obesity drug.

Background: The spread of microorganisms resistant to some antimicrobial agents necessitates the need to search for novel and effective antimicrobial agents. In this study, the antimicrobial activity of Terminalid catappa Linn. (Combretaceae) and Vitex doniana Sweet. (Verbenaceae), two Nigerian medicinal plants used in folk medicines for the management of various ailments related to microbial infections were evaluated., Objectives: To evaluate the antimicrobial activity of the crude ethanol extracts and fractions of the leaves and stem bark of T. catappa and V. doniana., Methodology: Four crude ethanol extracts and 16 (n-hexane, ethylacetate, n-butanol and aqueous) fractions of leaves and stem bark of T. catappa and V doniana were evaluated for in vitro antimicrobial activity against fifteen (15) strains of bacteria and fungi. The antimicrobial activity was determined in a 96-well plate using a resazurin based broth microdilution method. Two standard antimicrobial drugs ampicillin and nystatin were included as positive control., Results: The butanoL fraction of stem bark of T. catappa and ethanol crude extract of leaf of V don iana displayed the highest antibacterial activity with similar minimum inhibitory concentration (MIC) value of 93.75 microg/mL against S. aureus and B. subtilis. Furthermore, the ethyl acetate fraction of stem bark of T. catappa showed the highest antifungal activity with MIC of 187.5 microg/mL against A. sydowi. Amp icillin had MIC of 15.6 and 31.3 microg/mL against S. aureus and B. subtili, respectively while nystatin produced MIC of 3.9 microg/mL against A. sydowi., Conclusion: Termninalia catappa and Vitex doniana may serve as useful sources of plant derived antimicrobial agents.

Ethnopharmacological Relevance: Terminalia catappa L. (Combretaceae) is a medicinal plant listed as a pharmacopeia vegetable from Caribbean to treat gastritis. The objective of this study was to evaluate the gastroprotective and healing effect of the aqueous fraction (FrAq) obtained from the leaves of Terminalia catappa and to determine the antiulcer mechanism of action in experimental rodent models and its activity to Helicobacter pylori., Material and Methods: In rodents, the FrAq was challenged by different necrotizing agents, such as absolute ethanol and ischemia-reperfusion injury. The antiulcer mechanism of action of FrAq was assessed and the healing effects of the fraction after seven and 14 days of treatment was evaluated by matrix metalloproteinase activity (MMP-2 and MMP-9). The toxicological effect of subacute treatment with FrAq during 14 days of treatment was also analyzed. The anti-Helicobacter pylori activity was determined by microdilution. The phytochemical study of the fraction was analyzed by experiments with FIA-ESI-IT-MS(n) (Direct Flow Analysis-ionization Electrospray Ion Trap Tandem Mass Spectrometry) and high performance liquid chromatography (HPLC) coupled to a photodiode array (PDA)., Results: Oral treatment with FrAq (25mg/kg) significantly decreased the number of ulcerative lesions induced by ethanol and ischemia/reperfusion injury. The action of FrAq was mediated by the activation of defensive mucosa-protective factors, such as increases in mucus production, the nitric oxide (NO) pathway and endogenous prostaglandins. Oral treatment with FrAq for seven and 14 days significantly reduced the lesion area (80% and 37%, respectively) compared to the negative control group. Analyses of MMP-9 and MMP-2 activity from gastric mucosa confirmed the accelerated gastric healing effect of FrAq. This extract also presented considerable activity against Helicobacter pylori. The mass spectrum and MS/MS of the aqueous fraction indicates the existence of many different phenolic compounds, including punicalagin, punicalin, and gallagic acid, among others., Conclusions: We concluded that FrAq from Terminalia catappa leaves has excellent preventive and curative effects on acute and chronic induced gastric ulcers and showed an important profile against Helicobacter pylori., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The present study was designed to evaluate in vitro anti-proliferative potential of extracts from four Indian medicinal plants, namely Anogeissus latifolia, Terminalia bellerica, Acacia catechu and Moringa oleiferna. Their cytotoxicity was tested in nine human cancer cell lines, including cancers of lung (A549), prostate (PC-3), breast (T47D and MCF-7), colon (HCT-16 and Colo-205) and leukemia (THP-1, HL-60 and K562) by using SRB and MTT assays. The findings showed that the selected plant extracts inhibited the cell proliferation of nine human cancer cell lines in a concentration dependent manner. The extracts inhibited cell viability of leukemia HL-60 and K562 cells by blocking G0/G1 phase of the cell cycle. Interestingly, A. catechu extract at 100 μg/mL induced G2/M arrest in K562 cells. DNA fragmentation analysis displayed the appearance of a smear pattern of cell necrosis upon agarose gel electrophoresis after incubation of HL-60 cells with these extracts for 24 h.

Purpose: The present study was conducted to assess the effectiveness of Terminalia chebula on plaque and gingival inflammation and compare it with the gold standard chlorhexidine (CHX 0.2%) and distilled water as control (placebo)., Materials and Methods: A double-blind randomised control trial was conducted among undergraduate students who volunteered. They were randomly allocated into three study groups: 1) Terminalia chebula mouthwash (n = 30); 2) chlorhexidine (active control) (n = 30); 3) distilled water (placebo) (n = 30). Assessment was carried out according to plaque score and gingival score. Statistical analysis was carried out to compare the effect of both mouthwashes. ANOVA and post-hoc LSD tests were performed using SPSS version 17 with p ≤ 0.05 considered statistically significant., Results: Our result showed that Terminalia chebula mouthrinse is as effective as chlorhexidine in reducing dental plaque and gingival inflammation. The results demonstrated a significant reduction of gingival bleeding and plaque indices in both groups over a period of 15 and 30 days as compared to the placebo., Conclusion: The results of the present study indicate that Terminalia chebula may prove to be an effective mouthwash. Terminalia chebula extract mouthrinse can be used as an alternative to chlorhexidine mouthrinse as it has similar properties without the side-effects of the latter.

Background: The present study compares the protective properties of aqueous extracts of six medicinal plants, Phyllanthus emblica, Terminalia chebula (black and yellow), Terminalia arjuna, Balsamodendron Mukul and Alium sativum against lipid per-oxidation in mice brain., Methods: The antioxidant activities were analyzed by lipid per-oxidation assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay, total antioxidant activity and metal chelation., Results: The extracts (fruits and bark) showed inhibition against thiobarbituric acid reactive species (TBARS) induced by pro-oxidant (10 µM FeSO4) in mice brain. Moreover, the free radical scavenging activities of the extracts was evaluated by the scavenging of DPPH radical (IC₅₀, 23.23 ± 1.2 µg/ml (Phyllanthus emblica), 20.24 ± 0.9 µg/ml (Terminalia chebula yellow) and 17.33 ± 1.1 µg/ml (Terminalia chebula black), 19.44 ± 0.45 µg/ml (Terminalia arjuna), 56.59 ± 2.1 µg/ml (Balsamodendron Mukul) and < 200 µg/ml (Alium sativum)., Conclusion: The higher antioxidant and inhibitory effect of Terminalia chebula black in this study could be attributed to its significantly higher phenolic content, Fe(II) chelating ability, reducing ability and free radical scavenging activity. Therefore oxidative stress in brain could be potentially prevented by the intake of these plants.

The polyphenolic fractions of fruits: Terminalia catappa, Carissa carandas, Ziziphus nummularia; spice oilseeds: thymol, mustard, fenugreek and poppy seeds; and herb: green and black teas were analyzed for their total phenolics, flavonoids and antimicrobial potential. All fractions from fruits, except anthocyanin of C. carandas, displayed substantial antibacterial activity in accordance to their phenolic contents, the difference in activity being quite significant (p < 0.05), highest for T. catappa (minimum inhibitory concentration, MIC: 7.8-1000 microg/mL) and lowest for C. carandas (MIC: 62.5-1000 microg/mL). With few exceptions, both green and black teas' fractions inhibited the tested strains, however, green tea fractions (MIC: 15.63-125 microg/mL) were more active than black (MIC: 31.25-1000 microg/mL) and neutral were more active than their corresponding acidic fractions. Oil fractions of all oilseeds were found to be more active than their polyphenolic fractions, their antibacterial action decreased in the order thymol > mustard > fenugreek > poppy seeds (p < 0.05). Though the fruits used for the study are underutilized and have been emphasized for processed products, they may potentially be important to fight against pathogenic bacteria in view of their MICs. The teas and oilseeds, though a small part of total food intake, are more functional and active against the tested bacterial species and may find potential applications in therapeutics and food preservation.

Current novel therapeutic agents for the treatment of sickle cell anaemia (SCA) focus on increasing foetal haemoglobin (HbF) levels in SCA patients. Unfortunately, the only approved HbF-inducing agent, hydroxyurea, has long-term unpredictable side effects. Studies have shown the potential of plant compounds to modulate HbF synthesis in primary erythroid progenitor stem cells. We isolated a novel HbF-inducing Terminalia catappa distilled water active fraction (TCDWF) from Terminalia catappa leaves that induced the commitment of erythroid progenitor stem cells to the erythroid lineage and relatively higher HbF synthesis of 9.2- and 6.8-fold increases in both erythropoietin (EPO)-independent and EPO-dependent progenitor stem cells respectively. TCDWF was differentially cytotoxic to EPO-dependent and EPO-independent erythroid progenitor stem cell cultures as revealed by lactate dehydrogenase release from the cells. TCDWF demonstrated a protective effect on EPO-dependent and not EPO-independent progenitor cells. TCDWF induced a modest increase in caspase 3 activity in EPO-independent erythroid progenitor stem cell cultures compared with a significantly higher (P˂0.05) caspase 3 activity in EPO-dependent ones. The results demonstrate that TCDWF may hold promising HbF-inducing compounds, which work synergistically, and suggest a dual modulatory effect on erythropoiesis inherent in this active fraction., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Pentacyclic triterpenoids improve epidermal barrier function and induce collagen production. Here, their effects on cutaneous aging by means of objective instrumental measurements were elucidated., Methods: Reconstituted human epidermis, cultivated keratinocytes and fibroblasts were incubated with Terminalia arjuna triterpenes (T. arjuna bark extract), and mRNA and protein expression of various genes was determined using microarray analysis, qRT-PCR and ELISA techniques. Clinical efficacy of T. arjuna bark extract versus vehicle control cream was elucidated in 30 patients and transepidermal water loss (TEWL), skin hydration and elasticity were measured. Another 30 female patients in their postmenopausal phase were treated with a similar regime, and skin sebum content, cutaneous blood microcirculation and skin density/echogenicity were assessed., Results: Incubation with T. arjuna triterpenes increased FGF-2, TSP-1, TGF-β and CTGF expression, and VEGF secretion in vitro. Elevated lactate dehydrogenase release upon sodium dodecyl sulphate challenge was reversed by the application of T. arjuna bark extract. T. arjuna bark extract decreased TEWL, improved skin moisturization, reduced scaliness and led to significantly improved skin elasticity. Also, increases in blood microflow and skin sebum content as well as improved skin thickness/echogenicity were noted on postmenopausal skin, resulting in visible reduction of sagging skin on the jowls as demonstrated by digital photography., Conclusion: T. arjuna bark extract appears as an innovative active ingredient that exerts versatile antiaging properties in vitro and in vivo.

Purpose: To evaluate and compare the effect of triphala extract mouthrinse and chlorhexidine on dental plaque and gingivitis., Materials and Methods: In this double blind, crossover study, 120 qualifying boarding-school students aged 13-16 years were randomised into three groups: 10% triphala, 0.2% chlorhexidine and negative control. The study was conducted in 3 phases of 1-month duration each and a washout period of 15 days. During the experimental period, subjects rinsed with the allocated mouthrinse once daily for 30 s under supervision. The plaque and gingival status was assessed using the Turesky modification of the Quigley and Hein plaque index (QHI) and the gingival index (Löe and Silness) at baseline and at the end of each phase. The results were tested for significance at P < 0.05., Results: Triphala and chlorhexidine yielded a significant reduction in plaque and gingival index scores as compared to negative control (P < 0.001). No significant difference was found between the scores obtained with triphala and chlorhexidine mouthwashes., Conclusion: The antiplaque and antigingivitis activity of triphala closely parallels that of chlorhexidine.