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1.
An Acad Bras Cienc ; 94(4): e20210265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36102393

RESUMO

Terminalia L. has a pantropical distribution, almost exclusively constituting tropical Combretaceae. In this work, a comprehensive synopsis of all the native species of Terminalia s.s. in the Brazilian Amazon is presented, including diagnostic characters, identification key, illustrations, geographic distribution maps, diversity and richness patterns with a new occurrence in Brazil, and a table with conservation status and number of records/ protected areas and their protected areas for all species. This information seeks to support the identification of these tree species, in addition to actions to conserve trees in the Brazilian Amazon.


Assuntos
Terminalia , Árvores , Brasil
2.
Biomed Pharmacother ; 154: 113543, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36057223

RESUMO

Tumor-associated macrophages (TAMs) are the major immunosuppressive components infiltrating the tumor microenvironment (TME). Targeting TAMs has emerged as a promising strategy to remodel immunosuppressive TME and enhance T-cell mediated anti-tumor immunity for cancer therapy. In this study, we investigate the effect and mechanism of total tannin fraction of Terminalia bellirica (Gaertn.) Roxb. (TB-TF) against hepatocellular carcinoma (HCC) using established Hepa1-6 orthotopic mouse model and murine bone marrow derived macrophage polarization model. Here we showed that TB-TF significantly inhibited orthotopic tumor growth and promoted the polarization of M2-TAMs toward the anti-tumor M1 phenotype in vivo. Further studies showed that TB-TF reversed tumor-conditioned medium induced M2 polarization of macrophages as indicated by increased expression of TNF-α, IL-1ß, and iNOS, and decreased expression of Arg-1, thereby re-educating macrophages co-cultured with tumor-conditioned medium into M1 phenotype. In addition, we found that TB-TF also promoted T cell infiltration mediated by chemokines such as CCL5 and CXCL10, and restored the cytotoxic function of CD8+T cells as evidenced by upregulated expression of Granzyme B, Perforin, and IFN-γ. Our data suggest TB-TF as a promising anti-cancer agent, mediates its anti-tumor effects via remodeling the tumor immunosuppressive microenvironment, indicating its potential in the immunotherapy for hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Terminalia , Animais , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/farmacologia , Neoplasias Hepáticas/metabolismo , Camundongos , Taninos/farmacologia , Taninos/uso terapêutico , Microambiente Tumoral , Macrófagos Associados a Tumor
3.
Molecules ; 27(16)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36014464

RESUMO

Intestinal ischemia/reperfusion (II/R) injury is a common life-threatening complication with high morbidity and mortality. Chebulae Fructus Immaturus, the unripe fruit of Terminalia chebula Retz., also known as "Xiqingguo" or "Tibet Olive" in China, has been widely used in traditional Tibetan medicine throughout history. The phenolic acids' extract of Chebulae Fructus Immaturus (XQG for short) has exhibited strong antioxidative, anti-inflammation, anti-apoptosis, and antibacterial activities. However, whether XQG can effectively ameliorate II/R injuries remains to be clarified. Our results showed that XQG could effectively alleviate II/R-induced intestinal morphological damage and intestinal barrier injury by decreasing the oxidative stress, inflammatory response, and cell death. Transcriptomic analysis further revealed that the main action mechanism of XQG protecting against II/R injury was involved in activating PPARα and inhibiting the NF-κB-signaling pathway. Our study suggests the potential usage of XQG as a new candidate to alleviate II/R injury.


Assuntos
Hidroxibenzoatos/farmacologia , Traumatismo por Reperfusão , Terminalia , Animais , Camundongos , NF-kappa B/metabolismo , PPAR alfa , Extratos Vegetais , Traumatismo por Reperfusão/tratamento farmacológico , Terminalia/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-35940042

RESUMO

The phytochemical profiles of ethno-medicinal plants from Southern Asia have been extensively studied, due to their wide utilization in various traditional systems of India, Bhutan, Maldives, Nepal and China. Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. are the two most important and widely utilized medicinal plants across the traditional system in India. The herbal products comprising the fruits of these two plants, example Triphala, Vyoshadi-Gulgulu Gulika and also marketed Ayurvedic products like Pilonil Tablet are proven to have high medicinal value and biotherapeutic efficacy. The current study is an effort to develop highly precise, sensitive and reproducible HP-TLC protocol for the standardization herbal preparations comprising of hydro-alcoholic extract of selected Terminalia species as their major ingredients. The selected herbal products were assessed through HP-TLC for quantifying gallic acid and quercetin, followed by their visualization using DPPH*, Anisaldehyde and Vanillin as derivatizing reagent. The USP official protocol was followed for the method development using digitally optimized HP-TLC system. The results demonstrated good sensitivity and regression value of 99.999% for proposed method with optimized chromatographic analysis. The developed protocol was validated in accordance with ICH guidelines and all the parameters were found to be within the specified limits. Thus, the proposed HP-TLC method would surely serve as a classical tool for analysis and standardization of Terminalia species and their traditional products.


Assuntos
Plantas Medicinais , Terminalia , Antioxidantes/análise , Frutas/química , Extratos Vegetais/química , Plantas Medicinais/química , Polifenóis/análise , Terminalia/química
5.
J Sep Sci ; 45(18): 3412-3421, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35819997

RESUMO

Screening and identification of active components from traditional Chinese medicines is rather challenging due to the diversity and complexity of chemical components. Herein, a comprehensive strategy based on a spectrum-effect relationship model and LC-MS analysis was developed to screen active components from Terminalia chebula fruits. The water extract of T. chebula fruits was subjected to macroporous resin column and then eluted successively with water and 30%, 50%, 70%, and 95% ethanol. The 30% ethanol eluate fractions of eighteen batches from T. chebula fruits were used for the spectrum-effect relationship study. The IC50 values for acetylcholinesterase inhibitory and 2,2-diphenyl-1-picrylhydrazyl scavenging activities were measured, LC fingerprints were established, and 15 common peaks were specified. The spectrum-effect relationship between common peaks and IC50 values was investigated by principal component analysis, gray relational analysis, partial least square and multiple linear regression. The 30% ethanol eluate fraction was further characterized by LC-MS analysis. The chromatographic peaks (Peaks 1, 2, 3, 5, 12, 14, 15) making great contributions to the efficacy were screened through a spectrum-effect relationship model, and sixteen components were further identified. The results suggested that the proposed strategy is simple and effective for acquiring active components from a complex matrix.


Assuntos
Terminalia , Acetilcolinesterase , Antioxidantes/análise , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Etanol , Frutas/química , Espectrometria de Massas , Extratos Vegetais/química , Terminalia/química , Água/análise
6.
J Drugs Dermatol ; 21(7): 784-788, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35816074

RESUMO

For decades, retinoids have been considered the gold standard of treatment for a variety of skin conditions.1,2 As the bioavailable form of vitamin A, retinoic acid has demonstrated the ability to reduce skin discoloration, stimulate collagen production, reduce rhytids, improve acne, and uneven skin texture.3,4 Retinoic acid is a potent drug with high bioavailability. Challenges with such a product include skin sensitivity and retinoid dermatitis.1,5 This potential irritation and discomfort may hinder patient compliance reducing visible results. The non-prescription vitamin A ingredient retinol is an effective and less irritating alternative, as it is converted into retinoic acid within the skin, causing little to no irritation when used topically. Intensive Age Refining Treatment: 0.5% pure retinol night by PCA SKIN® contains 0.5% retinol, protected and delivered into the skin with a multi-layered liposomal delivery technology. This development addresses the inherent instability of retinol,1,2,3 as well as the mitigation of irritation with the goal of enhancing patient compliance and visible results. This formulation also features niacinamide and terminalia chebula to further support the anti-aging benefits of retinol. The 12-week in vivo use of this potent, yet non-irritating retinol topical demonstrates improved patient compliance and satisfaction due to tolerability and enhanced efficacy in the improvement in overall signs of healthy skin. J Drugs Dermatol. 2022;21(7):784-788. doi:10.36849/JDD.6621.


Assuntos
Envelhecimento da Pele , Terminalia , Envelhecimento , Humanos , Niacinamida/efeitos adversos , Retinoides , Tretinoína/efeitos adversos , Vitamina A/efeitos adversos
7.
Phytomedicine ; 104: 154318, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35830757

RESUMO

BACKGROUND: Terminalia chebula (TC) is a traditional medicinal plant used for treating various diseases in humans. However, pharmacological mechanisms underlying the effects of TC in atopic treatment remain unelucidated. HYPOTHESIS/PURPOSE: We investigated the therapeutic effects of TC extract in a mouse model of atopic dermatitis (AD) in vivo and the anti-inflammatory mechanism in vitro. STUDY DESIGN/METHODS: For the in vivo study, AD was induced by Dermatophagoides farinae extract (Dfe) in NC/Nga mice. After 14 days of oral administration, the effects of TC concentrations of 30, 100, and 300 mg/kg were analyzed by assessing morphological changes visually; measuring serum levels of inflammatory chemokines/cytokines, IgE, histamine, MDC, TARC, RANTES, and TSLP using ELISA kits; and counting infiltrated mast cells. For in vitro analyses, we used IFNγ/TNF-α-stimulated human keratinocyte cell lines to study the mechanism of action. The production of chemokines/cytokines in the IFNγ/TNF-α-stimulated HaCaT cells was measured using ELISA and a bead array kit. The signaling pathways were analyzed by western blotting and the expression of the transcriptional factors using RT-PCR and luciferase assay. RESULTS: Administration of TC significantly alleviated AD-like symptoms in vivo and decreased the ear thickness, dermatitis score, keratinization, and mast cell infiltration. It also resulted in decreased serum levels of IgE, histamine, and inflammation-related mediators MDC, TARC, RANTES, and TSLP compared with those in the Dfe treatment group. Moreover, TC downregulated the expression of the inflammatory chemokines RANTES and MDC in IFNγ/TNF-α-stimulated HaCaT cells. TC inhibited phosphorylated STAT1/3 and NK-κB subunits and nuclear translocation of NF-κB. It also suppressed the transcription of IFNγ, IL-6, IL-8 and MCP-1 in the IFNγ/TNF-α-stimulated HaCaT cells. TC and its constituents, chebulic acid, gallic acid, corlagin, chebulanin, chbulagic acid, ellagic acid, and chebulinic acid, strongly inhibited the nuclear translocation of NF-κB, STAT1, and STAT3 and decreased the expression of inflammatory cytokines at the mRNA level. CONCLUSIONS: Overall, TC extract alleviated AD-like symptoms by regulating anti-inflammatory factors in vivo and suppressing STAT1/3 and NF-κB signaling in vitro. In addition, our results show the in vivo effect of partial improvements in AD, as well as the in vitro effect on inflammatory factors by the constituents of TC. This finding provides that TC extract and its components could be potential therapeutic drugs for AD.


Assuntos
Dermatite Atópica , Terminalia , Animais , Anti-Inflamatórios/uso terapêutico , Quimiocina CCL5/metabolismo , Quimiocina CCL5/farmacologia , Quimiocina CCL5/uso terapêutico , Quimiocinas/metabolismo , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Histamina , Humanos , Imunoglobulina E , Queratinócitos , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/uso terapêutico , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3 , Fator de Necrose Tumoral alfa/metabolismo
8.
J Ethnopharmacol ; 296: 115512, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35788037

RESUMO

ETHNOPHARMACOLOGICAL SIGNIFICANCE: Medicinal plants from the Terminalia genus are widely used as remedies against many infectious diseases, including malaria. As such, Terminalia ivorensis A. Chev. and Terminalia brownii Fresen. are famous due to their usefulness in traditional medicines to treat malaria and yellow fever. However, further information is needed on the extent of anti-Plasmodium potency of extracts and fractions from these plants and their phytochemical profile. AIM OF THE STUDY: This study was designed to investigate the in vitro antiplasmodial activity and to determine the chemical profile of promising extracts and fractions from T. ivorensis and T. brownii stem bark. MATERIALS AND METHODS: Crude aqueous, ethanolic, methanolic, hydroethanolic and ethyl acetate extracts were prepared by maceration from the stem barks of T. brownii and T. ivorensis. They were subsequently tested against chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) strains of P. falciparum using the parasite lactate dehydrogenase (PfLDH) assay. Extracts showing very good activity on both plasmodial strains were further fractionated using column chromatography guided by evidence of antiplasmodial activity. All bioactive extracts and fractions were screened for their cytotoxicity on Vero and Raw cell lines using the resazurin-based assay and on erythrocytes using the hemolysis assay. The phytochemical profiles of selected potent extracts and fractions were determined by UPLC-QTOF-MS analysis. RESULTS: Of the ten extracts obtained from both plant species, nine showed inhibitory activity against both P. falciparum strains (Pf3D7 and PfDd2), with median inhibitory concentration (IC50) values ranging from 0.13 µg/ml to 10.59 µg/ml. Interestingly, the aqueous extract of T. ivorensis (TiW) and methanolic extract of T. brownii (TbM) displayed higher antiplasmodial activities against both strains (IC50 0.13-1.43 µg/ml) and high selectivity indices (SI > 100). Their fractionation led to two fractions from T. ivorensis and two from T. brownii that showed very promising antiplasmodial activity (IC50 0.15-1.73 µg/mL) and SI greater than 100. The hemolytic assay confirmed the safety of crude extracts and fractions on erythrocytes. UPLC-MS-based phytochemical analysis of the crude aqueous extract of T. ivorensis showed the presence of ellagic acid (1) and leucodelphidin (2), while analysis of the crude methanol extract of T. brownii showed the presence of ellagic acid (1), leucodelphinidin (2), papyriogenin D (3), dihydroactinidiolide (4) and miltiodiol (5). CONCLUSIONS: The extracts and fractions from T. ivorensis and T. brownii showed very good antiplasmodial activity, thus supporting the traditional use of the two plants in the treatment of malaria. Chemical profiling of the extracts and fractions led to the identification of chemical markers and the known antimalarial compound ellagic acid. Further isolation and testing of other pure compounds from the active fractions could lead to the identification of potent antiplasmodial compounds.


Assuntos
Antimaláricos , Malária Falciparum , Malária , Plasmodium , Terminalia , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ácido Elágico/uso terapêutico , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais , Plasmodium falciparum , Espectrometria de Massas em Tandem , Terminalia/química
9.
Biomed Res Int ; 2022: 5870443, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35707383

RESUMO

Background: Dental/oral diseases are one of the significant public health problems globally. Herbal medicines for managing oral diseases are considered an effective alternative to synthetic compounds due to their lower side effect. Azadirachta indica, Terminalia chebula, Camellia sinensis, and Piper nigrum are used to control and prevent oral inflammations in dentistry. In this study, we have evaluated the protease inhibition activity of these plant extracts, and further, the binding mode of the active ingredient of these plants with trypsin was studied using molecular docking. Methods: In this study, protease inhibition activity was carried out using aqueous extracts of the plant parts such as Azadirachta indica (neem) twig, Terminalia chebula (Haritaki) fruit, Camellia sinensis (green tea) powder, and Piper nigrum (kali miri) seed. Next, to explore the binding mode of active ingredients azadirachtin, chebuligenic acid, catechin, and piperine with trypsin, we employed a molecular docking study using AutoDock4.2. Results: The results revealed that the Azadirachta indica plant extract showed an IC50 value of 96.19 µg mL-1, Camellia sinensis IC50 value of 188.50 µg mL-1, Piper nigrum IC50 value of 371.20 µg mL-1, and Terminalia chebula IC50 value of 639.48 µg mL-1, when compared with standard drug diclofenac sodium, had IC50 value 93.00 µg mL-1. Further, the docking result reveals that all the main active ingredients of these plants have significant binding affinity and prefer the same binding pocket of trypsin. Conclusion: Hence, our results show the importance of traditional plants Azadirachta indica, Terminalia chebula, green tea, and Piper nigrum to control oral disease conditions. As they show significant protease inhibition activity, hence, the active ingredient could act as a potential anti-inflammatory agent and further help to prevent or control oral disease conditions such as gingivitis and periodontitis.


Assuntos
Azadirachta , Piper nigrum , Plantas Medicinais , Terminalia , Odontologia , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Plantas Medicinais/química , Inibidores de Proteases , Chá , Terminalia/química , Tripsina
10.
Phytomedicine ; 103: 154245, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35696798

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid ß plaques (Aß) is a central hallmark of AD. Accumulating evidence suggest that shifting amyloid precursor protein (APP) metabolism pathway to non-amyloidogenic ways and inducing autophagy play key roles in AD pathology. In published reports, there is no research on the APP metabolic process of Terminalia chebula Retz. (T. Chebula). PURPOSE: The study aims to assess the effects of T. Chebula in AD transgenic SH-SY5Y cells to determine its underlying mechanisms on reducing Aß level by regulating APP metabolic process. METHODS: The effects of T. Chebula water extract (TWE) on APPswe transgenic SH-SY5Y cells were analyzed by cell viability. ELISA used to quantify extracellular Aß1-40 and Aß1-42 generations. Western blot and RT-PCR assays were chosen to detect the expression of proteins and genes. The acridine orange (AO) stain was used to label autophagic-vesicles. RESULTS: Treatment with TWE significantly suppressed the Aß1-40 and Aß1-42 generations of APPswe transgenic cells. TWE inhibited amyloidogenic pathway by reducing BACE1 expression, and promote non-amyloidogenic pathway by inducing ADAM10 level of APP metabolism. Additionally, TWE induced autophagy in APPswe transgenic cells involved in APP metabolism to shift the balance to non-amyloidogenic pathway. CONCLUSION: In summary, our finding first time expounded that TWE can inhibit the generation of Aß1-40 and Aß1-42 in APPswe transgenic SH-SY5Y cells, which were regulated APP metabolism tends to non-amyloid metabolism pathway and mediated by autophagy. The results presented a novel finding for AD treatment of traditional natural medicines.


Assuntos
Doença de Alzheimer , Neuroblastoma , Doenças Neurodegenerativas , Terminalia , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Ácido Aspártico Endopeptidases/genética , Autofagia , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo
11.
Chem Biodivers ; 19(7): e202200137, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35726787

RESUMO

Regulation of key digestive enzymes is currently considered an effective remedy for diabetes mellitus. In this study, bioactive constituents were purified from Terminalia boivinii fruits and identified by 1 H-NMR, 13 C-NMR and EI-MS. In vitro and in silico methods were used to evaluate α-glucosidase, α-amylase, and lipase inhibition activities. Compounds 1, 2, and 4-7 with IC50 values between 89 and 445 µM showed stronger α-glucosidase inhibitory activities than the antihyperglycemic drug acarbose (IC50 =1463.0±29.5 µM). However, the compounds showed lower inhibitory effects against α-amylase and lipase with IC50 values above 500 µM than acarbose (IC50 =16.7±3.5 µM) and ursolic acid (IC50 =89.5±5.6 µM), respectively. Lineweaver-Burk plots showed that compounds 1, 2, and 7 were non-competitive inhibitors, compounds 4 and 5 were competitive inhibitors and compound 6 was a mixed-type inhibitor. Fluorescence spectroscopic data showed that the compounds altered the microenvironment and conformation of α-glucosidase. Computer simulations indicated that the compounds and enzyme interacted primarily through hydrogen bonding. The findings indicated that the compounds were inhibitors of α-glucosidase and provided significant structural basis for understanding the binding activity of the compounds with α-glucosidase.


Assuntos
Terminalia , alfa-Glucosidases , Acarbose , Frutas/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Cinética , Lipase/metabolismo , Simulação de Acoplamento Molecular , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
12.
Sci Rep ; 12(1): 10711, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35739183

RESUMO

Rising prevalence of type 2 diabetes mellitus (T2DM) in sub-Saharan Africa has necessitated surveys of antidiabetic medicinal plants. This study assessed the antidiabetic mechanism of Terminalia catappa aqueous leaf extract (TCA) in high fat/low dose streptozotocin-induced type 2 diabetic rats. T2DM was induced by a combination of high-fat diet and low dose STZ (30 mg/kg bw) and the animals were administered with TCA (400 and 800 mg/kg bw) orally daily for 28 days. Biochemical parameters and indices for diabetes including renal function tests and pancreatic histology were evaluated. Relative expression of hepatic insulin resistance, signalling and glucose transport genes were also assessed. Induction of T2DM resulted in significant (p < 0.05) weight loss, dysregulated glucose level and clearance, electrolyte imbalance and disrupted diabetic biochemical parameters. Diabetes onset also perturbed ß-cell function and insulin resistance indices, damaged pancreas microanatomy, while disrupting the expression of insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and glucose transporter isoform 4 (GLUT-4) mRNA. Oral treatment of diabetic animals with TCA significantly (p < 0.05) ameliorated alterations due to T2DM induction in a manner comparable with glibenclamide. These results suggest TCA exerts its antidiabetic action by reversing insulin resistance, improving glucose transport and activating PI3K/AKT signalling.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Resistência à Insulina , Extratos Vegetais , Terminalia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Estreptozocina , Terminalia/química
13.
Biomarkers ; 27(5): 488-495, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35400254

RESUMO

BACKGROUND: The cardio-protective effects of Terminalia catappa and Terminalia chebula are well-recognized in Ayurveda for its antimicrobial, antidiabetic and antioxidant potentials. The present study evaluates the effects of T. catappa leaves (Tct.LE) and T. chebula fruits (Tce.FE) against doxorubicin (DOX)-induced rats through analysis of the cardiac biomarkers, tricarboxylic acid (TCA) cycle enzymes and respiratory chain enzymes for their cardio-protective properties. MATERIALS AND METHODS: This study includes 42 adult male Albino Wistar rats randomized into seven groups for 21-days. Groups were categorized as control; DOX (1.5 mg/kg) induced negative control; basal diet with 300 mg/kg of Tct.LE, with 300 mg/kg Tce.FE; DOX with 300 mg/kg of Tct.LE, Tce.FE, and propranolol (25 mg/kg). RESULTS AND DISCUSSION: The doses of 300 mg/kg of both plants have a significant effect on the TCA cycle, respiratory and lysosomal enzymes activity. The troponin levels are significantly reduced in plant treated group than the DOX-treated rats when compared with the control and propranolol treated group. Likewise, the increased level of creatine kinase-muscle/MB, creatine kinase and lipid profile in the DOX-treated animals were significantly reduced upon being treated with extracts. CONCLUSION: The cardio-protective activity of Tct.LE leaves and Tce.FE indicate its potential use in the management of cardiovascular diseases.


Assuntos
Cardiomiopatias , Terminalia , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/prevenção & controle , Creatina Quinase , Doxorrubicina/efeitos adversos , Frutas , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Propranolol , Ratos , Ratos Wistar , Terminalia/química
14.
Brain Res Bull ; 184: 76-87, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35398540

RESUMO

As a psychoactive substance abused worldwide, methamphetamine (METH) abuse leads to multiple neurodegenerative symptoms including memory deficits. Terminalia chebula retzius extracts (TREs) isolated by our lab have great antioxidant activity and its effect on METH-induced memory deficits has not been investigated yet. The present study was designed to investigate the protective effect of TREs on METH induced cell apoptosis in vitro and memory deficits in vivo. The results showed that TREs treatment attenuated free radical release and improved cell survival of primary hippocampal neurons after METH injury. In the Morris water maze task, TREs treatment reversed METH-induced learning and memory deficits in acquisition and retention. Moreover, TREs reduced oxidative stress in the serum and hippocampus of mice. Additionally, extracellular regulated protein kinases (ERK1/2) pathway and the nuclear factor E2-related factor 2 (Nrf2) pathway were inactivated after METH treatment, and were significantly activated after TREs pretreatment. These findings suggest that TREs may exert potent neuroprotective effect via activation of both ERK and Nrf2 pathways, thus providing a basis for its potential use for ameliorating memory deficits induced by METH.


Assuntos
Metanfetamina , Terminalia , Animais , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Metanfetamina/toxicidade , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Terminalia/metabolismo
15.
Med Sci (Basel) ; 10(1)2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35323216

RESUMO

Anogeissus acuminata is used to treat wounds, diarrhoea, dysentery, and skin ailments. However, its hepatoprotective effect against ethanol-induced liver damage is yet to be reported. The phenolic-enriched ethyl acetate fraction of Anogeissus acuminata (AAE) was evaluated for hepatoprotective activity against ethanol-induced liver toxicity in rats. The intoxicated animals were treated with a phenolic-rich fraction of Anogeissus acuminata (AAE) (100 and 200 mg/kg) and silymarin (100 mg/kg). The antioxidant activity of AAE was analysed. Biochemical markers (ALT, AST, ALP, GGT, and TBL) for liver injury in ethanol-administered animals resulted in higher levels of key serum biochemical injury markers, as evidenced by increased levels of ALT (127.24 ± 3.95), AST (189.54 ± 7.56), ALP (263.88 ± 12.96), GGT (91.65 ± 3.96), and TBL (2.85 ± 0.12) compared to Group I ALT (38.67 ± 3.84), AST (64.45 ± 5.97), GGT (38.67 ± 3.84), and TBL (0.53 ± 064) (p < 0.05). AAE administration decreased serum biochemical liver injury markers as manifested in Group III animals' ALT (79.56 ± 5.16), AST (151.76 ± 6.16), ALP (184.67 ± 10.12), GGT (68.24 ± 4.05), TBL (1.66 ± 0.082) (p < 0.05), and Group IV ALT (55.54 ± 4.35), AST (78.79 ± 4.88), ALP (81.96 ± 9.43), GGT (47.32 ± 2.95), TBL (0.74 ± 0.075) (p < 0.05). Group IV exhibited the most significant reduction in serum biochemical markers as compared to Group III (p < 0.05) and close to silymarin-treated Group V ALT (44.42 ± 3.15), AST (74.45 ± 5.75), ALP (67.32 ± 9.14), GGT (42.43 ± 2.54), TBL (0.634 ± 0.077). Gene expression indices and histoarchitecture were evaluated to demonstrate the potential of AAE. The bioactive fraction of Anogeissus acuminata was rich in phenolics and flavonoid content. GC-MS analysis identified gallic acid, palmitic acid, cis-10-heptadecenoic acid, 9-octadecenoic acid, epigallocatechin, 2,5-dihydroxyacetophenone, and catechin. Oral administration of AAE (100 and 200 mg/kg) lowered the elevated levels of the biochemical markers and interleukin, and enhanced the level of enzymatic antioxidant. It also downregulated the expression level of proapoptotic genes and upregulated the expression level of the antiapoptotic gene along with improved liver histopathology.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Silimarina , Terminalia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Etanol , Fenóis/farmacologia , Fenóis/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/metabolismo , Ratos , Silimarina/farmacologia , Silimarina/uso terapêutico , Terminalia/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 47(6): 1618-1624, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35347961

RESUMO

Aconiti Kusnezoffii Radix Cocta is one of the most commonly used medicinal materials in Mongolian medicine. Due to the strong toxicity of Aconiti Kusnezoffii Radix Cocta, Mongolian medicine often uses Chebulae Fructus, Glycyrrhizae Radix et Rhizoma to reduce the toxicity, so as to ensure the curative effect of Aconiti Kusnezoffii Radix Cocta while ensuring its clinical curative effect, but the mechanism is not clear. The aim of this study was to investigate the effects of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Aconiti Kusnezoffii Radix Cocta on the mRNA transcription and protein translation of cytochrome P450(CYP450) in the liver of normal rats. Male SD rats were randomly divided into negative control(NC) group, phenobarbital(PB) group(0.08 g·kg~(-1)·d~(-1)), Chebulae Fructus group(0.254 2 g·kg~(-1)·d~(-1)), Glycyrrhizae Radix et Rhizoma group(0.254 2 g·kg~(-1)·d~(-1)), Aconiti Kusnezoffii Radix Cocta group(0.254 2 g·kg~(-1)·d~(-1))and compatibility group(0.254 2 g·kg~(-1)·d~(-1),taking Aconiti Kusnezoffii Radix Cocta as the standard). After continuous administration for 8 days, the activities of total bile acid(TBA), alkaline phosphatase(ALP), amino-transferase(ALT) and aspartate aminotransferase(AST)in serum were detected, the pathological changes of liver tissue were observed, and the mRNA and protein expression levels of CYP1 A2, CYP2 C11 and CYP3 A1 were observed. Compared with the NC group, the serum ALP, ALT and AST activities in the Aconiti Kusnezoffii Radix Cocta group were significantly increased, and the ALP, ALT and AST activities were decreased after compatibility. At the same time, compatibility could reduce the liver injury caused by Aconiti Kusnezoffii Radix Cocta. The results showed that Aconiti Kusnezoffii Radix Cocta could inhibit the expression of CYP1 A2, CYP2 C11 and CYP3 A1, and could up-regulate the expression of CYP1 A2, CYP2 C11 and CYP3 A1 when combined with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma. The level of translation was consistent with that of transcription. The compatibility of Chebulae Fructus and Glycyrrhizae Radix et Rhizoma with Aconiti Kusnezoffii Radix Cocta could up-regulate the expression of CYP450 enzyme, reduce the accumulation time of aconitine in vivo, and play a role in reducing toxicity, and this effect may start from gene transcription.


Assuntos
Sistema Enzimático do Citocromo P-450 , Fígado , Animais , Sistema Enzimático do Citocromo P-450/genética , Medicamentos de Ervas Chinesas , Glycyrrhiza , Masculino , Extratos Vegetais , Ratos , Ratos Sprague-Dawley , Terminalia
17.
PLoS One ; 17(3): e0266094, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35358239

RESUMO

OBJECTIVES: Owing to extraordinary healing power, Terminalia species have been used in traditional medicine systems to treat various diseases. Many folklore uses of Terminalia neotaliala (Madagascar's almond) included treating arterial hypertension, diabetes, diarrhea, dysentery, colic, oral and digestive candidiasis, intestinal parasitic infections, inflammatory skin conditions, postpartum care, and mycotic infections but nevertheless scientifically explored for its medicinal and pharmacological importance. Therefore, the current study intended to prepare methanolic extract and its fractionation with hexane, chloroform, and butanol followed by evaluation of their polyphenolic content, biological activities, and LCMS analysis. The biological study included antioxidant activity and enzyme inhibition assay i.e., α-glucosidase and urease. The insight study of biologically active secondary metabolites of butanol fraction (BUAE) was performed through LCMS. METHODS: The total phenolic content (TPC) and total flavonoid content (TFC) of hydroalcoholic and its fractions were estimated using the Folin-Ciocalteu and aluminum chloride method. The total tannin content (TTC) was determined using the Folin-Denis spectrophotometric method. Similarly, the antioxidant potential of HAAE, HEAE, CFAE, and BUAE was determined using four methods as DPPH (1,1-diphenyl-2-picrylhydrazyl), 2,2-azinobis(3-ethylbenothiazoline)-6-sulfonic acid, cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP). The sample extracts were also evaluated against two clinically important enzymes i.e., α-glucosidase and urease. RESULTS: The BUAE (butanol aerial fraction) showed the highest TPC (234.79 ± 0.12 mg.GAE.g-1 DE), TFC (320.75 ± 12.50 mg.QE.g-1 DE), and TTC (143.36 ± 4.32 mg.TA.Eq.g-1 DE). The BUAE also showed the highest scavenging potential determined by DPPH (642.65 ± 1.11 mg.TEq.g-1 DE) and ABTS (543.17 ± 1.11 mg.TEq.g-1 DE), and the metal-reducing capacity determined by CUPRAC (1510.41 ± 4.45 mg.TEq.g-1 DE) and FRAP (739.81 ± 19.32 mg.TEq.g-1 DE). The LCMS of BUAE identified 18 different biologically active phytoconstituents validating a rich source of hydrolyzable tannins including ellagitannins and gallitannins. CONCLUSION: The present study concluded that T. neotaliala is a rich source of polyphenols capable of neutralizing the damage caused by free radical accumulation in the cells and tissues. The significant antioxidant results and identification of high molecular weight hydrolyzable tannins enlightened the medicinal importance of T. neotaliala.


Assuntos
Antioxidantes , Terminalia , Antioxidantes/química , Antioxidantes/farmacologia , Butanóis , Flavonoides , Taninos Hidrolisáveis , Fenóis/química , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Urease , alfa-Glucosidases
18.
Ann Hepatol ; 27(4): 100701, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35351639

RESUMO

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) ranks third on the list of the leading cause for cancer death globally. The treatment of HCC patients is unsatisfactory. However, the traditional Chinese medicine Chebulae Fructus has potential efficacy in the treatment of HCC. MATERIALS AND METHODS: We mined the active ingredients of Chebulae Fructus and its main targets from the Traditional Chinese Medicine Systems Pharmacology database. HCC-related datasets were downloaded from The Cancer Genome Atlas database and differentially expressed genes (DEGs) in HCC were obtained by differential expression analysis. Top10 small molecule compounds capable of reversing HCC pathology were screened by the Connectivity Map database based on DEGs. Ellipticine, an extract of Chebulae Fructus, had the potential to reverse HCC pathology. Protein-Protein Interaction (PPI) networks of DEGs in HCC were constructed using STRING. Eighteen potential targets of Chebulae Fructus for the treatment of HCC were obtained by taking intersection of DEGs in HCC with targets corresponding to the active constituents of Chebulae Fructus. In addition, MTT assay was also employed to examine the effect of ellipticine on HCC cell viability. RESULTS: It has been shown that ellipticine and ellagic acid have antitumor activity. Random Walk with Restart analysis of PPI networks was performed using potential targets as seeds, and the genes with the top 50 affinity coefficients were selected to construct a drug-active constituent-gene interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of key genes involved in the treatment of HCC with Chebulae Fructus demonstrated that these genes were mainly enriched in signaling pathways related to tumor metabolism such as cAMP signaling pathway and Ras signaling pathway. Finally, it was verified by MTT assay that proliferation of HCC cells could be remarkably hindered. CONCLUSIONS: We excavated ellipticine, a key active constituent of Chebulae Fructus, by network pharmacology, and elucidated the signaling pathways involved in Chebulae Fructus, providing a theoretical basis for the use of Chebulae Fructus for HCC clinical application.


Assuntos
Carcinoma Hepatocelular , Elipticinas , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Farmacologia em Rede , Extratos Vegetais , Mapas de Interação de Proteínas , Terminalia
19.
J Pharm Pharmacol ; 74(5): 718-729, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35134979

RESUMO

OBJECTIVES: Hydrolysable tannin fraction (HTF) derived from Terminalia chebula fruit pericarps was assessed for its anti-inflammatory potential in LPS-induced RAW 264.7 cells. Its molecular mechanism was also established and compared with individual tannins - chebulagic acid (CH) and corilagin (CO). METHODS: The effect of HTF on LPS-stimulated RAW 264.7 cells was studied by estimating the release of NO, ROS, cytokines and changes in nuclear morphology by DAPI staining. Furthermore, the effect of HTF, CO and CH was compared with the expression of p65, p38 and pERK proteins by immunoblotting and the mRNA transcript level of COX-2, iNOS and TNF-α by quantitative PCR. The in-silico interactions of various hydrolysable tannins present in HTF with molecular targets of inflammation were studied using Maestro software. KEY FINDINGS: HTF at the dose levels of 25, 50 and 100 µg/ml was able to decrease the release of NO, ROS and cytokines from LPS-induced RAW 264.7 cells without disturbing the cell nuclear morphology. Investigation of molecular mechanism revealed that inhibition of NF-κB and MAPK signalling pathways was responsible for its anti-inflammatory action. The effect of HTF was higher than the individual tannins CH and CO. CONCLUSION: HTF can be developed as an effective anti-inflammatory agent.


Assuntos
NF-kappa B , Terminalia , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Frutas , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais , Células RAW 264.7 , Espécies Reativas de Oxigênio , Transdução de Sinais , Taninos/farmacologia
20.
Molecules ; 27(3)2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35164341

RESUMO

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


Assuntos
Antivirais/farmacologia , Hepacivirus/enzimologia , Serina Proteases/química , Serina Proteases/metabolismo , Taninos/farmacologia , Terminalia/química , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Antivirais/efeitos adversos , Antivirais/química , Benzopiranos/farmacologia , Domínio Catalítico , Simulação por Computador , Glucosídeos/farmacologia , Hepacivirus/efeitos dos fármacos , Taninos Hidrolisáveis/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Farmacologia em Rede , Extratos Vegetais/farmacologia , Ligação Proteica , Conformação Proteica , Taninos/efeitos adversos , Taninos/química , Proteínas não Estruturais Virais/antagonistas & inibidores
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