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1.
Arch Microbiol ; 206(1): 25, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38108905

RESUMO

Plant extracts have been used to treat microbiological diseases for centuries. This study examined plant triterpenoids tormentic acid (TA) and 23-hydroxycorosolic acid (HCA) for their antibiofilm effects on Staphylococcus aureus strains (MTCC-96 and MTCC-7405). Biofilms are bacterial colonies bound by a matrix of polysaccharides, proteins, and DNA, primarily impacting healthcare. As a result, ongoing research is being conducted worldwide to control and prevent biofilm formation. Our research showed that TA and HCA inhibit S. aureus planktonic growth by depolarizing the bacterial membrane. In addition, zone of inhibition studies confirmed their effectiveness, and crystal violet staining and biofilm protein quantification confirmed their ability to prevent biofilm formation. TA and HCA exhibited substantial reductions in biofilm formation for S. aureus (MTCC-96) by 54.85% and 48.6% and for S. aureus (MTCC-7405) by 47.07% and 56.01%, respectively. Exopolysaccharide levels in S. aureus biofilm reduced significantly by TA (25 µg/mL) and HCA (20 µg/mL). Microscopy, bacterial motility, and protease quantification studies revealed their ability to reduce motility and pathogenicity. Furthermore, TA and HCA treatment reduced the mRNA expression of S. aureus virulence genes. In silico analysis depicted a high binding affinity of triterpenoids for biofilm and quorum-sensing associated proteins in S. aureus, with TA having the strongest affinity for TarO (- 7.8 kcal/mol) and HCA for AgrA (- 7.6 kcal/mol). TA and HCA treatment reduced bacterial load in S. aureus-infected peritoneal macrophages and RAW264.7 cells. Our research indicates that TA and HCA can effectively combat S. aureus by inhibiting its growth and suppressing biofilm formation.


Assuntos
Staphylococcus aureus , Triterpenos , Triterpenos/farmacologia , Carga Bacteriana , Biofilmes
2.
Eur J Med Chem ; 258: 115629, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37437351

RESUMO

The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is highly contagious infection that breaks the healthcare systems of several countries worldwide. Till to date, no effective antiviral drugs against COVID-19 infection have reached the market, and some repurposed drugs and vaccines are prescribed for the treatment and prevention of this disease. The currently prescribed COVID-19 vaccines are less effective against the newly emergent variants of concern of SARS-CoV-2 due to several mutations in viral spike protein and obviously there is an urgency to develop new antiviral drugs against this disease. In this review article, we systematically discussed the anti-SARS-CoV-2 and anti-inflammatory efficacy of two flavonoids, baicalein and its 7-O-glucuronide, baicalin, isolated from Scutellaria baicalensis, Oroxylum indicum, and other plants as well as their pharmacokinetics and oral bioavailability, for development of safe and effective drugs for COVID-19 treatment. Both baicalein and baicalin target the activities of viral S-, 3CL-, PL-, RdRp- and nsp13-proteins, and host mitochondrial OXPHOS for suppression of viral infection. Moreover, these compounds prevent sepsis-related inflammation and organ injury by modulation of host innate immune responses. Several nanoformulated and inclusion complexes of baicalein and baicalin have been reported to increase oral bioavailability, but their safety and efficacy in SARS-CoV-2-infected transgenic animals are not yet evaluated. Future studies on these compounds are required for use in clinical trials of COVID-19 patients.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Humanos , Vacinas contra COVID-19 , Tratamento Farmacológico da COVID-19 , Flavonoides/farmacologia , Antivirais/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
3.
RSC Adv ; 13(10): 6747-6759, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36860543

RESUMO

Here, we report a simple, efficient, and green protocol for the one-pot synthesis of pyrano[2,3-c]pyrazole derivatives via a sequential three-component strategy using aromatic aldehydes, malononitrile and pyrazolin-5-one in a water-SDS-ionic liquid system. This is a base and volatile organic solvent-free approach that could be applicable to a wide substrate scope. The key advantages of the method over other established protocols are very high yield, eco-friendly conditions, chromatography-free purification and recyclability of the reaction medium. Our study revealed that the N-substituent present in pyrazolinone controls the selectivity of the process. N-unsubstituted pyrazolinone favours the formation of 2,4-dihydro pyrano[2,3-c]pyrazoles whereas under identical conditions N-phenyl substituent pyrazolinone favours the formation 1,4-dihydro pyrano[2,3-c]pyrazoles. Structures of the synthesized products were established by NMR and X-ray diffraction techniques. Energy optimized structures and energy gaps between the HOMO-LUMO of some selected compounds were estimated using density functional theory to explain the extra stability of the 2,4-dihydro pyrano[2,3-c]pyrazoles over 1,4-dihydro pyrano[2,3-c]pyrazoles.

4.
J Am Nutr Assoc ; 42(6): 573-587, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35984397

RESUMO

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer. Its incidence is high in certain geographic regions, and it is correlated with chewing tobacco. Epidermal growth factor receptor (EGFR), induced by tobacco carcinogens, is overexpressed in OSCC, leading to poor prognosis. Thus, EGFR inhibitors are promising agents against OSCC. High cost and toxicity of existing EGFR inhibitors necessitate alternative EGFR-targeted therapy. Here, we tested the antitumor potential of ethyl acetate fraction of an ethnomedicinal tree, Oroxylum indicum stem bark extract (OIEA) in a 4-nitroquinoline-1-oxide (4NQO)-induced oral carcinogenesis model. METHODS: OIEA was prepared by solvent extraction method, and subsequently its in vitro radical scavenging activities were measured. High-performance liquid chromatography (HPLC) analysis of OIEA was done to identify the constituent active compounds. Hemolytic, trypan blue exclusion, and MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assays were performed in normal and cancer cells to select an optimum dose of OIEA for antitumor activity study in 4NQO-induced oral cancer in F344 rats. Measurement of tumor volume, weight, and cell count was followed by tumor cell cycle analysis and comet and annexin V/Propidium Iodide (PI) assay. Pro-apoptotic markers were detected by western blot testing. Molecular docking was done to predict the interaction between OIEA active component and EGFR or phosphatidylinositol-3-kinase (PI3K), which was further validated biologically. Finally, hepatic and renal function testing and histopathology were performed. RESULTS: OIEA reduced tumor burden and increased survivability of the tumor-bearing rats significantly as compared to untreated tumor bearers. HPLC revealed oroxylin A as the predominant bioactive component in OIEA. Molecular docking predicted significant binding between oroxylin A and EGFR as well as PI3K, which was confirmed by western blot analysis of in vivo samples. OIEA also ameliorated hepato-, renal- and myelotoxicity induced by 4NQO. CONCLUSION: OIEA reduces 4NQO-induced OSCC by modulating the EGFR/PI3K/AKT signaling cascade and also ameliorated toxicity in tumor bearers.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Ratos , Animais , Neoplasias Bucais/induzido quimicamente , Proteínas Proto-Oncogênicas c-akt/análise , Fosfatidilinositol 3-Quinases/análise , Fosfatidilinositol 3-Quinase/análise , Casca de Planta/química , Simulação de Acoplamento Molecular , Ratos Endogâmicos F344 , Extratos Vegetais/farmacologia , Receptores ErbB/análise , Carcinoma de Células Escamosas de Cabeça e Pescoço
5.
Microb Pathog ; 139: 103901, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31790796

RESUMO

Formation of biofilm is the major cause of Pseudomonas aeruginosa associated pathological manifestations in the urinary tract, respiratory system, gastrointestinal tract, skin, soft tissues etc. Triterpenoid group of compounds have shown their potential in reducing planktonic and biofilm form of bacteria. Sarcochlamys pulcherrima (Roxb.) Gaud. is an ethnomedicinal plant traditionally used for its anti-microbial and anti-inflammatory property. In the present study two triterpenoids, have been isolated from this plant, characterised and evaluated for their antibacterial and antibiofilm potential against P. aeruginosa. Compounds were characterised as 2α, 3ß, 19α-trihydroxy-urs-12-ene-28-oic acid (Tormentic acid) and 2α, 3ß, 23-trihydroxyurs-12-ene-28-oic acid (23-hydroxycorosolic acid) through spectroscopic studies viz. infrared (IR), nuclear magnetic resonance (NMR) and mass spectroscopy (MS). Depolarization of bacterial membrane and zone of inhibition studies revealed that both the compounds inhibited the growth of planktonic bacteria. Compounds were also found to inhibit the formation of P. aeruginosa biofilm. Inhibition of biofilm found to be mediated through suppressed secretion of pyoverdin, protease and swarming motility of P. aeruginosa. Gene expression study, in silico binding analysis, in vivo bacterial load and tissue histology observations also supported the antibiofilm activity of both the compounds. In vitro and in vivo study showed that both compounds were non-toxic. The study has explored the antibacterial and antibiofilm effect of two triterpenes isolated for the first time from S. pulcherrima.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Urticaceae/química , Antibacterianos/química , Estrutura Molecular , Extratos Vegetais/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Triterpenos/química
6.
FEBS J ; 284(12): 1830-1854, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28398698

RESUMO

The recurrence of breast cancer in patients is a persistent challenge to the medical fraternity. Breast tumor contains a small population of cells with high tumor initiating and metastatic potential, known as cancer stem cells (CSCs), which are resistant to existing chemotherapeutics. CSCs contribute to the aggressiveness of triple negative breast cancers (TNBCs), thereby necessitating the identification of molecular targets on breast CSCs. TNBC cell line MDA-MB-231, in comparison with MCF-7, demonstrated a higher expression of epidermal growth factor receptor (EGFR). Thus, the naturally occurring flavanone, chrysin, with limited potential as a chemotherapeutic agent, was structurally modified by designing an analog with EGFR binding affinity using a molecular docking approach and subsequently synthesised. Chrysin analog CHM-09 and known EGFR inhibitors demonstrated a comparable anti-proliferative, anti-migratory activity along with the induction of apoptosis and cell cycle arrest in MDA-MB-231. Furthermore, sorted CD24- /CD44+ -breast CSCs and CD24+ -breast cancer cells from MDA-MB-231 demonstrated a markedly high expression of EGFR in the former than in the latter. CHM-09 and EGFR inhibitors could perturb EGF-induced EGFR signalling of breast CSC proliferation, migration, mammosphere formation and mesenchymal tri-lineage differentiation. CHM-09 or EGFR inhibitors not only led to inactivation of EGFR downstream signalling pathways such as Akt, extracellular signal regulated kinase and signal transducer and activator of transcription 3, but also induction of mesenchymal-epithelial transition as confirmed by decreased N-cadherin and increased E-cadherin expression. Finally, combinatorial treatment of EGFR inhibitors and doxorubicin led to significant increase in breast CSCs responsiveness to a chemotherapeutic drug. The results of the present study suggest that EGFR is a therapeutic target in breast CSCs and that abrogation of EGFR signalling along with chemotherapeutic drugs is an effective approach against breast cancer.


Assuntos
Antineoplásicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Células-Tronco Neoplásicas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Feminino , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Células Tumorais Cultivadas
7.
Nutr Cancer ; 68(4): 689-707, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27144503

RESUMO

Parkia javanica is a leguminous tree, various parts of which are used as food and folklore medicine by the ethnic groups of northeastern India. The present study investigates the in vitro and in vivo anticancer effect of aqueous methanol extract of P. javanica fruit (PJE). HPLC analysis was done to establish the fingerprint chromatogram of PJE and its in vitro radical scavenging activity was measured. PJE caused significant cytotoxicity in sarcoma-180 (S-180), A549, AGS, and MDA-MB435S cancer cells in vitro. Exploration of the mechanistic details in S-180 cells suggested that the reduced cell viability was mediated by induction of apoptosis. Increased expression of proapoptotic proteins such as p53, p21, Bax/Bcl2, cytochrome c (Cyt c), caspase 9, and cleaved poly(ADP-ribose) polymerase, and decrease in proliferative and antiapoptotic markers (Ki-67, Proliferating Cell Nuclear Antigen [PCNA], Bcl-2) validated the anticancer effect of PJE. A decline in the relative fluorescence emission upon staining S-180 cells with Rhodamine 123 (Rh 123), enhanced expression of cytosolic Cyt c and mitochondrial Bax, and inhibition of apoptosis in the presence of caspase-9 inhibitor in PJE-treated cells indicated intrinsic pathway of apoptosis. Liver function test and hepatic antioxidant enzymes demonstrated non-toxicity of PJE. Finally, the detection of PJE in sera by HPLC confirmed its bioavailability.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Fabaceae/química , Extratos Vegetais/farmacologia , Sarcoma 180/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Caspase 9/metabolismo , Inibidores de Caspase/farmacologia , Linhagem Celular Tumoral , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/sangue , Extratos Vegetais/química , Sarcoma 180/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Asian Pac J Trop Med ; 7S1: S332-41, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25312146

RESUMO

OBJECTIVE: To explore anti-enteric properties of Dillenia pentagyna Roxb. (D. pentagyna) fruit extract fractions of different polarities by comparative antimicrobial activity against municipal sewage microflora and to assess its urease inhibition potential. METHODS: Different polar fractions of D. pentagyna fruit extracts were studied by antimicrobial susceptibility test with several adjustments in this resource limited setup. Tests were done against municipal sewage microbes at various bacterial load (initially with 1.0 McFarland followed by 1.5 McFarland) using basal (nutrient agar) and selective medium (MacConkey's agar with and without supplementation of 5% NaCl). All assays statistically scaled with a gradient for uniformity and comparison with ciprofloxacin standard. Fraction with highest activity was studied for urease inhibition potential by kinetic method. RESULTS: DP-47 separated by 30% ethyl acetate (EtOAc) in CHCl3 from CHCl3 extract had slightly higher antimicrobial potency (y=0.758x+7.571) as dissolved in methanol than in dimethylsulfoxide (y=0.300x+6.000). EtOAc extract fractioned by 10% methanol in EtOAc (DP-43) was more potent antimicrobial (y=1.428x+8.392) and soluble in water. Butanol extract fractioned by water (DP-50) showed highest antimicrobial potency (y=3.384x+2.000) than both DP-47 and DP-43 in disk diffusion assays. In higher microbial load DP-50 was potent antimicrobial (y=1.538x+3.000) and completely inhibited any vegetative growth at lower load of 0.5 McFarland. In selective environment DP-50 was effective (y=1.076x+7.500 in MacConkey's, y=1.307x+6.000 in 5% NaCl supplemented). It was evident that enteric pathogens may not easily develop resistance against DP-50 and at high concentration it inhibited urease activity by 94.87%. The standard inhibition by thiourea (1%) is 33.914%. CONCLUSIONS: Highly polar fraction of D. pentagyna Roxb. fruit extract DP-50 have potential antimicrobial activity against sewage microflora in basal and selective culture indicating its potential against non-fastidious, coliforms and Vibrio pathogens. Urease inhibition indicates efficacy against Helicobactor pylory.

9.
Eur J Med Chem ; 87: 328-35, 2014 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-25264585

RESUMO

One new flavonol methyl ether (1), along with four known compounds from the leaves of methanol extract of Vitex peduncularis Wall and three known compounds from the leaves of methanol extract of Vitex pinnata Linn (Verbenaceae) were isolated. The chemical structure of the new compound was established by detailed spectroscopic studies. The in vitro antileishmanial activities of 1 against both Leishmania donovani promastigote and amastigote forms were evaluated. To characterize the effector mechanism of compound 1 against Leishmania parasite infected THP-1 macrophage cells, RT-PCR analysis of inducible nitric oxide synthase 2 (iNOS2) was done followed by measurement of nitric oxide generation by Griess reaction. Pentostam (sodium antimonygluconate) was used as reference drug. Compound 1 exhibited better antileishmanial activity than sodium antimonygluconate (SAG) (having IC50 values for promastigote, 2.4 and 58.5 µM and for amastigotes, 0.93 and 36.2 µM, respectively). Compound 1 was less toxic than SAG towards THP-1 having CC50 of 123.7 µM and 364.3 µM, respectively. Moreover, compound 1 was found to induce a potent host-protective response by enhancing NO generation and iNOS2 expression in infected macrophages to prevent the progression of Leishmania parasite.


Assuntos
Flavonóis/química , Flavonóis/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Leishmania donovani/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/genética , Folhas de Planta/química , Vitex/química , Linhagem Celular , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/parasitologia , Leishmania donovani/citologia , Leishmania donovani/fisiologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Éteres Metílicos/química , Nitritos/metabolismo
10.
Nat Prod Commun ; 7(1): 1-2, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22428227

RESUMO

A new iridoid, shanzhiol (1), was isolated from the aerial parts of Mussaenda roxburghii. The structure was established by spectroscopic (including 2D NMR) and chemical methods. Shanzhiol (1) showed mild antibacterial activity against both Staphylococcus aureus and Escherichia coli with a MIC of 100 microg/mL by the broth dilution method.


Assuntos
Iridoides/isolamento & purificação , Rubiaceae/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Iridoides/química , Iridoides/farmacologia , Staphylococcus aureus/efeitos dos fármacos
11.
Chem Pharm Bull (Tokyo) ; 54(5): 679-81, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16651765

RESUMO

A new C-alkylglucoside, diospyrodin [beta-1C-(1'S*,2'R*,3'R*,4'S*-1',2',3',4',5'-pentahydroxypentyl)-glucopyranoside] (1) has been isolated as its nonaacetate from the leaves and stems of Diospyros nigra. Its structure was elucidated on the basis of chemical and spectral properties and a single crystal X-ray analysis. It showed antimicrobial activity against Gram-positive and Gram-negative bacteria.


Assuntos
Antibacterianos/química , Diospyros/química , Glucosídeos/química , Acetilação , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Glucosídeos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Relação Estrutura-Atividade , Difração de Raios X
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