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1.
Phytochem Anal ; 35(4): 690-707, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38212263

RESUMO

INTRODUCTION: This research explores sustainable applications for waste generated from fenugreek (Trigonella foenum-graecum), a plant with both nutritional and medicinal uses. The study specifically targets waste components as potential sources of nutrients and bioactive compounds. OBJECTIVES: The focus is to conduct detailed metabolic profiling of fenugreek waste, assess its anti-inflammatory properties by studying its cyclooxygenase (COX) inhibitory effect, and correlate this effect to the metabolite fingerprint. MATERIALS AND METHODS: Ethanolic extracts of fenugreek fruit pericarp and a combination of leaves and stems were subjected to untargeted metabolic profiling using liquid chromatography-mass spectrometry integrated with online database searches and molecular networking as an effective dereplication strategy. The study also scrutinized the COX inhibitory capabilities of these extracts and saponin-rich fractions prepared therefrom. Molecular docking was employed to investigate the specific interactions between the identified saponins and COX enzymes. RESULTS: The analysis led to the annotation of 81 metabolites, among which saponins were predominant. The saponin-rich fraction of the fruit pericarp extract displayed the strongest COX-II inhibitory activity in the in vitro inhibition assay (IC50 value of 81.64 ± 3.98 µg/mL). The molecular docking study supported the selectivity of the identified saponins towards COX-II. The two major identified saponins, namely, proto-yamogenin 3-O-[deoxyhexosyl (1 → 2)] [hexosyl (1 → 4)] hexoside 26-O-hexoside and trigofenoside A, were predicted to have the highest affinity to the COX-II receptor site. CONCLUSION: In the present study, we focused on the identification of COX-II inhibitory saponins in fenugreek waste through an integrated approach. The findings offer valuable insights into potential anti-inflammatory and cancer chemoprotective applications of fenugreek waste.


Assuntos
Inibidores de Ciclo-Oxigenase 2 , Metabolômica , Simulação de Acoplamento Molecular , Saponinas , Espectrometria de Massas em Tandem , Trigonella , Trigonella/química , Saponinas/química , Saponinas/farmacologia , Saponinas/análise , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Metabolômica/métodos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ciclo-Oxigenase 2/metabolismo
2.
Bioorg Chem ; 139: 106743, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37490810

RESUMO

The aim of the present study is to explore the potential anticancer effect of the cardenolide; acovenoside A against non-small cell lung cancer (NSCLC), understand its molecular mechanism in inducing apoptosis and show the effect of its combination with carboplatin and taxol. MTT assay showed that the combination of acovenoside A with taxol and carboplatin caused 78.9% cytotoxicity reflecting the synergistic effect. The triple combination showed the best growth inhibition efficiency where the number of cells at the G2/M phase was decreased and boosted up apoptotic and necrotic activity. The combination also showed the most remarkable increase in gene expression of Bax and p53 and the least level of Bcl2. The gene expression of miRNA181a and miRNA630 was significantly upregulated in cell lines treated with the combination. The present study has proven that the underlying mechanism of acovenoside A is partially attributed to the upregulation of miR-630 and miR-181a gene expressions which in turn targets the intrinsic apoptosis genes as p53, Bax and Bcl2 as well as caspase 3. The present study is the first to address the valuable effect of using acovenoside A together with carboplatin and taxol in the treatment of NSCLC via exerting apoptotic, antiproliferative, and cytotoxic effects..


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carboplatina/farmacologia , Paclitaxel/farmacologia , Neoplasias Pulmonares/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células , Linhagem Celular Tumoral
3.
Phytother Res ; 37(12): 5464-5472, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37675925

RESUMO

Hypertension is a serious concern as it is one of the causes of kideny failure and pulmonary fibrosis. An important therapeutic strategy for treating chronic hypertension is to inhibit the angiotensin converting enzyme (ACE). ACE inhibition reduces kidney damage, pulmonary artery pressure, and high blood pressure. Due to their high efficacy and low risk of side effects, natural renin-angiotensin system inhibitors have drawn increasing attention over the past decades. Alkaloids, amino acids, anthocyanidins, flavonoids, glucosinolates, isoflavonoids, phenolic acids, polyphenolics, and triterpenoids are among the bioactive metabolites pocessing an impressive ACE inhibitory activity. Many herbs including Rosmarinus officinalis, Hibiscus sabdariffa, Curcuma longa, Rauwolfia serpentina, Emblica officinalis, Cynara scolymus, Punica granatum, Mucuna pruriens, Capsicum annuum, and Moringa olifera were found having ACE inhibitory activities comparable to captopril and enalpril. These enticing natural ACE inhibitors deserve to be a safeguard medicine against hypertension, respiratory distress syndrome, and chronic kidney diseases. More clinical trials are required before new natural compounds and herbs can be used to treat chronic hypertension and its ramifications, such as respiratory distress syndrome and kidney failure.


Assuntos
Hipertensão , Insuficiência Renal Crônica , Síndrome do Desconforto Respiratório , Humanos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Sistema Renina-Angiotensina , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Síndrome do Desconforto Respiratório/tratamento farmacológico
4.
Eur Arch Otorhinolaryngol ; 280(10): 4555-4560, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37300643

RESUMO

PURPOSE: Adenoidectomy, either alone or with tonsillectomy, is a common surgical procedure in the field of pediatric otorhinolaryngology. Resonance function may be altered postoperatively in the form of hypernasality, which is usually transient. This study aimed to investigate the effect of adenoid size on post-adenoidectomy hypernasality in children with a normal palate. METHODS: Seventy-one children with different degrees of adenoid hypertrophy were included in this prospective observational study. Endoscopic assessment of the adenoid size and preoperative and postoperative evaluation of speech (at 1 and 3 months) with auditory perceptual assessment (APA) and nasometry were performed. RESULTS: APA showed preoperative hyponasality in 59.1% of children and was found to be significantly related to the adenoid size, with more hyponasality in grades 3 and 4. One month postoperatively, hypernasality was detected in 26.7% of patients and was found to be related to the preoperative adenoid size with higher hypernasality in grades 3 and 4. Three months postoperatively, all patients had gained normal nasality except one (1.4%) who was subjected to a longer follow-up period. Nasometric assessment showed significant differences at the three visits (pre, 1, and 3 months postoperatively), with a negative correlation between the grade of adenoid size and nasalance scores preoperatively and a significant positive correlation between them at 1 month postoperatively. However, no significant correlation was detected at 3 months postoperatively. CONCLUSION: Transient hypernasality may develop in some patients after adenoidectomy, especially in children with a larger preoperative adenoid size. However, transient hypernasality generally resolves spontaneously within 3 months.


Assuntos
Tonsila Faríngea , Tonsilectomia , Distúrbios da Voz , Criança , Humanos , Adenoidectomia/métodos , Tonsila Faríngea/cirurgia , Tonsilectomia/efeitos adversos , Fala , Distúrbios da Voz/cirurgia , Palato
5.
J Craniofac Surg ; 34(1): e74-e78, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35882240

RESUMO

BACKGROUND: Children with cleft palate are more liable to have obstructive sleep apnea than children with normal palate due to narrow airways. Tonsillar hypertrophy is a common cause of pediatric obstructive sleep apnea; hence, it is not surprising to be encountered during cleft palate repair. The aim of this study was to evaluate the feasibility of tonsillectomy and Furlow palatoplasty performed as a 1-stage operation in patients presenting with submucous cleft palate (SMCP) and tonsillar hypertrophy. MATERIALS AND METHODS: Eleven pediatric patients with SMCP and hypertrophied tonsils were included in this case series study. Furlow palatoplasty and tonsillectomy were performed for the patients in 1 sitting. The evaluation of velopharyngeal function was done preoperatively and postoperatively via auditory-perceptual-assessment, nasometry, and flexible nasopharyngoscopy. In addition, the Epworth sleepiness scale for children/adolescents was administered to the parents to assess daytime sleepiness of their children. RESULTS: The speech improved postoperatively. Auditory-perceptual-assessment showed significant reductions in hypernasal speech, nasal air escape, and weak pressure consonants. In addition, nasometry revealed significantly decreased nasalance scores for nasal and oral sentences. A postoperative increased velar movement was observed with a significant improvement in velopharyngeal closure. The preoperative Epworth sleepiness scale for children/adolescents assessment revealed excessive daytime sleepiness in 8 patients, with significant improvement of scores postoperatively. CONCLUSIONS: Removal of hypertrophied tonsils during the repair of SMCP with Furlow palatoplasty did not negatively affect speech outcome or velar movement postoperatively. It is logical to perform both procedures simultaneously in 1 sitting to avoid postoperative sleep-related breathing disorder, which may necessitate a second stage operation.


Assuntos
Fissura Palatina , Apneia Obstrutiva do Sono , Tonsilectomia , Insuficiência Velofaríngea , Adolescente , Humanos , Criança , Fissura Palatina/cirurgia , Fissura Palatina/complicações , Tonsila Palatina/cirurgia , Tonsilectomia/efeitos adversos , Sonolência , Insuficiência Velofaríngea/cirurgia , Insuficiência Velofaríngea/etiologia , Resultado do Tratamento , Hipertrofia/cirurgia , Hipertrofia/complicações , Estudos Retrospectivos , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/complicações , Palato Mole/cirurgia
6.
Mar Drugs ; 17(8)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349625

RESUMO

Breast cancer is the most common cancer type and a primary cause of cancer mortality among females worldwide. Here, we analyzed the anticancer efficacy of a novel bromochlorinated monoterpene, PPM1, a synthetic analogue of polyhalogenated monoterpenes from Plocamium red algae and structurally similar non-brominated monoterpenes. PPM1, but not the non-brominated monoterpenes, decreased selectively the viability of several triple-negative as well as triple-positive breast cancer cells with different p53 status without significantly affecting normal breast epithelial cells. PPM1 induced accumulation of triple-negative MDA-MB-231 cells with 4N DNA content characterized by decreased histone H3-S10/T3 phosphorylation indicating cell cycle arrest in the G2 phase. Western immunoblot analysis revealed that PPM1 treatment triggered an initial rapid activation of Aurora kinases A/B/C and p21Waf1/Cip1 accumulation, which was followed by accumulation of polyploid >4N cells. Flow cytometric analysis showed mitochondrial potential disruption, caspase 3/7 activation, phosphatidylserine externalization, reduction of the amount polyploid cells, and DNA fragmentation consistent with induction of apoptosis. Cell viability was partially restored by the pan-caspase inhibitor Z-VAD-FMK indicating caspase contribution. In vivo, PPM1 inhibited growth, proliferation, and induced apoptosis in MDA-MB-231 xenografted onto the chick chorioallantoic membrane. Hence, Plocamium polyhalogenated monoterpenes and synthetic analogues deserve further exploration as promising anticancer lead compounds.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Monoterpenos/farmacologia , Antineoplásicos/farmacologia , Mama/efeitos dos fármacos , Mama/metabolismo , Neoplasias da Mama/metabolismo , Inibidores de Caspase/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Fase G2/efeitos dos fármacos , Histonas/metabolismo , Humanos , Células MCF-7 , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Plocamium/química , Rodófitas/química
7.
Stem Cells ; 35(7): 1733-1746, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28436144

RESUMO

Muscle regeneration depends on satellite cells (SCs), quiescent precursors that, in consequence of injury or in pathological states such as muscular dystrophies, activate, proliferate, and differentiate to repair the damaged tissue. A subset of SCs undergoes self-renewal, thus preserving the SC pool and its regenerative potential. Unacylated ghrelin (UnAG) is a circulating hormone that protects muscle from atrophy, promotes myoblast differentiation, and enhances ischemia-induced muscle regeneration. Here we show that UnAG increases SC activity and stimulates Par polarity complex/p38-mediated asymmetric division, fostering both SC self-renewal and myoblast differentiation. Because of those activities on different steps of muscle regeneration, we hypothesized a beneficial effect of UnAG in mdx dystrophic mice, in which the absence of dystrophin leads to chronic muscle degeneration, defective muscle regeneration, fibrosis, and, at later stages of the pathology, SC pool exhaustion. Upregulation of UnAG levels in mdx mice reduces muscle degeneration, improves muscle function, and increases dystrophin-null SC self-renewal, maintaining the SC pool. Our results suggest that UnAG has significant therapeutic potential for preserving the muscles in dystrophies. Stem Cells 2017;35:1733-1746.


Assuntos
Distrofina/genética , Grelina/genética , Músculo Esquelético/metabolismo , Distrofia Muscular Animal/metabolismo , Regeneração/genética , Células Satélites de Músculo Esquelético/metabolismo , Acilação , Animais , Contagem de Células , Diferenciação Celular , Distrofina/metabolismo , Fibrose , Regulação da Expressão Gênica , Grelina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Músculo Esquelético/patologia , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/patologia , Fenótipo , Células Satélites de Músculo Esquelético/patologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
J Nat Prod ; 80(12): 3203-3210, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29190084

RESUMO

We investigated the cytotoxic potential of the cardenolide glycoside acovenoside A against non-small-cell lung cancer cells. Lung cancer is the leading cause of cancer-related mortality and the second most common cancer diagnosed. Epidemiological studies revealed a direct correlation between the regular administration of cardiac glycosides and a lower incidence of various cancers. Acovenoside A, isolated from the pericarps of Acokanthera oppositifolia, potently inhibited proliferation and induced cytotoxicity in A549 non-small-cell lung cancer cells with an IC50 of 68 ± 3 nM after 48 h of exposure. Compared to the antineoplastic agent doxorubicin, acovenoside A was more potent in inhibiting the viability of A549 cancer cells. Moreover, acovenoside A exhibited selectivity against cancer cells, being significantly less toxic to lung fibroblasts and nontoxic for peripheral blood mononuclear cells. Analysis of the cell cycle profile in acovenoside A-treated A549 cells revealed mitotic arrest, due to accumulation of the G2/M regulators cyclin B1 and CDK1, and cytokinesis failure. Furthermore, acovenoside A affected the mitochondrial membrane integrity and induced production of radical oxygen species, which resulted in induction of canonical apoptosis, manifested by caspase 3 activation and DNA fragmentation. Based on our results, acovenoside A warrants further exploration as a potential anticancer lead.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cardenolídeos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Mitose/efeitos dos fármacos , Células A549 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Doxorrubicina/farmacologia , Estudos Epidemiológicos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Neoplasias Pulmonares/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
9.
Molecules ; 22(12)2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29186050

RESUMO

Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the flavonolignan cinchonain-I and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH) and ferric reducing antioxidant power (FRAP) assay, and in the model organism Caenorhabditis elegans. Additionally, the extract exhibited promising hepatoprotective activities in D-galactosamine (D-GaIN) treated rats. A significant reduction in the elevated levels of aspartate aminotransferase (AST), total bilirubin, gamma-glutamyltransferase (GGT), and malondialdehyde (MDA) and increase of glutathione (GSH) was observed in rats treated with the bark extract in addition to D-galactosamine when compared with rats treated with D-galactosamine alone. In conclusion, T. fischeri is apromising candidate for health-promoting and for pharmaceutical applications.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Meliaceae/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Animais , Biomarcadores , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cromatografia Líquida de Alta Pressão , Hepatócitos/efeitos dos fármacos , Masculino , Meliaceae/metabolismo , Estrutura Molecular , Compostos Fitoquímicos/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas em Tandem
10.
J Pharmacol Exp Ther ; 358(2): 262-70, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27247000

RESUMO

The current study aimed to investigate the protective effect of the cardenolide glycoside acovenoside A (AcoA) against doxorubicin-induced cardiotoxicity in mice. AcoA was isolated from the pericarps of Acokanthera oppositifolia to chemical homogeneity and characterized by means of one- and two-dimensional nuclear magnetic resonance spectroscopy. AcoA exhibited relatively low toxicity in mice (LD50 = 223.3 mg/kg bw). Repeated administration of doxorubicin induced cardiotoxicity manifested by reduced activity of myocardial membrane-bound ion pumps and elevated serum biomarkers of myocardial dysfunction, oxidative stress, and inflammation. Pretreatment of doxorubicin-exposed mice with AcoA (11.16 or 22.33 mg/kg bw, i.p.) for 2 weeks after 2 weeks of combined administration of AcoA and doxorubicin protected the animals dose dependently against doxorubicin-induced cardiotoxicity as indicated by normalization of the levels of different myocardial markers of oxidative stress (malondialdehyde, nitric oxide, total antioxidant capacity, and cardiac glutathione), serum myocardial diagnostic marker enzymes (serum cardiac troponin T, creatine kinase isoenzyme MB, aspartate aminotransferase, and lactate dehydrogenase), and inflammatory markers (c-reactive protein, tumor necrosis factor-α, and interleukin-6), as well as myocardial Na(+)/K(+)-ATPase activity. These effects were attributed to the negative impact of AcoA on transcription factors nuclear factor κB and interferon regulatory factor 3/7. Thus acovenoside A might act as a cardioprotective agent to prevent doxorubicin-induced cardiotoxicity.


Assuntos
Cardenolídeos/farmacologia , Cardiotônicos/farmacologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Animais , Apocynaceae/química , Biocatálise , Biomarcadores/sangue , Cardenolídeos/química , Cardenolídeos/isolamento & purificação , Cardiotônicos/química , Cardiotônicos/isolamento & purificação , Cardiotoxicidade/metabolismo , Cardiotoxicidade/patologia , DNA Topoisomerases Tipo II/metabolismo , Fatores Reguladores de Interferon/metabolismo , Masculino , Camundongos , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/enzimologia , Modelos Moleculares , Conformação Molecular , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo
11.
Angew Chem Int Ed Engl ; 53(45): 12205-9, 2014 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-25220828

RESUMO

The family of polyhalogenated monoterpenes from Plocamium counts over a hundred known members. Using glyceraldehyde acetonide as a chiral-pool precursor, an enantioselective and divergent strategy was developed that provides a blueprint for the synthesis of many of the small yet complex acyclic members of this family. The broad applicability of this approach is demonstrated with the short, eight-step synthesis of four natural products and three analogues. These syntheses are the first of any members of the acyclic polyhalogenated Plocamium monoterpenes and permitted the evaluation of their selectivity against a range of tumor cell lines.


Assuntos
Monoterpenos/síntese química , Neoplasias/tratamento farmacológico , Plocamium/química , Células HCT116 , Humanos , Monoterpenos/uso terapêutico , Estereoisomerismo
12.
J Ethnopharmacol ; 326: 117911, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38355028

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dolomiaea costus (Falc.), formerly Saussurea costus (Falc.) Lipsch., an ayurvedic medicinal plant, has long been recognized and utilized in diverse indigenous systems of medicine for its multifaceted therapeutic properties, including anti-inflammatory, carminative, expectorant, antiarthritic, antiseptic, aphrodisiac, anodyne, and antidiabetic effects. AIM OF THE STUDY: The potential and underlying mechanisms of D. costus root as an antidiabetic agent were investigated in this study. Additionally, the quantification of phenolic and flavonoid compounds, which dominate the extracts, was of particular interest in order to elucidate their contribution to the observed effects. MATERIALS AND METHODS: High-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was employed to analyze the chemical constituents in D. costus root aqueous extract (DCA) and D. costus root ethanolic extract (DCE). Furthermore, the inhibitory potentials of DCE and its respective fractions as well as DCA against α-amylase, α-glucosidase, and lipase enzymes were assessed. Subsequently, the efficacy of DCA and DCE extracts was evaluated using an established streptozotocin (STZ)-induced diabetic animal model; this involved administering the extracts at doses of 200 and 400 mg/kg bwt. and comparing them with a positive control (glibenclamide (Glib.) at 0.6 mg/kg bwt.). After induction of diabetes (except for negative control), all animals received the treatments orally for 21 days consecutively, followed by the collection of rat serum to assess various parameters including, glycemic and lipid profiles, liver and kidney functions, antioxidant activity, glycolysis, and gluconeogenesis pathways. RESULTS: The results of HPLC-ESI-MS/MS revealed that isochlorogenic acid A (8393.64 µg/g) and chlorogenic acid (6532.65 µg/g) were the predominant compounds in DCE and DCA, respectively. Both extracts exhibited notable antidiabetic properties, as evidenced by their ability to regulate blood glycemic and lipid profiles (glucose, insulin, HBA1C; HDL, TC, TGs), liver enzymes (ALT, ALP, AST), kidney function (urea, creatinine, uric acid), oxidative stress biomarkers (MDA), antioxidant enzymes (CAT, GSH, SOD), as well as glycolysis (glucokinase) and gluconeogenesis (G-6-P, FBP1) pathways. CONCLUSIONS: Furthermore, the administration of D. costus extracts significantly mitigated STZ-induced diabetic hyperglycemia. These results can be attributed, at least partially, to the presence of several polyphenolic compounds with potent antioxidant and anti-inflammatory activities.


Assuntos
Costus , Diabetes Mellitus Experimental , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Estreptozocina , Costus/química , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Espectrometria de Massas em Tandem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Metabolismo dos Carboidratos , Anti-Inflamatórios/farmacologia , Lipídeos/uso terapêutico , Glicemia
13.
Nat Prod Res ; 37(11): 1909-1916, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36067513

RESUMO

The ink that cephalopods secrete to hide and frighten the enemies contains a treasury rich in bioactive diverse compounds like DOPA, melanin, melanin synthase, tyrosinase, angiotensin converting enzyme, catecholamines, oligopeptides, polyphenols, flavonoids, alkaloids, polysaccharides, fatty acids and minerals. These groups of the aforementioned compounds have promising unique in-vitro and in-vivo biological activities like antioxidant activity, anti-inflammatory, vasopressin, anti-Parkinson, anti-cancer, anti-coagulant, antimicrobial, anti-retroviral, anti-ulcerogenic and immune boosting activities. Cephalopods ink can be offered in its raw state or after separation and purification of its chemical constituents for use as natural medicine to treat many diverse diseases.


Assuntos
Cefalópodes , Animais , Melaninas , Tinta , Anti-Inflamatórios/farmacologia , Polifenóis , Extratos Vegetais
14.
Nat Prod Res ; 37(24): 4280-4289, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36719419

RESUMO

Bacterial resistance to antibiotics poses a high level of danger worldwide. Bacterial resistance mechanisms are spreading globally, impeding our ability to treat common infectious diseases. Misuse and overuse of antibiotics accelerate microbial resistance to antibiotics. Despite the exerted efforts, none of the newly developed antibiotics are expected to be effective against the dangerous forms of antibiotic-resistant bacteria. Since many plants have been shown to contain powerful antimicrobial compounds that can act synergistically or alternatively to antibiotics, the demand for herbal medicines has recently increased to co-treat microbes that are resistant to antibiotics. Maximum benefit can be achieved when the pharmacokinetics and pharmacodynamics of natural products match the antibiotic. This review article refers to nine highly effective and key herbs to use alongside antibiotics to overcome crises of antibiotic resistance. Their unique molecular mechanisms of action have been highlighted.


Assuntos
Antibacterianos , Anti-Infecciosos , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos , Anti-Infecciosos/farmacologia , Bactérias , Extratos Vegetais
15.
Nat Prod Res ; 37(23): 4069-4079, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36625545

RESUMO

Dolomiaea costus (Falc.) Kasana & A.K. Pandey Family Asteraceae, formerly known as Saussurea costus (Falc.) Lipsch contains a rich treasury of diverse bioactive compounds such as monoterpenes, sesquiterpenes, triterpenes, sterols, cardenolides, flavonoids, coumarins, lignans, phenylpropanoids and alkaloids. The sesquiterpene lactones, costunolide and dehydrocostuslactone in D. costus, possess unique promising in vitro and in vivo biological activities for the prevention and cure of diverse ailments like Parkinson's disease, oxidative stress, hyperpigmentation, ulcerative colitis, breast cancer, hepatocellular carcinoma, colon cancer, prostate cancer, ovarian cancer, leukemia, stomach cancer, prostate cancer, lung cancer, osteosarcoma, neuroblastoma, allergy, type 2 diabetes, hepatotoxicity, bronchitis, pulmonary fibrosis, thrombosis and various microbial infections. Costunolide and dehydrocostuslactone are potential drug candidates that could lead to the development of new medications for a variety of difficult-to-treat diseases.


Assuntos
Asteraceae , Carcinoma Hepatocelular , Costus , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Neoplasias da Próstata , Masculino , Humanos , Compostos Fitoquímicos , Lactonas/farmacologia
16.
Nat Prod Res ; 37(2): 343-347, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34494929

RESUMO

As a result of our continuous research efforts to investigate the molecular mechanisms of Eucalyptus kino polyphenolics for healing liver solid tumors, in-vivo histopathological studies of the solid tumor tissues and in-silico molecular docking were carried out. Histopathology of female mice treated with a dose of 200 mg/kg Eucalyptus kino methanolic extract in combination with low level ionising γ-radiation (0.25 Gy) recovered a near-to-normal histological structure revealing a substantial number of cells with hyper-chromachia in nuclei, fibroblast lobules and necrotic cells. Analysis for matrix metalloproteinase-9 (MMP-9) by Western blot and also molecular docking study were conducted to evaluate and rank the potential of the individual components dominated in the extract to inhibit MMP-9 and TGF-ß. The current study presents new lead compounds for the design of novel MMP-9 and TGF-ß strong inhibitors of natural origin.


Assuntos
Eucalyptus , Neoplasias Hepáticas , Animais , Feminino , Camundongos , Expressão Gênica , Metaloproteinase 9 da Matriz/metabolismo , Simulação de Acoplamento Molecular , Fator de Crescimento Transformador beta/metabolismo
17.
Nat Prod Res ; 37(16): 2770-2775, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36190800

RESUMO

Breast cancer is the most devastating disease for women. There is a great demand for new sources to treat this disease. Medicinal plants are an indispensable source of bioactive compounds with wide range of pharmacological activities. In-vitro cytotoxic activity of Otostegia fruticosa methanolic extract against human breast cancer was studied using MCF-7 cell line. The extract showed mildly potent activity (IC50 = 51 ± 9.836 µg/mL) in comparison to the standard anticancer doxorubicin (IC50 = 7.467 ± 1.05 µg/mL). Potential compounds responsible for activity have been identified using Molecular Operating Environment (MOE) module on the major compounds detected by HPLC-MS/MS technique against estrogen alpha receptor (ERα+: PDB ID 2JF9). 3,5-di-O-dicaffeoylquinic acid, hyperoside and rutin showed similar binding and antagonistic interaction with the estrogen alpha receptor as tamoxifen in several poses. The retrieved results confirm that we can add this plant to a powerful arsenal that combats this insidious disease.

18.
Nat Prod Res ; : 1-10, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37427947

RESUMO

The main cause of cancer death among women is breast cancer. The most common type of breast cancer is the estrogen receptor positive breast cancer. Discovery of estrogen receptor provided a highly effective target for treatment of hormone-dependent breast cancer. Selective estrogen receptor inhibitors are useful for halting the growth of breast cancer cells and inducing apoptosis. Tamoxifen, a popular selective estrogen receptor modulator, can treat breast cancer but also has unfavourable side effects due to its estrogenic activity in other tissues. Many herbal remedies and bioactive natural compounds, such as genistein, resveratrol, ursolic acid, betulinic acid, epigallocatechin-3-gallate, prenylated isoflavonoids, zearalenol, coumestrol, pelargonidin, delphinidin, and biochanin A, have the ability to specifically modulate the estrogen receptor alpha. Moreover, several of these compounds speed up cell death by supressing estrogen receptor gene expression. This opens wide avenue to introduce number of natural medicines with a revolutionary therapeutic impact and few side effects.

19.
Nat Prod Res ; 36(10): 2654-2659, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33886378

RESUMO

30 secondary polyphenolic metabolites were characterised in Eucalyptus kino methanol extract using HPLC-MS/MS. The antitumor activity of the extract in combination with low level ionising radiation in female mice with solid tumors from inoculated Ehrlich ascites carcinoma cells was investigated. Tumor cell-inoculated mice received daily extract doses (100 mg/kg, 200 mg/kgBW) with or without a single exposure to 0.25 Gy γ-rays, and cis-platin as a reference anticancer drug. Changes in the tumor volume, oxidative state, levels of caspase-3, TGF-ß and Nf-κB were assessed by q-PCR. Surprisingly, a dose of 200 mg/kg extract together with γ-radiation remarkably reduced the tumor volume, improved the oxidative and apoptotic biomarker levels. In conclusion, results showed that a combination of kino extract with low level γ-radiation synergistically reduced tumor progression due to the antioxidant and anti-proliferative activities of the polyphenolics in the extract.


Assuntos
Carcinoma de Ehrlich , Eucalyptus , Extratos Vegetais , Polifenóis , Animais , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Eucalyptus/química , Feminino , Expressão Gênica , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Espectrometria de Massas em Tandem , Fator de Crescimento Transformador beta/metabolismo
20.
Nat Prod Res ; 36(22): 5766-5771, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34894897

RESUMO

Withania somnifera, Angelica sinensis, Glycyrrhiza glabra, and Simmondsia chinensis were acquired from the Egyptian market, profiled for their chemical constituents, screened for the in-vitro MAO-B inhibitory activity and evaluated for the total phenolic content. Thirty compounds were characterized in the selected herbs using HPLC-MS/MS. In-vitro MAO-B inhibitory activity and total phenolic content of the acquired herbs were compared with those of a prepared herbal formula consisting of a mixture of equal amounts of the four mentioned herbs. The most potent MAO-B inhibitory activity was exerted by the methanol extract of the prepared formula (IC50 of 712.19 ± 13.90 ng/mL) compared to selegiline (IC50 of 581.69 ± 11.35 ng/mL). The highest value of the total phenolic content was shown by Angelica sinensis methanolic extract (76.15 ± 0.1 mg/g) followed by Glycyrrhiza glabra methanolic extract (65.74 ± 0.1 mg/g), then the mixture's methanolic extract of the four herbs (37.04 ± 0.1 mg/g).


Assuntos
Monoaminoxidase , Doença de Parkinson , Humanos , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Egito , Fenóis/análise , Plantas , Extratos Vegetais/farmacologia , Metanol
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