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1.
Food Chem Toxicol ; : 113638, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36708865

RESUMO

Narirutin is a dietary flavanone found in lemons, oranges, passion fruit, bergamot and grapefruit. It possesses anti-allergic, cardioprotective, neuroprotective, hepatoprotective potential, and its enriched fraction suppresses the growth of prostate cancer cells; however, there is currently no information on the chemopreventive potential of narirutin alone against hormone-refractory prostate cancer cells (PC-3) and its mode of action. Thus, the chemopreventive possibility of narirutin was investigated in PC-3 cells by utilising cytotoxicity assays. Further, a mechanism was deduced targeting hyaluronidase, an early-stage diagnosis marker, by cell-free, cell-based and in silico studies. The results indicate that narirutin reduced the viability of PC-3 cells with the inhibitory concentration range of 66.87-59.80 µM. It induced G0/G1 phase arrest with a fold change of 1.12. Besides, it increased the generation of reactive oxygen species with a fold change of 1.34 at 100 µM. Narirutin inhibited hyaluronidase's activity in cell-free (11.17 µM) and cell-based assays (67.23 µM) and showed a strong binding interaction with hyaluronidase. Finally, the MD simulation analysis supported the idea that narirutin binding enhanced compactness and stability and created a stable complex with hyaluronidase. In addition, ADMET prediction indicates that it is a non-toxic, non-CYPs inhibitor and thus didn't alter the metabolism. The results reveal that narirutin may be a potential chemopreventive agent for hormone-resistant prostate cancer cells in addition to offering data for supporting diet-based nutraceutical agents to prevent prostate cancer.

2.
Plant Mol Biol ; 110(6): 545-563, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35997919

RESUMO

WD40 domain-containing proteins are one of the eukaryotes' most ancient and ubiquitous protein families. Little is known about the presence and function of these proteins in cyanobacteria in general and Anabaena in particular. In silico analysis confirmed the presence of WD40 repeats. Gene expression analysis indicated that the transcript levels of both the target proteins were up-regulated up to 4 fold in Cd and drought and 2-3 fold in heat, salt, and UV-B stress. Using a fluorescent oxidative stress indicator, we showed that the recombinant proteins were scavenging reactive oxygen species (ROS) (4-5 fold) more efficiently than empty vectors. Chromatin immunoprecipitation analysis (ChIP) and electrophoretic mobility shift assay (EMSA) revealed that the target proteins function as transcription factors after binding to the promoter sequences. The presence of kinase activity (2-4 fold) in the selected proteins indicated that these proteins could modulate the functions of other cellular proteins under stress conditions by inducing phosphorylation of specific amino acids. The chosen proteins also demonstrated interaction with Zn, Cd, and Cu (1.4-2.5 fold), which might stabilize the proteins' structure and biophysical functions under multiple abiotic stresses. The functionally characterized Alr0671 and All2352 proteins act as transcription factors and offer tolerance to agriculturally relevant abiotic stresses.


Alr0671 and All2352 are novel WD40 proteins of Anabaena capable of regulating biochemical functions and abiotic stress tolerance by acting as a transcription factor and mediating DNA-protein interaction.


Assuntos
Anabaena , Cádmio , Anabaena/genética , Estresse Fisiológico/genética , Secas , Fatores de Transcrição/genética , Proteínas de Plantas/genética
3.
Front Immunol ; 13: 952509, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032072

RESUMO

Wheezing-associated rhinovirus (RV) infections are associated with asthma development. We have shown that infection of immature mice with RV induces type 2 cytokine production and mucous metaplasia which is dependent on IL-33 and type 2 innate lymphoid cells (ILC2s) and intensified by a second heterologous RV infection. We hypothesize that M2a macrophages are required for the exaggerated inflammation and mucous metaplasia in response to heterologous RV infection. Wild-type C57Bl/6J mice and LysMCre IL4Rα KO mice lacking M2a macrophages were treated as follows: (1) sham infection on day 6 of life plus sham on day 13 of life, (2) RV-A1B on day 6 plus sham on day 13, (3) sham on day 6 and RV-A2 on day 13, or (4) RV-A1B on day 6 and RV-A2 on day 13. Lungs were harvested one or seven days after the second infection. Wild-type mice infected with RV-A1B at day 6 showed an increased number of Arg1- and Retnla-expressing lung macrophages, indicative of M2a polarization. Compared to wild-type mice infected with RV on day 6 and 13 of life, the lungs of LysMCre IL4Rα KO mice undergoing heterologous RV infection showed decreased protein abundance of the epithelial-derived innate cytokines IL-33, IL-25 and TSLP, decreased ILC2s, decreased mRNA expression of IL-13 and IL-5, and decreased PAS staining. Finally, mRNA analysis and immunofluorescence microscopy of double-infected LysMCre IL4Rα KO mice showed reduced airway epithelial cell IL-33 expression, and treatment with IL-33 restored the exaggerated muco-inflammatory phenotype. Conclusion: Early-life RV infection alters the macrophage response to subsequent heterologous infection, permitting enhanced IL-33 expression, ILC2 expansion and intensified airway inflammation and mucous metaplasia.


Assuntos
Interleucina-33 , Rhinovirus , Animais , Imunidade Inata , Inflamação , Linfócitos , Macrófagos , Metaplasia , Camundongos , RNA Mensageiro
4.
Phytother Res ; 36(2): 963-983, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35040205

RESUMO

MicroRNAs (miRNAs) are involved in cancer progression via translational degradation in a sequence-specific manner of the 3'-untranslated region (3'UTR) of messenger RNA (mRNA). The involvement of miRNA in the biological progression of various cancer types is considered to be a potential target. Primary miRNA (pri-miRNA) and precursor-miRNA (pre-miRNA) synthesize the miRNA by dicer-catalyzed processes thus targeting pri/pre-miRNA by phytochemicals is amongst the appropriate approaches for anticancer therapies. Flavonoids category of phytochemicals is well-known for its chemotherapeutic and chemopreventive potential against multiple cancer types. However, the molecular interactions of flavonoids with miRNAs are not reported so far. Thus, this study aims to identify the promising flavonoids as the antagonist of miRNAs (pre-miR21, pri-miR-208a, pri-miR-378a, pri-miR320b, pri-miR-300, pri-miR-19b, and pre-miR-20b) using molecular docking simulations studies. Among the tested flavonoids, narirutin showed highest binding energy (-11.7 kcal/mol) against pri-miR19b followed by pri-miR-378a (-11.4 kcal/mol) > pri-miR320b (-11.2 kcal/mol) = pri-miR-300 (-11.2 kcal/mol) > pri-miR-208a (-9.0 kcal/mol) > pre-miR-20b (- 8.3 kcal/mol). The molecular dynamic simulation experiment confirmed that narirutin destabilizes the tertiary structure of pri-miRNA in comparison to apo-RNA. The finding indicates that narirutin binding with pre-miRNA causes disruption of pri-RNA structure that creates a loss of DICER-pre-miRNA interactions by hindering the pre-miRNA synthesis, thereby affecting miRNA processing. Further pharmacokinetics and toxicity prediction revealed that it is non-carcinogenic, non-mutagenic, and does not inhibit the CYPs activity. Thus, narirutin could be a possible antagonist of oncogenic miRNAs, therefore could be useful for miRNA-targeted cancer prevention and treatment.


Assuntos
Flavanonas , MicroRNAs , Dissacarídeos , MicroRNAs/genética , MicroRNAs/metabolismo , Simulação de Acoplamento Molecular , Estudos Prospectivos , Processamento Pós-Transcricional do RNA
5.
Bioorg Med Chem Lett ; 50: 128340, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34469711

RESUMO

Substituted amide derivatives of C4-ageratochromene dimer analog (19) were synthesized through structural modification of precocene-I (4a), isolated from the essential oil of Ageratum conyzoides L. The target compounds (18-20, 23I-VI, 24I-VI, and 25I-VI) were evaluated for their bone-forming effect using osteoblast differentiation assay. Seven compounds (23I, 23II, 23IV, 23VI, 24III, 24VI, and 25VI) presented good activity within 1 pM-1 nM concentration. At 1 pM concentration, the most active compound i.e. 23II showed effective mineralization of osteoblast cells along with expression of osteogenic marker genes viz RUNX 2, BMP-2, and type 1 collagen (Type-1 col) without any toxicity towards osteoblast cells. Single crystal X-ray analysis of 18 and 20 revealed that the core nucleus of these molecules bear phenyl rings in a Trans-stilbenoid system and had a good structural correlation with 17ß-estradiol (1) and diethylstilbestrol (DES, 3). In-silico study about 23II showed its structural complementarities with the LBD of estrogen receptor (ER) which indicated possible ER-mediated activity of compounds.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzopiranos/síntese química , Benzopiranos/farmacologia , Conservadores da Densidade Óssea/síntese química , Conservadores da Densidade Óssea/farmacologia , Ageratum/química , Animais , Neoplasias da Mama , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Descoberta de Drogas , Feminino , Humanos , Camundongos , Modelos Moleculares , Estrutura Molecular , Osteoblastos , Receptores de Estrogênio/metabolismo , Relação Estrutura-Atividade
6.
Curr Biol ; 31(24): 5522-5532.e7, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34735792

RESUMO

Sex determination is a central process for sexual reproduction and is often regulated by a sex determinant encoded on a sex chromosome. Rules that govern the evolution of sex chromosomes via specialization and degeneration following the evolution of a sex determinant have been well studied in diploid organisms. However, distinct predictions apply to sex chromosomes in organisms where sex is determined in the haploid phase of the life cycle: both sex chromosomes, female U and male V, are expected to maintain their gene functions, even though both are non-recombining. This is in contrast to the X-Y (or Z-W) asymmetry and Y (W) chromosome degeneration in XY (ZW) systems of diploids. Here, we provide evidence that sex chromosomes diverged early during the evolution of haploid liverworts and identify the sex determinant on the Marchantia polymorpha U chromosome. This gene, Feminizer, encodes a member of the plant-specific BASIC PENTACYSTEINE transcription factor family. It triggers female differentiation via regulation of the autosomal sex-determining locus of FEMALE GAMETOPHYTE MYB and SUPPRESSOR OF FEMINIZATION. Phylogenetic analyses of Feminizer and other sex chromosome genes indicate dimorphic sex chromosomes had already been established 430 mya in the ancestral liverwort. Feminizer also plays a role in reproductive induction that is shared with its gametolog on the V chromosome, suggesting an ancestral function, distinct from sex determination, was retained by the gametologs. This implies ancestral functions can be preserved after the acquisition of a sex determination mechanism during the evolution of a dominant haploid sex chromosome system.


Assuntos
Marchantia , Evolução Molecular , Haploidia , Marchantia/genética , Filogenia , Cromossomos Sexuais/genética
7.
Plant Physiol Biochem ; 168: 353-372, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34700048

RESUMO

Oxidative stress is common consequence of abiotic stress in plants as well as cyanobacteria caused by generation of reactive oxygen species (ROS), an inevitable product of respiration and photosynthetic electron transport. ROS act as signalling molecule at low concentration however, when its production exceeds the endurance capacity of antioxidative defence system, the organisms suffer oxidative stress. A highly toxic metabolite, methylglyoxal (MG) is also produced in cyanobacteria in response to various abiotic stresses which consequently augment the ensuing oxidative damage. Taking recourse to the common lineage of eukaryotic plants and cyanobacteria, it would be worthwhile to explore the regulatory role of glyoxalase system and antioxidative defense mechanism in combating abiotic stress in cyanobacteria. This review provides comprehensive information on the complete glyoxalase system (GlyI, GlyII and GlyIII) in cyanobacteria. Furthermore, it elucidates the recent understanding regarding the production of ROS and MG, noteworthy link between intracellular MG and ROS and its detoxification via synchronization of antioxidants (enzymatic and non-enzymatic) and glyoxalase systems using glutathione (GSH) as common co-factor.


Assuntos
Antioxidantes , Cianobactérias , Plantas , Aldeído Pirúvico , Espécies Reativas de Oxigênio
8.
J Indian Soc Periodontol ; 25(5): 427-431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34667387

RESUMO

BACKGROUND: Periodontal disease is one of the leading causes of tooth loss in the geriatric population. Assessment of periodontal disease in a population is an important step in planning effective prevention and control programs for periodontal disease. Therefore, a study was carried out in old-age homes of Delhi to assess the periodontal status of 65-74-year-old elderly and recommend interventions to improve their periodontal health. MATERIALS AND METHODS: A cross-sectional study was conducted among 464 elderly from old-age homes of Delhi. Periodontal health status of the participants was determined using the WHO oral health assessment form. Community Periodontal Index (CPI) and loss of attachment (LOA) were recorded. Collected data were analyzed using SPSS version 23. Chi-square test was used to determine statistically significant difference among CPI scores and LOA according to age and gender. P ≤ 0.05 was considered statistically significant. RESULTS: The result of the study showed that 25.4% of the elderly had healthy periodontium, 71.1% had a periodontal pocket of 6 mm or more, and 2.40% had a pocket depth of 4-5 mm. Around 36% had 6-8 mm LOA and 34.70% had 9-11 mm LOA. The difference between CPI scores among gender and age group was not significant (P = 0.20, P = 0.096). However, the difference among gender for LOA was found significant (P = 0.014). CONCLUSION: The results from this study show that periodontal health of elderly residing in old-age homes is very poor. The periodontal status of this population can be enhanced by special collaborative efforts from the government and various nongovernmental organizations toward preventive and curative periodontal health services.

9.
NAR Genom Bioinform ; 3(2): lqab041, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34017946

RESUMO

RNA splicing, and variations in this process referred to as alternative splicing, are critical aspects of gene regulation in eukaryotes. From environmental responses in plants to being a primary link between genetic variation and disease in humans, splicing differences confer extensive phenotypic changes across diverse organisms (1-3). Regulation of splicing occurs through differential selection of splice sites in a splicing reaction, which results in variation in the abundance of isoforms and/or splicing events. However, genomic determinants that influence splice-site selection remain largely unknown. While traditional approaches for analyzing splicing rely on quantifying variant transcripts (i.e. isoforms) or splicing events (i.e. intron retention, exon skipping etc.) (4), recent approaches focus on analyzing complex/mutually exclusive splicing patterns (5-8). However, none of these approaches explicitly measure individual splice-site usage, which can provide valuable information about splice-site choice and its regulation. Here, we present a simple approach to quantify the empirical usage of individual splice sites reflecting their strength, which determines their selection in a splicing reaction. Splice-site strength/usage, as a quantitative phenotype, allows us to directly link genetic variation with usage of individual splice-sites. We demonstrate the power of this approach in defining the genomic determinants of splice-site choice through GWAS. Our pilot analysis with more than a thousand splice sites hints that sequence divergence in cis rather than trans is associated with variations in splicing among accessions of Arabidopsis thaliana. This approach allows deciphering principles of splicing and has broad implications from agriculture to medicine.

10.
Food Chem Toxicol ; 151: 112091, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33647348

RESUMO

Protein kinases associated with cancer genes play vital role in angiogenesis, invasion, motility, proliferation, and survival. Therefore, cancer prevention/treatment, targeting kinases with phytochemicals could be a promising approach. Given potential of phytochemicals in modulating cancer-associated kinases, present study aims to find inhibitory prospects of selected flavonoids for cancer-chemoprevention/treatment. The molecular docking interaction analysis was done by exploring binding potential of flavonoids with kinases (PI3K, Akt, mTOR, EGFR, MAPK, MKK4, Fyn, ZAP-70, B-Raf, JAK-2, STAT-1, STAT-3, STAT-4, STAT-5, and VEGF) involved in various carcinogenesis phases. Among flavonoids acacetin showed highest binding-energy against JAK-2 following Fyn > VEGF > PI3K > MKK4 > MAPK > BRaf > STAT-5 > STAT-1 > STAT-4 whereas pinostrobin depicts higher binding-energy with JAK-2 followed by B-Raf > MKK4 > VEGF > PI3K > MAPK > STAT-1 > STAT-4 > STAT-5. Further, molecular-dynamic simulation revealed that pinostrobin interacted with JAK-2 protein with binding-energy of -25.068 ± 1.08 kJ/mol whereas acacetin interacted with both JAK-2 and Fyn with binding-energies of -23.466 ± 0.9508 kJ/mol and-8.935 ± 1.3108 kJ/mol respectively. High binding-energy, low inhibition-constant, and drug-likeness of acacetin and pinostrobin provide a clue for their usage as a JAK-2 inhibitor which could be useful for molecular/cell-target based in-vitro and in-vivo investigations.


Assuntos
Flavanonas/farmacologia , Flavonas/farmacologia , Neoplasias/enzimologia , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Citocromo P-450 CYP2D6/efeitos dos fármacos , Dissacarídeos/farmacologia , Flavanonas/farmacocinética , Flavonas/farmacocinética , Flavonoides/farmacologia , Humanos , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas Quinases/efeitos dos fármacos , Proteínas Quinases/metabolismo , Termodinâmica
11.
Biochem Pharmacol ; 189: 114409, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33428895

RESUMO

MicroRNAs (miRNAs) are non-coding, conserved, single-stranded nucleotide sequences involved in physiological and developmental processes. Recent evidence suggests an association between miRNAs' deregulation with initiation, promotion, progression, and drug resistance in cancer cells. Besides, miRNAs are known to regulate the epithelial-mesenchymal transition, angiogenesis, autophagy, and senescence in different cancer types. Previous reports proposed that apart from the antioxidant potential, flavonoids play an essential role in miRNAs modulation associated with changes in cancer-related proteins, tumor suppressor genes, and oncogenes. Thus, flavonoids can suppress proliferation, help in the development of drug sensitivity, suppress metastasis and angiogenesis by modulating miRNAs expression. In the present review, we summarize the role of miRNAs in cancer, drug resistance, and the chemopreventive potential of flavonoids mediated by miRNAs. The potential of flavonoids to modulate miRNAs expression in different cancer types demonstrate their selectivity and importance as regulators of carcinogenesis. Flavonoids as chemopreventive agents targeting miRNAs are extensively studied in vitro, in vivo, and pre-clinical studies, but their efficiency in targeting miRNAs in clinical studies is less investigated. The evidence presented in this review highlights the potential of flavonoids in cancer prevention/treatment by regulating miRNAs, although further investigations are required to validate and establish their clinical usefulness.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Flavonoides/metabolismo , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Flavonoides/administração & dosagem , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Neoplasias/genética
12.
Int J Paediatr Dent ; 31(4): 459-467, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32762050

RESUMO

BACKGROUND: There is a need to validate OHRQoL measures in Hindi to assess the OHRQoL of Indian children. AIM: To develop a Hindi version of the CPQ11-14 and to appraise its validity and reliability for use among North Indian children aged 11-14 years. DESIGN: The cross-culturally adapted Hindi version of CPQ11-14 was achieved by forward translation, backward translation, committee review, and pretesting. A total of 1000 children were recruited from schools, chosen by two-stage cluster random sampling technique. After completing the self-administered questionnaire CPQ11-14 by the child, oral examination was conducted using decayed/missing/filled teeth (DMFT) index, malocclusion index, and Dean's fluorosis index. Test-retest reliability was checked on 100 participants after one week. RESULTS: The floor effect was present in 3.6% individuals, and there was no ceiling effect. Cronbach's alpha for the overall CPQ11-14 scale was 0.963. Intra-class correlation (ICC) coefficient was 0.952 for the entire scale. Cronbach's alpha value for test-retest was 0.918. There was a non-significant change in domain-level and overall median CPQ11-14 scores with an increase in DMFT scores. For malocclusion and fluorosis, there was a statistically significant increase in overall and domain-level scores with increased severity scores. CPQ11-14 and individual domains significantly correlated with both the global questions. CONCLUSION: Hindi version of CPQ11-14 is a reliable scale to assess OHRQoL in Hindi speaking 11- to 14-year-old children.


Assuntos
Comparação Transcultural , Saúde Bucal , Adolescente , Criança , Humanos , Percepção , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Instituições Acadêmicas , Inquéritos e Questionários
13.
J Biomol Struct Dyn ; 39(9): 3312-3323, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32362196

RESUMO

Cirsimaritin is a dimethoxy flavone, which is present in Ocimum sanctum, Microtea debilis, Artemisia judaica, Cirsium japonicum, and Lithocarpus dealbatus. Its antiproliferative potential has been explored in breast and gall bladder cancer cell lines. However, no reports are available on skin and squamous lung carcinoma. Also, the complete mode of action is unknown. Therefore, in the present study, the anticancer potential of cirsimaritin is explored in organ-specific cell lines by using MTT assay. Further, the inhibitory potential and binding interaction with the selected targets were analyzed through in vitro and in-silico analysis. Cirsimaritin showed selective anticancer activity against NCIH-520 cell-line (IC50 23.29 µM), also inhibited the proliferation of other cell-lines up to 48% at 100 µM. In NCIH-520 cell-line, cirsimaritin significantly increased the apoptosis of the cells at both the tested concentrations (10 and 100 µM), which was confirmed by Annexin-V signifying the induction of late apoptosis. Besides, an increase in the ROS levels of 1.6 fold (10 µM) and 1.8 fold (100 µM), circimaritin also inhibits the activity of ODC and CATD with the IC50 57.30 and 68.22 µM respectively. It exhibited a good binding score with the selected targets, follow Lipinski's rule of five and non-mutagenic. Hence, cirsimaritin is a potent molecule, which inhibits the proliferation of lung squamous cell lines by inducing apoptosis. It also inhibited the activity of ODC and CATD responsible for the progression phase in the cancer cells. Communicated by Ramaswamy H. Sarma.


Assuntos
Carcinoma de Células Escamosas , Flavonas , Neoplasias Pulmonares , Apoptose , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Flavonas/farmacologia , Humanos , Pulmão , Neoplasias Pulmonares/tratamento farmacológico
14.
Pharmacol Res ; 164: 105387, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33352232

RESUMO

Baicalin has been widely investigated against different types of malignancies both at the cellular and molecular levels over the past few years. Due to its remarkable anti-proliferative potential in numerous cancer cell lines, it has created immense interest as a potential chemotherapeutic modality compared to other flavonoids. Thus, this review focuses on the recent accomplishments of baicalin and its limitations in cancer prevention and treatment. Further, combination studies and nanoformulations using baicalin to treat cancer along with the metabolism, bioavailability, toxicity, and pharmacokinetics have been discussed. The present review explains biological source, and anti-proliferative potential of baicalin against cancers including breast, colon, hepatic, leukemia, lung, and skin, as well as the relevant mechanism of action to modulate diverse signaling pathways including apoptosis, cell cycle, invasion, and migration, angiogenesis, and autophagy. The anticancer mechanism of baicalin in orthotropic and xenograft mice models have been deliberated. The combination studies of baicalin in novel therapies as chemotherapeutic adjuvants have also been summarized. The low bioavailability, fast metabolism, and poor solubility, and other significant factors that limit the clinical use of baicalin have been examined as a challenge. The improvement in the pharmacokinetics and pharmacodynamics of baicalin with newer approaches and the gaps are highlighted, which could establish baicalin as an effective and safe compound for cancer treatment as well as help to translate its potential from bench to bedside.


Assuntos
Antineoplásicos Fitogênicos , Flavonoides , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Flavonoides/química , Flavonoides/farmacocinética , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Dent Res J (Isfahan) ; 17(5): 373-379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343846

RESUMO

BACKGROUND: The aim of the study was to assess the relationship between height and dental caries among 13-year-old adolescents in schools of Bangalore, India. MATERIALS AND METHODS: A cross-sectional study was undertaken on 1900 schoolchildren aged 13 years from both government and private schools of Bangalore using stratified random sampling. Demographic data; family-related factors; and general and oral health-related factors such as frequency of sugar consumption, dietary habits, oral hygiene practices, and dental attendance were interviewed using both open-ended and close-ended questions. Anthropometric measurements for height and weight were performed. Clinical examination was done and caries was recorded using the decayed, missing, and filled teeth (DMFT) index (WHO criteria, 1997). Data were analyzed using SPSS version 21.0, and descriptive statistics including percentages, mean, and frequencies were performed. Student's t-test and ANOVA were applied to find the significant differences between mean DMFT among groups. Categorical data were analyzed by Chi-square test for differences between groups. Pearson correlation coefficient was used to find the correlation among dental caries and height and body mass index (BMI).P value was set at a statistical significance level of 0.05. RESULTS: The prevalence of dental caries among the study population was 36.3% which was higher among girls as compared to boys. Dental caries was found to be significantly associated with socioeconomic status, family structure, birth order, use of oral hygiene aids, mouthrinsing, last dental visit, weight, and BMI. Height and BMI showed a strong negative correlation with dental caries. CONCLUSION: The present study showed a significant negative correlation between height and dental caries. However, since both caries and height are a dynamic phenomenon, hence a longitudinal study exploring the possible relationship should be considered.

16.
Curr Genomics ; 21(4): 295-310, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-33071622

RESUMO

BACKGROUND: Cyanobacteria are excellent model to understand the basic metabolic processes taking place in response to abiotic stress. The present study involves the characterization of a hypothetical protein Alr0765 of Anabaena PCC7120 comprising the CBS-CP12 domain and deciphering its role in abiotic stress tolerance. METHODS: Molecular cloning, heterologous expression and protein purification using affinity chromatography were performed to obtain native purified protein Alr0765. The energy sensing property of Alr0765 was inferred from its binding affinity with different ligand molecules as analyzed by FTIR and TNP-ATP binding assay. AAS and real time-PCR were applied to evaluate the iron acquisition property and cyclic voltammetry was employed to check the redox sensitivity of the target protein. Transcript levels under different abiotic stresses, as well as spot assay, CFU count, ROS level and cellular H2O2 level, were used to show the potential role of Alr0765 in abiotic stress tolerance. In-silico analysis of Alr0765 included molecular function probability analysis, multiple sequence analysis, protein domain and motif finding, secondary structure analysis, protein-ligand interaction, homologous modeling, model refinement and verification and molecular docking was performed with COFACTOR, PROMALS-3D, InterProScan, MEME, TheaDomEx, COACH, Swiss modeller, Modrefiner, PROCHECK, ERRAT, MolProbity, ProSA, TM-align, and Discovery studio, respectively. RESULTS: Transcript levels of alr0765 significantly increased by 20, 13, 15, 14.8, 12, 7, 6 and 2.5 fold when Anabaena PCC7120 treated with LC50 dose of heat, arsenic, cadmium, butachlor, salt, mannitol (drought), UV-B, and methyl viologen respectively, with respect to control (untreated). Heterologous expression resulted in 23KDa protein observed on the SDS-PAGE. Immunoblotting and MALDI-TOF-MS/MS, followed by MASCOT search analysis, confirmed the identity of the protein and ESI/MS revealed that the purified protein was a dimer. Binding possibility of Alr0765 with ATP was observed with an almost 6-fold increment in relative fluorescence during TNP-ATP binding assay with a λ max of 538 nm. FTIR spectra revealed modification in protein confirmation upon binding of Alr0765 with ATP, ADP, AMP and NADH. A 10-fold higher accumulation of iron was observed in digests of E. coli with recombinant vector after induction as compared to control, which affirms the iron acquisition property of the protein. Moreover, the generation of the redox potential of 146 mV by Alr0765 suggested its probable role in maintaining the redox status of the cell under environmental constraints. As per CFU count recombinant, E. coli BL21 cells showed about 14.7, 7.3, 6.9, 1.9, 3 and 4.9 fold higher number of colonies under heat, cadmium (CdCl2), arsenic (Na3AsO4), salt (NaCl), UV-B and drought (mannitol) respectively compared to pET21a harboring E. coli BL21 cells. Deterioration in the cellular ROS level and total cellular H2O2 concentration validated the stress tolerance ability of Alr0765. In-silico analysis unraveled novel findings and attested experimental findings in determining the role of Alr0765. CONCLUSION: Alr0765 is a novel CBS-CP12 domain protein that maintains cellular energy level and iron homeostasis which provides tolerance against multiple abiotic stresses.

17.
Food Chem Toxicol ; 145: 111708, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32866514

RESUMO

BACKGROUND: Acacetin is a di-hydroxy and mono-methoxy flavone present in various plants, including black locust, Damiana, Silver birch. Literature information revealed that acacetin exhibits an array of pharmacological potential including chemopreventive and cytotoxic properties in cancer cell lines, prevents ischemia/reperfusion/myocardial infarction-induced cardiac injury, lipopolysaccharide (LPS), 1-methyl-4-phenyl pyridinium ion (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced neuroinflammation, LPS and sepsis-induced lung injury, rheumatoid and collagen-induced arthritis, inhibit the microbial growth, obesity, viral-mediated infections as well as hepatic protection. PURPOSE: This review highlights the therapeutic potential of acacetin, with updated and comprehensive information on the biological sources, chemistry, and pharmacological properties along with the possible mechanism of action, safety aspects, and future research opportunities. STUDY DESIGN: The information was retrieved from various search engines, including Pubmed, SciFinder, Science direct, Inxight:drugs, Google scholar, and Meta cyc. RESULT: The first section of this review focuses on the detailed biological source of acacetin, chromatographic techniques used for isolation, chemical characteristics, the method for the synthesis of acacetin, and the available natural and synthetic derivatives. Subsequently, the pharmacological activities, including anti-cancer, anti-inflammatory, anti-viral, anti-microbial, anti-obesity, have been discussed. The pharmacokinetics data and toxicity profile of acacetin are also discussed. CONCLUSION: Acacetin is a potent molecule reported for its strong anti-inflammatory and anti-cancer activity, however further scientific evidence is essential to validate its potency in disease models associated with inflammation and cancer. There is limited information available for toxicity profiling of acacetin; therefore, further studies would aid in establishing this natural flavone as a potent candidate for research studies at clinical setup.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antimetabólitos/administração & dosagem , Flavonas/administração & dosagem , Inflamação/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Neoplasias/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Antimetabólitos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Flavonas/química , Humanos
18.
Curr Top Med Chem ; 20(21): 1898-1909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32648844

RESUMO

BACKGROUND: Since centuries plant-based compounds are known for the treatment of cancer in both traditional and contemporary medicine. The problems like target non-specificity and toxicity are well-known regarding anticancer drugs. Therefore, target specific search of novel entities is constant. Isothymusin is a dimethoxy, trihydroxy flavone present in plants like Ocimum sanctum, and Limnophilla geoffrayi. There are limited reports available on the anticancer potential of isothymusin. OBJECTIVES: The effects of isothymusin on redox status, cell cytotoxicity, and targets involved in the promotion and progression of the cancer cells have been investigated. METHODS: Antiproliferative efficacy was evaluated by MTT, Neutral Red Uptake, and Sulforhodamine-B assays. The spectrophotometric methods were adopted to study the effect against selected targets. Redox activity was assessed by in vitro antioxidant assays and the interaction study, ADMET profiling, and toxicity assessments were done in silico. RESULTS: Isothymusin scavenges the radicals, i.e., DPPH and nitric oxide with moderate ferric reducing potential. It affected the proliferation of leukemia, colon, skin, and breast cancer cell lines by more than 50% but moderately affected prostate, kidney, lung, hepatic, and breast adenocarcinoma (up to 48%). Isothymusin inhibited the enzymes associated with the promotion stage of cancer, including cycloxygenase- 2 and lipoxygenase-5. Additionally, it also inhibited the activity of proliferation markers like cathepsin- D, dihydrofolate reductase, hyaluronidase, and ornithine-decarboxylase. Besides, in silico studies supported the in vitro enzyme inhibition assays outcome. Toxicity studies showed promising results of chemical descriptors and non-skin-irritant, moderate ocular-irritancy, and in vitro Ames test confirmed non-mutagenic nature. CONCLUSION: Isothymusin showed radical scavenging and anti-proliferative activities, which may be taken up as a phytochemical lead for the synthesis of analogues possessing enhanced anticancer potential.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/síntese química , Flavonoides/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Picratos/antagonistas & inibidores , Relação Estrutura-Atividade
19.
Food Chem Toxicol ; 143: 111550, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32640357

RESUMO

Cirsilineol belonging to the flavones category have not been explored in detail for anti-proliferative potential, therefore selected for the investigation. Hence, the antiproliferative potential of cirsilineol has been established in NCIH-520 cells. Cirsilineol exhibited good binding-energy and inhibited the activity of ODC, CATD, DHFR, HYAL, LOX-5, and COX-2 up to 45.14% at 100 µM. It significantly inhibited the proliferation of NCIH-520 cells (81.96%) and likewise, the proliferation of other cell lines up to 48.50%. It also induced an increase in the sub-diploid cell population, which then leads to an increase in apoptosis by 2.64 and 5.12 fold at 10 µM and 100 µM respectively. Further, the Annexin-V-FITC assay confirmed the late apoptosis and necrosis in the NCIH-520 cell line induced by cirsilineol. The ROS production was enhanced by 1.16 and 2.22 folds at 10 µM and 100 µM respectively. Besides, cirsilineol revealed acceptable ADME properties, non-toxic and non-mutagenic compound. Altogether, these findings provide evidence that cirsilineol inhibited the proliferation of NCIH-520 cells by inducing ROS-mediated apoptosis and offer new insight into the anti-proliferative potential of cirsilineol, which can further be exploited to either synthesise new derivatives or its candid usage as a herbal lead for cancer treatment.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Flavonas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Espécies Reativas de Oxigênio
20.
Curr Pharm Biotechnol ; 21(3): 236-243, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31613725

RESUMO

BACKGROUND: Phenylpropylene biosynthesis pathway plays a crucial role in the vanillin and their derivative(s) production in the plants. The intermediate of vanillin synthesis i.e. cinnamic acid (CA) is converted into 2-Hydroxy 4-MethoxyBenzaldehyde (HMB) in Decalepis arayalpathra having a number of therapeutic value. OBJECTIVE: Microwave-assisted modifications in cinnamic acid were planned for potential anticancer properties with better yield and efficiency. The present study also confirms the presence of HMB and its precursor i.e. cinnamic acid in D. arayalpathra tubers. METHODS: We used a single step Microwave Assisted Synthesis (MAS) to modify cinnamic acid, and then examined the synthetic and natural cinnamic acid derivatives anticancer potential against six human cancer (K-562, WRL-68, A549, A431, MCF-7, and COLO-201) and two normal (L-132 and HEK-293) cell lines at 2, 10 and 50 µg/ml concentrations. RESULTS: ß-bromostyrene and ß -nitrostyrene have shown inhibition with IC50 values ranging 0.10-21 µM and 0.03-0.06 µM, respectively to the cancer cell lines. ß-bromostyrene was the most potent anticancer derivative of CA with better cellular safety and biocompatibility. CONCLUSION: The present study of microwave-assisted synthesis demonstrates a single-step modification in cinnamic acid. MAS is a fast, reliable, and robust method. The resultant compounds have shown in-vitro anticancer activity against human lung carcinoma and breast adenocarcinoma.


Assuntos
Antineoplásicos/síntese química , Técnicas de Química Sintética/métodos , Cinamatos/química , Micro-Ondas , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apocynaceae/química , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cinamatos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , Camundongos , Rizoma/química
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