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1.
Nanotechnology ; 35(36)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38861966

RESUMO

Synergistic cancer therapies have attracted wide attention owing to their multi-mode tumor inhibition properties. Especially, photo-responsive photoimmunotherapy demonstrates an emerging cancer treatment paradigm that significantly improved treatment efficiency. Herein, near-infrared-II responsive ovalbumin functionalized Gold-Genipin nanosystem (Au-G-OVA NRs) was designed for immunotherapy and deep photothermal therapy of breast cancer. A facile synthesis method was employed to prepare the homogeneous Au nanorods (Au NRs) with good dispersion. The nanovaccine was developed further by the chemical cross-linking of Au-NRs, genipin and ovalbumin. The Au-G-OVA NRs outstanding aqueous solubility, and biocompatibility against normal and cancer cells. The designed NRs possessed enhanced localized surface plasmon resonance (LSPR) effect, which extended the NIR absorption in the second window, enabling promising photothermal properties. Moreover, genipin coating provided complimentary red fluorescent and prepared Au-G-OVA NRs showed significant intracellular encapsulation for efficient photoimmunotherapy outcomes. The designed nanosystem possessed deep photothermal therapy of breast cancer and 90% 4T1 cells were ablated by Au-G-OVA NRs (80µg ml-1concentration) after 1064 nm laser irradiation. In addition, Au-G-OVA NRs demonstrated outstanding vaccination phenomena by facilitating OVA delivery, antigen uptake, maturation of bone marrow dendritic cells, and cytokine IFN-γsecretion for tumor immunosurveillance. The aforementioned advantages permit the utilization of fluorescence imaging-guided photo-immunotherapy for cancers, demonstrating a straightforward approach for developing nanovaccines tailored to precise tumor treatment.


Assuntos
Ouro , Imunoterapia , Raios Infravermelhos , Iridoides , Nanotubos , Ovalbumina , Ouro/química , Iridoides/química , Iridoides/farmacologia , Animais , Ovalbumina/química , Ovalbumina/imunologia , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Feminino , Nanotubos/química , Terapia Fototérmica/métodos , Fototerapia/métodos , Camundongos Endogâmicos BALB C , Humanos , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Células Dendríticas/imunologia , Ressonância de Plasmônio de Superfície
2.
Med Oncol ; 41(8): 186, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918260

RESUMO

This comprehensive review delves into the multifaceted aspects of genipin, a bioactive compound derived from medicinal plants, focusing on its anti-cancer potential. The review begins by detailing the sources and phytochemical properties of genipin, underscoring its significance in traditional medicine and its transition into contemporary cancer research. It then explores the intricate relationship between genipin's chemical structure and its observed anti-cancer activity, highlighting the molecular underpinnings contributing to its therapeutic potential. This is complemented by a thorough analysis of preclinical studies, which investigates genipin's efficacy against various cancer cell lines and its mechanisms of action at the cellular level. A crucial component of the review is the examination of genipin's bioavailability and pharmacokinetics, providing insights into how the compound is absorbed, distributed, metabolized, and excreted in the body. Then, this review offers a general and updated overview of the anti-cancer studies of genipin and its derivatives based on its basic molecular mechanisms, induction of apoptosis, inhibition of cell proliferation, and disruption of cancer cell signaling pathways. We include information that complements the genipin study, such as toxicity data, and we differentiate this review by including commercial status, disposition, and regulation. Also, this review of genipin stands out for incorporating information on proposals for a technological approach through its load in nanotechnology to improve its bioavailability. The culmination of this information positions genipin as a promising candidate for developing novel anti-cancer drugs capable of supplementing or enhancing current cancer therapies.


Assuntos
Iridoides , Neoplasias , Humanos , Iridoides/farmacologia , Iridoides/química , Iridoides/uso terapêutico , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Apoptose/efeitos dos fármacos
3.
Carbohydr Polym ; 339: 122174, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823938

RESUMO

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.


Assuntos
Regeneração Óssea , Liofilização , Gelatina , Ácido Hialurônico , Hidrogéis , Iridoides , Fibrina Rica em Plaquetas , Animais , Iridoides/química , Iridoides/farmacologia , Gelatina/química , Coelhos , Hidrogéis/química , Hidrogéis/farmacologia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Regeneração Óssea/efeitos dos fármacos , Fibrina Rica em Plaquetas/química , Engenharia Tecidual/métodos , Reagentes de Ligações Cruzadas/química , Alicerces Teciduais/química , Tíbia/efeitos dos fármacos , Tíbia/cirurgia
4.
Chem Pharm Bull (Tokyo) ; 72(6): 547-558, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38866476

RESUMO

Iridoids, which are a class of monoterpenoids, are attractive synthetic targets due to their diversely substituted cis-fused cyclopenta[c]pyran skeletons. Additionally, various biological activities of iridoids raise the value of synthetic studies on this class of compounds. Here, our synthetic efforts toward 11-noriridoids; (±)-umbellatolide B (6), (±)-10-O-benzoylglobularigenin (9) and 1-O-pentenylaucubigenin (34) are described. For the efficient synthesis of target compounds, common synthetic intermediates (tricyclic enones 17 and 26) were prepared by the Pauson-Khand reaction. The cleavage of the acetal bond on the tricyclic enones and 1,2-reduction introduced the two hydroxy groups on the cyclopentane ring of the core scaffold. Furthermore, the C3-C4 olefin part was constructed by the syn-elimination of a thiocarbonate moiety to obtain 34. The developed synthetic routes for 6, 9, and 34 will be useful for the preparation of iridoid analogs that have a polyfunctionalized core skeleton.


Assuntos
Iridoides , Iridoides/síntese química , Iridoides/química , Estrutura Molecular , Estereoisomerismo
5.
Biomed Mater ; 19(4)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38815598

RESUMO

Bacterial infection can lead to various complications, such as inflammations on surrounding tissues, which can prolong wound healing and thus represent a significant clinical and public healthcare problem. Herein, a report on the fabrication of a novel genipin/quaternized chitosan (CS) hydrogel for wound dressing is presented. The hydrogel was prepared by mixing quaternized CS and genipin under 35 °C bath. The hydrogels showed porous structure (250-500 µm) and mechanical properties (3000-6000 Pa). In addition, the hydrogels displayed self-healing ability and adhesion performance on different substrates. Genipin crosslinked quaternized CS hydrogels showed antibacterial activities againstE. coliandS. aureus. The CCK-8 and fluorescent images confirmed the cytocompatibility of hydrogels by seeding with NIH-3T3 cells. The present study showed that the prepared hydrogel has the potential to be used as wound dressing.


Assuntos
Antibacterianos , Bandagens , Quitosana , Reagentes de Ligações Cruzadas , Escherichia coli , Hidrogéis , Iridoides , Compostos de Amônio Quaternário , Staphylococcus aureus , Cicatrização , Quitosana/química , Iridoides/química , Animais , Camundongos , Hidrogéis/química , Cicatrização/efeitos dos fármacos , Células NIH 3T3 , Antibacterianos/química , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Compostos de Amônio Quaternário/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Porosidade
6.
Food Res Int ; 186: 114161, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729685

RESUMO

In this article, the synthesis of antioxidant peptides in the enzymatic hydrolysis of caprine casein was analyzed at three different time points (60 min, 90 min, and 120 min) using immobilized pepsin on activated and modified carbon (AC, ACF, ACG 50, ACG 100). The immobilization assays revealed a reduction in the biocatalysts' activity compared to the free enzyme. Among the modified ones, ACG 50 exhibited greater activity and better efficiency for reuse cycles, with superior values after 60 min and 90 min. Peptide synthesis was observed under all studied conditions. Analyses (DPPH, ß-carotene/linoleic acid, FRAP) confirmed the antioxidant potential of the peptides generated by the immobilized enzyme. However, the immobilized enzyme in ACG 50 and ACG 100, combined with longer hydrolysis times, allowed the formation of peptides with an antioxidant capacity greater than or equivalent to those generated by the free enzyme, despite reduced enzymatic activity.


Assuntos
Antioxidantes , Caseínas , Enzimas Imobilizadas , Glutaral , Cabras , Iridoides , Pepsina A , Peptídeos , Antioxidantes/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Caseínas/química , Animais , Pepsina A/metabolismo , Pepsina A/química , Glutaral/química , Peptídeos/química , Iridoides/química , Hidrólise , Carvão Vegetal/química
7.
Bioorg Chem ; 148: 107460, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38781668

RESUMO

A series of genipin derivatives were designed and synthesized as potential inhibitors targeted KRAS G12D mutation. The majority of these compounds demonstrated potential antiproliferative effects against KRAS G12D mutant tumor cells (CT26 and A427). Notably, seven compounds exhibited the anticancer effects with IC50 values ranging from 7.06 to 9.21 µM in CT26 (KRASG12D) and A427 (KRASG12D) cells and effectively suppressed the colony formation of CT26 cells. One representative compound SK12 was selected for further investigation into biological activity and action mechanisms. SK12 markedly induced apoptosis in CT26 cells in a concentration-dependent manner. Moreover, SK12 elevated the levels of reactive oxygen species (ROS) in tumor cells and exhibited a modulatory effect on the KRAS signaling pathway, thereby inhibiting the activation of downstream phosphorylated proteins. The binding affinity of SK12 to KRAS G12D protein was further confirmed by the surface plasmon resonance (SPR) assay with a binding KD of 157 µM. SK12 also exhibited notable anticancer efficacy in a nude mice tumor model. The relative tumor proliferation rate (T/C) of the experimental group (50 mg/kg) was 31.04 % (P < 0.05), while maintaining a commendable safety profile.


Assuntos
Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Iridoides , Camundongos Nus , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Iridoides/farmacologia , Iridoides/química , Animais , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Camundongos , Estrutura Molecular , Apoptose/efeitos dos fármacos , Descoberta de Drogas , Linhagem Celular Tumoral , Mutação , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismo
8.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2654-2665, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812166

RESUMO

This study established an ultrasound-assisted extraction-high performance liquid chromatography method for simulta-neously determinining the content of 11 bioactive compounds including iridoids, phenolic acids, and flavonoids in Lonicera japonica flowers. The flowers at six stages from the rice bud stage(ML) to the golden flower stage(JH) of L. japonica varieties 'Sijuhua' and 'Beihua No.1' in two planting bases in Shandong province were collected. The established method was employed to determine the content of 11 target compounds, on the basis of which the dynamics of active components in L. japonica sampels during different development stages was investigated. The correlation analysis was carried out to reveal the correlations of the content of iridoids, phenolic acids, and flavonoids. Furthermore, the antioxidant activities of samples at different developmental stages were determined, and the relationship between antioxidant activity and chemical components was analyzed by the correlation analysis. The results showed that the total content of the 11 components in 'Sijihua' changed in a "W" pattern from the ML to JH, being the highest at the ML and the second at the slight white stage(EB). The total content of 11 compounds in 'Beihua No.1' was the highest at the ML and decreased gra-dually from the ML to JH. The samples of 'Sijihua' had higher content of iridoids and lower content of phenolic acids than those of 'Beihua No.1'. The content of flavonoids and phenolic acids showed a positive correlation(R~2=0.90, P<0.05) in 'Sijihua' but no obvious correlation in 'Beihua No.1'. The antioxidant activity and phenolic acid content showed positive correlations, with the determination coefficients(R~2) of 0.84(P<0.05) in 'Beihua No.1' and 0.73(P<0.05) in 'Sijihua'. The antioxidant activity of both varieties was the strongest at the ML and the second at the EB. This study revealed that the content dynamics of iridoids, phenolic acids, and flavonoids in 'Sijihua' and 'Beihua No.1' cultivated in Shandong province during different developmental stages. The results indicated that the antioxidant activity of L. japonica flowers was significantly correlated with the content of phenolic acids at different deve-lopmental stages, which provided a basis for determining the optimum harvest time of L. japonica flowers.


Assuntos
Antioxidantes , Flavonoides , Flores , Lonicera , Lonicera/química , Lonicera/crescimento & desenvolvimento , Lonicera/metabolismo , Flores/química , Flores/crescimento & desenvolvimento , Flores/metabolismo , Antioxidantes/metabolismo , Antioxidantes/análise , Antioxidantes/química , China , Flavonoides/análise , Flavonoides/química , Flavonoides/metabolismo , Hidroxibenzoatos/análise , Hidroxibenzoatos/metabolismo , Metabolismo Secundário , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Iridoides/metabolismo , Iridoides/análise , Iridoides/química
9.
Molecules ; 29(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731491

RESUMO

Catnip (Nepeta cataria L.) plants produce a wide array of specialized metabolites with multiple applications for human health. The productivity of such metabolites, including nepetalactones, and natural insect repellents is influenced by the conditions under which the plants are cultivated. In this study, we assessed how field-grown catnip plants, transplanted after being propagated via either single-node stem cuttings or seeds, varied regarding their phytochemical composition throughout a growing season in two distinct environmental conditions (Pittstown and Upper Deerfield) in the state of New Jersey, United States. Iridoid terpenes were quantified in plant tissues via ultra-high-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-QqQ-MS), and phenolic compounds (phenolic acids and flavonoids) were analyzed via UHPLC with diode-array detection (UHPLC-DAD). The highest contents of total nepetalactones in Pittstown were found at 6 weeks after transplanting (WAT) for both seedlings and cuttings (1305.4 and 1223.3 mg/100 g, respectively), while in Upper Deerfield, the highest contents for both propagules were at 11 WAT (1247.7 and 997.1 mg/100 g, respectively) for seed-propagated and stem cuttings). The highest concentration of nepetalactones was associated with floral-bud to partial-flowering stages. Because plants in Pittstown accumulated considerably more biomass than plants grown in Upper Deerfield, the difference in nepetalactone production per plant was striking, with peak productivity reaching only 598.9 mg per plant in Upper Deerfield and 1833.1 mg per plant in Pittstown. Phenolic acids accumulated in higher contents towards the end of the season in both locations, after a period of low precipitation, and flavone glycosides had similar accumulation patterns to nepetalactones. In both locations, rooted stem cuttings reached their maximum nepetalactone productivity, on average, four weeks later than seed-propagated plants, suggesting that seedlings have, overall, better agronomic performance.


Assuntos
Nepeta , Estações do Ano , Nepeta/química , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/química , Compostos Fitoquímicos/análise , Flavonoides/análise , Flavonoides/química , Monoterpenos Ciclopentânicos , Sementes/química , Sementes/crescimento & desenvolvimento , Extratos Vegetais/química , Iridoides/química , Pironas
10.
Biomacromolecules ; 25(6): 3519-3531, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38742604

RESUMO

Elastic fibers provide critical elasticity to the arteries, lungs, and other organs. Elastic fiber assembly is a process where soluble tropoelastin is coacervated into liquid droplets, cross-linked, and deposited onto and into microfibrils. While much progress has been made in understanding the biology of this process, questions remain regarding the timing of interactions during assembly. Furthermore, it is unclear to what extent fibrous templates are needed to guide coacervate droplets into the correct architecture. The organization and shaping of coacervate droplets onto a fiber template have never been previously modeled or employed as a strategy for shaping elastin fiber materials. Using an in vitro system consisting of elastin-like polypeptides (ELPs), genipin cross-linker, electrospun polylactic-co-glycolic acid (PLGA) fibers, and tannic acid surface coatings for fibers, we explored ELP coacervation, cross-linking, and deposition onto fiber templates. We demonstrate that integration of coacervate droplets into a fibrous template is primarily influenced by two factors: (1) the balance of coacervation and cross-linking and (2) the surface energy of the fiber templates. The success of this integration affects the mechanical properties of the final fiber network. Our resulting membrane materials exhibit highly tunable morphologies and a range of elastic moduli (0.8-1.6 MPa) comparable to native elastic fibers.


Assuntos
Elastina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Elastina/química , Ácido Láctico/química , Ácido Poliglicólico/química , Iridoides/química , Tropoelastina/química , Reagentes de Ligações Cruzadas/química , Taninos/química , Peptídeos/química , Elasticidade
11.
Phytochemistry ; 223: 114144, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754799

RESUMO

Nine previously undescribed iridoids, ptehosides A-I (1-9), together with 12 known ones (10-21), were isolated from Pterocephalus hookeri (C.B. Clarke) Höeck. Their structures were elucidated using various spectroscopic methods including HR-ESI-MS, NMR, UV, IR and CD, etc. The cytotoxic activities of all isolates were evaluated using MTT method in three human cancer cell lines (Caco2, Huh-7, and SW982). As result, compound 9 exhibited substantial inhibitory activity on Caco2, Huh-7, and SW982 cells with IC50 values of 1.17 ± 0.05, 1.15 ± 0.05 and 1.14 ± 0.04 µM, respectively. A preliminary mechanism study showed that 9 arrested the cell cycle of SW982 cells in the G0/G1 phase and induced apoptosis by upregulating Bax expression and downregulating Bcl-2 expression.


Assuntos
Antineoplásicos Fitogênicos , Apoptose , Ensaios de Seleção de Medicamentos Antitumorais , Iridoides , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Iridoides/química , Iridoides/farmacologia , Iridoides/isolamento & purificação , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
12.
Ultrason Sonochem ; 106: 106899, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38733852

RESUMO

Chitosan nanoparticles (NPs) possess great potential in biomedical fields. Orifice-induced hydrodynamic cavitation (HC) has been used for the enhancement of fabrication of size-controllable genipin-crosslinked chitosan (chitosan-genipin) NPs based on the emulsion cross-linking (ECLK). Experiments have been performed using various plate geometries, chitosan molecular weight and under different operational parameters such as inlet pressure (1-3.5 bar), outlet pressure (0-1.5 bar) and cross-linking temperature (40-70 °C). Orifice plate geometry was a crucial factor affecting the properties of NPs, and the optimized geometry of orifice plate was with single hole of 3.0 mm diameter. The size of NPs with polydispersity index of 0.359 was 312.6 nm at an optimized inlet pressure of 3.0 bar, and the maximum production yield reached 84.82 %. Chitosan with too high or too low initial molecular weight (e.g., chitosan oligosaccharide) was not applicable for producing ultra-fine and narrow-distributed NPs. There existed a non-linear monotonically-increasing relationship between cavitation number (Cv) and chitosan NP size. Scanning electron microscopy (SEM) test indicated that the prepared NPs were discrete with spherical shape. The study demonstrated the superiority of HC in reducing particle size and size distribution of NPs, and the energy efficiency of orifice type HC-processed ECLK was two orders of magnitude than that of ultrasonic horn or high shear homogenization-processed ECLK. In vitro drug-release studies showed that the fabricated NPs had great potential as a drug delivery system. The observations of this study can offer strong support for HC to enhance the fabrication of size-controllable chitosan-genipin NPs.


Assuntos
Quitosana , Hidrodinâmica , Iridoides , Nanopartículas , Tamanho da Partícula , Quitosana/química , Nanopartículas/química , Iridoides/química , Pressão , Temperatura , Peso Molecular
13.
PLoS One ; 19(4): e0301086, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662719

RESUMO

There is still a great global need for efficient treatments for the management of SARS-CoV-2 illness notwithstanding the availability and efficacy of COVID-19 vaccinations. Olive leaf is an herbal remedy with a potential antiviral activity that could improve the recovery of COVID-19 patients. In this work, the olive leaves major metabolites were screened in silico for their activity against SARS-CoV-2 by molecular docking on several viral targets such as methyl transferase, helicase, Plpro, Mpro, and RdRp. The results of in silico docking study showed that olive leaves phytoconstituents exhibited strong potential antiviral activity against SARS-CoV-2 selected targets. Verbacoside demonstrated a strong inhibition against methyl transferase, helicase, Plpro, Mpro, and RdRp (docking scores = -17.2, -20, -18.2, -19.8, and -21.7 kcal/mol.) respectively. Oleuropein inhibited 5rmm, Mpro, and RdRp (docking scores = -15, -16.6 and -18.6 kcal/mol., respectively) respectively. Apigenin-7-O-glucoside exhibited activity against methyl transferase and RdRp (docking score = -16.1 and -19.4 kcal/mol., respectively) while Luteolin-7-O-glucoside inhibited Plpro and RdRp (docking score = -15.2 and -20 kcal/mol., respectively). The in vitro antiviral assay was carried out on standardized olive leaf extract (SOLE) containing 20% oleuropein and IC50 was calculated. The results revealed that 20% SOLE demonstrated a moderate antiviral activity against SARS-CoV-2 with IC50 of 118.3 µg /mL. Accordingly, olive leaf could be a potential herbal therapy against SARS-CoV-2 but more in vivo and clinical investigations are recommended.


Assuntos
Antivirais , Iridoides , Simulação de Acoplamento Molecular , Olea , Extratos Vegetais , Folhas de Planta , Polifenóis , SARS-CoV-2 , Olea/química , Antivirais/farmacologia , Antivirais/química , SARS-CoV-2/efeitos dos fármacos , Folhas de Planta/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Iridoides/farmacologia , Iridoides/química , Humanos , Glucosídeos Iridoides/farmacologia , Glucosídeos Iridoides/química , Glucosídeos/farmacologia , Glucosídeos/química , Metiltransferases/metabolismo , Metiltransferases/antagonistas & inibidores , COVID-19/virologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Proteases 3C de Coronavírus/química , Simulação por Computador , Tratamento Farmacológico da COVID-19 , Luteolina/farmacologia , Luteolina/química , RNA Helicases/metabolismo , RNA Helicases/antagonistas & inibidores , Apigenina/farmacologia , Apigenina/química
14.
Chemosphere ; 356: 141956, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604514

RESUMO

Emerging micropollutants, such as pharmaceuticals and microplastics (MPs), have become a pressing water environmental concern. The aim of this study is to synthesize chitosan sponges using graphene oxide (GO) and genipin (GP) for the removal of pharmaceuticals (diclofenac (DCF) and triclosan (TCS)) and MPs, verify their adsorption mechanisms, evaluate the effects of temperature, pH, and salinity on their adsorption capacities, and determine their reusability. The GO5/CS/GP sponge exhibited a macroporous nature (porosity = 95%, density = 32.6 mg/cm3). GO and cross-linker GP enhanced the adsorption of DCF, TCS, and polystyrene (PS) MPs onto the CS sponges. The adsorption of DCF, TCS, and PS MPs involved multiple steps: surface diffusion and pore diffusion of the sponge. The adsorption isotherms demonstrated that Langmuir model was the most fitted well model to explain adsorption of TCS (qm = 7.08 mg/g) and PS MPs (qm = 7.42 mg/g) on GO5/CS/GP sponge, while Freundlich model suited for DCF adsorption (qm = 48.58 mg/g). DCF adsorption was thermodynamically spontaneous and endothermic; however, the adsorption of TCS and PS MPs was exothermic (283-313 K). The optimal pH was 5.5-7 due to the surface charge of the GO5/CS/GP sponge (pHzpc = 5.76) and ionization of DCF, TCS, and PS MPs. As the salinity increased, DCF removal efficiency drastically decreased due to the weakening of electrostatic interactions; however, TCS removal efficiency remained stable because TCS adsorption was mainly caused by hydrophobic and π-π interactions rather than electrostatic interaction. The removal of PS MPs was enhanced by the electrostatic screening effects of high Na+ ions. PS nanoplastics (average size = 26 nm) were removed by the GO5/CS/GP sponge at a rate of 73.0%, which was better than that of PS MPs (41.5%). In addition, the GO5/CS/GP sponge could be recycled over five adsorption-desorption cycles.


Assuntos
Quitosana , Diclofenaco , Grafite , Iridoides , Microplásticos , Triclosan , Poluentes Químicos da Água , Grafite/química , Diclofenaco/química , Quitosana/química , Adsorção , Poluentes Químicos da Água/química , Triclosan/química , Microplásticos/química , Iridoides/química , Purificação da Água/métodos , Concentração de Íons de Hidrogênio
15.
J Agric Food Chem ; 72(17): 10106-10116, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629120

RESUMO

The authentication of ingredients in formulas is crucial yet challenging, particularly for constituents with comparable compositions but vastly divergent efficacy. Rehmanniae Radix and its derivatives are extensively utilized in food supplements, which contain analogous compositions but very distinct effects. Rehmanniae Radix, also a difficult-to-detect herbal ingredient, was chosen as a case to explore a novel HPTLC-QDa MS technique for the identification of herbal ingredients in commercial products. Through systematic condition optimization, including thin layer and mass spectrometry, a stable and reproducible HPTLC-QDa MS method was established, which can simultaneously detect oligosaccharides and iridoids. Rehmannia Radix and its processed products were then analyzed to screen five markers that could distinguish between raw and prepared Rehmannia Radix. An HPTLC-QDa-SIM method was further established for formula detection by using the five markers and validated using homemade prescriptions and negative controls. Finally, this method was applied to detect raw and prepared Rehmannia Radix in 12 commercial functional products and supplements.


Assuntos
Medicamentos de Ervas Chinesas , Rehmannia , Rehmannia/química , Cromatografia em Camada Fina/métodos , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão/métodos , Raízes de Plantas/química , Suplementos Nutricionais/análise , Espectrometria de Massas/métodos , Oligossacarídeos/análise , Oligossacarídeos/química , Iridoides/análise , Iridoides/química
16.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38673848

RESUMO

Alzheimer's disease is associated with protein aggregation, oxidative stress, and the role of acetylcholinesterase in the pathology of the disease. Previous investigations have demonstrated that geniposide and harpagoside protect the brain neurons, and cerium nanoparticles (CeO2 NPs) have potent redox and antioxidant properties. Thus, the effect of nanoparticles of Ce NPs and geniposide and harpagoside (GH/CeO2 NPs) on ameliorating AD pathogenesis was established on AlCl3-induced AD in mice and an aggregation proteins test in vitro. Findings of spectroscopy analysis have revealed that GH/CeO2 NPs are highly stable, nano-size, spherical in shape, amorphous nature, and a total encapsulation of GH in cerium. Treatments with CeO2 NPs, GH/CeO2 NPs, and donepezil used as positive control inhibit fibril formation and protein aggregation, protect structural modifications in the BSA-ribose system, have the ability to counteract Tau protein aggregation and amyloid-ß1-42 aggregation under fibrillation condition, and are able to inhibit AChE and BuChE. While the GH/CeO2 NPs, treatment in AD induced by AlCl3 inhibited amyloid-ß1-42, substantially enhanced the memory, the cognition coordination of movement in part AD pathogenesis may be alleviated through reducing amyloidogenic pathway and AChE and BuChE activities. The findings of this work provide important comprehension of the chemoprotective activities of iridoids combined with nanoparticles. This could be useful in the development of new therapeutic methods for the treatment of neurodegenerative diseases.


Assuntos
Acetilcolinesterase , Doença de Alzheimer , Cério , Iridoides , Fármacos Neuroprotetores , Cério/química , Cério/farmacologia , Iridoides/farmacologia , Iridoides/química , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Camundongos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Masculino , Nanopartículas/química , Nanopartículas Metálicas/química , Modelos Animais de Doenças
17.
Chem Biodivers ; 21(4): e202400188, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38372184

RESUMO

Two rare 5/5/5/6 four-ring system iridoids, allamancins A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compounds 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated in vitro. Compounds 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3±0.12 and 22.1±0.14 µM, respectively. Compounds 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.


Assuntos
Apocynaceae , Iridoides , Humanos , Iridoides/farmacologia , Iridoides/química , Células HeLa , Apocynaceae/química , Óxido Nítrico/metabolismo , Cristalografia por Raios X , Estrutura Molecular
18.
Chem Biodivers ; 21(2): e202301949, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326086

RESUMO

Five new iridoids, valeralides A-E (1-5), two new acyclic monoterpenoids, valeralides F (6) and G (7), together with two known iridoids (8 and 9), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated based on 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. The absolute configuration of compounds 1-4 were elucidated based on electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their inhibition on nitric oxide production, cytotoxicity and anti-influenza A virus activity.


Assuntos
Rizoma , Valeriana , Estrutura Molecular , Valeriana/química , Iridoides/química , Monoterpenos/análise , Raízes de Plantas/química
19.
J Asian Nat Prod Res ; 26(6): 690-698, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38192122

RESUMO

Two neolignan glycosides including a new one (1), along with seven iridoid glycosides (3 - 9) and nine flavonoid glycosides (10 - 18), were isolated from the leaves of Vaccinium bracteatum. Their structures were established mainly on the basis of 1D/2D NMR and ESIMS analyses, as well as comparison to known compounds in the literature. The structure of 1 with absolute stereochemistry was also confirmed by chemical degradation and ECD calculation. Selective compounds showed antiradical activity against ABTS and/or DPPH. Moreover, several isolates also suppressed the production of ROS in RAW264.7 cells and exerted neuroprotective effect toward PC12 cells.


Assuntos
Flavonoides , Glicosídeos , Lignanas , Folhas de Planta , Folhas de Planta/química , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/isolamento & purificação , Animais , Camundongos , Células PC12 , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , Estrutura Molecular , Lignanas/química , Lignanas/farmacologia , Lignanas/isolamento & purificação , Ratos , Células RAW 264.7 , Vaccinium/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Iridoides/química , Iridoides/farmacologia , Iridoides/isolamento & purificação , Glicosídeos Iridoides/química , Glicosídeos Iridoides/farmacologia , Glicosídeos Iridoides/isolamento & purificação , Espécies Reativas de Oxigênio , Picratos/farmacologia
20.
Phytochemistry ; 219: 113962, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38185394

RESUMO

Thirteen previously undescribed iridoids (1-13), together with five known iridoids (14-18) were isolated from the roots and rhizomes of Valeriana jatamansi Jones. Their structures with absolute configurations were elucidated by analysis of MS, NMR, optical rotation and their experimental and calculated electronic circular dichroism spectra. All of the isolated compounds were tested for their protective effects against α-hemolysin-induced cell death in A549 cells. Compounds 14, 16 and 17 showed moderate protective effects, and compounds 15 and 18 showed weak protective effects.


Assuntos
Nardostachys , Valeriana , Rizoma , Valeriana/química , Proteínas Hemolisinas/análise , Estrutura Molecular , Iridoides/farmacologia , Iridoides/química , Raízes de Plantas/química
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