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The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1-MCu9) and Zn II (MZn1-MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives' biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski's rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development.
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Complexos de Coordenação , Metformina , Cobre/química , Metformina/farmacologia , Zinco/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Simulação de Acoplamento Molecular , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Espectroscopia de Infravermelho com Transformada de Fourier , alfa-Glucosidases/químicaRESUMO
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial proliferation and bone destruction. Adenosine deaminase (ADA) is a key inflammatory enzyme that increases joint stiffness and pain in RA. In this study, we evaluated the in-silico, and in vivo inhibitory effect of quercetin isolated from Egyptian Fenugreek on ADA enzyme activity. We also determined the combinatorial effect of quercetin on methotrexate mediated anti-inflammatory efficacy and toxicity. In-silico molecular docking was conducted and confirmed in an in vivo RA rat model. The results showed that the inhibition constant of quercetin on joint ADA by docking and in-vitro was 61.9 and 55.5 mM, respectively. Therefore, quercetin exhibits anti-inflammatory effect in a rat RA model as evidenced by reducing the specific activity of ADA in joint tissues, lower jaw volume, enhance body weight, downregulate ADA gene expression, reduce levels of RA cytokines interleukin-1ß, interleukin-6, tumor necrosis factor-α, also, rheumatoid factor, C-reactive protein, and anti-cyclic citrullinated peptide RA biomarker levels. These findings demonstrate that the purified quercetin has a promising anti-inflammatory effect against RA disease through its inhibitory effects on the ADA enzyme. Furthermore, isolated quercetin improved the anti-inflammatory efficacy of methotrexate, reduced its toxic effects by increasing antioxidant enzymes and reducing oxidative stress.
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Artrite Reumatoide , Quercetina , Adenosina Desaminase , Animais , Artrite Reumatoide/tratamento farmacológico , Simulação de Acoplamento Molecular , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Cosmetic-containing herbals are a cosmetic that has or is claimed to have medicinal properties, with bioactive ingredients purported to have medical benefits. There are no legal requirements to prove that these products live up to their claims. The name is a combination of "cosmetics" and "pharmaceuticals". "Nutricosmetics" are related dietary supplements or food or beverage products with additives that are marketed as having medical benefits that affect appearance. Cosmetic-containing herbals are topical cosmetic-pharmaceutical hybrids intended to enhance the health and beauty of the skin. Cosmetic-containing herbals improve appearance by delivering essential nutrients to the skin. Several herbal products, such as cosmetic-containing herbals, are available. The present review highlights the use of natural products in cosmetic-containing herbals, as natural products have many curative effects as well as healing effects on skin and hair growth with minimal to no side effects. A brief description is given on such plants, their used parts, active ingredients, and the therapeutic properties associated with them. Mainly, the utilization of phytoconstituents as cosmetic-containing herbals in the care of skin and hair, such as dryness of skin, acne, eczema, inflammation of the skin, aging, hair growth, and dandruff, along with natural ingredients, such as for hair colorant, are explained in detail in the present review.
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Produtos Biológicos/uso terapêutico , Cosmecêuticos/uso terapêutico , Cosméticos/uso terapêutico , Envelhecimento da Pele/efeitos dos fármacos , Dermatopatias/tratamento farmacológico , Pele/metabolismo , HumanosRESUMO
Curcumin is the primary polyphenol in turmeric's curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin's bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.
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Doença Crônica/tratamento farmacológico , Curcumina/uso terapêutico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Disponibilidade Biológica , Doença Crônica/prevenção & controle , Curcumina/análogos & derivados , Curcumina/química , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanotecnologia , SolubilidadeRESUMO
Context Cyclophosphamide (CTX) is used to treat different cancer types, although it causes severe hepatotoxicity due to its oxidative stress effect. Rosmarinus officinalis, L. (Lamiaceae) has a therapeutic potential against hepatotoxicity due to its antioxidant activity. Objective The objective of this study is to investigate the phytochemical analysis of the methanol extract of Rosmarinus officianalis leaves (MEROL) and its efficacy against CTX-induced hepatotoxicity. Materials and methods The phytochemical analyses were assessed spectrophotometericaly. To assess the MEROL efficacy, 72 Swiss albino mice were divided into six groups. Group 1 was control, groups 2 and 3 included mice which were injected intraperitoneally (i.p.) with 100 or 200 mg/kg of MEROL at days 1, 4, 7, 10, 13 and 16; group 4 was injected (i.p.) with CTX (200 mg/kg) at day 17, groups 5 and 6 were injected (i.p.) with MEROL as groups 3 and 4 followed by 200 mg/kg CTX at day 17, respectively. At day 22, six mice from each group were sacrificed and the others were sacrificed at day 37. Results MEROL has a high content of total phenolics, saponins, total antioxidant capacity and DPPH radical scavenging activity. The median lethal dose (LD50) value of MEROL was 4.125 g/kg b.w. The inhibitory concentration 50 (IC50) value for DPPH radical scavenging was 55 µg/mL. Pretreatment with 100 mg/kg MEROL for 16 d ameliorated CTX-induced hepatotoxicity represented in lowering the levels of the aspartate aminotransferase (AST) and lipid profile and minimizing the histological damage. Conclusions Pretreatment with 100 mg/kg b.w. MEROL mitigated CTX-induced hepatotoxicity due to its antioxidant activity.
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Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Ciclofosfamida , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rosmarinus , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Biomarcadores/sangue , Compostos de Bifenilo/química , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Dose Letal Mediana , Fígado/metabolismo , Fígado/patologia , Masculino , Metanol/química , Camundongos , Fenóis/isolamento & purificação , Fenóis/farmacologia , Fitoterapia , Picratos/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta , Plantas Medicinais , Rosmarinus/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Solventes/química , Análise Espectral , Fatores de TempoRESUMO
CONTEXT: Cyclophosphamide (CTX) is a common anticancer agent used for the treatment of several malignancies. However, upon treatment, it induces severe toxicity due to its oxidative stress capability. Propolis, a natural product collected by honey bees, has shown several biological activities, such as free radical scavenging and antioxidant agent. OBJECTIVE: This study elucidates the protective effects of propolis against CTX-induced changes in mice. MATERIALS AND METHODS: Forty-eight male Swiss albino mice were divided into four groups; group 1 was intraperitoneally (i.p.) injected with 200 µL of phosphate buffer saline (PBS), group 2 was injected with 100 mg/kg/d propolis, group 3 was injected with a single dose of CTX (200 mg/kg), and group 4 was injected with a single dose of CTX (200 mg/kg) followed by propolis (100 mg/kg) for 7 consecutive days. After 12 d, mice were bled and then sacrificed to analyze the hematological, biochemical, and histological parameters. RESULTS: The results indicated that CTX-injected mice showed an increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine and a decrease in the total number of white blood cells (WBCs) and platelets. Moreover, dramatically changes in the histological architectures of the liver and kidney were observed. The mice that were injected with CTX/propolis showed an improvement in the levels of ALT, AST, urea, creatinine, WBCs, and platelets. Moreover, the histological picture of the liver and kidney was significantly improved. CONCLUSIONS: In conclusion, propolis might be considered an effective agent in ameliorating the toxicity resulted from CTX treatment.
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Antineoplásicos Alquilantes/toxicidade , Antioxidantes/farmacologia , Ciclofosfamida/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Própole/farmacologia , Animais , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacosRESUMO
New sugar hydrazones linked to norbornyl ring system, their oxadiazole acyclic nucleoside analogs and the corresponding thioglycosides were synthesized. The synthesized compounds were tested for their antimicrobial activity and displayed different degrees of activities or inhibitory actions. Their oxadiazole acyclic nucleoside analogs and thioglycosides showed higher activities.
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Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Norbornanos/síntese química , Norbornanos/farmacologia , Nucleosídeos/síntese química , Nucleosídeos/farmacologia , Oxidiazóis/síntese química , Oxidiazóis/farmacologia , Tioglicosídeos/síntese química , Tioglicosídeos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Streptomyces/efeitos dos fármacos , Streptomyces/crescimento & desenvolvimentoRESUMO
Chlorpyrifos (CPF) is a broad-spectrum insecticide widely employed in agricultural field for pest control. Exposure to CPF is associated with serious effects to the main organs, including kidneys. Significant evidence denotes that oxidative stress (OS) and inflammation are implicated in CPF toxicity. This study aimed to evaluate the potential of farnesol (FAR) to modulate inflammatory mediators and farnesoid-X-receptor (FXR) and Nrf2 in a rat model of CPF nephrotoxicity. CPF and FAR were orally supplemented for 28 days and blood and kidney samples were collected for investigations. CPF administration elevated blood creatinine and urea, kidney MDA and NO, and upregulated NF-κB p65, IL-1ß, TNF-α, iNOS, and caspase-3. In addition, CPF upregulated kidney Keap1, and decreased GSH, antioxidant enzymes, and Nrf2, FXR, HO-1 and NQO-1. FAR ameliorated creatinine and urea, prevented histopathological alterations, decreased MDA and NO, and enhanced antioxidants in CPF-administered rats. FAR modulated NF-κB p65, iNOS, TNF-α, IL-1ß, caspase-3, Keap1, HO-1, NQO-1, Nrf2 and FXR. In silico investigations revealed the binding affinity of FAR towards Keap1 and FXR, as well as NF-κB, caspase-3, iNOS, and HO-1. In conclusion, FAR prevents CPF-induced kidney injury by attenuating OS, inflammation, and apoptosis, effects associated with modulation of FXR, Nrf2/HO-1 signaling and antioxidants.
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Clorpirifos , Farneseno Álcool , Rim , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Receptores Citoplasmáticos e Nucleares , Animais , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Clorpirifos/toxicidade , Masculino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Ratos , Farneseno Álcool/farmacologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Ratos Wistar , Mediadores da Inflamação/metabolismo , Inseticidas/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Nefropatias/metabolismo , Antioxidantes/farmacologiaRESUMO
BACKGROUND: Venomous marine cone snails produce unique neurotoxins called conopeptides or conotoxins, which are valuable for research and drug discovery. Characterizing Conus venom is important, especially for poorly studied species, as these tiny and steady molecules have considerable potential as research tools for detecting new pharmacological applications. In this study, a worm-hunting cone snail, Conus flavidus inhabiting the Red Sea coast were collected, dissected and the venom gland extraction was subjected to proteomic analysis to define the venom composition, and confirm the functional structure of conopeptides. RESULTS: Analysis of C. flavidus venom identified 117 peptide fragments and assorted them to conotoxin precursors and non-conotoxin proteins. In this procedure, 65 conotoxin precursors were classified and identified to 16 conotoxin precursors and hormone superfamilies. In the venom of C. flavidus, the four conotoxin superfamilies T, A, O2, and M were the most abundant peptides, accounting for 75.8% of the total conotoxin diversity. Additionally, 19 non-conotoxin proteins were specified in the venom, as well as several potentially biologically active peptides with putative applications. CONCLUSION: Our research displayed that the structure of the C. flavidus-derived proteome is similar to other Conus species and includes toxins, ionic channel inhibitors, insulin-like peptides, and hyaluronidase. This study provides a foundation for discovering new conopeptides from C. flavidus venom for pharmaceutical use.
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The present work attempted to provide a comprehensive description of the morphoanatomical, histological, and ultrastructural characteristics of the tongue in the desert hedgehog (Paraechinus aethiopicus), and to correlate lingual modifications to the feeding lifestyle. Five adult male hedgehogs were utilized in our investigation. The macroscopic observations revealed elongated, with a moderately pointed apex, tongue and the tongue dorsum lacks both lingual prominence and median sulcus. The main subdivisions of the tongue are radix linguae (root), corpus linguae (body), and apex linguae (apex). The tongue dorsum carries two types of mechanical (conical and filiform) and gustatory (fungiform and circumvallate) papillae. The lingual apex is characterized by the existence of a unique encapsulated muscular structure. Additionally, the lingual glands were interposed between the muscular strands and no lingual glands were detected on the lingual apex. The dorsal surface of the lingual apex exhibited the highest level of keratinization as revealed by histochemical staining while the root showed moderate staining. The topography of the tongue was investigated by scanning electron microscopy (SEM). The obtained results are important to provide basic knowledge that can contribute to better understanding of the nourishment, feeding habits and behavior in this species. Furthermore, the addition of the newly investigated species may help us to determine the evolutionary relationships among species.
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Ouriços , Papilas Gustativas , Masculino , Animais , Língua , Papilas Gustativas/ultraestrutura , Microscopia Eletrônica de Varredura , Evolução BiológicaRESUMO
Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1ß, MCP-1, JNK1, and TGF-ß in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd.
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Cádmio , Cardiotoxicidade , Inflamassomos , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo , Ubiquinona , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/metabolismo , Cardiotoxicidade/prevenção & controle , NF-kappa B/metabolismo , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Masculino , Cádmio/toxicidade , Regulação para Baixo/efeitos dos fármacos , Antioxidantes/farmacologiaRESUMO
Drug-induced liver damage is a life-threatening disorder, and one major form of it is the hepatotoxicity induced by the drug cisplatin. In folk medicine, Licorice (Glycyrrhiza glabra (is used for detoxification and is believed to be a potent antioxidant. Currently, the magically self-renewable potential of bone marrow mesenchymal stem cells (BM-MSCs) has prompted us to explore their hepatoregenerative capability. The impact of G. glabra extract (GGE) and BM-MSCs alone and, in combination, on protecting against hepatotoxicity was tested on cisplatin-induced liver injury in rats. Hepatic damage, as revealed by liver histopathology and increased levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA), was elevated in rats by received 7 mg/kg of cisplatin intraperitoneally. The combination of GGE and BM-MSCs returned the enzyme levels to near the normal range. It also improved levels of liver superoxide dismutase (SOD) and glutathione (GSH) and reduced MDA levels. Additionally, it was found that when GGE and BM-MSCs were used together, they significantly downregulated caspase9 (Casp9), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and interleukin-1ß (IL-1ß), which are involved in severe proinflammatory and apoptotic signaling cascades in the liver. Moreover, combining GGE and BM-MSCs led to the normal result of hepatocytes in several examined liver histological sections. Therefore, our findings suggest that GGE may have protective effects against oxidative liver damage and the promising regenerative potential of BM-MSCs.
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Microcystis aeruginosa produces an abundant cyanotoxin (microcystins (MCs) in freshwater supplies. MCs have adverse health hazards to animals and humans. Microcystin-leucine-arginine (microcystin-LR or MC-LR) is the most studied among these MCs due to their high toxicity. So, this study was designed to evaluate the possible therapeutic role of the natural algal food supplement, Spirulina platensis (SP), against MC-LR-induced toxic effects in male Wistar rats. Forty rats were randomly divided into five groups. Control and SP groups orally administered distilled water and SP (1000 mg/kg/daily), respectively, for 21 days. MC-LR group was intraperitoneally injected with MC-LR (10 µg/kg/day) for 14 days. MC-LR-SP500 and MC-LR-SP1000 groups were orally treated with SP (500 and 1000 mg/kg, respectively) for 7 days and concomitantly with MC-LR for 14 days. MC-LR induced oxidative hepatorenal damage, cardiotoxicity, and neurotoxicity greatly, which was represented by reduction of reduced glutathione content and the activities of glutathione peroxidase, catalase, and superoxide dismutase and elevation of concentrations of nitric oxide and malondialdehyde in renal, hepatic, brain, and heart tissues. In addition, it increased serum levels of urea, creatinine, tumor necrosis factor-alfa, interleukin-1beta and interleukin-6 and serum activities of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase-MB. However, S. platensis restored normal levels of measured serum parameters, ameliorated MC-LR-induced oxidative damage, and normalized tissue antioxidant biomarkers. In conclusion, SP alleviated MC-induced organ toxicities by mitigating oxidative and nitrosative stress and lipid peroxidation.
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Toxinas Marinhas , Microcistinas , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Fígado/metabolismo , Masculino , Microcistinas/metabolismo , Microcistinas/toxicidade , Estresse Oxidativo , Ratos , Ratos Wistar , SpirulinaRESUMO
In this focused progress review, the most widely accepted methods of transdermal drug delivery are hypodermic needles, transdermal patches and topical creams. However, microneedles (MNs) (or microneedle arrays) are low-invasive 3D biomedical constructs that bypass the skin barrier and produce systemic and localized pharmacological effects. In the past, biomaterials such as carbohydrates, due to their physicochemical properties, have been extensively used to manufacture microneedles (MNs). Due to their wide range of functional groups, carbohydrates enable the design and development of tunable properties and functionalities. In recent years, numerous microneedle products have emerged on the market, although much research needs to be undertaken to overcome the various challenges before the successful introduction of microneedles into the market. As a result, carbohydrate-based microarrays have a high potential to achieve a future step in sensing, drug delivery, and biologics restitution. In this review, a comprehensive overview of carbohydrates such as hyaluronic acid, chitin, chitosan, chondroitin sulfate, cellulose and starch is discussed systematically. It also discusses the various drug delivery strategies and mechanical properties of biomaterial-based MNs, the progress made so far in the clinical translation of carbohydrate-based MNs, and the promotional opportunities for their commercialization. In conclusion, the article summarizes the future perspectives of carbohydrate-based MNs, which are considered as the new class of topical drug delivery systems.
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Hyperuricemia represents a risk factor for the progression of chronic kidney disease. Oxidative stress and inflammation are implicated in the mechanisms underlying hyperuricemia-mediated kidney injury. Monolluma quadrangula possesses several beneficial effects; however, its effect on hyperuricemia has not been investigated. This study evaluated the renoprotective and xanthine oxidase (XO) inhibitory activity of M. quadrangula in hyperuricemic rats. Phytochemical investigation revealed the presence of six known flavonoid isolated for the first time from this species. The rats received M. quadrangula extract (MQE) and potassium oxonate (PO) for 7 days. In vitro assays showed the radical scavenging and XO inhibitory activities of MQE, and in silico molecular docking revealed the inhibitory activity of the isolated flavonoids towards XO. Hyperuricemic rats showed elevated serum uric acid, creatinine, urea, and XO activity, and renal pro-inflammatory cytokines, MDA and NO, and decreased GSH, SOD, and catalase. MQE ameliorated serum uric acid, urea, creatinine, and XO activity, and renal pro-inflammatory cytokines. In addition, MQE attenuated renal oxidative stress, enhanced antioxidants, downregulated URAT-1, and GLUT-9 and upregulated OAT-1 in PO-induced rats. In conclusion, M. quadrangula attenuated hyperuricemia and kidney impairment by suppressing XO activity, oxidative stress and inflammation, and modulating urate transporters.
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Hiperuricemia , Animais , Catalase , Creatinina , Citocinas , Flavonoides/toxicidade , Hiperuricemia/induzido quimicamente , Inflamação , Rim , Simulação de Acoplamento Molecular , Ácido Oxônico , Extratos Vegetais/farmacologia , Ratos , Superóxido Dismutase , Ureia/farmacologia , Ácido Úrico , Xantina OxidaseRESUMO
Polymeric nanocomposites have been outstanding functional materials and have garnered immense attention as sustainable materials to address multi-disciplinary problems. MXenes have emerged as a newer class of 2D materials that produce metallic conductivity upon interaction with hydrophilic species, and their delamination affords monolayer nanoplatelets of a thickness of about one nm and a side size in the micrometer range. Delaminated MXene has a high aspect ratio, making it an alluring nanofiller for multifunctional polymer nanocomposites. Herein, we have classified and discussed the structure, properties and application of major polysaccharide-based electroactive hydrogels (hyaluronic acid (HA), alginate sodium (SA), chitosan (CS) and cellulose) in biomedical applications, starting with the brief historical account of MXene's development followed by successive discussions on the synthesis methods, structures and properties of nanocomposites encompassing polysaccharides and MXenes, including their biomedical applications, cytotoxicity and biocompatibility aspects. Finally, the MXenes and their utility in the biomedical arena is deliberated with an eye on potential opportunities and challenges anticipated for them in the future, thus promoting their multifaceted applications.
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Neurodegenerative disorders (NDs) including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis have various disease-specific causal factors and pathological features. A very common characteristic of NDs is oxidative stress (OS), which takes place due to the elevated generation of reactive oxygen species during the progression of NDs. Furthermore, the pathological condition of NDs including an increased level of protein aggregates can further lead to chronic inflammation because of the microglial activation. Carotenoids (CTs) are naturally occurring pigments that play a significant role in averting brain disorders. More than 750 CTs are present in nature, and they are widely available in plants, microorganisms, and animals. CTs are accountable for the red, yellow, and orange pigments in several animals and plants, and these colors usually indicate various types of CTs. CTs exert various bioactive properties because of its characteristic structure, including anti-inflammatory and antioxidant properties. Due to the protective properties of CTs, levels of CTs in the human body have been markedly linked with the prevention and treatment of multiple diseases including NDs. In this review, we have summarized the relationship between OS, neuroinflammation, and NDs. In addition, we have also particularly focused on the antioxidants and anti-inflammatory properties of CTs in the management of NDs.
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Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Carotenoides/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Carotenoides/classificação , Carotenoides/farmacologia , Humanos , Estresse Oxidativo/efeitos dos fármacosRESUMO
BACKGROUND: Lung diseases including chronic obstructive pulmonary disease (COPD), infections like influenza, acute respiratory distress syndrome (ARDS), asthma and pneumonia lung cancer (LC) are common causes of sickness and death worldwide due to their remoteness, cold and harsh climatic conditions, and inaccessible health care facilities. PURPOSE: Many drugs have already been proposed for the treatment of lung diseases. Few of them are in clinical trials and have the potential to cure infectious diseases. Plant extracts or herbal products have been extensively used as Traditional Chinese Medicine (TCM) and Indian Ayurveda. Moreover, it has been involved in the inhibition of certain genes/protiens effects to promote regulation of signaling pathways. Natural remedies have been scientifically proven with remarkable bioactivities and are considered a cheap and safe source for lung disease. METHODS: This comprehensive review highlighted the literature about traditional plants and their metabolites with their applications for the treatment of lung diseases through experimental models in humans. Natural drugs information and mode of mechanism have been studied through the literature retrieved by Google Scholar, ScienceDirect, SciFinder, Scopus and Medline PubMed resources against lung diseases. RESULTS: In vitro, in vivo and computational studies have been explained for natural metabolites derived from plants (like flavonoids, alkaloids, and terpenoids) against different types of lung diseases. Probiotics have also been biologically active therapeutics against cancer, anti-inflammation, antiplatelet, antiviral, and antioxidants associated with lung diseases. CONCLUSION: The results of the mentioned natural metabolites repurposed for different lung diseases especially for SARS-CoV-2 should be evaluated more by advance computational applications, experimental models in the biological system, also need to be validated by clinical trials so that we may be able to retrieve potential drugs for most challenging lung diseases especially SARS-CoV-2.
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Tratamento Farmacológico da COVID-19 , Pneumopatias , Suplementos Nutricionais , Humanos , Pneumopatias/tratamento farmacológico , Medicina Tradicional Chinesa , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Fitoterapia , Extratos Vegetais/farmacologia , SARS-CoV-2RESUMO
Sentinel lymph node (SLN) sampling is important for evaluating the nodal stage of breast cancer when the axillary nodes are clinically free of metastasis. The intraoperative frozen section (IFS) of SLN is used for lymph node assessment. This meta-analysis aims to provide evidence about the diagnostic accuracy and the applicability of IFS of SLN in breast cancer patients. Data were collected by searching PubMed, Cochrane, Scopus, and Web of Science electronic databases for trials matching our eligibility criteria. The statistical analysis included the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and pooled studies' diagnostic odds ratio outcomes. The analyses were conducted using the Open Meta-analyst software. This meta-analysis pooled the results of 110 studies. The overall sensitivity of IFS for SLN metastasis was 74.7%; 95% CI [72.0, 77.2], P < 0.001. It was 31.4% 95% CI [25.2, 38.3], P < 0.001 for the micro-metastasis, and 90.2%; 95% CI [86.5, 93.0], P < 0.001 for the macro-metastasis. The overall specificity was 99.4%; 95% CI [99.2, 99.6], P < 0.001. The overall positive likelihood ratio was 121.4; 95% CI [87.9, 167.6], P < 0.001, and the overall negative likelihood ratio was 0.226; 95% CI [0.186, 0.274], P < 0.001. The overall diagnostic odds ratio of IFS for diagnosing SLN metastasis was 569.5; 95% CI [404.2, 802.4], P < 0.001. The intraoperative frozen section of SLN has good sensitivity for diagnosing breast cancer macro-metastasis. However, the sensitivity is low for micro-metastasis. The specificity is very satisfactory.
Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Neoplasias da Mama/patologia , Feminino , Secções Congeladas , Humanos , Metástase Linfática/patologia , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodosRESUMO
BACKGROUND: Diverse and unique bioactive neurotoxins known as conopeptides or conotoxins are produced by venomous marine cone snails. Currently, these small and stable molecules are of great importance as research tools and platforms for discovering new drugs and therapeutics. Therefore, the characterization of Conus venom is of great significance, especially for poorly studied species. METHODS: In this study, we used bioanalytical techniques to determine the venom profile and emphasize the functional composition of conopeptides in Conus taeniatus, a neglected worm-hunting cone snail. RESULTS: The proteomic analysis revealed that 84.0% of the venom proteins were between 500 and 4,000 Da, and 16.0% were > 4,000 Da. In C. taeniatus venom, 234 peptide fragments were identified and classified as conotoxin precursors or non-conotoxin proteins. In this process, 153 conotoxin precursors were identified and matched to 23 conotoxin precursors and hormone superfamilies. Notably, the four conotoxin superfamilies T (22.87%), O1 (17.65%), M (13.1%) and O2 (9.8%) were the most abundant peptides in C. taeniatus venom, accounting for 63.40% of the total conotoxin diversity. On the other hand, 48 non-conotoxin proteins were identified in the venom of C. taeniatus. Moreover, several possibly biologically active peptide matches were identified, and putative applications of the peptides were assigned. CONCLUSION: Our study showed that the composition of the C. taeniatus-derived proteome is comparable to that of other Conus species and contains an effective mix of toxins, ionic channel inhibitors and antimicrobials. Additionally, it provides a guidepost for identifying novel conopeptides from the venom of C. taeniatus and discovering conopeptides of potential pharmaceutical importance.