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1.
Environ Res ; 227: 115771, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-36967001

RESUMEN

Malignant melanoma is the most dangerous type of skin cancer. It is becoming more common globally and is increasingly resistant to treatment options. Despite extensive research into its pathophysiology, there are still no proven cures for metastatic melanoma. Unfortunately, current treatments are frequently ineffective and costly, and have several adverse effects. Natural substances have been extensively researched for their anti-MM capabilities. Chemoprevention and adjuvant therapy with natural products is an emerging strategy to prevent, cure or treat melanoma. Numerous prospective drugs are found in aquatic species, providing a plentiful supply of lead cytotoxic chemicals for cancer treatment. Anticancer peptides are less harmful to healthy cells and cure cancer through several different methods, such as altered cell viability, apoptosis, angiogenesis/metastasis suppression, microtubule balance disturbances and targeting lipid composition of the cancer cell membrane. This review addresses marine peptides as effective and safe treatments for MM and details their molecular mechanisms of action.


Asunto(s)
Antineoplásicos , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Péptidos/farmacología , Péptidos/uso terapéutico , Apoptosis , Melanoma Cutáneo Maligno
2.
Phytother Res ; 37(4): 1590-1605, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36752350

RESUMEN

Usually, in aerobic metabolism, natural materials including nucleic acids, proteins, and lipids can experience auxiliary injury by oxidative responses. This damage produced by reactive oxygen/nitrogen species has been identified as "oxidative stress." As a natural polyphenol got from red wine and peanuts, resveratrol is one of the most eminent anti-aging mixtures. Based on many studies', resveratrol hinders destructive effects of inflammatory causes and reactive oxygen radicals in several tissues. The nuclear erythroid 2-related factor 2 is a factor related to transcription with anti-inflammatory, antioxidant possessions which is complicated by enzyme biotransformation and biosynthesis of lipids and carbohydrates. This review provides current understanding and information about the character of resveratrol against oxidative stress and regulation of inflammation via Nrf2 signaling pathway.


Asunto(s)
Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Humanos , Resveratrol/uso terapéutico , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal , Inflamación/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Especies de Nitrógeno Reactivo , Lípidos
3.
Molecules ; 28(4)2023 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-36838577

RESUMEN

Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3's ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC50 value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy.


Asunto(s)
Diabetes Mellitus Experimental , Ratones , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , alfa-Glucosidasas/metabolismo , Antioxidantes/química , Extractos Vegetales/química , Succinimidas , alfa-Amilasas
4.
Mar Drugs ; 20(8)2022 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-35892934

RESUMEN

Prostate cancer (PCa) is the leading cause of cancer death in men, and its treatment is commonly associated with severe adverse effects. Thus, new treatment modalities are required. In this context, natural compounds have been widely explored for their anti-PCa properties. Aquatic organisms contain numerous potential medications. Anticancer peptides are less toxic to normal cells and provide an efficacious treatment approach via multiple mechanisms, including altered cell viability, apoptosis, cell migration/invasion, suppression of angiogenesis and microtubule balance disturbances. This review sheds light on marine peptides as efficacious and safe therapeutic agents for PCa.


Asunto(s)
Antineoplásicos , Neoplasias de la Próstata , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Organismos Acuáticos/química , Línea Celular Tumoral , Supervivencia Celular , Humanos , Masculino , Péptidos/farmacología , Péptidos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico
5.
Molecules ; 27(3)2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35164185

RESUMEN

Cancer is the second most fatal disease worldwide, with colon cancer being the third most prevalent and fatal form of cancer in several Western countries. The risk of acquisition of resistance to chemotherapy remains a significant hurdle in the management of various types of cancer, especially colon cancer. Therefore, it is essential to develop alternative treatment modalities. Naturally occurring alkaloids have been shown to regulate various mechanistic pathways linked to cell proliferation, cell cycle, and metastasis. This review aims to shed light on the potential of alkaloids as anti-colon-cancer chemotherapy agents that can modulate or arrest the cell cycle. Preclinical investigated alkaloids have shown anti-colon cancer activities and inhibition of cancer cell proliferation via cell cycle arrest at different stages, suggesting that alkaloids may have the potential to act as anticancer molecules.


Asunto(s)
Alcaloides/química , Alcaloides/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Alcaloides/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Descubrimiento de Drogas , Humanos
6.
Molecules ; 27(13)2022 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-35807304

RESUMEN

Diabetes mellitus is a multifactorial chronic metabolic disorder, characterized by altered metabolism of macro-nutrients, such as fats, proteins, and carbohydrates. Diabetic retinopathy, diabetic cardiomyopathy, diabetic encephalopathy, diabetic periodontitis, and diabetic nephropathy are the prominent complications of diabetes. Inflammatory mediators are primarily responsible for these complications. Curcumin, a polyphenol derived from turmeric, is well known for its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. The regulation of several signaling pathways effectively targets inflammatory mediators in diabetes. Curcumin's anti-inflammatory and anti-oxidative activities against a wide range of molecular targets have been shown to have therapeutic potential for a variety of chronic inflammatory disorders, including diabetes. Curcumin's biological examination has shown that it is a powerful anti-oxidant that stops cells from growing by releasing active free thiol groups at the target location. Curcumin is a powerful anti-inflammatory agent that targets inflammatory mediators in diabetes, and its resistant form leads to better therapeutic outcomes in diabetes complications. Moreover, Curcumin is an anti-oxidant and NF-B inhibitor that may be useful in treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase and aldose reductase inhibitors. Through its anti-oxidant and anti-inflammatory effects, and its suppression of vascular endothelial development and nuclear transcription factors, curcumin has the ability to prevent, or reduce, the course of diabetic retinopathy. Curcumin improves insulin sensitivity by suppressing phosphorylation of ERK/JNK in HG-induced insulin-resistant cells and strengthening the PI3K-AKT-GSK3B signaling pathway. In the present article, we aimed to discuss the anti-inflammatory mechanisms of curcumin in diabetes regulated by various molecular signaling pathways.


Asunto(s)
Curcumina , Diabetes Mellitus , Nefropatías Diabéticas , Aldehído Reductasa , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes , Curcumina/farmacología , Curcumina/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Humanos , Mediadores de Inflamación/metabolismo , Fosfatidilinositol 3-Quinasas
7.
Molecules ; 27(8)2022 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-35458669

RESUMEN

Cancer is a major health problem across the globe, and is expeditiously growing at a faster rate worldwide. The endoplasmic reticulum (ER) is a membranous cell organelle having inextricable links in cellular homeostasis. Altering ER homeostasis initiates various signaling events known as the unfolded protein response (UPR). The basic purpose of the UPR is to reinstate the homeostasis; however, a continuous UPR can stimulate pathways of cell death, such as apoptosis. As a result, there is great perturbation to target particular signaling pathways of ER stress. Flavonoids have gained significant interest as a potential anticancer agent because of their considerable role in causing cytotoxicity of the cancerous cells. Luteolin, a flavonoid isolated from natural products, is a promising phytochemical used in the treatment of cancer. The current study is designed to review the different endoplasmic reticulum stress pathways involved in the cancer, mechanistic insights of luteolin as an anticancer agent in modulating ER stress, and the available luteolin patent formulations were also highlighted. The patents were selected on the basis of pre-clinical and/or clinical trials, and established antitumor effects using patent databases of FPO IP and Espacenet. The patented formulation of luteolin studied so far has shown promising anticancer potential against different cancer cell lines. However, further research is still required to determine the molecular targets of such bioactive molecules so that they can be used as anticancer drugs.


Asunto(s)
Antineoplásicos , Neoplasias , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Estrés del Retículo Endoplásmico , Humanos , Luteolina/farmacología , Luteolina/uso terapéutico , Neoplasias/tratamiento farmacológico , Respuesta de Proteína Desplegada
8.
Expert Rev Mol Med ; 23: e22, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34906269

RESUMEN

Biomacromolecules have gained much attention as biomedicine carriers in recent years due to their remarkable biophysical and biochemical properties including sustainability, non-toxicity, biocompatibility, biodegradability, long systemic circulation time and ability to target. Recent developments in a variety of biological functions of biomacromolecules and progress in the study of biological drug carriers suggest that these carriers may have advantages over carriers of synthetic materials in terms of half-life, durability, protection and manufacturing facility. Despite the full pledge advancements in the applications of biomacromolecules, its clinical use is hindered by certain factors that allow the pre-mature release of loaded cargos before reaching the target site. The delivery therapeutics are degraded by systemic nucleases, cleared by reticulo-endothelial system, cleared by pulmonary mucus cilia or engulfed by lysosome during cellular uptake that has led to the failure of clinical therapy. It clearly indicates that there is a wide range of gaps in the results of experimental work and clinical applications of biomacromolecules. This review focuses mainly on the barriers (intracellular/extracellular) and hurdles to the delivery of biomacromolecules with special emphasis on siRNA as well as the delivery of antisense oligos in multiple pulmonary diseases, particularly focusing on lung cancer. Also, the challenges posed to such delivery and possible solutions have been highlighted.


Asunto(s)
Portadores de Fármacos , Enfermedades Pulmonares , Sistemas de Liberación de Medicamentos , Humanos , Pulmón , ARN Interferente Pequeño/genética
9.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 171-176, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817350

RESUMEN

Datura metel has been recommended in several human disorders including a remedy for liver toxicity. The current study was designed to evaluate the hepatoprotective effect of methanolic extract of D. metel in animal model. Acute toxicity of methanolic crude extract of Datura metel (MEDM) was studied in animals in various doses 500-2000 mg/kg. Mice of either sex were divided into groups (n=6). One group received normal saline intraperitonially as negative control, while other gentamicin 100mg/kg for 8 days as positive control. 3rd group received 50mg/kg silymarin as standard, 4th group received 100mg/kg of MEDM, 5th group received 200mg/kg MEDM while 6th group received 300mg/kg MEDM and gentamicin 100mg/kg for 8 days. The blood samples were collected on 9th day and the animals were then dissected and the liver of all the animals were isolated. MEDM was found safe in acute toxicity test at various doses up to 2000 mg/kg. The levels of serum glutamic pyruvic transaminase and alkaline phosphatase were elevated significantly with gentamicin treatment which significantly down-regulated by MEDM (100, 200 and 300 mg/kg) in a dose dependent manner.. The histological examination showed that the MEDM has markedly treated the inflammatory infiltrate, fatty changes and congested blood vessels which were induced by gentamicin.  The findings of our study thus proved the absolute of MEDM in acute toxicity test; followed by significant hepatoprotective effect in gentamicin induced hepatotoxic mice.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Datura metel/química , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/metabolismo , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Evaluación Preclínica de Medicamentos , Femenino , Gentamicinas , Hígado/metabolismo , Hígado/patología , Masculino , Metanol/química , Ratones , Fitoterapia/métodos , Extractos Vegetales/química , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Pruebas de Toxicidad Aguda/métodos
10.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 9-16, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817374

RESUMEN

Dryopteris ramosa (D. ramosa) is one of the most traded medicinally important plants of Himalayan region. Apart from other uses, D. ramosa is traditionally also used to treat gastric ulcers and as a laxative. The present study was designed to investigate the role of methanolic crude extract of Dryopteris Ramosa (MEDR) in acute toxicity, against loperamide induced constipated mice model, antiulcer effect of methanolic extract of D. Ramosa and cholinomimetic like effect of methanolic extract of D. Ramosa. The crude extract was investigated for the presence of active compounds (secondary metabolites) such as alkaloids, flavonoids, carbohydrates, glycosides, terpenoids, phenolic compounds, saponins, and tannins following the standard methods. The antiulcer effect was investigated in mice using the ethanol induced ulcer model at various doses i.e. 50 mg/kg, 100 mg/kg and 200 mg/kg doses. Constipation was induced in the mice via loperamide (3mg/kg body weight). The control group received normal saline. Different doses of plant extracts (50, 100, 150 and 200 mg/kg body weight/day) were administered for 7 days. Various parameters like feeding characteristics, gastrointestinal transit ratio, body weight, fecal properties and the possible mechanism of action of D. Ramosa on intestinal motility were monitored. Various Phytochemicals like saponins, glycosides, flavonoids, tannins, phenols, carbohydrate, alkaloids and triterpenes were found in D. Ramosa. The acute toxicity study showed that MEDR was associated with no mortality except mild and moderate sedation at the highest tested doses (1500 and 2000 mg/kg). MEDR also showed significant antiulcer activity against ethanol-induced ulcerogenesis. The extract enhanced the intestinal motility, normalized the body weight of constipated mice and increased the fecal volume which are indications of laxative property of the herb. The 200 mg/kg body weight dose of the extract was found effective. The presence of various Phytochemicals such as flavonoids, glycosides and tannins might be responsible for the antiulcer activity of D. Ramosa. This study provides the scientific background for the folkloric use of D. Ramosa as antiulcer agent. The laxative action of the extract compares positively with Duphalac, (standard laxative drug). These findings have therefore evidence scientific background to the folkloric use of the herb as a laxative agent.


Asunto(s)
Estreñimiento/prevención & control , Dryopteris/química , Laxativos/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Úlcera Gástrica/prevención & control , Alcaloides/farmacología , Animales , Estreñimiento/inducido químicamente , Etanol , Flavonoides/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Laxativos/química , Loperamida , Metanol/química , Ratones , Fitoterapia/métodos , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Saponinas/farmacología , Úlcera Gástrica/inducido químicamente , Taninos/farmacología , Pruebas de Toxicidad Aguda/métodos
11.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-34360782

RESUMEN

Colorectal carcinogenesis is the second most common cause of mortality across all types of malignancies, followed by hepatic and stomach cancers. Chemotherapy and radiotherapy are key approaches to treating cancer patients, but these carry major concerns, such as a high risk of side effects, poor accessibility, and the non-selective nature of chemotherapeutics. A number of natural products have been identified as countering various forms of cancer with fewer side effects. The potential impact of vitamins and minerals on long-term health, cognition, healthy development, bone formation, and aging has been supported by experimental and epidemiological studies. Successful treatment may thus be highly influenced by the nutritional status of patients. An insufficient diet could lead to detrimental effects on immune status and tolerance to treatment, affecting the ability of chemotherapy to destroy cancerous cells. In recent decades, most cancer patients have been taking vitamins and minerals to improve standard therapy and/or to decrease the undesirable side effects of the treatment together with the underlying disease. On the other hand, taking dietary supplements during cancer therapy may affect the effectiveness of chemotherapy. Thus, micronutrients in complementary oncology must be selected appropriately and should be taken at the right time. Here, the potential impact of micronutrients on gastro-intestinal and hepatic cancers is explored and their molecular targets are laid down.


Asunto(s)
Neoplasias Colorrectales , Suplementos Dietéticos , Neoplasias Hepáticas , Micronutrientes , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Micronutrientes/inmunología , Micronutrientes/uso terapéutico
12.
Molecules ; 27(1)2021 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-35011412

RESUMEN

Nuclear factor erythroid 2 p45-related factor (2Nrf2) is an essential leucine zipper protein (bZIP) that is primarily located in the cytoplasm under physiological conditions. Nrf2 principally modulates endogenous defense in response to oxidative stress in the brain.In this regard, Nrf2 translocates into the nucleus and heterodimerizes with the tiny Maf or Jun proteins. It then attaches to certain DNA locations in the nucleus, such as electrophile response elements (EpRE) or antioxidant response elements (ARE), to start the transcription of cytoprotective genes. Many neoplasms have been shown to have over activated Nrf2, strongly suggesting that it is responsible for tumors with a poor prognosis. Exactly like curcumin, Zinc-curcumin Zn (II)-curc compound has been shown to induce Nrf2 activation. In the cancer cell lines analyzed, Zinc-curcumin Zn (II)-curc compound can also display anticancer effects via diverse molecular mechanisms, including markedly increasing heme oxygenase-1 (HO-1) p62/SQSTM1 and the Nrf2 protein levels along with its targets. It also strikingly decreases the levels of Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1) protein.As a result, the crosstalk between p62/SQSTM1 and Nrf2 could be used to improve cancer patient response to treatments. The interconnected anti-inflammatory and antioxidative properties of curcumin resulted from its modulatory effects on Nrf2 signaling pathway have been shown to improve insulin resistance. Curcumin exerts its anti-inflammatory impact through suppressing metabolic reactions and proteins such as Keap1 that provoke inflammation and oxidation. A rational amount of curcumin-activated antioxidant Nrf2 HO-1 and Nrf2-Keap1 pathways and upregulated the modifier subunit of glutamate-cysteine ligase involved in the production of the intracellular antioxidant glutathione. Enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). A variety of in vivo, in vitro and clinical studies has been done so far to confirm the protective role of curcumin via Nrf2 regulation. This manuscript is designed to provide a comprehensive review on the molecular aspects of curcumin and its derivatives/analogs via regulation of Nrf2 regulation.


Asunto(s)
Curcumina/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Proteínas Portadoras , Curcumina/química , Curcumina/uso terapéutico , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/etiología , Neoplasias/metabolismo , Neoplasias/patología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Unión Proteica , Transducción de Señal/efectos de los fármacos , Activación Transcripcional
13.
Cell Mol Biol (Noisy-le-grand) ; 66(4): 208-213, 2020 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-32583780

RESUMEN

Datura metel is traditionally used as a remedy for renal toxicity. However, the nephroprotection has not been scientifically validated yet. To evaluate the nephroprotective like effect of methanolic extract of D. metel in gentamicin induced mice model, mice of either sex were divided into groups. One group received normal saline as negative control. The 2nd group received gentamicin 100mg/kg for 8 days as positive control, 3rd group received 50mg/kg silymarin as standard, while the reaming groups received 100, 200 and 300 mg/kg of MEDM and gentamicin 100mg/kg, for 8 days. The blood and urine samples were collected on 9th day, animals were then dissected and whole kidneys were removed and preserved in formalin for later histological examinations. The level of serum creatinine, blood urea nitrogen, urine creatinine and urine urea were significantly (P<0.05) elevated and the renal MDA level was also elevated significantly (P<0.05) by gentamicin in mice. After the treatment of test animals with MEDM, the elevated level of serum and urine biomarkers by gentamicin were reversed by MEDM. The nephroprotective effect was found in dose dependent manner. As the MEDM significantly protected the nephrotoxicity via its antioxidant effect. The findings of our study thus proved the scientific background for the nephroprotective effect of MEDM.


Asunto(s)
Datura metel/química , Gentamicinas/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Creatinina/orina , Modelos Animales de Enfermedad , Femenino , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Renales/sangre , Enfermedades Renales/orina , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Fitoquímicos/análisis , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Urea/orina
14.
Molecules ; 25(18)2020 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-32906577

RESUMEN

Inflammation is a physiological response to different pathological, cellular or vascular damages due to physical, chemical or mechanical trauma. It is characterized by pain, redness, heat and swelling. Current natural drugs are carefully chosen as a novel therapeutic strategy for the management of inflammatory diseases. Different phytochemical constituents are present in natural products. These phytochemicals have high efficacy both in vivo and in vitro. Among them, flavonoids occur in many foods, vegetables and herbal medicines and are considered as the most active constituent, having the ability to attenuate inflammation. Kaempferol is a polyphenol that is richly found in fruits, vegetables and herbal medicines. It is also found in plant-derived beverages. Kaempferol is used in the management of various ailments but there is no available review article that can summarize all the natural sources and biological activities specifically focusing on the anti-inflammatory effect of kaempferol. Therefore, this article is aimed at providing a brief updated review of the literature regarding the anti-inflammatory effect of kaempferol and its possible molecular mechanisms of action. Furthermore, the review provides the available updated literature regarding the natural sources, chemistry, biosynthesis, oral absorption, metabolism, bioavailability and therapeutic effect of kaempferol.


Asunto(s)
Antiinflamatorios/farmacología , Suplementos Dietéticos , Quempferoles/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/uso terapéutico , Disponibilidad Biológica , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Fraccionamiento Químico , Flavonoides/química , Flavonoides/farmacología , Humanos , Quempferoles/química , Quempferoles/aislamiento & purificación , Quempferoles/uso terapéutico , Fitoquímicos/química , Fitoquímicos/farmacología , Plantas Medicinales/química , Relación Estructura-Actividad , Pruebas de Toxicidad
15.
J Pak Med Assoc ; 68(9): 1345-1349, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30317262

RESUMEN

OBJECTIVE: To determine frequency of maternal hypotension during spinal anaesthesia for elective caesarean section by comparing fixed dose with height and weight-adjusted dose of hyperbaric 0.5% bupivacaine. METHODS: This randomised controlled trial was carried out at Pakistan Naval Ship Shifa Hospital, Karachi, and comprised patients with singleton pregnancy who were randomly divided into two groups. After preloading with 10ml/kg of Ringers lactate, Group A received fixed dose of 10mg of 0.5% hyperbaric bupivacaine, while Group B received dose according to height and weight using Harten's dose chart. Patients were made supine with wedge placed below the right hip. Variation in blood pressure was recorded and hypotension was treated with phenylephrine. Data was analysed with SPSS 16.. RESULTS: There were 80 subjects divided into groups of 40(50%) each. Hypotension occurred in 20(50%) subjects in group A and in 15(37.5%) patients in group B(p>0.05). Median dose of 0.5% bupivacaine in group B was 9(IQR=0.5)mg and minimum dose was 8mg. Additional analgesia with ketamine was given to 2(5%) patients in group A and 3(7.5%) patients in group B. CONCLUSIONS: Fixed dose of 10mg of hyperbaric 0.5% bupivacaine had similar results to height and weight-adjusted dose of bupivacaine in spinal anaesthesia for caesarean section.


Asunto(s)
Anestesia Obstétrica/métodos , Anestesia Raquidea/métodos , Bupivacaína , Cesárea/métodos , Adulto , Anestésicos Locales/administración & dosificación , Anestésicos Locales/efectos adversos , Pesos y Medidas Corporales/métodos , Bupivacaína/administración & dosificación , Bupivacaína/efectos adversos , Relación Dosis-Respuesta a Droga , Cálculo de Dosificación de Drogas , Femenino , Humanos , Embarazo , Resultado del Tratamiento
16.
Curr Drug Targets ; 25(10): 670-682, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38752634

RESUMEN

Diabetes Mellitus (DM) is referred to as hyperglycemia in either fasting or postprandial phases. Oxidative stress, which is defined by an excessive amount of reactive oxygen species (ROS) production, increased exposure to external stress, and an excessive amount of the cellular defense system against them, results in cellular damage. Increased DNA damage is one of the main causes of genomic instability, and genetic changes are an underlying factor in the emergence of cancer. Through covalent connections with DNA and proteins, quercetin has been demonstrated to offer protection against the creation of oxidative DNA damage. It has been found that quercetin shields DNA from possible oxidative stress-related harm by reducing the production of ROS. Therefore, Quercetin helps to lessen DNA damage and improve the ability of DNA repair mechanisms. This review mainly focuses on the role of quercetin in repairing DNA damage and compensating for drug resistance in diabetic patients. Data on the target topic was obtained from major scientific databases, including SpringerLink, Web of Science, Google Scholar, Medline Plus, PubMed, Science Direct, and Elsevier. In preclinical studies, quercetin guards against DNA deterioration by regulating the degree of lipid peroxidation and enhancing the antioxidant defense system. By reactivating antioxidant enzymes, decreasing ROS levels, and decreasing the levels of 8-hydroxydeoxyguanosine, Quercetin protects DNA from oxidative damage. In clinical studies, it was found that quercetin supplementation was related to increased antioxidant capacity and decreased risk of type 2 diabetes mellitus in the experimental group as compared to the placebo group. It is concluded that quercetin has a significant role in DNA repair in order to overcome drug resistance in diabetes.


Asunto(s)
Daño del ADN , Reparación del ADN , Diabetes Mellitus , Estrés Oxidativo , Quercetina , Especies Reactivas de Oxígeno , Quercetina/farmacología , Quercetina/uso terapéutico , Humanos , Reparación del ADN/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Resistencia a Medicamentos , Animales
17.
PLoS One ; 19(10): e0297398, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39365759

RESUMEN

5-Lipoxygenase (5-LOX) is a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes, leading to asthma. Developing potent 5-LOX inhibitors are highly attractive. In this research the previously synthesized isoxazole derivatives has been investigated against 5-LOX inhibitory and antioxidant in vitro assay. The compound 3 caused concentration dependent inhibition of 5-LOX with overall IC50 value of 8.47 µM. The investigated compounds C5 also exhibited good 5-LOX inhibitory effect. The IC50 demonstrated for C5 was 10.48. Among the 10 synthesized compounds, the potential 5-LOX inhibitory effect was reported for C6. The most potent compound which showed excellent free radical scavenging effect was C3 having IC50 value of 10.96 µM. The next most potent antioxidant activity was reported for C5 which non-significantly showed free radical scavenging effect. The IC50 value observed for C5 was 13.12 µM. Compound C6 also showed potent dose dependent antioxidant effect with IC50 value of 18.87 µM having percent inhibition of 91.63±0.55, 88.45±0.49, 83.53±0.45, 78.42±0.66 and 73.72±0.64 at concentration 1000-62.5 µg/mL respectively. Among the tested compounds, C6 was found most potent which showed significant 5-LOX percent inhibition assay and also reported the minimum IC50 value comparable to the reference drug. The in vitro 5-LOX enzymes inhibition assays of C5 and C3 also showed excellent percent inhibition and good potency next to C6. We concluded that amongst the investigated designed molecules the C3 was found best potent and showed significant dose dependent antioxidant activity against DPPH screening. The IC50 value reported for C3 was found good as compared to standard drug. Moreover, C5 and C6 also showed excellent free radical scavenging effect against DPPH assay. Computational methods have also been employed to explore the probable interaction model of inhibitors and enzyme active sites, and also to correlate the results of in silico and in vitro studies.


Asunto(s)
Antioxidantes , Araquidonato 5-Lipooxigenasa , Isoxazoles , Inhibidores de la Lipooxigenasa , Inhibidores de la Lipooxigenasa/farmacología , Inhibidores de la Lipooxigenasa/química , Antioxidantes/farmacología , Antioxidantes/química , Araquidonato 5-Lipooxigenasa/metabolismo , Isoxazoles/farmacología , Isoxazoles/química , Simulación del Acoplamiento Molecular , Humanos , Relación Estructura-Actividad , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química , Concentración 50 Inhibidora , Picratos/antagonistas & inhibidores , Picratos/química , Compuestos de Bifenilo
18.
Front Chem ; 12: 1360719, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562526

RESUMEN

The process of developing of new drugs is greatly hampered by their inadequate physicochemical, pharmacokinetic, and intrinsic characteristics. In this regard, the selected chloro indolinone, (Z)-6-chloro-3-(2-chlorobenzylidene)indolin-2-one (C1), and nitro indolinone, (Z)-6-chloro-3-(2-nitrobenzylidene)indolin-2-one (C2), were subjected to SwissADME and density function theory (DFT) analysis. For compounds C1 and C2, the BOILED-Egg pharmacokinetic model predicted intestinal absorption, blood-brain barrier (BBB) penetration, and p-glycoprotein interaction. According to the physicochemical analysis, C1 has exceptional drug-like characteristics suitable for oral absorption. Despite only being substrates for some of the major CYP 450 isoforms, compounds C1 and C2 were anticipated to have strong plasma protein binding and efficient distribution and block these isoforms. The DFT study using the B3LYP/6-311G(d,p) approach with implicit water effects was performed to assess the structural features, electronic properties, and global reactivity parameters (GRP) of C1 and C2. The DFT results provided further support for other studies, implying that C2 is more water-soluble than C1 and that both compounds can form hydrogen bonds and (weak) dispersion interactions with other molecules, such as solvents and biomolecules. Furthermore, the GRP study suggested that C1 should be more stable and less reactive than C2. A concentration-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was shown by both C1 and C2. In brief, this finding has provided a strong foundation to explore further the therapeutic potential of these molecules against a variety of human disorders.

19.
Phytomedicine ; 134: 155949, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39217652

RESUMEN

BACKGROUND: Cancer is one of the leading causes of death and a great threat to people around the world. Cancer treatment modalities include surgery, radiotherapy, chemotherapy, radiochemotherapy, hormone therapy, and immunotherapy. The best approach is to use a combination of several types. Among the treatment methods mentioned above, chemotherapy is frequently used, but its activity is hampered by the development of drug resistance and many side effects. In this regard, the use of medicinal plants has been discussed, and in recent decades, the use of isolated phytochemicals came into the focus of interest. By critically evaluating the available evidence and emphasizing the unique perspective offered by this review, we provide insights into the potential of daidzein as a promising therapeutic agent, as well as outline future research directions to optimize its efficacy in clinical settings. PURPOSE: To summarized the therapeutic potential of daidzein, an isoflavone phytoestrogen in the management of several human diseases with the focuses on the current status and future prospects as a therapeutic agent. METHODS: Several search engines, including PubMed, GoogleScholar, and ScienceDirect, were used, with the search terms "daidzein", "daidzein therapeutic potential", or individual effects. The study included all peer-reviewed articles. However, the most recent publications were given priority. RESULTS: Daidzein showed protective effects against malignant diseases such as breast cancer, prostate cancer but also non-malignant diseases such as diabetes, osteoporosis, and cardiovascular diseases. Daidzein activates multiple signaling pathways leading to cell cycle arrest and apoptosis as well as antioxidant and anti-metastatic effects in malignant cells. Moreover, the anticancer effects against different cancer cells were more prominent and discussed in detail. CONCLUSIONS: In short, daidzein represents a promising compound for drug development. The comprehensive potential anticancer activities of daidzein through various molecular mechanisms and its therapeutic/clinical status required further detail studies.


Asunto(s)
Isoflavonas , Fitoestrógenos , Fitoterapia , Isoflavonas/farmacología , Humanos , Fitoestrógenos/farmacología , Fitoestrógenos/uso terapéutico , Neoplasias/tratamiento farmacológico , Fitoquímicos/farmacología , Animales , Antineoplásicos Fitogénicos/farmacología , Plantas Medicinales/química
20.
Heliyon ; 10(18): e37911, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39323861

RESUMEN

Background: Vigna unguiculata, belonging to the Fabaceae family, commonly known as cowpea is an important edible legume, distributed mainly across the African and Asian countries. Traditionally, the plant has an outstanding background for the management of multiple diseases, animal feeding and human consumption. Objective: This review aims to mainly focus on the traditional applications, pharmacological activities, phytochemistry as well as nutritious composition of the V. unguiculata. Methods: Data present in the literature on the V. unguiculata, were collected from major scientific databases including Science Direct, SpringerLink, Google Scholar, Medline Plus, Web of Science, PubMed and Elsevier. Results: Number of compounds have been isolated including flavonoids, steroids, alkaloids, phenolic compounds, saponins, fatty acids, tannins, carbohydrates, vitamins, amino acids, carotenoids and fibers from various parts of plant. These compounds exhibit widespread pharmacological potentials both in-vitro and in-vivo including anthelmintic, antibacterial, antinociceptive, thrombolytic, antidiabetic, hypocholestrolemic and antiatherogenic effect, antimicrobial, anti-sickling, antioxidant, anti-covid activity, anticancer and neurobehavioral activities. These compounds have strong pharmacological background and might be responsible for the traditional uses of this plant that are not investigated. Conclusion: It is concluded that V. unguiculata possessed strong pharmacological, nutritious and phytochemical potential, therefore, it is strongly recommended for additional comprehensive investigations in order to determine its clinical utility.

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