RESUMEN
According to the World Health Organization, cancer is the foremost cause of mortality globally. Various phytochemicals from natural sources have been extensively studied for their anticancer properties. Allicin, a powerful organosulfur compound derived from garlic, exhibits anticancer, antioxidant, anti-inflammatory, antifungal, and antibacterial properties. This review aims to update and evaluate the chemistry, composition, mechanisms of action, and pharmacokinetics Allicin. Allicin has garnered significant attention for its potential role in modulating Fas-FasL, Bcl2-Bax, PI3K-Akt-mTOR, autophagy, and miRNA pathways. At the molecular level, allicin induces the release of cytochrome c from the mitochondria and enhances the activation of caspases-3, -8, and -9. This is accompanied by the simultaneous upregulation of Bax and Fas expression in tumor cells. Allicin can inhibit excessive autophagy by activating the PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Allicin-loaded nano-formulations efficiently induce apoptosis in cancer cells while minimizing toxicity to normal cells. Safety and clinical aspects are meticulously scrutinized, providing insights into the tolerability and adverse effects associated with allicin administration, along with an overview of current clinical trials evaluating its therapeutic potential. In conclusion, this review underscores the promising prospects of allicin as a dietary-derived medicinal compound for cancer therapy. It emphasizes the need for further research to elucidate its precise mechanisms of action, optimize delivery strategies, and validate its efficacy in clinical settings.
Asunto(s)
Apoptosis , Disulfuros , Neoplasias , Transducción de Señal , Ácidos Sulfínicos , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéutico , Humanos , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Garlic (Allium sativum L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many in vitro and in vivo studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, ß-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and ß-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.
Asunto(s)
Ajo , Ajo/química , Humanos , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Fitoquímicos/uso terapéutico , Fitoquímicos/farmacología , Ácidos Sulfínicos/uso terapéutico , Ácidos Sulfínicos/farmacología , DisulfurosRESUMEN
OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.
Asunto(s)
Neoplasias de la Mama , Receptor ErbB-2 , Trastuzumab , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Trastuzumab/uso terapéutico , Trastuzumab/farmacología , Estudios Prospectivos , Anciano , Receptor ErbB-2/metabolismo , Paclitaxel Unido a Albúmina/uso terapéutico , Paclitaxel Unido a Albúmina/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Acrilamidas/uso terapéutico , Terapia Neoadyuvante/métodos , Proto-Oncogenes Mas , Ácidos Sulfínicos/uso terapéutico , Ácidos Sulfínicos/farmacología , Aminoquinolinas/uso terapéutico , Aminoquinolinas/farmacología , Resultado del TratamientoRESUMEN
The main objective of this review is to highlight the therapeutic potential of allicin, a defense molecule in garlic known for its diverse health benefits, and address the key challenges of its bioavailability and stability. The research further aims to evaluate various formulation strategies and nanotechnology-based delivery systems that can resolve these issues and improve allicin's clinical efficacy, especially in cancer therapy. We conducted a comprehensive review of the available literature and previous studies, focusing on the therapeutic properties of allicin, its bioavailability, stability issues, and novel formulation strategies. We assessed the mechanism of action of allicin in cancer, including its effects on signaling pathways, cell cycle, apoptosis, autophagy, and tumor development. We also evaluated the outcomes of both in vitro and in vivo studies on different types of cancers, such as breast, cervical, colon, lung, and gastric cancer. Despite allicin's significant therapeutic benefits, including cardiovascular, antihypertensive, cholesterol-lowering, antimicrobial, antifungal, anticancer, and immune-modulatory activity, its clinical utility is limited due to poor stability and unpredictable bioavailability. Allicin's bioavailability in the gastrointestinal tract is dependent on the activity of the enzyme alliinase, and its stability can be affected by various conditions like gastric acid and intestinal enzyme proteases. Recent advances in formulation strategies and nanotechnology-based drug delivery systems show promise in addressing these challenges, potentially improving allicin's solubility, stability, and bioavailability. Allicin offers substantial potential for cancer therapy, yet its application is hindered by its instability and poor bioavailability. Novel formulation strategies and nanotechnology-based delivery systems can significantly overcome these limitations, enhancing the therapeutic efficacy of allicin. Future research should focus on refining these formulation strategies and delivery systems, ensuring the safety and efficacy of these new allicin formulations. Clinical trials and long-term studies should be carried out to determine the optimal dosage, assess potential side effects, and evaluate their real-world applicability. The comparative analysis of different drug delivery approaches and the development of targeted delivery systems can also provide further insight into enhancing the therapeutic potential of allicin.
Asunto(s)
Disulfuros , Neoplasias , Humanos , Disponibilidad Biológica , Ácidos Sulfínicos/uso terapéutico , Ácidos Sulfínicos/metabolismo , Ácidos Sulfínicos/farmacología , Resultado del Tratamiento , Neoplasias/tratamiento farmacológicoRESUMEN
Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC50) of allicin was 25-72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin's promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections.
Asunto(s)
Infecciones Fúngicas Invasoras , Mucorales , Micosis , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Mucorales/metabolismo , Anfotericina B/farmacología , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéutico , Disulfuros/farmacología , Micosis/tratamiento farmacológico , Infecciones Fúngicas Invasoras/tratamiento farmacológicoRESUMEN
Dairy farming is the most important economic activity in animal husbandry. Mastitis is the most common disease in dairy cattle and has a significant impact on milk quality and yield. The natural extract allicin, which is the main active ingredient of the sulfur-containing organic compounds in garlic, has anti-inflammatory, anticancer, antioxidant, and antibacterial properties; however, the specific mechanism underlying its effect on mastitis in dairy cows needs to be determined. Therefore, in this study, whether allicin can reduce lipopolysaccharide (LPS)-induced inflammation in the mammary epithelium of dairy cows was investigated. A cellular model of mammary inflammation was established by pretreating bovine mammary epithelial cells (MAC-T) with 10 µg/mL LPS, and the cultures were then treated with varying concentrations of allicin (0, 1, 2.5, 5, and 7.5 µM) added to the culture medium. MAC-T cells were examined using RT-qPCR and Western blotting to determine the effect of allicin. Subsequently, the level of phosphorylated nuclear factor kappa-B (NF-κB) was measured to further explore the mechanism underlying the effect of allicin on bovine mammary epithelial cell inflammation. Treatment with 2.5 µM allicin considerably decreased the LPS-induced increase in the levels of the inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in cow mammary epithelial cells. Further research revealed that allicin also inhibited the phosphorylation of inhibitors of nuclear factor kappa-B-α (IκB-α) and NF-κB p65. In mice, LPS-induced mastitis was also ameliorated by allicin. Therefore, we hypothesize that allicin alleviated LPS-induced inflammation in the mammary epithelial cells of cows probably by affecting the TLR4/NF-κB signaling pathway. Allicin will likely become an alternative to antibiotics for the treatment of mastitis in cows.
Asunto(s)
Disulfuros , Mastitis Bovina , FN-kappa B , Ácidos Sulfínicos , Animales , Bovinos , Femenino , Ratones , Disulfuros/uso terapéutico , Células Epiteliales/metabolismo , Inflamación/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos , Mastitis Bovina/tratamiento farmacológico , FN-kappa B/metabolismo , Transducción de Señal , Ácidos Sulfínicos/uso terapéutico , Receptor Toll-Like 4/metabolismoRESUMEN
Allicin, a thiosulfonate extract from freshly minced garlic, has been reported to have various biological effects on different organs and systems of animals and human. It can reduce oxidative stress, inhibit inflammatory response, resist pathogen infection and regulate intestinal flora. In addition, dozens of studies also demonstrated allicin could reduce blood glucose level, protect cardiovascular system and nervous system, and fight against cancers. Allicin was widely used in disease prevention and health care. However, more investigations on human cohort study are needed to verify the biological or clinical effects of allicin in the future. In this review, we summarized the biological effects of allicin from previous outstanding and valuable studies and provided useful information for future studies on the health effects of allicin.
Asunto(s)
Disulfuros , Ajo , Animales , Humanos , Disulfuros/farmacología , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Cardiovascular diseases (CVDs) are a group of diseases in which the common denominator is the affection of blood vessels, heart tissue, and heart rhythm. The genesis of CVD is complex and multifactorial; therefore, approaches are often based on multidisciplinary management and more than one drug is used to achieve the optimal control of risk factors (dyslipidemia, hypertension, hypertrophy, oxidative stress, endothelial dysfunction, inflammation). In this context, allicin, a sulfur compound naturally derived from garlic, has shown beneficial effects on several cardiovascular risk factors through the modulation of cellular mechanisms and signaling pathways. Effective pharmacological treatments for CVD or its risk factors have not been developed or are unknown in clinical practice. Thus, this work aimed to review the cellular mechanisms through which allicin exerts its therapeutic effects and to show why it could be a therapeutic option for the prevention or treatment of CVD and its risk factors.
Asunto(s)
Enfermedades Cardiovasculares , Ajo , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Disulfuros/uso terapéutico , Humanos , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéuticoRESUMEN
Garlic, Allium sativum, has long been utilized for a number of medicinal purposes around the world, and its medical benefits have been well documented. The health benefits of garlic likely arise from a wide variety of components, possibly working synergistically. Garlic and garlic extracts, especially aged garlic extracts (AGEs), are rich in bioactive compounds, with potent anti-inflammatory, antioxidant and neuroprotective activities. In light of these effects, garlic and its components have been examined in experimental models of Alzheimer's disease (AD), the most common form of dementia without therapy, and a growing health concern in aging societies. With the aim of offering an updated overview, this paper reviews the chemical composition, metabolism and bioavailability of garlic bioactive compounds. In addition, it provides an overview of signaling mechanisms triggered by garlic derivatives, with a focus on allicin and AGE, to improve learning and memory.
Asunto(s)
Enfermedad de Alzheimer , Productos Biológicos , Ajo , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Disulfuros , Ajo/química , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ácidos Sulfínicos/química , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéuticoRESUMEN
Fungal infections of the lung are an increasing problem worldwide and the search for novel therapeutic agents is a current challenge due to emerging resistance to current antimycotics. The volatile defence substance allicin is formed naturally by freshly injured garlic plants and exhibits broad antimicrobial potency. Chemically synthesised allicin was active against selected fungi upon direct contact and via the gas phase at comparable concentrations to the pharmaceutically used antimycotic amphotericin B. We investigated the suppression of fungal growth by allicin vapour and aerosols in vitro in a test rig at air flow conditions mimicking the human lung. The effect of allicin via the gas phase was enhanced by ethanol. Our results suggest that allicin is a potential candidate for development for use in antifungal therapy for lung and upper respiratory tract infections.
Asunto(s)
Micosis , Ácidos Sulfínicos , Disulfuros , Humanos , Pulmón , Micosis/tratamiento farmacológico , Ácidos Sulfínicos/química , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéuticoRESUMEN
Synergistic therapy against the resurgence of bacterial pathogenesis is a modern trend for antibacterial chemotherapy. The phytochemical allicin, found in garlic extract is a commendable antimicrobial agent that can be used in synergistic combination with modern antibiotics. Determination of optimal antibacterial combination for the target species is vital for maximizing efficacy, lowering toxicity, total eradication of the bacterial cells and minimization of the risk of resistance generation. In this present investigation, Hill function-based pharmacodynamics models were employed to elaborate various time-kill kinetics parameters. The bactericidal potency of the synergistic combinations of allicin and individual antibiotic was assessed in comparison to their monotherapy application viz. using sole allicin and sole antibiotics (levofloxacin, ciprofloxacin, oxytetracycline, rifaximin, ornidazole and azithromycin) on actively growing Bacillus subtilis and Escherichia coli bacteria. Here, all the synergistic combinations showed significantly better (t-test p-value < 0.05) killing effect and biofilm reduction potential compared to their respective monotherapy application, where the highest killing effect was observed with rifaximin-allicin combination (kill rate was more than 5.5 h-1). Moreover, the average inhibition potential to protein denaturation by the synergistic combination group was significantly higher (3.4 fold) than the sole antibiotic's group manifests reduction in the dose-related toxicity. The potential of synergism between antibiotics and allicin combination demonstrated greater killing efficiency at significantly lower concentration compared to monotherapy with increased kill rates in all cases.
Asunto(s)
Antibacterianos , Ácidos Sulfínicos , Antibacterianos/química , Antibacterianos/farmacología , Bacterias , Disulfuros , Sinergismo Farmacológico , Escherichia coli , Cinética , Pruebas de Sensibilidad Microbiana , Rifaximina/farmacología , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéuticoRESUMEN
Phytochemicals have attracted attention in the oncological field because they are biologically friendly and have relevant pharmacological activities. Thanks to the intense and unique spicy aroma, garlic is one of the most used plants for cooking. Its consumption is correlated to health beneficial effects towards several chronic diseases, such as cancer, mainly attributable to allicin, a bioactive sulfur compound stored in different plant parts in a precursor form. The objective of this review is to present and critically discuss the chemistry and biosynthesis of allicin, its pharmacokinetic profile, its anticancer mechanisms and molecular targets, and its selectivity towards tumor cells. The research carried out so far revealed that allicin suppresses the growth of different types of tumors. In particular, it targets many signaling pathways associated with cancer development. Future research directions are also outlined to further characterize this promising natural product.
Asunto(s)
Productos Biológicos , Ajo , Neoplasias , Disulfuros/uso terapéutico , Ajo/química , Humanos , Neoplasias/tratamiento farmacológico , Ácidos Sulfínicos/química , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéuticoRESUMEN
BACKGROUND: The tumor suppressor protein p53 is a most promising target for the development of anticancer drugs. Allicin (diallylthiosulfinate) is one of the most active components of garlic (Alliium sativum L.) and possesses a variety of health-promoting properties with pharmacological applications. However, whether allicin plays an anti-cancer role against breast cancer cells through the induction of p53-mediated apoptosis remains unknown. METHODS AND RESULTS: In this study, we investigate the anti-breast cancer effect of allicin in vitro by using MCF-7 and MD-MBA-231 cells. We found that allicin reduces cell viability, induces apoptosis and cell cycle arrest in both cells. Allicin activated p53 and caspase 3 expressions in both cells but produced different effects on the expression of p53-related biomarkers. In MDA-MB-231 cells, allicin up-regulated the mRNA and protein expression of A1BG and THBS1 while down-regulated the expression of TPM4. Conversely, the mRNA and protein expression of A1BG, THBS1 and TPM4 were all reduced in MCF-7 cells. Hence, allicin induces cell cycle arrest and apoptosis in breast cancer cells through p53 activation but it effects on the expression of p53-related biomarkers were dependent upon the specific type of breast cancer involved. CONCLUSIONS: These findings suggest that allicin induces apoptosis and regulates biomarker expression in breast cancer cell lines through modulating the p53 signaling pathway. Furthermore, our results promote the utility of allicin as compound for further studies as an anticancer drug targeting p53.
Asunto(s)
Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Puntos de Control del Ciclo Celular , Disulfuros/farmacología , Transducción de Señal , Ácidos Sulfínicos/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/fisiopatología , Caspasa 3/genética , Línea Celular Tumoral , Disulfuros/uso terapéutico , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Ácidos Sulfínicos/uso terapéutico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling. Recent evidence supports that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Recent studies have shown that garlic extract has protective effects in PAH, but the precise role of allicin, a compound derived from garlic, is unknown. Thus, we used allicin to evaluate its effects on inflammation and fibrosis in PAH. Male Wistar rats were divided into three groups: control (CON), monocrotaline (60 mg/kg) (MCT), and MCT plus allicin (16 mg/kg/oral gavage) (MCT + A). Right ventricle (RV) hypertrophy and pulmonary arterial medial wall thickness were determined. IL-1ß, IL-6, TNF-α, NFκB p65, Iκß, TGF-ß, and α-SMA were determined by Western blot analysis. In addition, TNF-α and TGF-ß were determined by immunohistochemistry, and miR-21-5p and mRNA expressions of Cd68, Bmpr2, and Smad5 were determined by RT-qPCR. Results: Allicin prevented increases in vessel wall thickness due to TNF-α, IL-6, IL-1ß, and Cd68 in the lung. In addition, TGF-ß, α-SMA, and fibrosis were lower in the MCT + A group compared with the MCT group. In the RV, allicin prevented increases in TNF-α, IL-6, and TGF-ß. These observations suggest that, through the modulation of proinflammatory and profibrotic markers in the lung and heart, allicin delays the progression of PAH.
Asunto(s)
Antiinflamatorios/uso terapéutico , Disulfuros/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Ácidos Sulfínicos/uso terapéutico , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/genética , Antígenos de Diferenciación Mielomonocítica/metabolismo , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/metabolismo , Citocinas/genética , Citocinas/metabolismo , Fibrosis , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Masculino , FN-kappa B/genética , FN-kappa B/metabolismo , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Ratas , Ratas Wistar , Proteína Smad5/genética , Proteína Smad5/metabolismoRESUMEN
The active ingredients allicin and curcumin have a wide range of actions against fungi, bacteria, and helminths. Therefore, the study was aimed to evaluate the efficacy of allicin (AL) and curcumin (CU) as antischistosomal drugs and their biochemical effects in normal and Schistosoma mansoni-infected mice. Praziquantel (PZQ) was administrated for two successive days while AL or CU was given for two weeks from the week 7th postinfection (PI). The possible effect of different regimens on Schistosoma worms was evaluated by measuring the percentage of the recovered worms, tissue egg load, and oogram pattern. Serum alanine transaminase activity and levels of triglycerides, cholesterol, and uric acid were measured. Liver tissue malondialdehyde and reduced glutathione levels besides, the activities of glutathione-S-transferase, superoxide dismutase and catalase were assessed for the oxidative/antioxidant condition. DNA electrophoresis of liver tissue was used to indicate the degree of fragmentation. There was a significant reduction in the recovered worms and egg load, with a marked change of oogram pattern in all treated groups with PZQ, AL, and CU in comparison with infected-untreated mice. PZQ, AL, and CU prevented most of the hematological and biochemical disorders, as well as significantly improved the antioxidant capacity and enhanced DNA fragmentation in the liver tissue of schistosomiasis mice compared to the infected-untreated group. These promising results suggest that AL and CU are efficient as antischistosomal drugs, and it would be beneficial to test their combination to understand the mechanism of action and the proper period of treatment leading to the best result.
Asunto(s)
Antioxidantes/uso terapéutico , Curcuma/química , Curcumina/uso terapéutico , Disulfuros/uso terapéutico , Ajo/química , Fitoterapia/métodos , Extractos Vegetales/uso terapéutico , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/uso terapéutico , Ácidos Sulfínicos/uso terapéutico , Animales , Fragmentación del ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Recuento de Huevos de Parásitos , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/parasitología , Resultado del TratamientoRESUMEN
Hepatic encephalopathy (HE) is a debilitating and life-threatening disease. Results from acute or chronic liver failure and is characterized by abnormal cerebral and neurological alterations. This study aimed at investigating the effect of allicin, the major functional component in freshly crushed garlic extract, on thioacetamide (TAA)-induced HE in rats. Induction of HE by a single dose of TAA (300 mg/kg; I.P.) was associated with a marked elevation in the serum levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, total protein, blood urea nitrogen and serum ammonia besides reduction in the serum level of albumin. Moreover, it was accompanied with an increase in the hepatic and brain levels of inflammatory mediators; TNF-α and IL-1ß as well as elevation of the hepatic and brain levels of oxidative stress biomarkers; reduced glutathione and lipid peroxidation evidenced by malondialdeyde. Oral administration of allicin (50, 100 and 200 mg/kg; P.O.) for 6 days prior to TAA injection restored the serum liver function, hepatic and brain levels of inflammatory mediators as well as oxidative stress biomarkers in a dose-dependent manner. From our results, it can be concluded that allicin has a protective effect on TAA-induced HE in rats in a dose-dependent manner due to its powerful antioxidant and anti-inflammatory properties.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/uso terapéutico , Sistema Nervioso Central/efectos de los fármacos , Disulfuros/uso terapéutico , Encefalopatía Hepática/inducido químicamente , Encefalopatía Hepática/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Sistema Nervioso Periférico/efectos de los fármacos , Ácidos Sulfínicos/uso terapéutico , Tioacetamida , Animales , Química Encefálica , Sistema Nervioso Central/patología , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Encefalopatía Hepática/patología , Pruebas de Función Hepática , Masculino , Estrés Oxidativo , Sistema Nervioso Periférico/patología , RatasRESUMEN
Acrylamide (AA) in heat-processed food leads to widespread concerns due to its hepatotoxicity. Allicin, a plant-derived antioxidant, possesses a significant protective effect on AA-induced hepatotoxicity, but the mechanism is still unclear. Herein, we investigated the mechanism in Kupffer cells and SD rats liver. Molecular docking, molecular dynamics simulation and LigPlus software speculated that allicin inhibited the activity of CYP2E1 expression by binding to its amino acid residues Phe116, Phe207, Leu210, Phe298, Ala299, Thr303, Val364 and Phe478 through hydrophobic interactions. Allicin decreased the reactive oxygen species (ROS) release and CYP2E1 protein expression and then alleviated the appearance of OS. Meanwhile, allicin significantly reduced ERS characteristic proteins GRP78, CHOP and UPR branch IRE1α pathway key proteins p-IRE, p-ASK, TRAF2 and XBP-1s expression. Simultaneously, allicin ameliorated OS and ERS activation, which inhibited the activation of the MAPK and NF-κB pathways, and down-regulated JNK, ERK, p38, p65 and IκBα phosphorylation. Allicin pre-treatment inhibited AA-induced inflammation as evidenced by reducing NLRP3 inflammasome activation, decreasing Cleaved-Caspase-1 expression as well as IL-1ß, IL-18, IL-6 and TNF-α secretion. Taken together, our data provide new insights into possible signaling pathways involved in allicin attenuating AA-induced hepatotoxicity in vivo and in vitro.
Asunto(s)
Acrilamida/toxicidad , Disulfuros/uso terapéutico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Inflamasomas/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ácidos Sulfínicos/uso terapéutico , Animales , Citocromo P-450 CYP2E1/metabolismo , Citocinas/metabolismo , Disulfuros/metabolismo , Macrófagos del Hígado/efectos de los fármacos , Hígado/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Simulación del Acoplamiento Molecular , Unión Proteica , Ratas Sprague-Dawley , Ácidos Sulfínicos/metabolismoRESUMEN
OBJECTIVE: This research was aimed to explore protective effects of allicin on rat model of myocardial infarction via JNK signaling pathway. METHODS: Rat myocardial ischemia model was established with subcutaneous injection of isoproterenol (ISO). Seventy-five rats were randomly divided into 5 groups (n = 15): sham group, ISO group, low-dose group (1.2 mg/kg/days for 7 days), medium-dose group (1.8 mg/kg/days for 7 days), and high-dose group (3.6 mg/kg/days for 7 days). Routine HE staining and Masson staining were performed to observe myocardial histopathology. The expression of oxidative stress-related indicators, heart tissue apoptosis-related proteins, and JNK and p-JNK proteins were measured for different groups. RESULTS: Compared with the sham group, the T wave value of the ISO group was significantly increased (p < 0.01). When allicin was administered, the T wave values at different time points in all groups were all decreased. Compared with the sham group, the ratio of eNOS, Bcl-2/Bax was significantly decreased, and p-eNOS, iNOS, caspase-3, caspase-9, and Cyt-c were significantly elevated in the ISO group (p < 0.05). After allicin was administered, significant changes in these proteins were observed in the medium- and high-dose groups. There was no significant change in the expression of JNK protein in the ISO group compared with the sham group; however, the expression of eNOS and p-JNK protein were significantly upregulated (p < 0.01) and the expression of p-eNOS and iNOS were significantly downregulated (p < 0.01). When allicin was administered, expression of p-JNK protein was significantly downregulated. CONCLUSION: Allicin can reduce oxidative stress damage and cardiomyocyte apoptosis in rat model of myocardial infarction and can significantly regulate JNK signaling pathway.
Asunto(s)
Antioxidantes/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Ácidos Sulfínicos/farmacología , Animales , Antioxidantes/uso terapéutico , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Disulfuros , Isoproterenol/toxicidad , Proteínas Quinasas JNK Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Infarto del Miocardio/inducido químicamente , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Ácidos Sulfínicos/uso terapéuticoRESUMEN
OBJECTIVES: Inhibitory effect of allicin with broad-spectrum antimicrobial activity on A. fumigatus and the regulation mechanism of inflammation and autophagy in vitro and in vivo. METHODS: The corresponding concentration of allicin was prepared according to the needs of the experiment. In vitro, 2 ml 5 × 104 of fungal spores suspension was added to the 6-well plate per hole, and different final concentrations of allicin (1 µl/ml, 2.5 µl/ml, 5 µl/ml, 10 µl/ml, 20 µl/ml, 30 µl/ml) were added. The fungal spores were stained by fluorescent dye SYTO 9 (green) every day, and the spore germination inhibition was detected by flow cytometry in different PH. RAW264.7 cells were cultured and stimulated by A. fumigatus spores for 3 h, then allicin solution was added. Then some cells were stained with ROS probe (green) and hochest33342 (blue). The effect of allicin on ROS was observed by fluorescence microscope. The other part of cells extracted protein from cell lysate and detected the effect of allicin on inflammatory factors and autophagy by Western-blotting. The green and red spots of RAW264.7 cells stably transfected with GFP-RFP-LC3 were observed by fluorescence microscopy. In vivo, A. fumigatus spore was injected intratracheally into mice, then allicin was injected intravenously at a concentration of 5 mg/kg/day for 7 consecutive days. The survival status, pulmonary fungal load and weight of mice was recorded continuously for 30 days and detected the changes of lung by pathological examination and immunohistochemistry. RESULTS: In vitro, allicin significantly inhibited the spore germination of A. fumigatus within 24 h in a dose-dependent manner and it had a stable inhibition on the spore germination of A. fumigatus in acidic environment. Cell experiments showed that allicin inhibited intracellular spore germination by inhibiting ROS production, inflammation and autophagy. In the animal experiment, the survival rate and body weight of allicin injection group were higher than that of non injection group, while the spore load of lung was lower than that of non injection group (P < 0.05). CONCLUSIONS: These results support that allicin reduces inflammation and autophagy resistance to A. fumigatus infection, It also provides a possible treatment for Aspergillus infectious diseases, i.e. early anti-inflammation, antibiotics or drugs that inhibit excessive autophagy.
Asunto(s)
Antiinflamatorios/uso terapéutico , Aspergilosis/tratamiento farmacológico , Autofagia , Depuradores de Radicales Libres/uso terapéutico , Ácidos Sulfínicos/uso terapéutico , Animales , Antiinflamatorios/farmacología , Aspergillus fumigatus/patogenicidad , Aspergillus fumigatus/fisiología , Disulfuros , Femenino , Depuradores de Radicales Libres/farmacología , Pulmón/metabolismo , Pulmón/microbiología , Ratones , Ratones Endogámicos BALB C , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Esporas Fúngicas/efectos de los fármacos , Ácidos Sulfínicos/farmacologíaRESUMEN
Garlic (Allium sativum L.) is a well-known spice widely utilised for its medicinal properties. There is an extensive record of the many beneficial health effects of garlic which can be traced back to as early as the ancient Egyptian era. One of the most studied properties of garlic is its ability to cure certain ailments caused by infections. In the 1940s, the antimicrobial activities exhibited by garlic were first reported to be due to allicin, a volatile compound extracted from raw garlic. Since then, allicin has been widely investigated for its putative inhibitory activities against a wide range of microorganisms. Allicin has demonstrated a preference for targeting the thiol-containing proteins and/or enzymes in microorganisms. It has also demonstrated the ability to regulate several genes essential for the virulence of microorganisms. Recently, it was reported that allicin may function better in combination with other antimicrobials compared to when used alone. When used in combination with antibiotics or antifungals, allicin enhanced the antimicrobial activities of these substances and improved the antimicrobial efficacy. Hence, it is likely that combination therapy of allicin with additional antimicrobial drug(s) could serve as a viable alternative for combating rising antimicrobial resistance. This review focuses on the antimicrobial activities exhibited by allicin alone as well as in combination with other substances. The mechanisms of action of allicin elucidated by some of the studies are also highlighted in the present review in order to provide a comprehensive overview of this versatile bioactive compound and the mechanistic evidence supporting its potential use in antimicrobial therapy.