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Asthma remains a significant global health challenge, demanding innovative approaches to treatment. Traditional medicine has a rich history of using natural products to alleviate asthmatic symptoms. However, transitioning from these traditional remedies to modern drug discovery approaches has provided fresh insights into the mechanisms and effectiveness of these natural products. This study provides our comprehensive review, which examines the current state of knowledge in the treatment of asthma. It delves into the mechanisms through which natural products ameliorate asthma symptoms, and it discusses their potential in the development of novel therapeutic interventions. Our analysis reveals that natural products, traditionally employed for asthma relief, exhibit diverse mechanisms of action. These include anti-inflammatory, bronchodilatory, immunomodulatory effects, and reducing gene expression. In the context of modern drug discovery, these natural compounds serve as valuable candidates for the development of novel asthma therapies. The transition from traditional remedies to modern drug discovery represents a promising avenue for asthma treatment. Our review highlights the substantial efficacy of natural products in managing asthma symptoms, underpinned by well-defined mechanisms of action. By bridging the gap between traditional and contemporary approaches, we contribute to the growing body of knowledge in the field, emphasizing the potential of natural products in shaping the future of asthma therapy.
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Diabetes, particularly type 2 diabetes (T2D), is the main component of metabolic syndrome. It is highly prevalent and has drastically increased with sedentary lifestyles, notably behaviors linked to ease of access and minimal physical activity. Central to this condition is insulin, which plays a pivotal role in regulating glucose levels in the body by aiding glucose uptake and storage in cells, and what happens to diabetes? In diabetes, there is a disruption and malfunction in insulin regulation. Despite numerous efforts, effectively addressing diabetes remains a challenge. This article explores the potential of photoactivatable drugs in diabetes treatment, with a focus on light-activated insulin. We discuss its advantages and significant implications. This article is expected to enrich the existing literature substantially, offering a comprehensive analysis of potential strategies for improving diabetes management. With its minimal physical intrusion, light-activated insulin promises to improve patient comfort and treatment adherence. It offers precise regulation and localized impact, potentially mitigating the risks associated with conventional diabetes treatments. Additionally, light-activated insulin is capable of explicitly targeting RNA and epigenetic factors. This innovative approach may pave the way for more personalized and effective diabetes treatments, addressing not only the symptoms but also the underlying biological causes of the disease. The advancement of light-activated insulin could revolutionize diabetes management. This study represents a pioneering introduction to this novel modality for diabetes management.
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Diabetes Mellitus Tipo 2 , Insulina , Humanos , Insulina/metabolismo , Glicemia , Diabetes Mellitus Tipo 2/metabolismo , Exercício FísicoRESUMO
Enhalus arcoides is a highly beneficial type of seagrass. Prior studies have presented proof of the bioactivity of E. acoroides, suggesting its potential to combat cancer. Therefore, this study aims to delve deeper into E. acoroides bioactive molecule profiles and their direct biological anticancer activities potentials through the combination of in-silico and in-vitro studies. This study conducted metabolite profile analysis on E. acoroides utilizing HPLC-ESI-HRMS/MS analysis. Two extraction techniques, ethanol and hexane, were employed for the extraction process. Furthermore, the in-silico study was conducted using molecular docking simulations on the HER2, EGFR tyrosine kinase and HIF-1α protein receptor. Afterward, the antioxidant activity of E. acoroides metabolites was examined to ABTS, and the antiproliferative activity was tested using an MTT assay. An in-silico study revealed its ability to combat breast cancer by inhibiting the HER2/EGFR/HIF-1α pathway through molecular docking. In addition, the MTT assay demonstrated that higher dosages of metabolites from E. acoroides increased the effectiveness of toxicity against cancer cell lines. Additionally, the study demonstrated that the metabolites possess the ability to function as potent antioxidants, effectively inhibiting a series of carcinogenic mechanisms. Ultimately, this study showed a new approach to unveiling the E. acoroides metabolites' anticancer activity through inhibiting HER2/EGFR/HIF-1α receptors, with great cytotoxicity and a potent antioxidant property to prevent a carcinogenic cascade.
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Neoplasias da Mama , Humanos , Feminino , Simulação de Acoplamento Molecular , Etanol , Receptores ErbBRESUMO
Metabolic dysfunction, which includes intra-abdominal adiposity, glucose intolerance, insulin resistance, dyslipidemia, and hypertension, manifests into metabolic syndrome and related diseases. Therefore, the discovery of new therapies in the fight against metabolic syndrome is very challenging. This study aims to reveal the existence of an edible bird nest (EBN) as a functional food candidate that may be a new alternative in fighting metabolic syndrome. The study included three approaches: in silico molecular docking simulation, in vitro, and in vivo in rats fed on cholesterol- and fat-enriched diets. Four terpenoids of Bakuchiol, Curculigosaponin A, Dehydrolindestrenolide, and 1-methyl-3-(1-methyl-ethyl)-benzene in EBN have been identified through LCMS/MS-QTOF. In molecular docking simulations, Bakuchiol and Dehydrolindestrenolide are considered very potent because they have higher inhibitory power on the four receptors (iNOS, ROS1 kinase, FTO, and lipase) than standard drugs. In vitro tests also provide insight into the antioxidant, antidiabetic, and antiobesity activities of EBN, which is quite feasible due to the smaller EC50 value of EBN compared to standard drugs. Interestingly, in vivo studies also showed significant improvements (p < 0.05) in the lipid profile, blood glucose, enzymatic levels, and inflammatory biomarkers in rats given high-dose dietary supplementation of EBN. More interestingly, high-dose dietary supplementation of EBN upregulates PGC-1α and downregulates HMG-CoA reductase. Comprehensively, it has been revealed that EBN can be novel functional foods for combating metabolic syndrome.
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Green algae are natural bioresources that have excellent bioactive potential, partly due to sulfated polysaccharides (SPs) which are still rarely explored for their biological activities. There is currently an urgent need for studies exploring the anticancer biological activity of SPs extracted from two Indonesian ulvophyte green algae: the sulfated polysaccharide of Caulerpa racemosa (SPCr) and the sulfated polysaccharide of Caulerpa lentillifera (SPCl). The method of isolating SPs and their assessment of biological activities in this study were based on previous and similar studies. The highest yield sulfate/total sugar ratio was presented by SPCr than that of SPCl. Overall, SPCr exhibits a strong antioxidant activity, as indicated by smaller EC50 values obtained from a series of antioxidant activity assays compared to the EC50 values of Trolox (control). As an anti-obesity and antidiabetic, the overall EC50 value of both SPs was close to the EC50 of the positive control (orlistat and acarbose). Even more interesting was that SPCl displayed wide-ranging anticancer effects on colorectal, hepatoma, breast cancer cell lines, and leukemia. Finally, this study reveals new insights in that SPs from two Indonesian green algae have the potential to be promising nutraceuticals as novel antioxidative actors, and to be able to fight obesity, diabetes, and even cancer.
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Caulerpa , Clorófitas , Sulfatos , Antioxidantes/farmacologia , Polissacarídeos/farmacologiaRESUMO
Green alga Caulerpa racemosa is an underexploited species of macroalgae, even though it is characterized by a green color that indicates an abundance of bioactive pigments, such as chlorophyll and possibly xanthophyll. Unlike chlorophyll, which has been well explored, the composition of the carotenoids of C. racemosa and its biological activities have not been reported. Therefore, this study aims to look at the carotenoid profile and composition of C. racemose and determine their biological activities, which include antidiabetic, anti-obesity, anti-oxidative, anti-inflammatory, and cytotoxicity in vitro. The detected carotenoids were all xanthophylls, which included fucoxanthin, lutein, astaxanthin, canthaxanthin, zeaxanthin, ß-carotene, and ß-cryptoxanthin based on orbitrap-mass spectrometry (MS) and a rapid ultra-high performance liquid chromatography (UHPLC) diode array detector. Of the seven carotenoids observed, it should be highlighted that ß-carotene and canthaxanthin were the two most dominant carotenoids present in C. racemosa. Interestingly, the carotenoid extract of C. racemosa has good biological activity in inhibiting α-glucosidase, α-amylase, DPPH and ABTS, and the TNF-α and mTOR, as well as upregulating the AMPK, which makes it a drug candidate or functional antidiabetic food, a very promising anti-obesity and anti-inflammatory. More interestingly, the cytotoxicity value of the carotenoid extract of C. racemosa shows a level of safety in normal cells, which makes it a potential for the further development of nutraceuticals and pharmaceuticals.
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Caulerpa , Clorófitas , Carotenoides/química , Antioxidantes/química , beta Caroteno/química , Cantaxantina , Hipoglicemiantes/farmacologia , Luteína/química , Zeaxantinas , Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
Epidemiological studies have associated red meat intake with risk of colorectal cancer. Experimental studies explain this positive association by the oxidative properties of heme iron released in the colon. This latter is a potent catalyst for lipid peroxidation, resulting in the neoformation of deleterious aldehydes in the fecal water of heme-fed rats. The toxicity of fecal water of heme-fed rats was associated to such lipid peroxidation. This study demonstrated that fecal water of hemoglobin- and beef-fed rats preferentially induced apoptosis in mouse normal colon epithelial cells than in those carrying mutation on Apc (Adenomatous polyposis coli) gene, considered as preneoplastic. Highlighting the importance of lipid peroxidation and neoformation of secondary aldehydes like 4-hydroxy-2-nonenal (HNE), we optimized the depletion of carbonyl compounds in the fecal water which turned out to abolish the differential apoptosis in both cell lines. To explain the resistance of preneoplastic cells towards fecal water toxicity, we focused on Nrf2, known to be activated by aldehydes, including HNE. Fecal water activated Nrf2 in both cell lines, associated with the induction of Nrf2-target genes related to aldehydes detoxification. However, the antioxidant defense appeared to be higher in preneoplastic cells, favoring their survival, as evidenced by Nrf2 inactivation. Taken together, our results suggest that Nrf2-dependent antioxidant response was involved in the resistance of preneoplastic cells upon exposure to fecal water of hemoglobin- and beef-fed rats. This difference could explain the promoting effect of red meat and heme-enriched diet on colorectal cancer, by initiating positive selection of preneoplastic cells.
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Antioxidantes/metabolismo , Neoplasias Colorretais/etiologia , Hemoglobinas/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Carne Vermelha/efeitos adversos , Aldeídos , Animais , Apoptose , Colo/metabolismo , Colo/patologia , Fezes , Inativação Metabólica , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Ratos Endogâmicos F344RESUMO
Epidemiology shows that red and processed meat intake is associated with an increased risk of colorectal cancer. Heme iron, heterocyclic amines, and endogenous N-nitroso compounds (NOC) are proposed to explain this effect, but their relative contribution is unknown. Our study aimed at determining, at nutritional doses, which is the main factor involved and proposing a mechanism of cancer promotion by red meat. The relative part of heme iron (1% in diet), heterocyclic amines (PhIP + MeIQx, 50 + 25 µg/kg in diet), and NOC (induced by NaNO2+ NaNO2; 0.17 + 0.23 g/L of drinking water) was determined by a factorial design and preneoplastic endpoints in chemically induced rats and validated on tumors in Min mice. The molecular mechanisms (genotoxicity, cytotoxicity) were analyzed in vitro in normal and Apc-deficient cell lines and confirmed on colon mucosa. Heme iron increased the number of preneoplastic lesions, but dietary heterocyclic amines and NOC had no effect on carcinogenesis in rats. Dietary hemoglobin increased tumor load in Min mice (control diet: 67 ± 39 mm²; 2.5% hemoglobin diet: 114 ± 47 mm², P = 0.004). In vitro, fecal water from rats given hemoglobin was rich in aldehydes and was cytotoxic to normal cells, but not to premalignant cells. The aldehydes 4-hydroxynonenal and 4-hydroxyhexenal were more toxic to normal versus mutated cells and were only genotoxic to normal cells. Genotoxicity was also observed in colon mucosa of mice given hemoglobin. These results highlight the role of heme iron in the promotion of colon cancer by red meat and suggest that heme iron could initiate carcinogenesis through lipid peroxidation. .