scholarly journals Micronized curcumin causes hyperlocomotion in zebrafish larvae

2021 ◽  
Author(s):  
Adrieli Sachett ◽  
Radharani Benvenutti ◽  
Carlos G Reis ◽  
Matheus Gallas-Lopes ◽  
Leonardo M Bastos ◽  
...  

Zebrafish larvae have been widely used in neuroscience and drug research and development. In the larval stage, zebrafish present a broad behavioral repertoire and physiological responses similar to adults. Curcumin (CUR), a major component of Curcuma longa L. (Zingiberaceae), has demonstrated the ability to modulate several neurobiological processes relevant to mental disorders in animal models. However, the low bioavailability of this compound can compromise its in vivo biological potential. Interestingly, it has been shown that micronization can increase the biological effects of several compounds. Thus, in this study, we compared the effects of acute exposure for 30 minutes to the following solutions: water (control), 0.1% DMSO (vehicle), 1 μM CUR, or 1 μM micronized curcumin (MC) in zebrafish larvae 7 days post-fertilization (dpf). We analyzed locomotor activity (open tank test), anxiety (light/dark test), and avoidance behavior (aversive stimulus test). Moreover, we evaluated parameters of oxidative status (thiobarbituric acid reactive substances and non-protein thiols levels). MC increased the total distance traveled and absolute turn angle in the open tank test. There were no significant differences in the other behavioral or neurochemical outcomes. The increase in locomotion induced by MC may be associated with a stimulant effect on the central nervous system, which was evidenced by the micronization process.

2021 ◽  
Author(s):  
Adrieli Sachett ◽  
Matheus Gallas-Lopes ◽  
Radharani Benvenutti ◽  
Matheus Marcon ◽  
Amanda M Linazzi ◽  
...  

Curcumin, a polyphenol extracted from the rhizome of Curcuma longa L. (Zingiberaceae), presents neuroprotective properties and can modulate neuronal pathways related to mental disorders. However, curcumin has low bioavailability, which can compromise its use. The micronization process can reduce the mean particle diameter and improve this compound bioavailability and therapeutic potential. In this study, we compared the behavioral (in the open tank test, OTT) and neurochemical (thiobarbituric acid reactive substances (TBARS) and non-protein thiols (NPSH) levels) effects of non-micronized curcumin (CUR, 10 mg/kg, i.p.) and micronized curcumin (MC, 10 mg/kg, i.p.) in adult zebrafish subjected to 90-minute acute restraint stress (ARS). ARS increased the time spent in the central area and the number of crossings and decreased the immobility time of the animals. These results suggest an increase in locomotor activity and a decrease in thigmotaxis behavior in the OTT. Furthermore, ARS also induced oxidative damage by increasing TBARS and decreasing NPSH levels. ARS-induced behavioral and biochemical effects were not blocked by any curcumin preparation. Therefore, we suppose that curcumin does not have anti-stress effects on the ARS in zebrafish.


2021 ◽  
Author(s):  
Adrieli Sachett ◽  
Matheus Gallas-Lopes ◽  
Radharani Benvenutti ◽  
Matheus Marcon ◽  
Gean Pablo S. Aguiar ◽  
...  

Curcumin, a polyphenol extracted from the rhizome of Curcuma longa L. (Zingiberaceae), is shown to have antioxidant, anti-inflammatory, neuroprotective, anxiolytic, and antidepressant properties in both preclinical and clinical studies. However, its low bioavailability is a limitation for its potential adoption as a therapeutic agent. The process of micronization can overcome this barrier by reducing the particle size and increasing the dissolution rate, potentially improving the bioavailability of the compounds of interest. In this study, we compared the in vitro antioxidant effects of curcumin (CUR) and micronized curcumin (MC) and studied their effects on behavioral and neurochemical parameters in zebrafish submitted to unpredictable chronic stress (UCS). MC (1 g/L) presented higher antioxidant activity in vitro as compared to CUR, as measured by iron-reducing antioxidant power (FRAP), 1,1-diphenyl-2-2-picyryl-hydrazyl radical removal (DPPH), and deoxyribose tests. UCS increased total distance traveled in the social interaction test (SI), while decreased crossings, time, and entries to the top area in the novel tank test (NTT). No effects of UCS were observed in the open tank test (OTT). The behavioral effects induced by UCS were not blocked by any curcumin preparation. UCS also decreased non-protein thiols (NPSH) levels, while increased glutathione reductase (GR) activity and thiobarbituric acid reactive substances (TBARS) levels on zebrafish brain. MC presented superior antioxidant properties than CUR in vivo, blocking the stress-induced neurochemical effects. Although this study did not measure the concentration of curcumin on the zebrafish brain, our results suggest that micronization increases the bioavailability of curcumin, potentiating its antioxidant activity both in vitro and in vivo. Our study also demonstrates that counteracting the oxidative imbalance induced by UCS is not sufficient to block its behavioral effects.


2021 ◽  
Author(s):  
Jessica Valadas ◽  
Adrieli Sachett ◽  
Matheus Marcon ◽  
Leonardo M Bastos ◽  
Angelo Piato

Ochratoxin A (OTA) is a mycotoxin produced by species of filamentous fungi widely found as a contaminant in food and with high toxic potential. Studies have shown that this toxin cause kidney and liver damage, however, data on the effects of exposure to OTA on the central nervous system are still scarce. Zebrafish (Danio rerio) is a teleost often used in translational research due to its physiological, genetic, and behavioral homology with mammals, in addition to being useful as an environmental bioindicator. Thus, this study aimed to investigate the effects of exposure to OTA on behavioral and neurochemical parameters in adult zebrafish. The animals were treated with different doses of OTA (1.38, 2.77, and 5.53 mg/kg) and submitted to behavioral evaluations in the open tank and social interaction tests. Subsequently, they were euthanized, and the brains were used to assess markers associated with oxidative status. In the open tank test OTA induced changes in distance, absolute turn angle, mean speed, and time-freezing. However, no significant effects were observed in the social interaction test. Moreover, OTA also induced alterations in neurochemical parameters with changes in non-protein thiols (NPSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). This study showed that OTA can affect neurobiological aspects in zebrafish even at low doses.


2020 ◽  
Vol 17 (1) ◽  
pp. 1
Author(s):  
Jana Späth ◽  
Malin Nording ◽  
Richard Lindberg ◽  
Tomas Brodin ◽  
Stina Jansson ◽  
...  

Environmental contextAdvanced wastewater treatment is required to remove pharmaceuticals and many other consumer chemicals from wastewater effluent. There are conflicting findings, however, on the toxicity of treated effluent, and its effect on living organisms is often neglected. We show that the effect-based removal efficiency of wastewater treatment technologies can be assessed by metabolomic methods, and that this approach contributes to a safer and more controlled water quality. AbstractThere are conflicting findings on the toxicity of effluent from wastewater treatment plants, and only limited possibilities for assessing the effect-based removal efficiency (EBRE) of different treatment techniques. We describe a metabolomics approach to detect perturbations in fatty acid catabolic pathways as a proxy for biological effects. Metabolites in three fatty acid pathways were analysed in a common damselfly larva (Coenagrion hastulatum) by liquid chromatography coupled to mass spectrometry. The larvae were exposed for one week to either conventionally treated effluent (activated sludge treatment), effluent additionally treated with ozone, or effluent additionally treated with biochar filtration, and results were compared with those from tap water control exposure. Five lipoxygenase-derived oxylipins (9,10,13-TriHOME, 9,12,13-TriHOME, 9-HODE, 9-HOTrE, and 13-HOTrE) decreased in response to conventionally treated effluent exposure. By using an additional treatment step, oxylipin levels were restored with exception of 9,10,13-TriHOME (ozonated effluent), and 9-HOTrE and 13-HOTrE (effluent filtered with biochar). Thus, exposure to wastewater effluent affected fatty acid metabolite levels in damselfly larvae, and a subset of the analysed metabolites may serve as indicators for biological effects in biota in response to effluent exposure. To that effect, our findings suggest a new metabolomics protocol for assessing EBRE.


2020 ◽  
Vol 21 ◽  
Author(s):  
Veena V ◽  
Harikrishnan A ◽  
Sunali Khanna

Background: Curcumin, a major active principle of Curcuma longa. There are more than 1700 citations in the Medline reflecting various biological effects of curcumin. Most of these biological activities are associated to the antioxidant, anti-inflammatory and antitumor activity of the molecule. Several reports suggest various targets of natural curcumin that includes growth factors, growth factor receptor, cytokines, enzymes and gene regulators of apoptosis. This review focuses on the improved curcumin derivatives that targets the cancer and inflammation. Methodology: In this present review, we explored the anticancer drugs with curcumin-based drugs under pre-clinical and clinical studies with critical examination. Based on the strong scientific reports of patentable and non-patented literature survey, we have investigated the mode of the interactions of curcumin-based molecules with the target molecules. Results: Advanced studies have added new dimensions of molecular response of cancer cells to curcumin at genomic level. However, poor bioavailability of the molecule seems to be the major limitation of the curcumin. Several researchers have involved to improve the curcumin derivatives to overcome this limitation. Sufficient data of clinical trials to various cancers that include multiple myeloma, pancreatic cancer and colon cancer are also discussed. Conclusion: The detailed analysis of structure activity relationship (SAR) and common synthesis of curcumin-based derivatives are discussed in review. Utilising the predictions of in silico coupled with validation reports of in vitro and in vivo studies have concluded many targets for curcumin. Among them, cancer related inflammation genes regulating curcumin-based molecules are very promising target to overcome hurdle in the multimodality therapy of cancer.


Author(s):  
Sidney J. Stohs ◽  
C. Y. O. Chen ◽  
Harry G. Preuss ◽  
Sidhartha D. Ray ◽  
Luke R. Bucci ◽  
...  

Abstract Background Numerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined. Methods Eight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis. Results Hydrolysis of blood plasma samples prior to extraction and reporting the results as “curcumin” obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed. Conclusions When enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products. Trial registration ClinicalTrails.gov, trial identifying number NCT04103788, September 24, 2019. Retrospectively registered.


2022 ◽  
Vol 23 (2) ◽  
pp. 639
Author(s):  
Kamila Kasprzak-Drozd ◽  
Tomasz Oniszczuk ◽  
Marek Gancarz ◽  
Adrianna Kondracka ◽  
Robert Rusinek ◽  
...  

Obesity is a global health problem needing urgent research. Synthetic anti-obesity drugs show side effects and variable effectiveness. Thus, there is a tendency to use natural compounds for the management of obesity. There is a considerable body of knowledge, supported by rigorous experimental data, that natural polyphenols, including curcumin, can be an effective and safer alternative for managing obesity. Curcumin is a is an important compound present in Curcuma longa L. rhizome. It is a lipophilic molecule that rapidly permeates cell membrane. Curcumin has been used as a pharmacological traditional medicinal agent in Ayurvedic medicine for ∼6000 years. This plant metabolite doubtless effectiveness has been reported through increasingly detailed in vitro, in vivo and clinical trials. Regarding its biological effects, multiple health-promoting, disease-preventing and even treatment attributes have been remarkably highlighted. This review documents the status of research on anti-obesity mechanisms and evaluates the effectiveness of curcumin for management of obesity. It summarizes different mechanisms of anti-obesity action, associated with the enzymes, energy expenditure, adipocyte differentiation, lipid metabolism, gut microbiota and anti-inflammatory potential of curcumin. However, there is still a need for systematic and targeted clinical studies before curcumin can be used as the mainstream therapy for managing obesity.


2020 ◽  
Vol 11 (2) ◽  
pp. 1716-1728
Author(s):  
Siti Nurul Najiha Othman ◽  
Pei Teng Lum ◽  
Aina Akmal Mohd Noor ◽  
Nurul Azima Mazlan ◽  
Puteri Zarith Sofea Yusri ◽  
...  

Malaysia is rich in natural and herbal resources which have the potential to be used as traditional medicine as well as cosmetics. These plant sources are used by the folklore to help in enriching their beauty. Leaves, fruits, flowers and roots of medicinal plants in Malaysia are used in cosmetic formulations to get different biological effects. Health issues with particular reference to skin issues, such as acne, dry skin, dull skin and alopecia can be alleviated by using these plants. Since time immemorial, herbal products have been used in maintaining and enhancing physical appearance of humans. Herbal cosmetics have growing demand in the world market and is an invaluable gift of nature. This review is about ten commonly available medicinal plants in Malaysia used in the cosmetic formulations which includes Aloe vera, Curcuma longa, Cocos nucifera, Cucumis sativus, Melaleuca alternifolia, Punica granatum, Garcinia mangostana, Carica papaya, Lawsonia inermis and Hibiscus rosasinensis. These are the ten plants that are commonly used traditionally in treating many skin conditions and hair problems. Different parts of the plant may produce different beneficial effects to the consumers. Using the herbal and natural ingredients in cosmetics alleviates the side effects almost to nil. This is predominantly lower than the side effects caused by synthetic cosmetics.


Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1228
Author(s):  
Mahdie Rahban ◽  
Mehran Habibi-Rezaei ◽  
Mansoureh Mazaheri ◽  
Luciano Saso ◽  
Ali A. Moosavi-Movahedi

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor that maintains the cell’s redox balance state and reduces inflammation in different adverse stresses. Under the oxidative stress, Nrf2 is separated from Kelch-like ECH-associated protein 1 (Keap1), which is a key sensor of oxidative stress, translocated to the nucleus, interacts with the antioxidant response element (ARE) in the target gene, and then activates the transcriptional pathway to ameliorate the cellular redox condition. Curcumin is a yellow polyphenolic curcuminoid from Curcuma longa (turmeric) that has revealed a broad spectrum of bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Curcumin significantly increases the nuclear expression levels and promotes the biological effects of Nrf2 via the interaction with Cys151 in Keap1, which makes it a marvelous therapeutic candidate against a broad range of oxidative stress-related diseases, including type 2 diabetes (T2D), neurodegenerative diseases (NDs), cardiovascular diseases (CVDs), cancers, viral infections, and more recently SARS-CoV-2. Currently, the multifactorial property of the diseases and lack of adequate medical treatment, especially in viral diseases, result in developing new strategies to finding potential drugs. Curcumin potentially opens up new views as possible Nrf2 activator. However, its low bioavailability that is due to low solubility and low stability in the physiological conditions is a significant challenge in the field of its efficient and effective utilization in medicinal purposes. In this review, we summarized recent studies on the potential effect of curcumin to activate Nrf2 as the design of potential drugs for a viral infection like SARS-Cov2 and acute and chronic inflammation diseases in order to improve the cells’ protection.


Sign in / Sign up

Export Citation Format

Share Document