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12 pages, 5670 KiB

Open AccessArticle

Cardiorenal Protective Effect of Costunolide against Doxorubicin-Induced Toxicity in Rats by Modulating Oxidative Stress, Inflammation and Apoptosis

by Wen Xing, Chaoling Wen, Deguo Wang, Hui Shao, Chunhong Liu, Chunling He and Opeyemi Joshua Olatunji

Molecules 2022, 27(7), 2122; https://doi.org/10.3390/molecules27072122 - 25 Mar 2022

Cited by 9 | Viewed by 2270

Abstract

Doxorubicin (DXB) is one of the most commonly used anticancer agents for treating solid and hematological malignancies; however, DXB-induced cardiorenal toxicity presents a limiting factor to its clinical usefulness in cancer patients. Costunolide (COST) is a naturally occurring sesquiterpene lactone with excellent anti-inflammatory, [...] Read more.

Doxorubicin (DXB) is one of the most commonly used anticancer agents for treating solid and hematological malignancies; however, DXB-induced cardiorenal toxicity presents a limiting factor to its clinical usefulness in cancer patients. Costunolide (COST) is a naturally occurring sesquiterpene lactone with excellent anti-inflammatory, antioxidant and antiapoptotic properties. This study evaluated the effect of COST on DXB-induced cardiorenal toxicity in rats. Rats were orally treated with COST for 4 weeks and received weekly 5 mg/kg doses of DXB for three weeks. Cardiorenal biochemical biomarkers, lipid profile, oxidative stress, inflammatory cytokines, histological and immunohistochemical analyses were evaluated. DXB-treated rats displayed significantly increased levels of lipid profiles, markers of cardiorenal dysfunction (aspartate aminotransferase, creatine kinase, lactate dehydrogenase, troponin T, blood urea nitrogen, uric acid and creatinine). In addition, DXB markedly upregulated cardiorenal malondialdehyde, tumor necrosis factor-α, interleukin-1β, interleukin-6 levels and decreased glutathione, superoxide dismutase and catalase activities. COST treatment significantly attenuated the aforementioned alterations induced by DXB. Furthermore, histopathological and immunohistochemical analyses revealed that COST ameliorated the histopathological features and reduced p53 and myeloperoxidase expression in the treated rats. These results suggest that COST exhibits cardiorenal protective effects against DXB-induced injury presumably via suppression of oxidative stress, inflammation and apoptosis. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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17 pages, 5973 KiB

Open AccessArticle

Anti-Inflammatory Effect of Phytoncide in an Animal Model of Gastrointestinal Inflammation

by Azra Memon, Bae Yong Kim, Se-eun Kim, Yuliya Pyao, Yeong-Geun Lee, Se Chan Kang and Woon Kyu Lee

Molecules 2021, 26(7), 1895; https://doi.org/10.3390/molecules26071895 - 26 Mar 2021

Cited by 5 | Viewed by 3407

Abstract

Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an [...] Read more.

Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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10 pages, 2231 KiB

Open AccessArticle

Spermidine Prevents Ethanol and Lipopolysaccharide-Induced Hepatic Injury in Mice

by Raghabendra Adhikari, Ruchi Shah, Karina Reyes-Gordillo, Jaime Arellanes-Robledo, Ying Cheng, Joseph Ibrahim and Pamela L. Tuma

Molecules 2021, 26(6), 1786; https://doi.org/10.3390/molecules26061786 - 22 Mar 2021

Cited by 12 | Viewed by 4298

Abstract

To date, there is no effective treatment for alcoholic liver disease, despite its prevalence world-wide. Because alcohol consumption is associated with oxidative stress-induced liver injury and pro-inflammatory responses, naturally occurring antioxidants and/or anti-inflammatories may be potential therapeutics. Spermidine is an abundant, ubiquitous polyamine [...] Read more.

To date, there is no effective treatment for alcoholic liver disease, despite its prevalence world-wide. Because alcohol consumption is associated with oxidative stress-induced liver injury and pro-inflammatory responses, naturally occurring antioxidants and/or anti-inflammatories may be potential therapeutics. Spermidine is an abundant, ubiquitous polyamine that has been found to display strong antioxidant and anti-inflammatory properties. To further investigate whether spermidine is an effective intervention for alcohol-induced liver disease, we examined its hepatoprotective properties using a two-hit, chronic ethanol and acute lipopolysaccharide (LPS)-induced mouse model of liver injury. We determined that spermidine administration prevented ethanol and LPS-induced increases in liver injury using plasma ALT as a readout. Furthermore, histological analysis of tissue from control and treated animals revealed that the pathology associated with ethanol and LPS treatment was prevented in mice additionally treated with spermidine. As predicted, spermidine also prevented ethanol and LPS-induced oxidative stress by decreasing the levels of both reactive oxygen species (ROS) and lipid peroxidation. We further determined that spermidine treatment prevented the nuclear translocation of nuclear factor κB (NFκB) by blocking the phosphorylation of the inhibitory protein, IκB, thereby preventing expression of pro-inflammatory cytokines. Finally, by measuring expression of known markers of hepatic stellate cell activation and monitoring collagen deposition, we observed that spermidine also prevented alcohol and LPS-induced hepatic fibrosis. Together, our results indicate that spermidine is an antioxidant thereby conferring anti-inflammatory and anti-fibrotic effects associated with alcoholic liver injury. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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20 pages, 2740 KiB

Open AccessArticle

Positive Effect of Cannabis sativa L. Herb Extracts on Skin Cells and Assessment of Cannabinoid-Based Hydrogels Properties

by Martyna Zagórska-Dziok, Tomasz Bujak, Aleksandra Ziemlewska and Zofia Nizioł-Łukaszewska

Molecules 2021, 26(4), 802; https://doi.org/10.3390/molecules26040802 - 4 Feb 2021

Cited by 46 | Viewed by 14806

Abstract

The skin is an organ that is constantly exposed to many external factors that can affect its structure and function. Due to the presence of different cannabinoid receptors on many types of skin cells, cannabinoids can interact directly with them. Therefore, as part [...] Read more.

The skin is an organ that is constantly exposed to many external factors that can affect its structure and function. Due to the presence of different cannabinoid receptors on many types of skin cells, cannabinoids can interact directly with them. Therefore, as part of this work, the impact of two types of Cannabis sativa L. herb extracts on keratinocytes and fibroblasts was assessed. The content of biologically active compounds such as phenols, flavonoids, chlorophylls and cannabinoids was evaluated. The antioxidant capacity of prepared extracts using the DPPH radical, H₂DCFDA probe and measurement of superoxide dismutase activity was also assessed. The cytotoxicity of hemp extracts was determined using the Alamar Blue, Neutral Red and LDH assays. The ability of the extracts to inhibit the activity of matrix metalloproteinases, collagenase and elastase, was assessed. Preparations of model hydrogels were also prepared and their effect on transepidermal water loss and skin hydration was measured. The obtained results indicate that hemp extracts can be a valuable source of biologically active substances that reduce oxidative stress, inhibit skin aging processes and positively affect the viability of skin cells. The analysis also showed that hydrogels based on cannabis extracts have a positive effect on skin hydration. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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28 pages, 7851 KiB

Open AccessArticle

Cosmetic and Dermatological Properties of Selected Ayurvedic Plant Extracts

by Martyna Zagórska-Dziok, Aleksandra Ziemlewska, Tomasz Bujak, Zofia Nizioł-Łukaszewska and Zofia Hordyjewicz-Baran

Molecules 2021, 26(3), 614; https://doi.org/10.3390/molecules26030614 - 25 Jan 2021

Cited by 29 | Viewed by 6016

Abstract

Due to the constantly growing interest in ingredients of natural origin, this study attempts to evaluate the possibility of using extracts from three Ayurvedic plants in preparations for the care and treatment of skin diseases. Therefore, studies of antioxidant properties were carried out [...] Read more.

Due to the constantly growing interest in ingredients of natural origin, this study attempts to evaluate the possibility of using extracts from three Ayurvedic plants in preparations for the care and treatment of skin diseases. Therefore, studies of antioxidant properties were carried out using DPPH and ABTS radicals, obtaining 76% and 88% of these radical scavenging, respectively. A significant decrease in the intracellular level of free radicals and an increase in the activity of the antioxidant enzyme-superoxide dismutase by almost 60% were also observed. In addition, the extracts were assessed for anti-inflammatory and anti-aging properties, obtaining over 70% inhibition of lipoxygenase activity and almost 40% of collagenase. Additionally, the cytoprotective properties of the obtained extracts on skin cells, keratinocytes and fibroblasts, were demonstrated. To assess the content of biologically active compounds, HPLC-electrospray ionization (ESI)-MS/MS multiple reaction monitoring (MRM) analyses were performed. The obtained results show that all three analyzed plants are a valuable source of biologically active substances with desired properties in the context of skin cell protection. Particularly noteworthy is the extract of Epilobium angustifolium L., for which the most promising results were obtained. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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26 pages, 4663 KiB

Open AccessArticle

Effect of Fermentation Time on Antioxidant and Anti-Ageing Properties of Green Coffee Kombucha Ferments

by Nizioł-Łukaszewska Zofia, Ziemlewska Aleksandra, Bujak Tomasz, Zagórska-Dziok Martyna, Zarębska Magdalena, Hordyjewicz-Baran Zofia and Wasilewski Tomasz

Molecules 2020, 25(22), 5394; https://doi.org/10.3390/molecules25225394 - 18 Nov 2020

Cited by 43 | Viewed by 8979

Abstract

Kombucha, also known as the Manchurian mushroom, is a symbiotic culture of bacteria and yeast, the so-called SCOBY. This paper presents a comprehensive evaluation of the ferments obtained from green coffee beans after different fermentation times with kombucha. Results for the ferments were [...] Read more.

Kombucha, also known as the Manchurian mushroom, is a symbiotic culture of bacteria and yeast, the so-called SCOBY. This paper presents a comprehensive evaluation of the ferments obtained from green coffee beans after different fermentation times with kombucha. Results for the ferments were compared to the green coffee extract that was not fermented. In this study, the antioxidant potential of obtained ferments was analyzed by assessing the scavenging of external and intracellular free radicals and the assessment of superoxide dismutase activity. Cytotoxicity of ferments on keratinocyte and fibroblast cell lines was assessed as well as anti-aging properties by determining their ability to inhibit the activity of collagenase and elastase enzymes. In addition, the composition of the obtained ferments and the extract was determined, as well as their influence on skin hydration and transepidermal water loss (TEWL) after application of samples on the skin. It has been shown that the fermentation time has a positive effect on the content of bioactive compounds and antioxidant properties. The highest values were recorded for the tested samples after 28 days of fermentation. After 14 days of the fermentation process, it was observed that the analyzed ferments were characterized by low cytotoxicity to keratinocytes and fibroblasts. On the other hand, the short fermentation time of 7 days had a negative effect on the properties of the analyzed ferments. The obtained results indicate that both green coffee extracts and ferments can be an innovative ingredient of cosmetic products. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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8 pages, 1307 KiB

Open AccessCommunication

A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs

by Ngoc Uy Nguyen and Brendan David Stamper

Molecules 2020, 25(20), 4629; https://doi.org/10.3390/molecules25204629 - 11 Oct 2020

Cited by 3 | Viewed by 2249

Abstract

Background: Structure-activity relationships describe the relationship between chemical structure and biologic activity and are capable of informing deliberate structural modifications to a molecule in order enhance drug properties. Methods: Here, we present a subtle, yet unique twist on structure-activity relationships in which a [...] Read more.

Background: Structure-activity relationships describe the relationship between chemical structure and biologic activity and are capable of informing deliberate structural modifications to a molecule in order enhance drug properties. Methods: Here, we present a subtle, yet unique twist on structure-activity relationships in which a collective biologic activity was measured among five cinnamon constituents with a shared phenylpropanoid template (cinnamic acid, cinnamaldehyde, chlorogenic acid, caffeic acid, and ferulic acid). This template-based approach utilized publicly available transcriptomic data through the Gene Expression Omnibus (GEO) to identify a fundamental biologic effect; in essence, a phenylpropanoid template effect. Results: The recurrent identification of cytokine-cytokine receptor interaction and neuroactive ligand receptor pathways in each individual treatment condition strongly supports the fact that changes in gene expression within these pathways is a hallmark of the phenylpropanoid template. With a template effect identified, future structural modifications can be performed in order to overcome pharmacokinetic barriers to clinical use (i.e., traditional structure-activity relationship experiments). Moreover, these modifications can be implemented with a high degree of confidence knowing that a consistent and robust template effect is likely to persist. Conclusion: We believe this template-based approach offers researchers an attractive and cost-effective means for evaluating multicomponent natural products during drug development. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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12 pages, 2042 KiB

Open AccessArticle

Atypical Antipsychotic Drug Ziprasidone Protects against Rotenone-Induced Neurotoxicity: An In Vitro Study

by Kazuki Terada, Ayumi Murata, Erina Toki, Shotaro Goto, Hirofumi Yamakawa, Shuichi Setoguchi, Daisuke Watase, Mitsuhisa Koga, Jiro Takata, Kazuhisa Matsunaga and Yoshiharu Karube

Molecules 2020, 25(18), 4206; https://doi.org/10.3390/molecules25184206 - 14 Sep 2020

Cited by 10 | Viewed by 2701

Abstract

Schizophrenia is a severe, chronic mental illness characterized by delusions, hallucinations, negative symptoms, and cognitive dysfunction. Recently, several studies have demonstrated that the pathogenesis of schizophrenia involves mitochondrial dysfunction and oxidative stress. However, the effect of antipsychotic drugs for these events has been [...] Read more.

Schizophrenia is a severe, chronic mental illness characterized by delusions, hallucinations, negative symptoms, and cognitive dysfunction. Recently, several studies have demonstrated that the pathogenesis of schizophrenia involves mitochondrial dysfunction and oxidative stress. However, the effect of antipsychotic drugs for these events has been poorly investigated. In the present study, we evaluated the neuroprotective effect of an atypical antipsychotic drug, ziprasidone (ZPD), on rotenone (ROT)-induced neurotoxicity involving oxidative stress in PC12 cells. Our data showed that ZPD treatment promoted the translocation of NF-E2-related factor-2 (Nrf2) from cytoplasm to nucleus and activated the expression of its target genes NAD(P)H quinone oxidoreductase (NQO-1), catalase (CAT), and heme oxygenase (HO-1). Additionally, ZPD prevented ROT-induced cell death and intracellular reactive oxygen species production. Interestingly, the use of serotonin 5-HT_1A receptor antagonist 1-(2-methoxyphenyl)-4 (4-(2-phtalimido) butyl) piperazine (NAN-190) completely blocked the protective effect of ZPD against ROT-induced cell death. Our results demonstrate the neuroprotective effect of ZPD against ROT-induced neurotoxicity and suggest that ZPD may be a potential candidate for the prevention of mitochondrial dysfunction and oxidative stress in schizophrenia. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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16 pages, 2793 KiB

Open AccessFeature PaperArticle

Measurement of Glutathione as a Tool for Oxidative Stress Studies by High Performance Liquid Chromatography

by Faisal Nuhu, Andrew Gordon, Roger Sturmey, Anne-Marie Seymour and Sunil Bhandari

Molecules 2020, 25(18), 4196; https://doi.org/10.3390/molecules25184196 - 13 Sep 2020

Cited by 52 | Viewed by 10972

Abstract

Background: Maintenance of the ratio of glutathione in the reduced (GSH) and oxidised (GSSG) state in cells is important in redox control, signal transduction and gene regulation, factors that are altered in many diseases. The accurate and reliable determination of GSH and GSSG [...] Read more.

Background: Maintenance of the ratio of glutathione in the reduced (GSH) and oxidised (GSSG) state in cells is important in redox control, signal transduction and gene regulation, factors that are altered in many diseases. The accurate and reliable determination of GSH and GSSG simultaneously is a useful tool for oxidative stress determination. Measurement is limited primarily to the underestimation of GSH and overestimation GSSG as a result of auto-oxidation of GSH. The aim of this study was to overcome this limitation and develop, optimise and validate a reverse-phase high performance liquid chromatographic (HPLC) assay of GSH and GSSG for the determination of oxidant status in cardiac and chronic kidney diseases. Methods: Fluorescence detection of the derivative, glutathione-O-pthaldialdehyde (OPA) adduct was used. The assay was validated by measuring the stability of glutathione and glutathione-OPA adduct under conditions that could affect the reproducibility including reaction time and temperature. Linearity, concentration range, limit of detection (LOD), limit of quantification (LOQ), recovery and extraction efficiency and selectivity of the method were assessed. Results: There was excellent linearity for GSH (r² = 0.998) and GSSG (r² = 0.996) over concentration ranges of 0.1 µM–4 mM and 0.2 µM–0.4 mM respectively. The extraction of GSH from tissues was consistent and precise. The limit of detection for GSH and GSSG were 0.34 µM and 0.26 µM respectively whilst their limits of quantification were 1.14 µM and 0.88 µM respectively. Conclusion: These data validate a method for the simultaneous measurement of GSH and GSSG in samples extracted from biological tissues and offer a simple determination of redox status in clinical samples. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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13 pages, 2542 KiB

Open AccessArticle

Effects of Thymus vulgaris L., Cinnamomum verum J.Presl and Cymbopogon nardus (L.) Rendle Essential Oils in the Endotoxin-induced Acute Airway Inflammation Mouse Model

by Eszter Csikós, Kata Csekő, Amir Reza Ashraf, Ágnes Kemény, László Kereskai, Béla Kocsis, Andrea Böszörményi, Zsuzsanna Helyes and Györgyi Horváth

Molecules 2020, 25(15), 3553; https://doi.org/10.3390/molecules25153553 - 4 Aug 2020

Cited by 19 | Viewed by 4122

Abstract

Thyme (TO), cinnamon (CO), and Ceylon type lemongrass (LO) essential oils (EOs) are commonly used for inhalation. However, their effects and mechanisms on inflammatory processes are not well-documented, and the number of in vivo data that would be important to determine their potential [...] Read more.

Thyme (TO), cinnamon (CO), and Ceylon type lemongrass (LO) essential oils (EOs) are commonly used for inhalation. However, their effects and mechanisms on inflammatory processes are not well-documented, and the number of in vivo data that would be important to determine their potential benefits or risks is low. Therefore, we analyzed the chemical composition and investigated the activity of TO, CO, and LO on airway functions and inflammatory parameters in an acute pneumonitis mouse model. The components of commercially available EOs were measured by gas chromatography–mass spectrometry. Airway inflammation was induced by intratracheal endotoxin administration in mice. EOs were inhaled during the experiments. Airway function and hyperresponsiveness were determined by unrestrained whole-body plethysmography on conscious animals. Myeloperoxidase (MPO) activity was measured by spectrophotometry from lung tissue homogenates, from which semiquantitative histopathological scores were assessed. The main components of TO, CO, and LO were thymol, cinnamaldehyde, and citronellal, respectively. We provide here the first evidence that TO and CO reduce inflammatory airway hyperresponsiveness and certain cellular inflammatory parameters, so they can potentially be considered as adjuvant treatments in respiratory inflammatory conditions. In contrast, Ceylon type LO inhalation might have an irritant effect (e.g., increased airway hyperresponsiveness and MPO activity) on the inflamed airways, and therefore should be avoided. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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Review

Jump to: Research

27 pages, 952 KiB

Open AccessReview

The Therapeutic Potential of Carnosine as an Antidote against Drug-Induced Cardiotoxicity and Neurotoxicity: Focus on Nrf2 Pathway

by Giuseppe Caruso, Anna Privitera, Barbara Moura Antunes, Giuseppe Lazzarino, Susan Marie Lunte, Giancarlo Aldini and Filippo Caraci

Molecules 2022, 27(14), 4452; https://doi.org/10.3390/molecules27144452 - 12 Jul 2022

Cited by 22 | Viewed by 4128

Abstract

Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs, antipsychotic, and immunosuppressant drugs are known to induce cardiotoxic and neurotoxic effects. Recent studies have demonstrated that the impairment of the nuclear factor erythroid 2–related factor 2 [...] Read more.

Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs, antipsychotic, and immunosuppressant drugs are known to induce cardiotoxic and neurotoxic effects. Recent studies have demonstrated that the impairment of the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway is a primary event in the pathophysiology of drug-induced cardiotoxicity and neurotoxicity. The Nrf2 pathway regulates the expression of different genes whose products are involved in antioxidant and inflammatory responses and the detoxification of toxic species. Cardiotoxic drugs, such as the anthracycline doxorubicin, or neurotoxic drugs, such as paclitaxel, suppress or impair the Nrf2 pathway, whereas the rescue of this pathway counteracts both the oxidative stress and inflammation that are related to drug-induced cardiotoxicity and neurotoxicity. Therefore Nrf2 represents a novel pharmacological target to develop new antidotes in the field of clinical toxicology. Interestingly, carnosine (β-alanyl-l-histidine), an endogenous dipeptide that is characterized by strong antioxidant, anti-inflammatory, and neuroprotective properties is able to rescue/activate the Nrf2 pathway, as demonstrated by different preclinical studies and preliminary clinical evidence. Starting from these new data, in the present review, we examined the evidence on the therapeutic potential of carnosine as an endogenous antidote that is able to rescue the Nrf2 pathway and then counteract drug-induced cardiotoxicity and neurotoxicity. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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14 pages, 898 KiB

Open AccessFeature PaperReview

Unveiling the Hidden Therapeutic Potential of Carnosine, a Molecule with a Multimodal Mechanism of Action: A Position Paper

by Giuseppe Caruso

Molecules 2022, 27(10), 3303; https://doi.org/10.3390/molecules27103303 - 20 May 2022

Cited by 20 | Viewed by 4294

Abstract

Carnosine (β-alanyl-L-histidine) is a naturally occurring endogenous dipeptide and an over-the-counter food supplement with a well-demonstrated multimodal mechanism of action that includes the detoxification of reactive oxygen and nitrogen species, the down-regulation of the production of pro-inflammatory mediators, the inhibition of aberrant protein [...] Read more.

Carnosine (β-alanyl-L-histidine) is a naturally occurring endogenous dipeptide and an over-the-counter food supplement with a well-demonstrated multimodal mechanism of action that includes the detoxification of reactive oxygen and nitrogen species, the down-regulation of the production of pro-inflammatory mediators, the inhibition of aberrant protein formation, and the modulation of cells in the peripheral (macrophages) and brain (microglia) immune systems. Since its discovery more than 100 years ago, a plethora of in vivo preclinical studies have been carried out; however, there is still substantial heterogeneity regarding the route of administration, the dosage, the duration of the treatment, and the animal model selected, underlining the urgent need for “coordinated/aligned” preclinical studies laying the foundations for well-defined future clinical trials. The main aim of the present position paper is to critically and concisely consider these key points and open a discussion on the possible “alignment” for future studies, with the goal of validating the full therapeutic potential of this intriguing molecule. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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13 pages, 965 KiB

Open AccessReview

The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches

by Stefania Schiavone, Maria Grazia Morgese, Paolo Tucci and Luigia Trabace

Molecules 2021, 26(15), 4700; https://doi.org/10.3390/molecules26154700 - 3 Aug 2021

Cited by 15 | Viewed by 4156

Abstract

Celastrol, the most abundant compound derived from the root of Tripterygium wilfordii, largely used in traditional Chinese medicine, has shown preclinical and clinical efficacy for a broad range of disorders, acting via numerous mechanisms, including the induction of the expression of several neuroprotective [...] Read more.

Celastrol, the most abundant compound derived from the root of Tripterygium wilfordii, largely used in traditional Chinese medicine, has shown preclinical and clinical efficacy for a broad range of disorders, acting via numerous mechanisms, including the induction of the expression of several neuroprotective factors, the inhibition of cellular apoptosis, and the decrease of reactive oxygen species (ROS). Given the crucial implication of these pathways in the pathogenesis of Central Nervous System disorders, both in vitro and in vivo studies have focused their attention on the possible use of this compound in these diseases. However, although most of the available studies have reported significant neuroprotective effects of celastrol in cellular and animal models of these pathological conditions, some of these data could not be replicated. This review aims to discuss current in vitro and in vivo lines of evidence on the therapeutic potential of celastrol in neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, and cadmium-induced neurodegeneration, as well as in psychiatric disorders, such as psychosis and depression. In vitro and in vivo studies focused on celastrol effects in cerebral ischemia, ischemic stroke, traumatic brain injury, and epilepsy are also described. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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19 pages, 1550 KiB

Open AccessReview

The Therapeutic Potential of Cannabis in Counteracting Oxidative Stress and Inflammation

by Michał Graczyk, Agata Anna Lewandowska and Tomasz Dzierżanowski

Molecules 2021, 26(15), 4551; https://doi.org/10.3390/molecules26154551 - 28 Jul 2021

Cited by 15 | Viewed by 5392

Abstract

Significant growth of interest in cannabis (Cannabis sativa L.), especially its natural anti-inflammatory and antioxidative properties, has been observed recently. This narrative review aimed to present the state of the art of research concerning the anti-inflammatory activity of all classes of cannabinoids [...] Read more.

Significant growth of interest in cannabis (Cannabis sativa L.), especially its natural anti-inflammatory and antioxidative properties, has been observed recently. This narrative review aimed to present the state of the art of research concerning the anti-inflammatory activity of all classes of cannabinoids published in the last five years. Multimodal properties of cannabinoids include their involvement in immunological processes, anti-inflammatory, and antioxidative effects. Cannabinoids and non-cannabinoid compounds of cannabis proved their anti-inflammatory effects in numerous animal models. The research in humans is missing, and the results are unconvincing. Although preclinical evidence suggests cannabinoids are of value in treating chronic inflammatory diseases, the clinical evidence is scarce, and further well-designed clinical trials are essential to determine the prospects for using cannabinoids in inflammatory conditions. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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17 pages, 601 KiB

Open AccessReview

Targeting Inflammation by Anthocyanins as the Novel Therapeutic Potential for Chronic Diseases: An Update

by Aleksandra Kozłowska and Tomasz Dzierżanowski

Molecules 2021, 26(14), 4380; https://doi.org/10.3390/molecules26144380 - 20 Jul 2021

Cited by 34 | Viewed by 4423

Abstract

Low-grade chronic inflammation (LGCI) and oxidative stress act as cooperative and synergistic partners in the pathogenesis of a wide variety of diseases. Polyphenols, including anthocyanins, are involved in regulating the inflammatory state and activating the endogenous antioxidant defenses. Anthocyanins’ effects on inflammatory markers [...] Read more.

Low-grade chronic inflammation (LGCI) and oxidative stress act as cooperative and synergistic partners in the pathogenesis of a wide variety of diseases. Polyphenols, including anthocyanins, are involved in regulating the inflammatory state and activating the endogenous antioxidant defenses. Anthocyanins’ effects on inflammatory markers are promising and may have the potential to exert an anti-inflammatory effect in vitro and in vivo. Therefore, translating these research findings into clinical practice would effectively contribute to the prevention and treatment of chronic disease. The present narrative review summarizes the results of clinical studies from the last 5 years in the context of the anti-inflammatory and anti-oxidative role of anthocyanins in both health and disease. There is evidence to indicate that anthocyanins supplementation in the regulation of pro-inflammatory markers among the healthy and chronic disease population. Although the inconsistencies between the result of randomized control trials (RCTs) and meta-analyses were also observed. Regarding anthocyanins’ effects on inflammatory markers, there is a need for long-term clinical trials allowing for the quantifiable progression of inflammation. The present review can help clinicians and other health care professionals understand the importance of anthocyanins use in patients with chronic diseases. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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12 pages, 688 KiB

Open AccessReview

Oxidative Stress in Down and Williams-Beuren Syndromes: An Overview

by Marta Ferrari and Stefano Stagi

Molecules 2021, 26(11), 3139; https://doi.org/10.3390/molecules26113139 - 24 May 2021

Cited by 13 | Viewed by 3561

Abstract

Oxidative stress is the result of an imbalance in the redox state in a cell or a tissue. When the production of free radicals, which are physiologically essential for signaling, exceeds the antioxidant capability, pathological outcomes including oxidative damage to macromolecules, aberrant signaling, [...] Read more.

Oxidative stress is the result of an imbalance in the redox state in a cell or a tissue. When the production of free radicals, which are physiologically essential for signaling, exceeds the antioxidant capability, pathological outcomes including oxidative damage to macromolecules, aberrant signaling, and inflammation can occur. Down syndrome (DS) and Williams-Beuren syndrome (WBS) are well-known and common genetic conditions with multi-systemic involvement. Their etiology is linked to oxidative stress with important causative genes, such as SOD-1 and NCF-1, respectively, of the diseases being primarily involved in the regulation of the redox state. Early aging, dementia, autoimmunity, and chronic inflammation are some of the main characteristics of these conditions that can be associated with oxidative stress. In recent decades, there has been a growing interest in the possible role of oxidative stress and inflammation in the pathology of these conditions. However, at present, few studies have investigated these correlations. We provide an overview of the current literature concerning the role of oxidative stress and oxidative damage in genetic syndromes with a focus on Down syndrome and WBS. We hope to provide new insights to improve the management of complications related to these diseases. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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26 pages, 9218 KiB

Open AccessReview

Ocular Delivery of Polyphenols: Meeting the Unmet Needs

by Luna Krstić, María J. González-García and Yolanda Diebold

Molecules 2021, 26(2), 370; https://doi.org/10.3390/molecules26020370 - 12 Jan 2021

Cited by 6 | Viewed by 4073

Abstract

Nature has become one of the main sources of exploration for researchers that search for new potential molecules to be used in therapy. Polyphenols are emerging as a class of compounds that have attracted the attention of pharmaceutical and biomedical scientists. Thanks to [...] Read more.

Nature has become one of the main sources of exploration for researchers that search for new potential molecules to be used in therapy. Polyphenols are emerging as a class of compounds that have attracted the attention of pharmaceutical and biomedical scientists. Thanks to their structural peculiarities, polyphenolic compounds are characterized as good scavengers of free radical species. This, among other medicinal effects, permits them to interfere with different molecular pathways that are involved in the inflammatory process. Unfortunately, many compounds of this class possess low solubility in aqueous solvents and low stability. Ocular pathologies are spread worldwide. It is estimated that every individual at least once in their lifetime experiences some kind of eye disorder. Oxidative stress or inflammatory processes are the basic etiological mechanisms of many ocular pathologies. A variety of polyphenolic compounds have been proved to be efficient in suppressing some of the indicators of these pathologies in in vitro and in vivo models. Further application of polyphenolic compounds in ocular therapy lacks an adequate formulation approach. Therefore, more emphasis should be put in advanced delivery strategies that will overcome the limits of the delivery site as well as the ones related to the polyphenols in use. This review analyzes different drug delivery strategies that are employed for the formulation of polyphenolic compounds when used to treat ocular pathologies related to oxidative stress and inflammation. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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23 pages, 1397 KiB

Open AccessReview

The Biological Activities and Therapeutic Potentials of Baicalein Extracted from Oroxylum indicum: A Systematic Review

by Nik Nur Hakimah Nik Salleh, Farah Amna Othman, Nur Alisa Kamarudin and Suat Cheng Tan

Molecules 2020, 25(23), 5677; https://doi.org/10.3390/molecules25235677 - 2 Dec 2020

Cited by 49 | Viewed by 6592

Abstract

In Southeast Asia, traditional medicine has a longestablished history and plays an important role in the health care system. Various traditional medicinal plants have been used to treat diseases since ancient times and much of this traditional knowledge remains preserved today. Oroxylum indicum [...] Read more.

In Southeast Asia, traditional medicine has a longestablished history and plays an important role in the health care system. Various traditional medicinal plants have been used to treat diseases since ancient times and much of this traditional knowledge remains preserved today. Oroxylum indicum (beko plant) is one of the medicinal herb plants that is widely distributed throughout Asia. It is a versatile plant and almost every part of the plant is reported to possess a wide range of pharmacological activities. Many of the important bioactivities of this medicinal plant is related to the most abundant bioactive constituent found in this plant—the baicalein. Nonetheless, there is still no systematic review to report and vindicate the biological activities and therapeutic potential of baicalein extracted from O. indicum to treat human diseases. In this review, we aimed to systematically present in vivo and in vitro studies searched from PubMed, ScienceDirect, Scopus and Google Scholar database up to 31 March 2020 based on keywords “Oroxylum indicum” and “baicalein”. After an initial screening of titles and abstracts, followed by a full-text analysis and validation, 20 articles that fulfilled all the inclusion and exclusion criteria were included in this systematic review. The searched data comprehensively reported the biological activities and therapeutic potential of baicalein originating from the O. indicum plant for anti-cancer, antibacterial, anti-hyperglycemia, neurogenesis, cardioprotective, anti-adipogenesis, anti-inflammatory and wound healing effects. Nonetheless, we noticed that there was a scarcity of evidence on the efficacy of this natural active compound in human clinical studies. In conclusion, this systematic review article provides new insight into O. indicum and its active constituent baicalein as a prospective complementary therapy from the perspective of modern and scientific aspect. We indicate the potential of this natural product to be developed into more conscientious and judicious evidencebased medicine in the future. However, we also recommend more clinical research to confirm the efficacy and safety of baicalein as therapeutic medicine for patients. Full article

(This article belongs to the Special Issue The Therapeutic Potential of Naturally Occurring Compounds in Counteracting Oxidative Stress and Inflammation: From Basic Science to Therapy)

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