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Frontiers in Endocrinology 2023Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD is multifactorial... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD is multifactorial and results from a complex interplay between mucosal immunity, environmental factors, and host genetics. Future therapeutics for GI disorders, including IBD, that are driven by oxidative stress require a greater understanding of the cellular and molecular mechanisms mediated by reactive oxygen species (ROS). In the GI tract, oxidative stressors include infections and pro-inflammatory responses, which boost ROS generation by promoting the production of pro-inflammatory cytokines. Nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) represent two important signaling pathways in intestinal immune cells that regulate numerous physiological processes, including anti-inflammatory and antioxidant activities. Natural antioxidant compounds exhibit ROS scavenging and increase antioxidant defense capacity to inhibit pro-oxidative enzymes, which may be useful in IBD treatment. In this review, we discuss various polyphenolic substances (such as resveratrol, curcumin, quercetin, green tea flavonoids, caffeic acid phenethyl ester, luteolin, xanthohumol, genistein, alpinetin, proanthocyanidins, anthocyanins, silymarin), phenolic compounds including thymol, alkaloids such as berberine, storage polysaccharides such as tamarind xyloglucan, and other phytochemicals represented by isothiocyanate sulforaphane and food/spices (such as ginger, flaxseed oil), as well as antioxidant hormones like melatonin that target cellular signaling pathways to reduce intestinal inflammation occurring with IBD.
Topics: Humans; Antioxidants; Reactive Oxygen Species; Anthocyanins; Oxidative Stress; Inflammatory Bowel Diseases; Hormones; Inflammation
PubMed: 37701897
DOI: 10.3389/fendo.2023.1217165 -
Gels (Basel, Switzerland) Nov 2023Hydrogels have gained significant popularity in agricultural applications in terms of minimizing waste and mitigating the negative environmental impact of agrochemicals.... (Review)
Review
Hydrogels have gained significant popularity in agricultural applications in terms of minimizing waste and mitigating the negative environmental impact of agrochemicals. This review specifically examines the utilization of environmentally friendly, shapable hydrogels composed of polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) in various casings for crop protection against different pests, fertilizing, and watering. To activate their effectiveness, PVA/PVP hydrogels were loaded with both hydrophilic and hydrophobic environmentally friendly pesticides, namely hydrogen peroxide (HP), the essential oil thymol, and urea as a fertilizer, either separately or in combination. This review covers various physical and chemical approaches used for loading, shaping, and controlling the release profiles of pesticides and fertilizers. Additionally, it explores the evaluation of the chemical composition, structure, classification, rheology, and morphology of the hydrogels as well as their impact on the thermal stability of the encapsulated pesticides and fertilizer, followed by biological tests. These hydrogels significantly contribute to the stabilization and controlled release of essential nutrients and biocides for plants, while maintaining excellent biocidal and fertilizing properties as well as sustainability characteristics. By shedding light on the latest insights into the concepts, applications, and results of these hydrogels, this review demonstrates their immense potential for widespread future use in agriculture.
PubMed: 37998985
DOI: 10.3390/gels9110895 -
Renal Failure Dec 2023Acute kidney injury (AKI) is a syndrome characterized by an accelerating decrease in renal function in a short time. Thymol is one of the main components of thyme...
Acute kidney injury (AKI) is a syndrome characterized by an accelerating decrease in renal function in a short time. Thymol is one of the main components of thyme species and has a variety of pharmacological effects. Here, we investigated whether thymol could ameliorate rhabdomyolysis (RM)-induced AKI and its related mechanism. Glycerol was used to induce RM-associated AKI in rats. Rats received thymol (20 mg/kg/day or 40 mg/kg/day) gavage 24 h before glycerol injection until 72 h after injection daily. Kidney injury was identified by measuring serum creatinine (Scr) and urea levels and by H&E and PAS staining and immunohistochemistry (the expression of proliferating cell nuclear antigen (PCNA)). Renal superoxide dismutase (SOD), malondialdehyde (MDA), and oxidative stress-related Nrf2/HO-1 signaling pathways were measured. The expression of the inflammatory markers TNF-α, IL-6, MCP-1, and NF-κB was assessed by ELISA and western blotting. Finally, the expression of the PI3K/Akt signaling pathway was detected by western blotting. Glycerol administration induced obvious renal histologic damage and increased Scr, urea, and PCNA expression. Notably, thymol treatment attenuated these structural and functional changes and prevented renal oxidative stress, inflammatory damage and PI3K/Akt pathway downregulation associated with glycerol-induced AKI. In conclusion, thymol might have potential applications in the amelioration of AKI via its antioxidant and anti-inflammatory effects and upregulation of the PI3K/Akt signaling pathway.
Topics: Rats; Animals; Glycerol; Proliferating Cell Nuclear Antigen; Thymol; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Acute Kidney Injury; Oxidative Stress; Kidney; Rhabdomyolysis; Urea
PubMed: 37417222
DOI: 10.1080/0886022X.2023.2227728 -
Life (Basel, Switzerland) Oct 2023The investigation of monoterpenes as natural products has gained significant attention in the search for new pharmacological agents due to their ability to exhibit a... (Review)
Review
The investigation of monoterpenes as natural products has gained significant attention in the search for new pharmacological agents due to their ability to exhibit a wide range in biological activities, including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, and vasodilating properties. In vitro and in vivo studies reveal their antidepressant, anxiolytic, and memory-enhancing effects in experimental dementia and Parkinson's disease. Chemical modification of natural substances by conjugation with various synthetic components is a modern method of obtaining new biologically active compounds. The discovery of new potential drugs among monoterpene derivatives is a progressive avenue within experimental pharmacology, offering a promising approach for the therapy of diverse pathological conditions. Biologically active substances such as monoterpenes, for example, borneol, camphor, geraniol, pinene, and thymol, are used to synthesize compounds with analgesic, anti-inflammatory, anticonvulsive, antidepressant, anti-Alzheimer's, antiparkinsonian, antiviral and antibacterial (antituberculosis) properties. Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, the conjugation of myrtenal with the established pharmacophore adamantane enables the augmentation of several of its pivotal properties. Myrtenal-adamantane derivatives exhibited a variety of beneficial characteristics, such as antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective properties, which are worth examining in more detail and at length.
PubMed: 37895468
DOI: 10.3390/life13102086 -
Animals : An Open Access Journal From... Jul 2023This study aimed to evaluate the effect of diets supplementing with various levels of thymol and carvacrol eutectic (TCE) on growth performance, serum biochemical...
This study aimed to evaluate the effect of diets supplementing with various levels of thymol and carvacrol eutectic (TCE) on growth performance, serum biochemical parameters, intestinal morphology, and the expression of intestinal nutrient absorption, barrier function- and inflammation-related genes in broiler chickens. A total of 640 one-day-old Arbor Acres male broilers with similar body weights were randomly divided into four groups (8 replicates/group, 20 broilers/replicate). Birds in the four experimental groups were fed a basal diet with TCE at 0, 30, 60, or 120 mg/kg. The results showed that the growth performance of birds during 22-42 d or 1-42 d, serum IgE and IgG content at 21 d of age, jejunal and ileal morphology, ileal , , and mRNA expression were significantly increased compared with the control group ( < 0.05), and the ileal mRNA expression quadratically decreased ( < 0.05) with increasing dietary TCE supplemented dosage, and its expression showed a linear downward trend (0.05 < < 0.1). Meanwhile, compared with the other three groups, birds fed diets with 30 mg/kg TCE presented better ( < 0.05) growth performance, intestinal morphology, and function. These results indicated that the optimal supplementation amount of TCE in the broiler diets was 30 mg/kg.
PubMed: 37444040
DOI: 10.3390/ani13132242 -
Insects Sep 2023In the United States, imported fire ants are commonly referred to as red imported fire ants ( Buren), black imported fire ants ( Forel), and hybrid imported fire ants (...
In the United States, imported fire ants are commonly referred to as red imported fire ants ( Buren), black imported fire ants ( Forel), and hybrid imported fire ants ( × ). They are significant pests, and their control heavily relies on synthetic insecticides. The extensive use of insecticides has led to public concern about their potential negative effects on human health and the well-being of wildlife and the environment. As an alternative, plant-derived natural compounds, particularly essential oils (EOs) and their main constituents, show promise as safe and environmentally friendly products for controlling fire ants. Repellants are useful in managing fire ants, and plant-derived natural repellants may serve as a safer and more environmentally friendly option. This study investigates the repellency of EO-derived compounds carvacrol, thymol, and their acetates against imported fire ant workers. The results revealed that carvacrol, a GRAS compound (Generally Recognized As Safe), was the most potent repellent against , , and their hybrid, with minimum repellent effective doses (MREDs) of 0.98 µg/g, 7.80 µg/g, and 0.98 µg/g, respectively. Thymol also exhibited strong repellency, with MREDs of 31.25 µg/g, 31.25 µg/g, and 7.8 µg/g, respectively. Furthermore, thyme-red essential oil, characterized by a thymol chemotype containing 48.8% thymol and 5.1% carvacrol, was found to effectively repel the hybrid ants with an MRED of 15.6 µg/g. In contrast, thyme essential oil, characterized by a linalool chemotype lacking thymol and carvacrol, did not exhibit any repellent effect, even at the highest tested dose of 125 µg/g. This study provides the first evidence of the potent repellency of carvacrol and thymol against imported fire ant workers, indicating their potential as promising repellents for fire ant control.
PubMed: 37887802
DOI: 10.3390/insects14100790 -
Polymers Dec 2023Unsaturated fatty acids, such as oleic acid (OA) and linoleic acid (LA), are promising antimicrobial and cytostatic agents. We modified OA and LA with thymol (TOA and...
Unsaturated fatty acids, such as oleic acid (OA) and linoleic acid (LA), are promising antimicrobial and cytostatic agents. We modified OA and LA with thymol (TOA and TLA, respectively) to expand their bioavailability, stability, and possible applications, and encapsulated these derivatives in polymeric nanoparticles (TOA-NPs and TLA-NPs, respectively). Prior to synthesis, we performed mathematical simulations with PASS and ADMETlab 2.0 to predict the biological activity and pharmacokinetics of TOA and TLA. TOA and TLA were synthesized via esterification in the presence of catalysts. Next, we formulated nanoparticles using the single-emulsion solvent evaporation technique. We applied dynamic light scattering, Uv-vis spectroscopy, release studies under gastrointestinal (pH 1.2-6.8) and blood environment simulation conditions (pH 7.4), and in vitro biological activity testing to characterize the nanoparticles. PASS revealed that TOA and TLA have antimicrobial and anticancer therapeutic potential. ADMETlab 2.0 provided a rationale for TOA and TLA encapsulation. The nanoparticles had an average size of 212-227 nm, with a high encapsulation efficiency (71-93%), and released TOA and TLA in a gradual and prolonged mode. TLA-NPs possessed higher antibacterial activity against and and pronounced cytotoxic activity against MCF-7, K562, and A549 cell lines compared to TOA-NPs. Our findings expand the biomedical application of fatty acids and provide a basis for further in vivo evaluation of designed derivatives and formulations.
PubMed: 38201737
DOI: 10.3390/polym16010072 -
Antioxidants (Basel, Switzerland) Jun 2023Thymol (THY) and 24-epibrassinolide (24-EPI) are two examples of plant-based products with promising therapeutic effects. In this study, we investigated the...
Thymol (THY) and 24-epibrassinolide (24-EPI) are two examples of plant-based products with promising therapeutic effects. In this study, we investigated the anti-inflammatory, antioxidant and anti-apoptotic effects of the THY and 24-EPI. We used zebrafish () larvae transgenic line (Tg(GFP)) to evaluate the recruitment of neutrophils as an inflammatory marker to the site of injury after tail fin amputation. In another experiment, wild-type AB larvae were exposed to a well known pro-inflammatory substance, copper (CuSO4), and then exposed for 4 h to THY, 24-EPI or diclofenac (DIC), a known anti-inflammatory drug. In this model, the antioxidant (levels of reactive oxygen species-ROS) and anti-apoptotic (cell death) effects were evaluated in vivo, as well as biochemical parameters such as the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), the biotransformation activity of glutathione-S-transferase, the levels of glutathione reduced and oxidated, lipid peroxidation, acetylcholinesterase activity, lactate dehydrogenase activity, and levels of nitric acid (NO). Both compounds decreased the recruitment of neutrophils in Tg(GFP), as well as showed in vivo antioxidant effects by reducing ROS production and anti-apoptotic effects in addition to a decrease in NO compared to CuSO4. The observed data substantiate the potential of the natural compounds THY and 24-EPI as anti-inflammatory and antioxidant agents in this species. These results support the need for further research to understand the molecular pathways involved, particularly their effect on NO.
PubMed: 37372027
DOI: 10.3390/antiox12061297 -
Plants (Basel, Switzerland) Jan 2024Thymol, a plant-derived monoterpene phenol known for its broad biological activity, has often been incorporated into chitosan-based biomaterials to enhance therapeutic... (Review)
Review
Thymol, a plant-derived monoterpene phenol known for its broad biological activity, has often been incorporated into chitosan-based biomaterials to enhance therapeutic efficacy. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we conducted a systematic literature review from 2018 to 2023, focusing on the biomedical implications of thymol-loaded chitosan systems. A review of databases, including PubMed, Scopus, and Web of Science was conducted using specific keywords and search criteria. Of the 90 articles, 12 were selected for the review. Thymol-loaded chitosan-based nanogels (TLCBS) showed improved antimicrobial properties, especially against multidrug-resistant bacterial antagonists. Innovations such as bipolymer nanocarriers and thymol impregnated with photosensitive chitosan micelles offer advanced bactericidal strategies and show potential for bone tissue regeneration and wound healing. The incorporation of thymol also improved drug delivery efficiency and biomechanical strength, especially when combined with poly(dimethylsiloxane) in chitosan-gelatin films. Thymol-chitosan combinations have also shown promising applications in oral delivery and periodontal treatment. This review highlights the synergy between thymol and chitosan in these products, which greatly enhances their therapeutic efficacy and highlights the novel use of essential oil components. It also highlights the novelty of the studies conducted, as well as their limitations and possible directions for the development of integrated substances of plant and animal origin in modern and advanced medical applications.
PubMed: 38337895
DOI: 10.3390/plants13030362 -
MedComm Oct 2023Immune checkpoint blockades are the most promising therapy in lung adenocarcinoma (LUAD). However, the response rate remains limited, underscoring the urgent need for...
Immune checkpoint blockades are the most promising therapy in lung adenocarcinoma (LUAD). However, the response rate remains limited, underscoring the urgent need for effective sensitizers. Interleukin 4 induced 1 (IL4I1) is reported to have immunoinhibitory and tumor-promoting effects in several cancers. However, the targetable value of IL4I1 in sensitizing the immunotherapy is not clear, and there is a lack of effective small molecules that specifically target IL4I1. Here, we show that silencing IL4I1 significantly remodels the immune microenvironment via inhibiting aryl hydrocarbon receptor (AHR) signaling, thereby enhancing the efficacy of anti-PD-1 antibody in LUAD, which suggests that IL4I1 is a potential drug target for the combination immunotherapy. We then identify thymol as the first small molecule targeting IL4I1 transcription through a drug screening. Thymol inhibits the IL4I1 expression and blocks AHR signaling in LUAD cells. Thymol treatment restores the antitumor immune response and suppresses the progression of LUAD in an orthotopic mouse model. Strikingly, the combination treatment of thymol with anti-PD-1 antibody shows significant tumor regression in LUAD mice. Thus, we demonstrate that thymol is an effective small molecule to sensitize the PD-1 blockade in LUAD via targeting IL4I1, which provides a novel strategy for the immunotherapy of LUAD.
PubMed: 37655051
DOI: 10.1002/mco2.355