Research

18 pages, 2162 KiB

Open AccessArticle

Trihexyphenidyl Alters Its Host’s Metabolism, Neurobehavioral Patterns, and Gut Microbiome Feedback Loop—The Modulating Role of Anacyclus pyrethrum

by Abdelmounaim Baslam, Hajar Azraida, Rachida Aboufatima, Mohamed Ait-El-Mokhtar, Ilham Dilagui, Samia Boussaa, Abderrahman Chait and Marouane Baslam

Antioxidants 2024, 13(1), 26; https://doi.org/10.3390/antiox13010026 - 21 Dec 2023

Viewed by 1066

Abstract

Trihexyphenidyl (THP)—a synthetic anticholinergic medication used to manage parkinsonism and extrapyramidal symptoms—has gained significant clinical recognition. However, there is a critical gap in understanding its withdrawal effects. This study investigates the intricate interplay between gut microbiota and oxidative stress during THP withdrawal. Furthermore, [...] Read more.

Trihexyphenidyl (THP)—a synthetic anticholinergic medication used to manage parkinsonism and extrapyramidal symptoms—has gained significant clinical recognition. However, there is a critical gap in understanding its withdrawal effects. This study investigates the intricate interplay between gut microbiota and oxidative stress during THP withdrawal. Furthermore, it explores the therapeutic potential of Anacyclus pyrethrum (AEAP) for alleviating the associated adverse effects. This comprehensive research combines behavioral tests, biochemical analysis, gut microbiome assessment utilizing matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), and oxidative stress measures. The results reveal that the chronic administration of THP leads to severe withdrawal syndrome, marked by heightened anxiety, depressive-like behaviors, increased cortisol levels, elevated oxidative stress, and gut dysbiosis. However, the administration of AEAP alongside THP shows a significant capacity to mitigate these deleterious effects. Co-treatment and post-treatment with AEAP increased bacterial density and diversity, promoting the proliferation of beneficial bacteria associated with improved gut health. Furthermore, AEAP administration reduced cortisol levels and exhibited potent antioxidant properties, effectively countering the THP-induced oxidative damage. This study highlights the withdrawal effects of THP and underscores the therapeutic potential of AEAP for managing these symptoms. The findings reveal its promising effects in alleviating behavioral and biochemical impairments, reducing oxidative stress, and restoring gut microbiota, which could significantly impact the clinical management of THP withdrawal and potentially extend to other substance withdrawal scenarios. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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25 pages, 5163 KiB

Open AccessArticle

Azadirachtin Attenuates Carcinogen Benzo(a) Pyrene-Induced DNA Damage, Cell Cycle Arrest, Apoptosis, Inflammatory, Metabolic, and Oxidative Stress in HepG2 Cells

by Annie John and Haider Raza

Antioxidants 2023, 12(11), 2001; https://doi.org/10.3390/antiox12112001 - 14 Nov 2023

Cited by 2 | Viewed by 922

Abstract

Azadirachtin (AZD), a limonoid from the versatile, tropical neem tree (Azadirachta indica), is well known for its many medicinal, and pharmacological effects. Its effects as an anti-oxidant, anti-inflammatory, and anti-cancer agent are well known. However, not many studies have explored the effects of [...] Read more.

Azadirachtin (AZD), a limonoid from the versatile, tropical neem tree (Azadirachta indica), is well known for its many medicinal, and pharmacological effects. Its effects as an anti-oxidant, anti-inflammatory, and anti-cancer agent are well known. However, not many studies have explored the effects of AZD on toxicities induced by benzo(a)pyrene (B(a)P), a toxic component of cigarette smoke known to cause DNA damage and cell cycle arrest, leading to different kinds of cancer. In the present study, using HepG2 cells, we investigated the protective effects of Azadirachtin (AZD) against B(a)P-induced oxidative/nitrosative and metabolic stress and mitochondrial dysfunction. Treatment with 25 µM B(a)P for 24 h demonstrated an increased production of reactive oxygen species (ROS), followed by increased lipid peroxidation and DNA damage presumably, due to the increased metabolic activation of B(a)P by CYP 450 1A1/1A2 enzymes. We also observed intrinsic and extrinsic apoptosis, alterations in glutathione-dependent redox homeostasis, cell cycle arrest, and inflammation after B(a)P treatment. Cells treated with 25 µM AZD for 24 h showed decreased oxidative stress and apoptosis, partial protection from DNA damage, and an improvement in mitochondrial functions and bioenergetics. The improvement in antioxidant status, anti-inflammatory potential, and alterations in cell cycle regulatory markers qualify AZD as a potential therapeutic in combination with anti-cancer drugs. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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17 pages, 3402 KiB

Open AccessArticle

Molecular Networking and Bioassay-Guided Preparation and Separation of Active Extract and Constituents from Vicia tenuifolia Roth

by Duc Dat Le, Soojung Yu, Thinhulinh Dang and Mina Lee

Antioxidants 2023, 12(10), 1876; https://doi.org/10.3390/antiox12101876 - 18 Oct 2023

Viewed by 1107

Abstract

Molecular networking drove the selection of material from V. tenuifolia organs that targeted active flavonoid glycosides. To optimize the extraction process, the flowers of V. tenuifolia were used to produce an anti-inflammatory extract. The effects of variables—organic solvent ratio; extraction time; and temperature—were [...] Read more.

Molecular networking drove the selection of material from V. tenuifolia organs that targeted active flavonoid glycosides. To optimize the extraction process, the flowers of V. tenuifolia were used to produce an anti-inflammatory extract. The effects of variables—organic solvent ratio; extraction time; and temperature—were investigated by the response of anti-inflammatory activity. Bioactivities-guided experiments helped identify fractions with high total phenolic and flavonoid content as well as antioxidant potential. Furthermore, one new compound (1), 19 first isolated together, and two known compounds were obtained and identified from the active fraction of this plant. Among them, compounds (15 and 22) were first reported for nuclear magnetic resonance (NMR) data from this study. All the isolates were evaluated for their anti-inflammatory capacity throughout, modulating nitric oxide (NO), interleukin (IL)-1β, and IL-8 production. Active compounds were further investigated for their regulation and binding affinity to the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins by Western blot and in silico approaches, respectively. The findings of this study suggested that the developed extract method, active fraction, and pure components should be further investigated as promising candidates for treating inflammation and oxidation. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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16 pages, 4563 KiB

Open AccessArticle

Potential Antioxidant and Anti-Inflammatory Effects of Lonicera japonica and Citri Reticulatae Pericarpium Polyphenolic Extract (LCPE)

by Se Hyo Jeong, Min Yeong Park, Pritam Bhagwan Bhosale, Abuyaseer Abusaliya, Chung Kil Won, Kwang Il Park, Eunhye Kim, Jeong Doo Heo, Hyun Wook Kim, Meejung Ahn, Je Kyung Seong, Hun Hwan Kim and Gon Sup Kim

Antioxidants 2023, 12(8), 1582; https://doi.org/10.3390/antiox12081582 - 08 Aug 2023

Cited by 2 | Viewed by 1782

Abstract

Dermatitis is an inflammatory condition of the outer layer of the skin that causes itching, blisters, redness, swelling, and often exudation, scabs, and peeling. Among them, purulent inflammation is a symptom that often occurs on the skin and appears in the form of [...] Read more.

Dermatitis is an inflammatory condition of the outer layer of the skin that causes itching, blisters, redness, swelling, and often exudation, scabs, and peeling. Among them, purulent inflammation is a symptom that often occurs on the skin and appears in the form of boils and acne. Various studies are being conducted to treat these inflammatory diseases. Accordingly, Lonicera japonica and Citri Reticulatae Pericarpium Polyphenolic Extract (LCPE), which uses herbal preparations such as Lonicera japonica, Citri Reticulatae Pericarpium, and Glycyrrhiza uralensis, has been used to suppress inflammation since ancient times, and its anti-inflammatory effect can be observed in skin keratinocytes after inducing inflammation. In this study, the major polyphenolic compounds in LCPE were quantitatively determined by analyzing the data through peak values using high-performance chromatography (HPLC-MS/MS) coupled with mass spectrometry. Additionally, bioactive compounds targeting 2,2-diphenyl-1-picrylhydrazyl (DPPH) were analyzed by ultrafiltration integrated with LC. Several compounds with the most significant effects were selected (chlorogenic acid, narirutin, and isorhamnetin). Skin keratinocytes induced by lipopolysaccharide (LPS) were treated with LCPE to show its anti-inflammatory effects. After LCPE treatment, inflammation-mediating cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were decreased. In addition, nuclear factor kappa (NF-кB) and mitogen-activated protein kinase (MAPK) were inhibited in important pathways related to inflammation. Lastly, molecular modeling was performed to determine binding scores with inflammation-related proteins using molecular docking for the selected compounds. According to these results, LCPE is effective in treating keratinocytes induced by LPS and reducing inflammation and has potential antioxidant effects, and the polyphenol components have been identified. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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16 pages, 1751 KiB

Open AccessArticle

Ferulic, Sinapic, 3,4-Dimethoxycinnamic Acid and Indomethacin Derivatives with Antioxidant, Anti-Inflammatory and Hypolipidemic Functionality

by Panagiotis Theodosis-Nobelos, Georgios Papagiouvannis and Eleni A. Rekka

Antioxidants 2023, 12(7), 1436; https://doi.org/10.3390/antiox12071436 - 17 Jul 2023

Cited by 7 | Viewed by 1340

Abstract

A series of thiomorpholine and cinnamyl alcohol derivatives, conjugated with cinnamic acid-containing moieties, such as ferulic acid, sinapic acid and 3,4-dimethoxycinnamic acid, were synthesized and tested for their antioxidant, anti-inflammatory and hypolipidemic properties. An indomethacin ester with 2,6-di-tert-butyl-4-(hydroxymethyl)phenol was also prepared [...] Read more.

A series of thiomorpholine and cinnamyl alcohol derivatives, conjugated with cinnamic acid-containing moieties, such as ferulic acid, sinapic acid and 3,4-dimethoxycinnamic acid, were synthesized and tested for their antioxidant, anti-inflammatory and hypolipidemic properties. An indomethacin ester with 2,6-di-tert-butyl-4-(hydroxymethyl)phenol was also prepared for reasons of comparison. The majority of the compounds demonstrated considerable antioxidant capacity and radical scavenging activity, reaching up to levels similar to the well-known antioxidant trolox. Some of them had an increased anti-inflammatory effect on the reduction of carrageenan-induced rat paw edema (range 17–72% at 150 μmol/kg), having comparable activity to the NSAIDs (non-steroidal anti-inflammatory drugs) used as reference. They had moderate activity in soybean lipoxygenase inhibition. All the tested compounds exhibited a significant decrease in lipidemic indices in Triton-induced hyperlipidemia in rats, whilst the most active triglycerides and total cholesterol decreased by 72.5% and 76%, respectively, at 150 μmol/kg (i.p.), slightly better than that of simvastatin, a well-known hypocholesterolemic drug, but with negligible triglyceride-lowering effect. Since our designed compounds seem to exhibit multiple pharmacological activities, they may be of use in occasions involving inflammation, oxidative stress, lipidemic deregulation and degenerative conditions. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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15 pages, 1348 KiB

Open AccessArticle

Anti-Inflammatory, Anti-Oxidative and Anti-Apoptotic Effects of Thymol and 24-Epibrassinolide in Zebrafish Larvae

by Germano A. B. Lanzarin, Luís M. Félix, Sandra M. Monteiro, Jorge M. Ferreira, Paula A. Oliveira and Carlos Venâncio

Antioxidants 2023, 12(6), 1297; https://doi.org/10.3390/antiox12061297 - 18 Jun 2023

Viewed by 1577

Abstract

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 (Danio rerio) larvae transgenic line (Tg(mpx [...] Read more.

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 (Danio rerio) larvae transgenic line (Tg(mpxGFP)ⁱ¹¹⁴) 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(mpxGFP)ⁱ¹¹⁴, 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. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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20 pages, 2955 KiB

Open AccessArticle

Antioxidant and Anti-Inflammatory Capacities of Fractions and Constituents from Vicia tetrasperma

by Duc Dat Le, Kyung Hyun Min and Mina Lee

Antioxidants 2023, 12(5), 1044; https://doi.org/10.3390/antiox12051044 - 04 May 2023

Cited by 1 | Viewed by 1536

Abstract

The young leaves and shoots of V. tetrasperma are consumed daily as cooked vegetables and can provide various health benefits. The antioxidant and anti-inflammatory capacities of its total extract and fractions were accessed for the first time in this study. The bioactivities [...] Read more.

The young leaves and shoots of V. tetrasperma are consumed daily as cooked vegetables and can provide various health benefits. The antioxidant and anti-inflammatory capacities of its total extract and fractions were accessed for the first time in this study. The bioactivities guided the separation of the active fraction (EtOAc), leading to the identification of nine flavonoid glycoside compositions from this plant for the first time. In addition, the fractions and all isolates were evaluated for their inhibition against NO and IL-8 production in LPS-stimulated RAW264.7 and HT-29 cell lines, respectively. The most active ingredient was further assayed for its inhibitory abilities to iNOS and COX-2 proteins. Indeed, its mechanisms of action modes were confirmed by Western blotting assays through the reduction in their expression levels. An in silico approach revealed the substantial binding energies of docked compounds into established complexes to verify their anti-inflammatory properties. In addition, the presence of active components in the plant was validated by an established method on the UPLC-DAD system. Our research has boosted the value of this vegetable’s daily use and provided a therapeutic approach for the development of functional food products for health improvement regarding the treatment of oxidation and inflammation. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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13 pages, 1388 KiB

Open AccessArticle

Anti-Inflammatory, Neurotrophic, and Cytotoxic Oxylipins Isolated from Chaenomeles sinensis Twigs

by Da Yeong Lee, Kyoung Jin Park, Lalita Subedi, Gyu Sung Lee, Ji-Hyeok Lee, Won-Min Lee, Sang Un Choi, Seong-Min Hong, Sun Yeou Kim and Chung Sub Kim

Antioxidants 2023, 12(2), 284; https://doi.org/10.3390/antiox12020284 - 27 Jan 2023

Cited by 1 | Viewed by 1512

Abstract

Oxylipins are important biological molecules with diverse roles in human and plants such as pro-/anti-inflammatory, antimicrobial, and regulatory activity. Although there is an increasing number of plant-derived oxylipins, most of their physiological roles in humans remain unclear. Here, we describe the isolation, identification, [...] Read more.

Oxylipins are important biological molecules with diverse roles in human and plants such as pro-/anti-inflammatory, antimicrobial, and regulatory activity. Although there is an increasing number of plant-derived oxylipins, most of their physiological roles in humans remain unclear. Here, we describe the isolation, identification, and biological activities of four new oxylipins, chaenomesters A–D (1–4), along with a known compound (5), obtained from Chaenomeles sinensis twigs. Their chemical structures were determined by spectroscopic (i.e., NMR) and spectrometric (i.e., HRMS) data analysis including ¹H NMR-based empirical rules and homonuclear-decoupled ¹H NMR experiments. Chaenomester D (4), an omega-3 oxylipin, showed a potent inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells (NO production, 8.46 ± 0.68 μM), neurotrophic activity in C6 cells through the induction of the secretion of nerve growth factor (NGF, 157.7 ± 2.4%), and cytotoxicity in A549 human cancer cell lines (IC₅₀ = 27.4 μM). Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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19 pages, 4792 KiB

Open AccessArticle

Ishige okamurae Attenuates Neuroinflammation and Cognitive Deficits in Mice Intracerebroventricularly Injected with LPS via Regulating TLR-4/MyD88-Dependent Pathways

by Oh-Yun Kwon and Seung-Ho Lee

Antioxidants 2023, 12(1), 78; https://doi.org/10.3390/antiox12010078 - 29 Dec 2022

Cited by 2 | Viewed by 1485

Abstract

Neuroinflammation is one of the critical causes of neuronal loss and cognitive impairment. We aimed to evaluate the anti-neuroinflammatory properties of Ishige okamuae using mice intracerebroventricularly injected with lipopolysaccharides (LPS) and LPS-treated C6 glioma cells. We found that the short- and long-term memory [...] Read more.

Neuroinflammation is one of the critical causes of neuronal loss and cognitive impairment. We aimed to evaluate the anti-neuroinflammatory properties of Ishige okamuae using mice intracerebroventricularly injected with lipopolysaccharides (LPS) and LPS-treated C6 glioma cells. We found that the short- and long-term memory deficits of LPS-injected mice were improved by oral administration of Ishige okamurae extracts (IOE). LPS-induced neuronal loss, increase in amyloid-β plaque, and expression of COX-2 and iNOS were restored by IOE. In addition, LPS-induced activation of Toll-like receptor-4 (TLR-4) and its downstream molecules, such as MyD88, NFκB, and mitogen-activated protein kinases (MAPKs), were significantly attenuated in the brains of mice fed with IOE. We found that pretreatment of IOE to C6 glioma cells ameliorated LPS-induced expression of TLR-4 and its inflammatory cascades, such as MyD88 expression, reactive oxygen species production, MAPKs phosphorylation, and NFκB phosphorylation with consequent downregulation of COX-2, iNOS, proinflammatory cytokines, and nitric oxide expression. Furthermore, IOE (0.2 µg/mL) was found to have equivalent efficacy with 10 μM of MyD88 inhibitor in preventing LPS-induced inflammatory responses in C6 glioma cells. Taken together, these results strongly suggest that IOE could be developed as a promising anti-neuroinflammatory agent which is able to control the TLR-4/MyD88-dependent signaling pathways. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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10 pages, 1810 KiB

Open AccessArticle

Antioxidant and Anti-Inflammatory Activities of Sargassum macrocarpum Extracts

by Hoon Kim, Hyun Young Shin, Eun-Jin Jeong, Hak-Dong Lee, Ki Cheol Hwang, Kwang-Won Yu, Sullim Lee and Sanghyun Lee

Antioxidants 2022, 11(12), 2483; https://doi.org/10.3390/antiox11122483 - 16 Dec 2022

Viewed by 2060

Abstract

Oxidative stress and the inflammatory response are known to be the most important pathological factors for aging skin cells. Therefore, substances that protect skin cells from oxidative stress and inflammatory reactions of the skin have potential as functional ingredients for skin care. In [...] Read more.

Oxidative stress and the inflammatory response are known to be the most important pathological factors for aging skin cells. Therefore, substances that protect skin cells from oxidative stress and inflammatory reactions of the skin have potential as functional ingredients for skin care. In the present study, we investigated the potential of Sargassum macrocarpum as an anti-inflammatory candidate for inflammatory skin disease. Antioxidant and anti-inflammatory activities are desirable properties in such functional materials. The total polyphenol content as well as antioxidant and anti-inflammatory activities were evaluated in hot-water (HES) and ethanol (EES) extracts of S. macrocarpum. The polyphenol content was higher in the HES (HES: 115.9 ± 15.3 mg GA/g, EES: 3.9 ± 0.5 mg GA/g), and the HES also had ABTS (HES: IC₅₀ 1.0 ± 0.0 mg/mL, EES: IC₅₀ 16.09 ± 0.7 mg/mL) and DPPH (HES: IC₅₀ 6.50 ± 0.3 mg/mL, EES: IC₅₀ 35.3 ± 3.1 mg/mL) radical scavenging capacities as well as FRAP activity (HES: IC₅₀ 18.8 ± 0.4 mg/mL, EES: IC₅₀ n.d.). Compared with the EES at the equivalent concentration range (1.25–20 μg/mL), the HES exerted a more potent inhibitory activity on LPS-stimulated nitric oxide (10.3–43.1%), IL-6 (15.7–45.0%), and TNF-α (14.1–20.8%) in RAW 264.7 macrophage cells in addition to TNF-α and IFN-γ-facilitated IL-6 (10.9–84.1%) and IL-8 (7.7–73.2%) in HaCaT keratinocytes. These results suggested that water-soluble materials might be deeply involved in the antioxidant and anti-inflammatory activity in S. macrocarpum. General composition analysis indicated that the HES contains more carbohydrates and polyphenols than the EES, and the monosaccharide composition analysis suggested that fucose-containing sulfated polysaccharide and β-glucan might be potent anti-inflammatory candidates in the HES. The present study presents important preliminary results and a valuable strategy for developing novel anti-skin dermatitis candidates using a hot-water extract of S. macrocarpum. Full article

(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Compounds from Natural Products)

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