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Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 19658

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Dr. Matteo Brindisi

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IRCCS Humanitas Research Hospital, 20089 Milan, Italy
Interests: cancer; metabolism; inflammation; cell adhesion; CSCs; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Anna Rita Cappello

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Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: cancer; mitochondria; metabolism; metabolic rewiring; cancer stemness

Dr. Luca Frattaruolo

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Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: natural products; secondary metabolism; inflammation; oxidative stress; cancer metabolism

Special Issue Information

Dear Colleagues,

Plants and microbes have always been an invaluable source of natural bioactive compounds, and research on natural products has highlighted their interesting roles in several aspects of both human physiology and pathology, paving the way for notable improvements in public health.

An increasing number of studies show that oxidative stress and chronic inflammatory processes participate in the pathogenesis of various metabolic diseases. Indeed, these processes are able to induce a metabolic rewiring, which in turn leads to metabolic disorders, such as dyslipidemia, diabetes or cancer.

In this scenario, the research of natural products plays an important role, providing new tools in the control of these pathological processes. The main aim of this Special Issue is to extend our knowledge on the biological complexity of the aforementioned processes and the potential applications and efficacy of natural extracts and isolated compounds of plant or microbial origin for their prevention and treatment.

Original research articles and reviews detailing the identification and characterization of new natural bioactive compounds that are useful in the control of inflammation, oxidative stress and metabolic diseases are welcome, as well as articles describing new biological properties and molecular mechanisms of natural extracts and known natural compounds.

Dr. Matteo Brindisi
Prof. Dr. Anna Rita Cappello
Dr. Luca Frattaruolo
Guest Editors

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Keywords

natural products
inflammation
oxidative stress
metabolic disorders
secondary metabolites
metabolic rewiring
ROS

Published Papers (10 papers)

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Research

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18 pages, 2742 KiB

Open AccessArticle

Preventive Effect of Ecklonia cava Extract on DSS-Induced Colitis by Elevating Intestinal Barrier Function and Improving Pathogenic Inflammation

by Young-Mi Kim, Hye-Youn Kim, Ji-Tae Jang and Suntaek Hong

Molecules 2023, 28(24), 8099; https://doi.org/10.3390/molecules28248099 - 15 Dec 2023

Cited by 1 | Viewed by 1048

Abstract

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of Ecklonia cava extract (ECE), derived from an edible marine alga known for its anti-inflammatory and antioxidant properties, in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity, as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE alleviated dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathways known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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14 pages, 724 KiB

Open AccessArticle

Monoterpenoid Glycosides from the Leaves of Ligustrum robustum and Their Bioactivities (II)

by Shi-Hui Lu, Xiu-Xia Li, Hao-Jiang Zuo, Wei-Neng Li, Jia-Ping Pan and Jing Huang

Molecules 2023, 28(21), 7274; https://doi.org/10.3390/molecules28217274 - 26 Oct 2023

Viewed by 666

Abstract

Ligustrum robustum has been not only used as a heat-clearing and detoxicating functional tea (Ku-Ding-Cha) but also consumed as a hypotensive, anti-diabetic, and weight-reducing folk medicine. From the leaves of L. robustum, ten new monoterpenoid glycosides named ligurobustosides T₁₀ (1a), T₁₁ (1b), T₁₂ (2a), T₁₃ (2b), T₁₄ (3a), T₁₅ (3b), F₁ (4b), T₁₆ (5a), T₁₇ (5b), and E₁ (6b), together with five known ones (4a, 6a, 7, 8a, 8b), were separated and identified using the spectroscopic method and chemical method in this research. The results of biological tests exhibited that the fatty acid synthase (FAS) inhibitory action of compound 5 (IC₅₀: 4.38 ± 0.11 μM) was as strong as orlistat (IC₅₀: 4.46 ± 0.13 μM), a positive control; the α-glucosidase inhibitory actions of compounds 1–4 and 7–8, and the α-amylase inhibitory actions of compounds 1–8 were medium; the ABTS radical scavenging capacities of compounds 1–3 and 5–8 (IC₅₀: 6.27 ± 0.23 ~ 8.59 ± 0.09 μM) were stronger than l-(+)-ascorbic acid (IC₅₀: 10.06 ± 0.19 μM) served as a positive control. This research offered a theoretical foundation for the leaves of L. robustum to prevent diabetes and its complications. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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16 pages, 2922 KiB

Open AccessArticle

Glucosamine Improves Non-Alcoholic Fatty Liver Disease Induced by High-Fat and High-Sugar Diet through Regulating Intestinal Barrier Function, Liver Inflammation, and Lipid Metabolism

by Feng Li, Zhengyan Zhang, Yan Bai, Qishi Che, Hua Cao, Jiao Guo and Zhengquan Su

Molecules 2023, 28(19), 6918; https://doi.org/10.3390/molecules28196918 - 03 Oct 2023

Cited by 2 | Viewed by 1993

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a liver disease syndrome. The prevalence of NAFLD has continued to increase globally, and NAFLD has become a worldwide public health problem. Glucosamine (GLC) is an amino monosaccharide derivative of glucose. GLC has been proven to not only be effective in anti-inflammation applications, but also to modulate the gut microbiota effectively. Therefore, in this study, the therapeutic effect of GLC in the NAFLD context and the mechanisms underlying these effects were explored. Specifically, an NAFLD model was established by feeding mice a high-fat and high-sugar diet (HFHSD), and the HFHSD-fed NAFLD mice were treated with GLC. First, we investigated the effect of treating NAFLD mice with GLC by analyzing serum- and liver-related indicator levels. We found that GLC attenuated insulin resistance and inflammation, increased antioxidant function, and attenuated serum and liver lipid metabolism in the mice. Then, we investigated the mechanism underlying liver lipid metabolism, inflammation, and intestinal barrier function in these mice. We found that GLC can improve liver lipid metabolism and relieve insulin resistance and oxidative stress levels. In addition, GLC treatment increased intestinal barrier function, reduced LPS translocation, and reduced liver inflammation by inhibiting the activation of the LPS/TLR4/NF-κB pathway, thereby effectively ameliorating liver lesions in NAFLD mice. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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11 pages, 2077 KiB

Open AccessArticle

Study on the Cellular Anti-Inflammatory Effect of Torularhodin Produced by Sporidiobolus pararoseus ZQHL Isolated from Vinegar Fungus

by Chang Liu, Mei Han, Fuqiang Lv, Yaobin Gao, Xiaoyun Wang, Xujiao Zhang, Yahui Guo, Yuliang Cheng and He Qian

Molecules 2023, 28(3), 1436; https://doi.org/10.3390/molecules28031436 - 02 Feb 2023

Cited by 3 | Viewed by 1470

Abstract

The red stretcher bacterium Sporidiobolus pararoseus is a high producer of carotenoids such as torularhodin, but its presence in vinegar has not been detected. Moreover, torularhodin has several biological activities, but its effect on the LPS-induced RAW 264.7 inflammatory cell model has also yet to be elucidated. In this study, S. pararoseus was identified in different vinegar samples from China by ITS sequencing. Meanwhile, one of the strains was deeply resolved by whole genome sequencing and functional annotation and named S. pararoseus ZQHL. Subsequently, the antioxidant effect of the fungal carotenoid torularhodin was investigated using in vitro DPPH, ABTS, and cellular models. Finally, LPS-induced RAW 264.7 cells were used as an inflammation model to assess torularhodin’s protective effect on inflammatory cells and to determine whether the TLR4 pathway is associated with this process. The results indicate that torularhodin has good free radical scavenging ability in vitro and can contribute to cell viability. More importantly, torularhodin alleviated LPS-induced cellular inflammatory damage and reduced the expression of inflammatory factors such as TLR4, MyD88, and TNF-a. The mechanism may attenuate the cellular inflammatory response by inhibiting the TLR4 inflammatory pathway. In conclusion, torularhodin produced by S. pararoseus fungi in vinegar samples significantly scavenged free radicals in vitro and alleviated RAW 264.7 cellular inflammation by modulating the TLR4 pathway. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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13 pages, 2346 KiB

Open AccessArticle

Compounds from the Petroleum Ether Extract of Wedelia chinensis with Cytotoxic, Anticholinesterase, Antioxidant, and Antimicrobial Activities

by Md. Abdur Rashid Khan, Md. Aminul Islam, Kushal Biswas, Md. Yusuf Al-Amin, Md. Salim Ahammed, Md. Imran Nur Manik, KM Monirul Islam, Md. Abdul Kader, AHM Khurshid Alam, Shahed Zaman and Golam Sadik

Molecules 2023, 28(2), 793; https://doi.org/10.3390/molecules28020793 - 13 Jan 2023

Cited by 1 | Viewed by 1970

Abstract

Wedelia chinensis is a folk medicine used in many Asian countries to treat various ailments. Earlier investigations reported that the petroleum ether extract of the plant has potential biological activity, but the compounds responsible for activity are not yet completely known. Therefore, the current work was designed to isolate and characterize the compounds from the petroleum ether extract and to study their bioactivities. Four compounds including two diterepenes (-) kaur-16α-hydroxy-19-oic acid (1) and (-) kaur-16-en-19-oic acid (2), and two steroids β-sitosterol (3), and cholesta-5,23-dien-3-ol (4) were isolated and characterized. Among the compounds, the diterpenes were found to have more biological activities than the steroidal compounds. Compound 1 showed the highest cytotoxicity with LC₅₀ of 12.42 ± 0.87 μg/mL. Likewise, it possesses good antioxidant activity in terms of reducing power. On the contrary, compound 2 exerted the highest antiacetylcholinesterase and antibutyrylcholinesterase activity. Both the diterpenes showed almost similar antibacterial and antifungal activity. The identification of diterpenoid and steroid compounds with multifunctional activities suggests that W. chinensis may serve as an important source of bioactive compounds which should be further investigated in animal model for therapeutic potential in the treatment of different chronic diseases. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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13 pages, 564 KiB

Open AccessArticle

Phenylethanoid and Phenylmethanoid Glycosides from the Leaves of Ligustrum robustum and Their Bioactivities

by Shi-Hui Lu, Hao-Jiang Zuo, Jing Huang, Ran Chen, Jia-Ping Pan and Xiu-Xia Li

Molecules 2022, 27(21), 7390; https://doi.org/10.3390/molecules27217390 - 31 Oct 2022

Cited by 4 | Viewed by 1193

Abstract

The phytochemical study on the leaves of Ligustrum robustum, which have been used as Ku-Ding-Cha, led to the isolation and identification of three new phenylethanoid glycosides and three new phenylmethanoid glycosides, named ligurobustosides R₁ (1b), R_2–3 (2), R₄ (3), S₁ (4b), S₂ (5), and S₃ (6), and five reported phenylethanoid glycosides (7–11). In the bioactivity test, (Z)-osmanthuside B₆ (11) displayed strong fatty acid synthase (FAS) inhibitory activity (IC₅₀: 4.55 ± 0.35 μM) as the positive control orlistat (IC₅₀: 4.46 ± 0.13 μM), while ligurobustosides R₄ (3) and S₂ (5), ligupurpuroside B (7), cis-ligupurpuroside B (8), ligurobustoside N (9), osmanthuside D (10), and (Z)-osmanthuside B₆ (11) showed stronger ABTS radical scavenging activity (IC₅₀: 2.68 ± 0.05~4.86 ± 0.06 μM) than the positive control L-(+)-ascorbic acid (IC₅₀: 10.06 ± 0.19 μM). This research provided a theoretical basis for the leaves of L. robustum as a tea with function in treating obesity and diabetes. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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15 pages, 2024 KiB

Open AccessArticle

Comparison of the Antioxidant Activities and Polysaccharide Characterization of Fresh and Dry Dendrobium officinale Kimura et Migo

by Wang Zhang, Xinjie Liu, Xun Sun, Rongchun Han, Nianjun Yu, Juan Liang and An Zhou

Molecules 2022, 27(19), 6654; https://doi.org/10.3390/molecules27196654 - 07 Oct 2022

Cited by 9 | Viewed by 1784

Abstract

It is generally believed that fresh Dendrobium officinale (FDO) has more significant pharmacological activity than dried Dendrobium officinale (DDO); however, the difference has not been clearly shown. Our study compared their antioxidant properties both in vitro and in vivo, and the molecular weight arrangement and monosaccharide composition of the fresh Dendrobium officinale polysaccharides (FDOPs) and the dried Dendrobium officinale polysaccharides (DDOPs) were analyzed by HPLC-GPC and GC-MS. The results showed that the FDO and its polysaccharides had more significant effects on scavenging DPPH, ABTS, and hydroxyl radicals than the DDO. In addition, both the FDO and DDO significantly reduced lipid peroxidation levels and increased the SOD, T-AOC, CAT, and GSH levels in mice with acute liver damage caused by CCl₄, while the FDO and its polysaccharides were more effective. Histopathological analysis further verified the protective effect of the Dendrobium polysaccharides on CCl₄-induced liver injury. The determination of the polysaccharides revealed that the polysaccharide and mannose contents of the FDO were significantly higher than their dried counterparts, and the homogeneous arrangement of the polysaccharides in the FDO was degraded into three polysaccharide fragments of different molecular weights in the DDO. Overall, our data identified differences in the antioxidant activities of the FDO and DDO, as well as the reasons for these differences. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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16 pages, 3451 KiB

Open AccessArticle

Mass Spectrometric Identification of Licania rigida Benth Leaf Extracts and Evaluation of Their Therapeutic Effects on Lipopolysaccharide-Induced Inflammatory Response

by Thayse Evellyn Silva do Nascimento, Jorge A. López, Eder Alves Barbosa, Marcela Abbott Galvão Ururahy, Adriana da Silva Brito, Gabriel Araujo-Silva, Jefferson Romáryo Duarte da Luz and Maria das Graças Almeida

Molecules 2022, 27(19), 6291; https://doi.org/10.3390/molecules27196291 - 23 Sep 2022

Cited by 2 | Viewed by 1335

Abstract

Licania rigida Benth has been evaluated as an alternative drug to treat diseases associated with inflammatory processes. This study evaluated the anti-inflammatory effects of aqueous and hydroalcoholic leaf extracts of L. rigida with inflammation induced by lipopolysaccharides in in vitro and in vivo inflammation models. The phytochemical profile of the extracts, analyzed by ultra-fast liquid chromatography coupled with tandem mass spectrometry, revealed the presence of gallic and ellagic acids in both extracts, whereas isovitexin, ferulate, bulky amino acids (e.g., phenylalanine), pheophorbide, lactic acid, and pyridoxine were detected in the hydroalcoholic extract. The extracts displayed the ability to modulate in vitro and in vivo inflammatory responses, reducing approximately 50% of pro-inflammatory cytokine secretion (TNF-α, IL-1β, and IL-6), and inhibiting both NO production and leukocyte migration by approximately 30 and 40% at 100 and 500 µg/mL, respectively. Overall, the results highlight and identify, for the first time, the ability of L. rigida leaf extract to modulate inflammatory processes. These data suggest that the leaf extracts of this plant have potential in the development of herbal formulations for the treatment of inflammation. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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Review

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28 pages, 2966 KiB

Open AccessReview

Stilbenes, a Versatile Class of Natural Metabolites for Inflammation—An Overview

by Jameel M. Al-Khayri, Roseanne Mascarenhas, Himanshu Madapur Harish, Yashwanth Gowda, Vasantha Veerappa Lakshmaiah, Praveen Nagella, Muneera Qassim Al-Mssallem, Fatima Mohammed Alessa, Mustafa Ibrahim Almaghasla and Adel Abdel-Sabour Rezk

Molecules 2023, 28(9), 3786; https://doi.org/10.3390/molecules28093786 - 28 Apr 2023

Cited by 9 | Viewed by 3002

Abstract

Stilbenes are polyphenolic allelochemicals synthesized by plants, especially grapes, peanuts, rhubarb, berries, etc., to defend themselves under stressful conditions. They are now exploited in medicine for their antioxidant, anti-proliferative and anti-inflammatory properties. Inflammation is the immune system’s response to invading bacteria, toxic chemicals or even nutrient-deprived conditions. It is characterized by the release of cytokines which can wreak havoc on healthy tissues, worsening the disease condition. Stilbenes modulate NF-κB, MAPK and JAK/STAT pathways, and reduce the transcription of inflammatory factors which result in maintenance of homeostatic conditions. Resveratrol, the most studied stilbene, lowers the Michaelis constant of SIRT1, and occupies the substrate binding pocket. Gigantol interferes with the complement system. Besides these, oxyresveratrol, pterostilbene, polydatin, viniferins, etc., are front runners as drug candidates due to their diverse effects from different functional groups that affect bioavailability and molecular interactions. However, they each have different thresholds for toxicity to various cells of the human body, and thus a careful review of their properties must be conducted. In animal models of autoinflammatory diseases, the mode of application of stilbenes is important to their absorption and curative effects, as seen with topical and microemulsion gel methods. This review covers the diversity seen among stilbenes in the plant kingdom and their mechanism of action on the different inflammatory pathways. In detail, macrophages’ contribution to inflamed conditions in the liver, the cardiac, connective and neural tissues, in the nephrons, intestine, lungs and in myriad other body cells is explored, along with detailed explanation on how stilbenes alleviate the symptoms specific to body site. A section on the bioavailability of stilbenes is included for understanding the limitations of the natural compounds as directly used drugs due to their rapid metabolism. Current delivery mechanisms include sulphonamides, or using specially designed synthetic drugs. It is hoped that further research may be fueled by this comprehensive work that makes a compelling argument for the exploitation of these compounds in medicine. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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18 pages, 3387 KiB

Open AccessReview

Dioscorea spp.: Bioactive Compounds and Potential for the Treatment of Inflammatory and Metabolic Diseases

by Zhen Wang, Shengnan Zhao, Siyu Tao, Guige Hou, Fenglan Zhao, Shenpeng Tan and Qingguo Meng

Molecules 2023, 28(6), 2878; https://doi.org/10.3390/molecules28062878 - 22 Mar 2023

Cited by 10 | Viewed by 3982

Abstract

Dioscorea spp. belongs to the Dioscoreaceae family, known as “yams”, and contains approximately 600 species with a wide distribution. It is a major food source for millions of people in tropical and subtropical regions. Dioscorea has great medicinal and therapeutic capabilities and is a potential source of bioactive substances for the prevention and treatment of many diseases. In recent years, increasing attention has been paid to the phytochemicals of Dioscorea, such as steroidal saponins, polyphenols, allantoin, and, in particular, polysaccharides and diosgenin. These bioactive compounds possess anti-inflammatory activity and are protective against a variety of inflammatory diseases, such as enteritis, arthritis, dermatitis, acute pancreatitis, and neuroinflammation. In addition, they play an important role in the prevention and treatment of metabolic diseases, including obesity, dyslipidemia, diabetes, and non-alcoholic fatty liver disease. Their mechanisms of action are related to the modulation of a number of key signaling pathways and molecular targets. This review mainly summarizes recent studies on the bioactive compounds of Dioscorea and its treatment of inflammatory and metabolic diseases, and highlights the underlying molecular mechanisms. In conclusion, Dioscorea is a promising source of bioactive components and has the potential to develop novel natural bioactive compounds for the prevention and treatment of inflammatory and metabolic diseases. Full article

(This article belongs to the Special Issue Natural Compounds for Treatment and Prevention of Inflammation, Oxidative Stress and Metabolic Disorders)

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