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      Aqueous Thunbergia laurifolia leaf extract alleviates paraquat-induced lung injury in rats by inhibiting oxidative stress and inflammation

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          Abstract

          Background

          Paraquat (PQ) has been reported to have a high mortality rate. The major target organ of PQ poisoning is the lungs. The pathogenesis of PQ-induced lung injury involves oxidative stress and inflammation. Unfortunately, there is still no effective antidote for PQ poisoning. We hypothesized that aqueous Thunbergia laurifolia (TL) leaf extract is a possible antidote for PQ-induced lung injury.

          Methods

          The total phenolic content and caffeic acid content of an aqueous extract of TL leaves were analyzed. Male Wistar rats were randomly divided into four groups ( n = 4 per group): the control group (administered normal saline), the PQ group (administered 18 mg/kg body weight (BW) PQ dichloride subcutaneously), the PQ + TL-low-dose (LD) group (administered PQ dichloride subcutaneously and 100 mg/kg BW aqueous TL leaf extract by oral gavage) and the PQ + TL-high-dose (HD) group (administered PQ dichloride subcutaneously and 200 mg/kg BW aqueous TL leaf extract by oral gavage). Malondialdehyde (MDA) levels and lung histopathology were analyzed. In addition, the mRNA expression of NADPH oxidase (NOX), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) was assessed using reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of IL-1β and TNF-α was analyzed using immunohistochemistry.

          Results

          The total phenolic content of the extract was 20.1 ± 0.39 μg gallic acid equivalents (Eq)/mg extract, and the caffeic acid content was 0.31 ± 0.01 μg/mg. The PQ group showed significantly higher MDA levels and NOX, IL-1β and TNF-α mRNA expression than the control group. Significant pathological changes, including alveolar edema, diffuse alveolar collapse, hemorrhage, leukocyte infiltration, alveolar septal thickening and vascular congestion, were observed in the PQ group compared with the control group. However, the aqueous TL leaf extract significantly attenuated the PQ-induced increases in MDA levels and NOX, IL-1β and TNF-α expressions. Moreover, the aqueous TL leaf extract ameliorated PQ-induced lung pathology.

          Conclusion

          This study indicates that aqueous TL leaf extract can ameliorate PQ-induced lung pathology by modulating oxidative stress through inhibition of NOX and by regulating inflammation through inhibition of IL-1β and TNF-α expressions. We suggest that aqueous TL leaf extract can be used as an antidote for PQ-induced lung injury.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12906-022-03567-4.

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          Most cited references36

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          ROS function in redox signaling and oxidative stress.

          Oxidative stress refers to elevated intracellular levels of reactive oxygen species (ROS) that cause damage to lipids, proteins and DNA. Oxidative stress has been linked to a myriad of pathologies. However, elevated ROS also act as signaling molecules in the maintenance of physiological functions--a process termed redox biology. In this review we discuss the two faces of ROS--redox biology and oxidative stress--and their contribution to both physiological and pathological conditions. Redox biology involves a small increase in ROS levels that activates signaling pathways to initiate biological processes, while oxidative stress denotes high levels of ROS that result in damage to DNA, protein or lipids. Thus, the response to ROS displays hormesis, given that the opposite effect is observed at low levels compared with that seen at high levels. Here, we argue that redox biology, rather than oxidative stress, underlies physiological and pathological conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal

            Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.
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              Role of ROS and RNS Sources in Physiological and Pathological Conditions

              There is significant evidence that, in living systems, free radicals and other reactive oxygen and nitrogen species play a double role, because they can cause oxidative damage and tissue dysfunction and serve as molecular signals activating stress responses that are beneficial to the organism. Mitochondria have been thought to both play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction through several mechanisms, including stimulation of opening of permeability transition pores. Until recently, the functional significance of ROS sources different from mitochondria has received lesser attention. However, the most recent data, besides confirming the mitochondrial role in tissue oxidative stress and protection, show interplay between mitochondria and other ROS cellular sources, so that activation of one can lead to activation of other sources. Thus, it is currently accepted that in various conditions all cellular sources of ROS provide significant contribution to processes that oxidatively damage tissues and assure their survival, through mechanisms such as autophagy and apoptosis.
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                Author and article information

                Contributors
                spalipoch@hotmail.com , sarawoot.pa@wu.ac.th
                Journal
                BMC Complement Med Ther
                BMC Complement Med Ther
                BMC Complementary Medicine and Therapies
                BioMed Central (London )
                2662-7671
                22 March 2022
                22 March 2022
                2022
                : 22
                : 83
                Affiliations
                [1 ]GRID grid.412867.e, ISNI 0000 0001 0043 6347, School of Medicine, , Walailak University, ; 222 Thaiburi, Thasala District, Nakhon Si Thammarat, 80161 Thailand
                [2 ]GRID grid.412867.e, ISNI 0000 0001 0043 6347, Research Institute for Health Sciences, , Walailak University, ; Nakhon Si Thammarat, 80160 Thailand
                [3 ]GRID grid.412867.e, ISNI 0000 0001 0043 6347, Center of Scientific and Technological Equipment, , Walailak University, ; Nakhon Si Thammarat, 80160 Thailand
                [4 ]GRID grid.412867.e, ISNI 0000 0001 0043 6347, School of Medicine, , Walailak University, ; Nakhon Si Thammarat, 80160 Thailand
                [5 ]GRID grid.412867.e, ISNI 0000 0001 0043 6347, Research Excellence Center for Innovation and Health Product, , Walailak University, ; Nakhon Si Thammarat, 80160 Thailand
                [6 ]GRID grid.412867.e, ISNI 0000 0001 0043 6347, School of Pharmacy, , Walailak University, ; Nakhon Si Thammarat, 80160 Thailand
                [7 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Department of Pathobiology, Faculty of Science, , Mahidol University, ; Bangkok, 10400 Thailand
                Article
                3567
                10.1186/s12906-022-03567-4
                8939148
                35317802
                5cb3db28-81bc-4331-824f-12892565d405
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 11 November 2020
                : 11 March 2022
                Funding
                Funded by: This research was supported by a grant from the Institute of Research and Development (under contract WU 61111), Walailak University, Thailand.
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2022

                paraquat,thunbergia laurifolia,lung injury,oxidative stress,inflammation,malondialdehyde,nadph oxidase,interleukin 1 beta,tumor necrosis factor alpha

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