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      Pharmacological effects and the related mechanism of scutellarin on inflammation-related diseases: a review

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          Abstract

          Inflammation is a biological response of multicellular organisms caused by injuries, pathogens or irritants. An excessive inflammatory response can lead to tissue damage and various chronic diseases. Chronic inflammation is a common feature of many diseases, making the search for drugs to treat inflammation-related diseases urgent. Scutellarin, a natural flavonoid metabolite, is widely used in the treatment of various inflammation-related diseases for its anti-inflammatory, anti-oxidant and anti-cancer activities. Scutellarin can inhibit key inflammatory pathways (PI3K/Akt, MAPK, and NF-κB, etc.) and activate the anti-oxidant related pathways (Nrf2, ARE, ect.), thereby protecting tissues from inflammation and oxidative stress. Modern extraction technologies, such as microwave-assisted, ultrasound assisted, and supercritical fluid extraction, have been utilized to extract scutellarin from Scutellaria and Erigeron genera. These technologies improve efficiency and retain biological activity, making scutellarin suitable for large-scale production. Scutellarin has significant therapeutic effects in treating osteoarthritis, pulmonary fibrosis, kidney injury, and cardiovascular diseases. However, due to its low bioavailability and short half-life, its clinical application is limited. Researchers are exploring innovative formulations (β-cyclodextrin polymers, triglyceride mimetic active ingredients, and liposome precursors, etc.) to improve stability and absorption rates. Despite these challenges, the potential of scutellarin in anti-inflammatory, anti-oxidant, and anti-cancer applications remains enormous. By optimizing formulations, exploring combination therapies, and conducting in-depth mechanistic research, scutellarin can play an important role in treating various inflammatory diseases, providing patients with more and effective treatment options.

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          Most cited references106

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          ERK/MAPK signalling pathway and tumorigenesis

          Mitogen-activated protein kinase (MAPK) cascades are key signalling pathways that regulate a wide variety of cellular processes, including proliferation, differentiation, apoptosis and stress responses. The MAPK pathway includes three main kinases, MAPK kinase kinase, MAPK kinase and MAPK, which activate and phosphorylate downstream proteins. The extracellular signal-regulated kinases ERK1 and ERK2 are evolutionarily conserved, ubiquitous serine-threonine kinases that regulate cellular signalling under both normal and pathological conditions. ERK expression is critical for development and their hyperactivation plays a major role in cancer development and progression. The Ras/Raf/MAPK (MEK)/ERK pathway is the most important signalling cascade among all MAPK signal transduction pathways, and plays a crucial role in the survival and development of tumour cells. The present review discusses recent studies on Ras and ERK pathway members. With respect to processes downstream of ERK activation, the role of ERK in tumour proliferation, invasion and metastasis is highlighted, and the role of the ERK/MAPK signalling pathway in tumour extracellular matrix degradation and tumour angiogenesis is emphasised.
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            PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside

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              Mechanisms of NF-κB p65 and strategies for therapeutic manipulation

              The transcription factor NF-κB is a critical regulator of immune and inflammatory responses. In mammals, the NF-κB/Rel family comprises five members: p50, p52, p65 (Rel-A), c-Rel, and Rel-B proteins, which form homo- or heterodimers and remain as an inactive complex with the inhibitory molecules called IκB proteins in resting cells. Two distinct NF-κB signaling pathways have been described: 1) the canonical pathway primarily activated by pathogens and inflammatory mediators, and 2) the noncanonical pathway mostly activated by developmental cues. The most abundant form of NF-κB activated by pathologic stimuli via the canonical pathway is the p65:p50 heterodimer. Disproportionate increase in activated p65 and subsequent transactivation of effector molecules is integral to the pathogenesis of many chronic diseases such as the rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and even neurodegenerative pathologies. Hence, the NF-κB p65 signaling pathway has been a pivotal point for intense drug discovery and development. This review begins with an overview of p65-mediated signaling followed by discussion of strategies that directly target NF-κB p65 in the context of chronic inflammation.
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                Author and article information

                Contributors
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                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                12 August 2024
                2024
                : 15
                : 1463140
                Affiliations
                [1] 1 School of Medicine , Institute of Translational Medicine , Yangzhou University , Yangzhou, China
                [2] 2 Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases , Yangzhou University , Yangzhou, China
                Author notes

                Edited by: Xianyu Li, China Academy of Chinese Medical Sciences, China

                Reviewed by: Xiangwei Chang, Anhui University of Chinese Medicine, China

                Jianmei Zhang, Sungkyunkwan University, Republic of Korea

                Taoyun Wang, Suzhou University of Science and Technology, China

                *Correspondence: Hanqing Pang, hanqingpang@ 123456126.com
                [ † ]

                These authors have contributed equally to this work and share first authorship

                Article
                1463140
                10.3389/fphar.2024.1463140
                11345237
                39188946
                7ab4d68a-ef7b-472b-bb8b-3a62023b99ba
                Copyright © 2024 Zhou, Gu, Zhu, Zhu, Chen, Shi, Yang, Lu and Pang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 July 2024
                : 01 August 2024
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study is funded by the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University) (CMEMR2022-B11), the Natural Science Research of Jiangsu Higher education Institution of China (22KJB360018), and the China Postdoctoral Science Foundation (2024M752727).
                Categories
                Pharmacology
                Review
                Custom metadata
                Ethnopharmacology

                Pharmacology & Pharmaceutical medicine
                scutellarin,inflammation,nf-κb,mapk,pi3k/akt,nrf2/are
                Pharmacology & Pharmaceutical medicine
                scutellarin, inflammation, nf-κb, mapk, pi3k/akt, nrf2/are

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