Oroxylin A Exerts Its Antitumor Effects in Human Gallbladder Cancer &lt;i&gt;via&lt;/i&gt; Inhibition of the PTEN/PI3K/AKT Signaling Pathway

Xuan, Liqian; Zhang, Jiajun; Ji, Jianmei; Hu, Jun; Li, Fu

doi:10.1248/bpb.b20-00262

Cited by 8 publications

(3 citation statements)

References 30 publications

(34 reference statements)

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“…135 , Kaempferol also blocks the EGFR-related pathway. 136 Other flavonoids including scutellarin, 137 pectolinarigenin, 138,139 oroxylin A, 140 baicalein, 141−143 quercetin, 144 dihydromyricetin, 145 icariin, 146 hesperetin, 147 naringenin, 148 naringin, 149 morin, 150 and myricetin 151 inhibit the invasion, migration, and proliferation of different types of cancer cells and induce apoptosis, autophagy, and cell cycle arrest in several cancer cells through the activation of PTEN and subsequently down-regulation of the P13K/Akt signaling pathway.…”

Section: Discussion: Redox Regulation and Therapeutic Perspectives Of...mentioning

confidence: 99%

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety

Sarkar

Chaudhary

Jamaddar

et al. 2022

Chem. Res. Toxicol.

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The cost-effectiveness of presently used therapies is a problem in overall redox-based management, which is posing a significant financial burden on communities across the world. As a result, sophisticated treatment models that provide notions of predictive diagnoses followed by targeted preventive therapies adapted to individual patient profiles are gaining global acclaim as being beneficial to patients, the healthcare sector, and society as a whole. In this context, natural flavonoids were considered due to their multifaceted antioxidant, anti-inflammatory, and anticancer effects as well as their low toxicity and ease of availability. The aim of this review is to focus on the capacity of flavonoids to modulate the responsiveness of various diseases and ailments associated with redox toxicity. The review will also focus on the flavonoids' pathway-based redox activity and the advancement of redox-based therapies as well as flavonoids' antioxidant characteristics and their influence on human health, therapeutics, and chemical safety. Research findings indicated that flavonoids significantly exhibit various redox-based therapeutic responses against several diseases such as inflammatory, neurodegenerative, cardiovascular, and hepatic diseases and various types of cancer by activating the Nrf2/Keap1 transcription system, suppressing the nuclear factor κB (NF-κB)/IκB kinase inflammatory pathway, abrogating the function of the Hsp90/Hsf1 complex, inhibiting the PTEN/PI3K/Akt pathway, and preventing mitochondrial dysfunction. Some flavonoids, especially genistein, apigenin, amentoflavone, baicalein, quercetin, licochalcone A, and biochanin A, play a potential role in redox regulation. Conclusions of this review on the antioxidant aspects of flavonoids highlight the medicinal and folk values of these compounds against oxidative stress and various diseases and ailments. In short, treatment with flavonoids could be a novel therapeutic invention in clinical trials, as we hope.

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Section: Discussion: Redox Regulation and Therapeutic Perspectives Of...mentioning

confidence: 99%

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety

Sarkar

Chaudhary

Jamaddar

et al. 2022

Chem. Res. Toxicol.

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“…Subsequently, OA could downregulate different signaling pathways, including the nuclear factor kappa B (NF-κB) pathway, the signal transducer, and the activator of transcription 3 (STAT3) pathway; Wnt/β-catenin pathway and Notch-1 that have been implicated in tumorigenesis [ 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ]. Likewise, OA also regulates other pathways, such as endoplasmic reticulum (ER) stress-mediated pathway, phosphatase, and tensin homolog deleted on the chromosome 10/phosphatidylinositol 3-kinase/a serine threonine-protein kinase (PTEN/PI3K/Akt) pathway, the extracellular signal-regulated kinase (ERK 1/2) pathway, etc., [ 62 , 83 , 92 , 93 , 94 , 95 , 96 ].…”

Section: Molecular Targets Of Oamentioning

confidence: 99%

Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases

et al. 2022

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There have been magnificent advancements in the understanding of molecular mechanisms of chronic diseases over the past several years, but these diseases continue to be a considerable cause of death worldwide. Most of the approved medications available for the prevention and treatment of these diseases target only a single gene/protein/pathway and are known to cause severe side effects and are less effective than they are anticipated. Consequently, the development of finer therapeutics that outshine the existing ones is far-reaching. Natural compounds have enormous applications in curbing several disastrous and fatal diseases. Oroxylin A (OA) is a flavonoid obtained from the plants Oroxylum indicum, Scutellaria baicalensis, and S. lateriflora, which have distinctive pharmacological properties. OA modulates the important signaling pathways, including NF-κB, MAPK, ERK1/2, Wnt/β-catenin, PTEN/PI3K/Akt, and signaling molecules, such as TNF-α, TGF-ꞵ, MMPs, VEGF, interleukins, Bcl-2, caspases, HIF-1α, EMT proteins, Nrf-2, etc., which play a pivotal role in the molecular mechanism of chronic diseases. Overwhelming pieces of evidence expound on the anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer potentials of this flavonoid, which makes it an engrossing compound for research. Numerous preclinical and clinical studies also displayed the promising potential of OA against cancer, cardiovascular diseases, inflammation, neurological disorders, rheumatoid arthritis, osteoarthritis, etc. Therefore, the current review focuses on delineating the role of OA in combating different chronic diseases and highlighting the intrinsic molecular mechanisms of its action.

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“…Flavonoids display multiple biological properties such as antioxidation, through direct interaction with ROS; anticancer, by modulating several cellular pathways involved in tumor growth and apoptosis, anti-inflammation, and other effects ( de Almeida et al, 2020 ; de Amorim et al, 2020 ; Lakshmi et al, 2020 ; Xuan et al, 2020 ).…”

Section: Natural Products As Therapeutic Molecules: Flavonoids Of Green Teamentioning

confidence: 99%

Green Tea Polyphenol Epigallocatechin-Gallate in Amyloid Aggregation and Neurodegenerative Diseases

et al. 2021

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The accumulation of protein aggregates in human tissues is a hallmark of more than 40 diseases called amyloidoses. In seven of these disorders, the aggregation is associated with neurodegenerative processes in the central nervous system such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). The aggregation occurs when certain soluble proteins lose their physiological function and become toxic amyloid species. The amyloid assembly consists of protein filament interactions, which can form fibrillar structures rich in β-sheets. Despite the frequent incidence of these diseases among the elderly, the available treatments are limited and at best palliative, and new therapeutic approaches are needed. Among the many natural compounds that have been evaluated for their ability to prevent or delay the amyloidogenic process is epigallocatechin-3-gallate (EGCG), an abundant and potent polyphenolic molecule present in green tea that has extensive biological activity. There is evidence for EGCG’s ability to inhibit the aggregation of α-synuclein, amyloid-β, and huntingtin proteins, respectively associated with PD, AD, and HD. It prevents fibrillogenesis (in vitro and in vivo), reduces amyloid cytotoxicity, and remodels fibrils to form non-toxic amorphous species that lack seed propagation. Although it is an antioxidant, EGCG in an oxidized state can promote fibrils’ remodeling through formation of Schiff bases and crosslinking the fibrils. Moreover, microparticles to drug delivery were synthesized from oxidized EGCG and loaded with a second anti-amyloidogenic molecule, obtaining a synergistic therapeutic effect. Here, we describe several pre-clinical and clinical studies involving EGCG and neurodegenerative diseases and their related mechanisms.

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Oroxylin A Exerts Its Antitumor Effects in Human Gallbladder Cancer <i>via</i> Inhibition of the PTEN/PI3K/AKT Signaling Pathway

Cited by 8 publications

References 30 publications

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety

Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases

Green Tea Polyphenol Epigallocatechin-Gallate in Amyloid Aggregation and Neurodegenerative Diseases

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