Oxidative toxicity in diabetes and Alzheimer’s disease: mechanisms behind ROS/ RNS generation

Ahmad, Waqar; Ijaz, Bushra; Shabbiri, Khadija; Ahmed, Fayyaz; Rehman, Sidra

doi:10.1186/s12929-017-0379-z

Cited by 252 publications

(158 citation statements)

References 142 publications

(137 reference statements)

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“…Numerous molecular, clinical, epidemiological, etc. data supports a pathophysiological link between AD and DM (Ahmad et al, 2017). Cognitive decline related to DM is characterized by mild to moderate impairment, and an increased risk of developing AD and other forms of dementia (Toth, 2014).…”

Section: Introductionmentioning

confidence: 55%

In vitro evaluation of antioxidant, antineurodegenerative and antidiabetic activities of Ocimum basilicum L., Laurus nobilis L. leaves and Citrus reticulata Blanco peel extracts

Duletić-Laušević¹,

Oalđe²,

Alimpić-Aradski³

2019

Lekovite sirovine

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Ocimum basilicum (sweet basil) and Laurus nobilis (bay leaves or laurel) have been used in traditional medicine for centuries, and also extensively employed as spices for adding aroma and flavor to various food products. Citrus reticulata (mandarin) is mainly used in food industry for juice production, while its peel as main byproduct contains high concentration of valuable substances. The samples were collected in Lastva Grbaljska (Montenegrin coast) and purchased from the market. Since the oxidative stress results in development of numerous diseases, among them neurodegeneration and diabetes, the antioxidant activity, antineurodegenerative and antidiabetic activities were analyzed, aiming to compare potential of plants cultivated under natural conditions and commercially purchased from the market, as well as to compare the effect of different solvents applied in the extraction process. Water, methanol and acetone extracts of leaves and peel were tested by DPPH and total reducing power (TRP) methods for determination of antioxidant activity, and by acetylcholinesterase (AChE) and αglucosidase inhibition assays for analyzing the other activities. Total phenolic (TPC) and flavonoid (TFC) contents were also determined. The acetonic extract of L. nobilis from Lastva showed the highest TPC, DPPH, TRP, and α-glucosidase inhibition, while water extract of commercial L. nobilis exhibited the highest AChE inhibition. The leaves of L. nobilis are demonstrated to be promising antioxidant, antineurodegenerative and antidiabetic agent.

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Section: Introductionmentioning

confidence: 55%

In vitro evaluation of antioxidant, antineurodegenerative and antidiabetic activities of Ocimum basilicum L., Laurus nobilis L. leaves and Citrus reticulata Blanco peel extracts

Duletić-Laušević¹,

Oalđe²,

Alimpić-Aradski³

2019

Lekovite sirovine

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“…The generalized term reactive oxygen species (ROS) encompasses various species, including singlet oxygen, the superoxide anion (O 2 · − ), the hydroxyl radical (HO · ), the hydroperoxy radical (HOO · ), alkoxide radicals (RCOO · ), thiyl peroxyl radicals (RSOO · ) and non‐radical molecules, such as hydrogen peroxide (H 2 O 2 ), nitric oxide (NO) and peroxynitrite (ONOO · − ), all of which have inherent chemical properties that confer reactivity to different biological targets . ROS, generally considered toxic byproducts of metabolism, are considered as drivers of diabetes, cancer, rheumatoid arthritis, cardiovascular diseases and neurodegenerative diseases . Recent studies suggest that ROS, acting as important signalling messengers, play an important role in a broad variety of cellular processes, such as cell proliferation, the expression of genes and proteins, post‐translational modification and the balance of cellular homeostasis .…”

Section: Introductionmentioning

confidence: 99%

Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties

Huang

2019

Acta Physiologica

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Oxidative stress is recognized as free radical dyshomeostasis, which has damaging effects on proteins, lipids and DNA. However, during cell differentiation and proliferation and other normal physiological processes, free radicals play a pivotal role in message transmission and are considered important messengers. Organisms maintain free radical homeostasis through a sophisticated regulatory system in which these "2faced" molecules play appropriate roles under physiological and pathological conditions. Reactive oxygen species (ROS), including a large number of free radicals, act as redox signalling molecules in essential cellular signalling pathways, including cell differentiation and proliferation. However, excessive ROS levels can induce oxidative stress, which is an important risk factor for diabetes, cancer and cardiovascular disease. An overall comprehensive understanding of ROS is beneficial for understanding the pathogenesis of certain diseases and finding new therapeutic treatments.This review primarily focuses on ROS cellular localization, sources, chemistry and molecular targets to determine how to distinguish between the roles of ROS as messengers and in oxidative stress. K E Y W O R D Shomeostasis, oxidative stress, reactive oxygen, redox signalling, signalling pathways 2 of 16 | HUANG ANd LI for the development of new therapeutic strategies for cancer and cardiovascular disease. | SOURCES AND PHYSICOCHEMICAL PROPERTIES OF ROS | ROS sourcessecond messengers, what are the corresponding acceptors for these special ROS? To better recognize ROS, a new tool that can monitor changes in ROS levels and position in real time must be developed. Determining how to utilize the characteristics of ROS to treat diseases, such as cardiovascular disease, diabetes, autoimmune diseases, cancer and Alzheimer's diseases, is worth further exploration.

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“…Alternatively, silibinin's inhibition of the toxic effects of Aβ 1–42 is independent of GLP‐1R/PKA pathway (Yang et al, ). Aβ and amylin coadministration enhanced ROS levels on INS‐1 cells; ROS toxicity remains an undisputed cause and link between AD and T2DM (Ahmad, Ijaz, Shabbiri, Ahmed, & Rehman, ). The antioxidative activity of silibinin has been described in numerous studies in that the activity is attributed to direct radical scavenging, chelation of iron and copper, inhibition of ROS‐producing enzymes, and/or activation of antioxidant enzymes (Surai, ).…”

Section: Discussionmentioning

confidence: 99%

Silibinin protects rat pancreatic β‐cell through up‐regulation of estrogen receptors' signaling against amylin‐ or Aβ_1–42‐induced reactive oxygen species/reactive nitrogen species generation

Yang

Sun

et al. 2019

Phytotherapy Research

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Amylin and amyloid-β (Aβ) were found to induce reactive oxygen species (ROS) and reactive nitrogen species (RNS) in rat pancreatic β-cell line, INS-1 cells, leading to cell death. In this study, we report on reciprocal relationship between the expression of estrogen receptors (ERs) α and β (ERα and ERβ) and generation of ROS/RNS in amylin/Aβ 1-42 -treated INS-1 cells. That is, pharmacological activation of ERs in INS-1 cells significantly decreases ROS/RNS generation, but blockage of ERs increases ROS/RNS generation. Silibinin is a natural polyphenolic flavonoid isolated from milk thistle with phytoestrogen activities, also known as silybin. Treatment with silibinin down-regulated ROS/RNS production induced by treatment with amylin/Aβ 1-42 in the cells. Silencing ERs expression with siRNAs targeting ERs showed that the protective effect of silibinin was markedly weakened, indicating that silibinin protection is largely attributed to activation of ERs' signaling. The binding of silibinin to ERs implies that the protective effect of silibinin on amylin/Aβ 1-42 -treated INS-1 cells owes to down-regulation of ROS/RNS through the activation of ERs phosphorylation. Amylin and Aβ 1-42 cotreatment enhanced furthermore ROS/RNS generation and cytotoxicity through further down-regulation of ERs phosphorylation, and this was reversed by silibinin. Silibinin also protects INS-1 cells from amylin and Aβ 1-42 cotreatment. These results indicate that protective effect of silibinin is mediated by enhancement of ERs phosphorylation that depresses ROS/RNS generation in amylin/Aβ 1-42 -treated INS-1 cells. KEYWORDS amylin, Aβ 1-42 , estrogen receptors (ERs), reactive nitrogen species (RNS), reactive oxygen species (ROS), silibinin

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Oxidative toxicity in diabetes and Alzheimer’s disease: mechanisms behind ROS/ RNS generation

Cited by 252 publications

References 142 publications

In vitro evaluation of antioxidant, antineurodegenerative and antidiabetic activities of Ocimum basilicum L., Laurus nobilis L. leaves and Citrus reticulata Blanco peel extracts

In vitro evaluation of antioxidant, antineurodegenerative and antidiabetic activities of Ocimum basilicum L., Laurus nobilis L. leaves and Citrus reticulata Blanco peel extracts

Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties

Silibinin protects rat pancreatic β‐cell through up‐regulation of estrogen receptors' signaling against amylin‐ or Aβ_1–42‐induced reactive oxygen species/reactive nitrogen species generation

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Oxidative toxicity in diabetes and Alzheimer’s disease: mechanisms behind ROS/ RNS generation

Cited by 252 publications

References 142 publications

In vitro evaluation of antioxidant, antineurodegenerative and antidiabetic activities of Ocimum basilicum L., Laurus nobilis L. leaves and Citrus reticulata Blanco peel extracts

In vitro evaluation of antioxidant, antineurodegenerative and antidiabetic activities of Ocimum basilicum L., Laurus nobilis L. leaves and Citrus reticulata Blanco peel extracts

Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties

Silibinin protects rat pancreatic β‐cell through up‐regulation of estrogen receptors' signaling against amylin‐ or Aβ1–42‐induced reactive oxygen species/reactive nitrogen species generation

Contact Info

Product

Resources

About

Silibinin protects rat pancreatic β‐cell through up‐regulation of estrogen receptors' signaling against amylin‐ or Aβ_1–42‐induced reactive oxygen species/reactive nitrogen species generation