Quercitrin from Toona sinensis (Juss.) M.Roem. Attenuates Acetaminophen-Induced Acute Liver Toxicity in HepG2 Cells and Mice through Induction of Antioxidant Machinery and Inhibition of Inflammation

Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event in APAP-induced liver injury. Accordingly, N-acetyl cysteine, a known scavenger of reactive oxygen species (ROS), is recommended as an effective clinical antidote against APAP-induced acute liver injury (AILI) when it is given at an early phase; however, the narrow therapeutic window limits its use. Hence, the development of novel therapeutic approaches that can offer broadly protective effects against AILI is clearly needed. To this end, it is necessary to better understand the mechanisms of APAP hepatotoxicity. Up to now, in addition to mitochondrial oxidative stress, many other cellular processes, including phase I/phase II metabolism, endoplasmic reticulum stress, autophagy, sterile inflammation, microcirculatory dysfunction, and liver regeneration, have been identified to be involved in the pathogenesis of AILI, providing new targets for developing more effective therapeutic interventions against APAP-induced liver injury. In this review, we summarize intracellular and extracellular events involved in APAP hepatotoxicity, along with emphatic discussions on the possible therapeutic approaches targeting these different cellular events.

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“… 7 days Balb/c mice, 300 mg/kg i.p. ↓Oxidative stress, inflammation [112] Caffeic acid 10–30 mg/kg p.o. 7 days ICR mice, 400 mg/kg p.o.…”

Section: Targeting Mitochondrial Oxidative Stress and Dysfunction Formentioning

confidence: 99%

“… Balb/c mice, 300 mg/kg i.p. ↑SOD, CAT and GPx; ↓inflammation [112] Methanol extract of pomegranate peels 50 mg/kg p.o. for 14 days Wistar rats, 750 mg/kg i.p.…”

Section: Targeting Mitochondrial Oxidative Stress and Dysfunction Formentioning

confidence: 99%

Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions

et al. 2018

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“…In addition, another investigation in 2012 reported that TSL could ameliorate the antioxidant enzymes activity in H 2 O 2 induced oxidative rats liver which would be beneficial for the hepatic detoxification (Yu et al, 2012). Recently, Truong et al (2016) reported that the quercitrin extracted from the T. sinensis attenuated acetaminophen-induced acute liver toxicity in HepG2 Cells and mice, and the related mechanisms is correlated to activating defensive genes and inhibiting pro-inflammatory mediators via suppressing JNK and p38 pathway.…”

Section: Hepatoprotective Effectmentioning

confidence: 99%

Toona sinensis: a comprehensive review on its traditional usages, phytochemisty, pharmacology and toxicology

Peng

Liu

et al. 2019

Revista Brasileira de Farmacognosia

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a b s t r a c tToona sinensis (Juss.) M.Roem, Meliaceae, a deciduous plant native to eastern and southeastern Asia, is widely used in Traditional Chinese Medicine. This paper was aimed to summarize the current advances in traditional usage, phytochemistry, pharmacology and toxicology of T. sinensis. In this review, various types of data of T. sinensis are discussed in the corresponding parts of this paper, and perspectives for possible future studies of this plant are discussed. The main constituents of T. sinensis are terpenoids, phenylpropanoids and flavonoids, etc., and its pharmacological activities include anti-tumor effects, antioxidant activities, anti-diabetic effects and anti-inflammatory effects. Although a series of phytochemical and pharmacological researches of this plant have been conducted, the active constituents and action mechanism of these activities should be also further explored. Furthermore, the present review also indicates that T. sinensis has potentials to develop into drugs for treating various diseases with high efficacy and low toxicity, particularly in cancer, diabetes and inflammatory disorders. In conclusion, the paper provides a full-scale profile of the traditional usage, phytochemistry, pharmacology and toxicology of T. sinensis, and also provides potential therapeutic uses and drug development prospects of this plant.

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“…They mainly refer to two benzene rings (A ring and B ring) as the mother nucleus, which are linked by a central three carbon chain (C chain). The series of compounds with the C6-C3-C6 basic carbon skeleton contain a plurality of hydroxyl groups (OH) and are highly polar [6, 7]. The basic structure is shown in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Quercetin and Quercitrin Attenuates the Inflammatory Response and Oxidative Stress in LPS-Induced RAW264.7 Cells: In Vitro Assessment and a Theoretical Model

Tang

Diao

Shu

et al. 2019

BioMed Research International

191

100

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Background Nowadays, atmospheric pollutants, ultraviolet rays, and other factors cause the imbalance of cell redox, resulting in skin oxidative damage. There is an interaction between inflammatory response and oxidative stress, which often involve networks of reactions and serve to amplify each other. Quercetin and quercitrin, with strong antioxidant and anti-inflammatory properties, were widely applied in cardiovascular disease, osteoporsis, pulmonary disease, etc. However, the regulation mechanism of quercetin and quercitrin on various inflammatory skin diseases is still not clear. Purpose In this study, quercetin and quercitrin were used to investigate whether they had anti-inflammatory and anti-ROS effects. Besides, theoretical calculation method was also adopted to preliminarily explore the mechanism of the anti-inflammatory and antioxidant effects of these two substances. Methods CCK-8 assay was employed to investigate the cytotoxicity. The concentration of NO measured by Griess Reaction System. Moreover, the inflammatory factors (TNF-α, IL-1β, and IL-6) were reduced in LPS-stimulated RAW264.7 cells were tested by ELISA kits. The trend of ROS changes was detected by DCFH-DA method. Finally, the mechanism of the anti-inflammatory and antioxidant effects of these two substances was carried out by DMol3 package in Materials Studio. Results CCK-8 assay results guided that the safe concentration of quercetin and quercitrin was lower than 15.0 μg/mL and 22.4 μg/mL, respectively. Also, the concentration of NO could significantly be inhibited by quercetin and quercitrin. Besides, the ELISA results showed that TNF-α, IL-1β, and IL-6 were reduced in LPS-stimulated RAW264.7 cells after interfering with quercetin and quercitrin. The trend of ROS changes was similar to that of inflammatory factors. Finally, the theoretical calculation illustrated that the oxygen atom on B rings may be the main site of electron cloud density changes, which may suggest a possible mechanism for the anti-inflammatory and ROS scavenging effects of quercetin and quercitrin. Conclusions This experiment shows that LPS can induce the overactivating of macrophages and the activated macrophages can subsequently induce inflammatory storms and oxidative stress. Both quercetin and quercitrin can inhibit LPS-induced macrophage inflammation and oxidative stress by experiment and theoretical calculations.

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Quercitrin from Toona sinensis (Juss.) M.Roem. Attenuates Acetaminophen-Induced Acute Liver Toxicity in HepG2 Cells and Mice through Induction of Antioxidant Machinery and Inhibition of Inflammation

Cited by 40 publications

References 55 publications

Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions

Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions

Toona sinensis: a comprehensive review on its traditional usages, phytochemisty, pharmacology and toxicology

Quercetin and Quercitrin Attenuates the Inflammatory Response and Oxidative Stress in LPS-Induced RAW264.7 Cells: In Vitro Assessment and a Theoretical Model

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