Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice

Ullah, Hanif; Khan, Ashrafullah; Baig, Muhammad Waleed; Ullah, Naseem; Ahmed, Naveed; Tipu, Muhammad Khalid; Ali, Hussain; Khan, Salman

doi:10.1186/s12906-020-02906-7

Cited by 62 publications

(38 citation statements)

References 49 publications

(91 reference statements)

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“…These changes are coupled to an increase in oxidative stress 64 . Oxidative stress is known to stimulate NLRP3 inflammasome activation and IL1B maturation 22 – 24 , 65 , 66 . Interestingly, differential gene expression and pathway analysis of RNA-sequencing data in wild-type mice treated solely with WY-14643 revealed activation of some acute inflammatory response pathways.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

et al. 2020

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Exploring the molecular mechanisms that prevent inflammation during caloric restriction may yield promising therapeutic targets. During fasting, activation of the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) promotes the utilization of lipids as an energy source. Herein, we show that ligand activation of PPARα directly upregulates the long non-coding RNA gene Gm15441 through PPARα binding sites within its promoter. Gm15441 expression suppresses its antisense transcript, encoding thioredoxin interacting protein (TXNIP). This, in turn, decreases TXNIP-stimulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, caspase-1 (CASP1) cleavage, and proinflammatory interleukin 1β (IL1B) maturation. Gm15441-null mice were developed and shown to be more susceptible to NLRP3 inflammasome activation and to exhibit elevated CASP1 and IL1B cleavage in response to PPARα agonism and fasting. These findings provide evidence for a mechanism by which PPARα attenuates hepatic inflammasome activation in response to metabolic stress through induction of lncRNA Gm15441.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

et al. 2020

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“…The pharmacokinetic parameters of the continentalic acid were assessed using Swiss target prediction software ( http://www.swisstargetprediction.ch/ ) as reported previously [ 39 ]. The various parameters that were assessed during the current study includes physicochemical properties, lipophilicity, aqueous solubility, absorption and pharmacokinetic parameters were evaluated.…”

Section: Methodsmentioning

confidence: 99%

Attenuation of LPS-induced acute lung injury by continentalic acid in rodents through inhibition of inflammatory mediators correlates with increased Nrf2 protein expression

Ali

Khan

Ali

et al. 2020

BMC Pharmacol Toxicol

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Background Acute lung injury (ALI) together with acute respiratory distress syndrome (ARDS) are associated with high rate of mortality and morbidity in patients. In the current study, the anti-inflammatory effects of continentalic acid (CNT) in LPS-induced acute lung injury model was explored. Methods The acute lung injury model was established by administering LPS (5 mg/kg) intraperitonealy. Following LPS administration, the survival rate, temperature changes and lung Wet/Dry ratio were assessed. The antioxidants (GSH, GST, Catalase and SOD) and oxidative stress markers (MDA, NO, MPO) were evaluated in all the treated groups. Similarly, the cytokines such as IL-1β, IL-6 and TNF-α were analyzed using ELISA assay. The histological changes were determined using H and E staining, while Nrf2 and iNOS level were determined using immunohistochemistry analysis. The molecular docking analysis was performed to assess the pharmacokinetics parameters and interaction of the CNT with various protein targets. Results The results showed that CNT dose dependently (10, 50 and 100 mg/kg) reduced mortality rate, body temperature and lungs Wet/Dry ratio. CNT post-treatment significantly inhibited LPS-induced production of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. The CNT post-treatment markedly improved the hematological parameters, while significantly reduced the MPO (indicator of the neutrophilic infiltration) activity compared to the LPS treated group. Furthermore, the CNT (100 mg/kg) post-administration remarkably inhibited the lung Wet/Dry ratio. The CNT (100 mg/kg) treated group showed marked reduction in the oxidative stress markers such as malonaldehyde (MDA) and Nitric oxide (NO) concentration, while induced the level of the anti-oxidant enzymes such as GST, GSH, Catalase and SOD. Similarly, the CNT markedly reduced the iNOS expression level, while induced the Nrf2 protein expression. Additionally, the molecular docking study showed significant binding interaction with the Nrf2, p65, Keap1, HO-1, IL-1β, IL-6, TNF-α and COX-2, while exhibited excellent physicochemical properties. Conclusion The CNT showed marked protection against the LPS-induced lung injury and improved the behavioral, biochemical and histological parameters. Furthermore, the CNT showed significant interaction with several protein targets and exhibited better physicochemical properties.

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“…1 In addition phenol and flavonoid rich plants and compounds have been reported to exert natural antioxidant effects. 27,28 This may explain the observed antioxidant and hepatoprotection produced by the extract in paracetamol-induced liver toxicity. Similarly, silymarin is a polyphenolic flavonoid derived from Silybum marianum which has shown different pharmacological potentials like anti-inflammatory, hepatoprotective and as an antioxidant as shown in this study.…”

Section: Resultsmentioning

confidence: 95%

Hepatoprotective Effect of Andropogon gayanus against Paracetamol- and Carbon Tetrachloride-Induced Liver Toxicity in Rats

2021

TJNPR

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The liver is one of the principal organs in the body and is involved in synthesis, metabolism, storage and detoxification. 1 It's role in the metabolism of xenobiotics makes it particularly susceptible to severe toxicities which are often in form of circulatory, neoplastic, and microbial insults. 2,3 Diseases of the liver are widespread and lead to a lot of deaths worldwide. These diseases are predominantly hepatitis due to viral infections, alcohol-mediated liver injury, liver cirrhosis and liver cells carcinoma. 3,4 Adequate therapeutic measures are hence required to reduce the incidence and associated deaths. Orthodox drugs available for the management of liver diseases usually predispose to adverse effects especially after prolonged use. 5 In addition, due to high cost; they are often not easily accessed by rural dwellers. 6 Hence, newer therapeutic options that are more accessible and affordable with fewer side effects have been sought for by studying medicinal plants. 6,7 Andropogon gayanus Kunth also known as Gamba grass in English is a widely accessible and used plant medicine of the Poaceae family. It is a nutritive forage 8 locally known as Gamba or Tsaure and Eruwa ako among the Hausa and Yourba natives of Nigeria respectively.

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Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice

Cited by 62 publications

References 49 publications

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

Attenuation of LPS-induced acute lung injury by continentalic acid in rodents through inhibition of inflammatory mediators correlates with increased Nrf2 protein expression

Hepatoprotective Effect of Andropogon gayanus against Paracetamol- and Carbon Tetrachloride-Induced Liver Toxicity in Rats

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