Glabridin attenuates paracetamol-induced liver injury in mice via CYP2E1-mediated inhibition of oxidative stress

Bhatt, Shipra; Sharma, Ankita; Dogra, Ashish; Sharma, Priyanka; Kumar, Amit; Kotwal, Pankul; Bag, Swarnendu; Misra, Prashant; Singh, Gurdarshan; Kumar, Ajay; Sangwan, Payare L.; Nandi, Utpal

doi:10.1080/01480545.2021.1945004

Cited by 13 publications

(13 citation statements)

References 32 publications

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“…Leakage of hepatic biochemical enzyme markers occurs due to MTX treatment-associated alteration in the hepatic transport and membrane permeability during liver injury. , Further, MTX treatment elevates oxidative stress involving the Nrf2 pathway, leading to apoptosis and organ damage. , In the present study, we also found similar observations upon MTX treatment. It is reported that glabridin did not cause cytotoxicity using various cell lines ( in vitro ) even at high concentrations up to 100 μM. ,, Yuan et al described that glabridin has the ability to restrict toxicological alterations in the liver using monosodium iodoacetate-induced osteoarthritic rats ( in vivo ) . We reported earlier that pretreatment of glabridin can prevent the MTX-induced hepatotoxicity upon a single high-dose administration of MTX using a mice model ( in vivo ) .…”

Section: Discussionmentioning

confidence: 76%

“…It is reported that glabridin did not cause cytotoxicity using various cell lines ( in vitro ) even at high concentrations up to 100 μM. 28 , 50 , 51 Yuan et al described that glabridin has the ability to restrict toxicological alterations in the liver using monosodium iodoacetate-induced osteoarthritic rats ( in vivo ). 28 We reported earlier that pretreatment of glabridin can prevent the MTX-induced hepatotoxicity upon a single high-dose administration of MTX using a mice model ( in vivo ).…”

Section: Discussionmentioning

confidence: 99%

“…Glabridin in a pure form (purity >99%) was obtained from the NPMC Division of our institute. 51 The dose of glabridin was selected at three dose levels from 10 to 40 mg/kg body weight daily based on our previous experimentation. 37 MTX dose was selected at 3 mg/kg body weight once a week following the earlier reported literature.…”

Section: Methodsmentioning

confidence: 99%

“…Liver tissue (50 mg each) in 100 mM sodium phosphate buffer containing 5 mM EDTA (750 μL) and 25% of orthophosphoric acid (200 μL) was homogenized at first for the estimation of GSH. The studies mentioned above were performed using our earlier reported protocol. , …”

Section: Methodsmentioning

confidence: 99%

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Glabridin Plays Dual Action to Augment the Efficacy and Attenuate the Hepatotoxicity of Methotrexate in Arthritic Rats

et al. 2022

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Glabridin is chemically an isoflavane class of natural phenols and is found mainly in the roots of Glycyrrhiza glabra . It has several beneficial pharmacological actions for the management of inflammatory disorders as well as can counteract drug-induced toxic effects. On the other hand, methotrexate (MTX) is the first-line disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis. However, its treatment is associated with major side effects like hepatotoxicity. In the quest to explore a suitable combination therapy that can improve the efficacy and reduce the hepatotoxicity of MTX, we hypothesized that glabridin might serve the purpose for which there is no literature precedent to date. We explored the antiarthritic efficacy of MTX in the presence or the absence of glabridin using Mycobacterium-induced arthritic model in rats. The results of reduction in paw swelling, inhibition of serum cytokines (TNF-α, IL-6, and IL-1β), and improvement in the bone joints from radiological and histopathological findings suggest that glabridin can substantially augment the antiarthritic efficacy of MTX. Further, results of concomitant glabridin treatment with MTX in the experimental time frame demonstrate that glabridin could considerably prevent the MTX-induced hepatic alteration in serum biochemical markers (SGPT and SGOT) and oxidative stress markers (malondialdehyde (MDA) and glutathione reduced (GSH)). Moreover, glabridin showed a marked effect in impeding the regulation of NF-κB/IκBα and Nrf2/Keap1 pathways in the hepatic tissues. The results of simultaneous administration of glabridin with MTX in the rat model indicate that glabridin had no pronounced effect of causing severe alteration in the pharmacokinetic behavior of MTX. In summary, glabridin can significantly potentiate the antiarthritic efficacy of MTX and can also minimize its hepatotoxicity via the inhibition of inflammation and oxidative stress. Further research should be performed to develop glabridin as a phytotherapeutics for the improved efficacy and better tolerability of MTX at the reduced dose level of MTX.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Glabridin Plays Dual Action to Augment the Efficacy and Attenuate the Hepatotoxicity of Methotrexate in Arthritic Rats

et al. 2022

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“…In addition, glabridin also attenuates the activity of NF-κB signaling pathway in liver tissues. 107 The protecting activity of glabridin against liver damage might be associated with inhibition of CYP2E1 and suppression of oxidative stress and NF-κB pathway. Another study shows that glabridin has been screened to inhibit against CYP3A4 competitively.…”

Section: Hepatoprotectionmentioning

confidence: 99%

Review on the Diverse Biological Effects of Glabridin

Zhang¹,

Wu²,

Zhong³

et al. 2023

DDDT

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Glabridin is a prenylated isoflavan from the roots of Glycyrrhiza glabra Linne and has posed great impact on the areas of drug development and medicine, due to various biological properties such as anti-inflammation, anti-oxidation, anti-tumor, anti-microorganism, bone protection, cardiovascular protection, neuroprotection, hepatoprotection, anti-obesity, and anti-diabetes. Many signaling pathways, including NF-κB, MAPK, Wnt/β-catenin, ERα/SRC-1, PI3K/AKT, and AMPK, have been implicated in the regulatory activities of glabridin. Interestingly, glabridin has been considered as an inhibitor of tyrosinase, P-glycoprotein (P-gp), and CYP2E1 and an activator of peroxisome proliferator-activated receptor γ (PPARγ), although their molecular regulating mechanisms still need further investigation. However, poor water solubility and low bioavailability have greatly limited the clinical applications of glabridin. Hopefully, several effective strategies, such as nanoemulsions, microneedles, and smartPearls formulation, have been developed for improvement.

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Glabridin plays dual action to intensify anti-metastatic potential of paclitaxel via impeding CYP2C8 in liver and CYP2J2/EETs in tumor of an orthotopic mouse model of breast cancer

Jamwal

Chand

Dash

et al. 2023

Chemico-Biological Interactions

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Glabridin attenuates paracetamol-induced liver injury in mice via CYP2E1-mediated inhibition of oxidative stress

Cited by 13 publications

References 32 publications

Glabridin Plays Dual Action to Augment the Efficacy and Attenuate the Hepatotoxicity of Methotrexate in Arthritic Rats

Glabridin Plays Dual Action to Augment the Efficacy and Attenuate the Hepatotoxicity of Methotrexate in Arthritic Rats

Review on the Diverse Biological Effects of Glabridin

Glabridin plays dual action to intensify anti-metastatic potential of paclitaxel via impeding CYP2C8 in liver and CYP2J2/EETs in tumor of an orthotopic mouse model of breast cancer

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