Glabridin ameliorates methotrexate-induced liver injury via attenuation of oxidative stress, inflammation, and apoptosis

Dogra, Ashish; Gupta, Divya; Bag, Swarnendu; Ahmad, Irfan; Bhatt, Shipra; Nehra, Ekta; Dhiman, Shakti Kumar; Kumar, Amit; Singh, Gurdarshan; Abdullah, Sheikh Tasduq; Sangwan, Payare L.; Nandi, Utpal

doi:10.1016/j.lfs.2021.119583

Cited by 30 publications

(24 citation statements)

References 27 publications

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“… 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 ). 37 In the current investigation, glabridin and MTX were treated simultaneously in the arthritic rats for a longer time period. Results suggest that glabridin can restrict the enhancement in hepatic marker enzyme levels (SGOT and SGPT) and minimize oxidative stress (MDA and GSH).…”

Section: Discussionmentioning

confidence: 96%

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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: 96%

“… 32 − 36 We also reported earlier that glabridin could combat the MTX-induced hepatotoxicity via inhibiting oxidative stress, inflammation, and apoptosis using a mice model. 37 …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Nrf2 controls the expression of antioxidant enzymes in management of oxidant stress [ 154 ]. Flavonoids derived from licorice exhibited reliable antioxidant activity through the regulation of Nrf2 protein expression.…”

Section: Antioxidationmentioning

confidence: 99%

“…In addition, licochalcone A prevented ROS-driven oxidative stress in primary human fibroblasts in vitro by activating the cytoprotective phase II enzymes and stimulating the antioxidant transcription factor Nrf2 [ 156 ]. Glabridin displayed the antioxidant defense mechanism of liver via upregulating Nrf2 protein expression to lower the ROS formation and ameliorate oxidative stress exerting the hepatoprotective effect against MTX [ 154 ].…”

Section: Antioxidationmentioning

confidence: 99%

Pharmacological Effects and Underlying Mechanisms of Licorice-Derived Flavonoids

Wang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Glycyrrhizae Radix et Rhizoma is the most frequently prescribed natural medicine in China and has been used for more than 2,000 years. The flavonoids of licorice have garnered considerable attention in recent decades due to their structural diversity and myriad pharmacological effects, especially as novel therapeutic agents against inflammation and cancer. Although many articles have been published to summarize different pharmacological activities of licorice in recent years, the systematic summary for flavonoid components is not comprehensive. Therefore, in this review, we summarized the pharmacological and mechanistic data from recent researches on licorice flavonoids and their bioactive components.

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“…Its protective effects were including the reduction of AST, ALT, TNF-α, IL-1β, IL-6, and IL-12 serum levels, diminish caspase-3 and NF-κB expression, the elevation of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), peroxidase, and glutathione reductase liver content, and restoration of tissue lesions (Chauhan et al, 2020). Dogra et al showed that glabridin (10-40 mg/kg), one of the components of licorice, attenuated liver oxidative stress, inflammation, and apoptosis induced by methotrexate (40 mg/kg) in the Swiss mice model (Dogra et al, 2021).…”

Section: Methotrexatementioning

confidence: 99%

The genus Glycyrrhiza (Fabaceae family) and its active constituents as protective agents against natural or chemical toxicities

Heidari

Mehri

Hosseinzadeh

2021

Phytotherapy Research

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Licorice is the dried roots and rhizomes of various species of the genus Glycyrrhiza (Fabaceae) that have been used in folk medicine from ancient times. Many important research projects have established several beneficial effects for this medicinal herb, including antiinflammatory, antimicrobial, antiviral, antiprotozoal, antioxidant, antihyperglycemic, antihyperlipidemic, hepatoprotective, and neuroprotective. Licorice contains important bioactive components, such as glycyrrhizin (glycyrrhizic, glycyrrhizinic acid), liquiritigenin, liquiritin, and glycyrrhetinic acid. The protective effects of licorice and its main chemical components against toxins and toxicants in several organs including the brain, heart, liver, kidney, and lung have been shown. In this comprehensive review article, the protective effects of these constituents against natural, industrial, environmental, and chemical toxicities with attention on the cellular and molecular mechanism are introduced. Also, it has been revealed that this plant and its main compounds can inhibit the toxicity of different toxins by the antioxidant, antiinflammatory, and anti‐apoptotic properties as well as the modulation of Inhibitor of kappaB kinase (IKK), Extracellular signal‑regulated protein kinase1/2 (ERK1/2), p38, inducible nitric oxide synthase, and nuclear factor‐κB (NF‐κB) signaling pathways. More high‐quality investigations in both experimental and clinical studies need to firmly establish the efficacy of licorice and its main constituents against toxic agents.

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Glabridin ameliorates methotrexate-induced liver injury via attenuation of oxidative stress, inflammation, and apoptosis

Cited by 30 publications

References 27 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

Pharmacological Effects and Underlying Mechanisms of Licorice-Derived Flavonoids

The genus Glycyrrhiza (Fabaceae family) and its active constituents as protective agents against natural or chemical toxicities

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