The naturally occurring flavonoid nobiletin reverses methotrexate resistance via inhibition of P-glycoprotein synthesis

Li, Rui; Song, Yurong; Li, Chenxi; Zhang, Zhengjia; Xue, Zeyu; Huang, Qingcai; Yu, Liuchunyang; Zhu, Dongjie; Cao, Zhiwen; Lü, Aiping; Lü, Cheng; Liu, Yuanyan

doi:10.1016/j.jbc.2022.101756

Cited by 8 publications

(3 citation statements)

References 33 publications

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“…The role of p-glycoprotein in resistance to MTX and its efficacy plays a vital role, as it has been described experimentally in rats [ 123 ] and also in vitro [ 124 ]. To support our team’s hypothesis, it has been also shown that naturally occurring flavonoid nobiletin reverses MTX resistance via inhibition of P-glycoprotein synthesis in CIA-FLS/MTX cells through the PI3K/AKT/HIF-1α pathway [ 125 ].…”

Section: Discussionmentioning

confidence: 91%

Rhodiola rosea L. Extract, a Known Adaptogen, Evaluated in Experimental Arthritis

et al. 2023

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Rhodiola rosea L. extract (RSE) is mostly known for its adaptogen properties, but not for its antiarthritic activities, therefore monotherapy and combination with low-dose methotrexate (MTX) was studied. The collagen-induced arthritis (CIA) model was used to measure the functional score, and the change in hind paw volume (HPV). Both parameters had significant antiarthritic effects. Based on these preliminary results, an adjuvant arthritis (AA) model was further applied to assess another parameters. The experiment included these animal groups: healthy controls, untreated AA, AA administered with RSE (150 mg/kg b.w. daily, p.o.), AA administered by MTX (0.3 mg/kg b.w. twice a week, p.o.), and AA treated with the combination of RSE+MTX. The combination of RSE+MTX significantly reduced the HPV and increased the body weight. The combination significantly decreased HPV when compared to MTX monotherapy. The plasmatic levels of inflammatory markers (IL-6, IL-17A, MMP-9 and CRP) were significantly decreased by MTX+RSE treatment. The RSE monotherapy didn’t influence any of the inflammatory parameters studied. In CIA, the RSE monotherapy significantly decreased the arthritic parameters studied. In summary, the combination of RSE and sub-therapeutic MTX was significantly effective in AA by improving inflammatory and arthritic parameters.

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Section: Discussionmentioning

confidence: 91%

Rhodiola rosea L. Extract, a Known Adaptogen, Evaluated in Experimental Arthritis

et al. 2023

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“…The H&E staining score evaluation criteria were as follows: it could be divided into five degrees of zero to four points according to the edema, structural damage, and inflammatory cell infiltration of lesions, from light to heavy. The score was measured ( Liu et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…The blots were developed using the ECL Western blot Kit (LabLead, E1050) on the gel imaging system (ChampgelTM 5,000 plus, SINSAGE, China). The exposure time for blots ranged from 100 ms to 3 s. Film density was measured using ImageJ densitometry software and was normalized against glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (#60004-1-Ig, Proteintech) ( Liu et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Screening of potentially active compounds against rheumatoid arthritis in the Juan-Bi decoction using systems pharmacology and animal experiments

Liu,

Fu,

Liu

et al. 2024

Front. Cell Dev. Biol.

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Background: The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear.Aim: The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches.Method: Botanical drugs and compounds in the JBD were acquired from multiple public TCM databases. All compounds were initially screened using absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physicochemical properties, and then a target prediction was performed. RA pathological genes were acquired from the DisGeNet database. Potential active compounds were screened by constructing a compound–target–pathogenic gene (C-T-P) network and calculating the cumulative interaction intensity of the compounds on pathogenic genes. The effectiveness of the compounds was verified using lipopolysaccharide (LPS)-induced RAW.264.7 cells and collagen-induced arthritis (CIA) mouse models.Results: We screened 15 potentially active compounds in the JBD for RA treatment. These compounds primarily act on multiple metabolic pathways, immune pathways, and signaling transduction pathways. Furthermore, in vivo and in vitro experiments showed that bornyl acetate (BAC) alleviated joint damage, and inflammatory cells infiltrated and facilitated a smooth cartilage surface via the suppression of the steroid hormone biosynthesis.Conclusion: We screened potential compounds in the JBD for the treatment of RA using systems pharmacology approaches. In particular, BAC had an anti-rheumatic effect, and future studies are required to elucidate the underlying mechanisms.

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Flavonoids as P-glycoprotein inhibitors for multidrug resistance in cancer: an in-silico approach

Kumar

Kalra

Jangid

et al. 2022

Journal of Biomolecular Structure and Dynamics

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The naturally occurring flavonoid nobiletin reverses methotrexate resistance via inhibition of P-glycoprotein synthesis

Cited by 8 publications

References 33 publications

Rhodiola rosea L. Extract, a Known Adaptogen, Evaluated in Experimental Arthritis

Rhodiola rosea L. Extract, a Known Adaptogen, Evaluated in Experimental Arthritis

Screening of potentially active compounds against rheumatoid arthritis in the Juan-Bi decoction using systems pharmacology and animal experiments

Flavonoids as P-glycoprotein inhibitors for multidrug resistance in cancer: an in-silico approach

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