Total Flavonoids from Radix Glycyrrhiza Exert Anti‐Inflammatory and Antitumorigenic Effects by Inactivating iNOS Signaling Pathways

Abstract

Inducible nitric oxide synthase (iNOS) plays an important role in inflammation, which has also been considered as a major driver of breast cancer disease progression. Radix Glycyrrhiza (RG) has been broadly used for its anti-inflammatory and antitumorigenic effects. However, the mechanisms of regulation of iNOS in inflammation and cancer have not been fully explored. Total flavonoids isolated from RG (TFRG) exhibited anti-inflammatory activity through the regulation of ERK/NF-κB/miR-155 signaling and suppression of iNOS expression in LPS/IFN-γ stimulated RAW264.7 macrophages without cytotoxicity. TFRG also markedly reduced tumor mass of breast cancer cell MDA-MB-231 xenografts with suppression of iNOS expression, formation of 3-nitrotyrosine (3-NT), and inactivation of protumorigenic JAK2/STAT3 signaling pathway. These results suggested that TFRG limited the development of breast cancer and inflammation due to its property of iNOS inhibition.

Antioxidant, Anti-Inflammatory and Antiproliferative Effects of the Vitis vinifera L. var. Fetească Neagră and Pinot Noir Pomace Extracts

“…It was reported that polyphenols can suppress NF-kB activation and translocation into the nucleus of the activated B cells ( Annunziata et al., 2020 ). Plant extracts with anti-inflammatory effects mediated by iNOS inhibition and nitro-oxidative stress reduction may be an adjuvant alternative therapeutic option for tumor cells proliferation and metastasis inhibition ( Jiang et al., 2018 ). Turpentine administration significantly increased NOx (p < 0.001), and pretreatment with GP extracts caused a concentration-dependent reduction of NOx, the fresh GP extracts having a stronger inhibitory effect than the fermented GP extracts.…”

“…The toxicity hypothesis indicates that high levels of NO induce mitochondrial respiratory inhibition, ATP depletion, DNA deamination, oxidation, and nitration. The hypothesis of the cytoprotective role of NO states that NO protects cells against lipid peroxidation by reaction with sulfhydryl groups in proteins (Jiang et al, 2018). Because flavonols inhibit NO production (Semwal et al, 2016) and NO accumulation (Dai et al, 2013), the reduction of NO may be correlated with the polyphenol content.…”

Screening Five Qi-Tonifying Herbs on M2 Phenotype Macrophages

“…Extracts were dissolved with DMSO before use. TFRG was obtained as described previously [10], and no endotoxin existed in it by endotoxin test.…”

Фармакологічний Профіль Фітокомпозиції Нормоцикл У Терапії Гормональних Дисбалансів У Жінок

“…В исследовании Y.X. Jiang [33] доказано, что растительные экстракты Radix Glycyrrhiza, обладающие противовоспалительной активностью, нацелены на iNOS, соответственно, снижают окислительный/нитрозативный стресс и являются полезными химиопревентивными агентами против развития рака молочной железы и/или метастазов. В исследовании моделировали мышам рак молочной железы путем инъекции онкоклеток MDA-MB-231, которые взяли из биоптата опухоли ткани молочной железы у пациенток с диагнозом «рак молочной железы эстрогензависимый».…”