Liquiritin from Glycyrrhiza uralensis Attenuating Rheumatoid Arthritis via Reducing Inflammation, Suppressing Angiogenesis, and Inhibiting MAPK Signaling Pathway

Abstract

Among the various treatments, induction of synoviocyte apoptosis by natural products during a rheumatoid arthritis (RA) pathological condition can be considered to have vast potential. However, it is unclear that liquiritin, a kind of natural flavonoid extracted from the roots of Glycyrrhiza uralensis, induced the apoptosis of the synovial membrane and its molecular mechanism. In this study, interleukin-1β (IL-1β)-RA-FLS cells were incubated with different concentrations of liquiritin. An MTT assay, Hoechst 33342 staining, JC-1 staining, and Western blot were used to check the viability, cell apoptosis, mitochondrial membrane potential changes, and the expression of related proteins, respectively. In vivo, a TUNEL assay and HE staining of tissue were used for histopathological evaluation. Our results showed that liquiritin significantly inhibited the proliferation of IL-1β-induced-RA-FLS, promoted nuclear DNA fragmentation, and changed the mitochondrial membrane potential to accelerate cell apoptosis. Liquiritin downregulated the ratio of Bcl-2/Bax and inhibited the VEGF expression and phosphorylation of JNK and P38. Moreover, liquiritin improved the clinical score of rheumatism, inflammatory infiltration, and angiogenesis and induced apoptosis of the synovial tissue in vivo. Hence, liquiritin ameliorates RA by reducing inflammation, blocking MAPK signaling, and restraining angiogenesis.

Liquiritin Alleviates Pain Through Inhibiting CXCL1/CXCR2 Signaling Pathway in Bone Cancer Pain Rat

“…In our present study, the mechanical withdrawal threshold showed a significant decrease on day 6 and continued to decline at a certain speed until day 18, which was in line with the previous research results (Hu et al, 2013;Ni et al, 2019a). LQ is one of the major constituents of Glycyrrhiza radix that exerts antiinflammatory effect (Li et al, 2018), pro-apoptotic effect (Wei et al, 2017), neurotrophic effect (Chen et al, 2009), and anti-RA (Zhai et al, 2019). In addition, intragastric administration of LQ reduced hyperalgesia in a dose-dependent manner and inhibited the activation of glia (astrocyte and microglia) on CCI induced neuropathic pain (Zhang M. T. et al, 2017).…”

“…Liquiritin (LQ) ( Figure 1) is one of the major constituents of Glycyrrhizae Radix, which has a great potential in medical applications and pharmacological activities, such as in preventing inflammation and relieving pain, cancer, cough, and allergic reactions (Zhang and Ye, 2009;Xie et al, 2017;Li et al, 2018). Zhai et al have reported that LQ ameliorates rheumatoid arthritis (RA) by reducing proinflammatory cytokines (IL-6) and blocking MAPK signalling (Zhai et al, 2019). In vivo studies have revealed that LQ is used for effective treatment of neuropathic pain by downregulating the cytokines including TNF-a and IL-6, suggesting it as a promising anti-inflammatory and anti-nociceptive drug (Zhang M. T. et al, 2017).…”

An artificial intelligence system reveals liquiritin inhibits SARS-CoV-2 by mimicking type I interferon

“…The intake food, body weights were all kept at normal level (Figure 3e, f). As reported in literatures, liquiritin has no significantly cytotoxic effects in L-02, GES-1, IMR-90 and 293T cells with different concentrations (30, 60, 90, 120, and 150 µM) and the MTT assay results confirmed that 345 µM liquiritin has no influence on the viability of RA-FLS cells 16,17 .…”

The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

“…EST-1 and Runx2 are osteogenic differentiation-specific transcription factors that regulate the transcription of multiple genes (45,46) that play important roles in the formation and differentiation of osteoblasts, differentiation and maturation of chondrocytes, formation and absorption of osteoclasts and production of bone matrix proteins (47,48). In addition, in rheumatoid arthritis, a number of other signaling pathways that may regulate MMPs have also been identified, such as Nrf2/HO-1 signaling (49), NF-κB inflammatory signaling (50,51), mitochondrial/caspase-mediated pathways (52) or mitogen-activated protein kinase signaling pathway (53); however, its role in HMGB1-induced chondrocyte apoptosis requires further investigation. The results of the present study also indicated that HMGB1 may promote chondrocyte dysfunction by upregulating EST-1 and Runx2.…”