Licochalcone B

Osteosarcoma (OS), a prevalent bone tumor, remains an aggressive malignancy with limited targeted options. Neural cell adhesion molecule 1 (NCAM1) has been implicated in the progression of several tumors. Licochalcone B, a compound extracted from Glycyrrhiza uralensis Fisch, has shown antitumor effects on cancers. However, the role of NCAM1 and the therapeutic efficacy of Licochalcone B via regulating NCAM1 in OS remains unclear.

To elucidate the oncogenic properties of NCAM1 and evaluate Licochalcone B as a therapeutic agent targeting NCAM1 in OS.

Bulk and single-cell RNA-seq clinical cohorts were integrated to profile the transcriptional characteristics and clinical significance of NCAM1 in OS. To gain insights into the pro-tumorigenic effect of NCAM1 and the therapeutic potential of Licochalcone B via binding NCAM1, in vitro and in vivo experiments were performed.

Elevated NCAM1 expression in OS presented an independent value for predicting poor patient survival. NCAM1 overexpression accelerated cell proliferation, migration, invasion and tumor growth, which were attenuated by Licochalcone B. Additionally, Licochalcone B facilitated oxidative stress-related ferroptosis which was partially rescued by NCAM1 overexpression. Notably, NCAM1 expression in malignant cells shaped an immunosuppressive spectrum in OS cells and was related to an exhausted CD8⁺ T-cell landscape, which was disrupted by Licochalcone B via the restoration of ferroptosis. Mechanistically, Licochalcone B repressed the phosphorylation of ERK5 and NF-κB P65 proteins via downregulating NCAM1 expression.

Licochalcone B exerts its antitumor effects in OS by targeting NCAM1, which may serve as a promising therapeutic agent for improving patient outcomes.

Pulmonary fibrosis (PF) is a progressive, fatal lung disease. Yujie Recipe (YJR), a traditional Chinese medicine, is used clinically for pulmonary disorders, but the active constituents and underlying mechanisms remain unclear.

To evaluate the therapeutic effects of YJR in a bleomycin-induced pulmonary fibrosis (BIPF) mouse model and to systematically identify its key bioactive constituents along with their underlying molecular mechanisms, providing novel mechanistic insights and potential therapeutic candidates for PF.

Bleomycin was used to induce BIPF mice model, while YJR was administered at multiple doses to evaluate its anti-PF effects. An integrated approach combining phytochemical profiling, computational and cellular assays was employed to uncover the anti-PF constituents in YJR and their anti-fibrotic mechanisms.

Yujie Recipe (YJR) dose-dependently attenuated bleomycin-induced pulmonary fibrosis (BIPF) in mice by activating Nrf2-ARE signaling and suppressing the NF-κB/NLRP3 inflammatory signaling. Nrf2 ablation abolished the protective effects of YJR and restored NF-κB/NLRP3 activation, highlighting the central role of Nrf2 in mediating its anti-fibrotic activity. Phytochemical analysis identified 146 lung-exposed compounds, of which 20 predicted bioactives were tested for Nrf2 agonist activity. Licochalcone B (LCB), apigenin (APG), and formononetin (FN) were confirmed as potent Nrf2 agonists. In vitro, they dose-dependently reduced ROS accumulation and inhibited TGF-β1-challenged migration and myofibroblast differentiation of MRC-5 fibroblasts, as indicated by decreased α-SMA, collagen I, and fibronectin.

YJR exerts anti-fibrotic effects via suppressing NF-κB/NLRP3 pathway in a Nrf2-dependent manner, while licochalcone B, apigenin, and formononetin are identified as key anti-fibrotic constituents.