Aberrant NLRP3 activation has been implicated in the pathogenesis of numerous inflammation-associated diseases. However, no small molecular inhibitor that directly targets NLRP3 inflammasome has been approved so far. In this study, we show that Atranorin (C 19 H 18 O 8 ), the secondary metabolites of lichen family, effectively prevents NLRP3 inflammasome activation in macrophages and dendritic cells. Mechanistically, Atranorin inhibits NLRP3 activation induced cytokine secretion and cell pyroptosis through binding to ASC protein directly and therefore restraining ASC oligomerization. The pharmacological effect of Atranorin is evaluated in NLRP3 inflammasome-driven disease models. Atranorin lowers serum IL-1β and IL-18 levels in LPS induced mice acute inflammation model. Also, Atranorin protects against MSU crystal induced mice gouty arthritis model and lowers ankle IL-1β level. Moreover, Atranorin ameliorates intestinal inflammation and epithelial barrier dysfunction in DSS induced mice ulcerative colitis and inhibits NLRP3 inflammasome activation in colon. Altogether, our study identifies Atranorin as a novel NLRP3 inhibitor that targets ASC protein and highlights the potential therapeutic effects of Atranorin in NLRP3 inflammasome-driven diseases including acute inflammation, gouty arthritis and ulcerative colitis.
With the rapid improvement of power conversion efficiency (PCE), perovskite solar cells (PSCs) have broad application prospects and their industrialization will be the next step. Nevertheless, the performance and long-term stability of the devices are limited by the defect-induced nonradiative recombination centers and ions’ migration inside the perovskite films. Here, usnic acid (UA), an easy-to-obtain and efficient natural biomaterial with a hydroxyl functional group (−OH) and four carbonyl groups (−C═O) was added to MAPbI3 perovskite precursor to regulate the crystallization process by slowing the crystallization rate, thereby expanding the crystal size and preparing perovskite films with low defect density. In addition, UA anchors the uncoordinated Pb2+ and suppresses the migration of I-ions, which enhances the stability of the perovskite film. Consequently, an impressive PCE exceeding 20% was achieved for inverted structure MAPbI3-based PSCs. More impressively, the optimized PSCs maintained 78% of the initial PCE under air with high humidity (RH ≈ 65%, 25–30 °C) for 1000 h. UA can be extracted from the plant, usnea, making it inexpensive and easy to obtain. Our work demonstrates the application of the plant material in PSCs and their industrialization, which is significant nowadays.
Objectives
The Sonic hedgehog (SHH) signaling is essential in animal development and tissue homeostasis. Aberrant activation of SHH pathway has been implicated in tumorigenesis and progression of several cancers, including ovarian cancer. Therefore, targeting SHH pathway may pave the way for successful ovarian cancer treatment.
Methods
To identify the potential SHH inhibitors from traditional Chinese medicines, we herein employed two in vitro cell models. In addition, western blotting and quantitative real-time PCR were performed to evaluate the inhibitory activity of Anemarrhenasaponin I (An-I) on SHH signaling in ovarian cancer cells. Cell proliferation assay and transwell assay were used to assess the effect of An-I on tumorigenicity. We also applied RNA-seq to examine the potential mechanism of An-I against ovarian cancer.
Results
Drug screening results showed that An-I drastically inhibited SHH signaling. More importantly, An-I effectively suppressed ovarian cancer cell proliferation and aggressiveness. RNA-seq-based transcriptome data showed that An-I affected ovarian cancer cells by suppressing SHH-WNT-Matrix metalloproteinases (MMPs) pathway.
Conclusions
An-I suppressed ovarian cancer progression by inhibiting SHH-WNT-MMP signaling transduction, providing a new treatment strategy for ovarian cancer.
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