The phytochemical constituents and protective effect of Fritillaria hupehensis on acute lung injury.

Acute lung injury (ALI), a severe respiratory disorder, frequently develops into acute respiratory distress syndrome (ARDS) without timely treatment and scores highly in terms of morbidity and mortality rates. Fritillaria hupehensis is a famous traditional Chinese medicine with antitussive, expectorant and anti-asthmatic effect. Here, the effects of F. hupehensis extracts on lipopolysaccharide (LPS)-induced ALI mice were evaluated for the first time. We showed ethyl acetate fraction (EAF) significantly reduced the leukocytes and neutrophils of bronchoalveolar lavage fluid (BALF) and the lung index as well as pro-inflammatory cytokines (TNF-α and IL-6) of lung homogenates but increasing the anti-inflammatory cytokines (IL-4 and IL-10). Additionally, the alleviation of EAF treatment on lung injury was verified through histopathological observations. Subsequent phytochemical investigation on bioactive fraction led to isolation of 17 compounds including two new, in which compounds 2, 5 and 6 exhibited better anti-inflammatory effect on LPS-induced 16 human airway epithelial (16HBE) cells model by inhibiting the production of CRP and PCT. Furthermore, compound 2 suppressed the LPS-induced upregulation of proteins containing p-p65, COX-2, Caspase-1 and IL-18. In summary, F. hupehensis alleviating LPS-induced ALI in mice may be associated with the anti-inflammatory activity of steroidal alkaloids by suppressing the NF-κB-regulated pro-inflammatory proteins.

Chemistry and bioactivities of natural steroidal alkaloids.

Steroidal alkaloids possess the basic steroidal skeleton with a nitrogen atom in rings or side chains incorporated as an integral part of the molecule. They have demonstrated a wide range of biological activities, and some of them have even been developed as therapeutic drugs, such as abiraterone acetate (Zytiga®), a blockbuster drug, which has been used for the treatment of prostate cancer. Structurally diverse natural steroidal alkaloids present a wide spectrum of biological activities, which are attractive for natural product chemistry and medicinal chemistry communities. This review comprehensively covers the structural classification, isolation and various biological activities of 697 natural steroidal alkaloids discovered from 1926 to October 2021, with 363 references being cited.

LINC00839 knockdown restrains the metastatic behavior of nasopharyngeal carcinoma by sponging miR-454-3p.

Long intergenic non-coding RNA 00839 (LINC00839) has been verified as a pro-metastasis factor in malignancies. However, the significance of LINC00839 in nasopharyngeal carcinoma (NPC) has yet to be illuminated, as well as its underlying mechanism. Here, we disclosed that LINC00839 is highly expressed in NPC. Deletion of LINC00839 suppresses NPC cells rapid growth, invasive capacity and EMT in vitro. Besides, LINC00839 is identified as a "sponge" for miR-454-3p, and upregulation of LINC00839 reverses miR-454-3p-mediated inhibition of aggressiveness in NPC cells. Furthermore, the expression of cellular-mesenchymal epithelial transition factor (c-Met), the downstream target of miR-454-3p, is downregulated by LINC00839 knockdown in NPC cells. In vivo, LINC00839 knockdown retards the tumor growth of NPC cells in the xenografted mice model. Collectively, attenuation of LINC00839 expression attenuates the aggressive properties of NPC cells via directly sponging the miR-454-3p and regulating c-Met expression.