ABSTRACT
OBJECTIVE Interleukin (IL)-1β, one of the principal inflammatory cytokines mainly secreted by mono?cytes and macrophages, is produced by cleavage of the inactive pro-IL-1βprecursor by caspase-1 via the NLRP3 inflam?masome complex. The fruits of Garcinia cambogia (Clusiaceae) are widely developed as health products for anti-obese purpose. 14-deoxygarcinol (DOG) is a polyisoprenylated benzophenone from the fruits of G. cambogia, which showed potent anti-inflammatory effect in our previous study. The objective of this study was to explore the anti-inflammatory mechanism of DOG and its roles in alleviating adipose tissue inflammation and insulin resistance. METHODS The anti-inflammatory effect of DOG was evaluated on LPS plus nigericin-induced THP-1 macrophages. The expression of NLRP3 inflammasome complex proteins was analyzed by Western blotting, immunofluorescence staining and co-immu?noprecipitation. The pro-inflammatory cytokines levels were determined by ELISA kits. RESULTS DOG increased the expression of Sirtuin 2 (SIRT2) deacetylase and enhanced its deacetylating activity to suppress the NLRP3 inflamma?some activation and IL-1βsecretion in THP-1 macrophages. Moreover, DOG attenuated macrophage conditioned medium-induced inflammatory responses in adipocytes and blocked THP-1 macrophages migration towards 3T3-L1 adipocytes. CONCLUSION DOG attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT2-mediated NLRP3 inflammasome inhibition, which might be used for the treatment of adipose tissue inflammation-related metabolic disorders.
ABSTRACT
Nagilactone E (NLE), a natural product with anticancer activities, is isolated from Podocarpus nagi. In this study, we reported that NLE increased programmed death ligand 1 (PD-L1) expressions at both protein and mRNA levels in human lung cancer cells, and enhanced its localization on the cell membrane. Mechanistically, NLE increased the phosphorylation and expression of c-Jun, and promoted the localization of c-Jun in the nucleus, while silencing of c-Jun by small interfering RNA (siRNA) reduced NLE-induced PD-L1. Further study showed that NLE activated the c-Jun N-terminal kinases (JNK), the upstream of c-Jun, and its inhibitor SP600125 reversed the NLE-increased PD-L1. Moreover, NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface. In summary, NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis, which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.
ABSTRACT
Pharmaceutical research has focused on the discovery and development of anticancer drugs. Clinical application of chemotherapy drugs is limited due to their severe side effects. In this regard, new naturally occurring anticancer drugs have gained increasing attention because of their potential effectiveness and safety. Fruits and vegetables are promising sources of anticancer remedy. Clausena (family Rutaceae) is a genus of flowering plants and includes several kinds of edible fruits and vegetables. Phytochemical and pharmacological studies show that carbazole alkaloids and coumarins from Clausena plants exhibit anticancer activity. This review summarizes research progresses made in the anticancer properties of plants belonging to Clausena; in particular, compounds with direct cytotoxicity, cell cycle arrest, apoptosis induction, and immune potentiation effects are discussed. This review reveals the potential use of plants from Clausena in preventing and treating cancer and provides a basis for development of relevant therapeutic agents.