14-Deoxygarcinol,a polyisoprenylated benzophenone from Garcinia cambogia,ameliorates inflammatory responses in adipose tissue via suppressing NLRP3 inflammasome

OBJECTIVE Interleukin(IL)-1β,one of the principal inflammatory cytokines mainly secreted by monocytes and macrophages,is produced by cleavage of the inactive pro-IL^(-1)βprecursor by caspase-1 via the NLRP3 inflammasome 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-immunoprecipitation.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 inflammasome activation and IL^(-1)βsecretion 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.

Effects of garcinone E on ovarian cancer cells:endoplasmic reticulum stress,apoptosis,migration and invasion inhibition

OBJECTIVE Garcinone E,a xanthone derivative isolated from mangosteen,has been reported to have cytotoxic capacities.We aim to study the anticancer effects of garcinone E on ovarian cancer cells.METHODS MTT assay,LDH release assay,Hoechst33342 staining,AnnexinⅤ/PI staining,and JC-1 staining were used to test the antitumor abilities on several ovarian cancer cell lines,and wound-healing assay,transwell assay,and gelatin zymography were carried out to examine the migratory and invasive effects of malignant ovarian cancer HEY cells.Relevant m RNA transcription and protein expression were evaluated by Western blotting.RESULTS Garcinone E treatment significantly inhibited the proliferation and caused cell death on ovarian cancer HEY,A2780 as well as A2780-palicitaxel resistant cells.It induced endoplasmic reticulum stress in HEY cells and activated IRE signaling pathway,which provided protection on HEY cells.Meanwhile,knocking down of IRE-1αby si RNA further activated caspase cascade and caused more cell death.On the other hand,garcinone E eliminated migrative ability of HEY cells by reducing the expression of Rho A and Rac,and it blockaded invasion by down-regulating the protein level of MMP-9 and-2,and up-regulating the protein level of TIMP-1 and-2.Garcinone E-reduced activities of MMP-9 and-2 were confirmed by gelatin zymography assay.CONCLUSION Our finding demonstrated that garcinone E exerts anticancer activities by inducing apoptosis,and suppressing migration and invasion on ovarian cancer cells,which demonstrated certain therapeutic potential of garcinone E on ovarian cancer.

Honokiol: A naturally occurring lignan with pleiotropic bioactivities

Honokiol is the dominant biphenolic compound isolated from the Magnolia tree,and has long been considered as the active constituent of the traditional Chinese herb,‘Houpo’,which is widely used to treat symptoms due to‘stagnation of qi’.Pharmacological studies have shown that honokiol possesses a wide range of bioactivities without obvious toxicity.Honokiol protects the liver,kidneys,nervous system,and cardiovascular system through reducing oxidative stress and relieving inflammation.Moreover,honokiol shows anti-diabetic property through enhancing insulin sensitivity,and anti-obese property through promoting browning of adipocytes.In vivo and in vitro studies indicated that honokiol functions as an anti-cancer agent through multiple mechanisms:inhibiting angiogenesis,promoting cell apoptosis,and regulating cell cycle.A variety of therapeutic effects of honokiol may be associated with its physiochemical properties,which make honokiol readily cross the blood brain barrier and the blood-cerebrospinal fluid barrier,with high bioavailability.In the future,more clinical researches on honokiol are needed to fully authenticate its therapeutic values.

Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells

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 cJun,and promoted the localization of c-Jun in the nucleus,while silencing of c-Jun by small interfering RNA(siRNA)reduced NLEinduced 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.

Anticancer carbazole alkaloids and coumarins from Clausena plants： A review

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.