Synthesis of 3-benzylidene-dihydrofurochromen-2-ones: promising intermediates for biflavonoid synthesis.

A route to 3-benzylidene dihydrofurochromen-2-ones from 2H-chromenes is described. Lactonization of 2H-chromenes was achieved using a two-step cyclopropanation-rearrangement sequence. Subsequent conversion of these intermediates to the corresponding α-benzylidene lactones was achieved by lithium enolate Aldol reaction, followed by base-promoted elimination of the aldolate mesylates. The alkene geometry was found to be base-dependent. While KO t Bu favored formation of the E-isomer, DBU showed a slight preference for the Z-isomer. In further studies, these 3-benzylidene dihydrofurochromen-2-ones were converted to polyaromatic structures possessing all the required functionality for biflavonoid synthesis.

The role of chamaejasmine in cellular apoptosis and autophagy in MG-63 cells.

BACKGROUND: Osteosarcoma (OS) is the most common malignant neoplasm in children and adolescents with a very high propensity for local invasion and poor response to current therapy. Anti-cancer effect of chamaejasmine is newly discovered from Stellera chamaejasmine L. Our study focuses on investigating the effect of chamaejasmine on the cellular apoptosis, proliferation, autophagy, and the underlying mechanisms in MG-63. METHODS: Our study investigated the concentration of chamaejasmine in MG-63 cells by MTT and verified that chamaejasmine inhibited cell invasion by transwell. We also used Hoechst staining as well as apoptotic associated-proteins in MG-63 cells. Meanwhile, we also detected the lysophagesome and autophagsome by Lysotracker. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) knockdown was performed with siRNA. RESULTS: Our results show that chamaejasmine exerts cellular growth inhibition, pro-apoptotic and pro-autophagic effect via activating AMPK in MG-63 cells. Furthermore, chamaejasmine significantly increases autophagic cell via the inhibition of mammalian target of rapamycin (mTOR) and activation of AMPK signaling pathways. Administrated with chamaejasmine also induces reactive oxygen species (ROS) generation, indicating cross-talking between these two primary modes of programmed cell death. CONCLUSION: Our results show that chamaejasmine promotes apoptosis and autophagy by activating AMPK/mTOR signaling pathways with involvement of ROS in MG-63 cells. Chamaejasmine is a promising anti-cancer agent in OS treatment, and further studies are needed to confirm its efficacy and safety in vivo or other cancer cells.

Chamaejasmine Isolated from Wikstroemia dolichantha Diels Suppresses 2,4-Dinitrofluoro-benzene-Induced Atopic Dermatitis in SKH-1 Hairless Mice.

Plants of the genus Wikstroemia have long been used as traditional medicines to treat diseases like pneumonia, rheumatism, and bronchitis. This study was designed to determine the effect of chamaejasmine, a biflavonoid present in W. dolichantha, on atopic dermatitis (AD)-like skin lesions in a 2,4-dinitrochlorobenzene (DNCB)-induced murine model of AD. Initially, we examined the anti-allergic activities of ten flavonoids from W. dolichantha by measuring ß-hexosaminidase release from RBL-2H3 cells. Subsequently, an SKH-1 hairless mouse model of AD was developed based on the topical application of DNCB. Chamaejasmine (0.5%) or pimecrolimus (1%, positive control) were applied to dorsal skins of DNCB-sensitized AD mice for two weeks. Serum IL-4 and IgE levels were determined using enzyme-linked immunosorbent assay kits and transepidermal water loss (TEWL) and skin hydration were measured using a Tewameter TM210 and a SKIN-O-MAT, respectively. Of the ten flavonoids isolated from W. dolichantha, chamaejasmine most potently inhibited DNP-specific IgE-induced degranulation in RBL-2H3 cells. Topical administration of chamaejasmine attenuated the clinical symptoms of DNCB-induced dermatitis (i.e., itching, dryness, erythema, and edema). Histological analyses demonstrated that dermal thickness and mast cell infiltration in dermis were significantly reduced by chamaejasmine. In addition, 0.5% chamaejasmine inhibited DNCB-induced increases in total IL-4 and IgE levels in serum, improved skin barrier function, and increased epidermis moisture. Our findings suggest chamaejasmine might be an effective therapeutic agent for the treatment of atopic diseases.

Chamaejasmine B Induces the Anergy of Vascular Endothelial Cells to VEGFA Pro-angiogenic Signal by Autophagic Regulation of VEGFR2 in Breast Cancer.

The neovascularization functions essentially for malignant upgrading and predicts poor prognosis in multiple cancers, which make it the highly effective strategy for clinical treatment. Unfortunately, the known anti-angiogenic therapies show low effectiveness against breast cancer. Recently, rebalancing the pro-angiogenic property in microenvironment shows great advantages and attracts increasing attention for breast cancer treatment. Herein, we for the first time reported that Chamaejasmine B (ICJ), extracted from Stellera chamaejasme L., possessed potent anti-angiogenic effect in breast cancer. By Transwell, tube formation and aortic-ring assays, ICJ efficiently suppressed the neovascularization potential in tumor-HUVEC co-culture model. In Matrigel plug assay, the efficacy of ICJ was further identified in vivo. Mechanistically, with little influence on HUVEC apoptosis, ICJ obviously induced autophagy as proved by the elevated LC3I/II ratio, dotted distribution of LC3 and upregulated Beclin-1. Moreover, by associating with LC3 and in turn, inhibiting the level of VEGFR2, the anti-angiogenesis efficacy was closely dependent on the initiation of autophagy. Above results proved that, by attenuating the pro-angiogenic communication through VEGFR2, ICJ is a novel angiogenic inhibitor and will be a promising supplement for anti-angiogenic chemotherapy for breast cancer.