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Context: Solidago virgaurea L. (Asteraceae) is traditionally used as an anti-inflammatory for the treatment of various symptoms including cystitis. However, little is known concerning the constituents responsible for this activity and the mechanism of their action. Objective: To assess the anti-inflammatory activity of the phenolic-rich fraction of S. virgaurea aerial parts in rats, isolate and assess the activity of the major compounds present. Materials and methods: An HPLC method was developed for the analysis of the phenolic-rich fraction (EtFr). The in vivo anti-inflammatory activity of the EtFr and four isolated compounds (at 25 and 50 mg/kg) were assessed in adult male rats using the carrageenan-induced rat paw oedema model. The levels of the pro-inflammatory cytokines (TNF-a and IL-1b) were measured using ELISA. Results: 3,5-O-Dicaffeoylquinic acid (1), 3,4-O-dicaffeoylquinic acid (2), 3,4,5-O-tricaffeoylquinic acid (3) and 4,5-O-dicaffeoylquinic acid (4) were isolated from EtFr. Compound 3 (50 mg/kg) showed a highly significant activity in inhibiting the oedema volume after 3 h (88% of the activity of indomethacin at 10 mg/kg). The EtFr and the isolated compounds largely inhibited the excessive production of the inflammatory mediators TNF-a and IL-1b. Discussion and conclusion: This is the first report of 3,4,5-tri-O-caffeoylquinic acid (3) in Solidago species. The tricaffeoylquinic acid (3) showed a significantly higher activity than the other three dicaffeoylquinic acids (1, 2, 4) and indomethacin in reduction of TNF-a and IL-1b concentrations (8.44 ± 0.62 and 5.83 ± 0.57 pg/mL compared to 12.60 ± 1.30 and 52.91 ± 5.20 pg/mL induced by indomethacin, respectively). ARTICLE HISTORY

In addition to four previously reported compounds: proximadiol (1), 5α-hydroxy-β-eudesmol (2), 1β-hydroxy-β-eudesmol (4) and 1β-hydroxy-α-eudesmol (5), two new sesquiterpenes, 5α-hydroperoxy-β-eudesmol (3) and 7α,11-dihydroxy-cadin-10(14)-ene (6) were isolated from the unsaponifiable fraction of the petroleum ether extract of Cymbopogon proximus STAPF. Isolation of compounds 2, 4 and 5 from the genus Cymbopogon is reported for the first time. The structure elucidation of these compounds was based primarily on 1D and 2D-NMR analyses.

The activating immune ligands, MICA/B, act as a "kill me" signal through the NKG2D receptor expressed on natural killer (NK) cells. Recently, the oncogenic miR-20a was found to mediate immune escape through repressing MICA/B levels in breast cancer (BC) cells. However, targeting miR-20a-MICA/B using natural compounds has rarely been investigated. Our group has successfully isolated 3'-O-acetylvitexin that showed cytotoxic effects against colon cancer cells but has never been evaluated in BC. Our aim is to investigate the effects of 3'-O-acetylvitexin on BC cell lines and to further elucidate its molecular mechanism of action. The results showed that 3'-Oacetylvitex in depicted a more pronounced dose-dependent repression of TNBC cellular viability, colonogenicity and migration capacity than Vitexin. 3'-O-acetylvitexin treatment resulted in a marked dose-dependent repression of miR-20a with a concomitant dose-dependent increase in MICA/B expression. In conclusion, 3'-O-acetylvitexin might act as a promising therapeutic agent for TNBC patients.

Background: Recently, a novel crosstalk between non-coding RNAs (ncRNAs) has been casted. However, this has been seldomly investigated in metastatic BC (mBC). H19 and miR-486-5p role in mBC is controversial. ICAM-1 is a recently recognized metastatic engine in mBC. Natural compounds were recently found to alter ncRNAs/target circuits. Yet, Hesperitin modulatory role in altering such circuits has never been investigated in mBC. Objective: The aim of this study is to investigate the impact of hesperitin on miR-486-5p/H19/ICAM-1 axis Methodology: BC patients (n=20) were recruited in the study. Bioinformatic analysis was performed using different prediction softwares. MDA-MB-231 and MCF-7 cells were cultured and transfected using several oligonucleotides or treated with serial dilutions of hesperitin. RNA was extracted and gene expression analysis was performed using q-RT-PCR. ICAM-1 protein levels were assessed using human ICAM-1 Elisa Kit. Cytotoxic potential of hesperitin against normal cells was assessed by LDH assay. Several functional analysis experiments were performed such as MTT, colony forming and migration assays. Results: The study showed that miR-486-5p and H19 has a paradoxical expression profiles in mBC patients. miR-486-5p mimics and H19 siRNAs repressed ICAM-1 and halted mBC hallmarks. A novel crosstalk between miR-486-5p and H19 was observed highlighting a bi-directional relationship between them. Hesperetin restored the expression of miR-486-5p, inhibited H19 lncRNA and ICAM-1 expression and selectively regressed mBC cell aggressiveness. Conclusion: miR-486-5p and H19 are inter-connected upstream regulators for ICAM-1 building up miR-486-5p/H19/ICAM-1 axis that has been successfully tuned in mBC cells by hesperitin