RESUMEN
Stilbenoids, a group of phytoalexin polyphenols produced by plants as a defence mechanism in response to stress conditions, are known for their anti-inflammatory potential. Pinosylvin, a naturally occurring molecule traditionally found in pinus trees, was here identified in Pinus nigra subsp. laricio var. calabrica from Southern Italy through HPLC analysis. Both this molecule and its well-known analogue resveratrol, the most famous wine polyphenol, were compared for their in vitro potential anti-inflammatory activity. Pinosylvin significantly inhibited the release of pro-inflammatory cytokines (TNF-α and IL-6) and NO mediator in LPS-stimulated RAW 264.7 cells. Moreover, its ability to inhibit the JAK/STAT signaling pathway was assessed: Western blot analyses showed a downregulation of both phosphorylated JAK2 and STAT3 proteins. Finally, in order to verify whether this biological activity could be attributed to a direct interaction of pinosylvin with JAK2, a molecular docking study was performed, confirming the capability of pinosylvin to bind the active site of the protein.
RESUMEN
Different phytochemical compounds have been demonstrated to modulate the JAK/STAT signaling pathway. Here, three Cachrys species from Southern Italy were investigated for both the phytochemical profile and the potential anti-inflammatory properties. The aerial parts were extracted with methanol through Naviglio Extractor®, an innovative solid-liquid extraction technique that allows to obtain high quality extracts by working with gradient pressure. Extracts were analyzed with GC-MS and standardized in furanocoumarin content, resulting rich in xanthotoxin, bergapten and isopimpinellin. Given the known ability of bergapten to inhibit the JAK/STAT signaling pathway by decreasing the levels of pro-inflammatory cytokines (TNF-α, IL-6) and inflammatory mediators (NO) in RAW 264.7 cells activated by LPS, Cachrys extracts were investigated for their biological properties. The results obtained in this study showed that Cachrys pungens extract, presenting the highest content in furanocoumarins (7.48 ± 0.48 and 2.94 ± 0.16 mg/50 mg of extract for xanthotoxin and bergapten, respectively), significantly decreased STAT3 protein levels, pro-inflammatory cytokines (TNF-α, IL-6) and increased IL-10 anti-inflammatory cytokine. Cachrys ferulacea significantly decreased JAK2 phosphorylation, being even more effective than bergapten. In conclusion, investigated extracts could be potential candidates for the search of novel anti-inflammatory agents acting via inhibiting the JAK/STAT signaling pathway.
RESUMEN
Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.
