Bone protective effects of purified extract from Ruscus aculeatus on ovariectomy-induced osteoporosis in rats.

Ruscus aculeatus is a source of steroidal saponins that could mimic sex hormones and could help alleviate the risk of fracture in osteoporotic patients. The aim of the present study was to evaluate the in vitro effects of an extract from R. aculeatus (ERA) on the proliferation of human osteoblast-like SaOS-2 cell line and to investigate the effects of the ERA administered orally for 10 weeks at three doses (50, 100 and 200 mg/kg) on the bone structure of rats with estrogen deficiency induced by bilateral ovariectomy. Bone turnover markers, hormones, histopathological and radiological disturbances were evidenced in the ovariectomized rats. ERA recovered most of the affected parameters in a dose-dependent manner similar to diosgenin and alendronate used as positive comparators. The main active compounds of ERA (ruscogenin and neoruscogenin) were docked into the Vit. D receptor and oestrogen receptors alpha and beta, and stable complexes were found with binding scores equal to those of estradiol and diosgenin. The findings of this study provide for the first time an insight into the effects of ERA on bone structure and suggest that ERA could be developed as a potential candidate for the prevention of postmenopausal osteoporotic complications.

Delineation of proapoptotic signaling of anthracene-shelled M2L4 metallacapsules and their synergistic activity with curcumin in cisplatin-sensitive and resistant tumor cell lines.

Since the introduction of cisplatin into clinical practice a few decades ago, the topic of metal-based drugs has expanded significantly. Recent examples emphasize on metallosupramolecules as an emerging class of compounds with diverse properties. They can trigger unique cellular events in malignant cells or serve as molecular hosts for various biologically active compounds, including anticancer agents. The anthracene-shelled M2L4 coordination nanocapsules under research have already proved very high anticancer potency with remarkable selectivity and lack of cross-resistance. In this study, we provide an oncopharmacological evaluation of the Pt(II)- and Pd(II)-clipped M2L4 nanocapsules; we report a thorough analysis of their synergistic effects in combined treatments with the pleiotropic anticancer agent curcumin. We examined changes in cellular expression of several apoptosis-related proteins in a panel of tumor cell lines with different chemosensitivity towards cisplatin, i.e. HT-29, HL-60 and its resistant strains HL-60/CDDP and HL-60/Dox, in order to assess the molecular mechanisms of their antitumor activity The results of the immunoassay concluded activation of the mitochondrial apoptotic pathway in all the screened tumor lines. A prevalent modulation of the extrinsic apoptotic signaling cascade was observed in the chemoresistant variants. Curcumin interactions of the tested compounds were estimated against the cisplatin-refractory cell line HT-29 via the Chou-Talalay method (CTM), whereby the palladium species yielded superior synergistic activity as compared to their platinum analogues.