Amaryllidaceae alkaloids from Crinum latifolium with cytotoxic, antimicrobial, antioxidant, and anti-inflammatory activities.

Four novel and potently bioactive Amaryllidaceae alkaloids, 4,8-dimethoxy-cripowellin C (1), 4,8-dimethoxy-cripowellin D (2), 9-methoxy-cripowellin B (3), and 4-methoxy-8-hydroxy-cripowellin B (4), together with one known alkaloid, cripowellin C (5) were isolated from the 95% EtOH extract of the bulbs of Crinum latifolium. Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR as well as spectroscopy high resolution mass spectrometry. All isolates were in vitro evaluated for their cytotoxic activity against seven lung cancer cell lines, in addition to antimicrobial activity for eight bacteria, scavenging potential using ABTS·+ and DPPH test, and anti-inflammatory activity for Cox-1 and Cox-2 which had not previously been tested for crinane-type alkaloids with the cleavage between C-1 and C-13. Consequently, alkaloids 1-5 exhibited potent cytotoxicity against all of seven tested tumor cell lines with (IC50 < 30 nM). Alkaloids 3 and 4 displayed the significant antimicrobial activity with IC50 values <0.50 mM and antioxidant activity in the ABTS·+ and DPPH test. Additionally, Alkaloids 1-5 exhibited comparable inhibition of Cox-1 (>64%) and Cox-2 (>90%) with positive control.

Effects of arsenic trioxide (As(2)O(3)) on airway remodeling in a murine model of bronchial asthma.

We investigated the effects of arsenic trioxide (As(2)O(3)) as a possible approach for preventing airway remodeling in a murine model of bronchial asthma induced by ovalbumin (OVA) challenge. Forty Balb/c mice were randomly assigned to 1 of 4 groups (10 mice/group) as follows: controls (challenged with sterile saline inhalation only); OVA-challenged, no treatment; OVA-challenged, treated with dexamethasone; and OVA-challenged, treated with As(2)O(3). All mice were sensitized by intraperitoneal injection with 10% OVA at 2 weeks prior to saline or OVA inhalation challenge. Challenges were for 8 weeks. After OVA challenge, typical asthma-like morphology changes in the bronchi and lung tissues were observed by hematoxylin-eosin staining and pulmonary function indices were reduced compared with controls. Changes in pulmonary indices and lung tissues were similar in the dexamethasone and As(2)O(3) groups and were in between those of the untreated and control groups. Compared with the untreated group, transforming growth factor ß1, vascular endothelial growth factor, and matrix metalloproteinase-9 protein levels and mRNA expression were decreased in lung tissues of the dexamethasone and As(2)O(3) groups. Our results suggest that steroids and As(2)O(3) can inhibit airway remodeling in chronic asthma by mechanisms related to inhibiting the expression of the 3 aforementioned mediators.