TL;DR: This study provides a sound mechanistic base for some of the traditional uses of the plant in hyperactive gut states, in addition to providing the first evidence for verapamil to possess additional AChE inhibitory activity.
Abstract: The aim of this investigation was to see if the crude extract of Sarcococca saligna (Ss.Cr) contains chemicals with gut function inhibitory activity by using in vitro and in vivo assays. Ss.Cr caused a dose-dependent (0.03 - 3 mg/mL) inhibitory effect on K+-induced contractions in rat stomach fundus, guinea-pig ileum and rabbit jejunum preparations. The calcium channel blocking(CCB) activity was confirmed when Ss.Cr caused a rightward shift in the Ca++ dose-response curves. It also potentiated, at lower do-ses (0.001 - 0.03 mg/mL), the contractile effect of a fixed dose of acetylcholine (ACh), similar to physostigmine, and suppressed the effect of ACh at higher doses (0.3 - 1.0 mg/mL). Both Ss.Cr and physostigmine inhibited acetylcholinesterase (AChE), in the in vitro assay, confirming the AChE inhibitory activity. In the in vivo studies, Ss.Cr exhibited antidiarrheal and antisecretory activities against castor oil-induced diarrhea and intestinal fluid accumulation in mice. Characteristic steroidal compounds of the plant (saracocine, saracodine, saracorine and alkaloid-C), exhibited a similar combination of AChE inhibitory and CCB activities. Thus this study provides a sound mechanistic base for some of the traditional uses of the plant in hyperactive gut states, in addition to providing the first evidence for verapamil to possess additional AChE inhibitory activity. Furthermore, these characteristic compounds with dual activity may be good candidates for further studies on their usefulness in Alzheimer's disease.
TL;DR: The structure-activity relationship (SAR) studies suggested that the major interaction of the enzyme-inhibitor complexes are due to hydrophobic and cation-pi interactions inside the aromatic gorge of these cholinesterases.
TL;DR: In this article, seven new steroidal alkaloids, 2-hydroxysalignarine-E, salignarine-F and salonine-C, were isolated from the MeOH extract of Sarcococca saligna, along with the six known alkalifiers dictyophlebine (8), epipachysamine-D, saracosine (10), iso-N-formylchonemorphine (11), sarcodinine (12), and alkaloid-C (13).
Abstract: Seven new steroidal alkaloids, 2-hydroxysalignarine-E (=(2′E,20S)-20-(dimethylamino)-2β-hydroxy-3β-(tigloylamino)pregn-4-ene; 1), 5,6-dihydrosarconidine (=(20S)-20-(dimethylamino)-3β-(methylamino)-5α-pregn-16-ene; 2), salignamine (=(20S)-20-(methylamino)-3β-methoxypregna-5,16-diene; 3), 2-hydroxysalignamine (=(20S)-20-(dimethylamino)-2β-hydroxy-3β-methoxypregna-5,16-diene; 4), salignarine-F (=(2′E, 20S)-20-(dimethylamino)-4β-hydroxy-3β-(tigloylamino)pregn-5-ene; 5), salonine-C (=(2′E,20S)-20-(dimethylamino)-3β-(tigloylamino)pregna-4,14-diene; 6), and N-[formyl(methyl)amino]salonine-B (=(20S)-20-[formyl(methyl)amino]-3β-methoxypregna-5,16-diene; 7) have been isolated from the MeOH extract of Sarcococca saligna, along with the six known alkaloids dictyophlebine (8), epipachysamine-D (9), saracosine (10), iso-N-formylchonemorphine (11), sarcodinine (12), and alkaloid-C (13). The structures of 1–7 were deduced from spectral data. Compounds 1–13 demonstrated significant activity against acetyl- and butyrylcholinesterase.
TL;DR: A set of 32 previously isolated and tested pregnane-type steroidal alkaloids inhibitors were investigated with respect to their IC(50) values against the AChE enzyme in order to derive CoMFA models using atom-based alignment.
TL;DR: The ethanol extract of S. saligna enhanced the antifungal activity of fluconazole against A. niger and A. treus and no enhancing effect was observed for this plant extract against Aspergillus fumigates at tested contents.
Abstract: Microbial resistance is a major drawback in chemotherapy of microbial or fungal infection disease. In this study, the antifungal activity of ethanol extract of a selected plant (Sarcococca saligna) has been investigated against clinical isolates of Aspergillus niger, Aspergillus treus, Aspergillus flavus, and Aspergillus fumigatus. Also, the enhancement of the antifungal activity of fluconazole by this extract was further evaluated against mentioned test strains. Conventional disk diffusion method was used to assay the antifungal activity of S. saligna ethanol extract in the absence and presence of fluconazole. The highest antifungal activity was observed against A. treus. The ethanol extract of S. saligna enhanced the antifungal activity of fluconazole against A. niger and A. treus and A. flavus. At the highest tested contents (4 mg/disk), 1.15-, 0.64-, and 2.47-fold increases in inhibition zone surface area were observed for A. niger, A. treus, and A. flavus, respectively. However, no enhancing effect was observed for this plant extract against Aspergillus fumigates at tested contents (0.5, 1, 2, 3, and 4 mg/disk). In a separate experiment, the general cytotoxicity of the ethanol extract of S. saligna was examined with brine shrimp assay. This plant extract showed low cytotoxicity against Artemia salina (LC50 = 186 µg/ml).