Spasmolytic Effect of Caulerpine Involves Blockade of Ca2+ Influx on Guinea Pig Ileum

Abstract

In this work, we investigated the spasmolytic effect of caulerpine, a bisindole alkaloid isolated from marine algae of the Caulerpa genus, on guinea pig ileum. Our findings indicated that caulerpine inhibited phasic contractions induced by carbachol (IC50 = 7.0 ± 1.9 × 10−5 M), histamine (IC50 = 1.3 ± 0.3 × 10−4 M) and serotonin (IC50 = 8.0 ± 1.4 × 10−5 M) in a non-selective manner. Furthermore, caulerpine concentration-dependently inhibited serotonin-induced cumulative contractions (pD′2 = 4.48 ± 0.08), shifting the curves to the right with Emax reduction and slope of 2.44 ± 0.21, suggesting a noncompetitive antagonism pseudo-irreversible. The alkaloid also relaxed the ileum pre-contracted by KCl (EC50 = 9.0 ± 0.9 × 10−5 M) and carbachol (EC50 = 4.6 ± 0.7 × 10−5 M) in a concentration-dependent manner. This effect was probably due to inhibition of Ca2+ influx through voltage-gated calcium channels (CaV), since caulerpine slightly inhibited the CaCl2-induced contractions in depolarizing medium without Ca2+, shifting the curves to the right and with Emax reduction. According to these results, the spasmolytic effect of caulerpine on guinea pig ileum seems to involve inhibition of Ca2+ influx through CaV. However, other mechanisms are not discarded.

The Bisindole Alkaloid Caulerpin, from Seaweeds of the Genus Caulerpa, Attenuated Colon Damage in Murine Colitis Model

“…The whole process of extraction and purification was performed in the Laboratory of Pharmaceutical Technology/UFPB. Figure 1 shows the chemical structure of CLP [ 24 ].…”

“…It is present in 80% of the species of algae of the genus Caulerpa; however, it can be found in other algae genera [ 19 ]. Diverse biological activities of CLP have been described, including antinociceptive, anti-inflammatory [ 20 ], antiviral [ 21 ], antituberculosis [ 22 ], antineoplastic [ 23 ], and antispasmodic [ 24 ]. Similar to CLP, other bisindole alkaloids have been shown to have anti-inflammatory activity in different parameters of inflammation and have presented different mechanisms of action, ranging from inhibition of the COX-2 pathway to inhibition of the NFκB and MAP kinase pathways and increased expression of adenosine A2A receptors (A2AR) that have anti-inflammatory activity [ 25 ].…”

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…Albeit an IC 50 for enzyme or receptor inhibition is provided, no mechanism of action studies were reported at the time of publication: alotaketal C ( 224 ) [215]; aspergentisyl A ( 225 ) [216]; A. terreus butyrolactone ( 226 ) [217]; caulerpine ( 227 ) [218]; conicasterol F ( 228 ) [219]; D. avara sesquiterpene ( 229 ) [220]; D. gigantea sterols ( 230 , 231 ) [221]; dysidavarone A ( 232 ) [222]; galvaquinone B ( 233 ) [223]; halicloic acids A and B ( 234 , 235 ) [224]; isochromophilone XI ( 236 ) [225]; leucettamols A and B ( 237 , 238 ) [226]; manadosterol A ( 239 ) [227]; marilines A1 and A2 ( 240 , 241 ) [228]; methyl sarcotroate B ( 242 ) [229]; P. citrinum sorbicillinoid ( 243 ) [230]; phosphoiodyn A ( 244 ) [231]; purpuroines A and D ( 245 , 246 ) [232]; santacruzamate A ( 247 ) [233]; sarcophytonolide N ( 248 ) [234]; sargassumol ( 249 ) [235]; sesquibastadin 1 ( 250 ) [236]; S. glaucum cembranoids ( 251 – 253 ) [237]; symplocin A ( 254 ) [238]; tsitsikammamine A derivative ( 255 ) [239]; V. lanosa bromophenol ( 256 ) [240] ; and X. testudinaria fatty acid ( 257 ) [241]. …”

1H NMR Spectroscopy and MVA to Evaluate the Effects of Caulerpin-Based Diet on Diplodus sargus Lipid Profiles

“…CAU shows structural similarity to endogenous indolamines that modulate animal behaviour and a reduction of aggressive behaviour was described in fish exposed to CAU high dose [ 28 ]. Moreover, as already reported in literature, this metabolite exerts a sedative effect via pathways involving serotonin 5-HT3 receptors [ 29 ]. Therefore, the lower difference in metabolic profiles observed for HD and C individuals may be also explained by the onset of anorexigenic effect with the consequent reduction of the amount of CAU ingested.…”