Warifteine and milonine, alkaloids isolated from Cissampelos sympodialis Eichl: cytotoxicity on rat hepatocyte culture and in V79 cells

Melo, Patrícia S.; Cavalcante, Horacinna Maria de Medeiros; Barbosa-Filho, José Maria; Diniz, Margareth de Fátima Formiga Melo; Medeiros, Isac Almeida de; Haun, Marcela

doi:10.1016/s0378-4274(03)00064-x

Cited by 34 publications

(31 citation statements)

References 28 publications

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“…Three independent end-point assays for in vitro cytotoxicity were used: the nucleic acid content (NAC), tetrazolium reduction (MTT) and neutral red uptake (NRU). As a result, milonine presented lesser toxicity than warifteine in both cell cultures [10].…”

Section: +mentioning

confidence: 89%

Cardiovascular Effects Elicited by Milonine, a New 8,14‐Dihydromorphinandienone Alkaloid

Cavalcante

Ribeiro

Silva

et al. 2010

Basic Clin Pharma Tox

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Abstract:The mechanisms underlying the cardiovascular responses evoked by milonine (i.v.), an alkaloid, were investigated in rats. In normotensive rats, milonine injections produced hypotension and tachycardia, which were attenuated after N w -nitro-L-arginine methyl esther (L-NAME; 20 mg ⁄ kg, i.v.). In phenylephrine (10 lM), pre-contracted mesenteric artery rings, milonine (10 )10 M to 3 · 10 )4 M) caused a concentration-dependent relaxation (EC 50 = 1.1 · 10 )6 M, E max = 100 € 0.0%) and this effect was rightward shifted after either removal of the vascular endothelium (EC 50 = 1.6 · 10 )5, p < 0.001), or after L-NAME 100 lM (EC 50 = 6.2 · 10 , p < 0.001). Milonine also reduced CaCl 2 -induced contraction in Ca 2+ -free solution containing KCl (60 mM). In conclusion, using combined functional and biochemical approaches, we demonstrated that the hypotensive and vasorelaxant effects produced by milonine are, at least in part, mediated by the endothelium, likely via nitric oxide release, activation of nitric oxide-cGMP pathway and opening of K + channels.

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Section: +mentioning

confidence: 89%

Cardiovascular Effects Elicited by Milonine, a New 8,14‐Dihydromorphinandienone Alkaloid

Cavalcante

Ribeiro

Silva

et al. 2010

Basic Clin Pharma Tox

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“…When testing the cytotoxicity of the alkaloids warifteine and milonine, Melo et al (2003) found similar IC 50 values in hepatocytes and fibroblasts and demonstrated that the toxic effects of both compounds are independent of the cytochrome P450 metabolism system.…”

Section: Discussionmentioning

confidence: 81%

Cytotoxicity, genotoxicity and mechanism of action (via gene expression analysis) of the indole alkaloid aspidospermine (antiparasitic) extracted from Aspidosperma polyneuron in HepG2 cells

et al. 2015

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Aspidospermine is an indole alkaloid with biological properties associated with combating parasites included in the genera Plasmodium, Leishmania and Trypanossoma. The present study evaluated the cytotoxicity (resazurin test), genotoxicity (comet assay) and mechanism of action (gene expression analysis via qRT-PCR) of this alkaloid in human HepG2 cells. The results demonstrated that treatment with aspidospermine was both cytotoxic (starting at 75 lM) and genotoxic (starting at 50 lM). There was no significant modulation of the expression of the following genes: GSTP1 and GPX1 (xenobiotic metabolism); CAT (oxidative stress); TP53 and CCNA2 (cell cycle); HSPA5, ERN1, EIF2AK3 and TRAF2 (endoplasmic reticulum stress); CASP8, CASP9, CASP3, CASP7, BCL-2, BCL-XL BAX and BAX (apoptosis); and PCBP4, ERCC4, OGG1, RAD21 and MLH1 (DNA repair). At a concentration of 50 lM (non-cytotoxic, but genotoxic), there was a significant increase in the expression of CYP1A1 (xenobiotic metabolism) and APC (cell cycle), and at a concentration of 100 lM, a significant increase in the expression of CYP1A1 (xenobiotic metabolism), GADD153 (endoplasmic reticulum stress) and SOD (oxidative stress) was detected, with repression of the expression of GR (xenobiotic metabolism and oxidative stress). The results of treatment with aspidospermine at a 100 lM concentration (the dose indicated in the literature to achieve 89 % reduction of the growth of L. amazonensis) suggest that increased oxidative stress and an unfolded protein response (UPR) occurred in HepG2 cells. For the therapeutic use of aspidospermine (antiparasitic), chemical alteration of the molecule to achieve a lower cytotoxicity/genotoxicity in host cells is recommended.

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“…Cytotoxic effects of isolated warifteine and milonine were demonstrated in cultured hepatocytes and V79 fi broblasts. However, milonine was less toxic than warifteine in both cell cultures (Melo et al, 2003).…”

Section: Introductionmentioning

confidence: 81%

Antidepressant effects of total tertiary alkaloid fraction of Cissampelos sympodialis Eichler in rodents

Mendonça-Netto¹,

Varela²,

Fechine³

et al. 2008

Rev. bras. farmacogn.

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Warifteine and milonine, alkaloids isolated from Cissampelos sympodialis Eichl: cytotoxicity on rat hepatocyte culture and in V79 cells

Cited by 34 publications

References 28 publications

Cardiovascular Effects Elicited by Milonine, a New 8,14‐Dihydromorphinandienone Alkaloid

Cardiovascular Effects Elicited by Milonine, a New 8,14‐Dihydromorphinandienone Alkaloid

Cytotoxicity, genotoxicity and mechanism of action (via gene expression analysis) of the indole alkaloid aspidospermine (antiparasitic) extracted from Aspidosperma polyneuron in HepG2 cells

Antidepressant effects of total tertiary alkaloid fraction of Cissampelos sympodialis Eichler in rodents

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