Ana Possenti

Antiulcerogenic activity of crude hydroalcoholic extract of Rosmarinus officinalis L.

Rosmarinus officinalis L. crude hydroalcoholic (70%) extract was evaluated for antiulcerogenic activity employing different experimental models. The crude hydroalcoholic extract (CHE) decreased the ulcerative lesion index produced by indomethacin, ethanol and reserpine in rats. No antisecretory activity was observed on pyloric ligation model. The previous administration of L-NAME, a NO-synthase inhibitor, did not reduce the antiulcerogenic activity of CHE in ethanol induced ulcer model, suggesting that the pharmacological mechanism has no relationship with nitric oxide (NO). Whereas when the animal groups were treated with indomethacin, using the same experimental model, CHE did not reduce the antiulcerogenic activity, suggesting that the pharmacological mechanism has no relationship with prostaglandins. The previous treatment with N-ethymaleimide, a thiol blocker, including mucosal nonprotein sulfhydryl groups, reduced the anitulcerogenic activity of CHE on ethanol induced ulcer model. This result suggests that the crude hydroalcoholic extract of R. officinalis L. has active substances that increase the mucosal nonprotein sulfhydryl groups content. In another hypothesis, the pharmacological mechanism could be attributed to the activity of antioxidant compounds found in the crude hydroalcoholic extract which can react with N-ethylmaleimide.

Evaluation of the antiulcerogenic activity of friedelan-3β-ol and friedelin isolated from Maytenus ilicifolia (Celastraceae)

An easy methodology for triterpene isolation is shown. Evaluation in rats for antiulcer activity of friedelan-3beta-ol 1 and friedelin 2. The two triterpenes isolated from the leaves of Maytenus ilicifolia, did not decrease gastric ulcers when tested on indometacine induced ulcer model in rats.

Cytotoxicity and antitumoral activity of dichloromethane extract and its fractions from Pothomorphe umbellata

The cytotoxicity of the dichloromethane crude extract (DCE), obtained from the aerial parts of Pothomorphe umbellata (L.) Miq (Piperaceae), was evaluated against nine human cancer cell lines (MCF-7, NCI-ADR/RES, OVCAR-3, PC-3, HT-29, NCI-H460, 786-O, UACC-62, K-562). The DCE presented antiproliferative activity with good potency against all cell lines at low concentrations (between 4.0 and 9.5 microg/mL) and with selectivity (1.55 microg/mL) for the leukemia cell line (K-652). DCE (100, 200, 300 and 400 mg/kg, ip) was also evaluated in the Ehrlich ascites tumor model. Both the survival number and the life span of the animals that died increased by at least 45 and 50%, respectively (8 animals per group), demonstrating P. umbellata extract potential anticancer activity. The results of the in vivo antitumor activity prompted the fractionation of the crude extract. The crude extract was submitted to dry column chromatography with dichloromethane-methanol (99:1). The column effluent fractions were extracted with methanol, dried under vacuum yielding fractions FR1 (less polar), FR2 (medium polarity), and FR3 (polar), which were analyzed for their growth inhibition or cytotoxic properties by a 48-h sulforhodamine B cell viability assay by measuring the total protein content. FR1 demonstrated high potency and cytotoxicity, a result compatible with the high toxicity of oxalic acid; FR2, containing 4-nerolidylcathecol, presented the lowest cytotoxic activity compared to the other two fractions but with selectivity for prostate cancer cell line; FR3, containing a mixture of steroids described in the literature as possessing various biological activities, also presented potent anticancer in vitro activity. These results suggest that P. umbellata DCE in vivo antitumor activity may be a consequence of the activity of different active principles.

In vitro and in vivo anticancer activity of extracts, fractions, and eupomatenoid-5 obtained from Piper regnellii leaves.

Despite numerous studies with the Piper genus, there are no previous results reporting in vitro or in vivo Piper regnellii (Miq.) C. DC. var. regnellii anticancer activity. The aim of this study was to investigate P. regnellii in vitro and in vivo anticancer activity and further identify its active compounds. In vitro antiproliferative activity was evaluated in 8 human cancer cell lines: melanoma (UACC-62), breast (MCF7), kidney (786-0), lung (NCI-H460), prostate (PC-3), ovary (OVCAR-3), colon (HT29), and leukemia (K-562). Total growth inhibition (TGI) values were chosen to measure antiproliferative activity. Among the cell lines evaluated, eupomatenoid-5 demonstrated better in vitro antiproliferative activity towards prostate, ovary, kidney, and breast cancer cell lines. In vivo studies were carried out with Ehrlich solid tumor on Balb/C mice treated with 100, 300, and 1000 mg/kg of P. regnellii leaves dichloromethane crude extract (DCE), with 30 and 100 mg/kg of the active fraction (FRB), and with 30 mg/kg of eupomatenoid-5. The i. p. administration of DCE, FRB, and eupomatenoid-5 significantly inhibited tumor progression in comparison to control mice (saline). Therefore, this study showed that neolignans of Piper regnellii have promising anticancer activity. Further studies will be undertaken to determine the mechanism of action and toxicity of these compounds.

In Vitro, In Vivo and In Silico Analysis of the Anticancer and Estrogen-like Activity of Guava Leaf Extracts

Anticancer drug research based on natural compounds enabled the discovery of many drugs currently used in cancer therapy. Here, we report the in vitro, in vivo and in silico anticancer and estrogen-like activity of Psidium guajava L. (guava) extracts and enriched mixture containing the meroterpenes guajadial, psidial A and psiguadial A and B. All samples were evaluated in vitro for anticancer activity against nine human cancer lines: K562 (leukemia), MCF7 (breast), NCI/ADR-RES (resistant ovarian cancer), NCI-H460 (lung), UACC-62 (melanoma), PC-3 (prostate), HT-29 (colon), OVCAR-3 (ovarian) and 786-0 (kidney). Psidium guajavas active compounds displayed similar physicochemical properties to estradiol and tamoxifen, as in silico molecular docking studies demonstrated that they fit into the estrogen receptors (ERs). The meroterpene-enriched fraction was also evaluated in vivo in a Solid Ehrlich murine breast adenocarcinoma model, and showed to be highly effective in inhibiting tumor growth, also demonstrating uterus increase in comparison to negative controls. The ability of guajadial, psidial A and psiguadials A and B to reduce tumor growth and stimulate uterus proliferation, as well as their in silico docking similarity to tamoxifen, suggest that these compounds may act as Selective Estrogen Receptors Modulators (SERMs), therefore holding significant potential for anticancer therapy.

Characterization of a refinement of the “pylorus ligation” model of rat gastric ulceration resulting in “no pain” and a more specific pharmacological response

INTRODUCTION The pharmacological assessment of the factors for gastric protection of a test substance should involve experimental models that can determine the involvement of cytoprotective factors, as well as their influence on the secretion of hydrochloric acid. The original protocol of pylorus ligation in rats proposed by Shay et al. in 1945, still in use today, provides a latency time of 240 min without considering the effect of postoperative pain in the mechanisms of peptic ulcer. This paper proposes a modification of this experimental protocol by eliminating the pain throughout the postoperative period, as a refinement of the test with consequent improvement of the pharmacological response. METHODS Adult male Wistar/Uni rats underwent surgical ligation of the pylorus and were kept anesthetized throughout the experimental period (4h) in contrast to the other experimental groups that followed the original protocol proposed by Shay et al., 1945. RESULTS We were able to determine effective doses for a positive control, as well as of a variety of secretagogues in the new experimental protocol proposed. DISCUSSION The suppression of post-surgical pain, through the use of anesthesia throughout the experimental period, brought several benefits for the study of gastric acid secretion, rendering a more homogeneous pharmacologic response in non-inbred animals, thus being an effective experimental procedure.