In vivo schistosomicidal activity of (±)-licarin A-loaded poly(ε-caprolactone) nanoparticles.

Schistosomiasis mansoni is an infectious parasitic disease caused by worms of the genus Schistosoma, and praziquantel (PZQ) is the medication available for the treatment of schistosomiasis. However, the existence of resistant strains reinforces the need to develop new schistosomicidal drugs safely and effectively. Thus, the (±)-licarin A neolignan incorporated into poly-Ɛ-caprolactone (PCL) nanoparticles and not incorporated were evaluated for their in vivo schistosomicidal activity. The (±)-licarin A -loaded poly(ε-caprolactone) nanoparticles and the pure (±)-licarin A showed a reduction in the number of worm eggs present in spleens of mice infected with Schistosoma mansoni. In addition, the (±)-licarin A incorporated in the concentration of 20 mg/kg and 200 mg/kg reduced the number of worms, presenting percentages of 56.3% and 41.7%, respectively.

In vitro and in silico cytotoxicity of hinokinin-loaded PLGA microparticle systems against tumoral SiHa cells.

This work aimed to synthesize poly (D, L-lactic-co-glycolic acid) (PLGA) microparticles containing hinokinin (HNK) and to evaluate their cytotoxic activity against tumoral SiHa cells and non-tumoral HaCaT cells. Hinokinin was incorporated into PLGA (PLGA-HNK) with an encapsulation efficiency of 84.18 ± 2.32%. PLGA and PLGA-HNK were characterized by SEM microscopy and showed spherical morphology with an average size of ∼3.33. Encapsulation efficiency was determined by a calibration curve using UV-vis spectroscopy. PLGA-HNK more active inhibiting proliferation of SiHa cells (IC50 = 14.68 µM) than free HNK (IC50 = 225.5 µM). In relation to HaCaT cells, PLGA-HNK showed no significant difference compared to the negative control. These results led to an increase in HNK bioavailability and thereby, biological activity. In silico prediction analysis suggests that HNK is cytotoxic against SiHa cells with E6 and MDM2 inhibition as possible main mechanism of action.

In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (-)-cubebin derivatives (-)-hinokinin and (-)-O-benzylcubebin.

(-)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (-)-hinokinin (HK) and (-)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 - cyclooxygenase-2) interaction in comparison with CUB and HK.

In vivo analgesic activity, toxicity and phytochemical screening of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine.

ETHNOPHARMACOLOGICAL RELEVANCE: Psidium cattleianum Sabine is extensively used in Brazilian traditional medicine to treat several diseases including painful disorders. Aim of the study to investigate the toxicity and the possible analgesic activities of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine (ELPCS), to support its use in folk medicine. To screen the major phytochemical constituents of this extract and evaluate their antioxidant activity. MATERIALS AND METHODS: ELPCS was assessed for its antioxidant activity using the DPPH model. Its analgesic activity was examined using mouse models of acetic acid-induced writhing and hot plate paw licking models. The major phytochemical constituents of the extract were screened; their toxicity on LLC-MK2 mammalian cells was evaluated. RESULTS: ELPCS exhibited significant peripheral analgesic activity at doses of 60, 80, 100, 200 and 400mg/kg in mice, but it did not display central analgesic activity and not was toxic to LLC-MK2 cell (LD50>400 µg/mL). The extract exhibited free radical scavenging activity as evidenced by IC50 values (15.9 µg/mL) obtained by the DPPH method. Phytochemical screening detected flavonoids, saponins, cardiac glycosides, anthraquinones, and tannins. CONCLUSIONS: The results of the experimental studies proved the analgesic activity of ELPCS and supported the traditional use of this plant.

In vitro efficacy of the essential oil of Piper cubeba L. (Piperaceae) against Schistosoma mansoni.

In this paper, cercariae, schistosomula, and adult Schistosoma mansoni worms were incubated in vitro with the essential oil of Piper cubeba (PC-EO) at concentrations from 12.5 to 200 µg/mL, and the viability was evaluated using an inverted microscopy. The effects of PC-EO at 100 and 200 µg/mL on the stages of S. mansoni were similar to those of the positive control (PZQ at 12.5 µg/mL), with total absence of mobility after 120 h. However, at concentrations from 12.5 to 50 µg/mL, PC-EO caused a reduction in the viability of cercariae and schistosomula when compared with the negative control groups (RPMI 1640 or dechlorinated water) or (RPMI 1640 + 0.1% DMSO or dechlorinated water + 0.1% DMSO). On the other hand, adult S. mansoni worms remained normally active when incubated with PC-EO at concentrations of 12.5 and 25 µg/mL, and their viabilities were similar to those of the negative control groups. In addition, at concentrations ranging from 50 to 200 µg/mL, separation of all the coupled adult worms was observed after 24 h of incubation, which is related to the fact of the reduction in egg production at this concentration. The main chemical constituents of PC-EO were identified by gas chromatography-mass spectrometry as being sabinene (19.99%), eucalyptol (11.87%), 4-terpineol (6.36%), ß-pinene (5.81%), camphor (5.61%), and δ-3-carene (5.34%). The cytotoxicity of the PC-EO was determined, and a significant cytotoxicity was only obtained in the concentration of 200 µg/mL after 24 h treatment. The results suggest that PC-EO possesses an effect against cercariae, schistosomula, and adult worms of the S. mansoni.

In vitro antileishmanial and antimalarial activities of tetrahydrofuran lignans isolated from Nectandra megapotamica (Lauraceae).

Seven tetrahydrofuran lignans, isolated from Nectandra megapotamica (Lauraceae), were evaluated for their in vitro antileishmanial and antimalarial activities. Among the evaluated compounds, machilin-G (1a) and veraguensin (2a) showed the highest antileishmanial activities, displaying for both compounds an IC(50) value of 18 microg/mL and an IC(90) value of 36 microg/mL, while galgravin (1b), nectandrin-A (1c), nectandrin-B (1d), calopeptin (2b) and ganshisandrine (3) were inactive against Leishmania donovani. In the antimalarial assay against Plasmodium falciparum, it was observed that calopeptin (2b) displayed moderate activity, with IC(50) values of 3800 ng/mL (D6 clone) and 3900 ng/mL (W2 clone), while the lignans 1a-1d, 2a and 3 were inactive. In order to compare the effect on the parasites with toxicity to mammalian cells, the cytotoxic activity of the isolated compounds were evaluated against the Vero cells, showing that all evaluated tetrahydrofuran lignans exhibited no cytotoxicity at the maximum dose tested.

Synthesis and biological activity evaluation of lignan lactones derived from (-)-cubebin.

The anti-inflammatory and analgesic effects of three dibenzylbutyrolactone lignans, (-)-hinokinin (2), (-)-6,6'-dinitrohinokinin (3), and (-)-6,6'-diaminohinokinin (4), obtained by partial synthesis from (-)-cubebin (1), were investigated using different animal models. It was observed that compounds (1) and (2) inhibited the edema formation in the rat paw edema assay at the same level and that all responses were dose dependent. Also, at the dose of 30 mg/kg, compounds 1, 2, 3, and 4 inhibited the edema formation by 53%, 63%, 54%, and 82%, respectively, at the third hour of the experiment. In the acetic acid-induced writhing test in mice, compounds 2 and 4 produced inhibition levels of 97% and 92%, respectively, while 3 displayed lower effect (75%), which was still higher than 1. The assayed compounds neither displayed activity in the cell migration test nor in the hot plate test.

Trypanocidal activity of (-)-cubebin derivatives against free amastigote forms of Trypanosoma cruzi.

Five (-)-cubebin derivative compounds, (-)-O-acetyl cubebin (3), (-)-O-benzyl cubebin (4), (-)-O-(N,N-dimethylaminoethyl)-cubebin (5), (-)-hinokinin (6) and (-)-6,6'-dinitrohinokinin (7), previously synthesised by our research group, were evaluated on in vitro assay against free amastigote forms of Trypanosoma cruzi, the asogic agent of Chagas' disease. It was observed that 6 was the most active compound (IC(50)=0.7 microM), and that 4 and 5 displayed moderate activity against the parasite, giving IC(50) values of 5.7 and 4.7 microM, respectively. In contrast, it was observed that compound 3 was inactive and that 7 displayed low activity with IC(50) values of congruent with 1.5 x 10(4) and 95.3 microM, respectively.