Candelaria C. Sánchez-Mateo

Antimicrobial studies on three species of Hypericum from the Canary Islands

The antimicrobial activity of several extracts and fractions of the aerial parts of Hypericum canariense, Hypericum glandulosum and Hypericum grandifolium was investigated using the disc diffusion and broth microdilution methods against twelve reference microorganisms (eight bacterial and four fungal strains). The methanol extract and chloroform fraction of H. canariense, as well as the methanol extracts, butanol and chloroform fractions of both H. glandulosum and H. grandifolium exhibited a good antibacterial activity against four Gram-positive bacteria (Bacillus cereus var. mycoides, Micrococcus luteus, Staphylococcus aureus and Staphylococcus epidermidis) and the Gram-negative bacterium Bordetella bronchiseptica with the diameters of growth inhibition area in the range 10-25 mm and MICs values between 0.03 and 0.29 mg/ml. Neither the infusions and aqueous fractions of the species studied nor the butanol fraction of H. canariense showed any antibacterial activity against the tested microorganisms. Amongst the active extracts, the minimum inhibitory concentration (MIC) determination showed that the H. canariense chloroform fraction was the most active against M. luteus, S. aureus and S. epidermidis. No antifungal activity was seen with any of the extracts or fractions tested. The results of this study support the use of these species in Canarian traditional medicine to treat skin infections.

Antidepressant effects of the methanol extract of several Hypericum species from the Canary Islands.

The aim of the present study was to investigate several neuropharmacological effects of the methanol extract of the aerial parts in blossom of Hypericum canariense, H. glandulosum, H. grandifolium and H. reflexum (Hypericaceae). These extracts did not alter significantly the locomotor activity, body temperature or the pentobarbital-induced sleeping time, with the exception of H. reflexum which significantly potentiated pentobarbital-induced sleeping time at both doses assayed (500 and 1000 mg/kg p.o.). Additionally, neither muscle relaxant nor anticholinergic activity was observed. These extracts antagonized the ptosis and/or motor depression induced by tetrabenazine and also shortened the immobility time in the forced swimming test. Moreover, the H. glandulosum and H. grandifolium extracts at 1000 mg/kg p.o. potentiated the head twitches induced by 5-HTP. These observations suggest that the methanol extract of the Hypericum species in doses of 500-1000 mg/kg p.o. possess antidepressant activity in mice, without inducing significant muscle relaxation, anticholinergic and sedative properties.

Phytochemical analysis and in vitro biological activity of three Hypericum species from the Canary Islands (Hypericum reflexum, Hypericum canariense and Hypericum grandifolium)

In the present work we carried out a phytochemical and biological investigation on three Hypericum species, i.e. Hypericum reflexum, Hypericum canariense and Hypericum grandifolium, from the Canary Islands where they are traditionally used as diuretic, wound healing, vermifuge, sedative and antidepressive agents. The polar extracts of the top flowering aerial parts, prepared by Soxhlet apparatus using a methanol-acetone (1:1) extracting mixture, were analyzed by HPLC-DAD and HPLC-MS for the content of eight biomarkers such as hypericin, hyperforin, chlorogenic acid, rutin, hyperoside, isoquercitrin, quercitrin and quercetin, whereas the hydrodistilled essential oils were analyzed by GC-FID and GC-MS. The three Hypericum species had different results in both polar and volatile constituents, H. reflexum being the only one endowed with a small amount of naphtodianthrones (hypericin and pseudohypericin), and containing high levels of chlorogenic acid, rutin and volatile mono- and sesquiterpenes. After chemical characterization, all products were in vitro biologically assayed for antiproliferative activity on human tumor cell lines by MTT assay, for antioxidant potential by DPPH, ABTS and FRAP assays, and for antimicrobial activity by the agar disc diffusion and microdilution methods. Results revealed interesting bioactivities and differences between polar extracts and essential oils, with the former being endowed with significant antioxidant activity and the latter with comparable inhibition effects on the tumor cells (A375, MDA-MB 231 and HCT 116) to that of cisplatin.

Hypericum grandifolium Choisy: A species native to Macaronesian Region with antidepressant effect

AIM OF THE STUDY Various species of Hypericum genus have been used in the Canary Islands as sedative, diuretic, vermifuge, wound healing, antihysteric and antidepressant agent. Studies have shown that methanol extract of Hypericum grandifolium Choisy is active in tetrabenazine-induced ptosis and forced swimming tests. In the current study, the aqueous, butanol and chloroform fractions obtained from the methanol extract as well as three sub-fractions derived from the chloroform fraction were evaluated for their central nervous effects in mice, particularly their antidepressant activity. MATERIALS AND METHODS The central nervous effect of different fractions and sub-fractions of Hypericum grandifolium was evaluated in mice using various behavioural models including locomotor and muscle relaxant activity, forced swimming test, effect on normal body temperature, barbiturate-induced sleep, tetrabenazine-induced syndrome and 5-hydroxytryptohan-induced head twitches and syndrome. RESULTS We found that the butanol and chloroform fractions and all sub-fractions showed an antidepressant effect in the forced swimming test, the chloroform fraction being the most active. They produced no effects or only a slight depression of locomotor activity. Chloroform fraction significantly increased the pentobarbital-induced sleeping time, produced a slight but significant hypothermia and antagonized tetrabenazine-induced ptosis, whereas the butanol fraction produced a slight potentiation of 5-HTP-induced head twitches and syndrome. CONCLUSIONS The present results, together with previous pharmacological and phytochemical data, indicated that Hypericum grandifolium possess antidepressant-like effects in mice and that different constituents, such as the flavonoids and the benzophenone derivatives, could be responsible at least in part for the antidepressant effects observed for this species.

HPLC-MS Analysis and Anti-Oedematogenic Activity of Hypericum grandifolium Choisy (Hypericaceae)

A study has been carried out on the chemical composition and in vivo anti-oedematogenic activity of several extracts from Hypericum grandifolium Choisy (Hypericaceae) collected in Tenerife (Canary Islands). The HPLC-MS analysis (HPLC-ESI/MS and HPLC-FT/MS) revealed the presence of hyperforin, flavonoids and probably benzophenone derivatives, while naphthodianthrones were absent. Pharmacological results revealed that the methanol extracts and the aqueous, butanol and chloroform fractions obtained therefrom possess anti-oedematogenic activity against TPA-induced ear oedema and carrageenan-induced paw oedema, the chloroform fraction being the most active. Subfractions derived from the chloroform fraction also showed anti-oedematogenic activity. From these results, it can be suggested that different constituents, such as the flavonoids and the benzophenone derivatives, could be responsible, at least in part, for the anti-oedematogenic effects observed for this species.

Neuropharmacological study of hetero[2,1]benzothiazepine derivatives analogues of tianeptine

Neuropharmacological studies were conducted in mice with a number of hetero[2,1]benzothiazepine derivatives, analogues of tianeptine. Seven of the 12 compounds under study potentiated the actions of 5-hydroxytryptophan (5-HTP, 50 mg/kg i.p.) and/or antagonised the hypothermia induced by high doses of apomorphine. Moreover, some of them inhibited the head twitches induced by 5-HTP (250 mg/kg i.p.) and the stereotyped behaviour and/or climbing behaviour of low doses of apomorphine. These compounds also produced a slight inhibition of exploratory behaviour in the holeboard test. On the other hand, no significant muscle relaxant, anticonvulsant and anxiolytic activities were observed at any dose employed. Together, these data suggest that some of the compounds under study exert antidepressant and neuroleptic effects in mice with no muscle relaxant, anxiolytic and anticonvulsant activities.

Phenolic acids, antioxidant and antiproliferative activities of Naviglio® extracts from Schizogyne sericea (Asteraceae)

Abstract Schizogyne sericea, well-known as ‘salado’, is a halophytic shrub widespread on coastal rocks of Tenerife (Canary Islands). This plant is used traditionally as analgesic, astringent, anti-inflammatory and vulnerary agent. In the present work, we have analysed the aqueous and ethanolic extracts of S. sericea for the content of phenolic acids by HPLC-DAD. The dynamic solid–liquid Naviglio® extractor was used to extract the flowering aerial parts. Aqueous extracts showed higher levels of phenolics than ethanolic extracts. S. sericea extracts were rich in chlorogenic and isochlorogenic acids. The Naviglio® extracts obtained were assayed for in vitro biological activities, namely antioxidant, antimicrobial and cytotoxicity on tumour cells by DPPH, ABTS, FRAP, agar disc-diffusion and MTT methods, respectively. Results showed that aqueous extracts, being richer in phenolic acids, are endowed with relevant radical scavenging activity (TEAC values in the range 208–960 μmol TE/g) while ethanolic extracts exhibited noteworthy antiproliferative effects on tumour cells.

Effects of Visnea mocanera extracts on the bleeding time, gastrointestinal transit and diuresis in rodents

The present study examined the effect of several extracts of Visnea mocanera L. on the bleeding time and gastrointestinal transit in mice using the Duke test and charcoal meal method, respectively; they were also investigated in order to examine their renal effects. Results showed that V. mocanera extracts significantly inhibited both the bleeding time and gastrointestinal transit in mice. No diuretic activity of these extracts were detected. In contrast, they significantly reduced the urine volume. The study provides experimental support to the therapeutic advocation of V. mocanera in ethnomedicine for the treatment of diarrhoea and the healing of wounds.

Antioxidant activity and cytotoxicity on tumour cells of the essential oil from Cedronella canariensis var. canariensis (L.) Webb & Berthel. (Lamiaceae)

Cedronella canariensis is a lemon-scented species of the family Lamiaceae endemic to the Canary Islands where it is used in the traditional medicine to prepare infusions or inhalations for anti-catarrhal, tonic, diuretic, hypoglycaemiant, hypotensive, anti-inflammatory and decongestant of the respiratory tract. In this work we investigated for the first time the antioxidant activity of the essential oil and its inhibitory effects on tumour cells (A375, MDA-MB-231, HCT 116) proliferation by DPPH, ABTS, FRAP and MTT assays, respectively. The oil, analysed by GC-ionisation flame detector and GC–MS, was characterised by pinocarvone (58.0%) and β-pinene (10.8%) as the major constituents, being typical of the chemotype ‘canariensis’. Noteworthy was the cytotoxic activity of the oil against the tumour cells examined, with IC50 values of 4.3, 7.3 and 11.4 μg/mL on A375, MDA-MB-231 and HCT 116 tumour cells, respectively, as well as the scavenging activity against the ABTS radical (IC50 of 10.5 μg/mL).

Bioactive Secondary Metabolites from Schizogyne sericea (Asteraceae) Endemic to Canary Islands.

Schizogyne sericea (Asteraceae) is a halophytic shrub endemic to the Canary Islands and traditionally employed as analgesic, astringent, anti‐inflammatory, and vulnerary. A comprehensive phytochemical investigation was conducted on the flowering aerial parts by analyzing both essential oil constituents and polar compounds. The essential oil was dominated by p‐cymene, with the noteworthy occurrence of β‐pinene and thymol esters. From the EtOH extract, eight compounds were isolated and structurally elucidated. Essential oil, polar fractions, and isolates (2), (4), and (5) were separately in vitro assayed for antiproliferative activity on human tumor cell lines (A375, MDA‐MB 231, and HCT116) by MTT assay, for antioxidant potential by DPPH, ABTS, and FRAP assays, and for antimicrobial activity by the agar disk diffusion method. Results revealed that essential oil and compounds 1 and 2 exert a strong inhibition on tumor cells, and in some cases, higher than that of cisplatin. Fractions containing thymol derivatives (1 and 2) and caffeoylquinic acid derivatives 4 and 5 displayed antioxidant activity comparable to that of Trolox, making S. sericea extract an interesting natural product with potential applications as preservative or in the treatment of diseases in which oxidative stress plays an important role.