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Origin of Macaronesian Sideritis L. (Lamioideae: Lamiaceae) inferred from nuclear and chloroplast sequence datasets.

Sideritis L. (Lamiaceae) comprises approximately 150 species of annuals and perennials distributed chiefly in the Mediterranean region. The majority of the species belong to the continental subgenus Sideritis which is divided into two perennial (Sideritis and Empedoclea) and two annual (Hesiodia and Burgsdorfia) sections. Twenty-three species are woody perennials endemic to the Macaronesian archipelagos of Madeira and the Canary Islands. In an effort to determine the continental origin of the insular group, we constructed independent phylogenies comprising sequence data from both chloroplast and nuclear markers. Sampling included 7 island taxa drawn from the Macaronesian subgenus Marrubiastrum and 25 continental taxa representing all four sections of subgenus Sideritis. Subgenus Marrubiastrum and the two continental perennial sections form well-supported monophyletic groups in both individual and combined analyses. The annual sections are not monophyletic in any analysis; further sampling of annual taxa is needed to resolve these relationships. All analyses identified Sideritis cossoniana, an annual species from Morocco, as the closest continental relative of the Macaronesian group. This contrasts with the hypothesis of earlier workers who suggested that the insular taxa were most closely related to eastern Mediterranean species of the genus. The phylogenies also demonstrate a distinct increase in woodiness among the Macaronesian species relative to their continental congeners, providing further support for the secondary nature of woodiness in island plants.

Biological Evolution↗

Analysis and retention behaviour in high-performance liquid chromatography of terpenic plant constituents (Sideritis spp.) with pharmacological interest.

Terpenoids are natural products with an important pharmacological interest, which are present in a number of medicinal plants. The species of Sideritis genus are valuable due to their high content in those compounds and they have been used in the Mediterranean area in folk medicine as anti-inflammatory and anti-ulcer agents. The present study describes a gradient elution reversed-phase method that uses diode array detection to determine ten pharmacologically active diterpenoids occurring in 12 species of Sideritis. First, we studied the chromatographic behaviour of standard diterpenoids to analyse the variation on retention time and the chromatographic properties with the mobile phase. Standard calibration curves were generated by plotting the area of peaks against a concentration range of the compounds. Second, the validated method was applied to the analyses of hexanic and methanolic extracts from 12 species of Sideritis, which were collected from different areas of Spain. Finally, we established for this plant a relationship between their use in folk medicine and their diterpenoid content.

Calibration↗

Antibacterial and antioxidant activities in Sideritis italica (Miller) Greuter et Burdet essential oils.

Sideritis italica (Miller) Greuter et Burdet is a widespread Lamiacea in the Mediterranean region used in traditional medicine. Essential oils were antibacterial against nine ATCC and as many clinically isolated Gram-positive and Gram-negative bacterial strains. Antibacterial activity was also found against Helicobacter pylori: a dose-dependant inhibition was shown between 5 and 25 microg/ml. The antibacterial activity of the oils was expressed as MICs (minimum inhibitory concentrations) and MBCs (minimum bactericidal concentrations). At a concentration between 3.9 and 250 microg/ml the oils showed a significant antibacterial effect against both Gram-negative and Gram-positive bacteria. In particular the ATCC strains Pseudomonas aeruginosa (MIC=3.9 microg/ml and 7.8 for flowerheads and leaves, respectively), Proteus mirabilis (MIC=15.6 and 7.8 microg/ml), Salmonella typhi (MIC=7.8 microg/ml) and Proteus vulgaris (MIC=15.6 microg/ml) were the most inhibited. Only Pseudomonas aeruginosa showed MBC at a concentration between 62.6 and 125 microg/ml. The antioxidant activity of the essential oils was evaluated by two cell free colorimetric methods: ABTS and DMPD; leaf oil is more active (4.29 +/- 0.02 trolox equivalents and 4.53 +/- 0.67 ascorbic acid equivalents by ABTS and DMPD, respectively). Finally the antioxidant activity of the essential oils was also evaluated by their effects on human whole blood leukocytes (WB) and on isolated polymorphonucleate (PMN) chemiluminescence. Comparing the effects of the oils from leaves and flowerheads on both PMN and WB chemiluminescence emission, we found no significant differences. Essential oils showed a dose-dependent and linear inhibitory activity on isolated PMN as well as on WB CL emission when PMA-stimulated. On the contrary, the inhibitory activity on resting cells was nonlinear. Our data represent an answer to the continual demand for new antibiotics and antioxidants for the continuous emergence of antibiotic-resistant strains and the growing interest in the substitution of synthetic antioxidants with natural ones. Furthermore, our finding of antibacterial and antioxidant activities in the essential oils from Sideritis italica flowerheads and leaves validated the use of the plant for medical purposes.

Anti-Bacterial Agents↗

Three acylated flavone glycosides from Sideritis syriaca.

From the aerial parts of Sideritis syriaca a new flavone glycoside, 5,8,3'-trihydroxy-4'-methoxyflavone 7-(6"'-O-acetylsophoroside) was identified together with apigenin 7-(6"-p-coumaroylglucoside) and apigenin 7-(4"-p-coumaroylglucoside) which are reported for the first time in the genus Sideritis. The compounds were characterized using 1H NMR, 13C NMR, MS and chemical methods.

Acylation↗

Isoscutellarein 7-glucosyl(1-->2)xyloside from sixteen species of Sideritis.

A new flavone diglycoside isolated from the aerial parts of Sideritis lutoela was characterized as isoscutellarein 7-O-beta-D-glucopyranosyl(1-->2) beta-D-xylopyranoside by means of spectral analyses, applying 2D NMR techniques and NOE experiments. Its presence in 15 other species of Sideritis is described.

Apigenin↗

Biological activities of some natural compounds from Sideritis sipylea Boiss.

In this work, several diterpenes including siderol, linearol and epicandicandiol were isolated from Sideritis sipylea Boiss collected from Izmir-Karaburun-Akdag, Turkey. In addition, diacetate derivatives of linearol and epicandicandiol were obtained. The antimicrobial activites of all these compounds against the bacteria Staphylococcus aureus (ATTC 25923), Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC 11230), Pseudomonas aeruginosa (ATCC 27853) and the fungus Candida albicans (ATCC 90028) were studied. Antimicrobal activity was measured by the well-diffusion method. Except for C. albicans all microorganisms were tested against antibiotic discs in comparison with the studied compounds.

Bacillus subtilis↗

Analgesic and antiinflammatory properties of Sideritis lotsyi var. Mascaensis.

The antiinflammatory, analgesic and antimicrobial activities of crude ethanol extracts of Sideritis lotsyi var. mascaensis (Lamiaceae), and chloroform and aqueous fractions were evaluated in mice using paw and ear oedema induced by carrageenan and 12-o-tetradecanoyl-phorbol-acetate (TPA), respectively, as inflammation models, the writhing test induced by acetic acid for evaluating analgesic activity and the disk-diffusion method for testing antimicrobial actions. The results obtained demonstrated significant topical antiinflammatory and analgesic activities for the ethanol extract and chloroform fraction, but no relevant antimicrobial activity against the microorganisms tested.

Acetic Acid↗

Studies on the analgesic and anti-inflammatory effects of Sideritis candicans Ait. var. eriocephala Webb aerial part.

Different extracts and fractions from Sideritis candicans Ait. var. eriocephala Webb aerial part were investigated for their analgesic, anti-inflammatory and antimicrobial activities in mice. Results indicated that the extracts assayed showed anti-nociceptive activities because they were able to reduce the nociceptive response to chemical pain stimuli, such as in the acetic acid-induced writhing test. Moreover the extracts also possessed anti-inflammatory activity against carrageenan-induced paw oedema and TPA-induced ear oedema, being the chloroform fraction the most active. Further fractionation and analysis of this fraction revealed that the analgesic and anti-inflammatory activities found could be related in part to the presence of phytosterols, alpha and beta amyrin triterpenic derivatives and ent-kaurene type diterpenes in this species, since some of these compounds are endowed with these activities.

Acetic Acid↗

Antioxidant activity of flavonoids from Sideritis raeseri.

Nine 7-o-allosyl glucosides of 5,8-dihydroxy substituted flavones were isolated from a fraction of the methanol extract of the aerial parts of Sideritis raeseri Boiss et Heldr. subsp. raeseri. The structures were identified by spectroscopic methods. The antioxidant activity of this fraction, evaluated by the Co(II) EDTA-induced luminol chemiluminescence and by the DPPH scavenging activity, was found to be moderate. The activity can be related with the presence of 5- and 8-o-disubstituted flavones.

Antioxidants↗

ent-Kauranoid derivatives from Sideritis moorei.

Seven new ent-kauranoid derivatives ent-7alpha,18-dihydroxykaur-16-en-3-one, ent-18-acetoxy-3beta,7alpha-dihydroxykaur-15-en-17-al, ent-3beta-acetoxy-7alpha,18-dihydroxykaur-15-en-17-al, ent-18-acetoxy-3beta,7alpha,17-trihydroxykaur-15-ene, ent-3beta-acetoxy-7alpha,17,18-trihydroxykaur-15-ene, ent-18-acetoxy-3beta,7alpha,17-trihydroxy-15beta,16beta-epoxykaurane and ent-3beta-acetoxy-7alpha,17,18-trihydroxy-15beta,16beta-epoxykaurane have been isolated from Sideritis moorei. The structures of these compounds have been established by spectroscopic means and chemical correlations.

Acetylation↗

Evaluation of the antinflammatory and analgesic activity of Sideritis canariensis var. pannosa in mice.

A previous chemical study of Sideritis canariensis var. pannosa demonstrated the presence of some important classes of related organic compounds with anti-inflammatory activities. In the present study, the crude ethanol extract and the chloroformic and aqueous fractions of S. canariensis have been examined for their antimicrobial actions through the disk-diffusion method and for their anti-inflammatory and analgesic effects in several animal models. No relevant antimicrobial activity against the tested microorganisms was found. The chloroformic fraction was the most interesting, exhibiting a good analgesic and anti-inflammatory activity.

Acetic Acid↗

Phytochemical and pharmacological studies on Sideritis taurica Stephan ex Wild.

Fatty acids (FA), hydrocarbons, alpha-amyrin, stigmasterol and beta-sitosterol were identified in the n-hexane extract of the aerial parts of Sideritis taurica Stephan ex Wild. Xanthotoxin, as well as 2-acetyl-3-hydroxy-5,6,8-trimethoxy-1,4-naphthoquinone were isolated from the methylene chloride extract of the plant. In addition to apigenin 7-O-beta-D-glucopyranoside and apigenin, previously reported from the plant, hypolaetin 7-O-beta-D-allopyranosyl-O-beta-D-glucopyranoside was isolated from the ethyl acetate extract. From the methanol extract, isoscutellarein 7-O-beta-D-allopyranosyl-O-beta-D-glucopyranoside was also isolated. Toxicity study of petroleum ether extract (f(1)), ethanolic extract (f(2)), dichloromethane fraction of f(2) (f(3)) and n-butanolic fraction of f(2) (f(4)) of the plant proved that it is relatively nontoxic. The tested extracts and fractions exhibited significant analgesic, anti-inflammatory, anti-ulcerogenic and antihyperglycaemic activities, but no anticonvulsant and antipyretic effects, as compared with control groups and reference drugs.

Animals↗

Extraction and identification of natural antioxidant from Sideritis euboea (mountain tea).

The dried aerial parts of the mountain tea Sideritis euboea were extracted using n-hexane, methanol, diethyl ether, ethyl acetate, and n-butanol. The residues were tested for their antioxidant activity on sunflower oil at 50 degrees C under UV light. The oxidation of the sunflower oil was measured using PV, absorbance E(1%)1 cm, and malondialdehyde by high-performance liquid chromatography (HPLC). The butanol extract showed the highest antioxidant activity and was further fractionated by silica and cellulose column chromatography and finally by HPLC. The activity of the final fraction on a range of vegetable oils was compared to that of common used antioxidants (BHT, alpha-tocopherol) using DPPH*, the Rancimat method, and the Schaal oven test. At a level of 400 ppm, the extracted kaempherol showed the highest antioxidant activity among all antioxidants tested. The final fraction was identified (using UV, 1H NMR, 13C NMR, mass spectroscopy, and melting point) as 3,5,7,4'-tetrahydroxy flavone (kaempherol).

Antioxidants↗

Preliminary evaluation on anti-inflammatory and analgesic effects of Sideritis syriaca L. herba extracts.

We studied the anti-inflammatory and analgesic activity of extracts of Sideritis syriaca L. herba. Samples were collected from the wild plant, dried, powdered, and extracted with hexane and methanol. The extracts were evaporated to dryness and then suspended in suitable solvent. They were then tested for anti-inflammatory activity in the carrageenin rat paw edema test and for analgesic activity in the Randall and Selitto test and in the tail-flick test. At 24 hours after the treatment, the gastric mucosa of each rat was observed macroscopically. Based on these results the hexane extract was fractionated by column chromatography, and the fractions were obtained tested in the same way. Results showed interesting anti-inflammatory activity only for the hexane extract and all the fractions obtained from it. All the extracts and all the other fractions showed both peripheral and central analgesic activity. In rats treated with the tested compounds hyperemia and ulcers were absent. The data from this preliminary study reveal interesting pharmacological properties of S. syriaca L. herba extracts related to the marked analgesic activity and the absence of gastric ulcerogenic activity. The same is for anti-inflammatory activity, but in this case it seems to be related only to the apolar fraction.

Analgesics↗

Rhoiptelenol and rhoiptelenone, two pentacyclic triterpenes from Sideritis macrostachya.

The pentacyclic triterpenes rhoiptelenol and rhoiptelenone have been isolated from Sideritis macrostachya. Rhoiptelenone is a new natural compound, whose structure has been determined as D:B-friedo-urs-5-en-3-one. The 1H and 13C NMR spectra of rhoiptelenol, rhoiptelenol acetate and glutinol have been reassigned. The natural occurrence of the D:B-friedo-ursene and D:B-friedo-oleanene derivatives has been examined.

Magnetic Resonance Spectroscopy↗