Zeliha S. Akdemir

Bioassay-guided isolation of anti-inflammatory, antinociceptive and wound healer glycosides from the flowers of Verbascum mucronatum Lam.

ETHNOPHARMACOLOGICAL RELEVANCE The leaves, flowers and whole aerial parts of Verbascum L. species have been used to treat respiratory problems, haemorrhoids and other types of inflammatory conditions in traditional Turkish medicine. AIM OF THE STUDY In order to evaluate this traditional information, the anti-inflammatory, antinociceptive and wound healing activities of Verbascum mucronatum Lam. which is used as haemostatic in Turkish folk medicine were investigated. MATERIALS AND METHODS In vivo inhibitory effect of the extracts on the carrageenan-induced hind paw edema model in mice was studied for the assessment of anti-inflammatory activity. Moreover, the wound healing potential of the plant were evaluated by using in vivo wound healing experimental models, i.e. incision and excision models on mice and rats, were comparatively assessed with a reference ointment Madecassol(®). Skin samples were also evaluated histopathologically. RESULTS The results of these experimental studies exhibited that Verbascum mucronatum displays anti-inflammatory, antinociceptive and wound healing activities. Through bioassay-guided fractionation and isolation procedures four iridoid glucosides, ajugol (1), aucubin (2), lasianthoside I (3), catalpol (4), two saponins, ilwensisaponin A (5) and C (6) and a phenylethanoid glycoside, verbascoside (7) were isolated and their structures were elucidated by spectral techniques. Verbascoside (7) was found to possess significant wound healing activity as well as antinociceptive and anti-inflammatory potentials, per os without inducing any apparent acute toxicity or gastric damage. CONCLUSION The experimental study revealed that Verbascum mucronatum displays remarkable antinociceptive, anti-inflammatory and wound healing activities.

Antinociceptive and Anti-Inflammatory Effects of Saponin and Iridoid Glycosides from Verbascum pterocalycinum var. mutense Hub.-Mor.

The anti-inflammatory and antinociceptive properties of four major compounds from the flowers of Verbascum pterocalycinum var. mutense were investigated. Saponin glycosides called ilwensisaponin A and C and iridoid glycosides known as ajugol and picroside IV were isolated from the methanolic extract. A dose-related anti-inflammatory and antinociceptive response were obtained in this study at doses of 100 and 200 mg/kg. The results of the evaluation of the anti-inflammatory activity induced by carrageenan and PGE1 showed that this species possesses active constituents that could diminish the cyclooxygenase activitiy. No effects were observed in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema model. Our results support the anti-inflammatory and analgesic effects of Verbascum pterocalycinum var. mutense. Ilwensisaponins A and C could explain in part the anti-inflammatory and analgesic activities of this species. Although antinociceptive and anti-inflammatory activities of ajugol and picroside IV were found insignificant in the statistical analysis, ilwensisaponin A and C showed notable activity without inducing any apparent acute toxicity as well as gastric damage.

An ethnopharmacological study on Verbascum species: from conventional wound healing use to scientific verification.

AIM OF THE STUDY The leaves, flowers, and whole aerial parts of Verbascum L. (Scrophulariaceae) species are used to treat eczema and other types of inflammatory skin conditions and as a desiccant for wounds in Turkish traditional medicine. In the present study, the methanolic extracts of 13 Verbascum species growing in Turkey, including Verbascum chionophyllum Hub.-Mor., Verbascum cilicicum Boiss., Verbascum dudleyanum (Hub.-Mor.) Hub.-Mor., Verbascum lasianthum Boiss., Verbascum latisepalum Hub.-Mor., Verbascum mucronatum Lam., Verbascum olympicum Boiss., Verbascum pterocalycinum var. mutense Hub.-Mor., Verbascum pycnostachyum Boiss. & Heldr., Verbascum salviifolium Boiss., Verbascum splendidum Boiss., Verbascum stachydifolium Boiss. & Heldr and Verbascum uschackense (Murb.) Hub.-Mor. were assessed for their in vivo wound healing activity. MATERIAL AND METHODS In vivo wound healing activity of the plants were evaluated by linear incision and circular excision experimental models subsequently histopathological analysis. The healing potential was comparatively assessed with a reference ointment Madecassol(®), which contains 1% extract of Centella asiatica. RESULTS The methanolic extracts of Verbascum olympicum, Verbascum stachydifolium and Verbascum uschackense demonstrated the highest activities on the both wound models. Moreover, the methanolic extracts of Verbascum latisepalum, Verbascum mucronatum, and Verbascum pterocalycinum var. mutense were found generally highly effective. On the other hand, the rest of the species did not show any remarkable wound healing effect. Results of the present study support the continued and expanded utilization of these plant species employed in Turkish folk medicine. CONCLUSION The experimental study revealed that Verbascum species display remarkable wound healing activity.

Anti-Inflammatory and Antinociceptive Potential of Major Phenolics from Verbascum salviifolium Boiss.

The potential effects of flavonoids, phenylethanoid and neolignan glycosides from the aerial parts of Verbascum salviifolium Boiss. were studied in the p-benzoquinone-induced writhing reflex, for the assessment of the antinociceptive activity, and in carrageenan- and PGE1- induced hind paw edema and 12-O-tetradecanoyl-13-acetate (TPA)-induced ear edema models in mice, for the assessment of the anti-inflammatory activity. Through bioassay-guided fractionation and isolation procedures ten compounds from the aqueous extract of the plant, luteolin 7-O-glucoside (1), luteolin 3′-O-glucoside (2), apigenin 7-O-glucoside (3), chrysoeriol 7-O-glucoside (4), β-hydroxyacteoside (5), martynoside (6), forsythoside B (7), angoroside A (8), dehydrodiconiferyl alcohol-9-O′-d-glucopyranoside (9) and dehydrodiconiferyl alcohol- 9′-O-β-d-glucopyranoside (10), were isolated and their structures were elucidated by spectral techniques. Results have shown that 1, 2, 3 and 5 significantly inhibited carrageenaninduced paw edema at a 200 mg/kg dose, while 1, 2 and 5 also displayed anti-inflammatory activity against the PGE1-induced hind paw edema model. However, all the compounds showed no effect in the TPA-induced ear edema model. The compounds 1 and 2 also exhibited significant antinociceptive activity

Cholinesterase inhibitory and antioxidant properties of Verbascum mucronatum Lam. and its secondary metabolites.

1 The aqueous extract of Verbascum mucronatum Lam. along with its fractions and secondary metabolites were assessed for their antioxidant, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activities. The antioxidant activity was evaluated by three methods: as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferrous ion-chelating effect, and ferric-reducing antioxidant power (FRAP) tests. The AChE activity was determined by the Ellman method using an ELISA microplate reader. Phytochemical investigations revealed the presence of four iridoid glucosides, ajugol (), aucubin (2), lasianthoside I (3) and catalpol (4), two saponins, ilwensisaponin A (5) and C (6), and a phenylethanoid glycoside, verbascoside (7), in Verbascum mucronatum. Their structures were elucidated by spectral techniques. The aqueous extract and fractions including the phenylethanoid glycoside 7 showed DPPH scavenger effect and had the best FRAP. Besides these results, one of the phenylethanoid fractions displayed the highest ferrous ion-chelating effect. While only 7 was found to possess moderate AChE inhibition, the extract, fractions, and all other tested compounds did not inhibit AChE and BChE

The in vivo anthelmintic efficacy of some Verbascum species growing in Turkey

Verbascum L. (Scrophulariaceae) species are used for desiccating wounds and as a fish poison in Anatolia as well as for diarrhea and dysentery of animals in several countries. To further evaluate their activity, methanolic extracts obtained from 13 Verbascum species growing in Turkey, including V. chionophyllum Hub.-Mor., V. cilicicum Boiss., V. dudleyanum (Hub.-Mor.) Hub.-Mor., V. lasianthum Boiss., V. latisepalum Hub.-Mor., V. mucronatum Lam., V. olympicum Boiss., V. pterocalycinum var. mutense Hub.-Mor., V. pycnostachyum Boiss. & Heldr., V. salviifolium Boiss., V. splendidum Boiss., V. stachydifolium Boiss. & Heldr. and V. uschackense (Murb.) Hub.-Mor. were evaluated for their in vivo anthelmintic activity. The extracts from V. lasianthum, V. latisepalum, V. mucronatum and V. salviifolum showed the highest inhibitory rates against Aspiculuris tetraptera at 100mg/kg in mice. Additionally, extracts from V. dudleyanum and V. pterocalycinum var. mutense were found generally highly effective. The remaining species did not show any activity. Results of the present study support the utilization of these plant species employed in Turkish folk medicine.

Secondary metabolites from the aerial parts of Verbascum dudleyanum and their biological activities

From the overground parts of Verbascum dudleyanum, six iridoid glycosides, aucubin, ajugol, catalpol, 6-O-α-L-rhamnopyranosylcatalpol, saccatoside, and 6-O-(3″-O-trans-p-coumaroyl)-α-L-rhamnopyranosylcatalpol, and two saponins, ilwensisaponin A and C, as well as a flavonoid, luteolin-7-O-β-glucopyranoside, together with an acetophenone glucoside, picein, were isolated. The structures of isolated compounds were elucidated by spectroscopic methods. These compounds showed biological acitivites.

Antinociceptive and Anti-inflammatory Activities of Seven Endemic Verbascum Species Growing in Turkey

The leaves, flowers, and whole aerial parts of Verbascum L. (Scrophulariaceae) species have been used to treat respiratory problems, eczema, and other types of inflammatory skin conditions in traditional Turkish medicine. Moreover, they have also been widely used as a folk medicine to produce a soothing and anti-inflammatory effect on the urinary tract. In order to evaluate their folkloric use, both antinociceptive and anti-inflammatory activities of seven endemic Verbascum species [V. chionophyllum Hub.-Mor., V. cilicicum Boiss., V. dudleyanum (Hub.-Mor.) Hub.-Mor., V. latisepalum Hub.-Mor., V. pycnostachyum Boiss. & Heldr., V. salviifolium Boiss., V. splendidum Boiss.] were investigated. Antinociceptive activity was investigated via p-benzoquinone–induced writhing test, and the anti-inflammatory activity was studied using carrageenan-induced hind paw edema, PGE2-induced hind paw edema, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema models in mice. The methanol extracts of the flowers of V. chionophyllum and V. pycnostachyum, and the aerial parts of V. latisepalum and V. salviifolium, displayed significant antinociceptive and anti-inflammatory activity at 200 mg/kg oral dose without inducing any apparent acute toxicity or gastric damage. On the other hand, extracts from the rest of the species did not show any remarkable anti-inflammatory and antinociceptive activity. Results of the current study support the continued and expanded use of these plant species employed in Turkish folk medicine.

Screening for Free Radical Scavenging and Cell Aggregation Inhibitory Activities by Secondary Metabolites from Turkish Verbascum species

Free radical scavenging and cell aggregation inhibitory activities of 36 secondary metabolites isolated from the methanolic extracts of Verbascum cilicicum Boiss., V. lasianthum Boiss. ex Bentham, V. pterocalycinum var. mutense Hub.-Mor., and V. salviifolium Boiss. (Scrophulariaceae) were investigated. The isolated compounds, 6-O-vaniloyl ajugol (1), ilwensisaponin A (2), ilwensisaponin C (3), verbascoside (4), β-hydroxyacteoside (5), martynoside (6), poliumoside (7), forsythoside B (8), angoroside A (9), dehydrodiconiferyl alcohol-9-O-β-D-glucopyranoside (10), dehydrodiconiferyl alcohol-9′-O-β-D-glucopyranoside (11), apigenin 7-O-β- glucopyranoside (12), luteolin 7-O-β-glucopyranoside (13), luteolin 3′-O-β-glucopyranoside (14) and chrysoeriol 7-O-β-glucopyranoside (15), exhibited a dose-dependent inhibition of bioautographic and spectrophotometric DPPH activities. Verbascoside (4) was the most active (IC50 4.0 μg/ml) comparing it to vitamin C (IC50 4.4 μg/ml) to inhibit phorbol 12-myristate 13-acetate (PMA)-induced peroxide-catalyzed oxidation of 2′,7′-dichlorofluorescein (DCFH) by reactive oxygen species (ROS) within human promyelocytic HL-60 cells. Ilwensisaponin A (2) (MIC 6.9 μg/ml) showed moderate in vitro activity on lymphocyte-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1)-mediated aggregation using the HL-60 cell line [positive control was cytochalasin B (MIC 2.3 μg/ml)]. None of the other compounds showed free radical scavenging and cell aggregation inhibitory activities.

The Therapeutic Activities of Selected Scrophulariaceae and Buddlejaceae Species and Their Secondary Metabolites Against Neurodegenerative Diseases

Abstract Verbascum, Scrophularia, and Buddleja species have been used in traditional medicine for centuries in almost all parts of the world. In this review, we discuss the current knowledge of the neuroprotective activities and mechanisms of these Scrophulariaceae and Buddlejaceae plants and their secondary metabolites.