Phlomis crinita Cav. From Algeria: A source of bioactive compounds possessing antioxidant and wound healing activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Phlomis crinita Cav. (Lamiaceae), locally known as "El Khayata" or "Kayat El Adjarah", is traditionally used in Algeria for its wound-healing properties. AIM OF THE STUDY: Investigate, for the first time, the phytochemical profile, safety, antioxidant and wound-healing activities of the flowering tops methanolic extract of P. crinita (PCME) collected from Bouira Province in the North of Algeria. MATERIALS AND METHODS: Preliminary phytochemical assays were carried out on PCME to quantify the main classes of bioactive compounds, such as total phenols, flavonoids, and tannins. An in-depth LC-DAD-ESI-MS analysis was carried out to elucidate the phytochemical profile of this plant species. Antioxidant activity was investigated by several colorimetric and fluorimetric assays (DPPH, TEAC, FRAP, ORAC, ß-carotene bleaching and ferrozine assay). The acute oral toxicity of PCME (2000 mg/kg b.w.) was tested in vivo on Swiss albino mice, whereas the acute dermal toxicity and wound-healing properties of the PCME ointment (1-5% PCMO) were tested in vivo on Wistar albino rats. Biochemical and histological analyses were carried out on biological samples. RESULTS: The phytochemical screening highlighted a high content of phenolic compounds (175.49 ± 0.8 mg of gallic acid equivalents/g of dry extract), mainly flavonoids (82.28 ± 0.44 mg of quercetin equivalents/g of dry extract). Fifty-seven compounds were identified by LC-DAD-ESI-MS analysis, belonging mainly to the class of flavones (32.27%), with luteolin 7-(6″-acetylglucoside) as the most abundant compound and phenolic acids (32.54%), with salvianolic acid C as the most abundant compound. A conspicuous presence of phenylethanoids (15.26%) was also found, of which the major constituent is forsythoside B. PCME showed a strong antioxidant activity with half-inhibitory activity (IC50) ranging from 1.88 to 37.88 µg/mL and a moderate iron chelating activity (IC50 327.44 µg/mL). PCME appears to be safe with Lethal Dose 50 (LD50) ≥ 2000 mg/kg b.w. No mortality or toxicity signs, including any statistically significant changes in body weight gain and relative organs' weight with respect to the control group, were recorded. A significant (p < 0.001) wound contraction was observed in the 5% PCMO-treated group with respect to the untreated and petroleum jelly groups between 8 and 20 days, whereas no statistically significant results were observed at the two lower doses (1 and 2% PCMO). In addition, the 5% PCMO-treated group showed a statistically significant (p < 0.05) wound healing activity with respect to the reference drug-treated group, showing, at the end of the study, the highest wound contraction percentage (88.00 ± 0.16%). CONCLUSION: PCME was safe and showed strong antioxidant and wound-healing properties, suggesting new interesting pharmaceutical applications for P. crinita based on its traditional use.

Analgesic effect of Centaurium erythraea and molecular docking investigation of the major component swertiamarin.

Centaurium erythraea Rafn is employed in Algerian traditional medicine for treating pain. The analgesic activity of the ethanolic extract (EE) from the flowering aerial parts of this plant was examined, and molecular docking of the main bioactive compound was performed. The EE, characterised by the iridoid swertiamarin, was administered to Wistar albino rats in pain models. Peripheral analgesic activity was evaluated using the acetic acid-induced writhing test, and a hot plate test was performed for central antinociceptive activity evaluation. Treatment with EE significantly decreased rats' writhing induced by acetic acid suggesting peripheral analgesic activity. Furthermore, the elevation of mean basal reaction time in the hot plate method indicated central analgesic activity. Molecular docking studies showed good docking energy with acceptable binding interactions of swertiamarin with cyclooxygenase-2 protein. This supports the analgesic activity of C. erythraea EE, justifying the traditional use of the plant as an analgesic herbal remedy.

In vivo wound healing effect of Italian and Algerian Pistacia vera L. resins.

Pistacia vera oleoresin is one of the natural products used traditionally for the management of wounds. However, there were no scientific reports documented so far on the wound healing activities to substantiate the claim. This study assesses the potential of the oleoresin of P. vera collected in Italy and Algeria for wound healing efficacy via in vivo circular wound excision model. Italian and Algerian oleoresins were subjected to purification and successive fractionation to obtain three matrices. The fractions have been characterized using GC-FID and GC-MS analyses. Oleoresins mixed with vaseline (5% w/w) were topically applied on wound excision induced on the dorsum of rabbits. Wound healing effects were evaluated by percent of wound contraction. Biopsies performed after healing were histologically assessed. Phytochemical results showed a high content of terpenoids components inducing an efficient wound healing effect determined by an in vivo study. Italian and Algerian oleoresins ointments showed significant wound contraction from day 8 to day 16 as compared to the negative control. The two ointments have not showed statistically difference as compared to Cicatryl, reference drug. These results have also been confirmed by the histological evaluation of the tissues involved. The absence of signs of toxicity on the skin of rabbits indicated the safety of the ointments. The study showed that both oleoresins have a very high effectiveness as wound healing agents and appear to justify their traditional use in wound healing in several countries and offer a scientific support to the treatment of traditional healers.

Chemical characterisation, hypoglycaemic and renoprotective effects of aqueous leaf extract of Limoniastrum guyonianum on fructose-induced metabolic syndrome in rats.

In the present study, we chemically characterised the aqueous leaf extract of Limoniastrum guyonianum by HPLC-TOF/MS and evaluated its effects on fructose-induced metabolic syndrome (MetS) in Wistar rats. MetS groups were given (10% w/v) fructose solution to drink ad libitum for 9 weeks, whereas, normal animals received ordinary water. LG extract was administrated to treated groups by gavage for the last 6 weeks of the experimental period. Fructose feeding as a liquid solution increased body weight, reduced insulin sensitivity, raised blood glucose level and provoked atherogenic dyslipidemia associated with renal oxidative stress and structural damage. Treating MetS rats with LG extract at doses of 100, 200 and 300 mg/kg b.w./day considerably ameliorated the fructose-induced alterations. From this study, it was concluded that aqueous leaf extract of L. guyonianum possesses hypoglycaemic, hypolipidemic, antioxidant and renoprotective abilities against fructose-induced metabolic syndrome in rats.

Artemisia herba-alba aqueous extract improves insulin sensitivity and hepatic steatosis in rodent model of fructose-induced metabolic syndrome.

CONTEXT: Fructose consumption is associated with the development of obesity and metabolic syndrome (MetS) in human and animal models. OBJECTIVE: This study investigates the ability of an aqueous extract of Artemisia herba-alba Asso (AH) to ameliorate fructose-induced MetS in Male Wistar rats. METHODS: AH extract at doses of 100, 200 and 400 mg/kg b.w./day was administered for six weeks to MetS animals. RESULTS: Liquid fructose (10% w/v) intake did not vary total animal body weight, whereas, it produced moderate hyperglycemia associated with metabolic and histological alterations. Treating MetS rats with AH extract improved insulin sensitivity, alleviated atherogenic dyslipidaemia and decreased lipid deposition in their hepatic tissues. Additionally, AH extract was found to raise GSH level and antioxidant enzymes (GPx, GST and CAT) activities in rat livers homogenates. CONCLUSION: The results here reported demonstrated, for the first time, that A. herba-alba have therapeutic proprieties against fructose-induced MetS in rodent model.

Phytochemical Profile, Safety Assessment and Wound Healing Activity of Artemisia absinthium L.

The aim of study was to validate, by in vitro and in vivo studies, the traditional use for wound-healing activity of Artemisia absinthium L. Reversed-phase liquid chromatography coupled with diode array detection and electrospray ion trap mass spectrometry (RP-LC-DAD-ESI-MS) analysis allowed to identify eleven polyphenols with chlorogenic acid as the most abundant compound (3.75 g/100 g of dry extract). After that, antibacterial activity as well as acute dermal and oral toxicity were assessed in animal models. In order to investigate the wound-healing activity of A. absinthium methanol extract, two ointments were formulated (MEO 5% and 10%). The ointment with the highest concentration of plant extract (10%) showed a statistically significant effect on the rats wound contraction, similar to that exerted by the reference drug Cicatryl-Bio. Moreover, A. absinthium methanol extract showed the best antibacterial activity against the Gram-negative Escherichia coli ATCC 10536 (MIC 1.25-2.5 mg/mL) and the Gram-positive Staphylococcus aureus ATCC 6538 (0.31-0.625 mg/mL). The absence of oral and topical toxicity of the treated animals allowed to establish the safety of the ointments. Overall, data collected in the present study support and validate the use of A. absinthium as a wound healing agent in the Algerian traditional medicine.

Glycosyl flavonoid profile, in vivo antidiabetic and in vitro antioxidant properties of Linaria reflexa Desf.

Aerial parts of Linaria reflexa, used in North African folk medicine for treating certain skin diseases, were investigated by HPLC-DAD-ESI/MS technique able to identify the glycosyl flavonoids pectolinarin (1), isolinariin A (2), isolinariin B (3), linariin (4), isolinariin D (5) and isolinariin E (6) as the most abundant components in both hydroalcoholic (HAE) and ultrasound-assisted (UAE) extracts profiles. Metabolite 5, isolated and fully characterised by extensive nuclear magnetic resonance (NMR) analysis, has been very recently reported from L. japonica together with the compound 6. Good antioxidant activities (DPPH radical scavenging, ß-carotene bleaching and reducing power assays) were observed for the extracts. The remarkable antidiabetic activity displayed by UAE (300 mg/kg) has yielded the most marked decrease in blood glucose levels of the alloxan diabetic rats (-72.09%), greater than the effects by the drug glybenclamide (-63.29%). This study reports the first correlation of antidiabetic activity of Linaria sp. extracts with their chemical composition.

Antidiabetic Effects of Aqueous Infusions of Artemisia herba-alba and Ajuga iva in Alloxan-Induced Diabetic Rats.

The aqueous infusions of the aerial parts of Artemisia herba-alba Asso and Ajuga iva Schreber, prepared in accordance with the traditional procedure used in the local folk medicine, have been analysed for their composition and content of phytochemical constituents and examined for their antidiabetic effectiveness in alloxan-induced diabetic rats. Oral administration of A. herba-alba and A. iva infusions was studied in normal and alloxan-induced diabetic rats, which were randomly divided into nine groups, each group consisting of six animals. The drug preparations (100, 200, and 300 mg/kg b. w.) of each plant were given orally to the rats of each group twice daily for 15 days. Compositional analysis of the aqueous infusions revealed the presence of several polyphenols as main components. A. herba-alba infusion was characterised by mono- and di-cinnamoylquinic acids, with 5-caffeoylquinic (chlorogenic) acid being the main compound, followed by 3,5-dicaffeoylquinic acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant among flavonoids. On the other hand, A. iva showed the exclusive presence of flavonoids, with the flavanone naringin present in relatively high levels together with several apigenin (flavone) derivatives. Oral administration of 300 mg/kg b. w. of the aqueous infusions of A. herba-alba and A. iva exhibited a significant reduction in blood glucose content, showing a much more efficient antidiabetic activity compared to glibenclamide, the oral hypoglycaemic agent used as a positive control in this study. These results suggest that A. herba-alba and A. iva possess significant antidiabetic activity, as they were able to improve the biochemical damage in alloxan-induced diabetes in rats.

Herbalists and wild medicinal plants in M'Sila (North Algeria): an ethnopharmacology survey.

ETHNOPHARMACOLOGICAL RELEVANCE: The main aim of this study was to identify, catalogue and document the large number of wild medicinal plants used in the M'Sila region (northern Algeria) for the treatment of several human pathologies. Another more ambitious aim is to contribute to overcoming the limits of an orally transmitted pharmacopoeia, attempting to exploit the large ethnopharmacology patrimony of the region for further pharmacological purposes. MATERIALS AND METHODS: Our field study was carried out over a period of three years (2008-2010). During this period, herbalists were interviewed using semi-structured questionnaires investigating the herbalist as a holder of information (gender, age and educational level) and about wild medicinal plants (local name, uses and part used). In addition, the relative importance value of the species was determined and informant consensus factor (ICF) was calculated for the medicinal plants included in the study. RESULTS: A total of 83 herbalists were interviewed; men dominate the practice of traditional medicine in the region. About 41% of them are between 31 and 40 years, and about a third (34%) are illiterate. The traditional herbal knowledge is passed from generation to generation in the verbal form, a writing tradition being almost totally absent. The interviewed herbalists identified and recorded 58 plants species and 50 genera belonging to 27 plant families. Lamiaceae and Asteraceae were the most represented plant families. The aerial parts were the most commonly used plant part, while infusion and decoction were the most common method of traditional drug preparation. CONCLUSIONS: The survey provides a veritable source of information on the herbalists and wild medicinal plants. Plants which are used in different parts of the world for the treatment of similar diseases may be deemed to be effective in pharmacological terms. These medicinal plants may be incorporated into the healthcare delivery system of the country.

Compositional analysis and in vivo anti-diabetic activity of wild Algerian Marrubium vulgare L. infusion.

Marrubium vulgare (Lamiaceae) is a plant traditionally used for the treatment of diabetes in Algeria. Compositional analysis of the aqueous infusion revealed the presence of fifteen metabolites, all belonging to the class of polyphenols. Particularly, seven flavonoids have been detected, together with 5-caffeoylquinic (chlorogenic) acid in small amounts; the extract is dominated by the presence of a series of complex molecules, characterized as verbascoside (acteoside) derivatives. Concerning the anti-diabetic effectiveness a series of in vivo experiments were carried out on albinos Wistar rats. Diabetes was induced in the animals by intra-peritoneal injection of alloxane; they were treated twice a day with aqueous extract from aerial part infusion (100, 200 and 300 mg/kg body weight) and glibenclamide (5mg/kg body weight) for 15 days. Oral administration of 200 and 300 mg/kg body weight of aqueous extract the Marrubium vulgare induced an significant effect antidiabetic and antihyperlipidemic (dose-dependent effect). A decrease in blood glucose by 50% for the dose 100 mg/kg and more than 60% for doses 200 and 300 mg/kg, as well as a significant lowering of total lipids, triglycerides, and total cholesterol levels in treated animals, compared with diabetic controls group (p<0.001), have been observed. Glibenclamide was used as reference and showed similar effects.