Chemical composition, antimicrobial activity, and antioxidant capacity of Micromeria flagellaris Baker and M. madagascariensis Baker: Two endemic species from Madagascar as sources of essential oils.

Background: The aerial parts of Micromeria madagascariensis Baker and M. flagellaris Baker are used by the population of the Vakinankaratra and Itasy regions (Madagascar) to treat breathing difficulty, fever and/or headache, wounds, and sores. Purpose: This work aimed to characterise plant materials from M. madagascariensis and M. flagellaris to report i) chemical composition, ii) antimicrobial properties, and iii) antioxidant capacity of the essential oils extracted from the aerial parts of these species. Materials and methods: The essential oils from M. madagascariensis (MMO) and M. flagellaris (MFO) were obtained by hydrodistillation. Their chemical composition was quantified using gas chromatography coupled with mass spectrometry (GC-MS). MMO and MFO were also tested against 7 microbial strains using the disk diffusion method and their antioxidant capacity was assessed using the DPPH scavenging assay. Results: Hydrodistillation yielded 0.26% MMO and 0.29% MFO (w/w) in relation to the fresh weight. Twenty-seven compounds were identified by GC-MS in MMO extract against 36 in MFO one. The main compounds in MMO were pulegone (24.67%), trans-menthone (24.67%), eucalyptol (8.12%), ß-caryophyllene (4.98%), α-guanene (4.47), iso-menthone (3.85%), iso-pulegone (3.34%), azulene (3.28%) and 2-isopropyl-5-methylcyclohexenone (2.82%). The main compounds in the MFO were eudesma-4,11-dien-2-ol (13.88%), δ-guanene (6.62%), pulegone (6.40%), cyperone (5.56%), 4-epi-dehydrobietinol acetate (5.39%), eucalyptol (5.12%), trans-menthone (4.67%), limonene (3.77%) and sabinene (2.29%). Regarding the chemotaxonomy, M. flagellaris was very different from M. madagascariensis and both species also differed from the other Micromeria species, as confirmed by multivariate statistical analysis. Both MMO and MFO exerted activities against a large microbial spectrum; the antimicrobial activity of MMO was higher than MFO one against S. pneumoniae and C. albicans due to the presence of pulegone as the main component. MFO showed an excellent scavenging capacity with an SC50 value of 2.17 ± 0.03 µg/mL. Conclusion: The biological properties of the essential oils extracted from the selected species may explain their therapeutic value showing that Malagasy Micromeria species may be very important as new natural sources of bioactive compounds. This study may promote the effectiveness and quality of Malagasy Micromeria species, contributing to sustainable development and commercial valorisation of traditional preparations based on natural local resources.

In silico ADMET and anti-inflammatory profiles of the stigmast-4-en-3-one and isolation of isovanillin as the antioxidant principle of Imperata cylindrica (L.) P. Beauv.

Imperata cylindrica (L.) P. Beauv. is an invasive species widely used in treatment of several diseases associated with pain and inflammation in different countries including Madagascar. This work aims to report the isolation of the antioxidant, analgesic and anti-nflammatory compounds from the methanol extract of I. cylindrica. The bio-guided method was used to isolate its bioactive compounds by combining chromatographic methods, writhing test in mice and antioxidant assays. Stigmast-4-en-3-one was isolated as one among the compounds responsible for the analgesic and anti-inflammatory properties and isovanillin as one among the antioxidant compounds from the extract. Stigmast-4-en-3-one showed a good oral pharmacokinetic profile and good binding affinities with some pro-inflammatory targets. It did not show any mutagenic effect, nor a carcinogenic one and had a low risk to be a cardiotoxic agent. All of our results provide scientific justification for its traditional medicinal use in the management of pain and inflammatory related diseases.

Quali-Quantitative Fingerprinting of the Fruit Extract of Uapaca bojeri Bail. (Euphorbiaceae) and Its Antioxidant, Analgesic, Anti-Inflammatory, and Antihyperglycemic Effects: An Example of Biodiversity Conservation and Sustainable Use of Natural Resources in Madagascar.

Antioxidants are important supplements for the human body for their roles in human life for the maintenance of homeostasis. Tapia fruits (Uapaca bojeri) are used by the riverain population of the Tapia forests in Madagascar as complementary foods. This study aims to quantify the main antioxidants in the U. bojeri fruits to verify their contribution to the enhancement of their anti-inflammatory and antihyperglycemic effects. Standard phytochemical screening was used for qualitative analysis, while spectrophotometric (TPC, TAC, and TFC) and chromatographic analyses (HPLC) were used to quantify several phytochemicals in U. bojeri fruits. The antioxidant activity was evaluated using DPPH and FRAP assays. The writhing test was used for the analgesic effects, the carrageenan-induced paw edema was used for the anti-inflammatory activity, and OGTT was used to test the anti-hyperglycemia property of the MEUB in mice. Several phytocompounds were detected and quantified in the fruits, including succinic acid (67.73%) as the main quantified compound. Fruits exerted a good antioxidant capacity and showed analgesic, anti-inflammatory, and antihyperglycemic activities in mice. Isolation of the bioactive compounds should be carried out to confirm these pharmacological properties and develop health-promoting food products or medicinal applications derived from this species.

Bio-guided isolation of androsta-1,4-dien-3,16-dione as a vasodilator active principle from the inflorescence of Ravenala madagascariensis Sonn. (Strelitziaceae).

Androsta-1,4-dien-3,16-dione was isolated for the first time from the plant kingdom of the ethanolic extract of the Ravenala madagascariensis' inflorescence by the bio-guided method. Its structure was elucidated by NMR and MS spectroscopic data analysis. The vascular effects of ethanol extracts, fractions and androsta-1,4-dien-3,16-dione were assessed on the phenylephrine pre-contracted isolated rat aorta. The isolated compound exerted the most potent vaso-relaxing effect (EC50 = 109.32 ± 15.82 µM) than the ethanol extract and fractions. The pharmacological mechanism of its vaso-relaxing action was analysed on isolated rat aorta using free-endothelial vascular tissue, specific contracting reagents (CaCl2 and KCl), antagonist (propranolol), enzyme inhibitors (L-NAME, methylene blue) and channel blocker (glibenclamide). Its vaso-relaxing activity could be due, at least partly, to the non-specific inhibition of the calcic influx.

Antioxidant, Anti-Inflammatory, and Antidiabetic Activities of Leaves and Stems of Uapaca bojeri Bail. (EUPHORBIACEAE), an Endemic Plant of Madagascar.

Uapaca bojeri is an endemic Malagasy plant used by the local population. This work aimed to evaluate antioxidant, anti-inflammatory, and antidiabetic activities of the methanol extracts of U. bojeri leaves and stems and to report their total phenolic content and the bioactive compound content by HPLC methods. Antioxidant capacity was determined by DPPH and ferric reducing antioxidant power (FRAP) assays. An in vivo carrageenan-induced paw oedema and acetic acid-induced writhing test in mice were used for anti-inflammatory activity evaluation. An oral glucose tolerance test was performed in mice to evaluate antidiabetic activity. The total bioactive compound content of leaves was higher than that of stems. Stem methanol extract inhibited the free radical DPPH more than the leaf methanol extract. Leaf methanol extract inhibited, in a dose-dependent manner, the carrageenan-induced paw oedema more than the stem extract, but their inhibition of the pain symptoms caused an acetic acid-induced decrease similar to the number of writhes in the dose-dependent case. The leaf and stem methanol extracts significantly reduced blood glucose levels after 30 min of glucose loading in mice compared to the control group blood glucose reduction. The presence of several bioactive compounds in U. bojeri contributed to the different biological activities, but isolation and identification of these bioactive molecules are necessary to confirm these pharmacological properties.

Self-nanoemulsifying drug delivery system to improve transcorneal permeability of voriconazole: in-vivo studies.

OBJECTIVE: This study investigates the effectiveness of self-nanoemulsifying drug delivery system (SNEDDS) in improving voriconazole transcorneal permeability. METHODS: Voriconazole-SNEDDS was prepared with isopropyl myristate, PEG 400, Tween 80® and Span 80® and was subjected for physicochemical characterization after reconstitution with NaCl 0.9% (1/9; v/v). In-vitro antifungal activity was assessed and compared with the marketed formulation. In-vivo studies, namely ocular irritation test via modified Draize test and pharmacokinetic study, were investigated using rabbit as animal model. KEY FINDINGS: Voriconazole-SNEDDS presented a droplet size of 21.353 ± 0.065 nm, a polydispersity index of 0.123 ± 0.003, a pH of 7.205 ± 0.006 and an osmolarity of 342.667 ± 2.517 mOsmol/l after reconstitution with NaCl 0.9%. Voriconazole-SNEDDS minimum inhibitory concentration (MIC90 ) was similar to the one of marketed formulation for Candida species while it was significantly lower (P < 0.001) for Aspergillus fumigatus. Draize test revealed that Voriconazole-SNEDDS was safe for ocular administration. Voriconazole maximum concentration (5.577 ± 0.852 µg/ml) from SNEDDS was higher than marketed formulation (Cmax  = 4.307 ± 0.623 µg/ml), and the Tmax was delayed to 2 h. The area under the concentration-time curve value of Voriconazole-SNEDDS was improved by 2.419-fold. CONCLUSION: Our results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery and this encourages further clinical studies.