Phenolic Composition and Bioactivity of Lavandula pedunculata (Mill.) Cav. Samples from Different Geographical Origin.

The aim of this study was to characterize the phenolic composition and evaluate the bioactivity of several samples of Lavandula pedunculata (Mill.) Cav, and to compare aqueous and hydroethanolic extracts. Plant materials were obtained by growing some accessions (seed samples) of various wild populations from different regions of Portugal conserved at the Portuguese Genebank in Braga. Phenolic compounds were analised by HPLC-DAD-ESI/MSn, antioxidant potential through in vitro assays (DPPH radical scavenging activity, reducing power and inhibition of lipid peroxidation), cytotoxicity on tumor cells (MCF-7, NCI-H460, HeLa and HepG2) and non-tumor (PLP2) cells, anti-inflammatory activity in rat RAW 264.7 macrophages, by the ability to inhibit NO production and antimicrobial potential by the microdilution method with INT dye (iodonitrotetrazolium chloride). Thirteen compounds were identified, being salvianolic acid B, rosmarinic acid and luteolin-7-O-glucuronide, the main compounds present, with values ranging between 44.3⁻582, 50.9⁻550, and 24.36⁻101.5 mg/g extract, respectively. L. pedunculata aqueous extract revealed a higher antioxidant potential (EC50 values between 14 to 530 µg/mL), which could be related to its higher concentration in phenolic compounds; however, the hydroethanolic extract showed a higher anti-inflammatory (lower EC50 values than 124 µg/mL) potential and antiproliferative capacity (lower GI50 values than 34 µg/mL). Thus, this study highlights the bioactive effects of this species and opens up possibilities of uses in food and pharmaceutical formulations. However, there are potential differences in such properties according to geographical origin of plant material, as in general, the samples from Alentejo presented higher results in all the bioactivities, compared with Trás-os-Montes samples.

Essential Oils from Côa Valley Lamiaceae Species: Cytotoxicity and Antiproliferative Effect on Glioblastoma Cells.

Lavandula pedunculata (Mill.) Cav., Mentha cervina L. and Thymus mastichina (L.) L. subsp. mastichina are representative species of the Côa Valley's flora, a Portuguese UNESCO World Heritage Site. L. pedunculata and T. mastichina are traditionally used to preserve olives and to aromatize bonfires on Saint John's Eve, while M. cervina is mainly used as a spice for river fish dishes. Despite their traditional uses, these aromatic plants are still undervalued, and literature regarding their bioactivity, especially anticancer, is scarce. In this work, the morphology of secretory structures was assessed by scanning electron microscopy (SEM), and the composition of essential oils (EOs) was characterized by gas chromatography-mass spectrometry (GC-MS). The study proceeded with cytotoxic evaluation of EOs in tumor and non-tumor cells with the cell death mechanism explored in glioblastoma (GB) cells. L. pedunculata EO presented the most pronounced cytotoxic/antiproliferative activity against tumor cells, with moderate cytotoxicity against non-tumor cells. Whereas, M. cervina EO exhibited a slightly lower cytotoxic effect against tumor cells and did not affect the viability of non-tumor cells. Meanwhile, T. mastichina EO did not induce a strong cytotoxic effect against GB cells. L. pedunculata and M. cervina EOs lead to cell death by inducing apoptosis in a dose-dependent manner. The present study suggests that L. pedunculata and M. cervina EOs have a strong cytotoxic and antiproliferative potential to be further studied as efficient antitumor agents.

Mediterranean Lavenders from Section Stoechas: An Undervalued Source of Secondary Metabolites with Pharmacological Potential.

Globally, climate change and wildfires are disrupting natural ecosystems, thus setting several endemic species at risk. The genus Lavandula is widely present in the Mediterranean region and its species, namely, those included in the section Stoechas, are valuable resources of active compounds with several biological assets. Since ancient times lavenders have been used in traditional medicine and for domestic purposes. These species are melliferous, decorative, and essential oil-producing plants with a high economic interest in the pharmaceutical, flavor, fragrance, and food industries. The essential oils of Lavandula section Stoechas are characterized by high amounts of 1,8-cineole, camphor, fenchone, and specifically for L. stoechas subsp. luisieri one of the major compounds is trans-α-necrodyl acetate. On the other hand, the diversity of non-volatile components like phenolic compounds, such as phenolic acids and flavonoids, make these species an important source of phytochemicals with pharmacological interest. Rosmarinic, caffeic, and salvianolic B acids are the major phenolic acids, and luteolin and eriodictyol-O-glucuronide are the main reported flavonoids. However, the concentration of these secondary metabolites is strongly affected by the plant's phenological phase and varies in Lavandula sp. from different areas of origin. Indeed, lavender extracts have shown promising antioxidant, antimicrobial, anti-inflammatory, and anticancer properties as well as several other beneficial actions with potential for commercial applications. Despite several studies on the bioactive potential of lavenders from the section Stoechas, a systematized and updated review of their chemical profile is lacking. Therefore, we carried out the present review that gathers relevant information on the different types of secondary metabolites found in these species as well as their bioactive potential.

Lavandula pedunculata Polyphenol-Rich Extracts Obtained by Conventional, MAE and UAE Methods: Exploring the Bioactive Potential and Safety for Use a Medicine Plant as Food and Nutraceutical Ingredient.

Nowadays, plant-based bioactive compounds (BCs) are a key focus of research, supporting sustainable food production and favored by consumers for their perceived safety and health advantages over synthetic options. Lavandula pedunculata (LP) is a Portuguese, native species relevant to the bioeconomy that can be useful as a source of natural BCs, mainly phenolic compounds. This study compared LP polyphenol-rich extracts from conventional maceration extraction (CE), microwave and ultrasound-assisted extraction (MAE and UAE). As a result, rosmarinic acid (58.68-48.27 mg/g DE) and salvianolic acid B (43.19-40.09 mg/g DE) were the most representative phenolic compounds in the LP extracts. The three methods exhibited high antioxidant activity, highlighting the ORAC (1306.0 to 1765.5 mg Trolox equivalents (TE)/g DE) results. In addition, the extracts obtained with MAE and CE showed outstanding growth inhibition for B. cereus, S. aureus, E. coli, S. enterica and P. aeruginosa (>50%, at 10 mg/mL). The MAE extract showed the lowest IC50 (0.98 mg DE/mL) for angiotensin-converting enzyme inhibition and the best results for α-glucosidase and tyrosinase inhibition (at 5 mg/mL, the inhibition was 87 and 73%, respectively). The LP polyphenol-rich extracts were also safe on caco-2 intestinal cells, and no mutagenicity was detected. The UAE had lower efficiency in obtaining LP polyphenol-rich extracts. MAE equaled CE's efficiency, saving time and energy. LP shows potential as a sustainable raw material, allowing diverse extraction methods to safely develop health-promoting food and nutraceutical ingredients.

Lavandula pedunculata (Mill.) Cav. Aqueous Extract Antibacterial Activity Improved by the Addition of Salvia rosmarinus Spenn., Salvia lavandulifolia Vahl and Origanum compactum Benth.

Lavender aqueous extracts are widely used in the Moroccan traditional medicine for their antibacterial properties. However, previous research have generally focused on investigating the antibacterial activity of lavender essential oils. The aim of this study is to evaluate the antibacterial activity of the Moroccan Lavandula pedunculata (Mill.) Cav. aqueous extract, alone, as well as in combination with extracts of other plant species known for their antibacterial activity: Salvia rosmarinus Spenn., Salvia lavandulifolia Vahl. and Origanum compactum Benth. We have tested the antibacterial activity of L. pedunculata, S. rosmarinus, S. lavandulifolia and O. compactum aqueous extracts individually and in combination against 34 strains using the agar dilution method. The combination effect was evaluated using the fractional inhibitory concentration (FIC). Polyphenol and tannin contents were determined using Folin-Ciocalteu reagent, and then some phenolic compounds were identified using UHPLC-MS. All the extracts displayed a large spectrum of antibacterial activity, especially against staphylococci, streptococci, Mycobacterium smegmatis and Proteus mirabilis. The minimum inhibitory concentration (MIC) values reached 0.15 ± 0.00 mg/mL for Staphylococcus warneri tested with S. lavandulifolia and 0.20 ± 0.07 mg/mL for Staphylococcus epidermidis tested with L. pedunculata or S. rosmarinus. Association of the L. pedunculata extract with S. rosmarinus, S. lavandulifolia and O. compactum showed synergistic effects (FIC ≤ 1). Moreover, the association of L. pedunculata with S. lavandulifolia was active against most of the Gram-negative strains resistant to the individual extracts. Determination of polyphenol and tannin contents showed the richness of the studied plants in these compounds. Additionally, chromatographic analysis demonstrated the high presence of rosmarinic acid in all the studied plant extracts. To our knowledge, this is the first study that shows the enhancing effect of the antibacterial activity of L. pedunculata aqueous extract combined with S. rosmarinus, S. lavandulifolia and O. compactum. These results confirm the effectiveness of the plant mixtures commonly used by traditional healers in Morocco and suggest that L. pedunculata might be used as an antibacterial agent either alone or, more efficiently, in combination with S. rosmarinus, S. lavandulifolia and O. compactum.

Antihyperglycemic Effect of Lavandula pedunculata: In Vivo, In Vitro and Ex Vivo Approaches.

Lavandula pedunculata (Mill.) Cav. (LP) is one of lavender species traditionally used in Morocco to prevent or cure diabetes, alone or in the form of polyherbal preparations (PHP). Therefore, the primary objective of this study was to test the antihyperglycemic effect of the aqueous extract of LP, alone and in combination with Punica granatum L. (PG) and Trigonella foenum-graecum L. (FGK). The secondary objective was to explore some mechanisms of action on the digestive functions. The antihyperglycemic effect of the aqueous extract of LP, alone and in combination with PG and FGK, was studied in vivo using an oral glucose tolerance test (OGTT). In addition, LP extract was tested on the activities of some digestive enzymes (pancreatic α-amylase and intestinal α-glucosidase) in vitro and on the intestinal absorption of glucose ex vivo using a short-circuit current (Isc) technique. Acute and chronic oral administration of LP aqueous extract reduced the peak of the glucose concentration (30 min, p < 0.01) and the area under the curve (AUC, p < 0.01). The effect of LP + PG was at the same amplitude to that of the positive control Metformin (MET). LP aqueous extract inhibited the pancreatic α-amylase with an IC50 almost identical to acarbose (0.44 ± 0.05 mg/mL and 0.36 ± 0.02 mg/mL, respectively), as well as the intestinal α-glucosidase, (IC50 = 131 ± 20 µg/mL) and the intestinal glucose absorption (IC50 = 81.28 ± 4.01 µg/mL) in concentration-dependent manners. LP aqueous extract exhibited potent actions on hyperglycemia, with an inhibition on digestive enzymes and glucose absorption. In addition, the combination with PG and FGK enhanced oral glucose tolerance in rats. These findings back up the traditional use of LP in type 2 diabetes treatment and the effectiveness of the alternative and combinative poly-phytotherapy (ACPP).

Ultrasonic-Assisted Extraction and Natural Deep Eutectic Solvents Combination: A Green Strategy to Improve the Recovery of Phenolic Compounds from Lavandula pedunculata subsp. lusitanica (Chaytor) Franco.

The present study aimed at evaluating the effectiveness of different natural deep eutectic solvents (NADES) on the extraction of phenolic compounds from Lavandula pedunculata subsp. lusitanica (Chaytor) Franco, on the antioxidant activity, and acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase (Tyr) inhibitory capacities. Ten different NADES were used in this research and compared with conventional solvents. Ultrasound-assisted extraction (UAE) for 60 min proved to be the best extraction condition, and proline:lactic acid (1:1) and choline chloride:urea (1:2) extracts showed the highest total phenolic contents (56.00 ± 0.77 mgGAE/gdw) and antioxidant activity [64.35 ± 1.74 mgTE/gdw and 72.13 ± 0.97 mgTE/gdw in 2.2-diphenyl-1-picrylhydrazyl (DPPH) and 2.2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods, respectively]. These extracts also exhibited enzymes inhibitory capacity particularly against Tyr and AChE. Even so, organic acid-based NADES showed to be the best extractants producing extracts with considerable ability to inhibit enzymes. Twenty-four phenolic compounds were identified by HPLC-HRMS, being rosmarinic acid, ferulic acid and salvianolic acid B the major compounds. The results confirmed that the combination of UAE and NADES provide an excellent alternative to organic solvents for sustainable and green extraction, and have huge potential for use in industrial applications involving the extraction of bioactive compounds from plants.

Metabolic profile and biological activities of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco: studies on the essential oil and polar extracts.

We investigated the metabolic profile and biological activities of the essential oil and polar extracts of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco collected in south Portugal. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that oxygen-containing monoterpenes was the principal group of compounds identified in the essential oil. Camphor (40.6%) and fenchone (38.0%) were found as the major constituents. High-performance liquid chromatography with diode array detection (HPLC-DAD) analysis allowed the identification of hydroxycinnamic acids (3-O-caffeoylquinic, 4-O-caffeoylquinic, 5-O-caffeoylquinic and rosmarinic acids) and flavones (luteolin and apigenin) in the polar extracts, with rosmarinic acid being the main compound in most of them. The bioactive compounds from L. pedunculata polar extracts were the most efficient free-radical scavengers, Fe(2+) chelators and inhibitors of malondialdehyde production, while the essential oil was the most active against acetylcholinesterase. Our results reveal that the subspecies of L. pedunculata studied is a potential source of active metabolites with a positive effect on human health.