Effect of Blueberry Supplementation on a Diet-Induced Rat Model of Prediabetes-Focus on Hepatic Lipid Deposition, Endoplasmic Stress Response and Autophagy.

Blueberries, red fruits enriched in polyphenols and fibers, are envisaged as a promising nutraceutical intervention in a plethora of metabolic diseases. Prediabetes, an intermediate state between normal glucose tolerance and type 2 diabetes, fuels the development of complications, including hepatic steatosis. In previous work, we have demonstrated that blueberry juice (BJ) supplementation benefits glycemic control and lipid profile, which was accompanied by an amelioration of hepatic mitochondrial bioenergetics. The purpose of this study is to clarify the impact of long-term BJ nutraceutical intervention on cellular mechanisms that govern hepatic lipid homeostasis, namely autophagy and endoplasmic reticulum (ER) stress, in a rat model of prediabetes. Two groups of male Wistar rats, 8-weeks old, were fed a prediabetes-inducing high-fat diet (HFD) and one group was fed a control diet (CD). From the timepoint where the prediabetic phenotype was achieved (week 16) until the end of the study (week 24), one of the HFD-fed groups was daily orally supplemented with 25 g/kg body weight (BW) of BJ (HFD + BJ). BW, caloric intake, glucose tolerance and insulin sensitivity were monitored throughout the study. The serum and hepatic lipid contents were quantified. Liver and interscapular brown and epidydimal white adipose tissue depots (iBAT and eWAT) were collected for histological analysis and to assess thermogenesis, ER stress and autophagy markers. The gut microbiota composition and the short-chain fatty acids (SCFAs) content were determined in colon fecal samples. BJ supplementation positively impacted glycemic control but was unable to prevent obesity and adiposity. BJ-treated animals presented a reduction in fecal SCFAs, increased markers of arrested iBAT thermogenesis and energy expenditure, together with an aggravation of HFD-induced lipotoxicity and hepatic steatosis, which were accompanied by the inhibition of autophagy and ER stress responses in the liver. In conclusion, despite the improvement of glucose tolerance, BJ supplementation promoted a major impact on lipid management mechanisms at liver and AT levels in prediabetic animals, which might affect disease course.

Azorean Black Tea (Camellia sinensis) Antidermatophytic and Fungicidal Properties.

The treatment of dermatophytoses, the most common human fungal infections, requires new alternatives. The aim of this study was to determine the antidermatophytic activity of the aqueous Azorean Black Tea extract (ABT), together with an approach to the mechanisms of action. The phytochemical analysis of ABT extract was performed by HPLC. The dermatophytes susceptibility was assessed using a broth microdilution assay; potential synergies with terbinafine and griseofulvin were evaluated by the checkerboard assay. The mechanism of action was appraised by the quantification of the fungal cell wall chitin and ß-1,3-glucan, and by membrane ergosterol. The presence of ultrastructural modifications was studied by Transmission Electron Microscopy (TEM). The ABT extract contained organic and phenolic acids, flavonoids, theaflavins and alkaloids. It showed an antidermatophytic effect, with MIC values of 250 µg/mL for Trichophyton mentagrophytes, 125 µg/mL for Trichophyton rubrum and 500 µg/mL for Microsporum canis; at these concentrations, the extract was fungicidal. An additive effect of ABT in association to terbinafine on these three dermatophytes was observed. The ABT extract caused a significant reduction in ß-1,3-glucan content, indicating the synthesis of this cell wall component as a possible target. The present study identifies the antidermatophytic activity of the ABT and highlights its potential to improve the effectiveness of conventional topical treatment currently used for the management of skin or mucosal fungal infections.

Aromatic Plant-Based Functional Foods: A Natural Approach to Manage Cardiovascular Diseases.

Aromatic plants and their essential oils have shown beneficial effects on the cardiovascular system and, therefore, are potential raw materials in the development of functional foods. However, despite their undeniable potential, essential oils present several limitations that need to be addressed, such as stability, poor solubility, undesirable sensory effects, and low bioavailability. The present review provides a current state-of-the-art on the effects of volatile extracts obtained from aromatic plants on the cardiovascular system and focuses on major challenges that need to be addressed to increase their use in food products. Moreover, strategies underway to overcome these limitations are pointed out, thus anticipating a great appreciation of these extracts in the functional food industry.

The Chemical Profile, and Antidermatophytic, Anti-Inflammatory, Antioxidant and Antitumor Activities of Withania chevalieri A.E. Gonç. Ethanolic Extract.

Withania chevalieri, endogenous from Cape Verde, is a medicinal plant used in ethnomedicine with a large spectrum of applications, such as treating skin fungal infections caused by dermatophytes. The aim of this work was to chemically characterize the W. chevalieri crude ethanolic extract (WcCEE), and evaluate its bioactivities as antidermatophytic, antioxidant, anti-inflammatory and anticancer, as well as its cytotoxicity. WcCEE was chemically characterized via HPLC-MS. The minimal inhibitory concentration, minimal fungicidal concentration, time-kill and checkerboard assays were used to study the antidermatophytic activity of WcCEE. As an approach to the mechanism of action, the cell wall components, ß-1,3-glucan and chitin, and cell membrane ergosterol were quantified. Transmission electron microscopy (TEM) allowed for the study of the fungal ultrastructure. WcCEE contained phenolic acids, flavonoids and terpenes. It had a concentration-dependent fungicidal activity, not inducing relevant resistance, and was endowed with synergistic effects, especially terbinafine. TEM showed severely damaged fungi; the cell membrane and cell wall components levels had slight modifications. The extract had antioxidant, anti-inflammatory and anti-cancer activities, with low toxicity to non-tumoral cell lines. The results demonstrated the potential of WcCEE as an antidermatophytic agent, with antioxidant, anti-inflammatory and anticancer activity, to be safely used in pharmaceutical and dermocosmetic applications.

Effect of Thymbra capitata (L.) Cav. on Inflammation, Senescence and Cell Migration.

Aromatic plants are reported to display pharmacological properties, including anti-aging. This work aims to disclose the anti-aging effect of the essential oil (EO) of Thymbra capitata (L.) Cav., an aromatic and medicinal plant widely used as a spice, as well as of the hydrodistillation residual water (HRW), a discarded by-product of EO hydrodistillation. The phytochemical characterization of EO and HRW was assessed by GC-MS and HPLC-PDA-ESI-MSn, respectively. The DPPH, ABTS, and FRAP assays were used to disclose the antioxidant properties. The anti-inflammatory potential was evaluated using lipopolysaccharide-stimulated macrophages by assessing NO production, iNOS, and pro-IL-1ß protein levels. Cell migration was evaluated using the scratch wound assay, and the etoposide-induced senescence was used to assess the modulation of senescence. The EO is mainly characterized by carvacrol, while the HRW is predominantly characterized by rosmarinic acid. The HRW exerts a stronger antioxidant effect in the DPPH and FRAP assays, whereas the EO was the most active sample in the ABTS assay. Both extracts reduce NO, iNOS, and pro-IL-1ß. The EO has no effect on cell migration and presents anti-senescence effects. In opposition, HRW reduces cell migration and induces cellular senescence. Overall, our study highlights interesting pharmacological properties for both extracts, EO being of interest as an anti-aging ingredient and HRW relevant in cancer therapy.

Vaginal Sheets with Thymbra capitata Essential Oil for the Treatment of Bacterial Vaginosis: Design, Characterization and In Vitro Evaluation of Efficacy and Safety.

We aimed to incorporate Thymbra capitata essential oil (TCEO), a potent antimicrobial natural product against bacterial vaginosis (BV)-related bacteria, in a suitable drug delivery system. We used vaginal sheets as dosage form to promote immediate relief of the typical abundant vaginal discharge with unpleasant odour. Excipients were selected to promote the healthy vaginal environment reestablishment and bioadhesion of formulations, while the TCEO acts directly on BV pathogens. We characterized vaginal sheets with TCEO in regard to technological characterization, predictable in vivo performance, in vitro efficacy and safety. Vaginal sheet D.O (acid lactic buffer, gelatine, glycerine, chitosan coated with TCEO 1% w/w) presented a higher buffer capacity and ability to absorb vaginal fluid simulant (VFS) among all vaginal sheets with EO, showing one of the most promising bioadhesive profiles, an excellent flexibility and structure that allow it to be easily rolled for application. Vaginal sheet D.O with 0.32 µL/mL TCEO was able to significantly reduce the bacterial load of all in vitro tested Gardnerella species. Although vaginal sheet D.O presented toxicity at some concentrations, this product was developed for a short time period of treatment, so this toxicity can probably be limited or even reversed when the treatment ends.

Advances in the Phytochemical Characterisation and Bioactivities of Salvia aurea L. Essential Oil.

The Salvia L. genus (Lamiaceae) is largely used in the pharmaceutical and food industry. Several species of biological relevance are extensively employed in traditional medicine, including Salvia aurea L. (syn. S. africana-lutea L.), which is used as a traditional skin disinfectant and in wounds as a healing remedy; nevertheless, these properties have not been validated yet. The aim of the present study is to characterise S. aurea essential oil (EO), unveiling its chemical composition and validating its biological properties. The EO was obtained by hydrodistillation and subsequently analysed by GC-FID and GC-MS. Different biological activities were assessed: the antifungal effect on dermatophytes and yeasts and the anti-inflammatory potential by evaluating nitric oxide (NO) production and COX-2 and iNOS protein levels. Wound-healing properties were assessed using the scratch-healing test, and the anti-aging capacity was estimated through the senescence-associated beta-galactosidase activity. S. aurea EO is mainly characterised by 1,8-cineole (16.7%), ß-pinene (11.9%), cis-thujone (10.5%), camphor (9.5%), and (E)-caryophyllene (9.3%). The results showed an effective inhibition of the growth of dermatophytes. Furthermore, it significantly reduced protein levels of iNOS/COX-2 and simultaneously NO release. Additionally, the EO exhibited anti-senescence potential and enhanced wound healing. Overall, this study highlights the remarkable pharmacological properties of Salvia aurea EO, which should be further explored in order to develop innovative, sustainable, and environmentally friendly skin products.

Thymus mastichina (L.) L. and Cistus ladanifer L. for skin application: chemical characterization and in vitro bioactivity assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Thymus mastichina (L.) L. (TM) and Cistus ladanifer L. (CL) are two Portuguese autochthonous species with traditional skin application in folk medicine. TM is majorly known for its antiseptic and wound healing properties, as an external anti-inflammatory agent and for its application in folk cosmetics and hygiene products. Its use in acne vulgaris has also been reported. CL is traditionally used in remedies for wounds, ulcers and other skin ailments such as psoriasis and eczema. Its application has been found useful due to its anti-inflammatory, astringent, wound healing and antiseptic properties. AIM OF THE STUDY: With this work, we aimed to investigate relevant bioactivities related with the traditional application of TM and CL essential oils (EOs) and hydrolates (by-products of EO production) in skin ailments. Specifically their in vitro antioxidant, anti-inflammatory, cytotoxic, wound healing and antimicrobial properties were evaluated. The chemical composition of both EOs and respective hydrolates was also characterized. MATERIALS AND METHODS: Chemical characterization of EOs and hydrolates was performed by GC-FID and GC-MS. Cellular biocompatibility was evaluated using the MTT assay in macrophages (RAW 264.7) and fibroblasts (L929) cell lines. Anti-inflammatory activity was investigated by studying nitric oxide (NO) production by macrophages with Griess reagent. Wound healing potential was evaluated with the scratch-wound assay. The antioxidant potential was studied by the DPPH scavenging method. Antimicrobial activity was evaluated by broth microdilution assay against relevant microbial strains and skin pathogens, namely Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus brasiliensis. RESULTS: The major compounds present in TM and CL EOs were 1,8-cineole and α-pinene, respectively. 1,8-cineole and E-pinocarveol were the major compounds in the correspondent hydrolates. CL EO presented the highest anti-inflammatory potential [EC50 = 0.002% (v/v)], still with significant cytotoxicity [IC50 = 0.012% (v/v)]. TM preparations presented anti-inflammatory potential, also presenting higher biocompatibility. The same profile was present on fibroblasts regarding biocompatibility of the tested preparations. CL EO and hydrolate increased fibroblasts' migration by 155.7% and 148.4%, respectively. TM hydrolate presented a milder activity than CL hydrolate, but wound healing potential was still present, increasing cell migration by 125.1%. All preparations presented poor antioxidant capacity. CL EO presented higher antimicrobial activity, with MICs ranging from 0.06% (v/v) to 2% (v/v), against different microorganisms. CONCLUSIONS: Anti-inflammatory and skin repairing potential were present for CL preparations. TM hydrolate presented an interesting biocompatible profile on both cell lines, also presenting anti-inflammatory potential. Furthermore, EOs from both species presented antimicrobial activity against a panel of different microorganisms. These in vitro bioactivities support some of their traditional skin applications, specifically regarding their antiseptic, wound healing and anti-inflammatory uses.

Forest Biomass as a Promising Source of Bioactive Essential Oil and Phenolic Compounds for Alzheimer's Disease Therapy.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit potential as source of safe and multi-target new therapeutic molecules for AD treatment. Meanwhile, Eucalyptus globulus extracts revealed important pharmacological activities, namely antioxidant and anti-inflammatory properties, which can contribute to the reported neuroprotective effects. This review summarizes the chemical composition of essential oil (EO) and phenolic extracts obtained from Eucalyptus globulus leaves, disclosing major compounds and their effects on AD-relevant pathological features, including deposition of amyloid-ß (Aß) in senile plaques and hyperphosphorylated tau in neurofibrillary tangles (NFTs), abnormalities in GABAergic, cholinergic and glutamatergic neurotransmission, inflammation, and oxidative stress. In general, 1,8-cineole is the major compound identified in EO, and ellagic acid, quercetin, and rutin were described as main compounds in phenolic extracts from Eucalyptus globulus leaves. EO and phenolic extracts, and especially their major compounds, were found to prevent several pathological cellular processes and to improve cognitive function in AD animal models. Therefore, Eucalyptus globulus leaves are a relevant source of biological active and safe molecules that could be used as raw material for nutraceuticals and plant-based medicinal products useful for AD prevention and treatment.

Natural Products in Cardiovascular Diseases: The Potential of Plants from the Allioideae Subfamily (Ex-Alliaceae Family) and Their Sulphur-Containing Compounds.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide and, together with associated risk factors such as diabetes, hypertension, and dyslipidaemia, greatly impact patients' quality of life and health care systems. This burden can be alleviated by fomenting lifestyle modifications and/or resorting to pharmacological approaches. However, due to several side effects, current therapies show low patient compliance, thus compromising their efficacy and enforcing the need to develop more amenable preventive/therapeutic strategies. In this scenario, medicinal and aromatic plants are a potential source of new effective agents. Specifically, plants from the Allioideae subfamily (formerly Alliaceae family), particularly those from the genus Allium and Tulbaghia, have been extensively used in traditional medicine for the management of several CVDs and associated risk factors, mainly due to the presence of sulphur-containing compounds. Bearing in mind this potential, the present review aims to gather information on traditional uses ascribed to these genera and provide an updated compilation of in vitro and in vivo studies validating these claims as well as clinical trials carried out in the context of CVDs. Furthermore, the effect of isolated sulphur-containing compounds is presented, and whenever possible, the relation between composition and activity and the mechanisms underlying the beneficial effects are pointed out.

Essential Oils in Respiratory Mycosis: A Review.

Respiratory mycosis is a major health concern, due to the expanding population of immunosuppressed and immunocompromised patients and the increasing resistance to conventional antifungals and their undesired side-effects, thus justifying the development of new therapeutic strategies. Plant metabolites, namely essential oils, represent promising preventive/therapeutic strategies due to their widely reported antifungal potential. However, regarding fungal infections of the respiratory tract, information is disperse and no updated compilation on current knowledge is available. Therefore, the present review aims to gather and systematize relevant information on the antifungal effects of several essential oils and volatile compounds against the main type of respiratory mycosis that impact health care systems. Particular attention is paid to Aspergillus fumigatus, the main pathogen involved in aspergillosis, Candida auris, currently emerging as a major pathogen in certain parts of the world, and Cryptococcus neoformans, one of the main pathogens involved in pulmonary cryptococcosis. Furthermore, the main mechanisms of action underlying essential oils' antifungal effects and current limitations in clinical translation are presented. Overall, essential oils rich in phenolic compounds seem to be very effective but clinical translation requires more comprehensive in vivo studies and human trials to assess the efficacy and tolerability of these compounds in respiratory mycosis.

Chemical composition and biological activity of essential oil of Teucrium scordium L. subsp. scordioides (Schreb.) Arcang. (Lamiaceae) from Sardinia Island (Italy).

The aim of this study is to demonstrate the antifungal, anti-inflammatory and anti-migratory potential of the essential oil of Teucrium scordium subsp. scordioides (Schreb.) Arcang, a plant widely used in traditional medicine in Sardinia. The oil was rich in germacrene D (25.1%), δ-cadinene (12.9%) and alloaromadendrene (11.3%). The yeast Cryptococcus neoformans and the dermatophytes Trichophyton rubrum, T. mentagrophytes var. interdigitale and Epidermophyton floccosum were the most susceptible fungi to the action of the oil. In lipopolysaccharide (LPS)-stimulated macrophages, the oil was able to decrease nitric oxide production by ca. 30% at 1.25 µL/mL, without affecting cell viability. In the scratch wound assay, it allowed for ca. 36% of wound closure after 18 h, thus showing anti-migratory properties. Overall, this study highlights the potential of this species to mitigate fungal infections associated with an inflammatory response. Furthermore, we also reported for the first time its anti-migratory capacity, thus suggesting anticancer properties.

Chemical characterization and bioactive potential of Thymus×citriodorus (Pers.) Schreb. preparations for anti-acne applications: Antimicrobial, anti-biofilm, anti-inflammatory and safety profiles.

ETHNOPHARMACOLOGICAL RELEVANCE: Thymus × citriodorus (Pers.) Schreb. is an interspecific hybrid between Thymus pulegioides and Thymus vulgaris, known for its pharmacological activities as diaphoretic, deodorant, antiseptic and disinfectant, the last mostly related with its antimicrobial activity. The folk use of other extracts, as hydrolates, have also been disseminated, as regulators of oily skin with anti-acne effect. AIM OF THE STUDY: We aimed to evaluate the anti-acne potential of two Thymus x citriodorus (TC) preparations, the essential oil (EO) and the hydrolate, to be used as active ingredients for skin applications. Specifically, we intend to validate their anti-acne potential by describing their activity on acne related bacteria, bacterial virulence, anti-oxidant and anti-inflammatory potential, and biocompatibility on inflammatory cells. Additionally, we aimed to report their ecotoxicity under the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), thus focusing not only on the consumer, but also on environmental safety assessment. MATERIALS AND METHODS: Minimum inhibitory concentration (MIC) against C. acnes, S. aureus and S. epidermidis was evaluated. Minimum lethal concentration (MLC) was also determined. The effect on C. acnes biofilm formation and disruption was evaluated with crystal violet staining. Anti-inflammatory activity was investigated on LPS-stimulated mouse macrophages (RAW 264.7), by studying nitric oxide (NO) production (Griess reagent) and cellular biocompatibility through MTT assay. In-vitro NO and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging potential were also evaluated. The ecotoxicity was evaluated using Daphnia magna acute toxicity assays. RESULTS: EO presented direct antimicrobial activity, with visual MICs ranging from 0.06% for S. epidermidis and C. acnes to 0.125% for S. aureus. MLCs were higher than the obtained MICs. Hydrolate revealed visual MIC only for C. acnes. TC essential oil was effective in preventing biofilm formation and disrupting preformed biofilms even at sub-inhibitory concentrations. Hydrolate showed a more modest anti-biofilm effect. Regarding anti-inflammatory activity, TC hydrolate has a higher cellular biocompatibility. Still, both plant preparations were able to inhibit at least 50% of NO production at non-cytotoxic concentrations. Both EO and hydrolate have poor anti-oxidant activities. Regarding the ecotoxicity, TC essential oil was classified under acute 3 category, while the hydrolate has proved to be nontoxic, in accordance to the GHS. CONCLUSIONS: These results support the anti-acne value of different TC preparations for different applications. TC hydrolate by presenting higher biocompatibility, anti-inflammatory potential and the ability to modulate C. acnes virulence, can be advantageous in a product for everyday application. On the other hand, EO by presenting a marked antimicrobial, anti-biofilm and anti-inflammatory activities, still with some cytotoxicity, may be better suited for application in acute flare-ups, for short treatment periods.

Chemical characterization and bioactivity of the essential oil from Santolina insularis, a Sardinian endemism.

Santolina insularis is a Sardinian endemism that is widely used in traditional medicine. The essential oil was obtained with a yield of 2.7% and is mainly characterized by ß-phellandrene (22.6%), myrcene (11.4%) and artemisia ketone (7.6%). The oil significantly reduced NO production without affecting macrophages viability. In addition, it substantially inhibited the expression of two key pro-inflammatory enzymes, iNOS and COX-2 (71% and 25% at 0.54 mg/mL). Furthermore, the oil had a promising antifungal activity being Cryptococcus neoformans (MIC = 0.13 mg/mL) and the majority of dermatophytes (MIC = 0.13 mg/mL) the most susceptible fungi. Moreover, it significantly decreased the yeast-to-hypha transition (80% inhibition at 0.13 mg/mL) on C. albicans long before showing inhibitory effects. Overall, these results show that S. insularis could be applied in the treatment of fungal infections and associated inflammatory response.

Blueberry Counteracts Prediabetes in a Hypercaloric Diet-Induced Rat Model and Rescues Hepatic Mitochondrial Bioenergetics.

The paramount importance of a healthy diet in the prevention of type 2 diabetes is now well recognized. Blueberries (BBs) have been described as attractive functional fruits for this purpose. This study aimed to elucidate the cellular and molecular mechanisms pertaining to the protective impact of blueberry juice (BJ) on prediabetes. Using a hypercaloric diet-induced prediabetic rat model, we evaluated the effects of BJ on glucose, insulin, and lipid profiles; gut microbiota composition; intestinal barrier integrity; and metabolic endotoxemia, as well as on hepatic metabolic surrogates, including several related to mitochondria bioenergetics. BJ supplementation for 14 weeks counteracted diet-evoked metabolic deregulation, improving glucose tolerance, insulin sensitivity, and hypertriglyceridemia, along with systemic and hepatic antioxidant properties, without a significant impact on the gut microbiota composition and related mechanisms. In addition, BJ treatment effectively alleviated hepatic steatosis and mitochondrial dysfunction observed in the prediabetic animals, as suggested by the amelioration of bioenergetics parameters and key targets of inflammation, insulin signaling, ketogenesis, and fatty acids oxidation. In conclusion, the beneficial metabolic impact of BJ in prediabetes may be mainly explained by the rescue of hepatic mitochondrial bioenergetics. These findings pave the way to support the use of BJ in prediabetes to prevent diabetes and its complications.

The Role of Essential Oils and Their Main Compounds in the Management of Cardiovascular Disease Risk Factors.

Cardiovascular diseases (CVDs) are a global health burden that greatly impact patient quality of life and account for a huge number of deaths worldwide. Despite current therapies, several side effects have been reported that compromise patient adherence; thus, affecting therapeutic benefits. In this context, plant metabolites, namely volatile extracts and compounds, have emerged as promising therapeutic agents. Indeed, these compounds, in addition to having beneficial bioactivities, are generally more amenable and present less side effects, allowing better patient tolerance. The present review is an updated compilation of the studies carried out in the last 20 years on the beneficial potential of essential oils, and their compounds, against major risk factors of CVDs. Overall, these metabolites show beneficial potential through a direct effect on these risk factors, namely hypertension, dyslipidemia and diabetes, or by acting on related targets, or exerting general cellular protection. In general, monoterpenic compounds are the most studied regarding hypotensive and anti-dyslipidemic/antidiabetic properties, whereas phenylpropanoids are very effective at avoiding platelet aggregation. Despite the number of studies performed, clinical trials are sparse and several aspects related to essential oil's features, namely volatility and chemical variability, need to be considered in order to guarantee their efficacy in a clinical setting.

Chemical characterization and bioactive potential of Artemisia campestris L. subsp. maritima (DC) Arcang. essential oil and hydrodistillation residual water.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia campestris L. is widely used in traditional medicine for their anti-inflammatory, antirheumatic, antimicrobial and antioxidant properties. A. campestris subsp. maritima Arcang., a halophyte plant ("madorneira" or "erva-lombrigueira" in Portugal), is traditionally used for gastric disorders, rheumatism and hypertension. AIM OF THE STUDY: The present study aims to characterize the essential oil (EO) and the hydrodistillation residual water (HRW), a by-product of the EO production, of Artemisia campestris subsp. maritima from Portugal and evaluate the antioxidant, antifungal, anti-inflammatory and wound healing activities of both extracts at concentrations without toxicity. MATERIALS AND METHODS: The phenolic profile of HRW was determined by HPLC-PDA-ESI/MSn and the EO was analyzed by gas chromatography (GC-FID and GC-MS). The antioxidant activity of both extracts were determined by several assays (ABTS, NO FRAP, ß-carotene and DPPH). The antifungal activity (MIC and MLC) was evaluated against yeasts, dermatophytes and Aspergillus strains using broth macrodilution methods. The anti-inflammatory potential was determined measuring the nitric oxide (NO) production by stimulated mouse leukemic macrophages (RAW 264.7). Cell viability was evaluated for RAW 264.7 and mouse fibroblasts (NIH/3T3). The wound healing activity was evaluated in mouse fibroblasts (NIH/3T3) by the scratch assay. RESULTS: The HRW is mainly characterized by hydroxycinnamic acids and the essential oil is characterized by high amounts of ß-pinene (54.5%), cadin-4-en-7-ol (9.5%), Z-ß-ocimene (6.0%) and Ƴ-terpinene (4.6%). Both extracts showed high antioxidant potential in different assays. Additionally, only the hydrodistillation residual water showed anti-inflammatory activity (IC50 of 330 µg/mL). On the other hand, only the EO showed antifungal activity, particularly against Epidermophyton floccosum (MIC and MLC values of 0.16 µL/mL), and wound healing activity. Bothe extracts were not cytotoxic to macrophages CONCLUSIONS: The by-product HRW contains safe bioactive compounds with antioxidant and anti-inflammatory effect and the EO shows antioxidant properties, antifungal activity against dermatophytes and wound healing effect in skin cells. Overall, our results support the interest and economic value of two extracts obtained from a Portuguese native species and provide scientific validation to some of its traditional uses.

Lavandula viridis L´Hér. Essential Oil Inhibits the Inflammatory Response in Macrophages Through Blockade of NF-KB Signaling Cascade.

Lavandula viridis L´Hér. is an endemic Iberian species with a high essential oil yield and a pleasant lemon scent. Despite these interesting features, this species remains unrecognized and poorly explored by the food and pharmaceutical industries. Nevertheless, it has been valued in traditional medicine being used against flu, circulatory problems and to relieve headaches. Since these disorders trigger inflammatory responses, it is relevant to determine the anti-inflammatory potential of L. viridis L´Hér. essential oil in an attempt to validate its traditional use and concomitantly to increment its industrial exploitation. Therefore, in the present study the chemical composition of this volatile extract as well as the effect on ROS production, inflammatory response and proteasome activity on LPS-stimulated macrophages were disclosed. Also, its safety profile on keratinocytes, hepatocytes and alveolar epithelial cells was depicted, envisioning a future human administration. The essential oil was characterized by high quantities of 1,8-cineole, camphor and α-pinene. From a pharmacological point of view, the essential oil showed a potent antioxidant effect and inhibited nitric oxide production through down-modulation of nuclear factor kappa B-dependent Nos2 transcription and consequently iNOS protein expression as well as a decrease in proteasomal activity. The anti-inflammatory activity was also evidenced by a strong inhibition of LPS-induced Il1b and Il6 transcriptions and downregulation of COX-2 levels. Overall, bioactive safe concentrations of L. viridis L´Hér. essential oil were disclosed, thus corroborating the traditional usage of this species and paving the way for the development of plant-based therapies.

Ficus plants: State of the art from a phytochemical, pharmacological, and toxicological perspective.

Ficus genus is typically tropical plants and is among the earliest fruit trees cultivated by humans. Ficus carica L. is the common fig, Ficus benjamina L. is the weeping fig, and Ficus pumila L. is the creeping fig. These species are commonly used in traditional medicine for a wide range of diseases and contain rich secondary metabolites that have shown diverse applications. This comprehensive review describes for Ficus genus the phytochemical compounds, traditional uses and contemporary pharmacological activities such as antioxidant, cytotoxic, antimicrobial, anti-inflammatory, antidiabetic, antiulcer, and anticonvulsant. An extended survey of the current literature (Science Direct, Scopus, PubMed) has been carried out as part of the current work. The trends in the phytochemistry, pharmacological mechanisms and activities of Ficus genus are overviewed in this manuscript: antimicrobial, antidiabetic, anti-inflammatory and analgesic activity, antiseizure and anti-Parkinson's diseases, cytotoxic and antioxidant. Health-promoting effects, recent human clinical studies, safety and adverse effects of Ficus plants also are covered. The medical potential and long-term pharmacotherapeutic use of the genus Ficus along with no serious reported adverse events, suggests that it can be considered as being safe.

Antifungal and anti-inflammatory potential of the endangered aromatic plant Thymus albicans.

Thymus albicans is an endemic species of the Iberian Peninsula with a vulnerable conservation status. In an attempt to contribute to the valorization of this species, the present study brings new insights on the antifungal and anti-inflammatory mechanism of action of T. albicans essential oil. The antifungal activity of the oil and its major compounds was assessed for the first time against standard and clinically isolated strains of yeasts and filamentous fungi. The effect on the two major virulence factors of Candida albicans (germ tube formation and biofilm disruption) was considered in more detail. At 0.08 µL/mL, the oil inhibited C. albicans germ tube formation by more than 40% and decreased biofilm biomass at MIC values, thus pointing out its antivirulent potential. The anti-inflammatory activity of the essential oil was investigated on LPS-stimulated mouse macrophages (RAW 264.7) by evaluating the levels of several pro-inflammatory mediators, namely nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). T. albicans oil reduced the production of nitrites, a NO derived sub-product, at non-cytotoxic concentrations of 0.32 and 0.64 µL/mL, by 27 and 41%, respectively. In addition, the iNOS protein levels of essential oil pre-treated cells were reduced by 14%. Overall, the high essential oil yield of T. albicans as well as its bioactive effects at concentrations without cytotoxicity, encourage further studies on the potential pharmacological applications of this species. Furthermore, these results raise awareness for the need to preserve endangered species that may hold relevant medicinal value.