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.

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.

Acanthus mollis Formulations for Transdermal Delivery: From Hydrogels to Emulsions.

Topical formulations of Acanthus mollis L. leaf and the optimization of the release of their active compounds and their topical bioavailability were investigated for the first time. In vitro, the release of active compounds from three formulations-an oil-in-water cream and two hydrogels (Carbopol 940 and Pluronic F-127)-was determined using Franz diffusion cells. Detection and quantification of the compounds was performed via high-performance liquid chromatography with a photodiode array (HPLC-PDA). DIBOA, a bioactive compound of this medicinal plant, exhibited release kinetics of the Weibull model for the Carbopol and Pluronic F-127 formulation, identifying it as a potential active agent to optimize the topical distribution of the formulations. The implications extend to applications in inflammation treatment and tyrosinase inhibition, suggesting that it can make a significant contribution to addressing skin conditions, including melanoma and various inflammatory diseases.

Synergistic Effect of DIBOA and Verbascoside from Acanthus mollis Leaf on Tyrosinase Inhibition.

Overexpression of melanin contributes to darkening of plant and fruit tissues and skin hyperpigmentation, leading to melasma or age spots. Although melanin biosynthesis is complex and involves several steps, a single enzyme known as tyrosinase is key to regulating this process. The melanogenesis pathway is initiated by oxidation of the starting material l-tyrosine (or l-DOPA) to dopaquinone by tyrosinase; the resulting quinone then serves as a substrate for subsequent steps that eventually lead to production of melanin. Medicinal plants are considered a good source of tyrosinase inhibitors. This study investigated the tyrosinase inhibitory activity of A. mollis leaf extracts and their phytochemicals. Significant activity was verified in the ethanol extract -EEt (IC50 = 1.21 µg/mL). Additionally, a kinetic study showed that this tyrosinase inhibition occurs by DIBOA (2,4-dihydroxy-1,4-benzoxazin-3-one) and verbascoside contribution through a non-competitive reaction mechanism. A synergistic effect on tyrosinase inhibition was observed in the binary combination of the compounds. In conclusion, both EEt and a mixture of two of its phytochemicals can be effective tyrosinase inhibitors and can be used as a bleaching agent for cosmetic formulations in the future.

Effect of Phenolic Compounds from Cymbopogon citratus (DC) Stapf. Leaves on Micellar Solubility of Cholesterol.

Dyslipidemias are one of the risk factors for cardiovascular diseases, the leading cause of death and hospitalization worldwide. One way to control cholesterol levels is to control the exogenous cholesterol intake in the body. Natural polyphenolic compounds, namely theaflavins from plant extracts such as black tea, showed the ability to inhibit the formation of the micellar structure, essential for the absorption of cholesterol in the intestine. There are several methodologies to determine this effect, many of which are expensive and time-consuming. Due to these facts, the main purposes of this work were to optimize an inexpensive colorimetric method to study, in vitro, the micellar solubility of cholesterol and applied it to plant extracts. In this work, Cymbopogon citratus leaf extracts, its phenolic fractions, and flavonoids were evaluated. The non-delipidified infusion (CcI) obtained a maximum percentage of micelle destruction of 59.22% for a concentration of 50 µg/mL and the delipidified infusion (CcdI) obtained a maximum percentage of micelle destruction of 58.01% for a concentration of 200 µg/mL. In the case of the fraction of phenolic acids (CcPAs), 23.85% of maximum micellar destruction was recorded for the concentration of 100 µg/mL, while for the fraction of flavonoids (CcF), the micellar destruction was 92.74% at 1 µg/mL, and for the tannin fraction (CcT) of 99.45% at 25 µg/mL. Luteolin presented a percentage of micelle destruction of 94.83% in the concentration of 1 ng/mL, followed by luteolin-7-O-glucoside with 93.71% and luteo-lin-6-C-glucoside with 91.26% at the concentrations of 25 ng/mL and 50 ng/mL, respectively. These results suggest the capability of polyphenols from Cymbopogon citratus to prevent the cholesterol absorption in the gut by micellar destruction, and its contribution for cholesterol-lowering activity.

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.

Agrimonia eupatoria L.: An integrative perspective on ethnomedicinal use, phenolic composition and pharmacological activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia eupatoria L., a plant which belongs to the Rosaceae family, is widespread in temperate regions, particularly throughout the northern hemisphere. In folk medicine, this plant species has been used for its astringent, anti-inflammatory, analgesic and hypotensive properties as well as in gastrointestinal disorders. As these biological properties have been linked to its phenolic composition, this plant species could be an interesting source of bioactive compounds with therapeutic potential. AIM OF THE STUDY: The aim of the present review is to provide a comprehensive overview of the scientific literature on A. eupatoria, particularly in regard to its ethnobotanics and ethnomedicinal uses, phenolic composition and biological and pharmacological activities. MATERIAL AND METHODS: Literature was retrieved from several bibliographic sources, namely PubMed, ScienceDirect and Google Scholar, since the first report on A. eupatoria in 1993. RESULTS: Regarding the phytochemical composition, A. eupatoria is rich in phenolic acids, flavonoids and tannins. The most commonly reported compounds are astragalin, cynaroside, hyperoside, isoquercitrin, isovitexin, rutin, catechin, procyanidin B3 and agrimoniin. In terms of bioactivity, extracts or fractions obtained from this plant species have shown antioxidant, antimicrobial, antidiabetic, antinociceptive and anti-inflammatory properties, among others. So far, two clinical studies with the infusion of A. eupatoria have shown hepatoprotective properties as well as a protective role in cardiovascular disease, metabolic disorders and diabetes. CONCLUSIONS: In this review, an integrative perspective on ethnomedicinal use, phenolic composition and pharmacological activity of A. eupatoria has been provided. As can be seen, this plant species exhibits several potential applications, including those beyond its traditional ethnomedicinal uses, as the safety of its consumption has been shown clinically. There still is limited pharmacological evidence that corroborates the ethnomedicinal uses of this plant species as well as regarding the specific bioactive compounds.

A review of the ethnomedicinal uses, chemistry, and pharmacological properties of the genus Acanthus (Acanthaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: The Acanthus genus belongs to the Acanthaceae family, and its species are distributed in all continents, mainly in tropical and subtropical regions. Several traditional applications are referred to, but few scientific studies validate them. Despite this, studies in animal models corroborate some of its uses in folk medicine, such as anticancer, antidiabetic, anti-inflammatory, and antinociceptive, which encourages the research on plants of this genus. AIM OF THE REVIEW: To our knowledge, this document is the first comprehensive review study that provides information on the geographic distribution, botanical characteristics, ethnomedicinal uses, phytochemicals, and pharmacological activities of some Acanthus species to understand the correlation between traditional uses, phytochemical, and pharmacological activities, providing perspectives for future studies. RESULTS: In traditional medicine, Acanthus species are mainly used for diseases of respiratory, nervous and reproductive system, gastrointestinal and urinary tract, and skin illness. The most used species are A. montanus, A. ilicifolius, and A. ebracteatus. Chemical compounds (125) from different chemical classes were isolated and identified in seven species, mainly from A. ilicifolius, about 80, followed by A. ebracteatus and A. montanus, appearing with a slightly lower number with fewer phytochemical profile studies. Isolated phytoconstituents have been mainly alkaloids, phenylpropanoid glycosides, and phenylethanoids. In addition, aliphatic glycosides, flavonoids, lignan glycosides, megastigmane derivatives, triterpenoids, steroids, fatty acids, alcohols, hydroxybenzoic acids, simple phenols were also cited. Scientific studies from Acanthus species extracts and their phytoconstituents support their ethnomedical uses. Antimicrobial activity that is the most studied, followed by the antioxidant, anti-inflammatory, and anticancer properties, underlie many Acanthus species activities. A. dioscoridis, A. ebracteatus, A. hirsutus, A. ilicifolius, A. mollis, A. montanus, and A. polystachyus have studies on these activities, A. ilicifolius being the one with the most publications. Most studies were essentially performed in vitro. However, the anticancer, antidiabetic, anti-inflammatory and antinociceptive properties have been studied in vivo. CONCLUSION: Acanthus species have remarkable phytoconstituents with different biological activities, such as antioxidant, antimicrobial, anti-inflammatory, antinociceptive, hepatoprotective, and leishmanicidal, supporting traditional uses of some species. However, many others remain unexplored. Future studies should focus on these species, especially pharmacological properties, toxicity, and action mechanisms. This review provides a comprehensive report on Acanthus genus plants, evidencing their therapeutic potential and prospects for discovering new safe and effective drugs from Acanthus species.

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.

Formulation Effects in the Antioxidant Activity of Extract from the Leaves of Cymbopogon citratus (DC) Stapf.

Cymbopogon citratus DC (Stapf.) is a perennial grass and it is distributed around the world. It is used as a condiment for food and beverage flavouring in the form of infusions and decoctions of its dried leaves. Our previous studies have shown antioxidant, anti-inflammatory and gastroprotective activities for the infusion and its phenolic fractions. The aim of the present work was to develop oral dosage forms from a Cymbopogon citratus extract to be used as a functional food with antioxidant properties. Initially, an essential oil-free infusion was prepared, lyophilized and characterized by HPLC-PDA. Total phenols were quantified with the Folin-Ciocalteu method and the antioxidant activity was assessed by DPPH assay. Gelatine capsules containing the extract with different excipients, selected after DSC and IR trials, were prepared. A formulation exhibiting better antioxidant behaviour in a gastric environment was attained. These results suggest that the proposed formulation for this extract could be a valuable antioxidant product and, consequently, make an important contribution to "preventing" and minimizing diseases related to oxidative stress conditions.

Inhibition of α-glucosidase by flavonoids of Cymbopogon citratus (DC) Stapf.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves extracts from Cymbopogon citratus (DC) Stapf. are widely used in traditional medicine exhibiting several in vivo biological activities, including antidiabetic. Several flavonoids, including aglycones and glycosides, were reported in this plant and previous studies suggested that flavonoids may interact with targets related to diabetes. AIM OF THE STUDY: Evaluated the hypoglycemic activity of C. citratus flavonoids through α-glucosidase inhibition and assess the structure-activity relationship using molecular docking studies. MATERIAL AND METHODS: An infusion of C. citratus leaves and its flavonoid-rich fraction were prepared. Five flavonoids from this fraction were isolated and structurally characterized by UV spectral analysis with shift reagents, HPLC-PDA-ESI/MSn and 1H NMR. The antidiabetic potential of C. citratus infusion, its flavonoid-rich fraction, glycosylated flavonoids and aglycones was evaluated trough the in vitro inhibition of yeast α-glucosidase. Posteriorly, molecular docking of the tested flavonoids was performed to investigate its possible interactions with the α-glucosidase pocket. RESULTS: The infusion of C. citratus, its flavonoid-rich fraction, luteolin and five flavone glycosides namely, luteolin 6-C-ß-glucopyranoside (isoorientin), luteolin 7-O-neohesperidoside (ionicerin), luteolin 7-O-ß-glucopyranoside (cynaroside), Luteolin 2″-O-rhamnosyl-C-(6-deoxy-ribo-hexos-3-ulosyl) (cassiaoccidentalin B), luteolin 6-C-α-arabinofuranosil-(1→2)-α-L-rhamnopyranoside (kurilesin A) showed higher inhibitory activity than the reference drug. This activity increased by the addition of a sugar moiety. However, the di-glycosides were less active than mono-glycosides. The docking studies showed interactions of sugar moieties and A or B rings with the catalytic pocket mainly through hydrogen bonds. CONCLUSIONS: Our results corroborate the potential of C. citratus as a medicinal plant for the treatment of diabetes and revealed that its flavonoid glycosides has hypoglycemic effect and can be explored as drug candidates to act as α-glucosidase inhibitors in the treatment of diabetes.

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.

Crepis vesicaria L. subsp. taraxacifolia Leaves: Nutritional Profile, Phenolic Composition and Biological Properties.

Crepis vesicaria subsp. taraxacifolia (Cv) of Asteraceae family is used as food and in traditional medicine. However there are no studies on its nutritional value, phenolic composition and biological activities. In the present work, a nutritional analysis of Cv leaves was performed and its phenolic content and biological properties evaluated. The nutritional profile was achieved by gas chromatography (GC). A 70% ethanolic extract was prepared and characterized by HLPC-PDA-ESI/MSn. The quantification of chicoric acid was determined by HPLC-PDA. Subsequently, it was evaluated its antioxidant activity by DPPH, ABTS and FRAP methods. The anti-inflammatory activity and cellular viability was assessed in Raw 264.7 macrophages. On wet weight basis, carbohydrates were the most abundant macronutrients (9.99%), followed by minerals (2.74%) (mainly K, Ca and Na), protein (1.04%) and lipids (0.69%), with a low energetic contribution (175.19 KJ/100 g). The Cv extract is constituted essentially by phenolic acids as caffeic, ferulic and quinic acid derivatives being the major phenolic constituent chicoric acid (130.5 mg/g extract). The extract exhibited antioxidant activity in DPPH, ABTS and FRAP assays and inhibited the nitric oxide (NO) production induced by LPS (IC50 = 0.428 ± 0.007 mg/mL) without cytotoxicity at all concentrations tested. Conclusions: Given the nutritional and phenolic profile and antioxidant and anti-inflammatory properties, Cv could be a promising useful source of functional food ingredients.

Vascular activity of infusion and fractions of Cymbopogon citratus (DC) Stapf. in human arteries.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC.) Stapf has been traditionally used mainly for inflammatory diseases and hypertension. However, the mechanisms underlying its vascular activity remain to be fully characterized and the fractions responsible for its cardiovascular activity are still unknown. AIM OF THE STUDY: In this study, we aimed to assess the vascular activity of Cymbopogon citratus in human arteries and to study the role of cyclooxygenase in its vasorelaxant effects. MATERIALS AND METHODS: Vascular effects of leaves infusion and three fractions (phenolic acids, flavonoids and tannins) were studied using distal segments of human internal thoracic arteries harvested from patients undergoing coronary revascularization, which were mounted as rings in tissue organ baths and maintained at 37 °C in Krebs Henseleit buffer. The effect on basal vascular tone, the effect on the noradrenaline-induced contraction and the vasorelaxant effects were assessed. The role of cyclooxygenase was evaluated with indomethacin. RESULTS: Our results showed a mild effect on the basal vessel tone of the infusion. A significant inhibition on the adrenergic-mediated vasoconstriction was observed for the infusion (0.0002 mg/mL) and the flavonoid fraction (0.2 mg/mL), despite a potentiation was observed in some conditions. A vasorelaxant effect was observed for both the infusion (6.46% of maximal relaxation) and the tannin fraction (26.91% of maximal relaxation, P < 0.05 vs. infusion). Incubation with indomethacin (10 µM) elicited a decrease in the vasorelaxation to the infusion (P < 0.05). CONCLUSIONS: These results suggest that cyclooxygenase may be involved in the vasorelaxation to the infusion of Cymbopogon citratus and that tannins are the compound fraction mainly responsible for this vasorelaxation.

Acanthus mollis L. leaves as source of anti-inflammatory and antioxidant phytoconstituents.

This work expands the phytochemical composition knowledge of Acanthus mollis and evaluates antioxidant and anti-inflammatory activities which could be related with its traditional uses. Extracts from leaves, obtained by sequential extraction, were screened using TLC and HPLC-PDA. The ethanol extract was the most active on DPPH assay (IC50 = 20.50 µg/mL) and inhibited nitric oxide (NO) production in RAW 264.7 macrophages (IC50 = 48.31 µg/mL). Significant amounts of cyclic hydroxamic and phenolic acids derivatives were detected. A lower antioxidant effect was verified for a fraction enriched with DIBOA derivatives (IC50 = 163.02 µg/mL), suggesting a higher contribution of phenolic compounds for this activity in ethanol extract. However, this fraction exhibited a higher inhibition of NO production (IC50 = 32.32 µg/mL), with absence of cytotoxicity. These results support the ethnomedical uses of this plant for diseases based on inflammatory processes. To our knowledge, it is the first report to the anti-inflammatory activity for DIBOA derivatives.

Urtica spp.: Phenolic composition, safety, antioxidant and anti-inflammatory activities.

Urtica dioica and other less studied Urtica species (Urticaceae) are often used as a food ingredient. Fifteen hydroxycinnamic acid derivatives and sixteen flavonoids, flavone and flavonol-type glycosides were identified in hydroalcoholic extracts from aerial parts of Urtica dioica L., Urtica urens L. and Urtica membranacea using HPLC-PDA-ESI/MSn. Among them, the 4-caffeoyl-5-p-coumaroylquinic acid and three statin-like 3-hydroxy-3-methylglutaroyl flavone derivatives were identified for the first time in Urtica urens and U. membranacea respectively. Urtica membranacea showed the higher content of flavonoids, mainly luteolin and apigenin C-glycosides, which are almost absent in the other species studied. In vitro, Urtica dioica exhibited greater antioxidant activity but Urtica urens exhibited stronger anti-inflammatory potential. Interestingly, statin-like compounds detected in Urtica membranacea have been associated with hypocholesterolemic activity making this plant interesting for future investigations. None of the extracts were cytotoxic to macrophages and hepatocytes in bioactive concentrations (200 and 350µg/mL), suggesting their safety use in food applications.

Gastroprotective effect of Cymbopogon citratus infusion on acute ethanol-induced gastric lesions in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Treatment of gastric ulcers with medicinal plants is quite common in traditional medicine worldwide. Cymbopogon citratus (DC) Stapf. leaves infusion has been used in folk medicine of many tropical and subtropical regions to treat gastric disturbances. The aim of this study was to assess the potential gastroprotective activity of an essential oil-free infusion from C. citratus leaves in acute gastric lesions induced by ethanol in rat. MATERIALS AND METHODS: The study was performed on adult male Wistar rats (234.0±22.7g) fasted for 24h but with free access to water. The extract was given orally before (prevention) or after (treatment) intragastric administration of absolute ethanol. Effects of dose (28 or 56mg/kg of body weight) and time of contact of the extract with gastric mucosa (1 or 2h) were also assessed. Animals were sacrificed, being the stomachs removed and the lesions were assessed by macroscopic observation and histopathology. RESULTS: C. citratus extract, given orally before or after ethanol, significantly (P<0.01) reduced gastric mucosal injury compared with control group (vehicle+ethanol). The effect does not appear to be dose-dependent. Results also suggested that the extract is more effective when the time of contact with gastric mucosa increases. CONCLUSIONS: The results of this assay confirm the gastroprotective activity of C. citratus extract on experimental gastric lesions induced by ethanol, contributing for the pharmacological validation of its traditional use.

Cymbopogon citratus industrial waste as a potential source of bioactive compounds.

BACKGROUND: Cymbopogon citratus (Cc), commonly known as lemongrass, is a very important crop worldwide, being grown in tropical countries. It is widely used in the food, pharmaceutical, cosmetic and perfumery industries for its essential oil. Cc aqueous extracts are also used in traditional medicine. They contain high levels of polyphenols, which are known for their antioxidant and anti-inflammatory properties. Hydrodistillation of lemongrass essential oil produces an aqueous waste (CcHD) which is discarded. Therefore a comparative study between CcHD and Cc infusion (CcI) was performed to characterize its phytochemical profile and to research its antioxidant and anti-inflammatory potential. RESULTS: HPLC-PDA/ESI-MS(n) analysis showed that CcI and CcHD have similar phenolic profiles, with CcHD presenting a higher amount of polyphenols. Additionally, both CcI and CcHD showed antioxidant activity against DPPH (EC50 of 41.72 ± 0.05 and 42.29 ± 0.05 µg mL(-1) respectively) and strong anti-inflammatory properties, by reducing NO production and iNOS expression in macrophages and through their NO-scavenging activity, in a dose-dependent manner. Furthermore, no cytotoxicity was observed. CONCLUSION: The data of this study encourage considering the aqueous solution from Cc leaf hydrodistillation as a source of bioactive compounds, which may add great industrial value to this crop.