Antifungal chemosensitization through induction of oxidative stress: A model for control of candidiasis based on the Lippia origanoides essential oil.

In this work, evaluated the antifungal chemosensitizing effect of the Lippia origanoides essential oil (EO) through the induction of oxidative stress. The EO was obtained by hydrodistillation and analyzed by GC-MS. To evaluate the antifungal chemosensitizing effect through induction of oxidative stress, cultures of the model yeast Saccharomyces cerevisiae ∆ycf1 were exposed to sub-inhibitory concentrations of the EO, and the expression of genes known, due be overexpressed in response to oxidative and mutagenic stress was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) method. Carvacrol and thymol were identified as the main components. The EO was effective in preventing or reducing the growth of the microorganisms tested. The gene expression profiles showed that EO promoted changes in the patterns of expression of genes involved in oxidative and mutagenic stress resistance. The combined use of the L. origanoides EO with fluconazole has been tested on Candida yeasts and the strategy resulted in a synergistic enhancement of the antifungal action of the azolic chemical product. Indeed, in association with EO, the fluconazole MICs dropped. Thus, the combinatorial use of L. origanoides EO as a chemosensitizer agent should contribute to enhancing the efficiency of conventional antifungal drugs, reducing their negative side effects.

Evaluation of Lippia scaberrima Sond. and Aspalathus linearis (Burm.f.) R. Dahlgren extracts on human CYP enzymes and gold nanoparticle synthesis: implications for drug metabolism and cytotoxicity.

BACKGROUND: Metabolism is an important component of the kinetic characteristics of herbal constituents, and it often determines the internal dose and concentration of these effective constituents at the target site. The metabolic profile of plant extracts and pure compounds need to be determined for any possible herb-drug metabolic interactions that might occur. METHODS: Various concentrations of the essential oil of Lippia scaberrima, the ethanolic extract of Lippia scaberrima alone and their combinations with fermented and unfermented Aspalathus linearis extract were used to determine the inhibitory potential on placental, microsomal and recombinant human hepatic Cytochrome P450 enzymes. Furthermore, the study investigated the synthesis and characterization of gold nanoparticles from the ethanolic extract of Lippia scaberrima as a lead sample. Confirmation and characterization of the synthesized gold nanoparticles were conducted through various methods. Additionally, the cytotoxic properties of the ethanolic extract of Lippia scaberrima were compared with the gold nanoparticles synthesized from Lippia scaberrima using gum arabic as a capping agent. RESULTS: All the samples showed varying levels of CYP inhibition. The most potent inhibition took place for CYP2C19 and CYP1B1 with 50% inhibitory concentration (IC50) values of less than 0.05 µg/L for the essential oil tested and IC50-values between 0.05 µg/L-1 µg/L for all the other combinations and extracts tested, respectively. For both CYP1A2 and CYP2D6 the IC50-values for the essential oil, the extracts and combinations were found in the range of 1 - 10 µg/L. The majority of the IC50 values found were higher than 10 µg/L and, therefore, were found to have no inhibition against the CYP enzymes tested. CONCLUSION: Therefore, the essential oil of Lippia scaberrima, the ethanolic extract of Lippia scaberrima alone and their combinations with Aspalathus linearis do not possess any clinically significant CYP interaction potential and may be further investigated for their adjuvant potential for use in the tuberculosis treatment regimen. Furthermore, it was shown that the cytotoxic potential of the Lippia scaberrima gold nanoparticles was reduced by twofold when compared to the ethanolic extract of Lippia scaberrima.

Biological effects of Lippia alba essential oil against Anopheles gambiae and Aedes aegypti.

The management of mosquito resistance to chemical insecticides and the biting behaviour of some species are motivating the search for complementary and/or alternative control methods. The use of plants is increasingly considered as a sustainable biological solution for vector control. The aim of this study was to evaluate the biological effects of the essential oil (EO) of Lippia alba harvested in Abidjan (Côte d'Ivoire) against Anopheles gambiae and Aedes aegypti mosquitoes. Phytochemical compounds were identified by GC-MS. Knockdown and mortality were determined according to the WHO test tube protocol. Contact irritancy was assessed by observing the movement of mosquitoes from a treated WHO tube to a second untreated tube. Non-contact repellency was assessed using a standardised high-throughput screening system (HITSS). Blood meal inhibition was assessed using a membrane feeding assay treated with EO. The EO was identified as the citral chemotype. The EO gave 100% KD60 in both species at a concentration of 1%. Mortalities of 100% were recorded with An. gambiae and Ae. aegypti at concentrations of 1% and 5% respectively. The highest proportions of females escaping during the contact irritancy test were 100% for An. gambiae at 1% concentration and 94% for Ae. aegypti at 2.5% concentration. The 1% concentration produced the highest proportions of repelled mosquitoes in the non-contact repellency tests: 76.8% (An. gambiae) and 68.5% (Ae. aegypti). The blood meal inhibition rate at a dose of 10% was 98.4% in Ae. aegypti but only 15.5% in An. gambiae. The citral chemotype of L. alba EO has promising biological effects in both species that make it a potentially good candidate for its use in mosquito control. The results obtained in this study encourage the further evaluation of L. alba EOs from other localities and of different chemotypes, under laboratory and field conditions.

Ippia Alba Essential Oil: A Promising Complementary Therapy for Breast Cancer.

Breast cancer remains a pressing global health issue, spurring exploration into innovative therapies. This review focuses on Lippia alba (Mill.) essential oil's potential as a complementary breast cancer treatment. With growing interest in natural approaches, Lippia alba shows promise in breast cancer management. The review will explore Lippia alba's multifaceted role in treatment, highlighting its anticancer effects on breast cancer cells, potential synergy with conventional treatments, safety profiles, and existing clinical evidence. It will also address knowledge gaps, stressing the need for further research to unlock Lippia alba's full therapeutic potential in breast cancer therapy. In a field craving novel therapies, this review offers a timely analysis. Despite the lack of existing reviews on this topic, Lippia alba's significance cannot be understated. As research progresses, this article will be a valuable resource for researchers and healthcare practitioners seeking to augment breast cancer management through complementary therapies.

Wound Healing Effect of Lippia sidoides and Myracrodruon urundeuva Nanogel.

Wound healing is a natural regenerative response to tissue injury and the conventional treatments consists of the use wound dressings with local administration of medicines, but, in some cases, are only partially effective and limited by toxicity or ineffective anti-microbial protection. Medicinal plants such as Lippia sidoides and Myracrodruon urundeuva have shown interesting pharmacological activities, allied to this, the association of these medicinal plants and nanotechnology, could mean an advantage in relation to classical approach. This study investigated the effect of a nanogel loaded with Lippia sidoides essential oil and Myracrodruon urundeuva extract (NAA) in an excisional wound healing model in rats. Animals were anesthetized and skin wounds were made using a metal punch. The groups were treated with vehicle, NAA or collagenase gel, for 7, 14 or 21 days and then sacrificed for tissue analysis. NAA did not show acute dermal irritation, further significantly reduced (p<0.05) the final wound area, accelerated the wound contraction and organization of collagen in the group treated for 14 days. The data presented here demonstrate the therapeutic potential for the use of nanotechnology associated with medicinal plants and provides evidence that corroborate with the use of L. sidoides and M. urundeuva as healing medicinal plants.

Supercritical CO2 extraction of naringenin from Mexican oregano (Lippia graveolens): its antioxidant capacity under simulated gastrointestinal digestion.

A supercritical CO2 method was optimized to recover naringenin-rich extract from Mexican oregano (Lippia graveolens), a flavanone with high antioxidant and anti-inflammatory activity. The effect of the extraction parameters like pressure, temperature, and co-solvent on naringenin concentration was evaluated. We used response surface methodology to optimize the naringenin extraction from oregano; the chemical composition by UPLC-MS of the optimized extract and the effect of simulated gastrointestinal digestion on its antioxidant capacity and total phenolic content were also evaluated. The optimum conditions were 58.4 °C and 12.46% co-solvent (ethanol), with a pressure of 166 bar, obtaining a naringenin content of 46.59 mg/g extract. Also, supercritical optimized extracts yielded high quantities of cirsimaritin, quercetin, phloridzin, apigenin, and luteolin. The results indicated that the naringenin-rich extract obtained at optimized conditions had higher total phenolic content, antioxidant capacity by TEAC and ORAC, and flavonoid content, compared with the methanolic extract, and the simulated gastrointestinal digestion reduced all these values.

Dietary supplementation with Lippia sidoides essential oil improves organ integrity but the specific activity of antioxidant enzymes is dose-dependent in Danio rerio.

The nutritional quality of food can affect the health of animals. This study examined the effects of dietary supplementation with Lippia sidoides essential oil (LSEO) on the physiology of Danio rerio. Four hundred fourty-eight fish were divided into 28 tanks and subjected to different dietary treatments: a control group with no supplementation, a group with grain alcohol supplementation and five groups with LSEO at concentrations of 0.25%, 0.50%, 0.75%, 1.00% and 1.25%. After 15 days, histological and enzymatic analyses were conducted. The 0.25% LSEO group exhibited lower glutathione peroxidase and catalase activity compared to the 1.00% group. Additionally, fish in the 0.25% LSEO group showed improved liver, kidney and splenic integrity indices. These findings support the inclusion of 0.25% LSEO in the diet of D. rerio, suggesting potential benefits for fish physiology and encouraging further research on phytotherapeutics in fish diets.

Water stress modulates terpene biosynthesis and morphophysiology at different ploidal levels in Lippia alba (Mill.) N. E. Brown (Verbenaceae).

Monoterpenes are the main component in essential oils of Lippia alba. In this species, the chemical composition of essential oils varies with genome size: citral (geraniol and neral) is dominant in diploids and tetraploids, and linalool in triploids. Because environmental stress impacts various metabolic pathways, we hypothesized that stress responses in L. alba could alter the relationship between genome size and essential oil composition. Water stress affects the flowering, production, and reproduction of plants. Here, we evaluated the effect of water stress on morphophysiology, essential oil production, and the expression of genes related to monoterpene synthesis in diploid, triploid, and tetraploid accessions of L. alba cultivated in vitro for 40 days. First, using transcriptome data, we performed de novo gene assembly and identified orthologous genes using phylogenetic and clustering-based approaches. The expression of candidate genes related to terpene biosynthesis was estimated by real-time quantitative PCR. Next, we assessed the expression of these genes under water stress conditions, whereby 1% PEG-4000 was added to MS medium. Water stress modulated L. alba morphophysiology at all ploidal levels. Gene expression and essential oil production were affected in triploid accessions. Polyploid accessions showed greater growth and metabolic tolerance under stress compared to diploids. These results confirm the complex regulation of metabolic pathways such as the production of essential oils in polyploid genomes. In addition, they highlight aspects of genotype and environment interactions, which may be important for the conservation of tropical biodiversity.

Comparison of chitosan nanoparticles containing Lippia citriodora essential oil and citral on the induction of apoptosis in A375 melanoma cells.

BACKGROUND: Using nanoparticles containing L. citriodora EO and citral has shown potential in treating skin disorders such as melanoma. METHODS: In this study, GC‒MS was used to analyze the chemical composition of L. citriodora essential oil (EO). The ion gelation method prepared free chitosan nanoparticles and chitosan nanoparticles containing L. citriodora EO and citral. The successful loading of the EO and citral was evaluated using ATR-FTIR. The DPPH assay measured the antioxidant effect of citral, L. citriodora EO, Citral-ChiNPs, L. citriodora-ChiNPs, and Free-ChiNPs. A375 melanoma cell viability was assessed using the MTT assay. The qPCR technique was employed to evaluate the expression of apoptotic genes, and flow cytometry was used to detect apoptosis. RESULTS: This study showed that in equal concentrations, the antioxidant properties of chitosan nanoparticles containing citral were greater than those of chitosan nanoparticles containing L. citriodora. The IC50 values of chitosan nanoparticles containing citral, L. citriodora EO, and their nonformulated states were 105.6, 199.9, 136.9, and 240 µg/ml, respectively. The gene expression results showed that the ratio of the expression of the apoptosis gene to the inhibitory gene was higher than 1 in all the samples, indicating that the conditions for apoptosis were present. Flow cytometry confirmed cell apoptosis, with 93.5 ± 0.3% in chitosan nanoparticles containing citral, 80 ± 0.2% in chitosan nanoparticles containing L. citriodora EO, 63 ± 0.3 in citral, and 42.03% in L. citriodora EO-treated cells. CONCLUSION: The results showed that using the Nano form of L. citriodora and citral increased their efficiency in apoptosis pathways and their toxicity against 375 melanoma cancer cells.

Application of MaxEnt modeling to evaluate the climate change effects on the geographic distribution of Lippia javanica (Burm.f.) Spreng in Africa.

Lippia javanica is a typical indigenous plant species mostly found in the higher elevation or mountainous regions in southern, central, and eastern Africa. The ongoing utilization of the species for ethnobotanical applications and traditional uses, coupled with the changing climate, increases the risk of a potential reduction in its geographic distribution range in the region. Herein, we utilized the MaxEnt species distribution modelling to build the L. javanica distribution models in tropical and subtropical African regions for current and future climates. The MaxEnt models were calibrated and fitted using 286 occurrence records and six environmental variables. Temperatures, including temperature seasonality [Bio 4] and the maximum temperature of the warmest month [Bio 5], were observed to be the most significant determinants of L. javanica's distribution. The current projected range for L. javanica was estimated to be 2,118,457 km2. Future model predictions indicated that L. javanica may increase its geographic distribution in western areas of the continent and regions around the equator; however, much of the geographic range in southern Africa may shift southwards, causing the species to lose portions of the northern limits of the habitat range. These current findings can help increase the conservation of L. javanica and other species and combat localized species loss induced by climate change and human pressure. We also emphasize the importance of more investigations and enhanced surveillance of traditionally used plant species in regions that are acutely susceptible to climate change.

Assessment of the in Vitro Antimelanoma Potential of Lippia microphylla Cham (Verbenaceae) Essential Oil.

Essential oils stand out among natural products for their complex composition, frequently described in the literature with a range of biological effects. This study evaluated the cytotoxic activity against several human cancer cell lines of essential oils extracted from the leaves of Lippia microphylla (EO-LM) Cham. (Verbenaceae). The melanoma cell line SK-MEL-28 was the most sensitive to the EO-LM, presenting an IC50 of 33.38±1.16 µg/mL. Afterward, the effects of EO-LM on the cell cycle, induction of apoptosis, and production of reactive oxygen species (ROS) were evaluated. We stated a significant increase in the sub-G1 population, indicating apoptosis, later confirmed by an increase of SK-MEL-28 cells labeled with Annexin V-FITC and by the formation of apoptotic bodies and membrane blebs, observed by confocal microscopy. Additionally, EO-LM reduced the production of ROS, indicating antioxidant activity. Therefore, EO-LM exhibits anti-melanoma activity in vitro, suggesting its potential as an anticancer agent.

Acute toxicity of essential oils of Aloysia triphylla (L'Hér.) Britton, Lippia gracilis Schauer, and Piper aduncum L. in Colossoma macropomum (Cuvier, 1818).

The aim of this study was to determine the acute toxicity of the essential oils (EOs) of Aloysia triphylla, Lippia gracilis and Piper aduncum in juvenile tambaqui (Colossoma macropomum), and evaluate the possible histopathological alterations in their gills. For the acute toxicity tests, juvenile tambaqui (n=24/treatment) were distributed in six treatments with three replicates, which comprised the control and five EO concentrations of A. triphylla (60, 80, 100, 120 and 140 mg L-1), L. gracilis (35, 40, 45, 50 and 55 mg L-1) and P. aduncum (42.5, 45, 47.5, 50 and 52.5 mg L-1), with an exposure period of 4 h. The mortality rate and severity of damage to the tambaqui gills were proportional to the increase in the concentration of the EO, with LC50-4 h values estimated at 109.57 mg L -1 for A. triphylla, 41.63 mg L -1 for L. gracilis and 48.17 mg L -1 for P. aduncum. The main morphological damages observed in the gills of the tambaqui exposed to the three EOs, were Grade I: hypertrophy and hyperplasia of lamellar epithelial cells, lamellar fusion, epithelial detachment, capillary dilation and constriction, proliferation of chloride cells and mucosal cells and edema; in low frequency Grade II damage as epithelial rupture and lamellar aneurysm. Necrosis (Grade III damage) was observed only in gill lamellae exposed to P. aduncum EO (47.5, 50.0 and 52.5 mg L-1). Concentrations of EOs below LC50-4 h can be used sparingly, for short periods of exposure for the treatment of diseases in tambaqui breeding.

Dendritogenic Potential of the Ethanol Extract from Lippia alba Leaves in Rat Cortical Neurons.

A reduced dendritic complexity, especially in regions such as the hippocampus and the prefrontal cortex, has been linked to the pathophysiology of some neuropsychiatric disorders, in which synaptic plasticity and functions such as emotional and cognitive processing are compromised. For this reason, the identification of new therapeutic strategies would be enriched by the search for metabolites that promote structural plasticity. The present study evaluated the dendritogenic potential of the ethanol extract of Lippia alba, an aromatic plant rich in flavonoids and terpenes, which has been widely used in traditional medicine for its presumed analgesic, anxiolytic, and antidepressant potential. An in vitro model of rat cortical neurons was used to determine the kinetics of the plant's effect at different time intervals. Changes in morphological parameters of the neurons were determined, as well as the dendritic complexity, by Sholl analysis. The extract promotes the outgrowth of dendritic branching in a rapid and sustained fashion, without being cytotoxic to the cells. We found that this effect could be mediated by the phosphatidylinositol 3-kinase pathway, which is involved in mechanisms of neuronal plasticity, differentiation, and survival. The evidence presented in this study provides a basis for further research that, through in vivo models, can delve into the plant's therapeutic potential.

Combinations of amitraz with essential oils from Lippia sidoides and Thymus vulgaris, thymol and thymol acetate for Rhipicephalus microplus control: studies under laboratory and field conditions.

This study aimed to assess the effect of combining amitraz with essential oils (EOs) from Thymus vulgaris and Lippia sidoides, as well as the monoterpenes thymol and thymol acetate, on Rhipicephalus microplus in laboratory conditions, and to select the most effective combination for testing in field conditions. The chemical analysis showed that EOs were mainly composed of monoterpenes, with thymol and p-cymene as the major compounds. In larval (LIT) and adult (AIT) immersion tests using different concentrations of the oils and terpenes mixed with amitraz, the results showed that both EOs and thymol improved the efficacy of amitraz against larvae and engorged females of R. microplus, whereas thymol acetate only enhanced activity against larvae. The most favorable outcome was obtained with the EO of L. sidoides combined with amitraz, resulting in 99 % and 100 % efficacy against larvae and engorged females, respectively. Furthermore, the combination of amitraz with thymol showed presented an efficacy of 94 % and 91 % against larvae and engorged females, respectively. Thus, for the other tests, the combination of thymol + amitraz was chosen due to the ease of working with pure thymol in bioassays, and easier standardization. The immersion test (thymol + amitraz) with semi-engorged females showed 100 % efficacy for the combination of thymol + amitraz, while in tests with different solvents (thymol + amitraz), ethanol being the most effective solvent among those tested (ethanol, Triton, and Tween), resulting in 95 % efficacy on engorged females. In the field test, in treatments with amitraz and thymol + amitraz, efficacy of 54 % and 74 % was observed on day + 3 and 33 % and 43 % on day + 7, respectively. Assessing the reproductive biology of females recovered from animals treated with amitraz or amitraz + thymol, in day + 7, efficacies of 33 % and 52 %, respectively, were observed. EOs from T. vulgaris and L. sidoides and thymol improved the acaricidal activity of amitraz on larvae and engorged females of R. microplus under laboratory conditions, while thymol acetate only enhanced activity against larvae. Thymol increased the efficacy of amitraz under field conditions, however for the development of a commercially available acaricide to R. microplus control, additional studies are needed to increase the efficacy. Further research is needed (by changing concentrations, adding other compounds and/or developing formulations) to increase acaricidal efficacy and develop new effective products to combat R. microplus infestations in cattle.

Comparative analysis indicates a simple protocol for DNA extraction of the aromatic plant Lippia alba.

An efficient method of genomic DNA extraction that provides high quality and yield is a crucial pre-requisite and limiting factor in plant genetic analysis. However, pure genomic DNA can be challenging to obtain from some plant species due to their sugar and secondary metabolite contents. Lippia alba is an important aromatic and medicinal plant, chemically characterized by the presence of tannins, flavonoids, anthocyanins, and essential oils, which interfere with the extraction of pure genomic DNA. In this scenario, optimizing the extraction methods and minimizing the effects of these compounds are necessary. This study compares six plant DNA extraction protocols based on the CTAB method. The quality and quantity of DNA samples obtained were determined by physical appearance by electrophoresis in agarose gels and spectrophotometry. The results highlight the difficulty in obtaining pure and clear bands for all tested methods, except for the polyvinylpyrrolidone (PVP)-based protocol created by our team, which was the better option for obtaining high-quality genomic DNA of L. alba. We conclude that adding PVP-40 into DNA extraction buffers can optimize the DNA extraction of L. alba and indicate this protocol for DNA extraction from other aromatic plants.

Chemical Composition, Anthelmintic Activity, and Mechanism of Action of Lippia dominguensis Mold. Essential Oil on Haemonchus contortus.

Gastrointestinal nematode parasitism is a major burden to small ruminant production globally, compounded by increasing anthelmintic resistance. Previous studies have identified essential oils (EOs) from the Lippia genus with antiprotozoal and anthelmintic effects. Lippia dominguensis Moldenke (Ld), an endemic specie from the Dominican Republic, has similar popular uses, however, is chemically and pharmacologically yet uncharacterized. Here, we investigated the in vitro anthelmintic activity of LdEO and its ultrastructural effects on eggs and adult nematodes of Haemonchus contortus multidrug-resistant isolated. The GC/MS analysis showed linalool (33.85 %), 1,8-cineole (30.88 %), and δ-terpineol (10.61 %) as the main EO constituents. The LdEO showed an IC50 =0.523 mg/mL in the egg hatch test, and the motility in the adult worm motility test was 95.8 % at 1 mg/mL. The confocal scanning laser microscopy of eggs indicated permeabilization or disruption of egg cell membranes as the possible mechanism of action of LdEO. The scanning electron microscopy of adult worms showed wrinkling, undulations, and cuticular disruptions. The LdEO displayed significant in vitro anthelmintic activity on eggs and adult worms of H. contortus. Additionally, the LdEO showed low oral toxicity in mice at 2,000 mg/kg. Thus, additional in vivo studies are justified to determine its anthelmintic efficacy in small ruminants.

Citral-rich fractions of Lippia alba essential oils as immunoresponsive and anti-Candida albicans additives for collagen membranes in guided bone regeneration.

PURPOSE: The aim of this study was to optimize the immunoresponsive and anti-Candida albicans (C. albicans) properties of guided bone regeneration-resorbable membranes (collagen) using additives based on synergistic mixtures of chlorhexidine with terpene-enriched fractions from Lippia alba essential oils (EO). METHODS: The anti-C. albicans activity of the fractions (individually or combined with chlorhexidine) was evaluated using planktonic and sessile cultures. J774A.1 murine macrophage cells were used to determine the cytotoxicity and immunoresponsive effects of the therapies. RESULTS: The anti-planktonic and anti-sessile performance of chlorhexidine on C. albicans was improved 2- to 4-fold by supplementation with citral-rich fractions. On macrophages, this fraction also exhibited a potentially cytoprotective action against the toxic effects of chlorhexidine, minimizing damage to the cell membrane, mitochondrial membrane potential, and nuclear integrity. Macrophages growing on collagen-membrane fragments and stimulated with the citral fraction (alone or with chlorhexidine) showed a significant increase in releasing the osteogenic cytokine TNF-α and enhancing the IL-4. CONCLUSION: This combined therapy appears as a promising platform for the development of a prophylactic or therapeutic biocidal solution that can optimize the pharmacological characteristics of chlorhexidine (epithelium tolerance and anti-C. albicans consolidation on surfaces), as well as potentiating the immunoresponsive properties of collagen membranes.

Chemical characterization, antinociceptive and anti-inflammatory effect of Lippia lacunosa, a species used by the Bandeirantes.

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia lacunosa Mart. & Schauer is an endemic plant from the Serra do Espinhaço mountain range located on the Atlantic plateau, Brazil. It is known as "chá de pedestre" and "rosmaninho" in folk medicine. This species has a characteristic mango aroma and is widely used by the population for flu, colds, sinus infections, coughing, relaxing baths, and foot baths after long walks. It is often confused with and, therefore, used interchangeably with L. rotundifolia and L. pseudothea. AIM OF THE STUDY: This study aimed to increase scientific knowledge on the ethnopharmacological use of Lippia lacunosa through the evaluation of the micromolecular composition and anti-inflammatory and antinociceptive activities of the hexane and ethanolic extracts, essential oil, and fractions in mice. MATERIALS AND METHODS: The chemical profile of L. lacunosa extracts and fractions were obtained by chromatographic methods such as Ultra-Performance Liquid Chromatography (UPLC), Gas Chromatography (GC), Column Chromatography (CC), and Thin Layer Chromatography (TLC). Carrageenan-induced paw edema was used to investigate the anti-inflammatory activity in mice. Mechanical allodynia induced by carrageenan and hot plate tests were employed to evaluate the antinociceptive activity. RESULTS: The main constituents found in the essential oil were the monoterpenes myrcene (13.81%), linalool (6.84%), ipsenone (21.2%), and myrcenone (25.44%); and sesquiterpenes elemol (7.30%) and spathulenol (3.15%). The chromatograph fractionation of essential oil yielded a fraction rich in the main compounds (F33), ipsenone and mircenone. In experimental models of paw edema and mechanical allodynia induced by carrageenan (600 µg, 30 µL, i.pl.), the administration of hexane extract, essential oil (50 or 100 mg/kg, p.o.) or majority fraction (10 mg/kg, p.o.) reduced paw edema. The ethanolic extract (100 mg/kg) reduced mechanical allodynia only in the 2 nd h of evaluation. On the other hand, the hexane extract (50 or 100 mg/kg) and essential oil (100 mg/kg), as well as the majority fraction (10 mg/kg), reduced mechanical allodynia throughout the evaluation period. The hexane extract, essential oil, and majority fraction F33 also reduced the heat-induced nociceptive response. Also, majority fraction F33 did not affect the time mice spent in the rota-rod apparatus. CONCLUSIONS: The elucidation of the composition of the essential oil and the demonstration of the activity of L. lacunosa in experimental models of acute inflammation and also in models of nociceptive and inflammatory pain can help to increase knowledge on the ancient ethnopharmacological use by the Bandeirantes, aiming at the evaluation of the species as a candidate for herbal medicine or phytopharmaceutical in the treatment of patients with inflammatory and painful conditions.

Lippia origanoides derivatives in vitro evaluation on polymicrobial biofilms: Streptococcus mutans, Lactobacillus rhamnosus and Candida albicans.

OBJECTIVE: This work evaluated the Lippia origanoides derivatives in vitro effect on polymicrobial biofilms of Streptococcus mutans, Lactobacillus rhamnosus and Candida albicans. Additionally, the cytotoxic effect of the oils on human skin keratinocytes (HaCaT) and fibroblasts of the periodontal ligament (FLP) cell lines was evaluated. DESIGN: The minimum inhibitory concentration, the inhibitory activity on monomicrobial (S. mutans) and polymicrobial biofilm (S. mutans, L. rhamnosus and C. albicans) of L. origanoides four essential oils and terpenes (thymol and carvacrol) were evaluated. The cytotoxic effect of each one of the compounds was measured, and all the tests were compared against chlorhexidine. RESULTS: All the evaluated compounds reached an inhibition percentage of S. mutans monomicrobial biofilms formation of 100 % at 600 µg/mL (p < 0.0001). The highest concentration (2 MIC) eradicated 100 % of S. mutans-preformed biofilms after 5 min L. origanoides carvacrol + thymol and thymol chemotypes showed marked reductions in topography, the number of microbial cells and extracellular matrix on polymicrobial biofilm. The cytotoxic effect of the compounds was very similar to chlorhexidine. CONCLUSIONS: L. origanoides essential oils have an inhibitory effect on mono and polymicrobial biofilms. The oils present a similar cytotoxic effect to chlorhexidine on HaCaT and FLP cell lines. However, including these compounds in formulations for clinical use is an exciting proposal yet to be investigated.

Antiproliferative Effect of Essential Oil Obtained from Oregano (Lippia palmeri S. Watson) Leaves Grown in Hydroponics and LED Light.

Nowadays, light-emitting diodes (LED) provide an alternative source to sunlight with specific intensity and wavelength that promotes plant growth. The features offered by LED could also stimulate the production of secondary metabolites of pharmaceutical interest. This work analyzed the cultivation of oregano (Lippia palmeri S. Watson) in a floating root hydroponic system supplemented by full-spectrum LED artificial light. Growth indicators like height, diameter, number of shoots, and leaf length and width were measured. The essential oil (EO) composition from the leaves of wild and hydroponic conditions found thymol (41.8 %) as the main product for the former and carvacrol (47 %) in hydroponics. The antiproliferative activity of EOs on human colorectal cancer HCT-15 shows that 6.4 µg/ml for hydroponic and 7.4 µg/ml for the wild plant reduce more than 50 % the cell viability. Overall, this study indicates that hydroponic conditions and full spectrum LED modifies the composition of the EO of L. palmeri on compared with the wild plant, which effectively induces cell growth inhibition in human colorectal cancer.