Supercritical Carbon Dioxide Extraction of Coumarins from the Aerial Parts of Pterocaulon polystachyum.

Pterocaulon polystachyum is a species of pharmacological interest for providing volatile and non-volatile extracts with antifungal and amebicidal properties. The biological activities of non-volatile extracts may be related to the presence of coumarins, a promising group of secondary metabolites. In the present study, leaves and inflorescences previously used for the extraction of essential oils instead of being disposed of were subjected to extraction with supercritical CO2 after pretreatment with microwaves. An experimental design was followed to seek the best extraction condition with the objective function being the maximum total extract. Pressure and temperature were statistically significant factors, and the optimal extraction condition was 240 bar, 60 °C, and pretreatment at 30 °C. The applied mathematical models showed good adherence to the experimental data. The extracts obtained by supercritical CO2 were analyzed and the presence of coumarins was confirmed. The extract investigated for cytotoxicity against bladder tumor cells (T24) exhibited significant reduction in cell viability at concentrations between 6 and 12 µg/mL. The introduction of green technology, supercritical extraction, in the exploration of P. polystachyum as a source of coumarins represents a paradigm shift with regard to previous studies carried out with this species, which used organic solvents. Furthermore, the concept of circular bioeconomy was applied, i.e., the raw material used was the residue of a steam-distillation process. Therefore, the approach used here is in line with the sustainable exploitation of native plants to obtain extracts rich in coumarins with cytotoxic potential against cancer cells.

Revisiting nature: a review of iridoids as a potential antileishmanial class.

Leishmaniasis still stands as one of the most prevalent neglected tropical diseases in the least developed and emerging countries. The recommended therapeutic arsenal to treat leishmaniasis is characterized by several shortcomings, and resistance has already been reported. Hence, this dramatic background highlights the pressing need to develop novel, affordable, and safe antileishmanial drugs. Multiple classes of natural compounds have been reported to possess antileishmanial activity. Among these classes, iridoids stand out as a special type of monoterpenoids with diverse biological properties-including their antileishmanial potential. This review aims to discuss the available literature between 1991 and 2020 related to the antileishmanial activity of the iridoid class. Throughout the past decades, various investigations attributed antileishmanial action to assorted iridoid types, including inhibitory potential towards validated drug targets and immunomodulatory activity. The latter deserves special attention due to the ability of some iridoids to improve the host's immune response against parasites. It opens the possibility of iridoids become adjuncts in leishmaniasis treatments by improving the efficacy of currently employed drugs. Furthermore, the present study intends to provide a convenient visual representation of which iridoids and Leishmania spp. species have been most investigated as a guide for further researches.

Optimization of Coumarins Extraction from Pterocaulon balansae by Box-Behnken Design and Anti-Trichomonas vaginalis Activity.

Trichomonas vaginalis causes trichomoniasis, a nonviral sexually transmitted infection with a high prevalence worldwide. Oral metronidazole is the drug of choice for the treatment of this disease, although high levels of T. vaginalis resistance to this agent are well documented in the literature. This study describes the anti-T. vaginalis activity of an optimized coumarin-rich extract from Pterocaulon balansae. Optimization was performed to maximize extraction of total coumarins by means of a 3-level Box-Behnken design, evaluating the effect of three factors: extraction time, plant : solvent ratio, and ethanol concentration. Optimum conditions were found to be 5 h extraction time and a plant : solvent ratio of 1% (w/v) and 60% (v/v) ethanol, which resulted in approximately 30 mg of total coumarins/g of dry plant. The coumarin-enriched extract exhibited a minimum inhibitory concentration of 30 µg/mL and an IC50 of 3.2 µg/mL against T. vaginalis, a low cytotoxicity, and a high selectivity index (18 for vaginal epithelial cells and 16 for erythrocytes). The coumarins permeation/retention profile through porcine vaginal mucosa was evaluated in Franz-type diffusion cells. After 8 h of kinetics, coumarins were detected in the tissue (4.93 µg/g) without detecting them in the receptor compartment. A significant increase of coumarins in the mucosa layers (8.18 µg/g) and receptor compartment (0.26 µg/g) was detected when a T. vaginalis suspension (2 × 105 trophozoites/mL) was previously added onto the mucosa. No alterations were visualized in the stratified squamous non-keratinized epithelium of the porcine vaginal mucosa after contact with the extract. Overall, these results suggest that the P. balansae coumarin-rich extract may have potential as a treatment for trichomoniasis.

In vitro protective effect of topical nanoemulgels containing Brazilian red propolis benzophenones against UV-induced skin damage.

The overexposure of the skin to ultraviolet (UV) radiation may lead to oxidative stress, resulting in severe damage. The prevention of skin injuries through the topical application of natural compounds rich in antioxidants, such as propolis extracts, has shown promising results. In Brazil, the "red propolis" extract has stood out due to its complex constitution, based mainly on polyprenylated benzophenones (BZP). However, although the use of red propolis extracts has been shown to be encouraging, their addition in topical formulations is limited by the low solubility of BZP. For this reason, this study aimed to develop topical nanoemulgels containing Brazilian red propolis (BRP) extract to increase the potential of topical application, and the evaluation of skin protection against UVA/UVB radiation damage by means of protein carbonylation, protein thiol content and TBARS assays. The nanoemulgels were obtained by adding gelling polymer to nanoemulsions that were previously prepared by spontaneous emulsification. In this sense, a nanoemulgel containing BRP extract-loaded nanoemulsions (H-NE) and a nanoemulgel containing BRP extract-loaded nanoemulsions with DOTAP (H-NE/DT) were prepared. The physicochemical characterization of nanoemulgels showed monodisperse populations of 200-300 nm. The H-NE zeta potential was -38 mV, while that of H-NE/DT was +36 mV. BZP content in the formulations was around 0.86 mg g-1. These parameters remained stable for 90 days under cold storage. H/NE and H-NE/DT presented a non-Newtonian pseudoplastic rheological behavior. Permeation/retention studies, through porcine ear skin, showed the highest BZP retention (18.11 µg cm-2 after 8 h) for H-NE/DT, which also demonstrated, in an in vitro study, the highest ability to protect skin against oxidative damage after UVA/UVB radiation exposure. The results concerning the antioxidant activity revealed that formulations containing the BRP n-hexane extract were the most promising in combating oxidative stress, probable due to the presence of polyprenylated BZP. Altogether, the outcomes of this study suggest that nanoemulgels have suitable characteristics for topical application, and may be an alternative for the prevention of oxidative skin damage caused by UVA/UVB radiation.

Antifungal activity of Allamanda polyantha seed extract and its iridoids promote morphological alterations in Cryptococcus spp.

Cryptococcosis, caused by Cryptococcus spp., is an invasive fungal infection of the central nervous system, associated with high mortality, affecting mainly immunocompromised patients. Due to the development of resistance to the current therapy, there is an urgent need for less toxic and more effective antifungal agents. In this study, we describe the antifungal activity against Cryptococcus spp. of an aqueous seed extract from Allamanda polyantha (ASEAP) and two iridoids, plumieride and plumieridine, isolated from this extract with an antifungal activity. The capsule formation and the morphological alterations were evaluated using fluorescent microscopy. The cytotoxic activity was also investigated. The minimal inhibitory concentration (MIC) values of ASEAP for Cryptococcus gattii were 70 and 36 µg/ml (for the R265 and R272 strains, respectively) and 563 µg/ml for Cryptococcus neoformans H99. ASEAP inhibited C. neoformans H99 capsule formation, an important virulence factor, and decreased the cell body size for both the C. gattii strains. H99 cells also presented morphological alterations, with defects in bud detachment and nuclear fragmentation. Plumieride and plumieridine presented higher MIC values than ASEAP, indicating that other compounds might contribute to antifungal activity and/or that combination of the compounds results in a higher antifungal activity.

Bioactive Dimeric Acylphloroglucinols from the Mexican Fern Elaphoglossum paleaceum.

Two new prenylated acylphloroglucinols, paleacenins A (1) and B (2), were isolated from the rhizome n-hexane and chloroform extracts of the fern Elaphoglossum paleaceum. Both compounds were found to possess the same geranylated filicinic acid moiety but have a different phloroglucinol ring substituent. Their structures were determined using 1H and 13C NMR spectroscopic, HRMS, and ECD analysis. The plant extracts and purified compounds were assayed for inhibition of monoamine oxidase (MAO) activity, and the n-hexane and chloroform extracts displayed 25.0% and 26.5% inhibition of MAO-A, respectively, as well as 42.5% and 23.7% inhibition of MAO-B, respectively. Compounds 1 and 2 exhibited IC50 values of 31.0 (1.3) µM for MAO-A and 4.7 (4.4) µM for MAO-B. Paleacenin A (1) showed a higher selective index (SI) toward MAO-B (SIMAO-B/MAO-A 0.1), and paleacenin B (2) exhibited selectivity to MAO-A (SIMAO-B/MAO-A, 3.5). The extracts showed cytotoxicity against a panel of prostate, cervix, breast, and colon cancer cell lines (IC50 values between 1.7 and 10.6 µg/mL); the pure compounds were more active against the prostate, cervix, and colon cancer cell lines. Paleacenins A (1) and B (2), with IC50 values of 46 and 41 µM, respectively, inhibited nitric oxide production by the RAW264.7 murine macrophage model.

Phloroglucinol derivatives from Hypericum species trigger mitochondrial dysfunction in Leishmania amazonensis.

Bioactive molecules isolated from plants are promising sources for the development of new therapies against leishmaniasis. We investigated the leishmanicidal activity of cariphenone A (1), isouliginosin B (2) and uliginosin B (3) isolated from Hypericum species. Promastigotes and amastigotes of Leishmania amazonensis were incubated with compounds 1-3 at concentrations 1-100 µm for 48 h. The anti-promastigote effect of compounds was also tested in combinations. The cytotoxicity against macrophages and human erythrocytes were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method and hemolysis assay, respectively. The compounds 1-3 showed high leishmanicidal activity against promastigotes, IC50 values of 10.5, 17.5 and 11.3 µm, respectively. Synergistic interactions were found to the associations of compounds 1 and 2 [Σ fractional inhibitory concentration (FIC) = 0.41], and 2 and 3 (ΣFIC = 0.28) on promastigotes. All Hypericum compounds induced mitochondrial hyperpolarization and reactive oxygen species production in promastigotes. The compounds showed low cytotoxicity toward mammalian cells, high selectivity index and killed intracellular amastigotes probably mediated by oxidative stress. These results indicate that these compounds are promising candidates for the development of drugs against leishmaniasis.

Antinociceptive Activity of Phloroglucinol Derivatives Isolated from Southern Brazilian Hypericum Species.

The south Brazilian Hypericum species have revealed the presence of a series of biologically active phloroglucinol derivatives. In this study, a mixture of japonicine A and an isomer with an unreported structure, named japonicine E, was isolated from the roots of H. polyanthemum. Additionally, uliginosin A from H. myrianthum, isouliginosin B from H. polyanthemum, hyperbrasilol B and isohyperbrasilol B from H. caprifoliatum and cariphenone A from H. carinatum were also isolated. The structures were elucidated using 1D- and 2D-NMR experiments and by comparison with previously reported data. The compounds japonicines A/E, uliginosin A, isouliginosin B, hyperbrasilol B and cariphenone A exhibited antinociceptive activity in the mice hot-plate test and did not induce motor impairment in the rotarod apparatus.

Skin Permeation and Oxidative Protection Effect of Soybean Isoflavones from Topical Nanoemulsions-a Comparative Study of Extracts and Pure Compounds.

Soybean isoflavone-rich extracts have been considered as promising skin antiaging products due to their antioxidant activity. This study investigates the effect of soybean isoflavone forms on porcine ear skin permeation/retention from topical nanoemulsions and their potential in protecting skin against oxidative damage caused by UVA/UVB light. Soybean non-hydrolyzed (SNHE) and hydrolyzed (SHE) extracts, mainly composed of genistin and genistein, were produced. Nanoemulsions containing SNHE (NESNHE) and SHE (NESHE) were prepared by spontaneous emulsification procedure and yielded monodispersed nanoemulsions. A delay of isoflavone release was observed after extracts incorporation into nanoemulsions when compared to a propyleneglycol dispersion of pure compounds. An increase of isoflavone skin retention from nanoemulsions was also achieved. However, from extracts, a higher amount of genistin (NESNHE) and a lower amount of genistein (NESHE) were detected in the skin in comparison to pure isoflavones. Finally, the protection of porcine ear skin by formulations against UVA/UVB oxidative stress was evaluated. Extract-loaded nanoemulsions offered better skin protection than pure isoflavones. Skin lipids were similarly protected by NESHE and NESNHE, whereas skin proteins were more protected by NESNHE. Overall, nanoemulsions containing isoflavone-rich soybean extracts may be considered a better topical formulation aiming skin protection from UVA/UVB oxidative damage.

Denudatin A, a Dimeric Acylphloroglucinol from Hypericum denudatum Presents an Antinociceptive Effect in Mice.

A new dimeric acylphloroglucinol, denudatin A (1), was isolated from the flowering aerials parts of Hypericum denudatum, along with the known phloroglucinols selancin A (2), hyperbrasilol A (3), uliginosin B (4), and isouliginosin B (5). The structure of 1 was elucidated using 1D, 2D NMR, and MS experiments, and by comparison with previously reported data for Hypericum dimeric acylphloroglucinols. Denudatin A (1) and selancin A (2) were administered orally to mice displaying antinociceptive activity in the hot plate test. The compounds did not induce motor impairment in the rotarod apparatus.

Characterization of Phloroglucinol-enriched Fractions of Brazilian Hypericum Species and Evaluation of Their Effect on Human Keratinocytes Proliferation.

In this study, a phytochemical and biological investigation on five South Brazilian Hypericum species (Hypericum caprifoliatum, Hypericum carinatum, Hypericum connatum, Hypericum myrianthum, and Hypericum polyanthemum) was carried out. The phloroglucinol-enriched fractions (PEF) of the flowering aerial parts were analyzed by high-performance liquid chromatography for the content of uliginosin A (1), japonicin A (2), uliginosin B (3), hyperbrasilol B (4), and the three benzopyrans, that is, 6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran (HP1) (5), 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran (HP2) (6), and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran (HP3) (7). After chemical characterization, the PEF were assayed for cell proliferation on human keratinocyte cell line by MTT. The H. carinatum and H. polyanthemum PEF demonstrated better results with an increase in cell proliferation (138.7% and 120.6%, respectively). The cell counting and Ki-67 assay with H. carinatum PEF confirmed the MTT results. The cell cycle distribution indicates an increase in the cells at S and G2/M phases, which is indicative of proliferation induction. In summary, the results indicate an induction of HaCaT proliferation by the treatment with H. carinatum PEF (at 10 and 15 µg/mL), suggesting a possible use as wound healing agent. Copyright © 2016 John Wiley & Sons, Ltd.

Nanoemulsions Containing a Coumarin-Rich Extract from Pterocaulon balansae (Asteraceae) for the Treatment of Ocular Acanthamoeba Keratitis.

This study describes the incorporation of a coumarin-rich extract from Pterocaulon balansae into nanoemulsions intended for the local treatment of ocular keratitis caused by Acanthamoeba. The n-hexane dewaxed extract of P. balansae was characterized by HPLC/PDA and UPLC/MS. The presence of four major coumarins was detected, where 5-methoxy-6,7-methylenedioxycoumarin was selected as a chemical marker. This extract was then incorporated into nanoemulsions composed of medium chain triglycerides and egg-lecithin, through spontaneous emulsification. Such a procedure yielded the formation of monodisperse nanoemulsions in a sub-300-nm range, regardless of the amount of extract incorporated (1.0-5.0 mg/mL). The amoebicidal activity against Acanthamoeba castellanii was both dose-dependent and incubation time-dependent. A reduction of 95% of trophozoite viability was detected after 24 h of incubation with a nanoemulsion at 1.25 mg/mL of coumarins, being a similar effect detected for chlorhexidine. These results suggest a potential of the formulations developed in this study as a new strategy for the treatment of ocular keratitis caused by Acanthamoeba.

Effects of diene valepotriates from Valeriana glechomifolia on Na+/K+-ATPase activity in the cortex and hippocampus of mice.

Diene valepotriates obtained from Valeriana glechomifolia present antidepressant-like activity, mediated by dopaminergic and noradrenergic neurotransmissions. Also, previous studies have shown inhibitory activity of diene valepotriates towards Na(+)/K(+)-ATPase from the rat brain in vitro. Nevertheless, in vivo studies regarding the action of diene valepotriates on this enzyme are still lacking. Considering that Na(+)/K(+)-ATPase cerebral activity is involved in depressive disorders, the aim of this study was to investigate the effects of acute (5 mg/kg, p. o.) and repeated (5 mg/kg, p. o., once a day for three days) diene valepotriate administration on Na(+)/K(+)-ATPase activity in the cortex and hippocampus of mice submitted or not submitted to the forced swimming test. In addition, the protein expression of Na(+)/K(+)-ATPase α1, α2, and α3 isoforms in the cortex of mice repeatedly treated with diene valepotriates (and submitted or not submitted to the forced swimming test) was investigated. Diene valepotriates significantly decreased mice immobility time in the forced swimming test when compared to the control group. Only the animals repeatedly treated with diene valepotriates presented increased Na(+)/K(+)-ATPase activity in the cerebral cortex, and the exposure to the forced swimming test counteracted the effects of the diene valepotriates. No alterations in the hippocampal Na(+)/K(+)-ATPase activity were observed. Repeated diene valepotriate administration increased the cortical content of the α2 isoform, but the α3 isoform protein expression was augmented only in mice repeatedly treated with diene valepotriates and forced to swim. Mice treated with the vehicle and submitted to the forced swimming test also presented an increase in the content of the α2 isoform, but no alterations in Na(+)/K(+)-ATPase activity. These results suggest that cortical Na(+)/K(+)-ATPase may represent a molecular target of the diene valepotriates in vivo and long-term regulatory mechanisms are involved in this effect. Also, the forced swimming test per se influences the protein expression of Na(+)/K(+)-ATPase isoforms and counteracts the effects of the diene valepotriates on cortical Na(+)/K(+)-ATPase.

Quantification of Coumarins in Aqueous Extract of Pterocaulon balansae (Asteraceae) and Characterization of a New Compound.

Plants from the genus Pterocaulon are popularly used as antifungal and wound-healing agents. Such activities have been related to coumarins, which are abundant in those plants. Coumarins are soluble in organic solvents, such as hexane and dichloromethane, and some of them are also soluble in hot water. Considering that infusion and decoctions of these plants are used in traditional medicine, the aim of this study was to identify and quantify the coumarins in the aqueous extract of Pterocaulon balansae. The aqueous extract was obtained by dynamic maceration and the compounds were characterized by UPLC-UV-MS analysis. A new coumarin and 5-methoxy-6,7-methylenedioxycoumarin, used for validation of the analytical HPLC method were obtained by partition of the aqueous extract with n-hexane. The HPLC method validated was linear, specific, and precise. Seven coumarins were characterized in the aqueous extract in a range of 0.584-54 mg/g of dry plant material. The main compound, 5,6-dimethoxy-7-(3'-methyl-2',3'-dihydroxybutyloxy)coumarin, is described for the first time in P. balansae together with a new compound, 5,6-dimethoxy-7-(2',3'-epoxy-3'-methylbutyloxy)coumarin.

Acylphloroglucinol derivatives from Hypericum andinum: antidepressant-like activity of andinin A.

A new dimeric acylphloroglucinol derivative, andinin A (1), was isolated from the underground plant parts of Hypericum andinum, along with three known dimeric acylphloroglucinols, uliginosin A (2), uliginosin B (3), and isouliginosin B (4). The structure of 1 was elucidated using 1D and 2D NMR and MS experiments and by comparison with previously reported data for Hypericum dimeric acylphloroglucinols. Andinin A (1) displayed antidepressant-like activity in a mouse forced-swimming test when administered orally at doses of 3, 10, and 30 mg/kg.

Antiprotozoal potential of Vismia species (Hypericaceae), medicinal plants used to fight cutaneous leishmaniasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Species of Vismia (Hypericaceae), known in Brazil as "lacre", are commonly used in traditional Amazonian medicine for the treatment of skin lesions, including those caused by Leishmania infection. AIM OF THE STUDY: Hexane extracts from the leaves of Vismia cayennensis, V. gracilis, V. sandwithii and V. guianensis, as well as from the fruits of the latter, in addition to the anthraquinones vismiaquinone, physcion and chrysophanol isolated from these species were explored for their anti-promastigote and anti-amastigote activity on Leishmania amazonensis. MATERIALS AND METHODS: Extracts were prepared by static maceration with n-hexane. The compounds, isolated by chromatographic techniques, were identified by spectroscopic methods (1H and 13C NMR). Promastigotes of L.amazonensis were incubated with hexane extracts (1-50 µg/mL) or anthraquinones (1-50 µM) and the parasite survival analyzed. The action of compounds on reactive oxygen species (ROS) production, mitochondrial membrane potential, and membrane integrity of promastigotes were evaluated by flow cytometer, and the cytotoxicity on mammalian cells using MTT assay. Furthermore, the activity of compounds against amastigotes and nitric oxide production were also investigated. RESULTS: Vismiaquinone and physcion were obtained from the leaves of V. guianensis. Physcion, as well as chrysophanol, were isolated from V. sandwithii. Vismia cayennensis and V. gracilis also showed vismiaquinone, compound detected in lower quantity in the fruits of V. guianensis. All extracts were active against the parasite, corroborating the popular use. The greatest activity against promastigotes was achieved with V. guianensis extract (IC50 4.3 µg/mL), precisely the most used Vismia species for treating cutaneous leishmaniasis. Vismiaquinone and physcion exhibited relevant activity with IC50 12.6 and 2.6 µM, respectively. Moreover, all extracts and anthraquinones tested induced ROS production, mitochondrial dysfunction, membrane disruption and were able to kill intracellular amastigote forms, being worthy of further in vivo studies as potential antileishmanial drugs. CONCLUSIONS: The overall data achieved in the current investigation scientifically validate the traditional use of Vismia species, mainly V. guianensis, as an anti-Leishmania agent. Furthermore, the promising results presented here indicate species of Vismia as potentially useful resources of Brazilian flora for the discovery of therapeutic solutions for neglected diseases.

Anti-Leishmania effect of icetexanes from Salvia procurrens.

BACKGROUND AND PURPOSE: Leishmaniasis is a globally prevalent vector-borne disease caused by parasites of the genus Leishmania. The available chemotherapeutic drugs present problems related to efficacy, emergence of parasite resistance, toxicity and high cost, justifying the search for new drugs. Several classes of compounds have demonstrated activity against Leishmania, including icetexane-type diterpenes, previously isolated from Salvia and other Lamiaceae genera. Thus, in this study, compounds of Salvia procurrens were investigated for their leishmanicidal and immunomodulatory activities. METHODS: The exudate of S. procurrens was obtained by rapidly dipping the aerial parts in dichloromethane. The compounds were isolated by column and centrifugal planar chromatography over silica gel. The effects on L. amazonensis growth, survival, membrane integrity, reactive oxygen species (ROS) generation, mitochondrial membrane potential and cytotoxicity of the compounds towards human erythrocytes, peripheral blood mononuclear cells and macrophages were evaluated. The effects on intracellular amastigote forms, nitric oxide (NO) and TNF-α production were also investigated. RESULTS: The exudate from the leaves afforded the novel icetexane 7-hydroxyfruticulin A (1) as well as the known demethylisofruticulin A (2), fruticulin A (3) and demethylfruticulin A (4). The compounds (1-4) were tested against promastigotes of L. amazonensis and showed an effective inhibition of the parasite survival (IC50 = 4.08-16.26 µM). In addition, they also induced mitochondrial ROS production, plasma membrane permeability and mitochondrial dysfunction in treated parasites, and presented low cytotoxicity against macrophages. Furthermore, all diterpenes tested reduced the number of parasites inside macrophages, by mechanisms involving TNF-α, NO and ROS. CONCLUSION: The results suggest the potential of 7-hydroxyfruticulin A (1) as well as the known demethylisofruticulin A (2),fruticulin A (3) and demethylfruticulin A (4) as candidates for use in further studies on the design of anti-leishmanial drugs.

Topical Nanoemulsions as Delivery Systems for Green Extracts of Pterocaulon balansae Aiming at the Treatment of Sporotrichosis.

Coumarins are benzopyrones found in several plant genera, including Pterocaulon (Asteraceae). These compounds represent an important source of new treatments, especially as antimicrobial and antifungal agents. In this study, two coumarin-rich extracts from Pterocaulon balansae using green technologies were obtained through aqueous maceration (AE) and supercritical fluid extraction (SFE). Such extracts were incorporated into nanoemulsions (NAE and NSFE) composed of a medium-chain triglyceride oil core stabilized by phospholipids. The nanoemulsions exhibited droplet sizes between 127 and 162 nm, pH above 5.0, and viscosity of approximately 1.0 cP, properties compatible with the topical route. The coumarins permeation/retention from formulations through ear porcine skin using Franz-type diffusion cells were evaluated. Whatever the extract, coumarins were distributed in skin layers, especially in the dermis in both intact and impaired (tape stripping) skin. In addition, a significant increase in coumarins that reached up to the receptor fluid was observed for impaired skin, with increases of approximately threefold for NAE and fourfold for NSFE. Finally, antifungal activity of nanoemulsions was evaluated according to minimum inhibitory concentrations, and the values were 250 µg/mL for all strains tested. The overall results demonstrated the feasibility of incorporating P. balansae extracts into nanoemulsions and showed a potential alternative for the treatment of sporotrichosis.

Larvicidal activity of lipophilic extract of Hypericum carinatum (Clusiaceae) against Aedes aegypti (Diptera: Culicidae) and benzophenones determination.

In this study, the larvicidal activity of an enriched fraction of the major lipophilic phenolic compounds from Hypericum carinatum Griseb. (Clusiaceae) was investigated against larvae of Aedes aegypti (Diptera: Culicidae), the main vector of dengue virus in Brazil. The larval mortality rate ranged 37.33 to 72.00 % at concentrations of 66-200 µg/mL. The effect demonstrated to be dose-dependent. The lethal concentration 50 % and confidence interval were 100 and 88-111 µg/mL, respectively. The results could be attributed to the presence of cariphenone A and cariphenone B in concentrations of 1.24 ± 0.04 and 0.56 ± 0.01 %, respectively, determined by high-performance liquid chromatography. Besides, the results reinforce the potential of genus Hypericum as source of alternative insecticides.

Iridoids as a Potential Hepatoprotective Class: A Review.

BACKGROUND: Liver disease rates are gradually increasing over the years, becoming a severe public health problem. The indiscriminate use of drugs associated with a rich fat diet, high consumption of alcoholic beverages, and exposure to viral infections and lipid peroxidative products are considered the chief factors for developing hepatic disorders. Owing to the absence of reliable hepatoprotective drugs in the therapeutic arsenal, since they present a high incidence of adverse reactions and/or lack of efficacy in some cases, liver diseases are widely treated with medicinal plants. Among them are the plants producing iridoids, which are believed to be good remedies for liver disease due to their bitter taste. The hepatoprotective effect of iridoids and extracts, rich in these compounds, has been demonstrated, both in vitro and in vivo. OBJECTIVE: This review aims to scrutinize the available literature related to the hepatoprotective activity of iridoids. METHODS: The information was obtained from scientific databases (Science Direct, PubMed, Web of Science, Scopus, ACS Publications, Wiley Online Library) until December, 2021. RESULTS AND CONCLUSION: A total of 63 hepatoprotective iridoids were found, including aucubin, catalpol and picroliv, a mixture of two iridoids. They are the target of a high number of studies, which revealed their protective action against different hepatotoxic agents and detailed action mechanisms.