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.

Campomanesia lineatifolia Ruiz & Pavón (Myrtaceae): Isolation of major and minor compounds of phenolic-rich extract by high-speed countercurrent chromatography and anti-inflammatory evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Campomanesia lineatifolia Ruiz & Pavón (Myrtaceae), an edible species found in Brazilian Forest, possesses leaves that are traditionally used for the treatment of gastrointestinal disorders in Brazil. Extracts of C. lineatifolia are rich in phenolics and exhibit antioxidant, and gastric antiulcer properties. Furthermore, Campomanesia spp. have been described to possess anti-inflammatory properties, but studies related to chemical constituents of C. lineatifolia are scarce in the literature. AIM OF THE STUDY: This work aims to identify the chemical composition of the phenolic-rich ethanol extract (PEE) from C. lineatifolia leaves and evaluate the anti-inflammatory activity that could be related to its ethnopharmacological use. MATERIALS AND METHODS: The high-speed countercurrent chromatography (HSCCC), using an isocratic and a step gradient elution method, and NMR, HPLC-ESI-QTOF-MS/MS were used to isolate and identify the chemicals of PEE, respectively. Lipopolysaccharide-(LPS)-stimulated THP-1 cells were used to evaluate the anti-inflammatory activities from PEE and the two majority flavonoids isolated by measure TNF-α and NF-κB inhibition assays. RESULTS: Fourteen compounds were isolated from the PEE, further identified by NMR and HPLC-ESI-QTOF-MS/MS, twelve of them are new compounds, and two others are already known for the species. The PEE, quercitrin and myricitrin promoted a concentration-dependent inhibition of TNF-α, and PEE promoted an inhibition of NF-κB pathway. CONCLUSIONS: PEE from C. lineatifolia leaves demonstrated significant anti-inflammatory activity that may be related to the traditional use to treat gastrointestinal disorders.

Anticoagulant and antiplatelet activity of aqueous extracts of Citrus sinensis and Lippia alba : interactions and potential for the development of antithrombotics.

Citrus sinensis and Lippia alba are herbal medicines widely used in the form of tea (infusion, decoction), which ethanolic extracts have already shown great anticoagulant activity in vitro . For this reason, they seem to be excellent candidates for the development of new antithrombotics and also have the potential to interact with them. The aim of this study was to evaluate the activity of aqueous extracts in blood coagulation and platelet aggregation, in addition to analysing the micromolecular composition of these species. Thrombin generation test (TGT) by the Calibrated Automated Thrombogram method and Platelet Aggregation Test by turbidimetry were performed to evaluate the biological activities, while the chemical composition was qualitatively evaluated using high-performance liquid chromatography. Aqueous extracts were elaborated according to the folk use. All extracts were effective in reducing thrombin formation in TGT. Infusion of L. alba and infusion and decoction of C. sinensis at a concentration of 0.6 mg/ml significantly reduced platelet aggregation induced by ADP, and only the decoction of L. alba at the same concentration was able to significantly reduce collagen-induced platelet aggregation. The presence of phenylpropanoids and flavonoids in C. sinensis and L. alba extracts was verified. Furthermore, hesperidin was identified in C. sinensis through coinjection. C. sinensis and L. alba are rich in phenolics and demonstrated an in-vitro effect on important processes of haemostasis (blood coagulation, platelet agreggation), corroborating the potential of C. sinensis and L. alba for the development of antithrombotics and interact with them.

Changes in antiparasitical activity of gold nanorods according to the chosen synthesis.

Gold nanorods (GNRs) are increasingly being studied for diagnostic and therapeutic purposes. Green synthesis based methods with natural compounds as additives stand out as a hope in terms of better synthesis methodology, with advantages of producing potentially less toxic and, perhaps, biologically active GNRs due to influence of natural additives used during synthesis. Exploring green chemistry using different natural phenolic compounds, the present work reveals different in vitro activity of GNRs evaluated against different parasites that causes skin infectious diseases compared to GNRs produced by convencional seed mediated method. This approach brings advantages in producing active GNRs, with ease calling, less cytotoxic and with a better selectivity index (SI) than GNRs synthesized by conventional seed mediated synthesis, opening new possibilities for therapies. Natural compounds used in green syntheses were gallic acid (GA), resveratrol (RSV) and a purified fraction of the hydroalcoholic extract of Stryphnodendron obovatum. GNRs exhibited great activity against Leishmania braziliensis, and the dermatophytes Tricophyton rubrum, T. interdigitale and Microsporum gypseum. The anti-Leishmania and antidermatophytic activity of GNRs reinforce the applicability of GNRs in biomedical field and the influence of synthesis method in biological activity, showing benefits related to the seedless synthesis with natural compounds. In addition, these preliminary results indicate the possibility of exploring at maximum the physical and chemical properties of GNRs in addition to the biological activity itself, such as the development of topical antiparasitic formulations for association with phototherapy.

Chemical Composition and In Vitro Anti-Helicobacter pylori Activity of Campomanesia lineatifolia Ruiz & Pavón (Myrtaceae) Essential Oil.

Helicobacter pylori is the most common cause of gastritis and peptic ulcers, and the number of resistant strains to multiple conventional antimicrobial agents has been increasing in different parts of the world. Several studies have shown that some essential oils (EO) have bioactive compounds, which can be attributed to antimicrobial activity. Therefore, EOs have been proposed as a natural alternative to antibiotics, or for use in combination with conventional treatment for H. pylori infection. Campomanesia lineatifolia is an edible species found in the Brazilian forests, and their leaves are traditionally used for the treatment of gastrointestinal disorders. Anti-inflammatory, gastroprotective, and antioxidant properties are attributed to C. lineatifolia leaf extracts; however, studies related to the chemical constituents of the essential oil and anti-H. pylori activity is not described. This work aims to identify the chemical composition of the EO from C. lineatifolia leaves and evaluate the anti-H. pylori activity. The EO was obtained by hydrodistillation from C. lineatifolia leaves and characterized by gas chromatography-mass spectrometry analyses. To assess the in vitro anti-H. pylori activity of the C. lineatifolia leaf's EO (6 µL/mL-25 µL/mL), we performed broth microdilution assays by using type cultures (ATCC 49503, NCTC 11638, both clarithromycin-sensitive) and clinical isolate strains (SSR359, clarithromycin-sensitive, and SSR366, clarithromycin-resistant). A total of eight new compounds were identified from the EO (3-hexen-1-ol (46.15%), α-cadinol (20.35%), 1,1-diethoxyethane (13.08%), 2,3-dicyano-7,7-dimethyl-5,6-benzonorbornadiene (10.78%), aromadendrene 2 (3.0%), [3-S-(3α, 3aα, 6α, 8aα)]-4,5,6,7,8,8a-hexahydro-3,7,7-trimethyl-8-methylene-3H-3a,6-methanoazulene (2.99%), α-bisabolol (0.94%), and ß-curcumene (0.8%)), corresponding to 98.09% of the total oil composition. The EO inhibited the growth of all H. pylori strains tested (MIC 6 µL/mL). To our knowledge, the current study investigates the relation between the chemical composition and the anti-H. pylori activity of the C. lineatifolia EO for the first time. Our findings show the potential use of the C. lineatifolia leaf EO against sensitive and resistant clarithromycin H. pylori strains and suggest that this antimicrobial activity could be related to its ethnopharmacological use.

Costus spiralis extract restores kidney function in cisplatin-induced nephrotoxicity model: Ethnopharmacological use, chemical and toxicological investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Costus spiralis (Jacq.). Roscoe (Costaceae) is traditionally used in Brazil for the treatment of kidney diseases such as pyelonephritis, urethra inflammation, kidney stones, and inflammatory conditions. There are reports of its use by Brazilian Indians since the 17th century when it was known as "pacocatinga." Currently, the use of the Costus species in Brazil is widespread, which was evidenced by the inclusion of the genus in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (RENISUS). AIM OF THE STUDY: This study aimed to confirm the ethnopharmacological use of Costus spiralis in the treatment of kidney diseases, toxicity study using animal models, and the phytochemistry of the species. MATERIALS AND METHODS: The chemical profile of Costus spiralis leaves extract (CSLE) was obtained for the hydroethanolic extract by ultra-performance liquid chromatography coupled to a mass spectrometer and ultraviolet detector with diode array (UPLC-UV/DAD-ESI-MS). The acute oral toxicity of the extract was predicted using the neutral red uptake cytotoxicity assay. Wistar rats were used in a model in vivo for confirmation of acute oral toxicity (2000 mg/kg p.o. for 14 days.) and determination of the effect on a cisplatin-induced nephrotoxicity model. RESULTS: The analysis by UPLC-UV/DAD-ESI-MS showed that the chemical composition of the extract is mostly di-glycosylated flavones of apigenin. In the extract were identified the flavones vicenin II and schaftoside. The quantification of total flavonoids by spectrometry showed 0.880%. CSLE proved to be safe for acute oral administration (2000 mg/kg) with an IC50 value of 222.9 µg/mL and predicted oral toxic dose of 523.82 µg/mL in a neutral red uptake cytotoxicity assay. The absence of death allows the classification of the extract in class 5 according to OECD 423 guidelines and therefore it can be considered as a high acute safety product, which is highly relevant, considering the wide popular use of the species. In the cisplatin-induced nephrotoxicity model, C. spiralis extract (5, 15, and 30 mg/kg) significantly improved renal function, reversing almost completely the effects on plasma creatinine levels and creatinine clearance (p < 0.001). CONCLUSIONS: This study demonstrates that oral administration of Costus spiralis extract leaves is safe and effective in restoring the renal function in rats in a cisplatin-induced nephrotoxicity. It is suggested that the observed activity is related to the flavonoids present. This hypothesis should be confirmed, and the participation of other secondary metabolites should be investigated in the future.

Antifungal effect of hydroethanolic extract of Fridericia chica (Bonpl.) L. G. Lohmann leaves and its therapeutic use in a vulvovaginal candidosis model.

Vulvovaginal candidosis (VVC) is one of the most frequent causes of gynecological consultations. Therefore, the development of new antifungal therapies against VVC is relevant. In this context, the leaves of Fridericia chica (Bonpl.) L. G. Lohmann are considered a therapeutic alternative since they are traditionally used in VVC therapy. However, no scientific evidence has supported this use against fungal vaginal infections. Then, we aimed to characterize the antifungal effect of a hydroethanolic extract of F. chica leaves (HEFc) and evaluate the therapeutic potential of this extract in a VVC model. HEFc inhibited the growth of C. albicans (256-1,204 µg/mL) and C. krusei (512 µg/mL) in vitro. HEFc inhibited yeast-to-hypha transition in C. albicans and has a low ability to induce resistance in this species. Intravaginal use of the HEFc at 50 mg/mL causes mycological cure in animals with VVC after 6 days of treatment, similar to the effect observed for the commercial antifungal nystatin. These results support the traditional use of F. chica leaves as a topical therapeutic option to treat VVC.

Mechanisms and interactions in concomitant use of herbs and warfarin therapy: An updated review.

This review is an updated and expanded version published in this journal in 2016. Warfarin pharmacotherapy is extremely complex, since in addition to being a low therapeutic index drug, it does not follow the dose-response pattern and has characteristics that predispose the occurrence of interactions, such as high binding rate to plasma proteins, metabolization by cytochrome P450 enzymes, further to acting in the complex process of blood coagulation, platelet activation, and inflammation. For these reasons, warfarin has great potential for interaction with drugs, foods, and herbal medicines. Herb-warfarin interactions, however, are still not very well studied; thus, the objective of this update is to present new information on the subject aiming to provide a scientific basis to help health professionals in the clinical management of these interactions. A literature review was performed from May to June 2021 in multiple databases and articles published in 2016 to 2021 were included. A total of 59 articles describing 114 herbal medicines were reported to interact with warfarin. Of the plants mentioned, 84% had the potential to increase warfarin effect and the risk of bleeding. Targets possibly involved in these interactions include the processes of blood coagulation, platelet activation, and inflammation, in addition to the pharmacokinetics and pharmacodynamics of warfarin. Despite these alarming numbers, however, the clinical management of interactions is known to be effective. Thus, it is important that the use of these herbal medicines be done with caution in anticoagulated patients and that studies of herb-drug interactions be encouraged in order to generate information to support the clinical management of patients.

TNF-α inhibition, antioxidant effects and chemical analysis of extracts and fraction from Brazilian guaraná seed powder.

Paullinia cupana Kunth., commonly named Guaraná, is a plant from Brazil used as stimulant. The aim of this study was to evaluate the potential of extracts and tannins-rich and methylxanthines-free fraction from guaraná in the anti-inflammatory and antioxidant effect in vitro. Extract 1 obtained good yields of tannins and methylxanthines and was used to identify a type-A procyanidin trimer by LC-ESI-MS. Fraction 4 was rich in tannins and absent of methylxanthines. The extracts and fraction exhibited strong capacity for scavenging DPPH radical with IC50 between 5.88 and 42.75-µg/mL and inhibited TNF-α release by LPS-activated THP-1 cells when compared with control cells and did not present toxicity to THP-1 cells. The fraction 4, rich in tannins, was highly active, with IC50 5.88 µg/mL by DPPH method and inhibited TNF-α release in 83.50% at 90 µg/mL. These results reinforced potential anti-inflammatory of guaraná and data for new therapeutic approaches.

New antiglaucomatous agent for the treatment of open angle glaucoma: Polymeric inserts for drug release and in vitro and in vivo study.

A benzamidine derivative from diminazene was tested for a novel activity: treatment of primary open-angle glaucoma. This drug was incorporated into mucoadhesive polymeric inserts prepared using chitosan (Chs) and chondroitin sulfate (CS). Of current interest is the mucoadhesion, which increases the contact time with the ocular surface, resulting in improved bioavailability; also, the inserts are made to act as a prolonged release system. In the present work the inserts were prepared by the solvent casting method using different polymeric proportions (30:70, 50:50, 75:25% w/w Chs:CS and 100% Chs). Thermal analysis and infrared spectroscopy both demonstrated physical dispersion of the active drug. The most promising was the 50:50% Chs:CS which demonstrated that it was not fragile and has an in vitro release profile of up to 180 minutes. In addition, it presented greater adhesion strength in relation to the other formulations. These physicochemical results corroborate the in vivo tests performed. In this sense, we also demonstrated that the treatment with the 50:50% insert can control the intraocular pressure (IOP) for at least 3 weeks and prevents damage to the retinal ganglion cells (RGCs) compared to the placebo insert. Thus, this indicates thus that the new drug is quite viable and promising in glaucoma treatment.

Development and validation of analytical method by HPLC-DAD for determination of vasodilator active in pharmaceutical ophthalmic forms

The substance 4-Aminobenzamidine dihydrochloride (4-AD) is one of the degradation products of diminazene aceturate and has demonstrated antiglaucomatous potential. Glaucoma is the second leading cause of blindness worldwide; thus, new therapeutic alternatives must be studied, for example, the molecule 4-AD vehiculated into polymeric inserts for prolonged release. The present work aims to develop and validate an analytical method to quantify 4-AD in pharmaceutical ophthalmic forms. A HPLC was used with UV-Vis detector, at 290 ƞm and ACE® C18 column (125 × 4.6 mm, 5 µm), in which the mobile phase consists of phosphate buffer (pH 7.4) and triethylamine (30 mmol/L), under an isocratic flow of 1.0 mL/min. The retention time of 3.2 minutes was observed. The method was developed and validated in accordance with ANVISA recommendations and ICH guides. The linearity range was established between the concentrations 5 and 25 µg/mL (correlation coefficient r = 0.993). The accuracy, repeatability, and intermediate precision tests obtained a relative standard deviation less than or equal to 5%. In addition, the method was considered selective, exact. and robust, with pH being its critical factor. Therefore, the HPLC analysis method is robust and can be used to quantify 4-AD in pharmaceutical forms for ocular application.(AU)

In Vitro Anticoagulant Activity of Mikania laevigata: Deepening the Study of the Possible Interaction Between Guaco and Anticoagulants.

Mikania laevigata, popularly known in Brazil as guaco, is widely used for respiratory disorders. As this plant is rich in coumarins, there is evidence of indications that it may cause bleeding and therefore should not be used concomitantly with anticoagulants. The basis of this information is very theoretical, with no clinical evidence of such contraindication. Thus, the aim of this study was to evaluate the in vitro effect of M. laevigata extract on blood coagulation through prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests, fibrinogen plasma concentration, and the new thrombin generation test, which investigate, with high sensibility, hemostatic changes (CAAE 60904316.6.0000.5149), besides evaluating its qualitative micromolecular composition, providing scientific evidence to support the management of patients taking warfarin. Ethanolic extracts of guaco leaves were incubated with a plasma pool of healthy individuals at concentrations of 1.67, 2.26, and 2.86 mg/mL. The presence of flavonoids, tannins, coumarins, and triterpenes was demonstrated by selective reagents in thin layer chromatography. Benzoylgrandifloric acid, cinnamoylgrandifloric acid, o-coumaric acid, coumarin, and quercetin-3-ß-glucoside were identified by coinjection in ultraperformance liquid chromatography. The extract at all concentrations prolonged TP and aPPT and reduced the potential for endogenous thrombin potential by the thrombin generation test. The control plasma had endogenous thrombin potential = 1465 nM/min, and after the addition of M. laevigata extract (2.26 mg/mL), this value was reduced to 1087 nM/min, indicating a lower generation of thrombin. Related to fibrinogen plasma concentration, concentrations of 2.26 and 2.86 mg/mL were effective in reducing plasma fibrinogen levels. These results allow us to conclude that the guaco extract demonstrated an anticoagulant effect in vitro, possibly interfering with intrinsic, extrinsic, and common coagulation pathways. A discussion on the contribution of the identified substances to the activity is also present.

Maltodextrin and Gum Arabic-Based Microencapsulation Methods for Anthocyanin Preservation in Juçara Palm (Euterpe edulis Martius) Fruit Pulp.

The juçara fruits (Euterpe edulis Martius), native to the Atlantic Forest, are rich in anthocyanins. To preserve the anthocyanins in juçara fruit pulp, this study aimed to evaluate the effectiveness of microencapsulation by spray drying and freeze drying with maltodextrin (dextrose equivalent 16.5 to 19.5) and gum arabic in different proportions. The obtained microparticles were characterized by quantifying the total polyphenol and anthocyanin contents, by performing differential scanning calorimetry, thermogravimetry, and infrared spectroscopy and by using scanning electron microscopy to analyze the morphology of the particles. The total amount of polyphenols in the fruit pulp was 750 ± 16.7 mg GAE/100 g of the freeze-dried sample. The total anthocyanins in the fruit pulp was 181.25 ± 5.36 (mg/100 g). The microparticles were formed by employing maltodextrin and gum arabic in a 1:1 proportion as the polymeric matrix; the mixtures of pulp and polymeric matrix were prepared in proportions of 2:3 and 2:1, preserving up to 83.69% of the anthocyanin content. Lyophilization of the 2:1 mixture resulted in an anthocyanin content of 116.89 ± 4.43 (mg/100 g), whereas lyophilization of the 2:3 mixture resulted in 151.68 ± 1.39 (mg/100 g) anthocyanin content, which did not differ from the value obtained by spray drying the 2:3 mixture (150.76 ± 5.79 (mg/100 g)). Thermal analyses showed that the microparticles obtained by freeze drying at a ratio of 2:3 presented greater resistance to degradation with increasing temperature. The incorporation of the pulp in the polymeric matrix was demonstrated by IR analyses. Microparticles obtained by freeze drying showed the formation of various-sized flakes, whereas those obtained by spray drying were spherical in shape. Microencapsulation is a possible alternative for improving the stability of the anthocyanins in this fruit.

A rapid simultaneous determination of methylxanthines and proanthocyanidins in Brazilian guaraná (Paullinia cupana Kunth.).

Paullinia cupana is a plant native to Brazil that is widely used in traditional medicine as a physical and mental stimulant. It is also used worldwide to produce soft drinks. A method for the simultaneous quantitation of seven markers in guaraná by HPLC-PDA was developed, and extraction methods for the determination of methylxanthines and tannins were investigated. Quantified substances were theobromine, theophylline, caffeine, catechin, epicatechin, procyanidins A2 and B2. Results confirmed the satisfactory selectivity and linearity (r2≥0.99) within the mass ranges. Repeatability (RSD≤2.80%), intermediate precision (RSD≤4.47%), accuracy (recoveries from 90.59%-104.67%), and robustness were demonstrated. Extract 1 presented the contents: 0.0177% (±1.02%) for theobromine, 0.0131% (±1.14%) for theophylline, 2.9429% (±1.27%) for caffeine, 0.4563% (±1.02%) for catechin, 0.5515% (±1.05%) for epicatechin, 0.0607% (±2.80%) for A2 and 0.1035% (±1.39%) for B2. The method for simultaneous quantitation of seven chemical markers in guaraná proved to be reliable using a simple and convenient HPLC setup.

In vivo efficacy of a biotherapic and eugenol formulation against Rhipicephalus microplus.

The control of Rhipicephalus microplus is essential to prevent cattle discomfort and economic losses. However, increased resistance and acaricides inefficiency lead producers to adopt strategies that could result in the accumulation of chemical residues in meat and milk with possibilities of poisoning in animals and people. This scenario demonstrates the necessity of research into the identification of novel, effective and environmentally safe therapeutic options for cattle tick control. The objectives of this study were to develop and assess the efficacy of R. microplus biotherapic and of 5% eugenol for the control of R. microplus in artificially infested calves. Eighteen male 6-month-old Holstein calves were divided into three groups of six animals. In Group 1, the animals did not receive medication (control group); in Group 2, the animals received 1 mL of R. microplus biotherapic at dilution 6CH (centesimal Hahnemannian), orally administered twice daily. And in Group 3, they received a single application of eugenol 5% in the pour-on formulation. The median efficacy for biotherapy and eugenol 5% was respectively 10.13 and 13.97%; however, upon analyzing reproductive efficiency, it is noteworthy that the biotherapic had 45.86% efficiency and was superior to the action of eugenol (12.03%) after 37 days of treatment. The ultrastructural study provided information about the effects of R. microplus biotherapic on the ovaries of engorged females and showed disorganization in the deposition of the oocyte exochorion. The results suggest hatchability inhibition of larvae, interference in R. microplus reproduction and future possibilities for eco-friendly control of R. microplus with biotherapic 6CH.

Review on mechanisms and interactions in concomitant use of herbs and warfarin therapy.

The effectiveness of warfarin, an oral anticoagulant originally derived from a plant, is strongly affected by patient's characteristics such as the age, presence of comorbidities, and concomitant use of another drug. Warfarin has the potential to interact with many drugs, medicinal plants, and food, which increases the risk of adverse events. A critical analysis of scientific literature was conducted to assess the interferences of medicinal plants with blood haemostasis and then with warfarin anticoagulation. We found 58 different plants that may alter the blood haemostasis and anticoagulation with warfarin. The herbs that showed the greatest potential to interact with warfarin include garlic, ginger, ginkgo, St. John's wort, and ginseng, i.e. plants normally consumed as food and also used for therapeutic purposes. The interactions between drugs and herbs are varied because of the complex chemical matrix of plants. Mainly coumarins, quinones, xanthones, terpenes, lignans, and vitamin K showed significant influence on warfarin treatment. In general, these plants can potentiate the effect of warfarin by stimulating anticoagulation in multiple ways, and the clinical outcome associated with this interaction is the increase of bleeding risk. Moreover, potential interactions between herbal products and drugs are a safety concern, especially for drugs with a narrow therapeutic index or for patients receiving drug treatment for chronic diseases, and both of these apply to warfarin pharmacotherapy. Therefore, this review article summarises the data on the influence of medicinal plants on warfarin treatment and analyses this information in view of the interaction targets. The relevant plants were categorised according to their target, and their effects are discussed in order to organise the isolated information and to highlight the need of further discussion and new studies on the safety of herbal medicines and warfarin.

Consumption of medicinal plants by patients with heart diseases at a pharmacist-managed anticoagulation clinic in Brazil.

BACKGROUND: Medicinal plants (MP) have been used for many years with the purpose of feeding and curing. Several MP may interfere in drug response and are not always considered as potential drug-interactors in clinical practice. OBJECTIVE: To investigate the consumption of MP by outpatients during a one-year follow-up. METHOD: Patients with cardiopathy diagnosis and indication(s) for long-term use of warfarin were recruited at a pharmacist-managed anticoagulation clinic of a Brazilian public hospital. This research employed a descriptive method. The consumption of MP was examined regarding the type, frequency and forms of use. RESULTS: A total of 280 patients were studied. Most patients were female (54.6 %) with an average age of 56.8 ± 13.1 years. The consumption of MP was reported by 46 (16.4 %) patients, totalizing 59 occurrences. Lemon, lemon balm and plantain were the most common MP. The main pharmacological uses involved the digestive, urinary, and respiratory tracts. Tea was the predominant form of consumption (87 %). Twelve (33.3 %) plants presented potential herb-warfarin interactions according to the literature. CONCLUSION: We described the consumption of MP among outpatients characterized by their complex disease status, propensity for adverse events, and socioeconomic limitations. These results may guide pharmacist interventions and procedures to prevent clinical complications.

Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats.

The aim of this study was to develop and evaluate the effects of chitosan inserts for sustained release of the angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE), in experimental glaucoma. Monolayer DIZE loaded inserts (D+I) were prepared and characterized through swelling, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and in vitro drug release. Functionally, the effects of D+I were tested in glaucomatous rats. Glaucoma was induced by weekly injections of hyaluronic acid (HA) into the anterior chamber and intraocular pressure (IOP) measurements were performed. Retinal ganglion cells (RGC) and optic nerve head cupping were evaluated in histological sections. Biodistribution of the drug was accessed by scintigraphic images and ex vivo radiation counting. We found that DIZE increased the swelling index of the inserts. Also, it was molecularly dispersed and interspersed in the polymeric matrix as a freebase. DIZE did not lose its chemical integrity and activity when loaded in the inserts. The functional evaluation demonstrated that D+I decreased the IOP and maintained the IOP lowered for up to one month (last week: 11.0 ± 0.7 mmHg). This effect of D+I prevented the loss of RGC and degeneration of the optic nerve. No toxic effects in the eyes related to application of the inserts were observed. Moreover, biodistribution studies showed that D+I prolonged the retention of DIZE in the corneal site. We concluded that D+I provided sustained DIZE delivery in vivo, thereby evidencing the potential application of polymeric-based DIZE inserts for glaucoma management.

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment.

Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.