A novel quercetin/ß-cyclodextrin transdermal gel, combined or not with therapeutic ultrasound, reduces oxidative stress after skeletal muscle injury.

A gel containing the inclusion complex of quercetin and ß-cyclodextrin was developed in order to verify its effects, isolated or using phonophoresis, on oxidative biomarkers after skeletal muscle injury. 30 male rats were divided into one of five groups: Control (CTRL), Muscle Injury (MI), Therapeutic Pulsed Ultrasound (TPU), Therapeutic Pulsed Ultrasound plus Quercetin (TPU plus gel-QUE) or Quercetin gel (QUE). Quercetin gel was complexed with ß-Cyclodextrin (ß-CD) using chromatography (HPLC). TPU and quercetin application occurred with 2, 12, 24, 48, 72, 96 hours intervals after injury. Gastrocnemius muscle was injured by mechanical trauma. Lipid peroxidation, superoxide dismutase activity, and catalase activity were assessed. The inclusion complex exhibited adequate entrapment efficiency, relative density and pH. The viscosity of the complex showed a non-Newtonian pseudoplastic behavior. Quercetin/ß-cyclodextrin gel reduced lipid peroxidation, superoxide dismutase activity and catalase activity compared to muscle injury group. Similarly, phonophoresis and TPU also reduced the levels of these oxidative biomarkers. In conclusion, quercetin/ß-cyclodextrin transdermal gel reduces oxidative stress biomarkers after skeletal muscle injury irrespective of using phonophoresis.

Alpha-terpineol complexed with beta-cyclodextrin reduces damages caused by periodontitis in rats.

BACKGROUND AND OBJECTIVE: This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (ßCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis. MATERIAL AND METHODS: Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-ßCD (ligature), and 25 mg/kg of αTPN-ßCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy. RESULTS: The treatment with αTPN-ßCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-ßCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis. CONCLUSION: The results obtained suggest that the treatment with αTPN-ßCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-ßCD.

Coriandrum sativum Extract Prevents Alarm Substance-Induced Fear- and Anxiety-Like Responses in Adult Zebrafish.

Anxiety disorders appear to involve distinct neurobiological mechanisms and several medications are available against this mental health problem. However, pharmacological therapeutic approaches display undesirable side effects for patients, particularly when long-term therapy is required. Some evidences have suggested that Coriandrum sativum extract (CSE) provide sedative and anxiolytic effects. We investigate if CSE could attenuate anxiety-like behaviors induced by novelty and alarm substance exposures in zebrafish. Adult zebrafish were injected with vehicle, clonazepam, or CSE (25, 50 or 100 mg/kg) and submitted to novel tank test. At the end, saline or alarm substance was added and anxiety-like responses were recorded. Twenty-four hours after, fish were submitted to the light/dark test. Novelty associated with alarm substance exposure decreased distance traveled and total time mobile in novel tank, and CSE (at 50 and 100 mg/kg) prevented these alterations similarly to clonazepam. Alarm substance reduced the time spent in white compartment (p = 0.0193 as compared with vehicle group). Clonazepam and CSE prevented this anxiogenic effect of alarm substance. CSE presents anxiolytic effects against alarm substance-induced locomotor and anxiogenic responses similarly to clonazepam. These data corroborate with the use of this plant in traditional medicine and provides a putative new pharmacological intervention for anxiety disorders.

Development of morin/hydroxypropyl-ß-cyclodextrin inclusion complex: Enhancement of bioavailability, antihyperalgesic and anti-inflammatory effects.

Morin is a flavonoid has been reported with several pharmacological effects such as, antioxidant, anti-inflammatory, anticancer, antidiabetic, etc. However, morin has low solubility in water, which decreases the bioavailability and limits its clinical application. In this way, to improve the pharmaceutical properties, morin was complexed in hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and its oral bioavailability and anti-inflammatory effects were evaluated. Initially, a phase solubility study was performed, which showed that HP-ß-CD would be the better cyclodextrin for the formation of complexes with morin. The morin/HP-ß-CD inclusion complex (1:1) was prepared by freeze-drying method. The sample obtained was characterized by DSC, FTIR, PXRD, SEM and 1H NMR techniques, evidencing the formation of morin/HP-ß-CD inclusion complex. In addition, complexation efficiency (98.3%) and loading content (17.63%), determined by HPLC demonstrated that morin was efficiently complexed in HP-ß-CD. In vitro dissolution study confirmed that morin/HP-ß-CD inclusion complex increased the solubility and dissolution rate of morin. The oral bioavailability of the morin/HP-ß-CD complex and free morin were evaluated through a pharmacokinetic study in rat plasma. The oral bioavailability of morin complexed with HP-ß-CD was increased by 4.20 times compared with the free morin. Hyperalgesia induced by carrageenan and carrageenan-induced pleurisy were carried out in mice to evaluate the antihyperalgesic and anti-inflammatory activities of free morin and inclusion complex. Morin/HP-ß-CD inclusion complex showed antihyperalgesic effect in inflammatory pain model and anti-inflammatory effect decreasing leukocyte migration and TNF-α levels at a lower dose than free morin. Therefore, the morin/HP-ß-CD inclusion complex improved the solubility, dissolution rate, oral bioavailability, antihyperalgesic and anti-inflammatory effects of morin. In this way, the morin/HP-ß-CD inclusion complex exhibits potential for development of new pharmaceutical product for future clinical applications.

The ethanol extract of Leonurus sibiricus L. induces antioxidant, antinociceptive and topical anti-inflammatory effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus sibiricus L. (Lamiaceae), popularly known as motherwort, or "erva-de-macaé" or "rubim" in Brazil, is a plant used for the treatment of inflammatory conditions, but few studies have evaluated this anti-inflammatory activity or other activities that may be relevant. AIM OF THE STUDY: This study was undertaken to investigate the antioxidant, antinociceptive and topical anti-inflammatory effects of the ethanol extract of L. sibiricus (EELs). MATERIALS AND METHODS: Chromatographic analysis, determination of total phenolic and flavonoid contents and in vitro antioxidant assays were performed, while the formalin test and ear inflammation induced by 12-0-tetradecanoylphorbol-13-acetate (TPA) were performed in mice. RESULTS: We observed that total phenolic and flavonoids content in EELs were respectively 60.1mg of gallic acid equivalent/g of extract and 15.4mg of catechin equivalent/g of extract. Chlorogenic, caffeic, p-coumaric and ferulic acids, as well as quercetin were identified in EELs. This extract also led to the consumption of the radicals 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and nitric oxide, increased the ferric reducing/antioxidant power (FRAP) and inhibited the spontaneous or FeSO4-induced in vitro lipid peroxidation. In the formalin test, oral pretreatment with EELs (400mg/kg) reduced (p<0.001) the licking/biting time in the second phase, but not in the first phase. In the ear inflammation induced by TPA, the concomitant topical administration of EELs (0.3-3mg/ear) significantly reduced the edema, myeloperoxidase activity, levels of tumoral necrosis factor-α and interleukin-1ß and lipoperoxidation, as well as increased FRAP in ear tissue when compared to vehicle-treated ears. CONCLUSIONS: These results indicate that EELs has antioxidant, antinociceptive and topical anti-inflammatory activities, supporting the use of this plant in folk medicine.

Hesperetin-loaded lipid-core nanocapsules in polyamide: a new textile formulation for topical drug delivery.

Chronic venous insufficiency is characterized by chronic reflux disorder of blood from the peripheral to the central vein, with subsequent venous hypertension and resulting changes in the skin. Traditionally, nonsurgical treatments relied on the use of compression therapy, and more recently a variety of flavonoids have been shown to have positive effects. There have also been developments of more effective drug delivery systems using various textiles and nanotechnology to provide new therapeutic options. Our objective was to use nanotechnology to develop a new formulation containing hesperetin (Hst), a substance not previously used in the treatment of chronic venous insufficiency, impregnated into textile fibers as a possible alternative treatment of venous diseases. We prepared the nanocapsules using the interfacial deposition of preformed polymer method with an Hst concentration of 0.5 mg/mL and then characterized the size and distribution of particles. To quantify the Hst in the samples, we developed an analytical method using high-performance liquid chromatography. Studies of encapsulation efficiency (98.81%±0.28%), microscopy, drug release (free-Hst: 104.96%±12.83%; lipid-core nanocapsule-Hst: 69.90%±1.33%), penetration/permeation, drug content (0.46±0.01 mg/mL) and the effect of washing the textile after drug impregnation were performed as part of the study. The results showed that nanoparticles of a suitable size and distribution with controlled release of the drug and penetration/permeation into the skin layers were achieved. Furthermore, it was established that polyamide was able to hold more of the drug, with a 2.54 times higher content than the cotton fiber; after one wash and after five washes, this relation was 2.80 times higher. In conclusion, this is a promising therapeutic alternative to be further studied in clinical trials.

Medicinal plants and natural molecules with in vitro and in vivo activity against rotavirus: A systematic review.

BACKGROUND: Rotaviruses can cause life-threatening health disorders, such as severe dehydrating gastroenteritis and diarrhea in children. Vaccination is the main preventive strategy to reduce rotavirus diarrhea and the severity of episodes, but vaccines are not fully effective and new episodes may occur, even in vaccinated children. The WHO recommends oral rehydration therapy and zinc supplementation for rotavirus-induced diarrhea management. There is little preclinical evidence to support the use of phytotherapeutics in the management of rotaviral infections. PURPOSE: We aim to review the use of medicinal plants and natural molecules in the management of rotavirus infections in experimental studies. METHODS: Articles, published in the English language between 1991 and 2016, were retrieved from PubMed, Scopus and Web of Science using relevant keywords. The scientific literature mainly focusing on plant natural products with therapeutic efficacies against experimental models of rotavirus, were identified and tabulated. In addition, an assessment of the reliability of animal experiments was determined under ``Risk of Bias'' criteria. CHAPTERS: After an initial search and a revision of the inclusion criteria, 41 reports satisfied the objectives of the study. 36 articles were found concerning the anti-rotaviral potential in rotavirus infected cell lines. Among the active secondary metabolites screened for rotavirus inhibition, the polyphenols of flavonoid structure had acquired the highest number of studies in our survey, compared to phenolic acids, stilbenoids, tannins, pectins, terpenoids and flavonoid glycosides. Also, many phytochemicals reduced the efficacy of viral capsid proteins foremost to their elimination and improved the tendency of host-cell inhibiting virus absorption or by prevention of viral replication. Furthermore, five in vivo studies reported that herbs, as well its components, reduced the duration and severity of diarrhea in mice and piglets. The anti-rotavirus efficacy were highlighted based on improvements in reduction on liquid stool, fecal virus shedding, small intestinal histology, levels of inflammation related cytokines and signaling receptors. However, the quality of the experiments in animal studies contained certain types of bias in terms of how they were conducted and reported. CONCLUSION: We identified and summarized studies on medicinal plants and natural molecules having anti-rotavirus activity in order to further future developments of cures for rotavirus gastroenteritis.

Effects of luteolin and quercetin 3-ß-d-glucoside identified from Passiflora subpeltata leaves against acetaminophen induced hepatotoxicity in rats.

Passiflora subpeltata has many beneficial effects in the treatment of various diseases including inflammation, pain and fever. This study was aimed to analyze the phytochemical compounds present in acetone extract of P. subpeltata leaves and to evaluate their performance against paracetamol induced hepatotoxicity activity. HPLC-DAD method was used to identify and quantify the phytochemical compounds. Hepatoprotective activity of acetone extract in the treatment of rat liver functions was monitored by the measurement of blood parameters and serum biochemical parameters such as SGOT, SGPT, ALP and in vivo antioxidant parameters viz. SOD, CAT and LPO. Further, liver tissues were also subjected to histopathological analysis. The HPLC-DAD results showed the luteolin and quercetin 3-ß-d-glucoside as newly identified compounds in P. subpeltata species. Pre-treatment with acetone extract of P. subpeltata leaves at 200 and 400mg/kg doses significantly elevated the WBC, RBC and HB counts and retained the serum biochemical and enzymatic antioxidants levels to normal level. Based on this detailed study we conclude that acetone extract of P. subpeltata leaves offered better protection against hepatotoxicity induced by the acetaminophen.