Enhancement of the functionality of women with knee osteoarthritis by a gel formulation with Caryocar coriaceum Wittm ("Pequi") nanoencapsulated pulp fixed oil.

Osteoarthritis (OA) is a degenerative joint disease that occurs when there is a change in the mechanical and biological properties of the articular cartilage and the subchondral bone; The condition is more prevalent in women than in men. Pequi oil (PO), which is extracted from the fruits of the pequi tree (Caryocar coriaceum Wittm), is widely used in traditional medicine in the Brazilian northeast for the management of inflammation and joint pain. The aim of this study was to develop a pharmaceutical formulation containing Carbopol® hydrogel nanoencapsulated with pequi pulp fixed oil (PeONC) and evaluate its therapeutic effect on functionality and pain in women with knee osteoarthritis. The study was divided into two stages: Stage 1 - preparation and physico-chemical characterization of the pharmaceutical formulation containing PeONC, cell viability assays and skin irritability testing. Step 2 - A double-blind randomized clinical trial evaluating knee symptoms, quality of life, pressure pain, function, muscle strength and range of motion. The nanoformulation was in a gel form, with a particle size of 209.5 ± 1.06 nm, a pH of 6.23 ± 0.45, a zeta potential of - 23.1 ± 0.4 mV, a polydispersity index of 0.137 ± 0.52, and containing nanocapsules with a spherical shape a polymeric wall and an oily nucleus. The gel showed no cytotoxicity and was not irritating to human skin. The treatment with PeONC increased the strength of the knee flexor and extensor muscles and the total motion range of the knee. In addition, the treatment reduced knee instability, pain, swelling, and locking; There was also an improvement in some items of the SF-36 quality of life questionnaire such as in respect of functional capacity and social aspects. In conclusion, PeONC was found to be a stable, safe formulation with no toxicity in respect of topical use in humans. Additionally, the treatment produced an increase in muscle strength and functionality that was associated with reduced knee symptoms and improved quality of life. Our findings showed that in a group of women treated with PeONC mitigated the symptoms of knee osteoarthritis.

Anti-inflammatory and modulatory effects of steroidal saponins and sapogenins on cytokines: A review of pre-clinical research.

BACKGROUND: Saponins are glycosides which, after acid hydrolysis, liberate sugar(s) and an aglycone (sapogenin) which can be triterpenoid or steroidal in nature. Steroidal saponins and sapogenins have attracted significant attention as important natural anti-inflammatory compounds capable of acting on the activity of several inflammatory cytokines in various inflammatory models. PURPOSE: The aim of this review is to collect preclinical in vivo studies on the anti-inflammatory activity of steroidal saponins through the modulation of inflammatory cytokines. STUDY DESIGN AND METHODS: This review was carried out through a specialized search in three databases, that were accessed between September and October, 2021, and the publication period of the articles was not limited. Information about the name of the steroidal saponins, the animals used, the dose and route of administration, the model of pain or inflammation used, the tissue and experimental method used in the measurement of the cytokines, and the results observed on the levels of cytokines was retrieved. RESULTS: Forty-five (45) articles met the inclusion criteria, involving the saponins cantalasaponin-1, α-chaconine, dioscin, DT-13, lycoperoside H, protodioscin, α-solanine, timosaponin AIII and BII, trillin, and the sapogenins diosgenin, hecogenin, and ruscogenin. The surveys were carried out in seven different countries and only articles between 2007 and 2021 were found. The studies included in the review showed that the saponins and sapogenins were anti-inflammatory, antinociceptive and antioxidant and they modulate inflammatory cytokines mainly through the Nf-κB, TLR4 and MAPKs pathways. CONCLUSION: Steroidal saponins and sapogenins are promising compounds in handling of pain and inflammation for the development of natural product-derived drugs. However, it is necessary to increase the methodological quality of preclinical studies, mainly blinding and sample size calculation.

Physicochemical characterization and cosmetic applications of Passiflora nitida Kunth leaf extract

Abstract Passiflora nitida Kunth, an Amazonian Passiflora species, is little studied, although the specie's high biological potential. Herein the plant's pharmacognostic characterization, extract production, antioxidant potential evaluation, and application of this extract in cosmetic products is reported. The physical chemical parameters analyzed were particle size by sieve analysis, loss through drying, extractive yield, total ash content, laser granulometry, specific surface area and pore diameter (SBET), differential scanning calorimetry, thermogravimetry (TG), and wave dispersive X-Ray fluorescence (WDXRF). Total phenol/flavonoid content, LC-MS/MS analysis, DPPH and ABTS antioxidant radical assays, cytotoxicity, melanin, and tyrosinase inhibition in melanocytes test provided evidence to determine the content of the major constituent. P. nitida dry extract provided a fine powder with mesopores determined by SBET, with the TG curve showing five stages of mass loss. The antioxidant potential ranged between 23.5-31.5 mg∙mL-1 and tyrosinase inhibition between 400-654 µg∙mL-1. The species presented an antimelanogenic effect and an inhibitory activity of cellular tyrosinase (26.6%) at 25 µg/mL. The LC-MS/MS analysis of the spray-dried extract displayed the main and minor phenolic compounds constituting this sample. The results indicate that P. nitida extract has promising features for the development of cosmetic formulations

Effectiveness of Ozone Therapy as an Adjunct Treatment for Lower-Limb Ulcers: A Systematic Review.

OBJECTIVE: To evaluate the effectiveness of topical ozone therapy as an adjuvant treatment in the healing of lower limb ulcers through a systematic literature review. DATA SOURCES: Three databases were used to search for studies conducted in the period up to and including September 2020: PubMed, Scopus, and the Web of Science. STUDY SELECTION: The search identified 44 studies, 7 of which met the eligibility criteria and were evaluated. DATA EXTRACTION: Study design, study location, number of patients, patient age, type of control, wound type, intervention type, equipment used to generate ozone (ozone generation), evaluation methodology, and main results were extracted from each study. DATA SYNTHESIS: A total of 506 patients 18 years or older with chronic wounds, such as venous or diabetic ulcers, on the lower limbs were enrolled. The majority of studies addressed diabetic foot ulcers. CONCLUSIONS: The ozone therapy protocols demonstrated a healing effect in all included studies, and none reported adverse effects. This reinforces the need for more controlled and randomized clinical trials to determine the effectiveness of this treatment and establish clinical criteria for its use.

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.

Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats / Efeitos Bradicárdicos e Antiarrítmicos do D-Limoneno em Ratos

Abstract Background: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities. Objectives: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats. Methods: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05). Results: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05). Conclusions: DL produces bradycardia and antiarrhythmic activity in rat heart.

Resumo Fundamento: O D-limoneno (DL) é um monoterpeno e o principal componente do óleo essencial de frutas cítricas. Ele apresenta atividades anti-hiperglicêmicas e vasodilatadoras. Objetivos: Este estudo avaliou os efeitos cardiovasculares e antiarrítmicos potenciais do DL em ratos. Métodos: Os parâmetros hemodinâmicos e eletrocardiográficos (ECG) foram mensurados em ratos Wistar machos que, sob anestesia, tiveram a aorta abdominal e a veia cava inferior canuladas e receberam eletrodos implantados subcutaneamente. Na abordagem in vitro, o coração foi removido e perfundido utilizando a técnica de Langendorff. O nível de significância adotado foi de 5% (p < 0,05). Resultados: DL, nas doses de 10, 20 e 40 mg/kg (i.v), produziu bradicardia intensa e persistente associada à hipotensão. A bradicardia com QTc prolongado foi observada no registro in vivo do ECG. No modelo in vivo de arritmia induzida por Bay K8644, DL (10 mg / kg) houve diminuição do escore da arritmia de 15,33 ± 3,52 para 4,0 ± 2,64 u.a (p < 0,05, n = 4). Em corações perfundidos isolados, o DL (10-3 M) promoveu reduções significativas na frequência cardíaca (de 228,6 ± 8,5 ms para 196,0 ± 9,3 bpm; p < 0,05) e na pressão desenvolvida do ventrículo esquerdo (de 25,2 ± 3,4 para 5,9 ± 1,8 mmHg; n = 5, p < 0,05). Conclusões: O DL produz bradicardia e atividade antiarrítmica no coração de ratos.

Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats.

BACKGROUND: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities. OBJECTIVES: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats. METHODS: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05). RESULTS: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05). CONCLUSIONS: DL produces bradycardia and antiarrhythmic activity in rat heart.

Evaluation of the Use of Compressive Stockings Impregnated With Hesperetin-Based Nanocapsules in the Healing of Venous Ulcers: A Case Report.

Venous ulcers are a more severe complication of chronic venous insufficiency, significantly compromising patient quality of life (QoL). Compressive stockings are still the gold standard treatment method with alternative therapies currently being evaluated. In this perspective, we investigate the influence of compressive stockings impregnated with hesperetin-based nanocapsules in the healing process of venous ulcers. Compressive stockings impregnated with hesperetin-based nanocapsules were applied to a consenting patient for 6 months following all relevant ethical principles for patient studies. The patient was evaluated at baseline (T0), 3 months (T3), and 6 months (T6), using photographic register (healing) probes to measure skin melanin, erythema and hydration parameters, and venous diameters, followed by questionnaires regarding QoL and pain perception. Healing was observed at the 3-month time point and with 91.6% and 93.1% of retraction area in larger ulcers of the right leg and lateral portion of the left leg, respectively. The deepest ulcer in a medial portion of the left leg healed 47.3%. A reduction of all measured skin parameters was observed, indicating a possible hesperetin effect. The scores of QoL and pain were, respectively, in the ranges of 91.6 to 31.2 and 7 to 0. Reduction in venous diameters also indicates healing function. These preliminary findings suggest that compressive stockings impregnated with hesperetin nanocapsules enhance venous ulcer healing. Further clinical trial controlled by placebo, involving a greater number of patients, is required to confirm the findings of this case report.

Flavonoids as Th1/Th2 cytokines immunomodulators: A systematic review of studies on animal models.

BACKGROUND: Flavonoids are naturally occurring compounds, extensively distributed in plants. T helper (Th)1 and Th2 cytokines balance plays an essential role in the reaction of inflammatory, allergic and infectious processes and transplantation rejection. PURPOSE: This systematic review focuses on various classes of flavonoids with a view to evaluate whether Th1/Th2 cytokine-mediated pathways of immunoenhancement could reduce immune overwhelming reactions. METHODS: Articles in English published from inception to December 2017 reporting flavonoids with immunomodulatory activity for the management of immune-mediated disorders were acquired from PubMed, EMBASE, Scopus and Web of Science and a animal experiments where Th1 and Th2 cytokines were investigated to assess the outcome of immunoregulatory therapy were included. CHAPTERS: 1809 publications were identified and 26 were included in this review. Ten articles described the effect of flavonoids on allergic inflammation in an animal model of asthma; eleven in vivo studies evaluated the immunomodulating and immunosuppressive effects of flavonoids on Th1/Th2 cytokines production and five reports described the regulatory role of flavonoids for Th1/Th2 cytokine responses to experimental arthritis and myocarditis. Modulation of Th1/Th2 cytokine balance, inhibition of eosinophil accumulation and remodeling of the airways and lungs, downregulation of Notch and PI3K signaling pathways, regulation of CD4 + /CD8 + lymphocytes ratio and decreasing inflammatory mediator expressions levels are among the most important immunopharmacological mechanisms for the retrieved flavonoids. CONCLUSION: Naturally occurring flavonoids discussed in the present article have optimal immunomodulation to prevent immune-mediated disorders through management of Th1/Th2 cytokine balance.

Antihypertensive potential of linalool and linalool complexed with ß-cyclodextrin: Effects of subchronic treatment on blood pressure and vascular reactivity.

Linalool (LIN) is a monoterpene alcohol present in some aromatic medicinal plants with biological activities that can impact cardiovascular diseases. This chemical class is highly volatile and ß-cyclodextrin (ß-CD) has been employed to improve the pharmacological properties of monoterpenes. Thus, the aim of this study was to evaluate the cardiovascular effects of LIN free focusing on the antihypertensive properties of this monoterpene and to study whether LIN, complexed in ß-cyclodextrin (LIN-ßCD) is able to improve the pharmacological activity of LIN. Spontaneously hypertensive rats (SHR) were randomly divided into 5 groups, each treated daily for 21 days, in the following manner: group 1 (vehicle solution); group 2 (captopril; 30 mg/kg/day); group 3 (LIN; 100 mg/kg/day); group 4 (LIN; 50 mg/kg/day) and group 5 (LIN/ß-CD; 50 mg/kg/day). Daily body weight measurements were conducted and mean arterial pressure and heart rate were measured every 5 days. The mesenteric artery from treated animals was tested for phenylephrine and sodium nitroprusside (SNP) sensitivity. The SHR treated with vehicle demonstrated progressive increase in mean arterial pressure and captopril, a positive control, induced a significant decrease. After 21 days of treatment, the blood pressure of the SHR treated by (-)-LIN (100 mg/kg) was significantly reduced. In addition, various important cardiovascular parameters improved, including: the treatment with LIN prevented the development of cardiac hypertrophy, increased levels of the anti-inflammatory cytokine (IL-10), increased vasodilator responsiveness and reduced sensitivity to the sympathetic agonist. Furthermore, the inclusion complex containing LIN in ß-CD produced a higher antihypertensive profile when compared with uncomplexed form. Taking together, our results suggested that LIN shown a potential antihypertensive effect and ß-CD may be an important tool to improve the cardiovascular activity of LIN and other water-insoluble compounds.

Inclusion Complexes of Copaiba (Copaifera multijuga Hayne) Oleoresin and Cyclodextrins: Physicochemical Characterization and Anti-Inflammatory Activity.

Complexation with cyclodextrins (CDs) is a technique that has been extensively used to increase the aqueous solubility of oils and improve their stability. In addition, this technique has been used to convert oils into solid materials. This work aims to develop inclusion complexes of Copaifera multijuga oleoresin (CMO), which presents anti-inflammatory activity, with ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by kneading (KND) and slurry (SL) methods. Physicochemical characterization was performed to verify the occurrence of interactions between CMO and the cyclodextrins. Carrageenan-induced hind paw edema in mice was carried out to evaluate the anti-inflammatory activity of CMO alone as well as complexed with CDs. Physicochemical characterization confirmed the formation of inclusion complex of CMO with both ß-CD and HP-ß-CD by KND and SL methods. Carrageenan-induced paw edema test showed that the anti-inflammatory activity of CMO was maintained after complexation with ß-CD and HP-ß-CD, where they were able to decrease the levels of nitrite and myeloperoxidase. In conclusion, this study showed that it is possible to produce inclusion complexes of CMO with CDs by KND and SL methods without any change in CMO's anti-inflammatory activity.

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.

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.

UVA-UVB photoprotective activity of topical formulations containing Morinda citrifolia extract.

Exposure to solar radiation, particularly its ultraviolet (UV) component, has a variety of harmful effects on human health. Some of these effects include sunburn cell formations, basal and squamous cell cancers, melanoma, cataracts, photoaging of the skin, and immune suppression. The beneficial photoprotective effects of topical formulations with the extract, Morinda citrifolia, have not been investigated. This present study aims to investigate the potential benefits of M. citrifolia topical application on the dorsal skin of mice, exposed to UVA-UVB light. Using 7 days of treatment, [before (baseline values) and 20 h after UV exposure], the thickness, skin barrier damage (TEWL), erythema, and histological alterations were evaluated. The results showed that the formulations containing the extract protected the skin against UV-induced damage.

Abarema cochliacarpos extract decreases the inflammatory process and skeletal muscle injury induced by Bothrops leucurus venom.

Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation.

A systematic review for anti-inflammatory property of clusiaceae family: a preclinical approach.

Background. Clusiaceae family (sensu lato) is extensively used in ethnomedicine for treating a number of disease conditions which include cancer, inflammation, and infection. The aim of this review is to report the pharmacological potential of plants of Clusiaceae family with the anti-inflammatory activity in animal experiments. Methods. A systematic review about experiments investigating anti-inflammatory activity of Clusiaceae family was carried out by searching bibliographic databases such as Medline, Scopus and Embase. In this update, the search terms were "anti-inflammatory agents," "Clusiaceae," and "animals, laboratory." Results. A total of 255 publications with plants this family were identified. From the initial 255 studies, a total of 21 studies were selected for the final analysis. Studies with genera Allanblackia, Clusia, Garcinia or Rheedia, and Hypericum showed significant anti-inflammatory activity. The findings include a decrease of total leukocytes, a number of neutrophils, total protein concentration, granuloma formation, and paw or ear edema formation. Other interesting findings included decreased of the MPO activity, and inflammatory mediators such as NF- κ B and iNOS expression, PGE2 and Il-1 ß levels and a decrease in chronic inflammation. Conclusion. The data reported suggests the anti-inflammatory effect potential of Clusiaceae family in animal experiments.

Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in ß-cyclodextrin.

Previously, we have demonstrated the analgesic-like property of p-cymene in rodents. Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems. Here, we used p-cymene/ß-cyclodextrin (ß-CD) complex and p-cymene (PC) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene. Male mice (26-30g) were pretreated with PC/ß-CD (20 or 40mg/kg, p.o.), PC (20 or 40mg/kg, p.o.) or vehicle (distilled water), 0.5h before painful tests and antinociceptive effect was evaluated at times: 0.5, 1, 2, 4, 8, and 16h after treatment. We evaluated the analgesic-like effect of PC/ß-CD and PC in acetic acid-induced abdominal writhes, hot-plate, carrageenan-induced paw edema and in rota-rod apparatus. Our results demonstrated that acute treatment with complex PC/ß-CD produced an antinocicepitve effect (p<0.01 or p<0.001) for 8h followed whereas isolated PC produced the same effect for 2h. Similar results were obtained in hot-plate test, PC/ß-CD, in all doses, significantly reduces (p<0.01 or p<0.001) nociceptive behavior for 8h while isolated PC for 1h, did so only in higher dose. Such results were unlikely to be caused by motor abnormality. Systemic pretreatment with PC/ß-CD and PC inhibited the development paw edema by carrageenan 1%, but PC/ß-CD did so during a longer period when compared with isolated monoterpene alone. Our results provide evidence to propose that the complex with ß-CD improved analgesic and anti-inflammatory effects of p-cymene.

Antinociceptive action and redox properties of citronellal, an essential oil present in lemongrass.

Citronellal (CT) is a monoterpenoid and the major constituent of the mixture of terpenoids that give the citronella oil its lemon scent. Citronella oil is widely used around the world for various purposes and is mainly obtained from plants of the Cymbopogon genus, which are known as "lemongrass." Considering these plants have been used worldwide for various medicinal purposes, the interest of researchers to understand the biological activities of monoterpenoids related to the Cymbopogon genus has been increasing. In the present work, we investigated the antinociceptive action and the redox properties of CT. Our results indicate that intraperitoneal injection of CT was effective in reducing nociceptive face-rubbing behavior in both phases of the formalin test, which was also naloxone-sensitive. CT also evoked antinociceptive response in the capsaicin and glutamate tests. The total radical-trapping antioxidant parameter and total antioxidant reactivity assays indicate that CT at doses of 0.1 and 1 mg/mL exerts a significant antioxidant activity, which is probably related to its ability to scavenge superoxide and nitric oxide, but not H(2)O(2) or hydroxyl radicals, as evaluated separately by specific in vitro tests. These results show for the first time the antinociceptive potential of CT and indicate that the antioxidant properties of this compound may rely on its mechanism of biological actions because CT-containing natural products are used to treat various diseases related to oxidative stress and reactive species.

Redox properties and cytoprotective actions of atranorin, a lichen secondary metabolite.

Atranorin (ATR) is a lichenic secondary metabolite with potential uses in pharmacology. Antinociceptive and antiinflammatory actions have been reported, and the use of atranorin-enriched lichen extracts in folk medicine is widespread. Nonetheless, very few data on ATR biological actions are available. Here, we evaluated free radical scavenging activities and antioxidant potential of ATR using various in vitro assays for scavenging activity against hydroxyl radicals, hydrogen peroxide, superoxide radicals, and nitric oxide. The total reactive antioxidant potential (TRAP) and total antioxidant reactivity (TAR) indexes and in vitro lipoperoxidation were also evaluated. Besides, we determined the cytoprotective effect of ATR on H(2)O(2)-challenged SH-SY5Y cells by the MTT assay. ATR exerts differential effects towards reactive species production, enhancing hydrogen peroxide and nitric oxide production and acting as a superoxide scavenger; no activity toward hydroxyl radical production/scavenging was observed. Besides, TRAP/TAR analysis indicated that atranorin acts as a general antioxidant, although it demonstrated to enhance peroxyl radical-induced lipoperoxidation in vitro. ATR was not cytotoxic, and also protected SH-SY5Y cells against H(2)O(2)-induced cell viability impairment. Our results suggest that ATR has a relevant redox-active action, acting as a pro-oxidant or antioxidant agent depending on the radical. Also, it will exert cytoprotective effects on cells under oxidative stress induced by H(2)O(2).

Anti-inflammatory and toxicity studies of atranorin extracted from Cladina kalbii Ahti in rodents

Atranorin (ATR) is the main compound from the lichen Cladina kalbii Ahti, which grows in the arid regions of northeastern Brazil. This study was conducted to evaluate the anti-inflammatory and toxicological properties of ATR. To evaluate anti-inflammatory properties, paw edema was induced by injecting 0.1 mL of carrageenan into the subplantar region of the right hind paw of rats, and leukocyte migration was induced by injection of 500 µL of carrageenan into the peritoneal cavity of mice. In addition, we determined ATR cytotoxicity in L929 cells by MTT assay and acute (5 g/kg-single dose) and subchronic (50 mg/kg-30 days) toxicity tests in Wistar rats. The results showed that ATR (100 mg/kg and 200 mg/kg) exhibited significant anti-inflammatory activity (paw edema and leukocyte migration). In the acute toxicity test, the animals showed hypoactivity and lethargy during the initial period (first 6 hours) and increase in total protein, total and indirect bilirubin, and alkaline phosphatase after 14 days in ATR-treated male rats. The subchronic toxicity test revealed increases in total protein, globulin, gamma-glutamyl transferase, alkaline phosphatase, and total and direct bilirubin in ATR-treated female rats. Histological analysis revealed no changes in the architecture and morphology of the organs. These results suggest that ATR has significant anti-inflammatory activity, with no significant acute and subchronic toxicity or cytotoxicity.

Atranorina (ATR) é o principal composto do líquen Cladina kalbii Ahti, que cresce em terras áridas do nordeste brasileiro. Este estudo foi realizado para avaliar as propriedades antiinflamatórias e toxicológicas da ATR. Para avaliar as propriedades antiinflamatórias, o edema de pata foi induzido, administrando-se 0,1 mL de carragenina na região subplantar da pata traseira direita e a migração leucocitária foi induzida pela injeção de 500 µL de carragenina no peritônio. Além disso, determinou-se a citotoxicidade da ATR, utilizando-se a linhagem celular L929, através do teste de MTT e dos testes de toxicidade aguda (5 g/kg - dose única) e subcrônica (50 mg/kg-30 dias) em ratos Wistar. Os resultados mostraram que nas doses de (100 mg/kg e 200 mg/kg) a ATR exibiu atividade antiinflamatória significativa nos ensaios de edema de pata e migração leucocitária. Nos testes de toxicidade aguda, os animais apresentaram hipoatividade e letargia no período inicial (primeiras 6 horas) e aumento das proteínas totais, bilirrubinas total e indireta e fosfatase alcalina depois de 14 dias nos machos tratados. Para o ensaio subcrônico, houve aumento das proteínas totais, gama-glutamil-transferase, fosfatase alcalina e bilirrubina total e direta nas fêmeas tratadas com ATR. Não foram encontradas alterações na arquitetura e morfologia das lâminas histológicas observadas. Esses resultados sugerem que a ATR apresenta atividade antiinflamatória significativa, sem apresentar significativa toxicidade aguda, subcrônica e citotoxicidade.