Effects of Resistance and Combined training on Vascular Function in Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of mortality in type 2 diabetes (T2D). Exercise can reduce the risk factors associated with CVD in T2D patients. However, research evaluating its beneficial effects in these patients has used different measurement protocols and types of exercise, complicating comparison. AIM: To assess the effects of resistance training (RT) and combined training (CT) on the vascular function of T2D patients. METHODS: A database search (MEDLINE, Scopus, and Web of Science) was performed to identify relevant articles that were published up to August 2017. Only original studies evaluating the effects of RT or CT interventions on vascular function in T2D patients were included. The articles were reviewed independently by at least three reviewers. The Cochrane guidelines were used to assess the methodological quality of the studies. Fourteen studies were finally included. Two studies only used RT and twelve studies used CT as intervention strategy. RESULTS AND CONCLUSIONS: The results show that resistance training is a useful means for primary treatment of vascular diseases and maintenance of vascular function in T2D patients. However, more studies are necessary to gain full knowledge of the beneficial effects and to identify tailored exercise plans to optimize these benefits. The information provided in this review may help to improve current treatment of vascular diseases in T2D patients and to design future studies.

The hearing of rural workers exposed to noise and pesticides.

n work environments, different physical and chemical agents that may pose a risk to workers' hearing health coexist. In this context, occupational hearing loss stands out. It has mostly been attributed to only noise exposure, although there are other agents, that is, pesticides that might contribute to occupational hearing loss. In this report, two cases will be presented that consider rural workers exposed to pesticides and intense noise generated by an adapted rudimentary vehicle. The noise measured in this vehicle was 88.3 dBA up to 93.4 dBA. Pure-tone audiometry, distortion product otoacoustic emissions, and high-frequency audiometry tests were performed. This report is unusual because of the short time of exposure to noise and pesticides and the hearing loss found, indicating a synergy between those agents.

Anti-hyperalgesic effect of Lippia grata leaf essential oil complexed with ß-cyclodextrin in a chronic musculoskeletal pain animal model: Complemented with a molecular docking and antioxidant screening.

BACKGROUND: Due to its unclear pathophysiology, the pharmacological treatment of fibromyalgia is a challenge for researchers. Studies using medicinal plants, such as those from the genus Lippia, complexed with cyclodextrins (CDs) have shown innovative results. OBJECTIVE: The present research intended to evaluate the effect of an inclusion complex containing ß-cyclodextrin (ßCD) inclusion complex with Lippia grata (LG) essential oil in a chronic musculoskeletal pain model, its central activity and its possible interaction with neurotransmitters involved in pain. METHODS: After acid saline-induced chronic muscle pain, male mice were evaluated for primary and secondary hyperalgesia and muscle strength. Moreover, an antagonist assay was performed to assess the possible involvement of the opioidergic, serotonergic and noradrenergic pathways. In addition, Fos protein in the spinal cord was assessed, and a docking study and antioxidant assays were performed. RESULTS: The treatment with LG-ßCD, especially in the dose of 24mg/kg, was able to significantly decrease (p<0.05) the paw withdrawal and muscle threshold. Furthermore, LG-ßCD was shown to affect the opioidergic and serotonergic pathways. There were no significant changes in muscle strength. Fos protein immunofluorescence showed a significant decrease in expression in the dorsal horn of the spinal cord. The main compounds of LG showed through the docking study interaction energies with the alpha-adrenergic and µOpioid receptors. In all antioxidant assays, LG exhibited stronger antioxidant activities than LG-ßCD. CONCLUSION: This study suggested that LG-ßCD could be considered as a valuable source for designing new drugs in the treatment of chronic pain, especially musculoskeletal pain.

The use of medicinal plants in venous ulcers: a systematic review with meta-analysis.

The aim of this study was to systematically review the use of medicinal plants for the treatment of varicose ulcers. The databases used in the search were: Medline/Pubmed, Scopus, Cinhal, Lilacs and Web of Science. The selection process was divided into two phases: the reading of titles and abstracts and the full reading of selected articles. The item description was compared with the checklist of the Consolidated Standards of Reporting Trials. The initial search produced 3505 articles and seven were selected for inclusion in the systematic review. Of the included studies, 7 (100%) evaluated the reduction of the ulcer area, 4 (57·14%) evaluated reepithelisation, 2 (28·57%) evaluated bacterial flora and 1 (14·28%) evaluated the oxygen pressure and percutaneous carbon dioxide. The level of evidence rating indicated that five studies (71·42%) were rated at level 2 and two (28·57%) were rated at level 3. The quality assessment was performed using the Jadad scale, which is prevalent in the literature. The quality score of the Jadad questionnaire ranges from 0 to 5; here, the studies analysed had an average of 2·5. A meta-analysis was performed on two studies that analysed the effects of Mimosa tenuiflora hydrogel in the treatment of venous ulcer and included 42 patients with a mean age of 60·5 years and a mean duration of treatment of 10·5 weeks. Heterogeneity was assessed using I2 ; we obtained a high value of 84%. We concluded that, despite the efficacy of the incorporation of Ageratina pichinchensis into the gel, the hydrogel that incorporated M. tenuiflora appeared to be a promising candidate for the management of venous ulcers.

Natural products assessed in animal models for orofacial pain – a systematic review

ABSTRACT Orofacial pain is related to tissues of the head, face, neck and all the intraoral structures; it is rather debilitating to the patient and also difficult to treat. There are relatively few studies dedicated to the use of natural products to alleviate orofacial pain in preclinical experiment models (performed in experimental animals which provide support for clinical trials). Main objectives of the present systematic review summarize the studies on natural products assessed in animal models for orofacial pain seeking to give evidence to future development of new pharmaceutical products to manage the orofacial pain. Our review includes a thorough search of literature using the terms of orofacial pain, facial pain, medicinal plants and natural products. This search was performed using to retrieve English language articles in Medline-PubMed, Scopus and Web of Science. A total of eighteen studies were included in our survey for the inclusion criteria. Firstly, this review identified 210 citations from electronic search, after removal of duplicates and screening for relevant titles and abstracts, a total of eighteen articles were selected to the inclusion criteria established. Our findings suggest that natural products can be a promising or a trump tool for the development of new drugs to treat orofacial pain conditions, but the researchers that deal with experimental preclinical trials of new drugs (including natural products or synthetic drugs) for orofacial pain conditions urgently need to show translational evidence (with clinical approach) of these compounds.

The effect of active learning methodologies on the teaching of pharmaceutical care in a Brazilian pharmacy faculty.

BACKGROUND: In recent years, pharmacists have been involved in expanded patient care responsibilities, for example patient counseling in self-medication, medication review and pharmaceutical care, which require graduates to develop the necessary competences. Consequently, reorientation of pharmacy education has become necessary. As such, active learning strategies have been introduced into classrooms to increase problem-solving and critical thinking skills of students. The objective of this study was to evaluate the performance and perceptions of competency of students in a new pharmaceutical care course that uses active learning methodologies. METHODS: This pharmaceutical care course was conducted in the first semester of 2014, in the Federal University of Sergipe. In the pharmaceutical care course, active learning methods were used, consisting of dialogic classroom expository, simulation and case studies. Student learning was evaluated using classroom tests and instruments that evaluated the perception of competency in pharmaceutical care practice. Furthermore, students' satisfaction with the course was evaluated. RESULTS: Thirty-three students completed the four evaluations used in the course (i.e., a discursive written exam, seminars, OSCE, and virtual patient); 25 were female (75.75%), and the median age was 23.43 (SD 2.82) years. The overall mean of student scores, in all evaluation methods was 7.97 (SD 0.59) on a scale of 0 to 10 points, and student performance on the virtual patient method was statistically superior to other methods. With respect to the perception of competency in pharmaceutical care practice, a comparison of pre- and post-test scores revealed statistically significant improvement for all evaluated competences. At the end of the semester, the students presented positive opinions of the pharmaceutical care course. CONCLUSIONS: The results suggest that an active learning course can enhance the learning of pharmaceutical care competences. In future studies it will be necessary to compare active learning to traditional methods.

Evaluation of the anti-inflammatory and antinociceptive effects of the essential oil from leaves of Xylopia laevigata in experimental models.

Xylopia laevigata (Annonaceae) is a medicinal plant used in folk medicine to treat pain and inflammation. Thus, we investigated the possible antioxidant, antinociceptive, and anti-inflammatory effects of X. laevigata leaf essential oil (EOX) in animal models. Our EOX sample showed the presence of γ-muurolene (17.78%), δ-cadinene (12.23%), bicyclogermacrene (7.77%), and α-copaene (7.17%) as main compounds. EOX presented a strong antioxidant potential according to the DPPH, TBARS, and nitrite production tests. Additionally, pretreatment with EOX, in mice, also significantly produced (P < 0.05 or P < 0.001) antinociceptive effect by reduction of nociceptive behavior (in formalin and writhing tests). The EOX showed c-Fos label in the olfactory bulb, piriform cortex, and periaqueductal gray. Acute administration of EOX exhibited a significant (P < 0.01 or P < 0.001) anti-inflammatory profile in the carrageenan-induced peritonitis and by the carrageenan-induced hindpaw edema tests in mice. Our results provide evidence for the use of X. laevigata by traditional medicine practitioners in the management of pain and inflammatory disorders.

Evidence for the involvement of spinal cord-inhibitory and cytokines-modulatory mechanisms in the anti-hyperalgesic effect of hecogenin acetate, a steroidal sapogenin-acetylated, in mice.

Hecogenin is a steroidal sapogenin largely drawn from the plants of the genus Agave, commonly known as 'sisal', and is one of the important precursors used by the pharmaceutical industry for the synthesis of steroid hormones. Hecogenin acetate (HA) is a steroidal sapogenin-acetylated that produces antinociceptive activity. Thus, we evaluate the antihyperalgesic profile of HA in mice in inflammatory models, as well as its possible involvement with c-fos expression on spinal cord area and cytokines to produces analgesic profile. Acute pretreatment with HA (5, 10, or 20 mg/kg; i.p.) inhibited the development of mechanical hyperalgesia induced by carrageenan, TNF-α, dopamine and PGE2. Additionally, the immunofluorescence data demonstrated that acute pretreatment with HA, at all doses tested, significantly inhibited Fos-like expression in the spinal cord dorsal horn normally observed after carrageenan-inflammation. Moreover, HA did not affect the motor performance of the mice as tested in the Rota rod test. This antinociceptive profile seems to be related, at least in part, to a reduction of pro-inflammatory cytokines, as IL-1ß. The present results suggest that HA attenuates mechanical hyperalgesia by blocking the neural transmission of pain at the spinal cord levels and by cytokines-inhibitory mechanisms.

Natural products evaluated in neuropathic pain models - a systematic review.

Chronic pain conditions, such as neuropathic pain, are a common problem that poses a major challenge to health-care providers due to its complex natural history, unclear aetiology and poor response towards therapy. Despite the large number of drugs available, the adherence is limited by the large range of side effects and pharmacological ineffectiveness. Thus, the search for new chemical entities that can act as promising molecules to treat chronic pain conditions has emerged. The natural products remain as the most promising sources of new chemical entities with applicability for the medical approach. Hence, we performed a systematic review analysing pre-clinical studies shown to be promising in a possible applicability in neuropathic pain. The search terms neuropathic pain, phytotherapy and medicinal plants were used to retrieve English language articles in LILACS, PUBMED and EMBASE published until 10 April 2013. From a total of 1529 articles surveyed, 28 met the inclusion and exclusion criteria established. The main chemical compounds studied were flavonoids (28%), terpenes (17%), alkaloids (14%), phenols (10%), carotenoids (10%) and others (21%). The mostly described animal models for the study of neuropathic pain included were chronic constriction injury (CCI - 32%), partial sciatic nerve ligation (PSNL - 28%), streptozotocin - induced diabetic (28%), alcoholic neuropathy (3.5%), sodium monoiodoacetate (MIA - 3.5%) and neuropathic pain induced by paclitaxel (3.5%). The opioids, serotonergic and cannabinoid systems are suggested as the most promising targets for the natural products described. Therefore, the data reviewed here suggest that these compounds are possible candidates for the treatment of chronic painful conditions, such as neuropathic pain.

Cardiovascular effects induced by linalool in normotensive and hypertensive rats.

Linalool is a monoterpene alcohol and constituent of several Brazilian aromatic medicinal plants, popularly used against hypertension. Cardiovascular effects induced by linalool were evaluated. In normotensive rats, (+/-)-linalool [1, 5, 10, and 20 mg/kg body weight (BW); intravenous (i.v.)]-induced hypotension was associated with tachycardia, which was attenuated by atropine (2 mg/kg BW) and N(G)-nitro-L-arginine methyl ester (20 mg/kg BW), but was not modified after indomethacin (5 mg/kg BW) administration. In hypertensive rats, linalool [200 mg/kg BW; oral (v.o.)] reduced blood pressure without changing the heart rate. In intact rings of rat mesenteric artery precontracted with 10 microM phenylephrine, linalool (from 6.4 x 10(-6) to 6.4 x 10(-3) M) induced relaxations in a concentration-dependent manner [E(max) = (115 +/- 13)%] that were not changed after atropine administration [E(max) = (105 +/- 2)%], and were not different from those obtained in endothelium-denuded rings precontracted with phenylephrine [E(max) = (108 +/- 7)%] or 80 mM KCl [E(max) = (113 +/- 7)%] or tetraethylammonium incubation [E(max) = (105 +/- 12)%]. Linalool (1.9 x 10(-3) M) antagonized the contractions induced by CaCl2 (3 x 10(-6)-10(-2) M) (maximal inhibition, 81%). Furthermore, linalool inhibited the contractions induced by 10 microM phenylephrine or 20 mM caffeine. In conclusion, these results demonstrate that linalool reduces blood pressure probably due to a direct effect on the vascular smooth muscle leading to vasodilation.

Detection of lung cancer using multiple genetic markers--a systematic review.

Lung cancer is the leading cause of cancer deaths worldwide, and has one of the lowest survival rates of any solid tumor. In recent years, several attempts have been conducted to improve an early or accelerated diagnosis due to better overall prognosis after therapy. The aim of this study was evaluating the use of genetic markers for diagnosis of lung cancer. This study was conducted in accordance to Transparent Reporting of Systematic Reviews and Meta-Analyses. Three Internet sources were used to search: MEDLINE-PubMed, EMBASE, and LILACS. The databases were searched for studies conducted in the period up to and including May 10, 2011. The following inclusion criteria were applied: lung cancer studies, and the use of genetic markers for diagnosis. Studies using animal models, review articles, meta-analyses, abstracts, conference proceedings, editorials/letters, case reports, incorrect study population, inadequate data, and cytology was not obtained, were excluded. A total of 1,901 abstracts/citations were identified for preliminary review. From 24 final selected studies, 17 referred to chromosomal markers diagnosis, eight to genes as marker, and one to both subjects. Fluorescence in situ hybridization (FISH) was applied in all studies. Despite the limitations of this study, application of genetic markers to lung cancer diagnosis seems to have prognosis value irrespective of detection methodology used. FISH was the main technique applied to diagnose genetics alterations and revealed a high specificity, although some authors reported low sensitivity.

Evidence for the involvement of descending pain-inhibitory mechanisms in the antinociceptive effect of hecogenin acetate.

Hecogenin is a sapogenin present in the leaves of species from the Agave genus, with a wide spectrum of reported pharmacological activities. The present study was undertaken to evaluate whether hecogenin acetate (1) has antinociceptive properties and to determine its mechanism of action. The nociceptive threshold was evaluated using the tail flick test in mice. Mice motor performance was evaluated in a Rotarod test. By using Fos expression as a marker of neural activation, the involvement of the periaqueductal gray in 1-induced antinociception was evaluated. Intraperitoneal administration of 1 (5-40 mg/kg) produced a dose-dependent increase in the tail flick latency time compared to vehicle-treated group (p < 0.01). Mice treated with 1 (40 mg/kg) did not show motor performance alterations. The antinociception of 1 (40 mg/kg) was prevented by naloxone (nonselective opioid receptor antagonist; 5 mg/kg), CTOP (µ-opioid receptor antagonist; 1 mg/kg), nor-BNI (κ-opioid receptor antagonist; 0.5 mg/kg), naltrindole (δ-opioid receptor antagonist; 3 mg/kg), or glibenclamide (ATP-sensitive K(+) channel blocker; 2 mg/kg). Systemic administration of 1 (5-40 mg/kg) increased the number of Fos positive cells in the periaqueductal gray. The present study has demonstrated for the first time that 1 produces consistent antinociception mediated by opioid receptors and endogenous analgesic mechanisms.

Chemical constituents and anticancer effects of the essential oil from leaves of Xylopia laevigata.

Xylopia laevigata, popularly known as "meiú" and "pindaíba", is a medicinal plant used in the folk medicine of the Brazilian Northeast for several purposes. The chemical constituents of the essential oil from leaves of X. laevigata, collected from wild plants growing at three different sites of the remaining Atlantic forest in Sergipe State (Brazilian Northeast), were analyzed by GC/FID and GC/MS. The effect of the essential oil samples was assessed on tumor cells in culture, as well on tumor growth in vivo. All samples of the essential oil were dominated by sesquiterpene constituents. A total of 44 compounds were identified and quantified. Although some small differences were observed in the chemical composition, the presence of γ-muurolene (0.60-17.99%), δ-cadinene (1.15-13.45%), germacrene B (3.22-7.31%), α-copaene (3.33-5.98%), germacrene D (9.09-60.44%), bicyclogermacrene (7.00-14.63%), and (E)-caryophyllene (5.43-7.98%) were verified as major constituents in all samples of the essential oil. In the in vitro cytotoxic study, the essential oil displayed cytotoxicity to all tumor cell lines tested, with the different samples displaying a similar profile; however, they were not hemolytic or genotoxic. In the in vivo antitumor study, tumor growth inhibition rates were 37.3-42.5%. The treatment with the essential oil did not significantly affect body weight, macroscopy of the organs, or blood leukocyte counts. In conclusion, the essential oil from the leaves of X. laevigata is chemically characterized by the presence of γ-muurolene, δ-cadinene, germacrene B, α-copaene, germacrene D, bicyclogermacrene, and (E)-caryophyllene as major constituents and possesses significant in vitro and in vivo anticancer potential.

Beneficial effects of the ethanol extract of Caesalpinia pyramidalis on the inflammatory response and abdominal hyperalgesia in rats with acute pancreatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia pyramidalis Tul. (Fabaceae) is a plant found in the Northeast of Brazil that is popularly used to treat inflammation. Acute pancreatitis (AP) is an inflammatory disease for which abdominal pain is a relevant symptom. As there is no specific therapy for AP, we investigated the effect of the ethanol extract from the inner bark of C. pyramidalis (EECp) on the AP induced by common bile duct obstruction (CBDO) in rats. MATERIAL AND METHODS: AP was induced in male Wistar rats (200-250 g, n=6-8) through laparotomy and subsequent CBDO. Animals were euthanized after 6 (G6h) or 24 h (G24h) of induction. In the G6h protocol, animals were pretreated with EECp (100-400 mg/kg, p.o.) or vehicle (Tween 80; 0.2%) 1h before CBDO or sham surgery. For the G24h protocol, rats were pretreated with EECp (400mg/kg, 1h before CBDO or 1 h before and 12 h after CBDO) or vehicle. The following parameters were measured: inflammatory/oxidative (myeloperoxidase activity and malondialdehyde formation in the pancreas and lung, leukocyte counts in the blood and serum nitrate/nitrite), enzymatic (serum amylase and lipase levels) and nociceptive (abdominal hyperalgesia). RESULTS: Induction of AP by CBDO significantly increased all the parameters evaluated in both G6h and G24h protocols when compared with the respective sham group. In the G6h protocol, the EECp pretreatment (400 mg/kg) significantly reduced all these parameters, besides completely inhibiting abdominal hyperalgesia. The same profile of reduction was observed from two administrations of EECp in the G24h protocol, while one single dose of EECp was able to significantly reduce pancreatic MDA, serum lipase levels, leukocyte counts in the blood and abdominal hyperalgesia without affecting the other parameters in the G24h protocol. Furthermore, rutin was found in the EECp. CONCLUSIONS: Our results demonstrated that EECp decreases inflammation, lipoperoxidation and hyperalgesia in CBDO-induced AP, making it of interest in future approaches to treat this condition.

Evaluation of the anti-inflammatory and antinociceptive properties of p-cymene in mice.

We attempted to identify the antinociceptive and anti-inflammatory actions of the monoterpene p-cymene. Firstly, behavioural screening was carried out to verify the influence of p-cymene [25, 50, and 100 mg/kg intraperitoneal (i.p.)] on the central nervous system (CNS) activity. The antinociceptive activity of p-cymene was evaluated by the acetic acid-induced writhing response, formalin, and hot-plate test, respectively. The leukocyte migration induced by injection of carrageenan was used to assess the anti-inflammatory activity. p-Cymene showed depressant activity on CNS after 4 h of treatment and also a possible action on the autonomous nervous system (ANS), mainly at the dose of 100 mg/kg (i.p.). It was found that p-cymene (50 and 100 mg/kg, i.p.) significantly (p < 0.05) reduced the writhing responses induced by acetic acid. p-Cymene also decreased the licking time in the first and second phase, respectively, of the formalin test. The results of the hot-plate test showed that all doses of p-cymene increased significantly the latency time of the response to the thermal stimulus in both licking and jumping parameters. In addition, there was a significantly (p < 0.05) decreased leukocyte migration at all doses of p-cymene. The experimental data demonstrate that p-cymene possesses antinociceptive and anti-inflammatory activities.

α-terpineol reduces mechanical hypernociception and inflammatory response.

α-Terpineol (TPN), a volatile monoterpene alcohol, is relatively non-toxic and one of the major components of the essential oils of various plant species. In this study, we tested for the antihypernociceptive activity of TPN (25, 50 or 100 mg/kg, i.p.) in mice using mechanical models of hypernociception induced by carrageenan (CG, 300 µg/paw) and the involvement of important mediators of its cascade signalling, such as tumour necrosis factor-α (TNF-α, 100 pg/paw), prostaglandin E2 (PGE2, 100 ng/paw) or dopamine (DA, 30 µg/paw). We also investigated the anti-inflammatory effect of TPN on the model of carrageenan-induced pleurisy and the LPS-induced nitrite production in murine macrophages. Pre-systemic treatment with TPN (25, 50 or 100 mg/kg, i.p.) inhibited the development of mechanical hypernociception induced by CG or TNF-α. A similar effect was also observed upon PGE2 and DA administration. In addition, TPN significantly inhibited the neutrophil influx in the pleurisy model. TPN (1, 10 and 100 µg/mL) also significantly reduced (p < 0.01) nitrite production in vitro. Our results provide information about the antinociceptive and anti-inflammatory properties of TPN on mechanical hypernociception and suggest that this compound might be potentially interesting in the development of new clinically relevant drugs for the management of painful and/or inflammatory disease.

Carvacrol attenuates mechanical hypernociception and inflammatory response.

Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 µg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.

Citral reduces nociceptive and inflammatory response in rodents

Citral (CIT), which contains the chiral enantiomers, neral (cis) and geranial (trans), is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001) against acetic acid (0.8 percent) induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05) only at higher dose (200 mg/kg) of CIT in the first phase of the test. CIT significantly reduce (p<0.001) nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg) significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg) significantly reduced (p<0.001) the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

Bioassay-guided evaluation of antinociceptive properties and chemical variability of the essential oil of Hyptis fruticosa.

The composition of three samples of essential oil (EO) extracted from the leaves and flowers of Hyptis fruticosa (Lamiaceae) were investigated by GC/MS and GC-FID. The variability of the constituents and biological activity were evaluated in the oil samples. Acetic acid-induced abdominal constrictions and formalin-induced pain tests in mice were used for screening the antinociceptive activity. The possible antagonism of the essential oils or morphine (MOR) antinociceptive effects by pretreatment with naloxone, showed no influence on the antinociceptive action of the oils in the acetic acid-induced writhing test. All examined oil samples presented antinociceptive activity. The oil sample obtained from the leaves collected during the vegetative growth stage, near São Cristóvão at Sítio Tujubeba exhibited the highest effect. The same oil sample had a main percentage of 1,8-cineole (18.70%). Nevertheless, the oil obtained from flowers collected at the same location, showed a significant difference (p < 0.05) in the response intensity in the first phase of paw licking (100 mg/kg) possibly due to the higher contents of α-pinene (20.51%) and ß-pinene (13.64%). The results provide evidence for the use of H. fruticosa by traditional medicine practitioners in the management of pain.

Characterisation of the anti-inflammatory and antinociceptive activities of the Hyptis pectinata (L.) Poit essential oil.

AIM OF THE STUDY: Hyptis pectinata Poit (Lamiaceae) is grown in the northeastern regions of Brazil and is popularly known as "sambacaitá" or "canudinho". It is extensively used in folk medicine to treat inflammatory conditions, bacterial infections, pain, and cancer. MATERIALS AND METHODS: Hyptis pectinata essential oil (EO, 10, 30, and 100mg/kg, p.o.) and the reference drugs morphine (5mg/kg, p.o.) and acetylsalicylic acid (ASA, 200mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortions and hot plate) or inflammation (formalin-induced licking response and the subcutaneous air-pouch model). To elucidate the EO's mechanism of action, animals were pre-treated with the opioid receptor antagonist naloxone (1mg/kg, i.p.), the cholinergic antagonist atropine (1mg/kg, i.p.), or l-nitro arginine methyl ester (l-NAME, 3mg/kg, i.p.) 30 min prior to the oral administration of the EO. RESULTS: The EO significantly inhibited the number of writhings and the time the animals spent licking their formalin-injected paws (second phase). The EO, at doses of 30 and 100mg/kg, increased baseline measurements and area under the curve measurements in the hot plate model, respectively. The administration of naloxone reversed the antinociceptive effect of the EO in the hot plate model. l-NAME significantly reversed the effects of the EO in the contortions and hot plate models. Atropine completely reversed the antinociceptive activity of the EO in all models. Additionally, the EO inhibited the inflammatory process induced by subcutaneous carrageenan injection by reducing cell migration, exudate volume, protein concentration, and inflammatory mediators (nitric oxide, prostaglandin E2, IL-6, and TNF-α) produced in the pouch. CONCLUSIONS: Our results indicate that the Hyptis pectinata essential oil exhibits antinociceptive effects, likely mediated by opioid and cholinergic receptors, and anti-inflammatory activity through the inhibition of nitric oxide and PGE2 production.