Potential anti-arthritic and analgesic properties of essential oil and viridiflorol obtained from Allophylus edulis leaves in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Viridiflorol was identified and isolated from the essential oil of Allophylus edulis leaves (EOAE). A. edulis was used as "tereré", which is a drink made by the infusion of herbs in cold water, to treat pain (toothache and headache). All anti-nociceptive (analgesic) and anti-arthritic properties of EOAE and viridiflorol have not been completely scientifically clarified. AIM OF THE STUDY: The aim of the present study was to investigate the analgesic (anti-hyperalgesic and anti-nociceptive) and anti-arthritic properties of EOAE and viridiflorol using in vivo models. MATERIALS AND METHODS: The oral administration (p.o.) of EOAE (30, 100 and 300 mg/kg), viridiflorol (30, 100 and 200 mg/kg), morphine (1 mg/kg, subcutaneous route (s.c.)) and the intraplantar (local) administration (i.pl.) of viridiflorol (100 µg/paw) were tested using formalin model in Swiss mice. EOAE (100 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), and dexamethasone (1 mg/kg, s.c.) were tested by zymosan-articular inflammation and in open-field models. Viridiflorol (0.3, 20 and 200 µg/paw) was also tested in carrageenan model, and viridiflorol (200 µg/paw) was also tested in tumor necrosis factor-α (TNF-α), and dopamine (DOPA) models. RESULTS: The oral administration of EOAE (100 and 300 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), morphine (1 mg/kg, s.c.) (MOR) and local administration of viridiflorol (100 µg/paw) significantly inhibited edema and nociception in formalin model. Oral treatments with EOAE and viridiflorol (200 mg/kg) did not cause motor impairment in the open field test since they did not reduce locomotor activity. EOAE, viridiflorol and dexamethasone significantly reduced mechanical hyperalgesia, edema, total leukocytes, polymorphonuclear cells, nitric oxide and protein exudation in the zymosan-induced articular inflammation model. The local administration of viridiflorol (200 µg/paw, i.pl.) significantly inhibited mechanical hyperalgesia and edema induced by carrageenan, TNF-α and DOPA. CONCLUSIONS: This study confirms the potential anti-arthritic, anti-nocicepttive and anti-hyperalgesic properties of EOAE and viridiflorol. These properties could explain, at least in part, the folk use of A. edulis against including pain (toothache and headache). Viridiflorol could be partially responsible for the EOAE anti-hyperalgesic, anti-nociceptive and anti-arthritic properties and its mechanism of action could involve the inhibition of TNF-α and DOPA pathways.

Chemical composition and effects of ethanolic extract and gel of Cochlospermum regium (Schrank) Pilg. Leaves on inflammation, pain, and wounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Cochlospermum regium is well-known as "Algodãozinho do cerrado" in folk Brazilian medicine, and is used to fight infections, inflammation and skin disorders. AIM OF THE STUDY: To identify the phytochemical constituents and the effects of the ethanolic extract of C. regium leaves (EECR) on inflammation and pain, and the effects of C. regium gel (GEECR) on wound healing. MATERIALS AND METHODS: Animals were treated with EECR (30-300 mg/kg) or GEECR (1.25 and 2.5%) and studies were conducted using carrageenan-induced pleurisy and paw edema tests, formalin-induced pain model, and excision wound model. RESULTS: In total, 25 compounds, including quercitrin, methyl gallate, and 1,2,3,4,6-pentagalloylhexose, with highest detectability were identified. The treatments reduced leukocyte migration, nitric oxide production, protein extravasation, edema, mechanical hyperalgesia, pain in both phases (neurogenic and inflammatory), cold hypersensitivity, and improved wound closure and tissue regeneration. CONCLUSIONS: The present findings established the anti-inflammatory, anti-nociceptive, and wound healing potential of the leaves of C. regium, confirming the potential therapeutic effect of this plant.

Contribution of spathulenol to the anti-nociceptive effects of Psidium guineense.

Objectives: Araçá-verdadeiro is the popular name of Psidium guineense (Myrtaceae), whose fruits and leaves are used in Brazilian folk medicine for treatment of inflammation and pain. The focus of the present research was an investigation of the anti-nociceptive, and anti-inflammatory effects of the essential oil from P. guineense (EOPG) leaves, and of spathulenol. The anxiolytic and antidepressive effects associated with chronic pain were also investigated in models of acute or persistent nociception or/and inflammatory pain.Methods and Results: Oral treatment with EOPG (10-100 mg/kg) or spathulenol (10 mg/kg) significantly inhibited formalin-induced nociceptive responses, both sensitivity to cold and edema. Oral treatment with EOPG (10 mg/kg) and spathulenol (10 mg/kg) did not reduce locomotor activity (open field test). Local administration of spathulenol (1000 µg/paw) significantly prevented formalin-induced nociceptive sensitivity to cold and paw edema, and carrageenan-induced mechanical hyperalgesia, paw edema and sensitivity to cold. In the Freund's complete adjuvant (CFA) model, oral treatment with EOPG (10 mg/kg) or spathulenol (10 mg/kg) for 21 days significantly inhibited all analyzed parameters. The percentage maximal inhibition by spathulenol was 76.00% (mechanical hyperalgesia), 71.90% (cold response), 85.00% (edema), 77.16% (myeloperoxidase activity), 97.72% (time in the closed arms in the elevated plus maze), and 49.00% (immobility time in the tail suspension test), in the CFA model. Models employed male Swiss mice, except for the CFA test, which employed C57bL6 male mice (n=6 /group).Conclusion: This study demonstrates that EOPG is an anti-nociceptive and anti-hyperalgesic agent, in acute and continuous treatment, and an anxiolytic and antidepressive agent when tested with the chronic pain experimental state.

Toxicological evaluation of ethanolic extract of leaves from Doliocarpus dentatus in Swiss mice.

Doliocarpus dentatus (Dilleniaceae) has been used in folk medicine to treat inflammation and pain; however, studies evaluating its toxicity potential, as well as its effects on anxiety and depression, are scarce. This study investigated the toxicological profile of an ethanolic extract from leaves of D. dentatus (EEDd), and its effects on anxiety and depression models in mice. Male and female mice received either a single dose (500, 1000 or 2000 mg/kg) or repeated doses (75, 150 or 300 mg/kg) of EEDd by oral gavage. During the subacute toxicity assay, behavioral tests were performed on days 4, 14, 21 and 28. No evidence of toxicity was observed in the animals in both acute and subacute tests. However, males treated with the highest dose presented a reduction in the absolute weight of the kidney, an elevation in the AST levels, in addition to an alteration in the urea levels. The treatment did not affect other biochemical parameters, and did not induce any depressive-like behavior. EEDd exhibited low toxicity after single and repeated exposures. Since some analyzed parameters were compromised, further toxicity studies should be carried out.

Visceral adiposity indicators and cardiovascular risk in hemodialytic patients.

OBJECTIVE: Cardiovascular diseases represent the main cause of death in chronic kidney disease (CKD). We aimed to evaluate the prevalence and association of the hypertriglyceridemia-waist phenotype (HWP) and visceral adiposity index (VAI) with cardiometabolic risk factors (CR) in patients with CKD on hemodialysis (HD). METHODS: The study is based on a cross-sectional design with 265 HD patients in two cities in northeastern Brazil. The VAI was calculated considering the variables body mass index (BMI), waist circumference (WC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-c). HWP was defined as the concomitant elevation of WC and TG. The Poisson Regression Model with robust variance estimation was adjusted considering a hierarchical approach for explanatory variables. Prevalence ratios (PR) were also estimated. The level of significance adopted was 5%. RESULTS: In our study HWP and VAI prevalence's were 29.82% and 58.49%, respectively. In the final model, there was an association between VAI and female gender (PR = 1.46; p < 0.0001) and high body fat (% BF) (PR = 1.33; p < 0.0019). HWP was associated with females (PR = 1.80; p = 0.002), alcohol consumption (PR = 1.58; p = 0.033), obesity (PR = 1.89; p = 0.0001), high %BF (PR = 1.76; p = 0.012) and reduced HDL-c (PR = 1.48; p = 0.035). CONCLUSION: The HWP stood out as the association with more CR factors, representing a promising method for tracking cardiometabolic risk in HD patients, mainly female.

Anti-inflammatory Properties of Ethanolic Extract and 2″-O-ß-D-Glucopyranosyl-vitexin Obtained from Alternanthera tenella Colla Whole Plant.

Six flavonoids were identified and isolated from the ethanolic extract of Alternanthera tenella Colla (Amaranthaceae) whole plant (EEAT) including 2″-O-ß-D-glucopyranosyl-vitexin (A19). Flavonoids have anti-inflammatory activity; however, the 2″-O-ß-D-glucopyranosyl-vitexin anti-inflammatory property was not totally explored. The aim of the present study was to investigate the anti-inflammatory effects of ethanolic extract from A. tenella whole plant and isolated flavone C-glycoside A19 in models of inflammation. The oral administration (p.o.) of EEAT (30, 100, and 300 mg/kg), A19 (0.1, 1, and 10 mg/kg), and prednisolone (3 mg/kg) were tested against the carrageenan-induced paw edema in Swiss mice. The EEAT (100 mg/kg, p.o.), A19 (1 mg/kg, p.o.), and prednisolone (3 mg/kg, p.o.) were tested in the zymosan-articular inflammation, carrageenan-pleurisy, and complete Freund's adjuvant (CFA) models in Swiss mice. In silico analysis and search for structural relationships between vitexin derivatives flavones present in the EEAT and TNF-α inhibitors were performed. EEAT, A19, and prednisolone significantly inhibited (i) edema, mechanical hyperalgesia in carrageenan-induced paw inflammation; (ii) leukocyte migration and protein extravasation in carrageenan-induced pleurisy; (iii) knee edema, mechanical hyperalgesia, and leukocyte migration in articular inflammation induced by zymosan. Still the CFA induced the increase in myeloperoxidase and N-acetylglucosaminidase activities, EEAT, A19, and prednisolone significantly inhibited these enzymes. The in silico analysis showed that molecules with similar structure to apigenin and vitexin have a potential inhibition on the TNF system. This study confirms the anti-inflammatory properties of EEAT and A19. The C-glycosylated flavone A19 could be responsible for the EEAT anti-edematogenic and anti-hyperalgesic effects and a potential TNF-α inhibitor.

Analgesic and anti-inflammatory articular effects of essential oil and camphor isolated from Ocimum kilimandscharicum Gürke leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from Ocimum kilimandscharicum Gürke (Lamiaceae) are popularly used against articular pain. AIM OF STUDY: The aim of this study was to test the anti-inflammatory and anti-hyperalgesic (analgesic) properties of the essential oil and camphor isolated from O. Kilimandscharicum leaves (EOOK) in 4 models including zymosan induced-articular inflammation model in mice. MATERIAL AND METHODS: For in vivo models, EOOK was tested in carrageenan-induced paw edema model with oral doses of 30, 100, and 300 mg/kg (oral administration = p.o.) and in zymosan-induced articular inflammation (including knee edema, leukocyte infiltration, mechanical hyperalgesia and nitric oxide), EOOK (100 mg/kg, p. o.) and camphor (30 mg/kg, p. o.) were tested. EOOK (100 mg/kg, p. o.) was tested in the rolling and also in the adhesion of leukocytes to the mesenteric microcirculation in situ model of carrageenan induced inflammation and EOOK (1, 3, 10, 30, and 60 µg/mL) was tested in vitro against neutrophils chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP). RESULTS: The treatment with EOOK significantly inhibited the carrageenan-induced edema, mechanical and cold hyperalgesia. Both, EOOK and camphor inhibited all articular parameters induced by zymosan. In situ intravitral microscopy analysis, EOOK significantly inhibited carrageenan-induced leukocyte rolling and adhesion. In vitro neutrophils chemotaxis, EOOK inhibited the leukocyte chemotaxis induced by fMLP. CONCLUSIONS: The present study showed that EOOK inhibited pain and inflammatory parameters contributing, at least in part, to explain the popular use of this plant as analgesic natural agent. This study also demonstrates that camphor and some known anti-inflammatory compounds present in EOOK could contribute for analgesic and anti-inflammatory articular properties.

Correlation Between Parathyroid Hormone Levels with Urinary Magnesium Excretion in Patients with Non-Dialysis Dependent Chronic Kidney Disease.

BACKGROUND: Disorders of mineral metabolism occur in most patients with chronic kidney disease (CKD). The aim of this work was to correlate parathyroid hormone (PTH) levels with urinary magnesium excretion in patients with non-dialysis dependent CKD. METHODS: Cross-sectional study. Concentrations of creatinine, magnesium, calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D] and alkaline phosphatase (ALP) were determined in blood samples. The assessment of urinary magnesium levels was performed by means of total daily excretion and by the excretion fraction (FEMg). RESULTS: The study evaluated 163 patients with a mean age of 60.7 ± 11.7 years and 51.0% were male. In the highest quartile of PTH (>89.5pg/mL), the mean levels of FEMg and ALP were higher (p<0.05). In the unadjusted regression analysis, the following variables were related to serum PTH levels: FEMg (odds ratio (OR) = 1.12; 95% confidence intervals (CI): 1.02-1.23), calcium (OR = 0.45; 95% CI: 0.22-0.90), ALP (OR = 1.02; 95% CI: 1.00-1.03) and eGFR (OR = 0.92; 95% CI: 1.00-1.03). After an adjusted analysis, only one FEMg and ALP will remain correlated with PTH. CONCLUSION: In patients with non-dialysis dependent CKD, FEMg and ALP were some variables that remained associated with PTH.

Analgesic and Anti-inflammatory Effects of Caryocar brasiliense.

BACKGROUND: Caryocar brasiliense, popularly known as pequi, is widely distributed in the Amazon rainforest and Brazilian savannah. The fruit obtained from pequi is used in cooking and has folk use as an anti-inflammatory and for the treatment of respiratory disease. Until now, these two properties had not been scientifically demonstrated for Pequi oil in a carrageenan model. OBJECTIVE: Our group determined the composition and safe use of Pequi oil from the Savannah of Campo Grande, and the anti-inflammatory and anti-nociceptive activities of this pequi oil were investigated in vivo models. MATERIALS AND METHODS: Doses of 300, 700, and 1000 mg/kg of Pequi oil were administered orally (p.o.) to Swiss male mice, and three parameters of inflammation (mechanical hyperalgesia, cold, hyperalgesia, and oedema) were analyzed in a carrageenan model to induce an inflammatory paw state. RESULTS AND DISCUSSION: The effects of Pequi oil were also carrageenan in pleurisy model, formalin, and acetic acid induced nociception. Oral administration of 1,000 mg/kg orally Pequi oil (p.o.) inhibited (*P<0.05), the migration of total leukocytes, but not alter plasma extravasation, in the pleurisy model when compared to control groups. The paw edema was inhibited with doses of 700 (P <0.05) and 1,000 mg (P<0.001) of pequi oil after 1, 2, and 4 hours after carrageenan. Pequi oil (1,000 mg/kg) also blocked the mechanical hyperalgesy and reduced cold allodynia induced by carrageenan in paw (P <0.05). Pequi oil treatment (1,000 mg/kg) almost blocked (P < 0.001) all parameters of nociception observed in formalin and acid acetic test. CONCLUSION: This is the first time that the analgesic and anti-inflammatory effects of Pequi oil have been shown.

Association between renal damage markers and carotid atherosclerosis in Afro-descendants with hypertension belonging to a minority ethnic group from Brazil.

Ethnicity appears to play an important role in the prevalence and severity of hypertension, renal disease, and atherosclerosis. A cross-sectional study was conducted, including 206 Afro-descendants with hypertension, living in the remaining quilombo communities. These subjects underwent a carotid intima-media thickness (CIMT) assessment. The presence of renal injury was assessed by: (1) The glomerular filtration rate (GFR) estimated by the formula CKD-EPI using creatinine and cystatin C and (2) Albuminuria (ACR ≥30 mg/g). The Poisson distribution model was set with robust variance to identify factors associated with carotid atherosclerosis. The statistical analysis was performed using the Stata 12.0 software, adopting a significance level of 5%. Most subjects were women (61.65%); the average age was 61.32 (±12.44) years. Subjects (12.62%) were identified with GFR <60 mL/min/1.73 m2 and 22.8% with albuminuria. Patients (59.22%) presented with a high CIMT. In the adjusted regression model, age ≥60 years (PR: 1.232 [CI 95%:1.091-1.390], p value = .001), ACR ≥30 mg/g (PR: 1.176 [CI 95%: 1.007-1.373], p = .040), and GFR/CKD-EPI using cystatin C (PR: 1.250 [CI 95%: 1.004-1.557], p = .045) were independently associated with carotid atherosclerosis. The occurrence of atherosclerotic lesions was high in the studied group. Age, albuminuria, and GFR (estimated by the formula CKD-EPI using cystatin C) influenced the prevalence of carotid atherosclerosis.

Usefulness of visceral adipose tissue estimation in the prevention of chronic kidney disease in hypertensive patients in primary health care.

BACKGROUND: studies have shown an association between obesity and a reduction in estimated glomerular filtration rate (eGFR). However, little is known regarding whether this association is related to total fat or, more specifically, to central or visceral fat. OBJECTIVE: this study evaluated the correlations among the nutritional indices that measure total, central and visceral obesity with eGFR. METHODS: a cross-sectional study, involving 288 hypertensive patients. Kidney function was estimated by GFR, using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Explanatory variables included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist stature ratio (WSR), estimated visceral adipose tissue (eVAT) and body fat percentage (BF%). RESULTS: the mean BMI was 27.8 ± 4.7 kg/m². Most of the patients (68.1%) were in the normal range of BF%, but regarding WC and eVAT, they were at very high risk (58.3% and 64.6%, respectively). In men, there were no correlations between nutritional indices and eGFR. In women, only eVAT remained negatively correlated with eGFR, estimated by MDRD and CKD-EPI equations, independent of BMI, smoking, physical inactivity, blood pressure, glycated hemoglobin, LDL and HDL cholesterol, uric acid and microalbuminuria. CONCLUSIONS: the majority of obesity indices were not associated with eGFR. Only eVAT was negatively associated with eGFR by MDRD and CKDEPI equations in hypertensive women. In primary health care, visceral adipose tissue estimation could support the identification of hypertensive women at increased risk for developing chronic kidney disease.

Sodium excretion and associated factors in urine samples of African descendants in Alcântara, Brazil: a population based study.

In most countries, salt intake has been excessive and constitutes one of the main risk factors for disease development, especially hypertension. Factors such as age, gender, sedentary lifestyle, smoking, African descent, obesity, dietary habits and family history of hypertension may be associated with high blood pressure. Studies show a positive association between the excretion of sodium and increased blood pressure. We evaluated the urinary excretion of sodium and associated factors in isolated urine samples of African descendants from remaining Quilombos. We performed a cross-sectional, population-based study with 1162 African descendants living in remaining quilombos in Alcântara, Maranhão, Brazil. Demographic, nutritional, clinical and laboratory data were analyzed. Urinary sodium excretion was estimated using the Kawasaki equation. A multivariate linear regression model was used to identify the variables related to sodium excretion. The average age was 37.6 ± 11.8 years and 51.2% were women. The prevalence of hypertension was 21.3%. The average urinary excretion of sodium was high, especially among the hypertensive (217.9 ± 90.1 vs. 199.2 ± 83.0 mmol/d; p = .002). After an adjusted analysis, only the waist circumference (odds ratios (OR) = 1.16; confidence intervals(CI)95%: 1.03-1.30), triglyceride (OR = 1.13; CI95%: 1.05-1.22), systolic blood pressure (OR = 1.19; CI95%: 1.08-1.32) and Chronic Kidney Disease Epidemiology (CKD-EPI;OR = 1.24; CI95%: 1.15-1.35) remained related to urinary sodium excretion. African descendants had a high rate of sodium excretion, especially among those who had hypertension. Abdominal adiposity, triglyceride and systolic blood pressure levels and renal function by CKD-EPI equation were associated to urinary sodium excretion.