F. A. Santos

Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils.

1,8‐Cineole (cineole), a terpenoid oxide present in many plant essential oils displays an inhibitory effect on some types of experimental inflammation in rats, i.e. paw oedema induced by carrageenan and cotton pellet‐induced granuloma. Cineole also inhibits in mice, the acetic acid‐induced increase in peritoneal capillary permeability and the chemical nociception induced by intraplantar formalin and intraperitoneal acetic acid. Activity was present in these tests, at an oral dose range of 100–400 mg/kg. In the formalin test, the antinociceptive effect of cineole was not reversed by pretreatment of mice with naloxone (1 mg/kg, s.c.), a µ‐opioid receptor antagonist, suggesting the involvement of a non‐opioid mechanism. Cineole demonstrated a significant inhibitory effect on locomotion and also potentiated the pentobarbital sleeping time in mice, indicating a plausible depressant effect on the central nervous system. The present results, when taken together with the recent reports that describe the inhibitory effects of cineole on the formation of prostaglandins and cytokines by stimulated monocytes in vitro, may provide additional evidence for its potential beneficial use in therapy as an antiinflammatory and analgesic agent.

Anti-inflammatory effect of kaurenoic acid, a diterpene from Copaifera langsdorffii on acetic acid-induced colitis in rats

Kaurenoic acid, a diterpene from Copaifera langsdorffii (Leguminaceae), was evaluated on rat colitis induced by acetic acid. Rats were pretreated orally (15 and 2 h before) or rectally 2 h before induction of colitis with kaurenoic acid (50 and 100 mg/kg) or vehicle (1 ml, 3% DMSO). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and, 24 h later, the colonic mucosal damage was analysed macroscopically for the severity of mucosal damage, the myeloperoxidase (MPO) activity and the malondialdehyde (MDA) levels in the colon segments. A marked reduction in gross damage score (52% and 42%) and wet weight of damaged colon tissue (39% and 32%) were observed in rats that received 100 mg/kg kaurenoic acid, respectively, by rectal and oral routes. This effect was confirmed biochemically by a two- to three-fold reduction of colitis associated increase in MPO activity, the marker of neutrophilic infiltration and by a marked decrease in MDA level, an indicator of lipoperoxidation in colon tissue. Furthermore, light microscopy revealed the marked diminution of inflammatory cell infiltration and submucosal edema formation in the colon segments of rats treated with the test compound. These findings indicate the anti-inflammatory potential of kaurenoic acid in acetic acid-induced colitis.

Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet

Excess visceral adiposity may predispose to chronic diseases like hypertension and type 2 diabetes with a high risk for coronary artery disease. Adipose tissue secreted cytokines and oxidative stress play an important role in chronic disease progression. To combat adiposity, plant-derived triterpenes are currently receiving much attention as they possess antioxidant and anti-inflammatory properties and the ability to regulate glucose and lipid metabolism. In the search for potential antiobese compounds from natural sources, this study evaluated the effects of oleanolic acid (OA), a pentacyclic triterpene commonly present in fruits and vegetables, in glucose tolerance test and on high-fat diet (HFD)-induced obesity in mice. Adult male Swiss mice treated or not with OA (10 mg/kg) were fed a HFD during 15 weeks. Sibutramine (SIB) treated group (10 mg/kg) was included for comparison. Weekly body weights, food and water consumption were measured, and at the end of study period, the levels of blood glucose and lipids, plasma hormone levels of insulin, ghrelin and leptin, and the visceral abdominal fat content were analysed. Mice treated with OA and fed a HFD showed significantly (p<0.05) improved glucose tolerance, decreased body weights, visceral adiposity, blood glucose, plasma lipids relative to their respective controls fed no OA. Additionally, OA treatment, while significantly elevating the plasma hormone level of leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than lipase. Sibutramine-treated group also manifested similar effects like OA except for blood glucose level that was not different from HFD control. These findings suggest that OA ameliorates visceral adiposity and improves glucose tolerance in mice and thus has an antiobese potential through modulation of carbohydrate and fat metabolism.

Anti-inflammatory effect of α, β-Amyrin, a pentacyclic triterpene from Protium heptaphyllum in rat model of acute periodontitis

Abstract.This study was aimed to evaluate the anti-inflammatory potential of triterpene α, β-amyrin in rats on acute phase periodontitis. Periodontitis was induced by ligature placement around the maxillary right second molar tooth. Rats (n = 8/group) were pretreated with α, β-amyrin (5 and 10 mg/kg, p. o.), two hours before the induction of periodontal inflammation. Sham-operated and positive controls (lumiracoxib and dexamethasone) were included. Six hours later, plasma levels of TNF-alpha were analysed. Rats were sacrificed at 24 h, and the gingival tissue analysed for myeloperoxidase (MPO) and thiobarbituric acid-reactive substances (TBARS), as measures of neutrophil influx and lipid-peroxidation, respectively α, β-Amyrin as well as dexamethasone significantly inhibited the periodontitis-associated increases of TNF-alpha, and the gingival MPO and TBARS. α, β-Amyrin effect was more prominent at 5 mg/kg. Lumiracoxib manifested varied influence on the studied parameters. These results provide evidence to show that α, β-Amyrin retards acute inflammation in rat model of periodontitis and warrant further study on its efficacy to prevent chronic periodontitis-associated bone loss.

Betulinic Acid, a Natural Pentacyclic Triterpenoid, Prevents Abdominal Fat Accumulation in Mice Fed a High-Fat Diet

In the search for potential antiobese agents from natural sources, this study investigated the effects of betulinic acid (BA), a pentacyclic triterpene from Clusia nemorosa L. (Clusiaceae), in mice on a high-fat diet (HFD). Adult male Swiss mice (n = 8) treated or not with BA (50 mg/L, in drinking water) were fed a HFD during 15 weeks. Mice treated with BA and fed a HFD showed significantly (P < 0.05) decreased body weights, abdominal fat accumulation, blood glucose, plasma triglycerides, and total cholesterol relative to their respective controls fed no BA. Additionally, BA treatment, while significantly elevating the plasma hormone levels of insulin and leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than the lipase. These findings suggest that BA has an antiobese potential through modulation of fat and carbohydrate metabolism, and it may be a suitable lead compound in the treatment of obesity.

Ursolic acid, a pentacyclic triterpene from Sambucus australis, prevents abdominal adiposity in mice fed a high-fat diet.

Currently, there is renewed interest in plant-based medicines and functional foods for the prevention and cure of obesity and its associated risk of cardiovascular disease and metabolic syndrome. In the search for potential anti-obesity compounds from natural sources, the effects of ursolic acid (UA), a pentacyclic triterpenoid widely found in medicinal herbs and fruits, was evaluated for its effects on blood glucose, lipids, and abdominal fat deposition in mice fed a high-fat diet (HFD). Adult male Swiss mice treated or not with UA (0.05%, 50 mg/L, in drinking water) were fed HFD for 15 weeks. A sibutramine (SIB)-treated group (0.05% in drinking water) was included as the positive control. Weekly body weights and food and water consumption were measured, and at the end of the study period, the levels of blood glucose and lipids, the plasma hormones insulin, ghrelin, and leptin, and the abdominal fat accumulation were analyzed. Mice treated with UA and fed HFD showed significantly (P<.05) decreased body weights, visceral adiposity, and levels of blood glucose and plasma lipids relative to their respective controls not fed UA. Also, a significant increase was observed in plasma leptin with a decrease in ghrelin, as well as of amylase and lipase activities. The SIB-treated group also manifested effects similar to those of UA except for the blood glucose level, which was not different from the HFD control. These findings suggest that UA ameliorates abdominal adiposity and decreases the levels of blood glucose and plasma lipids in mice and thus manifests an anti-obesity potential through absorptive and metabolic targets.

Antihyperglycemic and hypolipidemic effects of α, β-amyrin, a triterpenoid mixture from Protium heptaphyllum in mice

BackgroundPentacyclic triterpenes in general exert beneficial effects in metabolic disorders. This study investigated the effects of α, β-amyrin, a pentacyclic triterpene mixture from the resin of Protium heptaphyllum on blood sugar level and lipid profile in normal and streptozotocin (STZ)-induced diabetic mice, and in mice fed on a high-fat diet (HFD).FindingsMice treated with α, β-amyrin (10, 30 and 100 mg/kg, p.o.) or glibenclamide (10 mg/kg, p.o.) had significantly reduced STZ-induced increases in blood glucose (BG), total cholesterol (TC) and serum triglycerides (TGs). Unlike glibenclamide that showed significant reductions in BG, TC and TGs in normoglycemic mice, α, β-amyrin did not lower normal blood sugar levels but at 100 mg/kg, manifested a hypolipidemic effect. Also, α, β-amyrin effectively reduced the elevated plasma glucose levels during the oral glucose tolerance test. Moreover, the plasma insulin level and histopathological analysis of pancreas revealed the beneficial effect of α, β-amyrin in the preservation of beta cell integrity. In mice treated orally with α, β-amyrin (10, 30 and 100 mg/kg) or fenofibrate (200 mg/kg), the HFD-associated rise in serum TC and TGs were significantly less. The hypocholesterolemic effect of α, β-amyrin appeared more prominent at 100 mg/kg with significant decreases in VLDL and LDL cholesterol and an elevation of HDL cholesterol. Besides, the atherogenic index was significantly reduced by α, β-amyrin.ConclusionsThese findings reflect the potential antihyperglycemic and hypolipidemic effects of α, β-amyrin mixture and suggest that it could be a lead compound for drug development effective in diabetes and atherosclerosis.

Protective effect of anacardic acids from cashew (Anacardium occidentale) on ethanol-induced gastric damage in mice.

Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and antitumor properties. Despite these known effects, hitherto there were no published reports on their likely gastroprotective effects. The present study was designed to verify whether AAs afford gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2mL of ethanol (96%). Mice in groups were pretreated orally with AAs (10, 30 and 100mg/kg), misoprostol (50 microg/kg), or vehicle (2% Tween 80 in saline, 10mL/kg), 45min before ethanol administration. They were sacrificed 30min later, the stomachs excised, and the mucosal lesion area (mm(2)) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed. Treatments effects on ethanol-associated oxidative stress markers GSH, MDA, catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured in gastric tissue. Besides, the effects of AAs on gastric secretory volume and total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose-related gastroprotection against the ethanol damage and further prevented the ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and nitrate/nitrite. However, they failed to modify the gastric secretion or the total acidity. It was observed that the gastroprotection by AAs was greatly reduced in animals pretreated with capsazepine, indomethacin, l-NAME or glibenclamide. These results suggest that AAs afford gastroprotection principally through an antioxidant mechanism. Other complementary mechanisms include the activation of capsaicin-sensitive gastric afferents, stimulation of endogenous prostaglandins and nitric oxide, and opening of K(+)(ATP) channels. These combined effects are likely to be accompanied by an increase in gastric microcirculation.

Investigations on the antinociceptive effect of Psidium guajava leaf essential oil and its major constituents

The antinociceptive effect of leaf essential oil from Psidium guajava and its major constituents, β‐caryophyllene and α‐pinene was assessed using chemical (formalin and acetic acid) and thermal (hot‐plate) nociceptive tests in adult male albino mice. Oral administration of 100, 200 and 400 mg/kg of essential oil produced a significant antinociceptive effect in the formalin test and at 200 and 400 mg/kg in the acetic acid‐ induced writhing test. Of the major components only α‐pinene, but not the β‐caryophyllene, demonstrated significant antinociception in the formalin test. Neither the essential oil nor the major components could exert any significant effect in the hot‐plate test. Pretreatment of mice with caffeine (20 mg/kg, i.p.), significantly inhibited the antinociceptive effect of essential oil in the formalin test. Naloxone (1 mg/kg, s.c.), the opioid antagonist, however, failed to antagonize it. These results suggest that the antinociceptive effect of P. guajava essential oil is probably mediated by endogenously released adenosine.

Pentacyclic triterpenoids, α,β-amyrins, suppress the scratching behavior in a mouse model of pruritus

In the search for natural compounds useful against pruritus, α,β-amyrins, the pentacyclic triterpenes isolated from the resin of popular medicinal plant Protium heptaphyllum were examined on scratching behavior induced by dextran T40 and compound 48/80 in mice. The animals were pretreated orally with α,β-amyrins (50, 100 and 200 mg/kg) or cyproheptadine (10 mg/kg), an antagonist of histamine and serotonin receptors and 2 h later, they were given subcutaneous injections of dextran T40 (75 mg/kg) or compound 48/80 (3 mg/kg) into the rostral back, and scratching was quantified for 20 min. The scratching behavior induced by dextran T40 and compound 48/80 was significantly inhibited in mice pretreated with α,β-amyrins (100 and 200 mg/kg) or cyproheptadine (10 mg/kg), In addition, the compound 48/80-elicited degranulation of rat peritoneal mast cells (ex vivo) was also markedly reduced in animals pretreated with α,β-amyrins (100 mg/kg) or ketotifen (1 mg/kg), a known mast cell stabilizer. In the open-field test, α,β-amyrins (100 and 200 mg/kg)-pretreated mice showed no impairment of spontaneous locomotion, suggesting that these triterpenoids possess no sedative activity that could account for suppression of scratching behavior. These results clearly indicate the antipruritic effect of α,β-amyrins and suggest that this effect may be related to a stabilizing action on mast cell membrane.