Arabinan-rich pectic polysaccharide fraction from Malpighia emarginata fruits alleviates inflammatory pain in mice.

Malpighia emarginata (Malpighiaceae), popularly known as "acerola", is a tropical and subtropical fruit native to the Americas. Despite its high vitamin C content, which gives it a high antioxidant property, soluble dietary fibers, such as polysaccharides, are also abundant constituents of acerola (10% of the dried fruit). The acerola cold-water soluble (ACWS) fraction presented anti-fatigue and antioxidant effects in vivo and in vitro. To infer further systemic effects of ACWS, this study aimed to investigate the antinociceptive, anti-inflammatory, and antioxidant effects of ACWS in murine models of pain. In formalin-induced nociception, ACWS (0.1, 1, and 10 mg/kg) reduced only the inflammatory phase, and also (10 and 30 mg/kg) attenuated the acetic acid-induced writhing and leukocyte migration in the peritoneal cavity. The mechanical allodynia and paw edema induced by intraplantar injection of carrageenan were greatly reduced by ACWS (10 mg/kg). At the inflammatory pick induced by carrageenan (4 h), ACWS significantly reduced myeloperoxidase activity, TNF-α, IL-1ß, and PGE2 levels, and restored IL-10 levels. ACWS also exhibited antioxidant properties by decreasing lipid hydroperoxides content, increasing GSH levels, and restoring superoxide dismutase and catalase activities in the carrageenan model and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. Collectively, these results support the antinociceptive, anti-inflammatory, and antioxidant effects of ACWS and reveal a promising candidate for the treatment of inflammatory pain conditions.

Chemical composition, antioxidant and gastrointestinal properties of Sedum dendroideum Moc & Sessé ex DC leaves tea infusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is a medicinal plant employed in Mexican and Brasilian folk medicine as juice or infusion, as remedy for the treatment of different diseases, including gastric disorders. AIM OF THE STUDY: Although some studies carried out with Sedum dendroideum have demonstrated its gastroprotective effect, the purpose of this study was to elucidate the chemical constituents, antioxidant, cytotoxic and mechanisms underlying the gastrointestinal properties of Sedum dendroideum accordingly its traditional use, as fresh leaves tea infusion (SDI). MATERIALS AND METHODS: Chemical constituents were analyzed using high performance liquid chromatography and mass spectrometry (HPLC-MS). Antioxidant and cytotoxicity were evaluated in in vitro assays. The efficacy of the SDI on macroscopic ulcer appearance, mucus and GSH maintenance on ethanol- and indomethacin-induced ulcer models, gastric acid secretion and gastrointestinal motility were investigated. RESULTS: Phytochemical analysis by HPLC-MS revealed the presence of different flavonol glycosides, containing myricetin and quercetin, along with the kaempferol as aglycones. In vitro pharmacological investigation of SDI demonstrated potent antioxidant activity in DPPH assay (IC50: 13.25 ±â€¯3.37 µg/mL) and absence of cytotoxicity in Caco-2 cells by MTT method. Oral administration of SDI (ED50 of 191.00 ±â€¯0.08 mg/kg) in rats promoted gastroprotection against ethanol or indomethacin in rats through reinforcement of gastric wall mucus, GSH content and nitric oxide release, without present antisecretory properties. The gastroprotective effect was maintained when SDI (19 mg/kg) was administrated by intraperitoneal route. Furthermore, SDI (150 mg/kg) unchanged the gastric emptying but increase small bowel transit in mice through cholinergic pathways. CONCLUSIONS: Collectively, this study confirmed that Sedum dendroideum promotes gastroprotection through preventing of endogenous defense mechanisms, represented by mucus and GSH without changes gastric acid secretion. Sedum dendroideum tea infusion features a chemical profile that contributes to the antioxidant and gastric health-promoting effects, supporting the use in folk medicine for the treatment of gastrointestinal disorders.

Gastroprotective activity of a pectic polysaccharide fraction obtained from infusion of Sedum dendroideum leaves.

BACKGROUND: Sedum dendroideum, popularly known in Brazil as balsam, is traditionally used as a wound healing agent, to treat gastritis, and several other health problems. Some studies have shown that plant polysaccharides may have gastroprotective properties. PURPOSE: Considering the popular use of S. dendroideum and the gastroprotective activity of polysaccharides, the objective of this work was to obtain, to characterize, and to evaluate the gastroprotective activity of a polysaccharide fraction from this plant. METHODS: Polysaccharides of S. dendroideum were extracted with water by infusion, fractionated by freeze-thawing process and dialyzed at a 100 kDa cut-off membrane, and characterized by monosaccharide composition and NMR analysis. The gastroprotective activity of the pectic polysaccharide fraction RSBAL was evaluated in the ethanol-induced ulcer model in rats, followed by determination of the mucus and glutathione levels in the gastric tissue. RESULTS: RSBAL was constituted by a homogalacturonan and a homogalacturonan branched by side chains of arabinans and type II arabinogalactans. It reduced ethanol-induced gastric ulcers in rats, preserving mucus and glutathione levels in the stomach. CONCLUSION: This study demonstrated that polysaccharides could be related to the pharmacological activity of S. dendroideum.

Gastroprotective effects and structural characterization of a pectic fraction isolated from Artemisia campestris subsp maritima.

The aim of this study was to investigate the chemical structure and biological activity of a pectic fraction isolated from the aerial parts of A. campestris L. subsp. maritima Arcangeli. The chemical and spectroscopic analyses of the pectic fraction (ACP-E10) demonstrated that ACP-E10 was composed of homogalacturonan (HG) (60%) and rhamnogalacturonan-I (RG-I) (29%) regions. Side chains of the RG-I included mainly branched arabinans and type II arabinogalactans (AG-II). The molar mass of ACP-E10 determined by HPSEC-MALLS was 16,600g/mol. ACP-E10 was evaluated for its gastroprotective effect against ethanol-induced gastric lesions in rats. Oral pretreatment of animals with ACP-E10 (0.3, 3 and 30mg/kg) significantly reduced gastric lesions by 77±7.9%, 55±11.1% and 65±11.8%. ACP-E10 also maintained mucus and glutathione (GSH) contents in the gastric mucosa. In addition, ACP-E10 demonstrated antioxidant activity in vitro by the DPPH assay. These results demonstrated that the pectin from A. campestris had significant gastroprotective effects in vivo, which were likely attributable to their capacity to increase the protective defenses of gastric mucosa.

Acid-gastric antisecretory effect of the ethanolic extract from Arctium lappa L. root: role of H+, K+-ATPase, Ca2+ influx and the cholinergic pathway.

BACKGROUND: Arctium lappa L., popularly known as burdock, is a medicinal plant used worldwide. The antiulcer and gastric-acid antisecretory effects of ethanolic extract from roots of Arctium lappa (EET) were already demonstrated. However, the mechanism by which the extract reduces the gastric acid secretion remains unclear. Therefore, this study was designed to evaluate the antisecretory mode of action of EET. MATERIALS AND METHODS: The effects of EET on H+, K+-ATPase activity were verified in vitro, whereas the effects of the extract on cholinergic-, histaminergic- or gastrinergic-acid gastric stimulation were assessed in vivo on stimulated pylorus ligated rats. Moreover, ex vivo contractility studies on gastric muscle strips from rats were also employed. RESULTS: The incubation with EET (1000 µg/ml) partially inhibited H+, K+-ATPase activity, and the intraduodenal administration of EET (10 mg/kg) decreased the volume and acidity of gastric secretion stimulated by bethanechol, histamine, and pentagastrin. EET (100-1000 µg/ml) did not alter the gastric relaxation induced by histamine but decreased acetylcholine-induced contraction in gastric fundus strips. Interestingly, EET also reduced the increase in the gastric muscle tone induced by 40 mM KCl depolarizing solution, as well as the maximum contractile responses evoked by CaCl2 in Ca2+-free depolarizing solution, without impairing the effect of acetylcholine on fundus strips maintained in Ca2+ -free nutritive solution. CONCLUSION: Our results reinforce the gastric antisecretory properties of preparations obtained from Arctium lappa, and indicate that the mechanisms involved in EET antisecretory effects include a moderate reduction of the H+, K+-ATPase activity associated with inhibitory effects on calcium influx and of cholinergic pathways in the stomach muscle.

Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid.

Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity.

Anti-inflammatory effect of laser acupuncture in ST36 (Zusanli) acupoint in mouse paw edema.

Low-level laser therapy (LLLT) in acupuncture is a low-power laser applied to acupoints for providing luminous energy, capable to produce photobiological induction that results in biochemical, bioelectric, and bioenergetic effects. ST36 (Zusanli) is a point of acupuncture commonly used for treatment of several pathological alterations, such as inflammation, acute pain, and gastrointestinal disorders. In this study, we evaluated the anti-inflammatory effect of LLLT (830 nm, 4 J/cm(2)) in ST36 acupoint through the model of carrageenan-induced paw edema in mice and the possible mechanisms involved. Female Swiss mice were treated with LLLT in ST36 before the paw edema induction, which was measured by means of a digital micrometer and the temperature through a high-resolution digital thermograph. After this, the levels of reactive oxygen species (ROS), lipid hydroperoxides (LOOH), and reduced glutathione (GSH) were quantified. In another set of experiments, the paw edema was induced by bradykinin, histamine, and prostaglandin E2 (PGE2). LLLT in ST36 acupoint significantly inhibited the edema formation for 4 h after the carrageenan injection and reduced the paw temperature in 10 %. Furthermore, LLLT also reduced the levels of ROS (55 %) and LOOH (50 %) but, however, did not alter the GSH levels. LLLT in ST36 reduced the paw edema induced by bradykinin (30 min, 6 %, 60 min, 7 %), histamine (30 min, 11 %), and PGE2 (90 min, 10 %, 120 min, 16 %). In conclusion, these results prove that LLLT in ST36 acupoint produces a relevant anti-inflammatory effect, reducing edema, temperature, and free radicals levels in mice paw.

Arabinoxylan from Mucilage of Tomatoes (Solanum lycopersicum L.): Structure and Antinociceptive Effect in Mouse Models.

Tomato is a known functional food due to its content of bioactive compounds. Herein, polysaccharides were extracted from mucilage of tomatoes, and a purified fraction (PTOK) was analyzed by sugar composition, methylation, and NMR spectroscopy analysis. The results showed the presence of an arabinoxylan, having (1→4)-linked ß-d-Xylp units in the main chain, which carried a low proportion of branching (∼5.6%), at O-2 and O-3 position, with side chains constituted by single Araf or Xylp units. Intraperitoneal administration of the arabinoxylan in mice significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid and the inflammatory phase of nociception induced by 2.5% formalin, indicating that it had an antinociceptive effect on inflammatory pain models, amplifying the biological role displayed by arabinoxylans in the diet. Furthermore, this study reports the presence of an arabinoxylan in a dicotyledon plant, and also it is the first study of polysaccharides from mucilage of tomatoes.

Healing mechanisms of the hydroalcoholic extract and ethyl acetate fraction of green tea (Camellia sinensis (L.) Kuntze) on chronic gastric ulcers.

Green tea is an infusion of unfermented leaves of Camellia sinensis (L.) Kuntze (Theaceae), traditionally used for the treatment of obesity, hypercholesterolemia, and gastric complaints. This study evaluated the mechanisms involved in the gastric ulcer healing of the hydroalcoholic extract from green tea (GEt), its ethyl acetate fraction, (GEAc) and epigallocatechin gallate (EGCG) using the model of acetic acid-induced gastric ulcer in rats. The chronic gastric ulcer was induced by application of 80 % acetic acid on serosal mucosa of rats. After 7 days of oral treatment with GEt and GEAc, the ulcer area, mucin content, inflammatory parameters (MPO and NAG), and antioxidant system (GSH and LOOH levels, SOD and GST activities) were evaluated. In vitro, the scavenging activity of GEt and GEAc were also measured. The antisecretory action was studied on the pylorus ligature method in rats. Oral treatment with GEt and GEAc reduced significantly the gastric ulcer area induced by acetic acid. The gastric ulcer healing was accompanied by increasing of mucin content, restoration of GSH levels and SOD activity, and reduction of MPO and LOOH levels. In addition, GEt and GEAc reduced the DPPH free radicals in vitro. Furthermore, the oral treatment of animals with GEt and GEAc did not alter the gastric acid secretion or cause signs of toxicity. Collectively, these results showed that GEt had a pronounced antiulcer effect, possibly through maintenance of mucin content and reduction of inflammation and oxidative stress. In addition, the compounds present in its ethyl acetate fraction could be responsible for the extract activity.

Structure of an arabinogalactan from the edible tropical fruit tamarillo (Solanum betaceum) and its antinociceptive activity.

A structural characterization of polysaccharides obtained by aqueous extraction of ripe pulp of the edible exotic tropical fruit named tamarillo (Solanum betaceum) was carried out. After fractionation by freeze-thaw and α-amylase treatments, a fraction containing a mixture of highly-methoxylated homogalacturonan and of arabinogalactan was obtained. A degree of methylesterification (DE) of 71% and a degree of acetylation (DA) of 1.3% was determined by (1)H NMR spectroscopy and spectrophotometric quantification, respectively. A type I arabinogalactan was purified via Fehling precipitation and ultrafiltration through 50 kDa (cut-off) membrane. Its chemical structure was performed by sugar composition, HPSEC, methylation, carboxy-reduction and (13)C NMR spectroscopy analysis. Intraperitoneal administration of the arabinogalactan did not reduce the nociception induced by intraplantar injection of 2.5% formalin in mice, but significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid, indicating that fraction has an antinociceptive effect on the visceral inflammatory pain model.

Rhamnogalacturonan from Acmella oleracea (L.) R.K. Jansen: gastroprotective and ulcer healing properties in rats.

A rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen administered by oral route showed gastroprotective activity against acute lesions induced by ethanol. In this study, we investigated the gastric ulcer healing effect of RGal and its mechanisms of action. Intraperitoneal treatment of animals with RGal protected the gastric mucosa against acute lesions induced by ethanol, with participation of gastric mucus. Furthermore, in the chronic ulcer model, oral administration of RGal accelerates the gastric ulcer healing, accompanied by increasing of cellular proliferation and gastric mucus content, reducing inflammatory parameters and oxidative stress. In addition, the repeated 7 days-treatment of animals with RGal did not show alterations of clinical and behavioral symptoms, body and organs weights or plasmatic biochemical parameters. Collectively, these results showed that RGal has an interesting antiulcerogenic activity and could constitute an attractive molecule of interest for the development of new antiulcer agents.

Polysaccharides from prunes: gastroprotective activity and structural elucidation of bioactive pectins.

Prunes are the dried fruits from Prunus domestica. After the purification steps, two homogeneous polysaccharides were characterised, SF-50R and SF-50E and contained Ara:Gal:Rha:GalA in 47.8:31.5:10.7:10.0 and 39.6:50.3:5.1:5.0 molar ratios, respectively. Methylation analysis and (13)C NMR spectroscopy indicated that both fractions are constituted by rhamnogalacturonans with type I arabinogalactans as side chains, differing mainly in the proportions of the rhamnogalacturonan backbone, in the length of the (1→4)-ß-galactan chain and in the proportion of the arabinan side chain. Crude water extract (PWH) and fraction SF-50E were evaluated for their gastroprotective properties against ethanol-induced acute gastric lesions in rats. Oral administration of PWH (3 and 10mg/kg) reduced the gastric lesion area by 67±11% and 60±12%, respectively, while fraction SF-50E (10 and 30mg/kg) inhibited the lesion area by 84±12% and 83±12%, respectively. These results indicated that prune's polysaccharides act as gastroprotective agents in rats.

Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, Acmella oleracea (L.) R.K. Jansen, popularly known as "jambu", has been used by some communities from Amazon region to treat toothache. In this study we examined the antinociceptive effect of the ethanolic extract obtained from the flowers of Acmella oleracea (EEAO) in animal models of nociceptive (chemical and thermal) and neuropathic (partial sciatic nerve ligation) pain. MATERIALS AND METHODS: Adult male mice were treated by intraperitoneal route (i.p.) with EEAO before the induction of nociceptive response by formalin, capsaicin and cinnamaldehyde, thermal heat hyperalgesia (hot plate test) and mechanical allodynia (traumatic sciatic nerve injury). Acute toxicity and non-specific sedative effects were evaluated. RESULTS: EEAO (10, 30 and 100 mg/kg) reduced both neurogenic and inflammatory phases of the formalin- and also capsaicin- and cinnamaldehyde-induced orofacial nociception. Interestingly, EEAO at 100mg/kg (i.p.) also reversed capsaicin-induced heat hyperalgesia assessed as the latency to paw withdrawal in the hot plate test. Also in the hot plate test, paw withdrawal latency was increased by EEAO (100 mg/kg) and this response was only partially reversed by naloxone. Furthermore, EEAO (100 mg/kg) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 3 h. The estimated LD50 value was 889.14 mg/kg and EEAO did not alter the locomotion of animals in the open-field test. CONCLUSION: Taken together, our data show that EEAO produces prevalent antinociceptive effects and does not cause adverse effects. The presence of N-alkylamides, including spilanthol, suggests that the therapeutic effect of EEAO is related to its highest anesthetic activity.

Structure of a galactoarabinoglucuronoxylan from tamarillo (Solanum betaceum), a tropical exotic fruit, and its biological activity.

Tamarillo (Solanum betaceum) is a tropical exotic fruit whose polysaccharides were extracted from the ripe pulp. After various purification steps, homogeneous fractions (designated PTW, STK-1000R and PF) were analyzed by sugar composition, HPSEC, methylation and NMR spectroscopy analysis. The results showed that the fraction PTW consisted of a linear arabinan with (1→5)-linked α-l-arabinofuranosyl units. Fractions designated as STK-1000R and PF contained galactoarabinoglucuronoxylans, with (1→4)-linked ß-d-Xylp residues in the backbone, carrying branches exclusively at O-2. The polysaccharide in STK-1000R is less branched than that in the PF fraction (∼20.0% and 36.5%, respectively), with side-chains formed by (1→5)-linked α-l-Araf residues and (1→4)-linked α-d-GlcpA residues and with non-reducing end units formed by α-l-Araf, ß-Arap, ß-d-Galp, α-d-GlcpA and 4-O-Me-α-d-GlcpA. Intraperitoneal administration of the STK-1000R fraction in mice significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid and the inflammatory phase of nociception induced by 2.5% formalin, indicating that that fraction has an antinociceptive effect on inflammatory pain models.

Antiulcer and gastric antisecretory effects of dichloromethane fraction and piplartine obtained from fruits of Piper tuberculatum Jacq. in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper tuberculatum Jacq. (Piperaceae) is medicinally used as an analgesic and as a treatment for gastric complaints. Thus, the current study aimed to investigate the gastroprotective and antisecretory properties of the dichloromethane fraction of the fruit of Piper tuberculatum (DFPT) and piplartine, a compound isolated from the DFPT, in rats. MATERIALS AND METHODS: Gastric ulcers were induced in fasted rats by oral administration of absolute ethanol and then mucus content and glutathione (GSH) levels were measured. Mechanisms underlying the antisecretory action were studied through gastric H(+),K(+)-ATPase activity of highly purified rabbit gastric microsomes and pylorus ligature method in rats. RESULTS: In the acute toxicity test the values of estimated LD50 for oral and intraperitoneal administration of DFPT were 1.6266 and 0.2684g/kg, respectively. The DFPT (ED50=29mg/kg, p.o.) and piplartine (4.5mg/kg, p.o.) promoted gastroprotection against acute lesions induced by ethanol, effect that could be related with the maintenance of GSH levels in the gastric mucosa. However, only DFPT stimulated gastric mucus secretion. In vitro, the DFPT and piplartine inhibited the H(+),K(+)-ATPase activity and, in vivo DFPT and piplartine also reduced basal gastric acid secretion, as well as that stimulated by pentagastrin. CONCLUSIONS: These results demonstrate that DFPT and piplatine cause marked gastroprotective effects accompanied by the increase and maintenance of gastric mucus and GSH levels, as well as a reduction in gastric acid secretion through the gastrinergic pathway.

Chemical and biological characterization of polysaccharides isolated from Ilex paraguariensis A. St.-Hil.

The potential gastroprotection of polysaccharides (SP) isolated from maté (Ilex paraguariensis) leaves of different growth stages, under different sunlight conditions and of processing methods were evaluated. The SP consist of type I arabinogalactan (AG1) containing a (1→4)-linked ß-Galp chain, with substituents of arabinosyl units at O-6. This arabinogalactan seems to be attached to rhamnosyl units from a RG1, via 1→4 linkage. Oral administration of SP1, SP9, SP10, SP11 and SP12 inhibited the gastric lesions induced by ethanol in rats. Altogether, the present data indicate the therapeutic role of maté polysaccharides against gastric lesion and propose its use or of its crude plant extract as a phytotherapic medicine.

Antiulcer effect of bark extract of Tabebuia avellanedae: activation of cell proliferation in gastric mucosa during the healing process.

Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as 'ipê-roxo' and has been used in folk medicine as anti-inflammatory and in the treatment of ulcers, bacterial and fungal infections. This study evaluated the gastric ulcer healing property of the ethanolic extract (EET) of barks from Tabebuia avellanedae and investigated the mechanisms that may underlie this effect. Rats were treated with EET (twice a day for 7 days) after induction of chronic gastric ulcers by 80% acetic acid. Following treatment, histological and immunohistochemical analysis were performed in gastric ulcer tissues. Oral administration of EET (100 and 300 mg/kg) significantly reduced the gastric lesion induced by acetic acid in 44 and 36%, respectively. Histopathological evaluation demonstrated a contraction of gastric ulcer size, increase of mucus layer (periodic acid-Schiff stained mucin-like glycoproteins) and cell proliferation (proliferating cell nuclear antigen immunohistochemistry) in animals treated with EET (100 and 300 mg/kg). The results demonstrate that EET significantly accelerates healing of acetic acid induced gastric ulcer in rats through increase of mucus content and cell proliferation, indicating a potential usefulness for treatment of peptic ulcer diseases.

Evaluation of the antinociceptive, anti-inflammatory and gastric antiulcer activities of the essential oil from Piper aleyreanum C.DC in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper aleyreanum is a small tree that is widely distributed in tropical and subtropical regions, mostly in North and South America, and is used as an immunomodulator, analgesic and antidepressant in folk medicine. AIM OF THE STUDY: This study was designed to investigate the antinociceptive, anti-inflammatory and gastric antiulcer activities of the essential oils from the aerial parts of Piper aleyreanum (EOPa) in rodents. MATERIALS AND METHODS: The antinociceptive and anti-inflammatory effects of orally administered EOPa were evaluated in mice subjected to the formalin and pleurisy models, respectively. We also pretreated the rats with EOPa before acute ethanol-induced gastric lesions and measured gastric lesion extension and mucus and glutathione (GSH) levels in the gastric mucosa. Finally, we performed a phytochemical analysis of EOPa. RESULTS: The chemical composition of EOPa was analyzed by gas chromatography and mass spectrometry (GC/MS), which identified 35 compounds, representing 81.7% of total oil compounds. Caryophyllene oxide (11.5%), ß-pinene (9%), spathulenol (6.7%), camphene (5.2%), ß-elemene (4.7%), myrtenal (4.2%), verbenone (3.3%) and pinocarvone (3.1%) were the major oil constituents. The oral administration of EOPa (10-1000 mg/kg) significantly inhibited the neurogenic and inflammatory phases of formalin-induced licking, with ID50 values of 281.2 and 70.5 mg/kg, respectively. The antinociception caused by EOPa (100 mg/kg, p.o.) was not reversed by naloxone (1 or 5 mg/kg, i.p.) in the formalin test. EOPa (100-300 mg/kg, p.o.) did not affect animal motor coordination in an open-field model. In carrageenan-induced pleurisy, EOPa (1-100 mg/kg, p.o.) significantly decreased the total cell count, neutrophils and mononuclear cells with mean ID50 values of 53.6, 21.7 and 43.5 mg/kg, respectively. In addition, EOPa (1-30 mg/kg, p.o.) protected the rats against ethanol-induced gastric lesions with an ID50 value of 1.7 mg/kg and increased the mucus and GSH levels of the gastric mucosa to levels similar to those of the non-lesioned group. CONCLUSIONS: These data show for the first time that EOPa has significant antinociceptive and anti-inflammatory actions, which do not appear to be related to the opioid system. EOPa also has interesting gastroprotective effects related to the maintenance of protective factors, such as mucus production and GSH. These results support the widespread use of Piper aleyreanum in popular medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive, anti-inflammatory and gastroprotective properties.

Antinociceptive and anti-inflammatory potential of extract and isolated compounds from the leaves of Salvia officinalis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia officinalis L. has been used as a traditional herbal medicine for gastric disturbances and inflammatory processes. This study investigated the toxicological, antinociceptive and anti-inflammatory effects of the hydroalcoholic extract (HE) from leaves of Salvia officinalis and its isolated compounds in mice. MATERIALS AND METHODS: Mice were treated with HE before the induction of nociceptive response by chemical agents (acetic-acid, formalin, glutamate, capsaicin and cinnamaldehyde). Total leukocytes and plasma extravasation induced by acetic acid and paw oedema induced by glutamate, capsaicin and cinnamaldehyde were also measured. The antinociceptive effect of carnosol and ursolic acid/oleanolic acid were evaluated on formalin and cinnamaldehyde models. RESULTS: In the acute toxicity test the value of estimated LD50 for HE was 44.7579 g/kg. Oral administration of HE (10, 30 and 100 mg/kg) inhibited the number of writhings, total leukocytes and plasma extravasation induced by acetic acid. In the formalin test, HE reduced both neurogenic and inflammatory phases, effect that was affected by naloxone. The glutamate-, capsaicin- and cinnamaldehyde-induced nociception and paw oedema were reduced by HE at doses that did not affect the locomotor activity of mice in the open field test. Carnosol (10mg/kg) and ursolic acid/oleanolic acid (30 mg/kg) inhibited the inflammatory phase of formalin and the nociception and mechanical allodynia induced by cinnamaldehyde. CONCLUSIONS: These results demonstrate that HE presents significant anti-inflammatory and also antinociceptive effects on chemical behavioral models of nociception that involves an opioid mechanism. In addition, carnosol and ursolic acid/oleanolic acid contained in this plant appears to contribute for the antinociceptive property of the extract, possibly through a modulatory influence on TRPA1-receptors. However, further studies regarding the precise site and the mechanism of action of HE and carnosol and ursolic acid/oleanolic acid merited exploring further.

Involvement of Interleukin-10 in the Anti-Inflammatory Effect of Sanyinjiao (SP6) Acupuncture in a Mouse Model of Peritonitis.

In this study, we determined the anti-inflammatory effect of manual acupuncture at the Sanyinjiao or Spleen 6 (SP6) point on carrageenan-induced peritonitis in mice and investigated mechanisms that may underlie this effect. In the first set of experiments, male Swiss mice were allocated into five groups: the control (sterile saline), dexamethasone (DEXA), invasive sham-acupuncture (non-acupoint), SP6 acupuncture and carrageenan-treated groups. Ten minutes after needle retention or 30 min after DEXA treatment, mice received an intraperitoneal injection of carrageenan (750 µg/mouse). After 4 h, total leukocyte and differential cell counts (neutrophils and mononuclear), myeloperoxidase (MPO) activity, vascular permeability and cytokine levels were evaluated. In another set of experiments, adrenalectomized (ADX) mice were used to study the involvement of the adrenal gland on the therapeutic effects of acupuncture. Mice were allocated into two groups: the ADX and sham-operated animals (Sham ADX) that were subdivided into four subgroups each: the control (sterile saline), DEXA, SP6 acupuncture and carrageenan-treated groups. The SP6 and DEXA treatments inhibited the inflammatory cell infiltration, vascular permeability and MPO activity in carrageenan-injected mice. In addition, the SP6 treatment also increased interleukin (IL)-10 levels. In contrast, when the animals were adrenalectomized, the SP6 treatment failed to reduce total leukocyte and the plasma extravasation. In conclusion, this study clearly demonstrates the anti-inflammatory effect of SP6 acupuncture in a model of carrageenan-induced peritonitis. Our results demonstrated that SP6 acupuncture depends of the adrenal glands and increased IL-10 levels to produce its anti-inflammatory action.