Myricitrin exhibits antidepressant-like effects and reduces IL-6 hippocampal levels in the chronic mild stress model.

The flavonoid myricitrin showed an antidepressant-like effect in the tail suspension test and increased hippocampal neurogenesis, as well as demonstrating anti-inflammatory effects. Interestingly, inflammation has been linked to depression, and anti-inflammatory drugs showed promising results as antidepressant-like drugs. Thus, the present study evaluated the effects of myricitrin in the chronic mild stress (CMS) model, a translational and valid animal model of depression, using the mini-experiment design to improve the reproducibility of the findings. The sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were the readouts of depressive-like phenotypes induced by CMS. Relative adrenal weight was employed as an index of the hypothalamus-pituitary-adrenal (HPA) axis activation. Interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels were measured in the hippocampus. Myricitrin (10 mg/kg, intraperitoneally, for 14 days) reversed depressive-like behaviors induced by CMS (increased immobility in the FST, the TST and anhedonia), as well as decreased adrenal hypertrophy and hippocampal levels of IL-6 in stressed mice. Similar results were observed by imipramine (20 mg/kg, intraperitoneally, for 14 days), a serotonin and norepinephrine reuptake inhibitor (positive control). A significant correlation was observed between immobility time in the TST, and hippocampal IL-6 levels. Hippocampal TNF-α levels were not affected by CMS or drug treatment. In conclusion, myricitrin exhibited an antidepressant-like profile in CMS, and this effect may be associated with its anti-inflammatory activity.

Polygala sabulosa A.W. Bennett extract mitigates motor and cognitive deficits in a mouse model of acute ischemia.

Stroke is considered one of the leading causes of death worldwide. The treatment is limited; however, the Brazilian flora has a great source of natural products with therapeutic potentials. Studies with the medicinal plant Polygala sabulosa W. Bennett provided evidence for its use as an anti-inflammatory and neuroprotective drug. In the case of ischemic stroke due to lack of oxygen, both acute and chronic inflammatory processes are activated. Thus, we hypothesized that P. sabulosa (HEPs) has the potential to treat the motor and cognitive deficits generated by ischemic stroke. Male mice were subjected to global ischemia for 60 min, followed by reperfusion and orally treated with HEPs (100 mg/kg in saline + 3% tween 20) twice a day (12 h apart) for 48 h starting 3 h after surgery. Motor skills were assessed using grip force and open field tasks. Hippocampi were then collected for mRNA quantification of the cytokines IL-1-ß and TNF-α levels. After 48 h of acute treatment, spatial reference memory was evaluated in a Morris water maze test for another group of animals. We show that HEPs treatment significantly prevented motor weakness induced by ischemia. Brain infarct area was reduced by 22.25% with downregulation of the levels of IL-1ß and TNF-α mRNA. Learning performance and memory ability on Morris water maze task were similar to the sham group. Our data demonstrates the neuroprotective properties of HEPs through its anti-inflammatory activities, which prevent motor and cognitive impairments, suggesting that HEPs may be an effective therapy for ischemic stroke.

The potent insulin secretagogue effect of betulinic acid is mediated by potassium and chloride channels.

Betulinic acid (BA) has been described as an insulin secretagogue which may explain its potent antihyperglycemic effect; however, the exact role of BA as an insulinogenic agent is not clear. The aim of this study was to investigate the mechanism of BA on calcium influx and static insulin secretion in pancreatic islets isolated from euglycemic rats. We found that BA triggers calcium influx by a mechanism dependent on ATP-dependent potassium channels and L-type voltage-dependent calcium channels. Additionally, the voltage-dependent and calcium-dependent chloride channels are also involved in the mechanism of BA, probably due to an indirect stimulation of calcium entry and increased intracellular calcium. Additionally, the downstream activation of PKC, which is necessary for the effect of BA on calcium influx, is involved in the full stimulatory response of the triterpene. BA stimulated the static secretion of insulin in pancreatic islets, indicating that the abrupt calcium influx may be a key step in its secretagogue effect. As such, BA stimulates insulin secretion through the activation of electrophysiological mechanisms, such as the closure of potassium channels and opening of calcium and chloride channels, inducing cellular depolarization associated with metabolic-biochemical effects, in turn activating PKC and ensuring the secretion of insulin.

Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities.

The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2-11 were prepared by classical procedures. Including, five new esters derivatives 7-11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1-11 were confirmed by 1H NMR, 13C NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC50 = 12.48 µg/mL) and the lowest cytotoxic derivative (CC50 = 161.50 µg/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase.

Effects of two 6-quinolinyl chalcones on the integrity of plasma membrane of Paracoccidioides brasiliensis.

Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, yet few therapeutic options exist. Our aim was to search for new compounds with high efficacy, low toxicity, shorter treatment time and affordable cost. We studied two synthetic 6-quinolinyl chalcones, 3b and 3e, to determine their effects on VERO cells, antifungal activity, survival curve, interaction with other drugs and phenotypic effects against several isolates of Paracoccidioides spp. In this study, we verified that the compounds were not toxic, exhibited superior in vitro activity compared with that shown by trimethoprim-sulfamethoxazole, and after 5 days of treatment, decreased the fungal cell viability by approximately 70%. Additionally, no interactions were observed between the tested compounds and other drugs. We also found that these compounds induced morphological changes, such as shriveling of cells, fragmentation of the plasma membrane and cytoplasmic disorganization in vitro. The changes observed by microscopy assays corroborate the observation made with propidium iodide, where the number of cells stained with the compounds was higher than that observed after amphotericin B treatment. We observed an increase in the efflux of K+ and a loss of intracellular contents in cells treated with 3b and 3e, confirming their effects on fungal membranes. However, damage to the membrane was not associated with a decrease in membrane ergosterol levels. The experimental evidences showed no direct indications of cellular wall damage caused by these compounds. Thus, these results confirm the antifungal potential of 3b and 3e against Paracoccidioides spp. with possible action on the membrane.

Antinociceptive effect of hydroalcoholic extract and isoflavone isolated from Polygala molluginifolia in mice: evidence for the involvement of opioid receptors and TRPV1 and TRPA1 channels.

PURPOSE: The plants of the genus Polygala (Polygalaceae) have been used for a long time in folk medicine to treat pain and inflammation. The species Polygala molluginifolia is native to southern Brazil and is popularly known as "cânfora". The presented study analyzes the antinociceptive effect of hydroalcoholic extract from Polygala molluginifolia (HEPm) and an isoflavone (ISO) isolated from the extract, in behavioral models of pain in mice, as well as the mechanism underlying this effect. MATERIALS AND METHODS: The phytochemical analysis of HEPm was performed through a capillary electrophoresis analysis and colorimetric test. The antinociceptive effects of HEPm and ISO (10-1000 mg/kg, i.g.) were evaluated by applying the formalin test; mechanical and thermal hyperalgesia to postoperative pain in mice. The possible involvement of opioid receptors, TRPV1 and TRPA1 channels in the antinociceptive effect of HEPm and ISO were also evaluated. Finally, the nonspecific effects of HEPm and ISO were evaluated by measuring locomotor activity (Open-field Test) and corporal temperature. RESULTS: The 5,3',4'-trihydroxy-6″,6″-dimethylpyrano[2″,3″:7,6] isoflavone (ISO) was identified in HEPm by capillary electrophoresis analysis and selected for the experimental tests. The oral administration of HEPm or of ISO significantly inhibited the neurogenic and inflammatory phases of formalin-induced pain, edema formation and local hyperemia, without causing any change to locomotor activity. Acute and repeated treatment of animals with HEPm reduced mechanical and thermal (heat and cold) hyperalgesia in the postoperative pain. In addition, administering HEPm or ISO markedly reduced nociceptive behavior induced by the peripheral and central injection of TRPV1 and TRPA1 channels activators. Finally, the antinociception provided by the administration of HEPm or ISO was reversed by the preadministration of naloxone. CONCLUSIONS: Taken together, these results provide the first experimental evidence of the significant antinociceptive effect of HEPm and ISO in animal models of acute pain without causing sedation or locomotor dysfunction. This effect appears to be mediated, at least in part, by the activation of opioid receptors and/or by the inhibition of TRPV1 and TRPA1 channels. Moreover, this study adds new scientific evidence and highlights the therapeutic potential of the medicinal plant Polygala molluginifolia in the development of phytomedicines with analgesic properties.

Chemical constituents of Eugenia catharinae and their antioxidant activity.

Nine compounds were isolated from the leaves of Eugenia catharinae, namely monomethyl olivetol (1), ß-sitosterol (2), stigmasterol (3), uvaol (4), erythrodiol (5), rotundic acid (6), quercetin (7), catechin (8) and myricitrin (9). The structures of 1-9 were established through analysis of their spectroscopic (1H and 13C NMR) and spectrometric (MS) data. Compounds 1 and 6 are reported the first time in the Eugenia genus. In addition, these data were compared with those reported in the literature. The antioxidant activity of plant samples and compounds was measured using the DPPH radical scavenging assay. Flavonoids 7, 8, 9 and the ethanolic extract showed the best results, with IC50 values of 20.94 µM, 44.20 µM, 30.01 µM and 58.82 µg/mL, respectively.

7-prenyloxi-6-methoxycoumarin from Polygala sabulosa A.W. Bennett Regulates p38 MAPK and NF-kB Pathways Inhibiting the Inflammation Induced by Carrageenan in the Mouse Model of Pleurisy.

CONTEXT: Polygala sabulosa, popularly known as "timutu-pinheirinho," has been used in Brazilian folk medicine for the treatment of bowel and kidney disorders and as an expectorant. OBJECTIVE: Evaluate the anti-inflammatory effects of the crude extract (CE), acetonic fraction (Ac), and the main compound, 7-prenyloxi-6-methoxycoumarin (PC) on a mouse model of carrageenan-induced pleurisy. MATERIALS AND METHODS: A mouse model of carrageenan-induced pleurisy was used to investigate the effects of P. sabulosa CE, Ac and PC on leukocyte migration, exudate formation, activities of myeloperoxidase (MPO), and adenosine-deaminase (ADA), levels of tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß) and nitric oxide (NO). In addition, the effect of the plant material on lung histology was also evaluated. The effects of PC on the TNF-α, IL-1ß and NO synthase 2 (NOS2) mRNA expression, were also investigated. Finally, the effect of PC on the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) was also evaluated. RESULTS: CE, Ac and PC reduced inflammation in the pleural cavity and lungs. This effect was evidenced by reduction on all inflammatory parameters evaluated; the exception being the inability of the CE to inhibit exudate formation. In isolation, PC showed reduction on mRNA levels of TNF-α, IL-1ß and NOS2, and on activation of the NF-κB and p38 MAPK pathways. CONCLUSION: The presented results show that P. sabulosa has significant anti-inflammatory activity, as does its main compound, PC. Moreover, the results suggest that PC exerts its effects mainly by inhibited the NF-κB and p38 MAPK pathways.

Ameliorative potential of standardized fruit extract of Pterodon pubescens Benth on neuropathic pain in mice: Evidence for the mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant Pterodon pubescens Benth has been traditionally used for a long time to treat rheumatic diseases due to its anti-inflammatory and analgesic activities. The present study aims to evaluate the antinociceptive effect of ethanolic extract from P. pubescens fruits (EEPp) in a model of neuropathic pain in mice. MATERIALS AND METHODS: The phytochemical analysis of EEPp was performed through GC-MS, HPLC and colorimetric analysis. The antinociceptive effects of EEPp (30-300 mg/kg, i.g.) were evaluated on mechanical and thermal (cold or heat) hyperalgesia in neuropathic pain induced by partial sciatic nerve ligation (PSNL) in mice. We also investigated the effects of EEPp on the nociceptive response induced by intrathecal injection (i.t.) of ionotropic (AMPA, NMDA and kainate) and metabotropic (trans-ACPD) glutamate receptor agonists, proinflammatory cytokines such as IL-1ß and TNF-α, as well as TRPV1 and TRPA1 agonists. In addition, we also investigated the safety profile of prolonged treatment with EEPp in mice. RESULTS: The phytochemical analysis showed a higher amount terpenes, being nine sesquiterpenes and seven diterpenes with vouacapan skeletons, as well as a small amount of phenols and flavonoids. The exact mechanism by which EEPp promotes its antinociceptive effect is not yet fully understood, but its oral administration causes significant inhibition of glutamate-, kainate-, NMDA-, trans-ACPD-induced biting responses, as well as of proinflammatory cytokines (TNF-α and IL-1ß) and TRPV1 and TRPA1 channels activators (capsaicin and cinnamaldehyde, respectively). These results may indicate, at least in part, some of the mechanisms that are involved in this effect. In particular, EEPp decreases neuropathic pain and clearly shows, for the first time, a thermal and mechanical hyperalgesia reduction in the model of partial sciatic nerve ligation (PSNL), without inducing tolerance. Furthermore, the prolonged treatment with EEPp (300 mg/kg, i.g.) showed a cumulative effect over 24h, in the 15th day, after last treatment. In addition, the open-field test showed that doses up to 300 mg/kg in both treatments, acute and/or prolonged, did not affect the motor activity of mice. Also, EEPp showed no toxicity according to the serum levels of the renal and hepatic injury indicators or observed macroscopic organs, after PSNL. CONCLUSIONS: Taken together, these results provide the first experimental evidence of the significant antinociceptive effect of EEPp on neuropathic pain without causing side effects, such as sedation or locomotor dysfunction. Moreover, these results appear to be mediated, at least in part, by the inhibition of glutamatergic receptors, TRPV1 and TRPA1 channels and proinflammatory cytokines. Thus, this study adds new scientific evidence and highlights the therapeutic potential of the medicinal plant P. pubescens in the development of phytomedicines for the management of neuropathic pain.

Inhalation of Cedrus atlantica essential oil alleviates pain behavior through activation of descending pain modulation pathways in a mouse model of postoperative pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus atlantica essential oil (CaEO) presents analgesic and anti-inflammatory sedative properties. However, it remains unknown whether CaEO alleviates acute postoperative pain. MATERIALS AND METHODS: Here, we investigated the effect of CaEO on postoperative pain and its mechanisms related to the descending pain control in Swiss males mice induced by a plantar incision surgery (PIS) in the hindpaw. RESULTS: Inhalation of CaEO (5', 30' or 60') markedly reduced mechanical hypersensitivity. This effect was prevented by pre-treatment with naloxone or p-chlorophenylalanine methyl ester (PCPA, 100mg/kg, i.p.)-induced depletion of serotonin. In addition, p-alpha-methyl-para-tyrosin (AMPT, 100mg/kg, i.p.)-induced depletion of norepinephrine, intraperitoneal injection of the α2-adrenergic receptor antagonist yohimbine (0.15 mg/kg, i.p.) or haloperidol (1mg/kg, i.p.) an antagonist of dopaminergic (D1 and D2) receptors prevented the effect of CaEO on hypersensitivity. CONCLUSIONS: These findings suggest that CaEO alleviates postoperative pain by activating the descending pain modulation pathways on the opioidergic, serotonergic, noradrenergic (α2-adrenergic) and dopaminergic (dopamine D1 and D2 receptors) systems.

Pharmacological evidence favouring the traditional use of the root bark of Condalia buxifolia Reissek in the relief of pain and inflammation in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The Condalia buxifolia root bark infusion is used in traditional medicine in Brazil as antipyretic, anti-inflammatory and against dysentery. This study was designed to investigate whether the methanolic extract of the root bark of Condalia buxifolia (MECb) exhibits antinociceptive and anti-inflammatory effects in mice. Furthermore, also was investigated the involvement of glutamatergic and opioidergic system in the antinociceptive effect induced by MECb. MATERIALS AND METHODS: The antinociceptive and anti-inflammatory effects of intra-gastric gavage (i.g.) administered MECb (10-300 mg/kg) were evaluated in mice subjected to chemical (formalin, acetic-acid, glutamate) or thermal (hot plate) models of pain. The involvement of opioid system in the antinociceptive effect of the MECb was investigated in formalin test. Furthermore, a nonspecific effect of MECb was evaluated by measuring locomotor activity and exploratory behavior in open field test. Finally, was performed a phytochemical analysis of MECb. RESULTS: The phytochemical analysis of MECb was performed through HPLC analysis showing that the alkaloid Condaline-A is the main constituent. The intragastric administration of MECb (100-300 mg/kg) significantly inhibited the nociception caused by acetic acid (48 ± 2%), inflammatory phase (49 ± 3%) and paw edema (32 ± 6) caused by formalin, and MECb (100mg/kg, i.g.) also inhibited nociception caused by glutamate (41 ± 7%). In addition, MECb (100-300 mg/kg, i.g.) increased the paw withdrawal latency in hot-plate test, without affecting the locomotor activity and exploratory behavior in open field test. Finally, the antinociceptive effects of MECb (100mg/kg, i.g.) were significantly reversed by naloxone (1mg/kg, i.p.) in the formalin test. CONCLUSION: These data show, for the first time, that MECb has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system and the activation of opioid mechanism, besides present central effects. These results support the use of Condalia buxifolia in traditional medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive and anti-inflammatory properties.

Polygala molluginifolia A. St.-Hil. and Moq. prevent inflammation in the mouse pleurisy model by inhibiting NF-κB activation.

UNLABELLED: This study was conducted to investigate the anti-inflammatory activity of Polygala molluginifolia (Polygalaceae) on the mouse pleurisy model induced by carrageenan. P. molluginifolia is a plant native to southern Brazil that is popularly called "canfora". The Polygala genus is used to treat different pathologies, including inflammatory diseases, in traditional medicine. MATERIAL AND METHODS: The whole P. molluginifolia plant material was extracted by maceration with 96% ethanol. The crude hydroalcoholic extract (CE) was subjected to chromatographic procedures to produce various derivate fractions, including its aqueous (Aq), ethyl acetate (EtOAc), and hexane (Hex) fractions. Compound 1 (5,3',4'-trihydroxy-6″,6″-dimethylpyrano [2″,3″:7,6] isoflavone) (Iso), which was isolated from the EtOAc fraction, and Compound 2 (rutin) (Rut), which was isolated from the Aq fraction, were identified using ¹H and ¹³C NMR spectroscopy and quantified using an HPLC apparatus. RESULTS: The CE, the Aq, EtOAc, and Hex fractions, and the isolated compounds Iso and Rut were able to reduce cell migration and exudation. Furthermore, the plant material also decreased the myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and the nitric oxide (NO(x)), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) levels. In addition, Iso and Rut reduced the TNF-α and IL-1ß mRNA expression levels and significantly decreased NF-κB p65 phosphorylation. CONCLUSION: The results show that P. molluginifolia has a significant anti-inflammatory action and that this effect is due, at least in part, to the presence of Iso and Rut in large amounts. Moreover, this effect was found to be closely related to the inhibitory effects of the isolated compounds on the NF-κB pathway.

Anti-inflammatory action of hydroalcoholic extract, dichloromethane fraction and steroid α-spinasterol from Polygala sabulosa in LPS-induced peritonitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala sabulosa A. W. Bennett is a small herb popularly known as "timutu-pinheirinho" that is widely distributed in southern Brazil and that is used to treat disorders of the bowel and kidney and as a topical anesthetic and expectorant in folk medicine. This study was designed to investigate the anti-inflammatory properties of the hydroalcoholic extract (HEPs), CH2Cl2 fraction and the steroid α-spinasterol obtained from the aerial parts of Polygala sabulosa in a model of acute inflammation induced by intraperitoneal injection of bacterial lipopolysaccharide in mice. MATERIALS AND METHODS: The anti-inflammatory effect of HEPs (3-300 mg/kg, i.g.), CH2Cl2 fraction (0.003-30 mg/kg, i.g.) and steroid α-spinasterol (0.001-1mg/kg, i.p. or 1-10mg/kg, i.g.), were evaluated in mice subjected to the acute inflammation caused by intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 0.02 µg/kg). The anti-inflammatory activity of the HEPs, CH2Cl2 fraction and steroid were assessed by determining the total numbers of leukocytes and differential cell counts (neutrophils and mononuclear cells) and levels of pro-inflammatory (IL-1ß, TNF-α, IL-6) or anti-inflammatory (IL-10) cytokines in peritoneal fluid. RESULTS: The administration of HEPs (3-300 mg/kg, i.g.) completely inhibited inflammatory cell infiltration (300 mg/kg, i.g.) and it reduced TNF-α (100-300 mg/kg) and IL-1ß (100mg/kg) levels in LPS-injected mice. Furthermore, the administration of CH2Cl2 fraction (0.003-30 mg/kg, i.g.) or α-spinasterol (0.001-10mg/kg, by i.p. or i.g.) significantly reduces inflammatory cell infiltration in LPS-injected mice. Moreover, dexamethasone (0.5mg/kg, i.p., used as a positive control) inhibited inflammatory cell infiltration and reduced the levels of TNF-α, IL-1ß and IL-6 in LPS-injected mice. CONCLUSIONS: Taken together, these results provide the first experimental evidence demonstrating that HEPs have significant anti-inflammatory effects on LPS-induced inflammation. These effects appear to be, at least in part, due to the presence of α-spinasterol. These findings support the widespread use of Polygala sabulosa in popular medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with anti-inflammatory properties.

NMDA receptors and the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway are implicated in the antidepressant-like action of the ethanolic extract from Tabebuia avellanedae in mice.

Bark infusion of Tabebuia avellanedae Lorentz ex Griseb is consumed in tropical America folk medicine for the treatment of several diseases, including depressive disorders. It was recently demonstrated that the extract from this plant has antidepressant properties. The present study was aimed at investigating the contribution of N-methyl-D-aspartate (NMDA) receptors and the L-arginine-nitric oxide (NO)-cyclic guanosine 3'5'-monophosphate (cGMP) pathway to the antidepressant-like action of the ethanolic extract from T. avellanedae (EET) in the tail suspension test (TST). The anti-immobility effect of the extract (30 mg/kg, orally [p.o.]) was prevented by pretreatment of mice with NMDA (0.1 pmol/site, intracerebroventicular [i.c.v.]), L-arginine (750 mg/kg, intraperitoneally [i.p.]), and sildenafil (5 mg/kg, i.p.). Additionally, the combination of MK-801 (0.01 mg/kg, p.o.), 7-nitroindazole (25 mg/kg, i.p.), and 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (30 pmol/site, i.c.v.) with a subeffective dose of EET (1 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST, without causing significant alterations in the locomotor activity. Moreover, the administration of an effective dose of EET (30 mg/kg, p.o.) produced a reduction in NOx levels in the cerebral cortex. Conversely, a subeffective dose of EET (1 mg/kg, p.o.) caused no changes in the cortical NOx levels. Results suggest that the antidepressant-like effect of EET in the TST is dependent on a blockade of NMDA receptor activation and inhibition of NO-cGMP synthesis, significantly extending literature data about the antidepressant-like action of this plant and reinforcing the notion that this plant may be useful in the management of depressive disorders.

Pre-clinical anti-inflammatory aspects of a cuisine and medicinal millennial herb: Malva sylvestris L.

Malva sylvestris has been used since ancient times for its emollient, laxative and anti-inflammatory properties, being extensively used as salads, soups and teas. The preset study evaluated the topical anti-inflammatory action of M. sylvestris hydroalcoholic extract (HE) and its compounds in mice ear inflammation caused by 12-O-tetradecanoylphorbol-acetate in mice. The LC-MS analysis of the HE confirmed the presence of scopoletin, quercetin and malvidin 3-glucoside compounds in the HE of M. sylvestris. Topical application of the HE reduced ear oedema, polymorphonuclear cells influx (myeloperoxydase activity and histological analysis) and interleukin-1ß levels in the tissue. The topical application of the compound present in the HE, malvidin 3-glucoside was also able to inhibit ear oedema and leukocytes migration. The other tested compounds, scopoletin, quercetin and malvidin 3,5-glucoside were able to prevent the formation of oedema and cell infiltration, but with less effectiveness when compared to HE and malvidin 3-glucoside. Therefore, these results consistently support the notion that M. sylvestris leaves possesses topical anti-inflammatory activity, the compound malvidin 3-glucoside seems to be major responsible for this effect, with the participation of other anti-inflammatory compounds in the extract. Thus, as recommended by population, M. sylvestris can be used as a future treatment to skin disorders.

Relationship of chemical structure and anti-inflammatory activity of dihydrocorynantheol and its analogues.

BACKGROUND: Dihydrocorynantheol (DHC) is an alkaloid compound isolated from Esenbeckia leiocarpa Engl. that has demonstrated anti-inflammatory properties in experimental models. The aim of this study was to investigate whether the modification of the chemical structure of DHC could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan. METHODS: DHC was isolated from Esenbeckia leiocarpa Engl. Capillary electrophoresis, physical characteristics, spectral data produced by infrared analysis and nuclearmagnetic resonance ((1)H and (13)C), and mass spectrometry analysis were used to identify and elucidate DHC structure. The DHC compound was subjected to chemical structural modifications by nucleophilic substitution reactions, yielding five analogous compounds: acetyl (1), p-methylbenzoyl (2), benzoyl (3), p-methoxybenzoyl (4) and p-chlorobenzoyl (5). Swiss mice were used throughout the experiments. Pro-inflammatory parameters leukocyte migration, exudate concentrations and myeloperoxidase (MPO) activity were quantified in the fluid leakage from the mouse pleural cavities at 4 h after pleurisy induction. RESULTS: DHC and its analogues acetyl, p-methylbenzoyl, benzoyl, p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration and MPO activity (p < 0.05). Only DHC significantly decreased the exudate concentrations (p < 0.01). CONCLUSIONS: DHC was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan. We did not determine what physicochemical modifications altered the anti-inflammatory effect of DHC, but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the DHC.

Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L.

The aim of this study was to investigate the antidepressant-like effect of fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 (AcOEt1 and 2), hexane (HEX), ethanolic (ET), and essential oil-free (EOF) fractions, as well as essential oil, the isolated compounds carnosol and betulinic acid in the tail suspension test, a predictive test of antidepressant activity. Swiss mice were acutely administered by oral route (p.o.) with fractions, essential oil or isolated compounds, 60 min before the tail suspension test or open-field test. All of them produced a significant antidepressant-like effect: AcOEt1, ET, EOF fractions and essential oil (0.1-100mg/kg, p.o); HEX (0.1-10mg/kg, p.o) and AcOEt2 fraction (0.1-1mg/kg, p.o), carnosol (0.01-0.1mg/kg, p.o.) isolated from the HEX fraction and betulinic acid (10mg/kg, p.o.), isolated from the AcOEt1 and AcOEt2 fractions. No psychostimulant effect was shown in the open-field test, indicating that the effects in the tail suspension test are specific. This study suggests that carnosol and betulinic acid could be responsible for the anti-immobility effect of extracts from R. officinalis.

Antidepressant-like action of the bark ethanolic extract from Tabebuia avellanedae in the olfactory bulbectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia avellanedae Lorentz ex Griseb is a plant employed in tropical America folk medicine for the treatment of several diseases, including depressive disorders. AIM OF THE STUDY: To investigate the ability of Tabebuia avellanedae ethanolic extract (EET) administered chronically to cause an antidepressant-like effect in the tail suspension test (TST), a predictive test of antidepressant activity, and to reverse behavioral (hyperactivity, anhedonic-like behavior and increased immobility time in the TST) and biochemical changes induced by olfactory bulbectomy (OB), a model of depression, in mice. MATERIALS AND METHODS: Mice were submitted to OB to induce depressive-related behaviors, which were evaluated in the open-field test (hyperactivity), splash test (loss of motivational and self-care behavior indicative of an anhedonic-like behavior) and TST (increased immobility time). Phosphorylation levels of Akt, GSK-3ß, ERK1/2 and CREB, as well as BDNF immunocontent, were evaluated in the hippocampus of bulbectomized mice or sham-operated mice treated for 14 days by p.o. route with EET or vehicle. RESULTS: EET (10 and 30mg/kg) given 14 days by p.o route to mice reduced the immobility time in the TST without altering locomotor activity, an indicative of an antidepressant-like effect. EET per se increased both CREB (Ser(133)) and GSK-3ß (Ser(9)) phosphorylation (at doses of 10-30 and 30mg/kg, respectively) in sham-operated mice. OB caused hyperactivity, loss of motivational and self-care behavior, increased immobility time in the TST and an increase in CREB and ERK1 phosphorylation, as well as BDNF immunocontent. EET abolished all these OB-induced alterations except the increment of CREB phosphorylation. Akt (Ser(473)) and ERK2 phosphorylation levels were not altered in any group. CONCLUSIONS: EET ability to abolish the behavioral changes induced by OB was accompanied by modulation of ERK1 and BDNF signaling pathways, being a promising target of EET. Results indicate that this plant could constitute an attractive strategy for the management of depressive disorders, once more validating the traditional use of this plant.

Rosmarinus officinalis L. hydroalcoholic extract, similar to fluoxetine, reverses depressive-like behavior without altering learning deficit in olfactory bulbectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosemary, Rosmarinus officinalis L., has several therapeutic applications in folk medicine for the treatment of a wide range of diseases, including depression. AIM OF THE STUDY: To evaluate the ability of Rosmarinus officinalis hydroalcoholic extract (ROHE), as compared to the positive control fluoxetine, to reverse behavioral (hyperactivity, anhedonic behavior and learning deficit in water maze) and biochemical alterations (serum glucose level and acetylcholinesterase, AChE, activity) induced by an animal model of depression, the olfactory bulbectomy (OB) in mice. MATERIALS AND METHODS: Locomotor and exploratory behavior was assessed in the open-field, novel object and novel cage tests, anhedonic behavior was assessed in the splash test; cognitive deficits were evaluated in the water maze task. For the first set of experiments, ROHE (10-300 mg/kg) or fluoxetine (10mg/kg) was administered once daily (p.o.) for 14 days after OB and the behavioral tests were performed. For the second set of experiments, serum glucose and hippocampal and cerebrocortical AChE activity were determined in OB and SHAM-operated mice treated orally with ROHE (10mg/kg), fluoxetine (10mg/kg) or vehicle. RESULTS: ROHE (10-300 mg/kg), similar to fluoxetine, reversed OB-induced hyperactivity, increased exploratory and anhedonic behavior. OB needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of SHAM mice in the test session (24h later), demonstrating a selective deficit in spatial learning, which was not reversed by ROHE or fluoxetine. A reduced serum glucose level and an increased hippocampal AChE activity were observed in bulbectomized mice; only the latter effect was reversed by fluoxetine, while both effects were reversed by ROHE. CONCLUSIONS: ROHE exerted an antidepressant-like effect in bulbectomized mice and was able to abolish AchE alterations and hypoglycemia, but not spatial learning deficit induced by OB. Overall, results suggest the potential of Rosmarinus officinalis for the treatment of depression, validating the traditional use of this plant.

Oleaginous extract from the fruits Pterodon pubescens Benth induces antinociception in animal models of acute and chronic pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Pterodon pubescens Benth is a medicinal plant commonly used for therapeutic purposes in folk medicine for rheumatic diseases' treatment. In the present work we analyzed the chemical composition of the oleaginous extract of P. pubescens Benth (OEPp) and extended the antinociceptive effect of OEPp evaluating its role on animal models of acute and chronic pain. MATERIALS AND METHODS: The antinociceptive and antiedematogenic effects of OEPp (3-100mg/kg, i.g.) were evaluated in the formalin test; mechanical allodynia in the postoperative pain and complex regional pain syndrome type-I (CRPS-I) animal models; and thermal hyperalgesia was induced by plantar incision. Finally, we performed a phytochemical analysis of OEPp. RESULTS: The chemical composition of OEPp was analyzed by mass spectrometry (GC/MS) and eight sesquiterpene compounds were identified, i.e. three major sesquiterpene (E-cariofilene, γ-muurolene, biciclogermacrene), and nine vouacapane diterpenes, four of which showed in major concentration (6α-acetoxyvouacapane, 6α,7ß-dimetoxivouacapan-17-ene, 6α-acetoxy,7ß-hidroxyvouacapane, 6α,7ß-diacetoxycouacapane). Furthermore, the results of the present study demonstrate, for the first time, that the OEPp reduced mechanical allodynia in the postoperative pain and CRPS-I animal models. OEPp also increased the paw withdrawal latency in hot- and cold-plate tests in the postoperative pain model. In addition, the present work confirms and extends previous data from literature showing that systemic administration of OEPp caused significant inhibition against both phases of pain response to formalin intraplantar injection and edema formation. CONCLUSIONS: Together, present and previous findings show that OEPp given intra-gastrically caused significant inhibition against both phases of formalin intraplantar injection and effectively inhibited mechanical and thermal hyperalgesia in the postoperative pain and CRPS-I animal models.