Exploration of essential oil from Psychotria poeppigiana as an anti-hyperalgesic and anti-acetylcholinesterase agent: Chemical composition, biological activity and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from Psychotria poeppigiana Müll. Arg. (accepted as Palicourea tomentosa (Aubl.) Borhidi), Rubiaceae, has traditionally been used in medicine for treatments of inflammation and pain; Synonymously, Cephaelis elata for the treatment of dementia; However, few scientific studies have been evidence demonstrating this activity. AIM OF THE STUDY: The aim of this study was to investigate the chemical composition of P. poeppigiana essential oil obtained from leaves (EOPP) and its antioxidant, anti-inflammatory and acetylcholinesterase (AChE) activities. Molecular docking simulations were carried out with the main constituents. MATERIALS AND METHODS: EOPP (hydrodistillation) was analysed by gas chromatography-mass spectrometry (GC-MS). The fractionation of EOPP afforded germacrene D and bicyclogermacrene. The antioxidant activity of EOPP was determined by MDA assay. The inflammatory parameters were evaluated using CFA model (with paw edema, mechanical, thermal hyperalgesia, MPO and NAG) in EOPP (30, 100 and 300 mg/kg), germacrene D and bicyclogermacrene (30 mg/kg). The AChE inhibition was evaluated in rat brain structures and molecular docking simulations were carried out using Autodock v.4.3.2. RESULTS: GC-MS analysis identified 19 compounds, and the major compounds were germacrene D (29.38%) and bicyclogermacrene (25.21%). EOPP exhibited high antioxidant capacity (IC50 = 12.78 ± 1.36 µg/mL). All the tested doses of EOPP and both major constituents significantly inhibited cold and mechanical hyperalgesia and significantly blocked the increase in MPO activity 24 h after the CFA injection. There was significant AChE inhibition by EOPP and germacrene D in the cerebral cortex and hippocampus (>50%). Enzyme-ligand molecular modelling showed that the major constituents of EOPP interacted differently with AChE. CONCLUSIONS: The chemical compounds of the essential oil from the leaves of P. poeppigiana is based mainly on terpenes, the sesquiterpenes germacrene D (29.38%) and bicyclogermacrene (25.21%) being the major compounds. EOPP presented antioxidant, anti-inflammatory and anti-acetylcholinesterase (AChE) activities. Besides, enzyme-ligand molecular modelling showed the EOPP may act as an anti-hyperalgesic and AChE inhibitory agent. Taken together, these results might be in accordance with if folk use for pain- and inflammation-related symptoms.

Palicourea tomentosa (Aubl.) Borhidi: Microscopy, chemical composition and the analgesic, anti-inflammatory and anti-acetylcholinesterase potential.

ETHNOPHARMACOLOGICAL RELEVANCE: Palicourea tomentosa (Aubl.) Borhidi (synonym Psychotria poeppigiana Müll. Arg.) leaves are used in the popular treatments of inflammation and pain; however, there are no scientific studies demonstrating their activity as the methanolic extract of P. tomentosa. AIM OF STUDY: This study was undertaken to investigate the potential antioxidant, anti-acetylcholinesterase, anti-hyperalgesic, anti-nociceptive and anti-inflammatory properties, as well as the chemical composition and concentrations of constituents of the methanolic extract of P. tomentosa leaves (MEPT). The study also analyzes the micromorphology and histochemistry of leaves of P. tomentosa. MATERIALS AND METHODS: The MEPT was analysed by ultra-high-pressure liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS/MS). The concentrations of total phenols, flavonoids, flavonols and condensed tannin were determined. The micromorphology and histochemistry of leaves were performed using standard reagents, light and field emission scanning electron microscopy, beyond energy-dispersive X-ray spectroscopy. The antioxidant activity was evaluated for DPPH, ß-carotene and MDA. The anti-inflammatory activity of MEPT (30, 100, and 300 mg/kg) was assayed in carrageenan-induced models of paw oedema, mechanical hyperalgesia (Von Frey), cold allodynia (acetone) and pleurisy in mice. The anti-nociceptive potential of MEPT (30, 100, and 300 mg/kg) was evaluated by the formalin method in mice. The anti-acetylcholinesterase properties were evaluated in vivo in four rat brain structures. RESULTS: The total ion chromatogram of MEPT demonstrated two alkaloids, one coumarin, one iridoid and two terpene derivatives. The highest phenol, flavonoid, flavonol and condensed tannin concentrations were found in the extract. A comprehensive explanation of the leaf micromorphology and histochemistry was presented. MEPT was significantly inhibited by the DPPH, ß-carotene and MDA models. MEPT (30, 100 and 300 mg/kg) reduced the inflammation and hyperalgesic parameters in a carrageenan model and reduced formalin-induced nociception in both phases, which were cold sensitivity and oedema formation. The oral administration of 30 and 100 mg/kg MEPT significantly inhibited AChE activity in the frontal cortex. CONCLUSION: This is the first chemical and biological study performed with a P. tomentosa methanolic extract and anatomical and histochemical analysis. The present study showed that MEPT inhibited pain and inflammatory parameters contributing, at least in part, to explain the popular use of this plant as analgesic natural agent. Also, anatomical and histochemistry of leaves described in the present study provide microscopical information, which aids species identification.

Bioguided Fractionation, and Antioxidant, Antiproliferative, and Anti-Inflammatory Activity of Annona cacans Warm.

This study evaluated to determine the phenolic and flavonoids contents, and antioxidant, anti-inflammatory, and antiproliferative activity of the hydromethanolic extracts of the leaves, pulp, and seeds of Annona cacans. The isolation and structural identification of the constituent acetogenin, phenolic acid, and flavonoids were also reported. Antioxidant capacity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ethylbenzothiazoline-6-sulfonic acid (ABTS), and ß-carotene/linoleic acid methods. Cell proliferation was determined by spectrophotometric quantification of the cellular protein content using a sulforhodamine B assay. Anti-inflammatory activity was evaluated in paw edema model, to myeloperoxidase (MPO) activity induced by carrageenan in mice. Fractionation resulted in the isolation of one acetogenin (annoreticuin-9-one), two flavonoids (quercetin-3-O-ß-glucoside-6-O-α-rhamnoside and kaempferol-3-O-ß-glucoside), and one phenolic acid (p-coumaric acid). The pulp extract presented potent antioxidant activities by the DPPH (IC50 = 44.08 µg/mL) and ABTS (IC50 = 39.32 µg/mL) methods, as well as high contents of phenols (618.95 mg GA/g) and flavonoids (477.35 mg QE/g). The bioguided fractionation demonstrated that the ethyl acetate fraction of the pulp extract and annoreticuin-9-one showed potent antiproliferative activity against ovarian cancer (GI50 = 6.4 µg/mL). The anti-inflammatory activity demonstrated significant inhibition of edema compared to the control group in 2 and 4 h; in addition, the extracts inhibited the increase in MPO activity after 6 h, when compared to the DEX and control groups. For the first time, this study demonstrated antioxidant, anti-inflammatory, and antiproliferative activity, as well as compounds isolated, suggesting that A. cacans could also be potential sources for prevention of cancer and other diseases associated with oxidative stress.

Psychotria leiocarpa Extract and Vincosamide Reduce Chemically-Induced Inflammation in Mice and Inhibit the Acetylcholinesterase Activity.

Species from Psychotria are used in folk medicine against inflammatory diseases, respiratory disturbances, and anti-hallucinogenic. In the present study, the compound vincosamide (PL-1) was identified for the first time in methanolic extract of the Psychotria leiocarpa (ME-PL) leaves, as well as the anti-inflammatory and anticholinesteric effects in rodents and molecular docking simulations. The fractionation of the chloroform fraction (CF-PL) through chromatographic methods afforded the known compound PL-1. The anti-inflammatory activity of the ME-PL (30, 100, and 300 mg/kg) and PL-1 (3, 30, and 100 mg/kg) was analyzed using experimental models: paw edema, pleurisy, and mechanical and thermal hyperalgesia induced by carrageenan. The anticholinesterase activity of the ME-PL (30 and 100 mg/kg) and PL-1 (30 mg/kg) was showed by acetylcholinesterase (AChE) inhibitory in brain structures. The molecular docking simulations were performed using Molegro Virtual Docker v6.0. Overall, the results indicated that ME-PL and PL-1 demonstrated an anti-edematogenic effect in Cg-induced paw edema, leukocyte migration in the pleurisy model, and significantly reduced mechanical hyperalgesia, cold response to acetone in mice. The samples exhibited maximal inhibition of enzyme acetylcholinesterase (AChE) in the frontal cortex. The molecular coupling of PL-1 with the AChE showed significant interactions with the catalytic and peripheral site, corroborating the activity presented in the inhibition assay. The acute administration of ME-PL did not cause signs of toxicity in the treated animals. The results showed that P. leiocarpa inhibited AChE and anti-inflammatory activity, and alkaloid vincosamide could be responsible, at least in part, for the observed effects, supporting the popular use of this genus.

Anti-inflammatory Activity of Methanolic Extract and an Alkaloid from Palicourea crocea (Sw.) Roem and Schult.

Palicourea crocea (Sw.) Roem. and Schult., "douradinha," are used by treat inflammation (edema). Croceaine A (PC-1) was isolated from P. crocea (MEPC) leaves and studied for its antioxidant and anti-inflammatory activity, as well as concentrations of constituents and acute toxicity. The phenols and polyphenolics compounds and HPLC/DAD were determined. The antioxidant activity were evaluated for DPPH, ABTS, and MDA. MEPC (300, 100, and 300 mg/kg) and PC-1 (10 and 30 mg/kg) were tested for anti-inflammatory effects in paw edema, pleurisy, cold sensitivity, and mechanical hyperalgesia. Acute toxicity is also described. MEPC contained high concentrations of phenolic and flavonoid compounds (≤ 800.35 mg/g), as well as caffeic acid, ferulic acid, rutin, and quercetin, revealed by HPLC-DAD analysis. MEPC displayed antioxidant activity against ABTS radicals (IC50 = 68.5 µg/mL) and MDA (74%). MEPC and alkaloid PC-1 demonstrated an anti-edematogenic effect in Cg-induced paw edema in 2 and 4 h, and also significantly reduced mechanical hyperalgesia, cold response to acetone in mice, at 3 and 4 h after injection, as well as leukocyte migrationin the pleurisy model. No toxicity was detected by MEPC. For the first time, P. crocea was evaluated for its antioxidant, systemic anti-inflammatory, and anti-hyperalgesic activities.

Anti-inflammatory action of an alkaloid, fraction and extract from Alchornea glandulosa in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Alchornea glandulosa (Euphorbiaceae) has traditionally been used in medicine for treating immune-mediated inflammatory diseases. AIM OF STUDY: This work aimed to evaluate the anti-inflammatory effects of a methanolic extract of leaves from A. glandulosa (MEAG), as well as the ethyl acetate fraction (EAFAG) and isolated compound guanidine alkaloid N-1, N-2, N-3-triisopentenylguanidine (AG-1), in experimental in vivo models of inflammation in mice. We also investigated this extract's phenols, flavonoids and flavonol compounds. MATERIALS AND METHODS: MEAG (extracted by maceration with methanol), EAFAG (fraction resulting from the partition of the methanolic extract with ethyl acetate) and AG-1 (alkaloid isolated by chromatographic methods) were analysed. MEAG and EAFAG were analysed by HPLC/DAD. The effects of MEAG (30, 100 and 300 mg/kg), EAFAG (30, 100 and 300 mg/kg) and AG-1 (5 and 30 mg/kg) were studied in the following experimental mouse models: paw oedema and myeloperoxidase (MPO) activity, croton-oil-induced ear oedema, leukocyte migration in a pleurisy model induced by carrageenan and zymosan induction of joint inflammation. RESULTS: MEAG and EAFAG were analysed by LC/DAD, and phenolic acids (gallic acid and caffeic acid) and flavonoids (myricetin-3-O-α-rhamnopyranoside and quercetin) were detected. MEAG, EAFAG and AG-1 were used in the carrageenan-induced paw oedema model and showed maximum inhibitions of 60.10% (MEAG, 2 h, 300 mg/kg) and 66.21% (EAFAG, 2 h, 300 mg/kg). AG-1 at 5 mg/kg showed significant inhibition, ranging from 60.92% to 63.13%, at all evaluated times, and the 30 mg/kg dose showed inhibition of 42.12% (1 h) and 40.36% (2 h). MEAG (37%, 46.1% and 68.11%) and EAFAG (31%, 42.21% and 48.93%), at doses of 30, 100 and 300 mg/kg, respectively, significantly reduced the increase in MPO activity, and AG-1 (5 and 30 mg/kg) showed inhibition of 64.62% and 65.12%, respectively. In the pleurisy model, MEAG (300 mg/kg), EAFAG (300 mg/kg) and AG-1 (30 mg/kg) significantly reduced the migration of total leukocytes with maximal inhibition of 80.90%, 83.17% and 89.39%, respectively. In the croton oil model, pretreatment with MEAG (0.1, 0.3 and 1 mg/ear) increased the diameter of the right ear (30.32%, 48.87% and 53.09%, respectively). Finally, MEAG (100 and 300 mg/kg; 33.11% and 56.03%) and EAFAG (100 and 300 mg/kg; 36.89% and 50.53%) reduced zymosan-induced oedema formation. CONCLUSIONS: To the best of our knowledge, these results are the first to demonstrate that A. glandulosa exhibits oral and topical anti-inflammatory activity. This study detected alkaloid and phenol/polyphenolic compounds in A. glandulosa, which may help to explain the ethnobotanical use of this plant in traditional medicine in Brazil to treat immune-mediated inflammatory diseases.