In vitro and In vivo antimalarial activities of Avicennia africana P. Beauv. (Avicenniaceae) ethanolic leaf extract.

Background: The emergence of widespread drug-resistant strains of the malaria parasites militates against strives for more potent antimalarial drugs. Aim: The present study evaluated the antimalarial activity of A. africana ethanolic crude extract in vitro and in vivo against Plasmodium berghei -infected mice in anticipation of acquiring scientific evidence for it used by mangrove dwellers to treat malaria in Ghana. Methodology: The pulverized dried leaves were extracted with 70% ethanol (v/v) and screened for phytochemicals using standard protocols. The in vitro antimalarial activity was investigated against chloroquine-sensitive Plasmodium falciparum (Pf3D7 clones), MRA-102, Lot:70032033, via SYBR® Green I fluorescent assay method using positive control Artesunate (50-1.56 × 10-3 µg/mL). In the in vivo studies, doses (200-1500 mg/kg) of AAE were used in the 4-day suppressive and curative tests, using P. berghei-infected mice. Artemether/lumefantrine (1.14 mg/kg) and normal saline were used as positive and negative control respectively. Results: The phytochemical analysis revealed the presence of alkaloids, saponins, flavonoids, glycosides, tannins, terpenoids and phytosterols. The extract showed an IC50 of 49.30 ± 4.40 µg/mL in vitro and demonstrated complete parasite clearance at dose 1500 mg/kg in vivo with a suppressive activity of 100% (p < 0.0001) in the 4-day suppressive test. The extract demonstrated high curative activity (p < 0.0001) at 1500 mg/kg with 100% parasite inhibition and the oral LD50 > 5000 mg/kg in mice. Conclusion: The results demonstrated that A. africana crude extract has antimalarial activity both in vitro and in vivo supporting the traditional use of the plant to treat malaria.

In Vitro and In Vivo Effect of Xylopic Acid on Cytochrome P450 Enzymes.

INTRODUCTION: Xylopic acid (XA), the major constituent of the fruit of Xylopia aethiopica, has shown several pharmacological properties. Traditionally, the plant is used to treat several diseases and is being used in the preparation of several local foods despite the lack of information about its safety, food-drug interaction, and other pharmacokinetic properties. This study, therefore, investigated the effect of XA on rat liver cytochrome P450 (CYP) enzymes in vivo and in vitro. METHODS: Inhibition or induction of some isoforms of CYP450 enzymes: CYP 1A1/1A2, 1A2, 2B1/2B2, 3A4, 2D6, and 2C9 were investigated using microsomal fractions of the liver obtained from rats pretreated with a low dose of xylopic acid (LDT) 30 mg/kg, high dose of xylopic acid (HDT) 100 mg/kg, phenobarbitone (PC) 80 mg/kg, and ketoconazole (NC) 100 mg/kg, and a no-treatment group received distilled water, with (n = 5) animals in each group. The in vitro inhibition of CYP 3A4 was assessed by treating rat liver microsomes with XA. RESULTS: Xylopic acid induced CYP 1A1/1A2, 1A2, 2D6, and 2C9, inhibited CYP 3A4, and had no effect on 2B1/2B2. CONCLUSION: The findings would help mitigate toxicity and therapeutic failure especially in cases of coadministration of medications with food containing XA, with metabolism altered by the latter.

A Hydroethanolic Leaf Extract of Persicaria lanigera Possesses Antinociceptive Activity through Cytokine and Glutamatergic Pathways In Vivo.

Persicaria lanigera is used traditionally to treat pain. The antinociceptive properties of the hydroethanolic leaf extract of Persicaria lanigera (PLE) were evaluated in rats and mice. Mice were pretreated orally with PLE (30, 100, and 300 mg kg-1) and evaluated for antinociceptive effects in the acetic acid-, glutamate-, and formalin-induced nociception models. Additionally, mechanical hyperalgesia models were used to evaluate PLE's influence on TNF-α- and IL-1ß-induced hyperalgesia in rats. In the acetic acid-induced nociception model, 100 mg kg-1 PLE exhibited the highest antinociceptive activity of 95.13 ± 9.52% at p < 0.0001, followed by the 300 mg kg-1 (85.44 ± 5.75%; p < 0.0001) and then the 30 mg kg-1 (67.95 ± 18.55%; p < 0.01), compared to morphine 3 mg kg-1 i.p. (86.97 ± 9.52; p < 0.0001). PLE (30, 100, and 300 mg kg-1) also showed significant (p < 0.05) antinociceptive effect in phase two of the formalin-induced nociception with % inhibitions of 66.88 ± 12.17, 75.12 ± 9.01, and 89.12 ± 4.32%, respectively, compared to 3 mg/kg morphine (97.09 ± 2.84%). Similarly, PLE (30, 100, and 300 mg kg-1) significantly reduced pain in the glutamate-induced nociception model with % inhibitions of 79.28 ± 8.17, 90.54 ± 5.64, and 96.49 ± 1.43%, respectively, whereas ketamine (5 mg/kg i.p.) reduced nociception to be 59.94 ± 18.14%. All doses of PLE significantly reduced nociceptive scores in TNF-α- and IL-1ß-induced mechanical hyperalgesia (p < 0.01). Similarly, PLE significantly inhibited bradykinin-induced nociception. The hydroethanolic extract of Persicaria lanigera has antinociceptive effects; this is the first scientific report providing evidence to validate its traditional use for the management of pain.

Antinociceptive effect of the hydroethanolic leaf extract of Calotropis procera (Ait) R. Br. (Apocynaceae): Possible involvement of glutamatergic, cytokines, opioidergic and adenosinergic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Pain remains real and still a major problem in clinical medicine which requires new agents with improved efficacy for more therapeutic benefits. Plant sources can serve as a basis for the search for some novel drugs hence the analgesic effects of the hydroethanolic extract of Calotropis procera (CPE) which is widespread in Ghana and other tropical areas and used in folkloric medicine for painful and inflammatory conditions was evaluated. MATERIALS AND METHODS: The analgesic properties of orally administered CPE at doses of 30, 100, and 300 mg/kg were evaluated in thermal (tail immersion), chemical (acetic acid-writhing, formalin-induced paw licking, glutamate-induced nociception) and mechanical (Randall-Selitto) tests for analgesia. The involvement of tumour necrosis factor-alpha (TNF-α), interleukin 1ß (IL 1ß), bradykinin, and prostaglandin E2 (PGE2) on the analgesic effects of CPE were also evaluated in hypernociception assays measuring mechanical pain thresholds. RESULTS: The latency of tail withdrawal in the tail immersion test was significantly increased (p = 0.0001) while writhing induced by acetic acid was significantly reduced (p < 0.0001) on treatment with CPE (30-300 mg/kg). The extract also significantly inhibited both phase 1 and phase 2 nociceptive states induced by formalin comparable to morphine (p < 0.0001). Furthermore, the extract significantly attenuated hyper-nociception induced by TNF-α (p < 0.0001), interleukin 1ß (p = 0.0102), bradykinin (p < 0.0001), and prostaglandin E2 (p < 0.0001). Additionally, glutamate-induced paw licking was reduced significantly (p < 0.05). The antinociceptive effects exhibited by CPE (100 mg/kg) in the formalin test was reversed by systemic administration of naloxone (2 mg/kg) and theophylline (5 mg/kg) but not glibenclamide (8 mg/kg), granisetron (2 mg/kg), atropine (3 mg/kg), yohimbine (3 mg/kg, p.o.) nor nifedipine (10 mg/kg). CONCLUSION: Overall, the hydroethanolic leaf extract of Calotropis procera possesses analgesic properties that is mediated possibly through the glutaminergic, opioidergic, and adenosinergic pathways.

Protective effect of bergapten in acetic acid-induced colitis in rats.

Bergapten (5-methoxysporalen) is a furanocoumarin extracted from several species of citrus and bergamot oil. Bergamot essential oil is used traditionally in the management of inflammatory conditions. Previous studies on bergapten have explored mainly its in vitro anti-inflammatory activities which include suppression of the expression and release of pro-inflammatory cytokines such as TNF-α and interleukins as well as prostaglandins. Bergapten enhances the clearance of neutrophils and macrophages from the site of inflammation and reduces oxidative stress by inhibition of reactive oxygen species (ROS). Bergapten was assessed for its anti-inflammatory properties in acetic acid-induced colitis. Animals were obtained and randomly placed in six (6) groups (n = 5) after acclimatization. Colitis was induced by rectal administration using 4% v/v acetic acid in Sprague Dawley rats after pre-treatment for 5 days. Bergapten was administered at doses of 3, 10, and 30 mg kg-1 p.o. while the control group received saline 5 mL kg-1 p.o. and the standard drug employed was sulphasalazine at a dose of 500 mg kg-1. Assessments made for colon-weight-to-length ratio, colonic injury, and mucosal mast cell degranulation. There were reduced colon-weight-to-length ratios in animals treated with bergapten which was significant (p < 0.5) for doses 10 and 30 mg kg-1 compared to the disease control group Both macroscopic and microscopic damage were reduced as well, with a lesser percentage of degranulated mast cells. Macroscopic damage was reduced for bergapten at doses 10 and 30 mg kg-1 significantly at p < 0.5 and p < 0.001, respectively. Similarly, microscopic damage was reduced at p < 0.01 and p < 0.001 respectively for bergapten 10 and 30 mg kg-1. The reduction of degranulation by bergapten was significant at p < 0.001. There was generally reduced damage at inflammatory sites as well as decreased infiltration of inflammatory cells. Overall, bergapten reduces inflammation in acetic acid-induced colitis.