Acetic acid-induced colitis modulating potential of total crude alkaloidal extract of Picralima nitida seeds in rats.

PURPOSE: The total crude alkaloidal extract of Picralima nitida seeds (PNE) is known to possess anti-inflammatory activity among other therapeutic benefits although its benefits in colitis has not been investigated. The current study therefore seeks to investigate the anti-colitis potential of PNE using acetic acid-induced colitis model in rats. METHODS: Sprague Dawley rats were treated with oral 500 mg/kg sulphasalazine or 30, 100, and 300 mg/kg of PNE daily for 8 days with induction of colitis on the fourth day with acetic acid. Rats were killed 24 h after the last treatment and whole blood was obtained from the jugular vein for hematological analysis and biochemical assays. Colons were extirpated for assessment of macroscopic and histological damage to the colon. RESULTS: Treatment with PNE protected against colonic injury induced with acetic acid by decreasing mucosal ulceration, epithelial erosion, inflammatory cell infiltration, and colonic edema. Thus, PNE preserved mucosal architecture and suppressed goblet cells depletion. Moreover, treatment with PNE was associated with improved hematological parameters and reductions in the expression of serum tumor necrosis factor-alpha, interleukin-1ß, and p38 mitogen-activated protein kinase. Also, PNE treatment exerted antioxidant effects by reducing nitric oxide production and increasing glutathione levels. In addition, PNE inhibited colonic lipid peroxidation by decreasing myeloperoxidase activity and malondialdehyde production. CONCLUSION: It can be concluded that PNE attenuates intestinal oxidative and inflammatory damages following intrarectal acetic acid challenge. Thus, demonstrates potential for use in chronic intestinal inflammatory diseases such as ulcerative colitis.

Inflammation Modulating Activity of the Hydroethanol Stem Bark Extract of Bombax costatum in Murine Models.

Bombax costatum (Bombacaceae) is traditionally used as a decoction of the leaves, stem, and root to treat headaches, fever, and oedema that may be associated with inflammatory conditions. Thus, the aim of this study was to evaluate the effect of 70%v/v ethanolic extract of the stem bark of Bombax costatum on acute and chronic inflammation. The effect of Bombax costatum extract (10, 50, 100 mg kg-1, p.o) was studied in prostaglandin E2-induced paw oedema in Sprague-Dawley rats (n = 5). Subsequently, the effect of the extract on clonidine and haloperidol-induced catalepsy was also investigated in ICR mice (n = 5). Finally, the ability of the extract to inhibit chronic inflammation was studied using a rat adjuvant-induced arthritis model. Pre-emptive and therapeutic administration of the extract at all doses significantly suppressed the formation of oedema following prostaglandin E 2 administration. As a measure of indirect antihistaminic effect, treatment with the extract suppressed clonidine-induced catalepsy but not haloperidol-induced catalepsy. Moreover, Bombax costatum extract significantly inhibited joint inflammation and damage following injection of complete Freund's adjuvant. Treatment with the extract also inhibited the onset of polyarthritis; thus, suppressing the systemic spread of joint inflammation from ipsilateral limbs to contralateral limbs. In conclusion, the hydroethanol extract of the stem bark of Bombax costatum inhibits both acute and chronic inflammation.

Regulation of Nrf2 and NF-κB activities may contribute to the anti-inflammatory mechanism of xylopic acid.

Xylopic acid (XA) is a kaurene diterpene which naturally exists in African plants such as Xylopia aethiopica. It has been established to exhibit acute and chronic anti-inflammatory activities from our earlier studies. This current work sets out to shed light on the potential molecular target(s) of xylopic acid. Selection of investigated targets (NF-κB, Nrf2 and PTP1B) was based on an unbiased approach, using the SPiDER in silico prediction tool, and a candidate approach, examining well-known anti-inflammatory targets. Reporter gene assays were used to test for altered NF-κB and Nrf2 activities in transfected HEK or CHO cells, respectively, and immunoblot and flow cytometric analyses examined protein expression of the Nrf2/NF-kB target genes HO-1 and VCAM-1 in HUVEC. An effect of XA on PTP1B activity assay was studied using an in vitro enzyme assay with recombinant human enzyme and pNPP as substrate as well as by looking at insulin receptor phosphorylation in HepG2 cells. XA at 30 µM significantly (p < 0.001) inhibited the NF-κB-dependent reporter gene expression and enhanced activation of Nrf2 in a concentration-dependent manner when compared to the control. XA also marginally increased HO-1 protein expression levels while expression of VCAM-1 was reduced to 70% in XA-treated endothelial cells. However, XA did not show any sign of inhibition of PTP1B or a related phosphatase. Our findings suggest that the anti-inflammatory mechanism of XA entails the inhibitory effect on NF-κB and an increased activity of Nrf2, accompanied by increased expression of HO-1 and reduced expression of VCAM-1.

Resistance Modulation Action, Time-Kill Kinetics Assay, and Inhibition of Biofilm Formation Effects of Plumbagin from Plumbago zeylanica Linn.

Antimicrobial resistance (AMR) is a threat to the prevention and treatment of the increasing range of infectious diseases. There is therefore the need for renewed efforts into antimicrobial discovery and development to combat the menace. The antimicrobial activity of plumbagin isolated from roots of Plumbago zeylanica against selected organisms was evaluated for resistance modulation antimicrobial assay, time-kill kinetics assay, and inhibition of biofilm formation. The minimum inhibitory concentrations (MICs) of plumbagin and standard drugs were determined via the broth microdilution method to be 0.5 to 8 µg/mL and 0.25-128 µg/mL, respectively. In the resistance modulation study, MICs of the standard drugs were redetermined in the presence of subinhibitory concentration of plumbagin (4 µg/mL), and plumbagin was found to either potentiate or reduce the activities of these standard drugs with the highest potentiation recorded up to 12-folds for ketoconazole against Candida albicans. Plumbagin was found to be bacteriostatic and fungistatic from the time-kill kinetics study. Plumbagin demonstrated strong inhibition of biofilm formation activity at concentrations of 128, 64, and 32 µg/mL against the test microorganisms compared with ciprofloxacin. Plumbagin has been proved through this study to be a suitable lead compound in antimicrobial resistance drug development.

Investigation of Acid-Base Indicator Property of Plumbagin from Plumbago zeylanica Linn.

There has been an increasing interest in the search for colour indicators of natural origin for titrimetric analysis. This is due to some challenges associated with the currently used synthetic ones. This study evaluates and validates the acid-base indicator property of plumbagin isolated from Plumbago zeylanica Linn. Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) was isolated from the roots of Plumbago zeylanica Linn using silica gel chromatography and characterized using spectroscopic methods in comparison with those reported in the literature. Its acid-base indicator property was evaluated alongside phenolphthalein and methyl orange, after it was found to exhibit a sharp change in colour at various pH ranges. The plumbagin indicator was successfully used to assay ibuprofen powder and tablets (400 mg) using the British Pharmacopoeia (2013) method. Data obtained were analyzed statistically by Student's t-test and one-way ANOVA in GraphPad Prism (version 5.01, 2010). Analysis of the use of the plumbagin indicator in acid-base titrations between strong acids and strong bases and between weak acids and strong bases has been evaluated and validated according to the ICH guidelines. Plumbagin use in ibuprofen powder and tablets has also been verified. Plumbagin has been validated for use as an indicator suitable for different acid-base titrations and the analysis of ibuprofen.

Effects of an ethanol extract and the diterpene, xylopic acid, of Xylopia aethiopica fruits in murine models of musculoskeletal pain.

CONTEXT: Fruits of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) are used traditionally to manage arthritis, headache and other pain disorders. OBJECTIVE: The analgesic properties of the X. aethiopica ethanol fruit extract (XAE) and xylopic acid (XA) were evaluated in musculoskeletal pain models. MATERIALS AND METHODS: Acute muscle pain was induced in gastrocnemius muscle of Sprague-Dawley rats with 3% carrageenan (i.m.). Rats received XAE (30-300 mg/kg), XA (10-100 mg/kg) or morphine (1-10 mg/kg) after 12 h. Effects of XAE and XA on muscle pain were assessed by measuring post-treatment grip strength of the rats. Chronic muscle pain was similarly induced, but drug treatment was on the eighth day and effects of XAE and XA assessed with Randall-Selitto test for hyperlagesia. Acute-skeletal pain was induced in knee joints of rats with 3% carrageenan-kaolin mixture and effects determined 12-h later. Similar induction protocol was used for chronic knee pain with treatment and measurement as done for chronic muscle pain. RESULTS: XAE and XA significantly and dose-dependently ameliorated both acute muscle (ED50 mg/kg: XAE = 22.9; XA = 6.2) and skeletal hyperalgesia (XAE = 39.9; XA = 17.7) induced by 3% carrageenan. Similarly, chronic skeletal hyperalgesia was reduced by XAE and XA treatment similar to morphine (ED50: XAE = 13.0; XA = 4.6). This reduction was also seen in chronic muscle hyperalgesia (ED50: XAE = 79.1; XA = 42.7). XAE and XA significantly reduced the spread of hyperalgesia to contralateral limbs in both models of chronic hyperalgesia. CONCLUSION: These findings establish analgesic properties of the ethanol fruit extract of X. aethiopica and xylopic acid in musculoskeletal pain.