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Isolation and Pharmacological Characterization of Six Opioidergic Picralima nitida Alkaloids.

ABSTRACT: The seeds of the akuamma tree (Picralima nitida) have been used as a traditional treatment for pain and fever. Previous studies have attributed these effects to a series of indole alkaloids found within the seed extracts; however, these pharmacological studies were significantly limited in scope. Herein, an isolation protocol employing pH-zone-refining countercurrent chromatography was developed to provide six of the akuamma alkaloids in high purity and quantities sufficient for more extensive biological evaluation. Five of these alkaloids, akuammine (1), pseudo-akuammigine (3), akuammicine (4), akuammiline (5), and picraline (6), were evaluated against a panel of >40 central nervous system receptors to identify that their primary targets are the opioid receptors. Detailed in vitro investigations revealed 4 to be a potent kappa opioid receptor agonist, and three alkaloids (1-3) were shown to have micromolar activity at the mu opioid receptor. The mu opioid receptor agonists were further evaluated for analgesic properties but demonstrated limited efficacy in assays of thermal nociception. These findings contradict previous reports of the antinociceptive properties of the P. nitida alkaloids and the traditional use of akuamma seeds as analgesics. Nevertheless, their opioid-preferring activity does suggest the akuamma alkaloids provide distinct scaffolds from which novel opioids with unique pharmacologic properties and therapeutic utility can be developed.

SUBMITTER: Creed SM

PROVIDER: S-EPMC7932029 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDiabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia generally associated with oxidative stress. The present study aims at evaluating the antioxidant and antidiabetic potential of methanol and hydroethanol extracts of the stem bark and leaves of Pricralima nitida and the Sonchus oleraceus whole plant respectively.MethodsThe in vitro antioxidant activity was assessed using 1,1-Diphenyl-2-picrilhydrazyl (DPPH) for free radical-scavenging properties of the extracts, and the Folin-Ciocalteu method in determining their phenol contents. The antidiabetic activity was tested in mice following streptozotocin diabetes induction, and selected oxidative stress markers (Malondialdehyde, Hydrogen peroxides and Catalase) were measured in order to evaluate the level of oxidative stress in treated animals.ResultsThe in vitro antioxidant activity using DPPH showed IC50 ranging from 0.19?±?0.08 to 1.00?±?0.06 mg/mL. The highest activity was obtained with the hydroethanol extracts of S. oleraceus (0.19 mg/mL and P. nitida (0.24 mg/mL). Polyphenol contents ranged from 182.25?±?16.76 to 684.62?±?46.66 ?g Eq Cat/g. The methanol extract of P. nitida showed the highest activity, followed by the hydroethanol extract of S. oleraceus (616.89?±?19.20 ?Eq Cat/g). The hydroethanol extract of whole plants (150 mg/Kg) and methanol leave extract of P. nitida (300 mg/Kg) exhibited significant antidiabetic activities with 39.40% and 38.48% glycaemia reduction, respectively. The measurement of stress markers in plasma, liver and kidney after administration of both extracts showed significant reduction in MDA and hydrogen peroxide levels, coupled with a substantial increase in catalase activity.ConclusionsThese findings suggest that S. oleraceus whole plant and P. nitida leaves possess both antidiabetic and antioxidant properties, and therefore could be used as starting point for the development of herbal medicines and/or source of new drug molecules against diabetes.

Project description:Abstract 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‐1β, 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. Picralima nitida seeds (PNE) suppresses colon inflammation in acetic acid‐induced colitis model in rats. PNE inhibits expression of pro‐inflammatory cytokines. PNE exhibits antioxidant action in its anti‐inflammatory potential.

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Isolation and Pharmacological Characterization of Six Opioidergic Picralima nitida Alkaloids.

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