Anti-inflammatory and urease inhibitory iridoid glycosides from Nyctanthes arbor-tristis Linn

• Published in: Journal of ethnopharmacology 2024-01, Vol.319 (Pt 3), p.117368-117368, Article 117368
• Main Authors: Sana, Talea, Khan, Majid, Siddiqui, Bina S, Baig, Tariq Ahmad, Jabeen, Almas, Begum, Sabira, Hadda, Taibi B, Shah, Luqman
• Format: Article
• Language: English
• Subjects: Animals; anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; blood; chromatography; cytokines; cytotoxicity; ethanol; fibroblasts; fractionation; Iridoid Glycosides - pharmacology; Kinetics; loganin; luminescent assay; Mice; Molecular Docking Simulation; nitric oxide; Nyctanthes arbor-tristis; Plant Extracts - therapeutic use; Reactive Oxygen Species; spectroscopy; stomach ulcers; therapeutics; toxicity testing; traditional medicine; Tumor Necrosis Factor-alpha; Urease
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2023.117368

Nyctanthes arbor-tristis Linn. has been used by Ayruvedic physicians for the cure of different diseases including ulcers, gastric and inflammatory diseases. To isolate and identify compounds from this source and investigate their therapeutic potential for the treatment of gastric ulcer and related disorders. The ethanol extract of fresh aerial parts of N. arbor-tristis was used in the present studies which was subjected to a bio-assay guided fractionation followed by chromatographic separations. The structures of pure compounds were elucidated using various spectroscopic techniques. The inhibition of urease enzyme was evaluated by weatherburn indophenol method. Molecular docking studies were determined by using Molecular Operating Environment (MOE) version 2020.0901 version. The intracellular ROS production from phagocytes was determined by chemiluminescence assay and NO generation was detected by Griess method. The proinflammatory cytokine TNF-α was quantified by ELISA. Cytotoxic activity was assessed by MTT assay. One previously undescribed iridoid glycoside arborside F (1) and four known iridoid glycosides arborside A (2), arborside C (3), loganin (4) and 7-O-trans-cinnamoyl-6β-hydroxyloganin (5) were isolated and characterized in the present studies and their urease inhibitory activity was determined. Among these, 2 and 5 showed strong urease inhibition (IC  = 12.1 ± 1.74 and 14.1 ± 0.59 μM respectively) (standard acetohydroxamic acid IC  = 20.3 ± 0.42 μM), whereas rest of compounds showed moderate to low inhibition. Kinetic studies revealed that compounds 2 and 5 possess competitive type of inhibition. Molecular docking showed polar and non-polar interactions of compounds 2 and 5 with urease enzyme residues. Compounds 2 and 3 showed inhibition of ROS from whole blood (IC  = 1.6 ± 0.3 and 2.5 ± 0.09 μg/mL respectively) and PMNs (IC  = 1.5 ± 0.03 and 1.4 ± 0.0 μg/mL respectively). Compound 2 significantly inhibited nitric oxide and proinflammatory cytokine TNF-α (IC  = 18.2 ± 3.0 and 73.8 ± 6.6 μg/mL respectively). Compounds 1, 4 and 5 were inactive on ROS. All isolated compounds were non-toxic on normal mouse fibroblasts (NIH-3T3) cells. The ethno pharmacological repute of N. arbor-tristis in treating gastric and anti-inflammatory ailments is supported by present studies which resulted in isolation of a potent urease inhibitory and anti-inflammatory agent arborside A (2) a potential anti-ulcer and anti-inflammatory drug lead.