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

Bibliographic Details
Title: Anti-inflammatory and urease inhibitory iridoid glycosides from Nyctanthes arbor-tristis Linn.
Authors: Sana T; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Khan M; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Siddiqui BS; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan; Pakistan Academy of Sciences, 3-Constitution Avenue, G-5/2, Islamabad, Pakistan. Electronic address: siddiqui_bina@yahoo.com., Baig TA; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Jabeen A; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Begum S; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan., Hadda TB; Laboratoire de Chimie des Matériaux, Facultédes Sciences, Université Mohammed Premier, 60000, Oujda, Morocco., Shah L; Hazara University, Mansehra, 21300, Pakistan.
Source: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Jan 30; Vol. 319 (Pt 3), pp. 117368. Date of Electronic Publication: 2023 Oct 30.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE
Imprint Name(s): Publication: Limerick : Elsevier Sequoia
Original Publication: Lausanne, Elsevier Sequoia.
MeSH Terms: Plant Extracts*/therapeutic use , Urease*, Iridoid Glycosides/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Mice ; Animals ; Kinetics ; Molecular Docking Simulation ; Reactive Oxygen Species ; Tumor Necrosis Factor-alpha
Abstract: Ethnopharmacological Relevance: Nyctanthes arbor-tristis Linn. has been used by Ayruvedic physicians for the cure of different diseases including ulcers, gastric and inflammatory diseases.
Aim of the Study: To isolate and identify compounds from this source and investigate their therapeutic potential for the treatment of gastric ulcer and related disorders.
Material and Methods: 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.
Results: 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 (IC50 = 12.1 ± 1.74 and 14.1 ± 0.59 μM respectively) (standard acetohydroxamic acid IC50 = 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 (IC50 = 1.6 ± 0.3 and 2.5 ± 0.09 μg/mL respectively) and PMNs (IC50 = 1.5 ± 0.03 and 1.4 ± 0.0 μg/mL respectively). Compound 2 significantly inhibited nitric oxide and proinflammatory cytokine TNF-α (IC50 = 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.
Conclusions: 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.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Nitric oxide; Nyctanthes arbor-tristis Linn.; Reactive oxygen species; Tumor necrosis factor; Urease
Substance Nomenclature: 0 (Plant Extracts)
EC 3.5.1.5 (Urease)
0 (Iridoid Glycosides)
0 (Reactive Oxygen Species)
0 (Tumor Necrosis Factor-alpha)
0 (Anti-Inflammatory Agents)
Entry Date(s): Date Created: 20240221 Date Completed: 20240222 Latest Revision: 20240222
Update Code: 20260130
DOI: 10.1016/j.jep.2023.117368
PMID: 38380570
Database: MEDLINE
Description
ISSN:1872-7573
DOI:10.1016/j.jep.2023.117368