Background: Inflammation is generally connected to tumour progression and development. The secretory phospholipase A2IIa (sPLA2IIa) is an important inflammatory enzyme that catalyse the hydrolysis of membrane phospholipids into arachidonic and lysophosphatidic acid, which are the precursors for production of a lot of pro-inflammatory mediators like prostaglandins, prostacyclins, thromboxanes, leukotrienes and platelet activating factors, which involved in the proliferation, migration, invasion, and metastasis. Therefore, investigating safe and effective sPLA2IIa inhibitors as a therapeutic agent to treat cancer is indeed in need.
Methods: Anti-inflammatory function of corosolic acid was evaluated by docking it with sPLA2IIa enzyme, sPLA2IIa inhibition, calcium and substrate concentration-dependent assays; intrinsic fluorescence and UV-CD analysis; neutralisation of sPLA2IIa induced indirect hemolytic and edema. Evaluated the anticancer activity of corosolic acid by MTT assays and caspase-3 expression; the anti-tumour activity by EAC-induced cell line and interleukin 6 expression.
Results: The corosolic acid inhibits sPLA2IIa activity to 82.21±2.82%. The inhibition was evaluated by increasing calcium from 2.5 to 15 µM and substrate from 20 to 120 nM, it did not affect the level of inhibition. Corosolic acid altered the intrinsic fluorescence and UV-CD spectra of sPLA2IIa enzyme, indicating the direct interaction. It neutralised sPLA2IIa induced hemolytic activity from 97±1.23% to 15.75±1.44% and edema from 171.51±2.39% to 119.3±2.6%. Further, as antiproliferative activity, corosolic acid reduced the PC3 cell viability from 99.66±0.57% to 23±2.64% and suppressed LPS-induced IL-6 level from 94.35±2.2% to 34.36±2.4%. It increased mean survivability time from 30 to 38 days and displayed the drug-like qualities.
Conclusion: All the experimental results have proven the corosolic acid as an anti-inflammatory and anticancer molecule that may further be used to develop it as a drug.
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http://dx.doi.org/10.2147/JIR.S383441 | DOI Listing |
Eur J Med Chem
December 2024
College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, China. Electronic address:
Corosolic acid (CA), a natural triterpenoid, exhibits various biological activities and is often called as plant-derived insulin due to its significant hypoglycemic effects, making it especially beneficial for individuals with diabetes or high blood glucose levels. However, CA has notable in vitro toxicity, low water solubility, and poor pharmacokinetic properties. To address these limitations, a series of CA derivatives were synthesized, resulting in the identification of derivative H26, which demonstrates a significantly enhanced hypoglycemic effect, reduced toxicity, and improved pharmacokinetic characteristics compared to CA.
View Article and Find Full Text PDFBMC Genomics
December 2024
The Public Service Platform for Industrialization Development Technology of Marine Biological Medicine and Products of the State Oceanic Administration, Fujian Key Laboratory of Special Marine Bioresource Sustainable Utilization, Southern Institute of Oceanography, Key Laboratory of Developmental and Neural Biology College of Life Sciences, Fujian Normal University, Fuzhou, China.
Background: Cyclocarya paliurus is a high-value tree, and it contains a variety of bioactive secondary metabolites which have broad application prospects in medicine, food and health care. Triterpenoids can improve the bioactive function of C. paliurus health tea and also improve the efficacy of health care tea.
View Article and Find Full Text PDFJ Control Release
December 2024
Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Shanghai, 201203, China. Electronic address:
The pomegranate fruit is valued for its nutritional and medicinal properties, and the composition and content of primary and secondary metabolites are the main factors impacting its nutritional and medicinal properties. However, a deep understanding of metabolites in different parts of fruit is still lacking. Here, the peel, aril, and seed of mature pomegranate fruits were analyzed separately to compare metabolic component differences using UPLC/MS-MS.
View Article and Find Full Text PDFChem Biodivers
November 2024
College of Pharmacy, Drug Research and Development Center, Daegu Catholic University, Gyeongbuk, 38430, Republic of Korea.
In this study, a phytochemical investigation on the methanol extract of Potentilla chinensis led to the isolation of eleven triterpenoids including ursolic acid (1), pomolic acid (2), tormentic acid (3), 2-epi-corosolic acid (4), 3-epi-corosolic acid (ECA, 5), 3β-hydroxyurs-11-en-13β(28)-olide (6), euscaphic acid (7), 2-epi-tormentic acid (8), corosolic acid (9), uvaol (10), and 3-O-acetylpomolic acid (11). Among them, ECA (5) showed potential anti-osteoclastogenic activity. To the best of our knowledge, this represents the first isolation of ECA (5) from P.
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