New Lignanamides with Antioxidant and Anti-Inflammatory Activities Screened Out and Identified from Warburgia ugandensis Combining Affinity Ultrafiltration LC-MS with SOD and XOD Enzymes

Abstract

Warburgia ugandensis, also known as “green heart,” is widely used for the treatment of various diseases as a traditional ethnomedicinal plant in local communities in Africa. In this work, 9 and 12 potential superoxide dismutase (SOD) and xanthine oxidase (XOD) ligands from W. ugandensis were quickly screened out by combining SOD and XOD affinity ultrafiltration with LC-MS, respectively. In this way, four new lignanamides (compounds 11-14) and one new macrocyclic glycoside (compound 5), along with three known compounds (compounds 1, 3, and 7), were isolated and identified firstly in this species. The structures of the new compounds were elucidated by spectroscopic analysis, including NMR and UPLC-QTOF-MS/MS. Among these compounds, compound 14 showed the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azinobis-(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radical scavenging activities, and total ferric-reducing antioxidant power (FRAP) with IC50 values of 6.405 ± 0.362 µM, 5.381 ± 0.092 µM, and 17.488 ± 1.625 mmol TE/g, respectively. Moreover, compound 14 displayed the highest inhibitory activity on cyclooxygenase-2 (COX-2) with IC50 value of 0.123 ± 0.004 µM, and the ranking order of other compounds’ IC50 values was 13 > 11 > 7 > 1 > 12. The present study suggested that lignanamides might represent interesting new characteristic functional components of W. ugandensis to exert remarkable antioxidant and anti-inflammatory activities. Moreover, compound 14, a new arylnaphthalene lignanamide, would be a highly potential natural antioxidant and anti-inflammatory agent from W. ugandensis.

Potential Antioxidative and Anti-Hyperuricemic Components Targeting Superoxide Dismutase and Xanthine Oxidase Explored from Polygonatum Sibiricum Red.

“…Considering the complexity of chemical constituents and their diverse mechanisms of action, evaluating the antioxidant potential of a sample based on a single method is inappropriate. Thus, three different assays including DPPH, ABTS, and FRAP were employed in the current study to assess and compare the antioxidant activities of different P. sibiricum extracts [ 32 ]. As shown in Figure 1 , the EA fraction displayed the strongest scavenging effect on DPPH and ABTS free radicals assays with the IC 50 values of 90.47 ± 3.17 µg/mL and 8.96 ± 0.21 µg/mL, respectively.…”

“…The ABTS free radical scavenging activities of different P. sibiricum extracts were conducted following the method of Zhuang et al [ 32 ] with a few minor modifications. Briefly, the working ABTS radical cation (ABTS + ) solution was prepared by mixing equal volumes of potassium persulfate (4.9 mM in H 2 O) and ABTS (7 mM in H 2 O), which are further incubated in the dark for 12 to 16 h. The ABTS + stock solution was then diluted with methanol to obtain an absorbance of 0.700 ± 0.03 at 734 nm.…”

Flavonoids from Selaginella doederleinii Hieron and Their Antioxidant and Antiproliferative Activities

“…The structures of 12 other known compounds, 2 and 6-16, were established by comparison of their spectroscopic data with those reported in the literature as 3-(5,7dihydroxy-2-(4-methoxy-phenyl)-4-oxo-4H-chromen-8-yl)-4-methoxy-benzoic acid (2) [44], Sequoiaflavone (6) [45], 7,7 -dimethyl ether amentoflavone (7) [22], 2,3-dihydro-4 -methyl ether amentoflavone (8) [46], 2,3-dihydro-7,4 -dimethyl ether amentoflavone (9) [47], 2 ,3 -Dihydroamentoflavone (10) [48], 4 ,4 -dimethyl ether robustaflavone (11) [47], 2,3-dihydro-4 -methyl ether robustaflavone (12) [49], 5,4 -dihydroxy-7-methoxyflavone (13) [50], thevetiaflavone (14) [51,52], 2 ,3 -dihydrohinokiflavone (15) [53], and 7 -methyl ether tetrahydrohinokiflavone ( 16) [54].…”

“…However, sometimes an imbalance between the ROS production and antioxidant protection system happens, hence there is oxidative stress [5], which potentially causes diseases such as diabetes and cancers [7,8]. To mitigate this, the intake of antioxidants that directly scavenge the free radicals or turn on molecules and enzymes that stimulate redox homeostasis can protect body cells from ROS-induced damage [9,10]. Natural antioxidants have increasingly attracted research focus as synthetic antioxidants have been associated with adverse effects on humans [11].…”

Stimulation of ROS Generation by Extract of Warburgia ugandensis Leading to G0/G1 Cell Cycle Arrest and Antiproliferation in A549 Cells

“…In Africa, the bark, roots, and leaves of WU are used to treat many ailments. Due to the unsustainable harvesting of the bark and roots along with the fact that the natural propagation of WU is problematic, its availability has been declining throughout its nat- Up until now, there have been about 90 compounds isolated from WU, which are mainly composed of sesquiterpenes, flavonoids, fatty acids, lignanamides, and essential oils [25][26][27][28][29]. Some of the compounds isolated from other medicinal plants exhibiting anticancer activity have also been found in WU, such as cinnamosmolide, 6β-acetoxyisodrimenin, ungandensolide, futronolide, warburganal, polygodial, mukaadial, drimenol, and cinnamodial [30][31][32][33][34][35][36].…”