A Major Diplotaxis harra-Derived Bioflavonoid Glycoside as a Protective Agent against Chemically Induced Neurotoxicity and Parkinson’s Models; In Silico Target Prediction; and Biphasic HPTLC-Based Quantification

Abstract

Oxidative stress and chronic inflammation have a role in developing neurodegenerative diseases such as Parkinson’s disease (PD) and inflammatory movement disorders such as rheumatoid arthritis that affect millions of populations. In searching for antioxidant and anti-inflammatory molecules from natural sources that can counteract neurodegenerative diseases and arthritis, the flavonoid-rich extract of Diplotaxis harra (DHE) was selected based on its in vitro antioxidant and anti-inflammatory activities. DHE could inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages from 100% to the level of 28.51 ± 18.67 and 30.19 ± 5.00% at 20 μg/mL, respectively. A TLC bioautography of DHE fractions using 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) led to the isolation of a major antioxidant compound which was identified by X-ray diffraction analysis as isorhamnetin-3-O-β-D-glucoside (IR3G). IR3G also exhibited a potent anti-inflammatory activity, particularly by suppressing the upregulation of iNOS expression, similar to that of dexamethasone (DEX) at 10 μM to the level of 35.96 ± 7.80 and 29.34 ± 6.34%, respectively. Moreover, IR3G displayed a strong neuroprotectivity (>60% at 1.0−4–1.0−3 μM) against 6-hydroxydopamine (6-OHDA)-challenged SHSY5Y neuroblastoma, an in vitro model of dopaminergic neurons for Parkinson’s disease (PD) research. Accordingly, the in vivo anti-Parkinson potentiality was evaluated, where it was found that IR3G successfully reversed the 6-OHDA-induced locomotor deficit in a zebrafish model. A study of molecular docking and molecular dynamic (MD) simulation of IR3G and its aglycone isorhamnetin (IR) against human acetylcholine esterase (AChE), monoamine oxidase B (MAO-B), and Polo-like kinase-2 (PLK2) was performed and further outlined a putative mechanism in modulating neurodegenerative diseases such as PD. The free radical scavenging, anti-inflammatory through anti-iNOS and anti-COX-2 expression, and neuroprotective activities assessed in this study would present partial evidence for the potentiality of D. harra-derived IR3G as a promising natural therapeutic agent against neurodegenerative diseases and inflammatory arthritis. Finally, a biphasic HPTLC method was developed to estimate the biomarker IR3G in D. harra quantitatively.

Diplotaxis Genus: A Promising Source of Compounds with Nutritional and Biological Properties

“…Dexamethasone (DEX) was used as a positive control. The isolated compound, isorramnetin-3- O - β -D-glucoside, exhibited potent anti-inflammatory activity, notably suppressing the overexpression of iNOS by about 35.96% and 29.34%, respectively, and these effects are similar to those noted for DEX at 10 µM [ 42 ].…”

“…In aqueous extracts of the flowering aerial parts of D. harra, an IC 50 value of 2.11 mg mL −1 was obtained with the DPPH assay [41]. The ethanolic extract (95%) from aerial parts (pre-flowering) demonstrated significant antioxidative activity, with IC 50 values of 247.4 µg mL −1 for the ABTS assay and 203.7 µg mL −1 for the DPPH assay, along with a phenol content of 80.43 mg GAE g −1 and a flavonoid content of 54.26 mg QE g −1 [42]. In another study, antioxidant evaluation was also conducted using separated leaves, stems, flowers, siliques, seeds, and roots.…”

Targeting Transcriptional CDKs 7, 8, and 9 with Anilinopyrimidine Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and In Silico Studies

“…In this study, molecules with lower CDK9 docking scores than that of the (T9N) co-crystal of (4bcj) were confirmed as promising CDK9 inhibitors with superior inhibitory action and greater selectivity. MD simulations may indicate the physical movements of the protein and ligand complex in specific settings to confirm docking results and to compute binding free energies [44]. Because compound 5b showed remarkable CDK9 activity, it was chosen for MD simulation.…”

Polo-Like Kinase 2: From Principle to Practice

“…In neurodegenerative diseases, oral administration of potent selective inhibitors of PLK2 that could cross the blood-brain barrier significantly reduces the phosphorylation of α-Syn in rat brain, providing a direction for the treatment of PD ( 117 ). Isorhamnetin-3-O-β-D-glucoside (IR3G) could bind and inhibit PLK2 with high affinity and may inhibit macrophage function and exert strong anti-inflammatory activity, as well as combat neurotoxicity and motor loss induced by 6-OHDA in SHSY5Y cells ( 169 ). Oral administration of PLK2 inhibitor based on dihydropteridinone reduces p-Ser129 α-Syn in the cerebral cortex of rats by about 41-45% ( 170 ).…”