Flavonoids and Saponins from Two Chenopodium Species (C. foliosum Asch. and C. bonus-henricus L.)—Preliminary Evaluation for hMAO-A/B, Neuroprotective Activity, and Validated UHPLC-HRMS Quantification of Ethanolic Extract from C. foliosum

The development of more effective treatments for neurodegenerative disorders presents a significant challenge in modern medicine. Currently, scientists are focusing on discovering bioactive compounds from plant sources to prevent and treat neurodegenerative diseases. Fifteen flavonoids and saponins from <i>C. foliosum</i> Asch. and <i>C. bonus</i>-<i>henricus</i> L. were tested for their inhibitory activity on hMAO-A and hMAO-B. Five compounds (1 μM) exhibit a weak inhibitory effect on hMAO-A and show good inhibitory activity against the hMAO-B enzyme (30-35%), compared to the positive control selegiline (55%). These active compounds were examined on rat brain synaptosomes and mitochondria obtained by multiple differential centrifugations using a Percoll gradient. Their effects were also monitored on rat brain microsomes obtained by double differential centrifugation. The main parameters characterizing the functional-metabolic status of subcellular fractions are synaptosomal viability, GSH level, and MDA production. All tested compounds (50 μM) demonstrated significant neuroprotective and antioxidant activities across models of induced oxidative stress, including 6-OHDA, t-BuOOH, and Fe^2+/AA-induced lipid peroxidation. The plausible mechanisms of neuroprotection rely on MAO-B inhibition, the scavenging of ROS, stabilizing the cell membrane by reducing MDA production, and neutralizing free radicals by maintaining GSH levels. In addition, we developed and validated a UHPLC-HRMS method for identifying and simultaneously quantificatying flavonoids and saponins in the aerial parts of <i>C. foliosum</i>. Compounds 30-normedicagenic acid- HexA-Hex-TA <b>22f</b> and medicagenic acid-HexA-Hex-TA <b>25f</b> were considered new natural compounds.