An In-Depth Study on the Metabolite Profile and Biological Properties of Primula auriculata Extracts: A Fascinating Sparkle on the Way from Nature to Functional Applications

Abstract

The biological activity of the aerial part and rhizomes of Primula auriculata were assessed for the first time. The biological activities (antioxidant properties, enzyme inhibition, and AGE inhibition) as well as the phenolic and flavonoid contents of the ethyl acetate, ethanol, hydro-ethanol and water extracts of P. auriculata aerial parts and rhizomes were determined. Cell viability assays and gelatin zymography were also performed for MMP-2/-9 to determine the molecular mechanisms of action. The gene expression for MMPs was described with RT-PCR. The levels of various proteins, including phospho-Nf-κB, BCL-2, BAX, p-53, and cyclin D1 as well as RAGE were measured using Western blot analysis. The hydro-ethanol extract of the aerial part possessed the highest phenolic (56.81 mg GAE/g) and flavonoid (63.92 mg RE/g) contents. In-depth profiling of the specialized metabolites by ultra-high-performance liquid chromatography—high-resolution mass spectrometry (UHPLC-HRMS) allowed for the identification and annotation of 65 compounds, including phenolic acids and glycosides, flavones, flavonols, chalcones, dihydrochalcones, and saponins. The hydro-ethanol extract of the aerial parts (132.65, 180.87, 172.46, and 108.37 mg TE/g, for the DPPH, ABTS, CUPRAC, and FRAP assays, respectively) and the ethanol extract of the rhizomes (415.06, 638.30, 477.77, and 301.02 mg TE/g, for the DPPH, ABTS, CUPRAC, and FRAP assays, respectively) exhibited the highest free radical scavenging and reducing activities. The ethanol and hydro-ethanol extracts of both the P. auriculata aerial part and rhizomes exhibited higher inhibitory activity against acetylcholinesterase, while the hydro-ethanol extracts (1.16 mmol ACAE/g, for both the aerial part and rhizomes extracts) were more active in the inhibition of α-glucosidase. After the treatment of an HT-29 colorectal cancer cell line with the extracts, the apoptosis mechanism was initiated, the integrity of the ECM was remodeled, and cell proliferation was also taken under control. In this way, Primula extracts were shown to be potential drug sources in the treatment of colorectal cancer. They were also detected as natural MMP inhibitors. The findings presented in the present study appraise the bioactivity of P. auriculata, an understudied species. Additional assessment is required to evaluate the cytotoxicity of P. auriculata as well as its activity in ex vivo systems.

Phenolic Profile, Antioxidant and Enzyme Inhibitory Activities of Leaves from Two Cassia and Two Senna Species

“…Using Autodock Tools program ( , accessed on 10 June 2022) [ 66 ], docking grid files were generated using the coordinates of the cocrystal ligand in each crystal. The details of the docking procedure have been described in our previous studies [ 67 , 68 ]. The binding energy of the ligand poses were calculated, and protein–ligand interactions were examined using the Biovia DS Visualizer (Dassault Systèmes Biovia Software Inc, 2012, San Diego, CA, USA).…”

Unraveling the chemical profile, antioxidant, enzyme inhibitory, cytotoxic potential of different extracts from Astragalus caraganae

“…With the increase of ROS/antioxidant ratio, the reception of inflammatory signals such as lipopolysaccharide or tumor necrosis factor-alpha, NF-κB is phosphorylated and translocated to the nucleus and plays a role in the prognosis of many diseases along with the inflammation process. [64,65] Another protein required for downstream signaling and activation of NF-κB during the oxidative stress period is the AGE receptor protein RAGE. The AGE/RAGE interaction induced by increased ROS level activates NF-κB, an effector of the oxidative stress pathway in cells.…”

“…[68] In the mechanism of apoptosis, called programmed cell death, an increase in the antiapoptotic BCL-2 due to an increase in the amount of ROS, in turn, there is a decrease in the levels of the proapoptotic proteins BAX and p-53, as a result of which the cells become resistant to apoptosis, and the cell cycle is disrupted. [64,68,69] Various plants with high antioxidant potential are used for the improvement and rearrangement of ROS-induced impaired molecular signaling pathways. [5,64,70] In studies with Astragalus species, ROSinduced loss of cell cycle in cells is regulated thanks to bioactive components such as various flavonoids, saponins, and alkaloids contained in the plant.…”

“…[64,68,69] Various plants with high antioxidant potential are used for the improvement and rearrangement of ROS-induced impaired molecular signaling pathways. [5,64,70] In studies with Astragalus species, ROSinduced loss of cell cycle in cells is regulated thanks to bioactive components such as various flavonoids, saponins, and alkaloids contained in the plant. [5,71] This information in the literature shows parallelism with the results of Western blot (in Figure 4).…”

The three-dimension preclinical models for ferroptosis monitoring

“…Wu and Papagiannakopoulos 2020). Developing compounds that target anti-ferroptosis modulators could be a promising approach and particularly effective in tumor combination therapy (Kurt-Celep et al, 2022;.…”