Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities

Abstract

Amphiphilic macrocycles, such as p -sulfonatocalix[6]arenes ( p -SC6), have demonstrated great potential in designing synthetic nanovesicles based on self-assembly approaches. These supramolecular nanovesicles are capable of improving the solubility, stability, and biological activity of various drugs. In the present study, the biologically active harmala alkaloid-rich fraction (HARF) was extracted from Peganum harmala L . seeds. Ultraperformance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC/ESI-MS) analysis of HARF revealed 15 alkaloids. The reversed-phase high-performance liquid chromatography (RP-HPLC) analysis revealed three peaks: peganine, harmol, and harmine. The HARF was then encapsulated in p -SC6 nanocapsules employing a thin-film hydration approach. The designed nanocapsules had an average particle size of 264.8 ± 10.6 nm, and a surface charge of −30.3 ± 2.2 mV. They were able to encapsulate 89.3 ± 1.4, 74.4 ± 1.3, and 76.1 ± 1.7% of the three harmala alkaloids; harmine, harmol, and peganine; respectively. The in vitro drug release experiments showed the potential of the designed nanocapsules to release their cargo at a pH of 5.5 (typical of cancerous tissue). The IC 50 values of HARF encapsulated in p -SC6 (H/ p -SC6 nanocapsules) were 5 and 2.7 μg/mL against ovarian cancer cells (SKOV-3) and breast adenocarcinoma cells (MCF-7), respectively. The prepared nanocapsules were found to be biocompatible when tested on human skin fibroblasts. Additionally, the antioxidant activity of the designed nanocapsules was 5 times that of the free powder fraction; the IC 50 of the H/ p -SC6 nanocapsules was 30.1 ± 1.3 μg/mL, and that of the HARF was 169.3 ± 7.2 μg/mL. In conclusion, encapsulation of P. harmala alkaloid-rich fraction into self-assembled p -SC6 significantly increases its antioxidant and cytotoxic activities.

Chitosan-Coated PLGA Nanoparticles Loaded with Peganum harmala Alkaloids with Promising Antibacterial and Wound Healing Activities

“…H/CS/PLGA NPs revealed the highest antibacterial activity against S. aureus and E. coli , with MIC values of 0.125 and 0.06 mg/mL, respectively, compared to free HARF (MIC of 0.5 mg/mL) and CS/PLGA blank NPs (MIC of 0.18 mg/mL), as presented in Table 3 . The nanoparticles were shown to have decomposed in the wound environment, releasing the loaded HARF, which was rich with β-carboline and quinazoline alkaloids (harmine, harmol, harmaline, harmane, harmalol, and peganine) [ 8 , 9 ]. These alkaloids exerted their antibacterial action via the intercalation with bacterial DNA.…”

“…The extraction, isolation, and identification of the major alkaloids of P. harmala seeds were conducted as previously reported [ 8 , 9 ].…”

“…This mixture was added dropwise and dried over a carbon-coated copper 200 mesh grid, imaged, and photographed. The average particle size (nm) histogram of the NPs was produced using the image processing program ImageJ (NIH, Bethesda, MD, USA) [ 8 , 9 ].…”

“…Peganum harmala L. ( Zygophyllaceae family) is a plant that grows wildly in the Middle East and North Africa. Its seeds have been used as an antibacterial, antifungal, antipruritic, and antioxidant, and also in wound healing [ 8 , 9 ]. The seeds of P. harmala are rich in therapeutically active β-carboline and quinazoline alkaloids (harmala alkaloids).…”

“…The seeds of P. harmala are rich in therapeutically active β-carboline and quinazoline alkaloids (harmala alkaloids). These alkaloids, including harmine, harmol, harmaline, harmane, harmalol, and peganine, are responsible for the therapeutic activities of the harmala seeds [ 8 , 9 ]. The promising wound-healing ability of P. haramala extract was reported.…”