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PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities.

ABSTRACT: Antimicrobial drugs face numerous challenges, including drug resistance, systemic toxic effects, and poor bioavailability. To date, treatment choices are limited, which warrants the search for novel potent antivirals, including those extracted from natural products. The seeds of Peganum harmala L. (Zygophyllaceae family) have been reported to have antimicrobial, antifungal, and anticancer activities. In the present study, a 2-hydroxy propyl-β-cyclodextrin (HPβCD)/harmala alkaloid-rich fraction (HARF) host-guest complex was prepared using a thin-film hydration method to improve the water solubility and bioavailability of HARF. The designed complex was then co-encapsulated with ascorbic acid into PLGA nanoparticles coated with polyethylene glycol (HARF-HPßCD/AA@PLGA-PEG NPs) using the W/O/W multiple emulsion-solvent evaporation method. The average particle size, PDI, and zeta potential were 207.90 ± 2.60 nm, 0.17 ± 0.01, and 31.6 ± 0.20 mV, respectively. The entrapment efficiency for HARF was 81.60 ± 1.20% and for ascorbic acid was 88 ± 2.20%. HARF-HPßCD/AA@PLGA-PEG NPs had the highest antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.025 mg/mL). They also exhibited high selective antiviral activity against the H1N1 influenza virus (IC50 2.7 μg/mL) without affecting the host (MDCK cells). In conclusion, the co-encapsulation of HPCD-HARF complex and ascorbic acid into PLGA-PEG nanoparticles significantly increased the selective H1N1 killing activity with minimum host toxic effects.

SUBMITTER: Fahmy SA

PROVIDER: S-EPMC8780513 | biostudies-literature |

REPOSITORIES: biostudies-literature

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

Project description:Wound healing is a major healthcare concern, and complicated wounds may lead to severe outcomes such as septicemia and amputations. To date, management choices are limited, which warrants the search for new potent wound healing agents. Natural products loaded in poly (lactic-co-glycolic acid) (PLGA) coated with chitosan (CS) constitute a promising antibacterial wound healing formulation. In this work, harmala alkaloid-rich fraction (HARF) loaded into PLGA nanoparticles coated with chitosan (H/CS/PLGA NPs) were designed using the emulsion-solvent evaporation method. Optimization of the formulation variables (HARF: PLGA and CS: PLGA weight ratios, sonication time) was performed using the 33 Box-Behnken design (BBD). The optimal NPs were characterized using transmission electron microscopy (TEM) and Attenuated Total Reflection Fourier-Transformed Infrared Spectroscopy (ATR-FTIR). The prepared NPs had an average particle size of 202.27 ± 2.44 nm, a PDI of 0.23 ± 0.01, a zeta potential of 9.22 ± 0.94 mV, and an entrapment efficiency of 86.77 ± 4.18%. In vitro drug release experiments showed a biphasic pattern where an initial burst of 82.50 ± 0.20% took place in the first 2 h, which increased to 87.50 ± 0.50% over 72 h. The designed optimal H/CS/PLGA NPs exerted high antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.125 and 0.06 mg/mL, respectively) compared to unloaded HARF (MIC of 0.50 mg/mL). The prepared nanoparticles were found to be biocompatible when tested on human skin fibroblasts. Moreover, the wound closure percentage after 24 h of applying H/CS/PLGA NPs was found to be 94.4 ± 8.0%, compared to free HARF and blank NPs (68.20 ± 5.10 and 50.50 ± 9.40%, respectively). In conclusion, the three components of the developed nanoformulation (PLGA, chitosan, and HARF) have synergistic antibacterial and wound healing properties for the management of infected wounds.

| S-EPMC8464825 | biostudies-literature

Peganum harmala

Project description:Peganum harmala overview

| PRJNA747596 | ENA

Peganum harmala

Project description:Peganum harmala Raw sequence reads

| PRJNA692776 | ENA

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

Project description: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 IC50 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 IC50 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.

| S-EPMC8153973 | biostudies-literature

Structurally Diverse Alkaloids from the Seeds of Peganum harmala.

Project description:Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A-B (1-2); two rare thiazole derivatives, peganumals A-B (3-4); six new ?-carboline alkaloids, pegaharmines F-K (5-10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A-B, thiazole fragments in peganumals A-B, and a C-1 ?,?-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time. All isolates were tested for antiproliferative activities against the HL-60, PC-3, and SGC-7901 cancer cell lines, and compounds 9, 11, 12, and 13 exhibited moderate cytotoxicity against HL-60 cancer cell lines with IC50 values in the range of 4.36-9.25 ?M.

| S-EPMC5518681 | biostudies-literature

Differential gene expression of salt-stressed Peganum harmala L.

Project description:The response of Peganum harmala L. seedlings subjected to salinity was investigated through the observation of germination at the 4th, 6th and 8th days under normal and two salinity levels (150 and 200 mM NaCl). Genetic response of P. harmala was examined by quantitative estimation and electrophoretic separation of catalase and salt-soluble proteins. The gene expression of catalase and osmotin were investigated using RT-PCR. Final percentage of germination at the eighth day of germination was reduced from 85% in the control to 70 and 30% under the concentration of 150 and 200 mM. The catalase activity and protein content increased as the salinity increased compared to control seedlings. The electrophoretic separation of catalase and salt-soluble proteins exhibited stress-related isozymes and protein bands. RT-PCR of cat1, cat2-3 and cat3 and osmotin genes exhibited up-regulation and down-regulation of genes subsequent to salinity. The reduced germination percentage of salt stressed seedlings was attributed to oxidative damage and osmotic imbalance. The increased catalase activity and protein content were concluded as protective response of P. harmala seedlings to salinity induced oxidative stress and osmoregulation. The additional isozyme bands in the salt-stressed seedlings indicated modulation of CAT gene expression in response to elevated H2O2 subsequent to salinity. The stress specific gene expression was interpreted as molecular mechanism by which plants can tolerate salinity stress. The up-regulation of cat2-3 gene in relation to stress suggests it crucial role in salinity tolerance in P. harmala and further studies are needed for its sequence identification.

| S-EPMC6299858 | biostudies-literature

Diversity of antagonistic bacteria isolated from medicinal plant Peganum harmala L.

Project description:The antimicrobial activity of plant extract of Peganum harmala, a medicinal plant has been studied already. However, knowledge about bacterial diversity associated with different parts of host plant antagonistic to different human pathogenic bacteria is limited. In this study, bacteria were isolated from root, leaf and fruit of plant. Among 188 bacterial isolates isolated from different parts of the plant only 24 were found to be active against different pathogenic bacteria i.e. Escherichia coli, Methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium, Enterococcus faecalis and Pseudomonas aeruginosa. These active bacterial isolates were identified on the basis of 16S rRNA gene analysis. Total population of bacteria isolated from plant was high in root, following leaf and fruit. Antagonistic bacteria were also more abundant in root as compared to leaf and fruit. Two isolates (EA5 and EA18) exhibited antagonistic activity against most of the targeted pathogenic bacteria mentioned above. Some isolates showed strong inhibition for one targeted pathogenic bacterium while weak or no inhibition for others. Most of the antagonistic isolates were active against MRSA, following E. faecium, P. aeruginosa, E. coli and E. faecalis. Taken together, our results show that medicinal plants are good source of antagonistic bacteria having inhibitory effect against clinical bacterial pathogens.

| S-EPMC5562454 | biostudies-literature

Doxorubicin and CD?CUR inclusion complex co?loaded in thermosensitive hydrogel PLGA?PEG?PLGA localized administration for osteosarcoma.

Project description:Combination therapy is a promising and prevalent strategy for osteosarcoma treatment. Curcumin (CUR), as a chemosensitizer, improves the antitumor effect of first?line chemotherapy drugs. However, due to its poor solubility and instability in physiological conditions, the bioavailability of CUR is limited. In order to improve the physicochemical properties of natural CUR, ??cyclodextrin was adopted to generate a ??cyclodextrin curcumin (CD?CUR) inclusion complex. A thermosensitive hydrogel, poly(D,L?lactide?co?glycolide)-poly(ethylene?glycol)?poly(D,L?lactide?co?glycolide), was selected and synthesized to co?deliver doxorubicin (DOX) and CD?CUR to tumor sites. The dual?drug delivery system (gel+DOX+CD?CUR) was prepared by mixing drugs with hydrogels and had a perfect sol?gel phase transition temperature (18.3?C for 20% concentration). Both DOX and CUR were released from hydrogels in a sustained manner in PBS (pH 7.4) medium. The combination therapy based on DOX+CD?CUR exhibited higher antitumor activity than monotherapies in vitro. Combined CD?CUR therapy significantly downregulated Bcl?2 expression and upregulated caspase?3 expression, suggesting that DOX combined with CD?CUR treatment has a higher apoptosis?inducing efficiency. The antitumor efficiency of the gel+DOX+CD?CUR strategy was evaluated in K?7 tumor?bearing mice, and this localized combination therapy demonstrated a higher antitumor efficiency compared with free DOX+CD?CUR or single?drug strategies. There were no significant differences in body weight and histological changes of major organs in each group. Therefore, the present combination treatment based on hydrogel may be a feasible approach to co?deliver DOX and CD?CUR to osteosarcoma tumor sites in clinical practice.

| S-EPMC7307595 | biostudies-literature

Peganum harmala L.'s anti-growth effect on a breast cancer cell line.

Project description:This research was done to evaluate the induction of apoptosis in MDA-MB-231 breast cancer cell line by Peganum harmala's extract, in which a significant amount of ß-carbolines is included. The apoptosis incidence was assessed through Annexin-V-Flous kit. The expressions of genes through which intrinsic apoptosis pathway are involved, Bax, Bcl-2, Bid, and Puma, over the genes the expressions of which are linked to extrinsic apoptosis pathway, TRAIL, Caspase8, p21, and p53, were examined by RT-PCR and Real-time PCR. The results demonstrate that the extract decreases the growth rate of the cancer cell line through inducing apoptosis mechanism. As long as the expression of anti-apoptosis Bcl-2 gen reduced dramatically, an over-expression in Bax and Puma genes was monitored indicating activation of intrinsic apoptosis pathway. A notable over-expression observed with TRAIL and Caspase8 genes as well as Bid gene. The latter is an intermediate for both intrinsic and extrinsic pathways of apoptosis.

| S-EPMC4980734 | biostudies-literature

Complete chloroplast genome sequence of Peganum harmala, an important medicinal plant.

Project description:Peganum harmala is a perennial herbaceous plant belonging to the genus Peganum, Nitrariaceae and is mainly distributed in dry areas in the Mediterranean and many Asia countries. This plant species has high medicinal value and considerable ecological value. This article reports the first chloroplast genome of species in Peganum. The size of the P. harmala chloroplast genome is 160,070 bp, including a large single-copy (LSC) region (88,279 bp), a small single-copy (SSC) region (26,468 bp), and two reverse (IR) regions (18,856 bp). The P. harmala chloroplast genome consists of 132 genes, including 83 protein-coding genes, 38 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. The GC content of P. harmala chloroplast genome is 36.44%. Phylogenetic analysis showed that P. harmala and another Nitrariaceaeis species formed a single blade in the phylogenetic tree.

| S-EPMC7748625 | biostudies-literature

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