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Peganum harmala enhanced GLP-1 and restored insulin signaling to alleviate AlCl₃-induced Alzheimer-like pathology model.

ABSTRACT: Peganum harmala (P. harmala) is a folk medicinal herb used in the Sinai Peninsula (Egypt) as a remedy for central disorders. The main constituents, harmine and harmaline, have displayed therapeutic efficacy against Alzheimer's disease (AD); however, the P. harmala potential on sensitizing central insulin to combat AD remains to be clarified. An AD-like rat model was induced by aluminum chloride (AlCl₃; 50 mg/kg/day for six consecutive weeks; i.p), whereas a methanolic standardized P. harmala seed extract (187.5 mg/kg; p.o) was given to AD rats starting 2 weeks post AlCl₃ exposure. Two additional groups of rats were administered either the vehicle to serve as the normal control or the vehicle + P. harmala seed extract to serve as the P. harmala control group. P. harmala enhanced cognition appraised by Y-maze and Morris water maze tests and improved histopathological structures altered by AlCl₃. Additionally, it heightened the hippocampal contents of glucagon-like peptide (GLP)-1 and insulin, but abated insulin receptor substrate-1 phosphorylation at serine 307 (pS307-IRS-1). Besides, P. harmala increased phosphorylated Akt at serine 473 (pS473-Akt) and glucose transporter type (GLUT)4. The extract also curtailed the hippocampal content of beta amyloid (Aβ)42, glycogen synthase (GSK)-3β and phosphorylated tau. It also enhanced Nrf2, while reduced lipid peroxides and replenished glutathione. In conclusion, combating insulin resistance by P. harmala is a novel machinery in attenuating the insidious progression of AD by enhancing both insulin and GLP-1 trajectories in the hippocampus favoring GLUT4 production.

SUBMITTER: Saleh RA

PROVIDER: S-EPMC8187628 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Peganum harmala

Project description:Peganum harmala Raw sequence reads

| PRJNA692776 | ENA

Peganum harmala

Project description:Peganum harmala overview

| PRJNA747596 | ENA

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

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

Changes in the Soil Fungal Community Mediated by a Peganum harmala Allelochemical.

Project description:Plants can release phytotoxic allelochemicals into the environment, not only to suppress other plants' growth, but also alter community structure of soil microbiota, however, the mechanism are often complicated. We designed a consecutive cultivation procedure to evaluate the allelopathic effect of harmaline, the major active allelochemical produced by the desert plant Peganum harmala, on soil microorganisms. Harmaline was added to the soil at 20 μg/g, and after five generations of cultivation, the Chao1, Pielou, Shannon and Simpon indexes changed significantly. In particular, the relative abundances of the dominant fungi, Alternaria sp. and Fusarium sp., declined drastically by 84.90 and 91.90%, respectively. Further in vitro bioassays confirmed that harmaline indeed suppressed growth of 6 Alternaria and Fusarium strains isolated from P. harmala rhizosphere soil. We thus suspect that P. harmala might produce harmaline as an effective carry-on pesticide to defend against general pathogens such as Alternaria sp. and Fusarium sp. and favor itself. Our consecutive cultivation procedure has successfully magnified the core signals from the chaotic data, implying that it can be applied to measure the effects of other allelochemicals on soil microbiota.

| S-EPMC9243656 | biostudies-literature

NMR-based metabolomic profiling of Peganum harmala L. reveals dynamic variations between different growth stages.

Project description:Xerophytes play an active role in preventing soil denudation and desertification in arid and semi-arid areas. Peganum harmala L. (Zygophyllaceae family), a seasonally growing, poisonous and drought-tolerant plant, is widely distributed in the Xinjiang Uygur Autonomous Region and used as a traditional herbal medicine as well as, in winter, a fodder source. Previous research has focused on the pharmacological activity of isolated compounds and stress responses to growth environments. However, the metabolic profile of P. harmala and variations in its metabolites, including medicinally active and stress resistance components, have not been illustrated during different growth stages. Here, we collected plant samples in May, August, October and December. We determined the metabolic composition of methanol extracts using NMR spectroscopy, and comparisons of four growth stages were accomplished by applying statistical analysis. The results showed that vasicine, choline and sucrose were significantly elevated in samples harvested in May. Significantly higher amounts of betaine, lysine, 4-hydroxyisoleucine and proline were found in samples collected in August than in samples collected in other months, and the concentrations of phosphorylcholine, glucose, acetic acid and vasicinone were highest in December. The relationships between differential biomarkers and plant physiological states affected by diverse growth environmental factors were discussed. Our result deepened the understanding of metabolic mechanisms in plant development and confirmed the advantage of using NMR-based metabolomic treatments in quality evaluation when P. harmala is used for different purposes.

| S-EPMC6083650 | biostudies-literature

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