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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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Project description:Peganum harmala Raw sequence reads

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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

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 β-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 α,β-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 μM.

| S-EPMC5518681 | 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

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

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

Transcriptome Profiling Reveals the Response of Seed Germination of Peganum harmala to Drought Stress

Project description: Not available

| S-EPMC11207268 | biostudies-literature