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

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 (Aß)42, glycogen synthase (GSK)-3ß 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.

Antinociceptive effects of Peganum harmala L. alkaloid extract on mouse formalin test.

PURPOSE: To evaluate the effect of Peganum harmala (Syrian rue) a wild-growing flowering plant belonging to the family Zygophylaceae and found abundantly in Iran on formalin-induced pain response in mice. METHODS: Total alkaloid extract was prepared from dry seeds of Peganum harmala. All doses of extract were dissolved in normal saline and administered intraperitoneally 30 minutes before formalin injection to the mouse paw. Nociception was recorded 0-5 (early phase, A) and 15-40 (late phase, B) minutes after formalin injection. The alkaloid extract was subjected to silica gel column chromatography using a linear gradient with a CHCl3-MeOH system and different fractions collected. The effective fraction in formalin test were further purified and isolated by preparative thin layer chromatography (TLC) and identified on the basis of nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. RESULTS: Alkaloid extract in doses (mg/kg) used induced significant reduction in pain response when compared to control as follow: 16 (28.63%), 20 (59.15%), 24 (80.75%), 28 (90.14%) and 30 (100%) in the early phase and 20 (24.67%), 24 (59.93%), 28 (78.52%) and 30 (100%) in late phase. Observed responses in both phases of A and B were dose-dependent with r2 of 0.93 and 0.99 respectively. ED50 for phases of A and B were 27.87 and 24.63 mg/kg respectively (p<0.001 for all groups). CONCLUSION: Harmaline, the last step of extraction is the main effective antinociceptive agent of the Peganum harmala alkaloid extract.

Peganum harmala: its use in certain dermatoses.

The extract of Peganum harmala (Rutaceae) was used topically to treat certain dermatoses of inflammatory nature. Results were encouraging and proved the antibacterial, antifungal, antipruritic and probably antiprotozoal effects of the extract.