Alzheimer's Disease (AD) is a fatal age-related neurodegenerative condition with a multifactorial etiology contributing to 70% of dementia globally. The search for a multi-target agent to hit different targets involved in the pathogenesis of AD is crucial. In the present study, the neuroprotective effects of four Morus extracts were assessed in LPS-induced AD in mice. Among the studied species, M. macroura exhibited a profound effect on alleviating the loss of cognitive function, improved the learning ability, restored the acetylcholine esterase (AChE) levels to normal, and significantly reduced the tumor necrosis factor alpha (TNF-α) brain content in LPS-treated mice. To investigate the secondary metabolome of the studied Morus species, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-HRMS/MS), aided with feature-based molecular networking, was employed. Among the annotated features, aryl benzofurans and prenylated flavonoids were suggested as being responsible for the observed neuroprotective effect. Furthermore, some of the detected metabolites were proposed as new natural products such as moranoline di-O-hexoside (1), isomers of trimethoxy-dihydrochalcone-O-dihexoside (59 & 76), (hydroxy-dimethoxyphenyl)butenone-O-hexoside (82), and O-methylpreglabridin-O-sulphate (105). In conclusion, our findings advocate the potential usage of M. macroura leaves for the management of AD, yet after considering further clinical trials.
Alzheimer Disease , Metabolome , Morus , Neuroprotective Agents , Plant Extracts , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Neuroprotective Agents/pharmacology , Mice , Plant Extracts/pharmacology , Male , Morus/chemistry , Metabolome/drug effects , Tandem Mass Spectrometry , Disease Models, Animal , Chromatography, High Pressure Liquid , Humans , Brain/metabolism , Brain/drug effects
OBJECTIVE: To evaluate the hypocholesterolemic and hypotriglyceridemic activities of four Marrbium vulgare herb extracts using Triton WR-1339-induced hyperlipidemia in mice. METHODS: Hyperlipidemia was developed by intraperitoneal injection of Triton (200 mg/kg body weight). The animals were divided into main four groups of eight mice each: normal control group, hyperlipidemic control group, hyperlipidemic plus tween-40 control and treated group. The fourth one was divided into four subgroups, petroleum ether extract group, chloroform extract group, ethyl acetate extract group and methanol extract treated group each of them contains two sub-sub group for treating animals with two doses at 0.1 and 0.25 LD50. RESULTS: After 7 h and 24 h of treatment, the intragastric administration of all extracts caused a significant decrease of plasma total cholesterol. Triglyceride levels were also significantly lowered by all extracts while petroleum ether produced the lowest decreasing level. Similar results were observed for LDL-cholesterol concentrations. Furthermore, more polar extracts (methanol and ethyl acetate)-soluble fractions showed a significant ameliorative action on elevated atherogenic index (AI) and LDL/HDL-C ratios, while these atherogenic markers were not statistically suppressed by the chloroform and petroleum ether-soluble extract. CONCLUSION: The findings indicated that Marrubium may contain polar products able to lower plasma lipid concentrations and might be beneficial in treatment of hyperlipidemia and atherosclerosis.
