Molecular networking-guided investigation of the secondary metabolome of four Morus species and their in vivo neuroprotective potential for the mitigation of Alzheimer's disease.

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.

A multiplex metabolomic approach for quality control of Spirulina supplement and its allied microalgae (Amphora & Chlorella) assisted by chemometrics and molecular networking.

Microalgae species are of economic importance regarded as "green gold" being rich in bioactive compounds. Spirulina and Chlorella are the most popular microalgal species and are marketed as healthy food supplements. At the same time, Amphora holds potential as a source of healthy lipids and essential fatty acids. Yet, there are considerable variations in their reported chemical composition, and less is known about their compositional differences. A multiplexed metabolomic approach was adopted for the quality control (QC) of Spirulina supplements and to compare its constitutive metabolome to Chlorella and Amphora. The adopted protocol comprised gas chromatography-mass spectrometry (GC-MS), ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC-HRMS/MS), and ultraviolet-visible spectrophotometry (UV/Vis) for mapping their primary and secondary metabolome. Interestingly, UPLC-HRMS/MS analysis delineated the abundance of fatty acids in Amphora versus glycolipids enrichment in Spirulina, and porphyrins were the main pigments identified in Spirulina, with scarce occurrence in Chlorella. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) analysis of GC-MS data set revealed palmitic acid, 3-mannobiose, and glyceryl-glycoside as being most enriched in Spirulina, versus sucrose and leucine in Chlorella and Amphora, respectively. Despite being of low discriminatory potential, UV/Vis OPLS-DA modeling showed that Spirulina was distinguished with the UV absorbances of carotenoids and chlorophyll pigments, as indicated by its OPLS-DA derived S-plot. Our study provides a QC approach for the analysis of the microalgal species and poses alternative spectral and compositional markers for their discrimination.

Untargeted metabolomics-based molecular networking for chemical characterization of selected Apiaceae fruit extracts in relation to their antioxidant and anti-cellulite potentials.

Stress, obesity, hormonal changes, and aging have been connected to cellulite aggravation resulting in skin dimpled appearance, a very common painless skin disorder with a female preponderance. Several Apiaceae plants have been traditionally used for cosmetic applications. However, their screening for anti-cellulite potential has not been deeply investigated. In this work, UPLC-HRMS/MS coupled with molecular networking was employed to glean a holistic overview of the chemodiversity of the metabolome of nine Apiaceae fruits. Additionally, the extracts were screened for in vitro antioxidant and anti-cellulite activities. Apium graveolens and Petroselinum crispum revealed excellent free radical scavenging activity, remarkably increased lipolysis, and decreased adipogenesis. Furthermore, apigenin and its glycosides were identified to be the major components in both extracts, which might be responsible for the antioxidant activity and anti-cellulite potential. Conclusively, these results signify the potent antioxidant and anti-cellulite properties of A. graveolens and P. crispum fruit extracts, holding potential for the development of plant derived products for cellulite management.

HPLC-ESI- MS/MS analysis of beet (Beta vulgaris) leaves and its beneficial properties in type 1 diabetic rats.

The phenolic profile of the leaves of Beta vulgaris subspecies vulgaris variety rubra was investigated by high-performance liquid chromatography (HPLC) coupled to electrospray ionization high resolution mass spectrometric (ESI-HRMS-MS) detection. Mass spectrometry-based molecular networking was employed to dereplicate the known compounds. Twelve known compounds, seven of which are previously undescribed as constituents in the B. vulgaris leaves were dereplicated and assigned with various levels of identification confidence. The ameliorative effects of the aqueous methanolic extract of the leaves were assessed against alloxan induced diabetic rats. It was found that the extract significantly decreased (p < 0.001) serum glucose, lipid profile, ALT, AST, TNF-α, IL-1ß, IL-6, and hepatic MDA levels; and significantly increased (p < 0.001) hepatic TAO and GSH; and down-regulated the expression of hepatic NF-κB versus the untreated diabetic groups, in a dose-dependent manner. In molecular docking, all identified compounds exhibited good glide score against the PPAR-É£ target, confirming the in vivo observed activities. In conclusion, B. vulgaris has immunomodulatory / antioxidant effects that could be helpful in slowing the progression of diabetic complications.