UHPLC-Orbitrap-Fusion-TMS-Based Metabolomics Study of Phenylpropionamides in the Seed of Cannabis sativa L. against Alzheimer's Disease.

Phenylpropionamides in the seed of Cannabis sativa L. (PHS) have a protective effect on neuroinflammation and antioxidant activity. In this study, the UHPLC-Orbitrap-fusion-TMS-based metabolomics approach was used to analyze the serum samples and identify potential biomarkers in Streptozotocin (STZ) induced Alzheimer's disease (AD) rats. The results revealed that primary bile acid biosynthesis and taurine and hypotaurine metabolism were significantly correlated with STZ-induced AD rats. In addition, the key enzymes in these two pathways were verified at the protein level. The levels of cysteine dioxygenase type I (CDO1), cysteine sulfinic acid decarboxylase (CSAD), cysteamine (2-aminoethanethiol) dioxygenase (ADO), 7α-hydroxylase (CYP7A1), and sterol 12α-hydroxylase (CYP8B1) were the key enzymes affecting the two pathways in AD rats compared with the control group (CON). Furthermore, after a high-dose group of phenylpropionamides in the seed of Cannabis sativa L. (PHS-H) was administrated, the levels of CDO1, CSAD, CYP7A1, and CYP8B1 were all callback. These findings demonstrate for the first time that the anti-AD effect of PHS is associated with the regulation of primary bile acid biosynthesis and taurine and hypotaurine metabolism in STZ-induced AD rats.

Hydroxycinnamic acid derivatives isolated from hempseed and their effects on central nervous system enzymes.

New neuroprotective treatments of natural origin are being investigated. Both, plant extracts and isolated compounds have shown bioactive effects. Hempseed is known for its composition of fatty acids, proteins, fibre, vitamins, as well as a large number of phytochemical compounds. After a defatting process of the seeds, hydroxycinnamic acids and its amine derivatives are the majoritarian compounds in an ethyl acetate fraction (EAF). In the present study, we investigated in vitro effect on neuronal enzymes: MAO-A, MAO-B, tyrosinase and acetylcholinesterase. Besides, the effect of EAF on striatal biogenic amines in mice was evaluated. Both, EAF and isolated compounds (N-trans-caffeoyltyramine and N-trans-coumaroyltyramine), showed inhibitory action on MAO-A, MAO-B and tyrosinase. Furthermore, an increasing of biogenic amines was observed in the corpus striatum of the mice, after administration of EAF. These findings show that EAF and the hydroxycinnamic acid derivatives may represent a potential treatment in degenerative neuronal diseases.

Protective effect of phenylpropionamides in the seed of Cannabis Sativa L. on Parkinson's disease through autophagy.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. As one of the major degradation pathways, autophagy plays a pivotal role in maintaining the effective turnover of proteins and damaged organelles in cells. Lewy bodies composed of α-synuclein (α-syn) abnormally aggregated in the substantia nigra are important pathological features of PD, and autophagy dysfunction is considered to be an important factor leading to abnormal aggregation of α-syn. Phenylpropionamides (PHS) in the seed of Cannabis sativa L. have a protective effect on neuroinflammation and antioxidant activity. However, the therapeutic role of PHS in PD is unclear. In this study, the seeds of Cannabis sativa L. were extracted under reflux with 60% EtOH-H2O, and the 60% EtOH-H2O elution fraction was identified as PHS with the UPLC-QTOF-MS. The 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-induced PD model in C57BL/6 J mice was used for behavioral and pharmacodynamic experiments. Behavioral symptoms were improved, Nissl-stained and TH-positive neurons in the substantia nigra were significantly increased in PHS-treated MPTP-induced PD model mice. Compared with the model group, PHS treatment reduced the expression level of α-syn, and the expression of TH increased significantly by western blotting, compared with the model group, the PHS group suppressed Caspase 3 and Bax expression and promoted Bcl-2 expression and levels of p62 decreased significantly, the ratio of LC3-II/I and p-mTOR/mTOR in the PHS group had a downward trend, suggesting that the therapeutic effect of PHS on MPTP-induced PD model mice may be triggered by the regulation of autophagy.