Although Parkinson's disease (PD) is the second most common neurodegenerative disorder, the preventative or therapeutic agents for the treatment of PD are limited. Eucommia ulmoides Oliver (EuO) is widely used as a traditional herb to treat various diseases. EuO bark extracts have been reported to possess anti-PD activity. Here, we investigated whether extracts of EuO leaves (EEuOL) also have therapeutic effects on PD since similar components and clinical applications have been found between barks and leaves of this tree. We identified the chemical composition of EEuOL by HPLC-Q-TOF-MS and tested the anti-PD effect of EEuOL using the zebrafish PD model. As a result, 28 compounds including 3 phenolic acids, 7 flavonoids, and 9 iridoids were identified. EEuOL significantly reversed the loss of dopaminergic neurons and neural vasculature and reduced the number of apoptotic cells in zebrafish brain in a concentration-dependent manner. Moreover, EEuOL relieved locomotor impairments in MPTP-modeled PD zebrafish. We also investigated the underlying mechanism and found that EEuOL may activate autophagy, contributing to α-synuclein degradation, therefore alleviating PD-like symptoms. Molecular docking simulation implied the interaction between autophagy regulators (Pink1, Beclin1, Ulk2, and Atg5) and phenolic acids of EEuOL, affirming the involvement of autophagy in EEuOL-exerted anti-PD action. The overall results indicated the anti-PD effect of EEuOL, opening the possibility to use the extract in PD treatment.

Background: C-phycocyanin (C-PC), a phycobiliprotein from Spirulina platensis, has been confirmed to be an effective antioxidant. Duing to the large molecular weight protein, C-PC is hardly absorbed in the human gut and easy coagulates into lumps. In light of this, highly pure, easy absorption, and small molecular weight polypeptides has won the attention in the recent past. However, there are few studies on the C-PC bioactive peptides. Thus, the objective of this study was find natural multifunctional antioxidant peptides from C-PC and demonstrate their mechanisms.Method: In this study, novel antioxidant peptides from pancreatin hydrolysate of C-PC were isolated and purified by using a multi-bioassay-guided method. The DPPH and ABTS radical scavenging in vitro and antioxidant zebrafish model in vivo were used to evaluate the antioxidant activities. Furthermore, the underlying molecular mechanisms of these peptides were investigated by measuring the level of ROS, MDA, SOD, CAT and gene expression in Nrf2 signaling pathway.Results: Total three novel active peptides, MHLWAAK (Met-His-Leu-Trp-Ala-Ala-Lys), MAQAAEYYR (Met-Ala-Gln-Ala-Ala-Glu-Tyr-Tyr-Arg), and MDYYFEER (Met-ASP-Tyr-Tyr-Phe-Glu-Glu-Arg) were isolated and purified from pancreatin hydrolysate of C-PC. These synthesized peptides displayed high DPPH and ABTS radical scavenging ability. In addition, in a zebrafish model, the three peptides significantly protected zebrafish embryos from H2O2-induced oxidative injury without toxicity by inhibiting ROS generation, preventing MDA formation, and upregulating the activities of SOD and CAT. Further experiments showed that these peptides could significantly regulated oxidative stress via activating the Nrf2 signaling pathway.Conclusion: This study indicates that the antioxidant peptides from C-PC could serve as powerful antioxidants for preventing and treating various diseases associated with oxidative stress.

Armillaria mellea is a traditional Chinese medicinal and edible mushroom. Many cultured products of A. mellea have been used to develop commercial medicines in recent years. The chemical composition and activities of the major bioactive chemical components—polysaccharides—may be different because of differences in the raw materials used. Four polysaccharides (SP, CMP, CFBP and CFMP) were obtained from wild sporophores and cultured products (including mycelia, fermentation broth and fermentation mixture) of A. mellea. Their yields, carbohydrate contents, monosaccharide compositions, FT-IR spectra, NMR spectroscopy and antioxidant activities were investigated. All of the polysaccharides were composed of xylose, glucose and galactose without protein. Glucose was the dominant monosaccharide in SP, CMP and CFMP, whereas galactose was the dominant monosaccharide in CFBP. SP and CMP showed higher scavenging DPPH^• and ABTS^•+ activities and reducing power among four polysaccharides. The carbohydrate content and corresponding glucose percentage were positive influences on the antioxidant activities, whereas the corresponding xylose and galactose percentage were negative influences. A. mellea polysaccharides are potential natural antioxidants. Polysaccharides from cultured products, especially mycelia, are good substitutes for SP and are also potential sources for both dietary supplements and food industries.

Neptunea arthritica cumingii (Nac) is a marine snail with high nutritional and commercial value; however, little is known about its active peptides. In this study, two multi-functional peptides, YSQLENEFDR (Tyr-Ser-Gln-Leu-Glu-Asn-Glu-Phe-Asp-Arg) and YIAEDAER (Tyr-Ile-Ala-Glu-Asp-Ala-Glu-Arg), were isolated and purified from meat and visceral mass extracts of Nac using a multi-bioassay-guided method and were characterized by using liquid chromatography-tandem mass spectrometry. Both peptides showed high antioxidant, angiotensin-converting enzyme (ACE)-inhibitory, and anti-diabetic activities, with half-maximal effective concentrations values less than 1 mM. Antioxidant and ACE-inhibitory activities were significantly higher for YSQLENEFDR than for YIAEDAER. In a zebrafish model, the two peptides exhibited strong scavenging ability for reactive oxygen species and effectively protected skin cells against oxidative damage without toxicity. Molecular docking simulation further predicted the interactions of the two peptides and ACE. Stability analysis study indicated that the two synthetic peptides maintained their activities under thermal stress and simulated gastrointestinal digestion conditions. The low molecular weight, high proportion of hydrophobic and negatively-charged amino acids, and specific C-terminal and N-terminal amino acids may contribute to the observed bio-activities of these two peptides with potential application for the prevention of chronic noncommunicable diseases.