Late-onset Alzheimer's disease (AD), a neurodegenerative disease, is expected in the elderly population and adversely affects families and society. The extensive debate on the deposition of amyloid (Aβ), abnormal phosphorylation of Tau protein, and neuroinflammation hypothesis in the pathogenesis of AD has been recognized by many scholars. The blood-brain barrier (BBB) is an essential physical barrier that protects the brain from external material interference, and its integrity affects the process of AD. Apolipoprotein E4 (ApoE4) has shown a critical regulatory role in many studies and is a crucial protein that affects AD. Numerous current studies on ApoE4 are based on complementary hypotheses to the three hypotheses above, ignoring the effect of ApoE4 on BBB constitutive cells and the role of the BBB in AD. In this review, we summarize the findings of the role of ApoE4 in the composition of the BBB and the value of ApoE4 for maintaining BBB integrity, which may play an essential role in changing the progression of the disease.

Background:Phellinus igniarius (P. igniarius) is an important medicinal and edible fungus in China and other Southeast Asian countries and has diverse biological activities. This study was performed to comparatively investigate the therapeutic effects of wild and cultivated P. igniarius on hyperuricaemia and gouty arthritis in rat models.Methods: UPLC-ESI-qTOF-MS was used to identify the chemical constituents of polyphenols from wild P. igniarius (WPP) and cultivated P. igniarius (CPP). Furthermore, WPP and CPP were evaluated in an improved hyperuricaemia rat model induced by yeast extract, adenine and potassium oxonate, which was used to examine xanthine oxidase (XO) activity inhibition and anti-hyperuricemia activity. WPP and CPP therapies for acute gouty arthritis were also investigated in a monosodium urate (MSU)-induced ankle swelling model. UHPLC-QE-MS was used to explore the underlying metabolic mechanisms of P. igniarius in the treatment of gout.Results: The main active components of WPP and CPP included protocatechuic aldehyde, hispidin, davallialactone, phelligridimer A, hypholomine B and inoscavin A as identified by UPLC-ESI-qTOF-MS. Wild P. igniarius and cultivated P. igniarius showed similar activities in reducing uric acid levels through inhibiting XO activity and down-regulating the levels of UA, Cr and UN, and they had anti-inflammatory activities through down-regulating the secretions of ICAM-1, IL-1β and IL-6 in the hyperuricaemia rat model. The pathological progression of kidney damage was also reversed. The polyphenols from wild and cultivated P. igniarius also showed significant anti-inflammatory activity by suppressing the expression of ICAM-1, IL-1β and IL-6 and by reducing the ankle joint swelling degree in an MSU-induced acute gouty arthritis rat model. The results of metabolic pathway enrichment indicated that the anti-hyperuricemia effect of WPP was mainly related to the metabolic pathways of valine, leucine and isoleucine biosynthesis and histidine metabolism. Additionally, the anti-hyperuricemia effect of CPP was mainly related to nicotinate and nicotinamide metabolism and beta-alanine metabolism.Conclusions: Wild P. igniarius and cultivated P. igniarius both significantly affected the treatment of hyperuricaemia and acute gouty arthritis models in vivo and therefore may be used as potential active agents for the treatment of hyperuricaemia and acute gouty arthritis.

Neuronal injury and apoptosis are important causes of the occurrence and development of many neurodegenerative diseases, such as cerebral ischemia, Alzheimer’s disease, and Parkinson’s disease. Although the detailed mechanism of some diseases is unknown, the loss of neurons in the brain is still the main pathological feature. By exerting the neuroprotective effects of drugs, it is of great significance to alleviate the symptoms and improve the prognosis of these diseases. Isoquinoline alkaloids are important active ingredients in many traditional Chinese medicines. These substances have a wide range of pharmacological effects and significant activity. Although some studies have suggested that isoquinoline alkaloids may have pharmacological activities for treating neurodegenerative diseases, there is currently a lack of a comprehensive summary regarding their mechanisms and characteristics in neuroprotection. This paper provides a comprehensive review of the active components found in isoquinoline alkaloids that have neuroprotective effects. It thoroughly explains the various mechanisms behind the neuroprotective effects of isoquinoline alkaloids and summarizes their common characteristics. This information can serve as a reference for further research on the neuroprotective effects of isoquinoline alkaloids.

Background:Phellinus igniarius (P. igniarius) is a valuable medicinal and edible fungus with various biological activities such as anti-inflammation, antioxidation, and immune regulation. In this study, we explored the effects of P. igniarius on a gout model in vitro.Methods: The DPPH, ABTS, and FRAP methods were combined to determine and compare the antioxidant activities of wild P. igniarius total polyphenols (WPP) and cultivated P. igniarius total polyphenols (CPP) in vitro. Spectrophotometry was used to compare the inhibitory effect of WPP and CPP on xanthine oxidase (XO) activity to evaluate anti-hyperuricemia activity in vitro. HUVECs were stimulated with monosodium urate (MSU) crystals for 24 h to establish an acute gouty inflammation model in vitro. The protective effects were compared by measuring cell viability; the contents of ICAM-1, IL-1β, IL-6 and VCAM-1; the protein expressions of TLR4 and NLRP3; reactive oxygen species production; and the nuclear translocation of NF-κB p65. UHPLC-QE-MS technology was used to explore the potential metabolic mechanism of P. igniarius against gout.Results: WPP and CPP had strong antioxidant capacity, and the antioxidant capacity of CPP was similar to that of WPP. In a comparative experiment of xanthine oxidase activity inhibition by WPP and CPP, the IC₅₀ values were 88.19 μg/ml and 108.0 μg/ml, respectively. At a dose of 40 μg/ml, WPP and CPP significantly improved the decrease in cell viability induced by monosodium urate (150 μg/ml) and inhibited the increase in inflammatory factors such as ICAM-1, IL-1β, IL-6, and VCAM-1. The increase in TLR4 and NLRP3 protein expression induced by MSU crystals in HUVECs was also significantly inhibited by total polyphenols from wild and cultivated P. igniarius. In addition, both significantly improved MSU-induced ROS overproduction and NF-κB p65 nuclear translocation. WPP and CPP may primarily be involved in phenylalanine metabolism and lysophosphatidylcholine metabolism in their role in the treatment of gout.Conclusion: CPP and WPP both showed good antioxidant activity and xanthine oxidase inhibitory activity and had good therapeutic effects on the gout model in vitro. Furthermore, this study indicated that cultivated P. igniarius had a protective effect similar to that of wild P. igniarius, which would be expected to improve the shortage of wild P. igniarius and promote the development of the cultivated P. igniarius industry and product development.