Andrographolide Improves ApoE4-Mediated Blood-Brain Barrier Injury by Alleviating Inflammation.

The pathological and physiological studies of Alzheimer's disease (AD) have been in-depth, and apolipoprotein E4 (ApoE4) has been proven to be highly correlated with AD, and clinical and experimental data show that ApoE4 can cause blood-brain barrier (BBB) injury, and the change of BBB permeability is an important factor affecting the development of AD. Andrographolide (Andro), as the active component of the natural plant Andrographis paniculata, has been proven to have anti-inflammatory and antioxidant effects, which have potential neuroprotective effects. To verify the protective effect of Andro on BBB in a short term, our research group used atorvastatin (Atorva)-mediated zebrafish brain injury model and the ApoE4-mediated cell co-culture model of BBB injury to explore the protective effects and mechanisms of Andro on BBB injury. Studies have shown that Andro can inhibit the activation of CypA/NF-κB/MMP-9 signaling pathway and has achieved the effect of antagonizing the inhibition of ApoE4 on intercellular tight junction proteins (occludin, claudin-5, and ZO-1). At the same time, Andro can inhibit the secretion of cell adhesion molecules (VCAM-1 and ICAM-1) in cells, thereby delaying the occurrence and progression of neuroinflammation and playing a protective role in BBB. In conclusion, Andro is a potent natural product which can protect the blood-brain barrier.

Nuciferine reduces inflammation induced by cerebral ischemia-reperfusion injury through the PI3K/Akt/NF-κB pathway.

BACKGROUND: Cerebral ischemia has the characteristics of high incidence, mortality, and disability, which seriously damages people's health. Cerebral ischemia-reperfusion injury is the key pathological injury of this disease. However, there is a lack of drugs that can reduce cerebral ischemia-reperfusion injury in clinical practice. At present, a few studies have provided some evidence that nuciferine can reduce cerebral ischemia-reperfusion injury, but its specific mechanism of action is still unclear, and further research is still needed. OBJECTIVE: In this study, PC12 cells and SD rats were used to construct OGD/R and MCAO/R models, respectively. Combined with bioinformatics methods and experimental verification methods, the purpose of this study was to conduct a systematic and comprehensive study on the effect and mechanism of nuciferine on reducing inflammation induced by cerebral ischemia-reperfusion injury. RESULTS: Nuciferine can improve the cell viability of PC12 cells induced by OGD/R, reduce apoptosis, and reduce the expression of inflammation-related proteins; it can also improve the cognitive and motor dysfunction of MCAO/R-induced rats by behavioral tests, reduce the area of cerebral infarction, reduce the release of inflammatory factors TNF-α and IL-6 in serum and the expression of inflammation-related proteins in brain tissue. CONCLUSION: Nuciferine can reduce the inflammatory level of cerebral ischemia-reperfusion injury in vivo and in vitro models by acting on the PI3K/Akt/NF-κB signaling pathway, and has the potential to be developed as a drug for the treatment of cerebral ischemia-reperfusion injury.

Andrographolide derivative Andro-III modulates neuroinflammation and attenuates neuropathological changes of Alzheimer's disease via GSK-3ß/NF-κB/CREB pathway.

Andrographolide has anti-inflammatory and neuroprotective effects, making it a potential therapeutic option for Alzheimer's disease (AD). Our research group optimized its structure in a previous study to minimize the risk of renal toxicity, which would beneficial for future clinical research. This study aims to examine the impact of Andro-III on enhancing cognitive learning ability in 3xTg-AD mice, as well as the mechanisms involved. Andro-III improved spatial learning ability, prevented the loss of Nysted's vesicles, reduced the accumulation of ß-amyloid (Aß) and tau proteins, and suppressed microglial activation. Further research found that the expression of nuclear factor kappa-B RelA (NF-κB p65) expression and glycogen synthase kinase-3ß (GSK-3ß) activity were inhibited, while CREB was upregulated in brain tissue treated with Andro-III. Moreover, Andro-III downregulated the expression of IBA1 and inflammatory factors in microglial cells of mice induced by Aß. The regulation of the GSK-3ß/NF-κB/CREB pathway was similar to that observed in 3xTg-AD mice. Therefore, Andro-III modulates neuroinflammation and attenuates neuropathological changes of AD via the GSK-3ß/NF-κB/CREB pathway.

ApoE4-mediated blood-brain barrier damage in Alzheimer's disease: Progress and prospects.

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 (Aß), 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.

Medicinal fungus Phellinus igniarius alleviates gout in vitro by modulating TLR4/NF-kB/NLRP3 signaling.

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-1ß, 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-1ß, 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.