Triptolide (TP), an active constituent of Tripterygium wilfordii, possesses numerous pharmacological activities. However, its effects on cytochrome P450 enzymes (CYP450s) in rats remain unexplored. In this study, the effects of triptolide on the six main CYP450 isoforms (1A2, 2C9, 2C19, 2D6, 2E1, and 3A) were investigated both in vivo and in vitro. We monitored the body weight, survival proportions, liver index, changes in pathology, and biochemical index upon TP administration, in vivo. Using a cocktail probe of CYP450 isoform-specific substrates and their metabolites, we then carried out in vitro enzymatic studies in liver microsomal incubation systems via ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Finally, we verified our results at the messenger ribonucleic acid (mRNA) and protein level through quantitative real-time polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemical detection. The in vivo toxicity study confirmed that Sprague-Dawley (SD) rats exhibited dose-dependent hepatotoxicity after intragastric administration of TP [200, 400, and 600 μg/(kg.day)] for 28 days. In case of the CYP450 isoforms 3A, 2C9, 2C19, and 2E1, the in vitro metabolic study demonstrated a decrease in the substrate metabolic rate, metabolite production rate, and Vmax, with an increase in the Km value, compared with that observed in the control group. Additionally, a TP dose-dependent decrease in the mRNA levels was observed in the four major isoforms of CYP3A subfamily (3A1/3A23, 3A2, 3A9, and 3A62) and CYP2C9. A similar effect was also observed with respect to the protein levels of CYP2C19 and CYP2E1. This study suggests that TP can cause hepatotoxicity by reducing the substrate affinity, activity, and expression at the transcriptional and protein levels of the CYP450 isoforms 3A, 2C9, 2C19, and 2E1. TP also has the potential to cause pharmacokinetic drug interactions when co-administered with drugs metabolized by these four isoforms. However, further clinical studies are needed to evaluate the significance of this interaction.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent epidemiological studies suggest that echinacoside (ECH), a phenylethanoid glycoside found in Cistanche deserticola, has a protective effect against the development of PD. However, the detailed mechanisms of how ECH suppresses neuronal death have not been fully elucidated. In this study, we confirmed that ECH protects nigrostriatal neurons against 6‐hydroxydopamine (6‐OHDA)‐induced endoplasmic reticulum stress (ERS) in vivo and in vitro. ECH rescued cell viability in damaged cells and decreased 6‐OHDA‐induced reactive oxygen species accumulation in vitro. It also rescued tyrosine hydroxylase and dopamine transporter expression in the striatum, and decreased α‐synuclein aggregation following 6‐OHDA treatment in vivo. The validated mechanism of ECH activity was the reduction in the 6‐OHDA‐induced accumulation of seipin (Berardinelli–Seip congenital lipodystrophy 2). Seipin has been shown to be a key molecule related to motor neuron disease and was tightly associated with ERS in a series of in vivo studies. ECH attenuated seipinopathy by promoting seipin degradation via ubiquitination. ERS was relieved by ECH through the Grp94/Bip‐ATF4‐CHOP signal pathway.

The amyloid/tau/neurodegeneration (ATN) biomarker framework has greatly progressed the diagnosis and staging of Alzheimer's disease (AD). However, recent research highlights neuroinflammation as an equally critical factor in AD pathology across humans, rodents, and non‐human primates (NHPs). This review evaluates the combined use of ATN and neuroinflammatory biomarkers—such as glial fibrillary acidic protein (GFAP) (astrocytic marker) and triggering receptor expressed on myeloid cells 2 (TREM2)/ ionized calcium‐binding adapter molecule 1 (IBA‐1) (microglial markers)—in elucidating AD mechanisms, promoting early diagnosis, and shaping therapeutic strategies. It also summarizes the key features and translational potential of NHP models that closely mimic human AD pathology, highlighting the promising prospects of integrating these models with the ATN(X) biomarker system. These insights strengthen the link between biomarkers, NHP research, and clinical practice, opening new avenues for the early detection and treatment strategies of AD.Highlights: Neuroinflammation biomarkers, including glial fibrillary acidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2)/sTREM2, and YKL‐40, show strong clinical potential in Alzheimer's disease (AD). Incorporating neuroinflammation biomarkers into the ATN(X) framework may enhance diagnostic precision. Advanced non‐human primate (NHP) models closely replicate human brain pathology, addressing key limitations of mouse models. Measuring ATN(X) biomarkers in NHPs may improve clinical translation and support early diagnosis of AD. Optimizing NHP models—including ApoE4 status, injection protocols, and gene‐editing approaches—is crucial for reproducibility and efficiency.

Background: Evidence suggests that plant-based diets are associated with multiple health outcomes. However, in previous pooled studies, the lack of a standardized definition of plant-based diet has led to conflicting evidence regarding its relationship with health outcomes in middle-aged and elderly people. Methods and findings: Searches were conducted on PubMed, Embase, Cochrane Library and Web of Science databases from inception until July 10, 2024. We included studies that examined the association between (1) the standardized healthy plant-based diet index (hPDI) and unhealthy plant-based diet index (uPDI) and (2) cardiovascular disease (CVD), cardiovascular mortality (CVD mortality), frailty, and cognitive dysfunction. Dose–response analysis was performed to assess the relationships between (1) hPDI and uPDI and (2) CVD and frailty. Statistical analyses were performed using an inverse variance random-effects model, and results are reported as risk ratio (RR) with 95% confidence interval (CI) by combining the most adjusted RR, odds ratio (OR) and hazard ratio (HR) under the rare outcome assumption. A total of 25 cohort studies were included. Higher hPDI scores were associated with lower risks of CVD (RR = 0.81, 95% CI 0.71–0.93), CVD mortality (RR = 0.83, 95% CI 0.75–0.90), coronary heart disease (CHD) (RR = 0.79, 95% CI 0.70–0.88), stroke (RR = 0.91, 95% CI 0.86–0.96), ischemic stroke (RR = 0.86, 95% CI 0.79–0.94), cognitive dysfunction (RR = 0.75, 95% CI 0.66–0.84) and frailty (RR = 0.72, 95% CI 0.60–0.86). By contrast, higher uPDI scores were associated with increased risks of CVD (RR = 1.16, 95% CI 1.09–1.24), CVD mortality (RR = 1.14, 95% CI 1.05–1.23), frailty (RR = 1.52, 95% CI 1.10–2.08) and cognitive dysfunction (RR = 1.24, 95% CI 1.11–1.38). Dose–response analyses showed that increasing adherence to hPDI was associated with reduced risks of CVD and frailty, whereas increasing intake of hPDI was linked to increased risk of CVD and frailty. Conclusions: Our study suggests that adherence to hPDI is associated with favourable health outcomes in middle-aged and elderly people, except for hemorrhagic stroke. These findings highlight the potential benefits of hPDI for promoting healthy ageing.