Association between the risk and severity of Parkinson's disease and plasma homocysteine, vitamin B12 and folate levels: a systematic review and meta-analysis.

Background: Parkinson's disease (PD) is recognized as the second most prevalent progressive neurodegenerative disease among the elderly. However, the relationship between PD and plasma homocysteine (Hcy), vitamin B12, and folate has yielded inconsistent results in previous studies. Hence, in order to address this ambiguity, we conducted a meta-analysis to summarize the existing evidence. Methods: Suitable studies published prior to May 2023 were identified by searching PubMed, EMBASE, Medline, Ovid, and Web of Science. The methodological quality of eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Meta-analysis and publication bias were then performed using R version 4.3.1. Results: The results of our meta-analysis, consisting of case-control and cross-sectional studies, showed that PD patients had lower folate and vitamin B12 levels (SMD [95%CI]: -0.30[-0.39, -0.22], p < 0.001 for Vitamin B12; SMD [95%CI]: -0.20 [-0.28, -0.13], p < 0.001 for folate), but a significant higher Hcy level (SMD [95%CI]: 0.86 [0.59, 1.14], p < 0.001) than healthy people. Meanwhile, PD was significantly related to hyperhomocysteinemia (SMD [95%]: 2.02 [1.26, 2.78], p < 0.001) rather than plasma Hcy below 15 µmol/L (SMD [95%]: -0.31 [-0.62, 0.00], p = 0.05). Subgroup analysis revealed associations between the Hcy level of PD patients and region (p = 0.03), age (p = 0.03), levodopa therapy (p = 0.03), Hoehn and Yahr stage (p < 0.001), and cognitive impairment (p < 0.001). However, gender (p = 0.38) and sample size (p = 0.49) were not associated. Conclusion: Hcy, vitamin B12, and folic acid potentially predict the onset and development of PD. Additionally, multiple factors were linked to Hcy levels in PD patients. Further studies are needed to comprehend their roles in PD.

Influence of grapefruit juice on pharmacokinetics of triptolide in rats grapefruit juice on the effects of triptolide.

1. Triptolide, a major pharmacological component isolated from Tripterygium wilfordii Hook F (TWHF), is a substrate of both CYP3A4 and P-glycoprotein (P-gp). 2. This study investigates the effects of GFJ on the pharmacokinetics of triptolide in rats. 3. The pharmacokinetics of orally administered triptolide with or without GFJ pretreatment were investigated. A mechanistic study was also undertaken using the Caco-2 cell transwell model and rat liver microsomes incubation systems to support the in vivo pharmacokinetic data. 4. The results indicated that coadministration of GFJ could increase the systemic exposure of triptolide significantly, including area under the curve (828.58 ± 79.72 versus 541.53 ± 45.23 ng·h/mL) and maximum plasma concentration (273.58 ± 27.98 versus 193.67 ± 10.08 ng/mL). The apparent permeability of triptolide across the Caco-2 cell transwell model increased significantly with the pretreatment of GFJ (from 1.62 ± 0.25 × 10-6 to 2.51 ± 0.41 × 10-6 cm/s), and the metabolic stability of triptolide was also increased from 32.6 ± 5.1 to 52.5 ± 7.8 min with the pretreatment of GFJ, and the difference was significant (p < 0.05). 5. In conclusion, GFJ could increase the systemic exposure of triptolide in rats, when GFJ and triptolide was coadministered, and it might work mainly through increasing the absorption of triptolide by inhibiting P-gp, or through slowing down the metabolism of triptolide in rat liver by inhibiting the activity of CYP3A4.

Effects of type 2 diabetes mellitus on the pharmacokinetics of berberine in rats.

CONTEXT: Berberine is an active alkaloid isolated from Rhizoma coptidis [Coptis chinensis Franch. (Ranunculaceae)] that is widely used for the treatment of diabetes, hyperlipidemia and hypertension. However, the pharmacokinetics of berberine in normal rats and type 2 diabetes mellitus (T2DM) model rats are not clear. OBJECTIVE: This study compares the pharmacokinetics of berberine between normal and T2DM model rats. MATERIALS AND METHODS: The T2DM model rats were fed with high fat diet for 4 weeks, induced by low-dose (30 mg/kg) streptozotocin for 72 h and validated by determining the peripheral blood glucose level. Rats were orally treated with berberine at a dose of 20 mg/kg and then berberine concentration in rat plasma was determined by employing a sensitive and rapid LC-MS/MS method. RESULTS: The significantly different pharmacokinetic behaviour of berberine was observed between normal and T2DM model rats. When compared with the normal group, Cmax, t1/2 and AUC(0-t) of berberine were significantly increased in the model group (17.35 ± 3.24 vs 34.41 ± 4.25 µg/L; 3.95 ± 1.27 vs 9.29 ± 2.75 h; 151.21 ± 23.96 vs 283.81 ± 53.92 µg/h/L, respectively). In addition, oral clearance of berberine was significantly decreased in the model group (134.73 ± 32.15 vs 62.55 ± 16.34 L/h/kg). DISCUSSION AND CONCLUSION: In T2DM model rats, the pharmacokinetic behaviour of berberine was significantly altered, which indicated that berberine dosage should be modified in T2DM patients.