Therapeutic drug monitoring of perospirone: The lowest effective plasma concentration in patients with schizophrenia.

OBJECTIVES: This study investigated the effects of demographic factors such as age, sex and comedications on the plasma concentrations of perospirone in individuals diagnosed with schizophrenia. Additionally, the relationship between these plasma levels and the clinical efficacy of the medication was explored. METHODS: Data regarding the plasma concentration of perospirone in patients with schizophrenia were obtained from the Xi'an Mental Health Center and were retrospectively analysed. RESULTS: The study results revealed a range of 0.50-1.59 ng/mL for the 25th-75th percentile of perospirone concentration in the plasma, which ranged from 0.07 to 6.0 ng/mL. The plasma concentration of perospirone increased with the daily oral dose (r = 0.283, P < 0.05). Furthermore, patients with higher plasma perospirone concentrations and concentration-to-dose ratios (C/D) tended to be older or were women. Notably, the coadministration of valproate significantly reduced perospirone concentration and the C/D ratio by 54.7% and 35.3%, respectively (P < 0.01). Receiver operating characteristics curve analyses revealed that patients exhibited a good clinical response when their plasma perospirone concentrations were ≥ 1.17 ng/mL. CONCLUSION: The findings suggest that therapeutic drug monitoring of perospirone and adjustments to achieve steady-state concentrations of ≥ 1.17 ng/mL can be beneficial for optimising treatment for patients with schizophrenia.

Screening of rosmarinic acid from Salvia miltiorrhizae acting on the novel target TRPC1 based on the 'homology modelling-virtual screening-molecular docking-affinity assay-activity evaluation' method.

CONTEXT: Salvia miltiorrhizae Bunge (Lamiaceae) is a traditional Chinese medicine (TCM) for the treatment of 'thoracic obstruction'. Transient receptor potential canonical channel 1 (TRPC1) is a important target for myocardial injury treatment. OBJECTIVE: This work screens the active component acting on TRPC1 from Salvia miltiorrhizae. MATERIALS AND METHODS: TCM Systems Pharmacology Database and Analysis Platform (TCMSP) was used to retrieve Salvia miltiorrhiza compounds for preliminary screening by referring to Lipinski's rule of five. Then, the compound group was comprehensively scored by AutoDock Vina based on TRPC1 protein. Surface plasmon resonance (SPR) was used to determine the affinity of the optimal compound to TRPC1 protein. Western blot assay was carried out to observe the effect of the optimal compound on TRPC1 protein expression in HL-1 cells, and Fura-2/AM detection was carried out to observe the effect of the optimal compound on calcium influx in HEK293 cells. RESULTS: Twenty compounds with relatively good characteristic parameters were determined from 202 compounds of Salvia miltiorrhiza. Rosmarinic acid (RosA) was obtained based on the molecular docking scoring function. RosA had a high binding affinity to TRPC1 protein (KD value = 1.27 µM). RosA (50 µM) could reduce the protein levels (417.1%) of TRPC1 after oxygen-glucose deprivation/reperfusion (OGD/R) in HL-1 cells and it could inhibit TRPC1-mediated Ca2+ influx injury (0.07 ΔRatio340/380) in HEK293 cells. DISCUSSION AND CONCLUSIONS: We obtained the potential active component RosA acting on TRPC1 from Salvia miltiorrhizae, and we speculate that RosA may be a promising clinical candidate for myocardial injury therapy.

Cardioprotective effect of rosmarinic acid against myocardial ischaemia/reperfusion injury via suppression of the NF-κB inflammatory signalling pathway and ROS production in mice.

CONTEXT: Rosmarinic acid (RosA), a natural poly-phenolic compound isolated from a variety of Labiatae herbs, has been reported to have a range of biological effects. OBJECTIVE: To investigate the cardioprotective effects of RosA against myocardial ischaemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Male C57BL/6J mice were given RosA (100 mg/kg) via intragastric administration. After 1 week of administration, the mice were subjected to 30 min/24 h myocardial I/R injury. The mice were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + I/R, and RosA + I/R. Infarct size (IS), cardiac function (including EF, FS), histopathology, serum enzyme activities, ROS changes, cis aconitase (ACO) activity, and specific mRNA and protein levels were assessed in vivo. HL-1 cells were pre-treated with or without RosA (50 µM), followed by stimulation with 9 h/6 h of oxygen and glucose deprivation/re-oxygenation (OGD/R). The cells were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + OGD/R, and RosA + OGD/R. Lactate dehydrogenase (LDH) levels, ACO activity, ROS changes and protein levels were measured in vitro. RESULTS: Treatment with RosA reduced the following indicators in vivo (p < 0.05): (1) IS (14.5%); (2) EF (-23.4%) and FS (-18.4%); (3) the myocardial injury enzymes CK-MB (20.8 ng/mL) and cTnI (7.7 ng/mL); (4) DHE-ROS: (94.1%); (5) ACO activity (-2.1 mU/mg protein); (6) ogdh mRNA level (122.9%); and (7) OGDH protein level (69.9%). Moreover, treatment with RosA attenuated the following indicators in vitro (p < 0.05): (1) LDH level (191 U/L); (2) DHE-ROS: (165.2%); (3) ACO activity (-3.2 mU/mg protein); (4) ogdh mRNA level (70.0%); and (5) OGDH (110.1%), p-IκB-a (56.8%), and p-NF-κB (57.7%) protein levels. CONCLUSIONS: RosA has the potential to treat myocardial I/R injury with potential application in the clinic.