Sex-related differences in safety profiles, pharmacokinetics and tissue distribution of sinomenine hydrochloride in rats.

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum (Thunb.) Rehd. et Wils which exhibits significant analgesic, anti-inflammatory, and immunosuppressive effects. Sinomenine hydrochloride (SH) preparations, classified as natural disease-modifying antirheumatic drugs, are currently available for the treatment of rheumatoid arthritis and other rheumatic diseases. Our toxicity evaluation demonstrated that the median lethal dose of SH in female Sprague-Dawley (SD) rats was over 11 times greater than that in male SD rats, revealing striking sex-linked differences in the safety profile of SH. The present study was designed to investigate differences in the pharmacokinetics (PKs) and tissue distribution of SH between male and female SD rats after a single oral dose of 25 mg/kg. PK and tissue distribution studies were performed using a validated UPLC-MS/MS method. The results showed that SH-treated SD female rats displayed markedly greater drug exposure, and SH exhibited a longer half-life and slower clearance rate than comparable studies in male rats. Moreover, the tissue distribution study confirmed that the sinomenine concentration in female rats was considerably greater in the internal organs than in male rats. Our study demonstrates, for the first time, significant sex-related differences in the safety profile and PKs of SH, which may be associated with a distinct sex-dependent metabolic mechanism of sinomenine.

[Study on 5S rDNA sequence of two isolates of Trichinella from Guangxi].

OBJECTIVE: To analyze 5S ribosomal DNA (5S rDNA) sequences of two Trichinella isolates from Guangxi. METHODS: The fragments of 5S rDNA were obtained by PCR from the isolates of Debao and Nandan, and sequencing was made for the PCR products. Homogeneity, genetic distance matrix and phylogenetic tree were analyzed by related software. 5S rDNA sequences of the two isolates were compared separately with those of Trichinella species in GenBank. RESULTS: 5S rDNA sequences of three Trichinella isolates (Debao, Nandan and T. spiralis) showed the same length at 695 bp. There were 4 variable positions. The homogeneities of Debao and Nandan isolates with T. spiralis were 99.0% and 99.1% respectively. The homogeneities between Debao isolate and Nandan isolate was 98.8%. Compared with other Trichinella isolates in GenBank, they were all less than 94.2%. The evolutionary distance among isolates of Debao and Nandan and T. spiralis was 0.014. Meanwhile, the evolutionary distances between the Guangxi isolates and other Trichinella isolates in GenBank were more than 0.056. Phylogenetic tree analysis revealed that two isolates of Guangxi and T. spiralis located at the same node, revealing a close relationship. Bootstrap confidence values in two phylogenetic trees were 96 and 99, respectively. CONCLUSION: The two Trichinella isolates of Guangxi show a high homogeneity with T. spiralis, locate at the same nodes in phylogenetic tree,suggesting that the Debao and Nandan Trichinella isolates be identified as T. spiralis.