Effect of cytochrome P450 3A4 on tissue distribution of humantenmine, koumine, and gelsemine, three alkaloids from the toxic plant Gelsemium.

Humantenmine, koumine, and gelsemine are three indole alkaloids found in the highly toxic plant Gelsemium. Humantenmine was the most toxic, followed by gelsemine and koumine. The aim of this study was to investigate and analyze the effects of these three substances on tissue distribution and toxicity in mice pretreated with the Cytochrome P450 3A4 (CYP3A4) inducer ketoconazole and the inhibitor rifampicin. The in vivo test results showed that the three alkaloids were absorbed rapidly and had the ability to penetrate the blood-brain barrier. At 5 min after intraperitoneal injection, the three alkaloids were widely distributed in various tissues and organs, the spleen and pancreas were the most distributed, and the content of all tissues decreased significantly at 20 min. Induction or inhibition of CYP3A4 in vivo can regulate the distribution and elimination effects of the three alkaloids in various tissues and organs. Additionally, induction of CYP3A4 can reduce the toxicity of humantenmine, and vice versa. Changes in CYP3A4 levels may account for the difference in toxicity of humantenmine. These findings provide a reliable and detailed dataset for drug interactions, tissue distribution, and toxicity studies of Gelsemium alkaloids.

Antinociceptive effect of gelsenicine, principal toxic alkaloids of gelsemium, on prostaglandin E2-induced hyperalgesia in mice: Comparison with gelsemine and koumine.

Gelsemium elegans (G.elegans) is a plant of the Loganiaceae family, known for its indole alkaloids, including gelsemine, koumine, and gelsenicine. Gelsemine and koumine are well-studied active alkaloids with low toxicity, valued for their anti-anxiety and analgesic properties. However, gelsenicine, another important alkaloid, remains underexplored due to its high toxicity. This study focuses on evaluating the analgesic properties of gelsenicine and comparing them with gelsemine and koumine. The results indicate that all three alkaloids exhibit robust analgesic properties, with gelsemine, koumine, and gelsenicine showing ED50 values of 0.82 mg/kg, 0.60 mg/kg, and 8.43 µg/kg, respectively, as assessed by the hot plate method. Notably, the therapeutic dose of gelsenicine was significantly lower than its toxic dose (LD50 = 0.185 mg/kg). The study also investigated the mechanism of action by analyzing the expression levels of GlyRα3 and Gephyrin. The PGE2 model group showed decreased expression levels of GlyRα3 and Gephyrin, while groups treated with gelsemine, koumine, and gelsenicine were able to reverse this decrease. These results suggest that gelsenicine effectively alleviates PGE2-induced hyperalgesia by upregulating the expression of GlyRα3 and Gephyrin, which are key targets of the Gly receptor pathway.

Effect of heavy metal stress on emerging plants community constructions in wetland.

In this paper, we report the effects of heavy metals (HMs) (cadmium and mercury) on seed germination and seedling growth of Phragmites australis and Triarrhena sacchariflora, which are the two main typical emerging plants in Hongze Lake wetland. The results showed that there was a reduction in germination percentage, germination index and seedling length as HM concentration in the growing media increased for both treatments. The effect of HMs toxicity on seed germination and seedling growth of T. sacchariflora was more obvious than of P. australis. At the stage of seed germination, P. australis and T. sacchariflora were sensitive to Hg(2 + ) and Cd(2 + ), respectively, and Hg(2 + ) was more toxic than Cd(2 + ) at the stage of seedling growth. The effect of HMs toxicity is not invariable during plant growth. Compared to the stage of seedling growth, P. australis and T. sacchariflora are more susceptible to HMs at the stage of seed germination. In addition, we calculated the ecological thresholds of P. australis to Cd and Hg are 19.32 and 1.08 mg kg(-1), and that of T. sacchariflora to Cd is 4.62 mg kg(-1) based on the lab simulation. The results also indicated that the species of P. australis is more tolerant than T. sacchariflora to the HMs and is a better candidate for restoration in Hongze Lake wetland ecosystem.

Studies on the protective immunity of Schistosoma japonicum bivalent DNA vaccine encoding Sj23 and Sj14.

In order to explore the high performance bivalent DNA vaccine of Schistosoma japonicum, the fatty-acid-binding protein (Sj14) and the 23 kDa transmembrane protein (Sj23) two proteins were selected to construct the DNA-based vaccine. It was successful to construct a bivalent DNA vaccine using three strategies: the co-expression of two genes, a fusion gene expression and two kinds of plasmids in combination (cocktail vaccine). The bivalent DNA was proven to express well in vitro and in vivo by indirect immunofluorescence test (IIF) and reverse transcriptase-polymerase chain reaction (RT-PCR). The protective immunity of bivalent DNA vaccine was higher than that of univalent DNA vaccine (p<0.05). There were four groups of bivalent vaccine whose protective immunity was higher than 50%. Granuloma diameter reduction rates were in the range of 18-39%. There was no significant impact on immunity protection exerted by the four factors including dosage, inoculated times, inoculated routes and challenge time after the last immunization in three levels (p>0.05).