Senna and its main components sennosides are well-known effective laxative drugs and are used in the treatment of intestinal constipation in the world. Their potential side effects have attracted more attention in clinics but have little scientific justification. In this study, senna extract (SE), sennosides (SS), and sennoside A (SA) were prepared and used to generate diarrhea rats. The diarrhea rats were investigated with behaviors, clinical signs, organ index, pathological examination, and gene expression on multiple aquaporins (Aqps) including Aqp1, Aqp2, Aqp3, Aqp4, Aqp5, Aqp6, Aqp7, Aqp8, Aqp9, and Aqp11. Using qRT-PCR, the Aqp expression profiles were constructed for six organs including colon, kidney, liver, spleen, lung, and stomach. The Aqp alteration profiles were characterized and was performed with Principle Component Analysis (PCA). The SE treatments on the rats resulted in a significant body weight loss (p < 0.001), significant increases (p < 0.001) on the kidney index (27.72%) and liver index (42.55%), and distinguished changes with up-regulation on Aqps expressions in the kidneys and livers. The SS treatments showed prominent laxative actions and down regulation on Aqps expression in the colons. The study results indicated that the SE had more influence/toxicity on the kidneys and livers. The SS showed more powerful actions on the colons. We suggest that the caution should be particularly exercised in the patients with kidney and liver diseases when chronic using senna-based products.
<p><b>Abstract:</b><b></b></p><p><b><i>Objective:</i></b> To explore the target of anti-knee osteoarthritis (KOA) in the effective chemical compounds of piper longum L based on network pharmacological methods.<b></b></p><p><b><i>Methods</i></b>: The active chemical compounds of piper longum L were collected employing database retrieval on TCMSP, TCM-PTD, and literature mining. The Swiss Target Prediction service predicts the targets of active chemical compounds, and at the same time, the targets of the drugs treating knee osteoarthritis were collected by retrieving the OMIM and CTD databases. The targets were subjected to an alignment analysis to screen out piperine and we simulated the binding sites in vivo of compounds and proteins via AutoDock. After that, the rat models of knee osteoarthritis were established. The rats in model groups were given piperine treatment. The verification of the anti-KOA target PPARG and MAPK1 was done by Western blot and co-immunoprecipitation.</p><p><b><i>Results</i></b><i>: </i>Nine active ingredients were predicted. According to Lipinski's rule, piperine was speculated as a possible active ingredient. According to the possible targets of piperine and the KOA's possible targets, three co-targets of them were confirmed, PPARG and MAPK1 were related to knee osteoarthritis (KOA). Molecular docking results show that piperine can hinder the binding of PPARG protein ARG-212 and GLN-420 amino-acid residues to each other. After 20 weeks of piperine treating, Western blot found that piperine can significantly increase the expression level of PPARG and reduce the expression level of MAPK1 in model rats. The endogenous interaction between PPARG and MAPK1 was verified by co-immunoprecipitation.</p><p><b><i>Conclusion</i></b><i>:</i> Piper longum L can regulate the progression of knee osteoarthritis (KOA) by its active ingredient piperine,can affect the expression of PPARG and MAPK1 proteins, and PPARG and MAPK1 proteins have endogenous interactions.</p>
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