Background
We aimed to reveal the mechanism of functional constipation in the treatment of
Atractylodes macrocephala
Koidz. (AMK) and
Paeonia lactiflora
Pall. (PLP).
Methods
The main active ingredients of AMK and PLP were screened by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. A database of functional constipation targets was established by GeneCard and OMIM. An “ingredient‐target” network map was constructed with Cytoscape software (version 3.7.1), and molecular docking analysis was performed on the components and genes with the highest scores. The rats in the normal group were given saline, and those in the other groups were given 10 mg/kg diphenoxylate once a day for 14 days. The serum and intestinal tissue levels of adenosine monophosphate (cAMP), protein kinase A (PKA), and adenylyl cyclase (AC) of the rats and aquaporin (AQP)1, AQP3, and AQP8 were measured.
Results
AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation. After treatment with AMK, PLP, or mosapride, the serum and intestinal tissue levels of AC, cAMP, and PKA were significantly downregulated. Groups receiving AMK and PLP or mosapride exhibited a reduction in the level of AQP1, AQP3, and AQP8 to varying degrees.
Conclusion
Molecular docking analysis revealed that AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation. Studies have confirmed that AMK and PLP can also affect AC, cAMP, and PKA. AC, cAMP, and PKA in model rats were significantly downregulated. AQP expression is closely related to AC, cAMP, and PKA. AMK and PLP can reduce the expression of AQP1, AQP3, and AQP9 in the colon of constipated rats.
Purpose Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment. The objective of this study was to find new therapeutic agents and appropriate therapeutic methods and overcome the limitations of TNBC treatment. Methods P53 mutant TNBC cells were treated with eupaformosanin (Eup), a natural compound isolated from Eupatorium cannabinum Linn. Apoptosis and ferroptosis were detected in vitro and in vivo. RNA knockdown was used to investigate the role of mutant p53 in ferroptosis and apoptosis of Eup-induced cell death. A xenograft TNBC animal model was established to assess the anti-TNBC activity of Eup. Results MTT assay suggested that Eup strongly inhibited the viability of TNBC cells. Meanwhile, mitochondrial apoptosis contributed to the cell death in TNBC cells while mitochondrial membrane potential (MMP; Δψm) was disrupted, mitochondrial ROS (mt ROS) was enhanced, and related level of proteins was regulated. Apoptosis inhibitor Z-VAD rescued Eup-induced cell death. Afterwards, ferroptosis-induced cell death was demonstrated in TNBC cells, accompanied by lipid ROS accumulation, GSH depletion and iron increase. These events were blocked by ferroptosis inhibitors Fer-1 and DFO, indicating that ferroptosis facilitated Eup-induced cell death. Furthermore, Eup regulated mutant p53 ubiquitination, and mutant p53 signaling participated in Eup-induced apoptosis and ferroptosis, which were rescued when mutant p53 was silent in TNBC cells. Moreover, Eup exerted an anti-TNBC effect by inducing apoptosis and ferroptosis in vivo.Conclusion The natural compound Eup is a potential TNBC therapeutic agent that induces apoptosis and ferroptosis through ubiquitination of mutant p53.
Background: Yunpi-Huoxue-Sanjie (YP-SJ) formula is a Chinese herbal formula with unique advantages for the treatment of diabetic cardiovascular complications, such as diabetic cardiomyopathy (DCM). The aim of this study was to investigate the role of YP-SJ formula in regulating myocardial autophagy. To determine whether YP-SJ formula can be used as an adjuvant therapy for DCM, its therapeutic effects and mechanism in myocardial injury caused by type 2 diabetic mellitus (T2DM) rats were determined. Methods: A high-fat diet combined with low-dose streptozotocin (STZ) injection was used to induce DCM in rats. Biochemical reagents were used to analyze blood glucose levels, an enzyme-linked immunosorbent assay determined insulin levels, echocardiography assessed cardiac structure and function, histopathology was used to detect myocardial inflammation and fibrosis, myocardial autophagosomes were observed by transmission electron microscopy, and quantitative RT-PCR and Western blot analyses were used to detect the expression levels of autophagy-related proteins. Results: After treatment with YP-SJ formula, DCM rats’ metabolism was abnormal and myocardial inflammation, fibrosis, and cardiac dysfunction were significantly improved. In addition, compared with DCM, YP-SJ formula significantly increased the number of autophagosomes, the expression of forkhead box protein O1 (FoxO1) and autophagy related 12 (Atg12) ; the expression of phosphorylated FoxO1 and p62 was significantly decreased, and the level of myocardial autophagy was increased. Conclusions: YP-SJ formula can alleviate the myocardial damage caused by T2DM, and thus may serve as an alternative treatment for DCM.
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