Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process. Cirrhosis was induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α. Both YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups. YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.

Chaihu Shugan Powder (CHSGP) has significant clinical efficacy in the treatment of functional dyspepsia (FD), but the specific mechanism requires further study. The aim of this study was to investigate the therapeutic effect of CHSGP on FD rats and the underlying mechanism of the effect on interstitial cells of cajal (ICC) mitophagy. The tail-clamping stimulation method was utilized to establish an FD rat model in vivo. Gastric emptying rate and small intestinal propulsion rate test, H&E staining, and Immunohistochemistry were conducted to evaluate the therapeutic effects of CHSGP on FD rats. In vitro, the regulatory effect of CHSGP on CCCP-mediated ICC mitophagy was further investigated by CCK8, Transmission electron microscope, immunofluorescence co-staining, Quantitative polymerase chain reaction and Western blot to reveal the potential mechanisms of CHSGP inhibited ICC mitophagy. Animal experiments provided evidence that CHSGP promoted gastric motility, increased ICC numbers, reduced Parkin expression, and elevated USP30 expression in FD rats. In vitro, further mechanism research demonstrated that CHSGP decreased LC3Ⅱ/LC3Ⅰ、PINK1、Parkin、PHB2 protein expression and increased USP30 protein expression. Furthermore, CHSGP increased Mfn2 protein expression by suppressing activation of the PINK1/Parkin pathway when USP30 is knocked down, consequently reducing CCCP-induced ICC mitophagy. These results suggest that CHSGP may treat FD against CCCP-induced ICC mitophagy by the up-regulation of via PINK1/Parkin pathway.

Constipation is a common gastrointestinal disorder without effective treatment approach. Buzhongyiqi decoction (BZYQD) is a classical formula that has been commonly used for gastrointestinal disorders for nearly 1,000 years. In this study, we aimed to investigate the protective effect of BZYQD against loperamide-induced constipation and its potential mechanism. Rats with loperamide-induced constipation were orally administered BZYQD. BZYQD treatment obviously increased the small intestinal transit rate and alleviated colon tissue pathological damage. Subsequently, serum metabolomics study was performed to identify the metabolites affected by BZYQD. Metabolomics identified that the levels of 17 serum metabolites, including prostaglandin E₂ (PGE₂), arachidonic acid (AA), and inositol, were significantly changed in BZYQD-treated group compared with those in the loperamide-induced group. Pathway analysis revealed that those metabolites were mainly associated with arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, ascorbate and aldarate metabolism, inositol phosphate metabolism. Additionally, BZYQD treatment down-regulated the cyclooxygenase-2 expression and decrease production of the proinflammatory mediator PGE₂. Further study revealed that BZYQD administration decreased serum levels of the inflammatory factors IL-1β and TNF-α, inhibited phosphorylation of the nuclear transcription factor NF-κB, and down-regulated expression of the inflammatory factors IL-1β and IL-6 in the constipated rat colon. Moreover, BZYQD treatment also increased serum levels of inositol, motilin and gastrin, and promoted gastrointestinal motility. In conclusion, the present study suggested that BZYQD exerted a protective effect against loperamide-induced constipation, which may be associated with its role in regulation of multiple metabolic pathways.

Objective. Cinnamaldehyde (CA) is the main active component of Guizhi (Cinnamomi ramulus) to ameliorate adriamycin‐ (ADR‐) induced proteinuria in rats. However, the underlying mechanism of CA against proteinuria remains unclear. The aim of this study was to investigate the action mechanisms of CA to treat proteinuria. Methods. 13 rats were randomly selected from 78 SD rats as control group, and the other rats were injected with ADR (3 mg/kg/time) twice through tail vein on day 1 and day 8 for modeling. After modeling, the rats were randomly divided into 5 groups as follows: ADR group, ADR+CA low‐dose group, ADR+CA middle‐dose group, ADR+CA high‐dose group and Benazepril group with 13 rats in each group. The urine of SD rats was collected for 24 h, urine protein, creatinine and urea nitrogen were detected, renal index was calculated, and HE staining and western blot were performed. Results. The 24 h urine volume and urine protein, renal function, and renal histopathology got worse significantly in the ADR group. To western blot, CA downregulated the protein expression of ACE and Ang‐2 and upregulated the protein expression of ACE2 in RAS signaling pathway. Conclusion. The underlying action mechanism of CA to treat NS might mainly be achieved by regulating RAS signaling pathway.

Nephrotic syndrome (NS) is a common glomerular ailment caused by various factors and ranks as the second most frequently seen kidney disease. The study aims to investigate the potential therapeutic mechanism of cinnamaldehyde (CA) intervention in NS by utilizing computational pharmacology. Genes linked to NS were gathered from databases and then were used to construct a PPI network, of which the node importance values (Nim) were calculated utilizing an optimized algorithm. Functional enrichment analyses were performed to build a pathway network for NS. Afterward, CA’s potential targets were acquired from the Venn diagram by intersecting NS-related genes and CA-related genes. The predicted targets and pathways of CA intervention in NS were identified using a mathematical algorithm that evaluated the disruption of NS pathways by CA, considering Nim, the number of pathways, and other variables. Molecular docking and cellular experiments were included in validation. By the way, the research collected 687 genes related to NS and 195 genes related to CA, which were used to identify 26 potential targets of CA in NS treatment. The disruption of 166 NS pathways by 26 CA targets was evaluated, showing that the Antifolate resistance and NOD-like receptor pathway exhibited the highest disturbance scores. Besides, key targets that were identified through the algorithm included IL1B, TNF, CASP8, and MAPK1, which were subsequently validated through molecular docking. Experimental results demonstrated that CA inhibited LPS-induced IL-1β, IL-6, and TNF-α levels in R264.7 cells and reduced p-38MAPK, p-ERK, and p-Caspase8 protein expression. This study proposes an algorithm for evaluating drug molecule perturbations on pathways. By employing this optimized model, potential key targets for CA in the treatment of NS are identified, with the anti-inflammatory effect potentially mediated through the Caspase8/MAPK pathway.