Research Article
Effect of 3–3'diindolylmethane (DIM) on Acute Radiation Lung Injury in Mice Via the TGF-β1 Pathway
Issue:
Volume 11, Issue 4, July 2023
Pages:
66-72
Received:
2 September 2023
Accepted:
18 September 2023
Published:
28 October 2023
Abstract: Objective: We studied the effect of 3–3'diindole methane (DIM) on acute radiation-induced lung injury (RILI) in mice and the possible underlying mechanism. Methods: A total of 45 mice were divided into five groups using the random number table method, namely, blank group, drug group alone (75 mg/kg DIM by peritoneal perfusion), simple irradiation group (one-time irradiation of 16 Gy), irradiation + drug group (one-time irradiation of 16 Gy + intraperitoneal perfusion of 75 mg/kg DIM 30 min before irradiation), and irradiation + prednisone group (one-time irradiation of 16 Gy + intraperitoneal perfusion of 5 mg/kg prednisone 30 min before irradiationas a positive control group). The whole lung was irradiated with a single dose of 16 Gy X-ray. Mice were killed by cervical dislocation at 24 h, 1 week, 2 weeks, and 4 weeks after irradiation, following which the lung tissue samples were subjected to hematoxylin and eosin (HE) staining. In addition, the expression of transforming growth factor (TGF)-β1/vascular endothelial growth factor (VEGF) pathway-related proteins was studied. Results: Under the same irradiation dose, the degree of lung injury in model mice after the intervention of DIM drugs was significantly lower than that in mice in the simple irradiation group. DIM significantly reduced the expression of TGF-β/VEGF-1 (P< 0.05). Conclusion: 3-3'diindolyl methane (DIM) can be downregulated by TGF-β1 signaling pathway, thereby reducing the expression of VEGF in lung tissue, inhibiting radiation-induced oxidative stress and inflammatory factor release in mouse lung tissue, and reducing the degree of RILI. These prospective experimental research results provide necessary experimental and theoretical basis for the application of 3-3'diindolemethane and its derivatives as new radiation protective drugs in clinical tumor radiotherapy.
Abstract: Objective: We studied the effect of 3–3'diindole methane (DIM) on acute radiation-induced lung injury (RILI) in mice and the possible underlying mechanism. Methods: A total of 45 mice were divided into five groups using the random number table method, namely, blank group, drug group alone (75 mg/kg DIM by peritoneal perfusion), simple irradiation g...
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Research Article
Mechanism Study of GanDouLing Mitigating Liver Fibrosis in Wilson’s Disease via Regulating the PI3K/AKT/mTOR Pathway to Activate Autophagy
Shao-Peng Huang,
Sen Chen,
Huan Wu,
An Zhou,
Huai-Zhou Jiang,
Hai Bian,
Yun-Lai Wang,
Zheng-Rong Zhang,
Yi-Kang Cai,
Hui Jiang,
Peng Wu
Issue:
Volume 11, Issue 4, July 2023
Pages:
73-85
Received:
27 September 2023
Accepted:
25 October 2023
Published:
30 October 2023
Abstract: The hepatic copper accumulation characteristic of Wilson's disease (WD) leads to activation of hepatic stellate cells, extracellular matrix deposition, and the progression to liver fibrosis (LF), with specific therapeutic interventions for this condition notably deficient. Increasing evidence suggests the potential utility of GanDouLing (GDL) in addressing WD-related LF. In this study, the pharmacological effects of GDL on WD and LF were assessed by establishing a copper-induced human hepatic stellate cell (LX-2) model and elucidating potential mechanisms underlying GDL treatment. The findings indicate that GDL treatment significantly attenuates the viability of copper-induced LX-2 cells and reduces the expression of fibrotic markers. This inhibitory effect is mediated through the PAM pathway, as it can be reversed by activators such as IGF-1 or MHY1485. Furthermore, GDL treatment downregulates critical components of the PAM pathway at both mRNA and protein levels. Molecular docking simulations further confirm the strong affinity and stable binding between active constituents of GDL, such as luteolin and vestitol, and their target proteins (AKT1, PIK3CA, mTOR). In copper-induced LX-2 cells, GDL treatment upregulates autophagic indicators, including LC3, Beclin-1, and AO, while downregulating p62. TEM experiments reveal that GDL treatment increases the presence of autophagosomes in copper-induced LX-2 cells, thereby ameliorating mitochondrial damage. In conclusion, GDL exerts its inhibitory effects on copper-induced LX-2 cell activation by downregulating the PAM pathway. These findings provide a novel approach for addressing LF related to WD and support the utilization of herbal-based supplements and alternative therapies.
Abstract: The hepatic copper accumulation characteristic of Wilson's disease (WD) leads to activation of hepatic stellate cells, extracellular matrix deposition, and the progression to liver fibrosis (LF), with specific therapeutic interventions for this condition notably deficient. Increasing evidence suggests the potential utility of GanDouLing (GDL) in ad...
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