Biodistribution of andrographolide to assess the interior-exterior relationship between the lung and intestine using microPET

Abstract

Background: One classic traditional Chinese medicine theory is that the "lung and intestine are exterior-interiorly related"; however, this has not been confirmed experimentally. The aim of this study was to provide a biological basis for the theory by measuring the tissue distribution of andrographolide.

Methods: Acute pneumonia was induced in a mouse model by repeated stimulation with lipopolysaccharide. The distribution of andrographolide in mice was observed by positron emission tomography (PET) imaging with [¹⁸ F]-labeled andrographolide, and changes in the in vivo distribution before and after modeling were compared. Subsequently, the consistency of pathological changes in lung and intestine was confirmed by observation of pathological sections. Finally, the results were verified by cytokine detection.

Results: The value of organ uptake, pathological changes and inflammatory factor expression of the lung and intestine were consistent. The concentration of andrographolide in the lung and intestine increased significantly, and was confirmed by pathology and enzyme-linked immunosorbent assays (ELISA).

Conclusions: Micro-positron emission tomography (microPET) can be used to visually observe the distribution of medicinal ingredients in vivo, and [¹⁸ F]-andrographolide can be used as a tool to assess the interior-exterior relationship between the lung and intestine.

Keywords: Andrographolide; enteritidis; interior-exterior relationship; pneumonia; positron emission tomography.

Figure 1

(a) The synthetic strategy of [¹⁸F]‐AG; (b) Quality control of [¹⁸F]‐AG.

Figure 2

Biodistribution of [¹⁸F]‐AG. (a) Organ uptake (expressed as a percentage of the injected dose) for [¹⁸F]‐AG over time in the control group. (b) Organ uptake (expressed as a percentage of the injected dose) for [¹⁸F]‐AG over time in the model group () Brain () Heart () Lung () Liver () Kidney () stomach () intestine () muscle. (c) Whole body biodistribution of [¹⁸F]‐AG over time.

Figure 3

The uptake in organs. (a) Confirmation of NF‐κB inhibition activity of F‐AG by the luciferase reporter assay system. Each bar represents the means ± SEM, n = 6 per group. ^** P < 0.01 versus control group; ^*** P < 0.005 versus control group. (b) Changes in the absolute value of each organ after modeling. () Control () Model. (c)The lung uptake in the control and model group. () Control () Model. (d) The intestine uptake in the control and model groups. () Control () Model.

Figure 4

Histopathological changes of the lung. (a) H&E staining of the lung in the control group. (b) H&E staining of the lung in the model group. (c) Statistics of the proportion of injured bronchi. (d) Statistics of the lung index. ^** P < 0.01 versus control group; ^*** P < 0.005 versus control group.

Figure 5

Histopathological changes of the intestine. (a) HE staining of the intestine in the control group. (b) HE staining of the intestine in the model group. (c) The permeation of EB into the gut wall from the lumen in the intestine after 120 minutes of exposure in the control and model groups. (d) Statistics of the proportion of injured intestinal villi. (e) Statistics of the thickness of the wall of the intestine. ^* P < 0.05 versus control group; ^*** P < 0.005 versus control group.

Figure 6

Assay of inflammatory factors in the lung and intestine. (a) Detection of inflammatory factors in the lung () Con () Mod. (b) Detection of inflammatory factors in the intestine. ^* P < 0.05 versus control group; ^** P < 0.01 versus control group; ^*** P < 0.005 versus control group.