Betulinic acid attenuates cyclophosphamide-induced intestinal mucosa injury by inhibiting the NF-κB/MAPK signalling pathways and activating the Nrf2 signalling pathway

Ou, Zhaoping; Zhu, Lijuan; Huang, Cheng‐Long; Ma, Chaoyang; Kong, Li; Lin, Xiaobo; Gao, Xinyu; Huang, Lin; Wen, Lixin; Liang, Zengenni; Yuan, Zhihang; Wu, Jing; Yi, Jine

doi:10.1016/j.ecoenv.2021.112746

Cited by 25 publications

(18 citation statements)

References 53 publications

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“…In the mouse study, NMN supplementation significantly enhanced the jejunal gene expression of Nrf2, HO-1, GCLC and SOD2 which are mainly involved in the antioxidant defense system and downstream regulation of the intestinal barrier function. 25,26 To verify this, the SASP of D-gal induced IPEC-J2 cells was primarily evaluated as shown in Fig. 6.…”

Section: 6mentioning

confidence: 99%

Nicotinamide mononucleotide supplementation protects the intestinal function in aging mice and d-galactose induced senescent cells

Wang

Zhai

et al. 2022

Food Funct.

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Section: 6mentioning

confidence: 99%

Nicotinamide mononucleotide supplementation protects the intestinal function in aging mice and d-galactose induced senescent cells

Wang

Zhai

et al. 2022

Food Funct.

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“…The morphological changes were estimated by hematoxylin and eosin (H&E) staining according to previous studies. 26,27 In brief, the liver tissues were dehydrated and embedded after fixing with 4% paraformaldehyde. All samples were cut into slices with a thickness of 5 μm, stained with H&E (Servicebio Co. Ltd, Wuhan, China), and the morphological changes were observed under an optical microscope (Olympus, Tokyo, Japan) using an image capturing software (Nikon Eclipse Ci, Tokyo, Japan).…”

Section: Observation Of Morphological and Ultrastructural Changes In ...mentioning

confidence: 99%

“…Hepatic apoptosis was estimated using the TUNEL assay according to previous studies. 14,27 The liver samples were fixed, embedded, and cut into 3 µm slices. The sections were stained using the TUNEL kit, and the TUNEL-positive cells were stained green.…”

Section: Detection Of Hepatic Apoptosis By the Tunel Assaymentioning

confidence: 99%

Suppression of endoplasmic reticulum stress-associated pathways and hepatocyte apoptosis participates in the attenuation of betulinic acid on alcohol-provoked liver injury in mice

Kong

et al. 2022

Food Funct.

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“…Our results are consistent with previous reports that cell viability was reduced in a dose-dependent manner, tight junction proteins were down-regulated in a time-dependent manner, and apoptosis was increased in intestinal tissues or Caco-2 cells treated with MPA. Furthermore, DAO and ET, which are indicators of intestinal barrier permeability, are released into the bloodstream at a higher rate when the intestine is damaged [ 20 ]. MPA treatment was found to significantly increase the levels of DAO and ET in mouse serum, indicating that MPA induced the impairment of intestinal barrier function.…”

Section: Discussionmentioning

confidence: 99%

Mycophenolic Acid Induces the Intestinal Epithelial Barrier Damage through Mitochondrial ROS

Deng

Zhang

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Mycophenolic acid (MPA) may cause gastrointestinal adverse effects by damaging the intestinal epithelial barrier, the underlying mechanisms remain elusive. Studies have demonstrated that oxidative stress caused by reactive oxygen species (ROS) is linked to tight junction (TJ) proteins and apoptosis, both of which cause abnormalities in intestinal barrier function. Mitochondria, one of the main sources of ROS and abnormally high levels of ROS are linked to mitochondrial dysfunction. The aim of this study was to investigate whether MPA induces intestinal barrier dysfunction through regulation of the mitochondrial ROS. MPA-induced intestinal injury model in Kunming mice and Caco-2 cells. The effect of MPA on Caco-2 cell viability was measured by MTT; tissue diamine oxidase and endotoxin expression were determined by ELISA; expression of total proteins of ZO-1, occludin, Bax, Bcl-2, and mitochondrial proteins of Cytochrome C and Bax was measured by Western blot; and the localization of Cytochrome C with MitoTraker was observed by immunofluorescence staining. Caco-2 cell apoptosis, ROS levels, and mitochondrial membrane potential were detected by flow cytometry, while intramitochondrial ROS levels were observed by MitoSOX fluorescence staining. The results showed that MPA increased intracellular and mitochondrial ROS production to promote oxidative stress and the antioxidant NAC effectively restored ZO-1 and occludin expressions, reduced apoptosis in intestinal epithelial cells. Furthermore, we found that low concentrations of MPA caused mitochondrial damage, induced hyperpolarization of the mitochondrial membrane potential and the translocation of Cytochrome C and Bax proteins from the cytoplasm to the mitochondria. The mitochondrial protectant SS-31 reduces intracellular and intramitochondrial ROS, upregulates TJ, and reduces apoptosis. Our studies suggest that MPA-induced intestinal barrier dysfunction in vivo and in vitro is mediated, at least in part, by impairing mitochondrial function and promoting oxidative stress.

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Betulinic acid attenuates cyclophosphamide-induced intestinal mucosa injury by inhibiting the NF-κB/MAPK signalling pathways and activating the Nrf2 signalling pathway

Cited by 25 publications

References 53 publications

Nicotinamide mononucleotide supplementation protects the intestinal function in aging mice and d-galactose induced senescent cells

Nicotinamide mononucleotide supplementation protects the intestinal function in aging mice and d-galactose induced senescent cells

Suppression of endoplasmic reticulum stress-associated pathways and hepatocyte apoptosis participates in the attenuation of betulinic acid on alcohol-provoked liver injury in mice

Mycophenolic Acid Induces the Intestinal Epithelial Barrier Damage through Mitochondrial ROS

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