Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora

Yan, Shihai; Chang, Jiayin; Hao, Xuehui; Liu, Jiang; Tan, Xiying; Geng, Zhirong; Wang, Zhilin

doi:10.1016/j.phymed.2022.154217

Cited by 65 publications

(40 citation statements)

References 35 publications

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“…Alloprevotella genus (belonging to Bacteroidetes phylum) was known to produce short-chain fatty acids, which play an important role in maintaining intestinal health. 34 P70 could obviously retrieve its abundance in UC mice (Figure 5E,F). Lactobacillus (Firmicutes phylum) was widely considered as an important intestinal probiotic, which can preserve the tight junction structure and intestinal permeability by inhibiting the release of the proinflammatory factor TNF-α.…”

Section: ■ Discussionmentioning

confidence: 93%

“…In this study, DSS led to the decrease in the relative abundance of Bacteroidetes in mice, whereas P70 reversed this change. Alloprevotella genus (belonging to Bacteroidetes phylum) was known to produce short-chain fatty acids, which play an important role in maintaining intestinal health . P70 could obviously retrieve its abundance in UC mice (Figure E,F).…”

Section: Discussionmentioning

confidence: 99%

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Discovery, Preliminary Structure–Activity Relationship, and Evaluation of Oleanane-Type Saponins from Pulsatilla chinensis for the Treatment of Ulcerative Colitis

Zhang

et al. 2023

J. Med. Chem.

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To discover ulcerative colitis (UC) treatment agents, 28 oleanane-type triterpenoid saponins (1–28) including three new saponins, pulsatillosides P-R (1–3), were isolated from Pulsatilla chinensis. The isolated saponins could observably ameliorate UC by improving the intestinal epithelial cell barrier and intestinal flora in vivo. The structure–activity relationship indicated that the oligosaccharide chain at C-28 was essential for their anti-UC activities; the methyl group at the C-23 site of triterpene saponins showed important effects on anti-UC efficacy; the chain length of oligosaccharides at position C-28 had little effect on their anti-UC activities. In vivo investigation of representative saponins 1 and 13 further confirmed that 23-methyl-3,28-bisdesmosidic oleanane-type saponins inhibited the TNFα-NFκB-MLCK axis to improve the intestinal epithelial cell barrier of the colon in UC mice. These findings revealed the potential of 23-methyl-3,28-bisdesmosidic oleanane-type saponins from P. chinensis as promising candidates for the treatment of UC.

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Section: ■ Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Discovery, Preliminary Structure–Activity Relationship, and Evaluation of Oleanane-Type Saponins from Pulsatilla chinensis for the Treatment of Ulcerative Colitis

Zhang

et al. 2023

J. Med. Chem.

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“…Berberine, an isoquinoline alkaloid, has multiple pharmacological effects, including its purported antioxidant and antimicrobial properties for a series of diseases, such as obesity [ 25 ], diabetes [ 26 ], hyperlipidemia [ 27 ], heart failure [ 14 ], H. pylori infection [ 28 ], and colonic adenoma prevention [ 29 ]. Numerous hypotheses about the ways in which berberine may help with Alzheimer’s disease also have been raised, including retarding oxidative stress and neuroinflammation [ 13 , 30 ], limiting the pathogenesis of extracellular amyloid plaques and intracellular neurofibrillary tangles [ 13 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Berberine Rescues D-Ribose-Induced Alzheimer‘s Pathology via Promoting Mitophagy

Wang

Zou

et al. 2023

IJMS

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Mitochondrial dysfunction is considered an early event of Alzheimer disease (AD). D-ribose is a natural monosaccharide that exists in cells, especially in mitochondria, and can lead to cognitive dysfunction. However, the reason for this is unclear. Berberine (BBR) is an isoquinoline alkaloid that can target mitochondria and has great prospect in the treatment of AD. The methylation of PINK1 reinforces the burden of Alzheimer’s pathology. This study explores the role of BBR and D-ribose in the mitophagy and cognitive function of AD related to DNA methylation. APP/PS1 mice and N2a cells were treated with D-ribose, BBR, and mitophagy inhibitor Mdivi-1 to observe their effects on mitochondrial morphology, mitophagy, neuron histology, AD pathology, animal behavior, and PINK1 methylation. The results showed that D-ribose induced mitochondrial dysfunction, mitophagy damage, and cognitive impairment. However, BBR inhibition of PINK1 promoter methylation can reverse the above effects caused by D-ribose, improve mitochondrial function, and restore mitophagy through the PINK1–Parkin pathway, thus reducing cognitive deficits and the burden of AD pathology. This experiment puts a new light on the mechanism of action of D-ribose in cognitive impairment and reveals new insights in the use of BBR for AD treatment.

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“…Therefore, the change degree of intestinal microbiota diversity may be one of the differences between A/FA and western medicine 5-ASA. On the other hand, it is well established that diet can intervene in the immune system by regulating the gut microbiota composition and metabolites such as SCFAs, indoles and bile acids ( 56 ). Not surprisingly, FA displayed excellent prebiotic properties, including inhibiting the proliferation of conditioned pathogenic bacteria and promoting the growth of beneficial bacteria.…”

Section: Discussionmentioning

confidence: 99%

Fermented Astragalus and its metabolites regulate inflammatory status and gut microbiota to repair intestinal barrier damage in dextran sulfate sodium-induced ulcerative colitis

et al. 2022

Front. Nutr.

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Fermentation represents an efficient biotechnological approach to increase the nutritional and functional potential of traditional Chinese medicine. In this study, Lactobacillus plantarum was used to ferment traditional Chinese medicine Astragalus, the differential metabolites in the fermented Astragalus (FA) were identified by ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS), and the ameliorating effect of FA on dextran sulfate sodium (DSS)-induced colitis in mice were further explored. The results showed that 11 differential metabolites such as raffinose, progesterone and uridine were identified in FA, which may help improve the ability of FA to alleviate colitis. Prophylactic FA supplementation effectively improved DAI score, colon length and histopathological lesion in DSS-treated mice. The abnormal activation of the intestinal immune barrier in mice was controlled after FA supplementation, the contents of myeloperoxidase (MPO) and IgE were reduced and the contents of IgA were increased. The intestinal pro-inflammatory factors TNF-α, IL-1β, IL-6, and IL-17 were down-regulated and the anti-inflammatory factors IL-10 and TGF-β were up-regulated, suggesting that FA can intervene in inflammatory status by regulating the balance of Th1/Th2/Th17/Treg related cytokines. In addition, FA supplementation modified the structure of the intestinal microbiota and enriched the abundance of Akkermansia and Alistipes, which were positively associated with the production of short-chain fatty acids. These microbes and their metabolites induced by FA also be involved in maintaining the intestinal mucosal barrier integrity by affecting mucosal immunity. We observed that intestinal tight junction protein and mucous secreting protein ZO-1, occludin, and MUC2 genes expression were more pronounced in mice supplemented with FA compared to unfermented Astragalus, along with modulation of intestinal epithelial cells (IECs) apoptosis, verifying the intestinal mucosal barrier repaired by FA. This study is the first to suggest that FA as a potential modulator can more effectively regulate the inflammatory status and gut microbiota to repair the intestinal barrier damage caused by colitis.

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Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora

Cited by 65 publications

References 35 publications

Discovery, Preliminary Structure–Activity Relationship, and Evaluation of Oleanane-Type Saponins from Pulsatilla chinensis for the Treatment of Ulcerative Colitis

Discovery, Preliminary Structure–Activity Relationship, and Evaluation of Oleanane-Type Saponins from Pulsatilla chinensis for the Treatment of Ulcerative Colitis

Berberine Rescues D-Ribose-Induced Alzheimer‘s Pathology via Promoting Mitophagy

Fermented Astragalus and its metabolites regulate inflammatory status and gut microbiota to repair intestinal barrier damage in dextran sulfate sodium-induced ulcerative colitis

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