Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study

Chen, Yingxuan; Gao, Qin-Yan; Zou, Tian-Hui; Wang, Bangmao; Liu, Side; Sheng, Jian-qiu; Ren, Jianlin; Zou, Xiaoping; Liu, Zhanju; Song, Yanyan; Xiao, Bing; Sun, Xiaomin; Dou, Xiaotan; Cao, Hailong; Yang, Xiao-Ning; Li, Na; Kang, Qian; Zhu, Wei; Xu, Hui; Chen, Huimin; Cao, Xiao-Chuang; Fang, Jing‐Yuan

doi:10.1016/s2468-1253(19)30409-1

Cited by 124 publications

(94 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several clinical and preclinical studies also demonstrate the ameliorative effect of berberine against several disorders including metabolic, neurological, cardiological, and gastrointestinal problems (7,8). Additionally, [9] conducted a double-blind, randomized, placebo-controlled clinical trial, and found that BBR at 0.3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma (9). Therefore, BBR is currently gaining more attention due to its promising therapeutic effects on colorectal cancer (CRC).…”

Section: Introductionmentioning

confidence: 95%

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis

Chen

Zhang

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

Berberine (BBR) has been reported that it has effects on inhibiting colorectal cancer (CRC). However, the mechanism of BBR on CRC also remains largely unknown. Herein, we investigated the therapeutic effects of BBR on CRC from the perspective of gut microbiota and metabolic alterations, which can provide a holistic view to understand the effects of BBR on CRC. First, azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse was used as CRC animal model, then the degree of colorectal carcinogenesis in AOM/DSS mice with or without BBR administration was measured. The composition and abundance of gut microbiota was investigated by using 16S rRNA. Meanwhile, feces samples were analyzed with 1 H NMR spectroscopy to investigate the metabolic alterations. As a result, BBR significantly reduced intestinal tumor development with lower macroscopic polyps and ki-67 expression of intestinal tissue, and better colonic morphology in mice. Moreover, BBR altered the composition of gut microbiota in AOM/DSS mice obviously, which were characterized by a decrease of Actinobacteria and Verrucomicrobia significantly at the phylum level. At the genus level, it was able to suppress pathogenic species, such as f_Erysipelotrichaceae, Alistipes, and elevate some short-chain fatty acids (SCFA)-producing bacteria, including Alloprevotella, Flavonifractor, and Oscillibacter. Metabolic data further revealed that BBR induced metabolic changes in feces focus on regulating glycometabolism, SCFA metabolism and amino acid metabolism, which also provides evidence for alteration of the microbiota because these feces metabolites are the products of interactions between the host and the microbial community. This study showed that BBR induced alterations in microbiota and metabolic in AOM/DSS mice, which might providing new insight into the inhibition effects of BBR on CRC.

show abstract

Section: Introductionmentioning

confidence: 95%

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis

Chen

Zhang

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Berberine, the major pharmacological component of the Chinese herb Coptis chinensis (Huang-Lian), has been used to treat bacterial diarrhea. Recently, berberine was also shown to be effective in the treatment of colorectal adenoma recurrence, metabolic disorders, and neuropsychiatric disorders [25][26][27]. Owing to its poor oral bioavailability, berberine has been shown to function via modulation of the gut microbiota [28,29].…”

Section: Introductionmentioning

confidence: 99%

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation

et al. 2021

View full text Add to dashboard Cite

Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota–gut–brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

show abstract

“…arginine, l-homoarginine and l-tryptophan metabolism have been revealed to exert an influence on metabolism and lipid metabolism, which may provide a new explanation for BBR's anti-inflammatory effects. BBr has already been approved for clinical therapy in china, and a recent large-scale double-blind clinical trial has reported that BBr is safe and effective to prevent colorectal cancer (75). However, BBr has not been approved by Fda since the mechanism underlying its anti-inflammatory activity remains poorly understood.…”

Section: Genes Involved In the Tlr4/nf-κb And Mapk/ap-1 Pathwaymentioning

confidence: 99%

Anti‑inflammatory mechanism of berberine on lipopolysaccharide‑induced IEC‑18 models based on comparative transcriptomics

Zhang

Zhao

et al. 2020

Mol Med Rep

View full text Add to dashboard Cite

intestinal surface epithelial cells (iecs) have long been considered as an effective barrier for maintaining water and electrolyte balance, and are involved in the mechanism of nutrient absorption. When intestinal inflammation occurs, it is often accompanied by iec malfunction. Berberine (BBr) is an isoquinoline alkaloid found in numerous types of medicinal plants, which has been clinically used in china to treat symptoms of gastrointestinal pathogenic bacterial infection, especially bacteria-induced diarrhea and inflammation. In the present study, iec-18 rat intestinal epithelial cells were treated with lipopolysaccharide (lPS) to establish an in vitro model of epithelial cell inflammation, and the cells were subsequently treated with BBR in order to elucidate the anti-inflammatory mechanism. Transcriptome data were then searched to find the differentially expressed genes (deGs) compared between two of the treatment groups (namely, the lPS and lPS+BBr groups), and deGs were analyzed using Gene ontology, Kyoto encyclopedia of Genes and Genomes, Weighted Gene correlation network analysis and interactive Pathways explorer to identify the functions and pathways enriched with deGs. Finally, reverse transcription-quantitative Pcr was used to verify the transcriptome data. These experiments revealed that, comparing between the lPS and lPS+BBr groups, the functions and pathways enriched in deGs were 'dna replication', 'cell cycle', 'apoptosis', 'leukocyte migration' and the 'nF-κB and aP-1 pathways'. The results revealed that BBr is able to restrict dna replication, inhibit the cell cycle and promote apoptosis. it can also inhibit the classic inflammatory pathways, such as those mediated by NF-κB and aP-1, and the expression of various chemokines to prevent the migration of leukocytes. according to transcriptomic data, BBR can exert its anti-inflammatory effects by regulating a variety of cellular physiological activities, including cell cycle, apoptosis, inflammatory pathways and leukocyte migration.

show abstract

Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study

Cited by 124 publications

References 32 publications

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation

Anti‑inflammatory mechanism of berberine on lipopolysaccharide‑induced IEC‑18 models based on comparative transcriptomics

Contact Info

Product

Resources

About