Beneficial Regulatory Effects of Polymethoxyflavone—Rich Fraction from Ougan (Citrus reticulata cv. Suavissima) Fruit on Gut Microbiota and Identification of Its Intestinal Metabolites in Mice

Abstract

Polymethoxyflavones (PMFs) are special flavonoids in citrus fruits that have been suggested to be beneficial to human health. However, whether PMFs in citrus fruit alter human gut microbiota is not well understood. The aim of the present study was to investigate the effects of PMF-rich fraction from Ougan (Citrus reticulata cv. Suavissima) on gut microbiota and evaluate the intestinal metabolic profile of PMFs in Institute of Cancer Research mice. The main components of the PMF-rich fraction were nobiletin, tangeretin, and 5-demethylnobiletin. The composition of the gut microbiota was analyzed using 16S ribosomal DNA sequencing. The results showed that after oral administration, the composition of mice gut microbiota was significantly altered. The relative abundance of two probiotics, Lactobacillus and Bifidobacterium, were found to increase significantly. A total of 21 metabolites of PMFs were detected in mice intestinal content by high performance liquid chromatography electrospray ionization tandem mass spectrometry, and they were generated through demethylation, demethoxylation, hydroxylation, and glucuronidation. Our results provided evidence that PMFs have potential beneficial regulatory effects on gut microbiota that in turn metabolize PMFs, which warrants further investigation in human clinical trials.

Physiological effects of tangeretin and heptamethoxyflavone on obese C57BL/6J mice fed a high‐fat diet and analyses of the metabolites originating from these two polymethoxylated flavones

“…Rapid advancements have been made in understanding the underlying biochemical modes of action of PMFs in combatting diabetes and obesity. New pathways may occur via the influences of these compounds on gut microbiota and their production of numerous diverse metabolites (Chen et al., 2020). In this current study, the effects of TAN and HMF added to a HFD were investigated in C57BL‐6J mice with pre‐existing obesity.…”

Enzymatic Metabolism of Flavonoids by Gut Microbiota and Its Impact on Gastrointestinal Cancer

“…A flavonoid abundantly found in the citrus peel of tangerine and in citrus fruits with a reported impact on the human gut microbiome composition [87]. The administration of polymethoxyflavones (PMFs) composed of nobiletin, tangeretin and 5-demethylnobiletin as main components, significantly increased the richness of the microbial community, but not the diversity, suggesting a possible interaction between PMFs and gut microbiota [88]. Lactobacillus and Bifidobacterium, two important probiotics, significantly increased after oral administration of PMFs, indicating their beneficial health effects.…”

Network Pharmacology-Based Validation of the Efficacy of Huiyangjiuji Decoction in the Treatment of Experimental Colitis

“…In the context of SI-NI decoction, the anti-inflammatory function has been emphasized by the addition of PGM (Jin et al, 2020), PB (Tian et al, 2020), SCF (Panossian & Wikman, 2008;Li et al, 2020;Li et al, 2021), PCW as well as CC (Csikos et al, 2020). Moreover, focusing on the impaired gastrointestinal functions, AMK is included to improve gastrointestinal motility (Zhu et al, 2018;Yang et al, 2019) and restore immune homeostasis (Xiang et al, 2020), while CR maintains homeostasis of the gut microbiota (Chen et al, 2020) and inhibits inflammation (Ho & Lin, 2008;Herath et al, 2016). Combining various anti-inflammatory herbs with gutfriendly components has offered a promising therapeutic alternative for gut diseases, especially for UC and UC-CRC.…”