Effects of Microbial Metabolites of (−)-Epigallocatechin Gallate on Glucose Uptake in L6 Skeletal Muscle Cell and Glucose Tolerance in ICR Mice

Takagaki, Akiko; Yoshioka, Yasukiyo; Yamashita, Yoko; Nagano, Tomoya; Ikeda, Masaki; Hara-Terawaki, Aya; Seto, Ryota; Ashida, Hitoshi

doi:10.1248/bpb.b18-00612

Cited by 27 publications

(12 citation statements)

References 39 publications

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“…Modifying effects of EGCG on gut microbiota has been proposed as one of the potential mechanisms of anti-obesity activity of EGCG [ 26 ]. Moreover, recent studies have demonstrated that several microbial metabolites of EGCG generated in the gastrointestinal tract are absorbed into the systemic circulation [ 27 , 28 ] and effectively improve insulin sensitivity and glucose tolerance in rodent models [ 29 ]. Although we did not examine the levels of the metabolites in plasma or tissues, we speculated that the microbial metabolites of EGCG might contribute to the anti-obesity effects of EGCG treatment.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-Gallate Reduces Visceral Adiposity Partly through the Regulation of Beclin1-Dependent Autophagy in White Adipose Tissues

et al. 2020

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Epigallocatechin-3-gallate (EGCG) is a primary bioactive phytochemical in green tea. Its therapeutic potential in metabolic diseases has been reported; however, the molecular mechanisms of the anti-obesity effect of EGCG have not been fully elucidated. In this study, we examined the effects of EGCG on lipid metabolism and autophagy in adipose tissue. After 8 weeks of high-fat diet feeding, mice were treated with EGCG (20 mg/kg/day) for 2 weeks to test in vivo anti-obesity effects of EGCG. EGCG treatment improved glucose tolerance and caused body weight loss. Interestingly, reduced adipose tissue mass was more prominent in visceral compared to subcutaneous white adipose tissue. Mechanistically, EGCG treatment increased autophagic flux in white adipose tissue through the AMP-activated protein kinase-mediated signaling pathway. Adipocyte-specific knockout of Beclin1 mitigated the effects of EGCG on visceral adipose tissue mass and glucose tolerance, indicating that the anti-obesity effect of EGCG requires Beclin1-dependent autophagy. Collectively, our data demonstrated that EGCG has anti-obesity effects through the upregulation of Beclin1-dependent autophagy and lipid catabolism in white adipose tissue (WAT).

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Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-Gallate Reduces Visceral Adiposity Partly through the Regulation of Beclin1-Dependent Autophagy in White Adipose Tissues

et al. 2020

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“…In the large intestine, there are 11 colonic microbial ring-fission metabolites of EGC (EGC-M1–M11) (Table 1, Figure 1) as described by Takagaki et al, i.e. 1-(3,4,5-trihydroxyphenyl) 3-(2,4,6-trihydroxyphenyl)-propan-2-ol (EGC-M1), 4-dehydroxylated epigallocatechin (EGC-M2), 1-(3,5-dihydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)-propan-2-ol (EGC-M3), 4-hydroxy-5-(3,5-dihydroxyphenyl) valeric acid (EGC-M4), 5-(3,5-dihydroxyphenyl)-γ-valerolactone (EGC-M5), 4-hydroxy-5-(3,4,5-trihydroxyphenyl) valeric acid (EGC-M6), 5-(3,4,5-trihydroxyphenyl)-γ-valerolactone (EGC-M7), 3-(3,5-dihydroxyphenyl) propionic acid (EGC-M8), 5-(3,5-dihydroxyphenyl) valeric acid (EGC-M9), 5-(3,4,5-trihydroxyphenyl) valeric acid (EGC-M10), and 5-(3-hydroxyphenyl) valeric acid (EGC-M11) [39,40,41]. Among them, EGC-M5 and EGC-M7 were found to be the main metabolites in mice, rat, and human plasma, urine, and bile [42].…”

Section: Bioactivity Of Egcg and Its Metabolites In The Brainmentioning

confidence: 99%

“…There was a significant decrease in SBP 2 h after administration (150 mg/kg) of EGC-M7 and 4 h after administration (200 mg/kg) of EGC-M5, compared to the control group [67]. More recently, EGCG microbial metabolites were found to have antidiabetic effects in vitro and in vivo [41]. Glucose uptake ability of EGCG metabolites was measured with differentiated rat L6 myoblast cells by using 2-deoxyglucose.…”

Section: Bioactivity Of Catechin Ring-fission Metabolitesmentioning

confidence: 99%

Function of Green Tea Catechins in the Brain: Epigallocatechin Gallate and its Metabolites

Pervin

Unno

Takagaki³

et al. 2019

IJMS

Self Cite

158

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Over the last three decades, green tea has been studied for its beneficial effects, including anti-cancer, anti-obesity, anti-diabetes, anti-inflammatory, and neuroprotective effects. At present, a number of studies that have employed animal, human and cell cultures support the potential neuroprotective effects of green tea catechins against neurological disorders. However, the concentration of (−)-epigallocatechin gallate (EGCG) in systemic circulation is very low and EGCG disappears within several hours. EGCG undergoes microbial degradation in the small intestine and later in the large intestine, resulting in the formation of various microbial ring-fission metabolites which are detectable in the plasma and urine as free and conjugated forms. Recently, in vitro experiments suggested that EGCG and its metabolites could reach the brain parenchyma through the blood–brain barrier and induce neuritogenesis. These results suggest that metabolites of EGCG may play an important role, alongside the beneficial activities of EGCG, in reducing neurodegenerative diseases. In this review, we discuss the function of EGCG and its microbial ring-fission metabolites in the brain in suppressing brain dysfunction. Other possible actions of EGCG metabolites will also be discussed.

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“…Some inhibitory compounds bind to and result in the structural alteration of α‐glucosidase (Fang et al., ; Liu, Zhang, Wei, & Lin, ). Furthermore, one flavonoid, epigallocatechin gallate, suppresses glucose uptake in skeletal muscle cells and shows glucose tolerance in mice (Takagaki et al., ); thus, catechin‐like compounds may also affect glucose uptake. Based on these results, we hypothesize that C7G and E7G inhibit α‐amylase and α‐glucosidase activity through direct binding.…”

Section: Resultsmentioning

confidence: 99%

Isolation and Characterization of Antihyperglycemic Compounds from Vigna angularis Extracts

Kuriya

Nishio

Ono

et al. 2019

Journal of Food Science

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Functional foods that inhibit α‐amylase and α‐glucosidase activity are effective for regulating the blood glucose level and preventing hyperglycemia. Extracts of adzuki beans (ABs, Vigna angularis), widely eaten in East Asia, can inhibit α‐amylase and α‐glucosidase activity. In this study, we identified and evaluated the components in an AB water extract (ABWE) after boiling, which is an essential process for cooking ABs. The ABWE before boiling inhibited α‐amylase and α‐glucosidase activity and the boiled ABWE showed slightly stronger inhibitory effects. High‐performance liquid chromatography, liquid chromatography‐mass spectrometry, and nuclear magnetic resonance analyses identified (+)‐catechin 7‐O‐β‐d‐glucopyranoside (C7G), (+)‐epicatechin 7‐O‐β‐d‐glucopyranoside (E7G), and (+)‐catechin as the bioactive components in boiled ABWE. Interestingly, the quantity of E7G significantly increased after boiling (from 0% to 17.1 ± 1.3%). E7G showed stronger inhibition of α‐amylase and α‐glucosidase than C7G; the IC50 values for α‐amylase were 0.74 ± 0.04 mg/mL (C7G) and 0.40 ± 0.09 mg/mL (E7G), and for α‐glucosidase the IC50 values were 0.085 ± 0.032 mg/mL (C7G) and 0.051 ± 0.007 mg/mL (E7G). Our findings suggest that C7G and E7G are the main active components in ABWE as they inhibit α‐amylase and α‐glucosidase and their inhibitory effect is not lost after boiling. These results support the effectiveness of boiled ABs in the promotion of health. Practical Application We identified (+)‐catechin 7‐O‐β‐d‐glucopyranoside (C7G), (+)‐epicatechin 7‐O‐β‐d‐glucopyranoside (E7G), and (+)‐catechin in adzuki bean extracts and commercially available boiled adzuki bean products. Interestingly, the E7G content was increased by boiling, and this compound showed strong inhibitory activity toward α‐amylase and α‐glucosidase. These results support the consumption of boiled adzuki beans to prevent acute rises in blood glucose level.

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Effects of Microbial Metabolites of (−)-Epigallocatechin Gallate on Glucose Uptake in L6 Skeletal Muscle Cell and Glucose Tolerance in ICR Mice

Cited by 27 publications

References 39 publications

Epigallocatechin-3-Gallate Reduces Visceral Adiposity Partly through the Regulation of Beclin1-Dependent Autophagy in White Adipose Tissues

Epigallocatechin-3-Gallate Reduces Visceral Adiposity Partly through the Regulation of Beclin1-Dependent Autophagy in White Adipose Tissues

Function of Green Tea Catechins in the Brain: Epigallocatechin Gallate and its Metabolites

Isolation and Characterization of Antihyperglycemic Compounds from Vigna angularis Extracts

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