Fructus Gardeniae-induced gastrointestinal injury was associated with the inflammatory response mediated by the disturbance of vitamin B6, phenylalanine, arachidonic acid, taurine and hypotaurine metabolism

Zhou, Jing; Yao, Nan; Wang, Shuxia; An, Dongchen; Cao, Kangna; Wei, Jiali; Li, Ning; Zhao, Di; Wang, Lirui; Chen, Xijing; Lu, Yang

doi:10.1016/j.jep.2019.01.041

Cited by 38 publications

(22 citation statements)

References 38 publications

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“…Gardeniae fructus became cytotoxic to the cells at a lower concentration and steadily decreased the cell viability down to 60% viability at the highest concentration. A recent in vivo study reported that administering Gardeniae fructus at medium high and high concentration (equivalent to 10g/day/person and 20g/day/person) caused GI injury (worse in small intestine and colon than stomach), such as mucus, white cells, and red cells present in stool or inflammation in GI tract [15]. This finding correlates with our cell viability results of the colorectral cells treated with Gardeniae fructus.…”

Section: Discussionsupporting

confidence: 91%

“…Considering the potential intolerances that might be caused by this herb, the maximum concentration needs to be carefully identified. As the Chinese Pharmacopoeia (Edition 2015) states, the safe dose range of Gardeniae fructus is 6-10 g/day/person [15]. Currently, 0.05 g of extracted Gardeniae fructus (0.5 g of dry content) is used in one RCM-107 capsule, and the suggested daily dosage according to the Therapeutic Goods Administration (TGA) is two capsules, three times a day.…”

Section: Discussionmentioning

confidence: 99%

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The Effects of a Weight-Loss Herbal Formula RCM-107 and Its Eight Individual Ingredients on Glucagon-Like Peptide-1 Secretion—An In Vitro and In Silico Study

Luo

Gill

Feltis

et al. 2020

IJMS

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Obesity is a multifactorial disease that can lead to other health issues. Glucagon-like peptide-1(GLP-1), as one of the satiety signal, has been linked with appetite suppression and weight loss. Due to the limitations of GLP-1 and its analogues, alternative treatments such as herbal therapies have become popular. The herbal formula RCM-107 has demonstrated its inhibitory effects on lipid and carbohydrate absorption in our previous work. However, no published data described its effects on GLP-1 secretion. Therefore, this study aimed to determine the effects of RCM-107 and its individual ingredients on GLP-1 secretion via enzyme-linked immunosorbent assay (ELISA). Furthermore, molecular docking was performed to predict the key chemical compounds that are likely to be GLP-1 receptor agonists. Gardeniae fructus, one of the ingredients in RCM-107, demonstrated significantly greater effects on inducing GLP-1 secretion than the positive control epigallocatechin gallate (EGCG). Two Gardeniae fructus ligands, 3-epioleanolic acid and crocin were predicted to bind to the active form of GLP-1 receptor at the binding pocket with residues known for the receptor activation, suggesting that they could potentially serve as receptor agonists. Overall, this study reported the effects of researched herbs on GLP-1 secretion and proposed two compounds that may be responsible for antiobesity via GLP-1 receptor activation.Int. J. Mol. Sci. 2020, 21, 2854 2 of 13 hunger. It is known as an incretin hormone, secreted by enteroendocrine L cells in the gastrointestinal tract (GI) [5]. The amount of GLP-1 secretion is in response to calory intake. It can be stimulated by both fats and carbohydrates, while protein has only a minor impact [6]. The existing two major molecular forms of GLP-1 include GLP-1 (7-36) and GLP-1 (7-37), while the circulating active GLP-1 is mainly found in the form of GLP-1(7-36) [7].Reports showed that native GLP-1 has a very short half-life (less than 2 min) in vivo as a result of degradation by dipeptidyl peptidase-4 (DPP-4) in plasma [7,8]. Liraglutide, a stable GLP-1 analogue, was approved by FDA for treating obesity in 2014. It can suppress appetite and increase satiety by activating the GLP-1 receptor, which is located in the hypothalamus, gastrointestinal tract and pancreas. However, it is a daily injectable treatment that is also relatively high cost [6,9].Due to these limitations on GLP-1 and its analogues, cost-effective herbal supplements, including natural products, medicinal plant extracts and Chinese herbal medicine, are popular alternatives for weight reduction. Natural products such as epigallocatechin gallate (EGCG) [5], geniposide [10], berberine [11] and ginsenoside metabolite compound K [12] have been shown to stimulate GLP-1 secretion in in vitro experiments.In this paper, we have investigated the commercially available RCM-107 formula (Slimming Plus), a modification of our previously studied RCM-104 formula, which demonstrated significant effects on weight loss in clinical trials [13]. RCM-107 co...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

The Effects of a Weight-Loss Herbal Formula RCM-107 and Its Eight Individual Ingredients on Glucagon-Like Peptide-1 Secretion—An In Vitro and In Silico Study

Luo

Gill

Feltis

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…Studies have shown that VB6 participates in cellular and humoral immunity during the process of immune response. VB6 deficiency can cause a decline in immunity and affect the expression of certain inflammatory factors (IFN-γ, IL-8), and plays an important role in inflammation caused by gastrointestinal injury ( Zhou et al., 2019 ). As a multifactorial disease, gastrointestinal diseases is ultimately caused by the imbalance between acid secretion and cytoprotective factors.…”

Section: Discussionmentioning

confidence: 99%

UPLC-Q-TOF/MS-Based Serum and Urine Metabonomics Study on the Ameliorative Effects of Palmatine on Helicobacter pylori–Induced Chronic Atrophic Gastritis

et al. 2020

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Objective: The main objective of this study was to investigate the ameliorative effects of Palmatine (Pal) on Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG) Method: Body function, serum biochemical indicators and histopathology were used to evaluate the pharmacodynamics of Pal on CAG rats. The target genes expression levels were verified and assessed by RT-PCR and immunohistochemistry (IHC). Moreover, UPLC-Q-TOF/MS analysis based on urine and serum was performed to identify the potential metabolites in the pathological process of CAG induced by H. pylori. Metabolic pathway analysis was performed to elucidate the metabolic network associated with Pal treatment of CAG. Results: Pal (10, 20, 40 mg/kg/day) significantly restored the body function of CAG rats, reduced the serum biochemical indicators, and maintained the integrity of the gastric mucosal epithelial barrier while alleviated gastric histological damage. Metabolomics analysis shows that the therapeutic effect of Pal on CAG involves 10 metabolites and 10 metabolic pathways, of which the Taurine and hypotaurine metabolism, Glycerophospholipid metabolism and Pentose and glucuronate interconversions are closely related to the gastrointestinal protection of Pal, and these metabolic pathways crosstalk with each other due to the internet hub of citric acid cycle. Conclusions: Metabolomics was used for the first time to identify potential biomarkers of CAG and to illuminate the therapeutic mechanism of Pal on CAG induced by H. pylori. The results provided a new insight for further research on CAG treatment.

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“…Taurine is involved in multiple biological pathways and has a variety of pharmacological activities, such as eye and brain development, immune function, osmoregulation, as well as antioxidant and anti-in ammatory activities. Previous studies have shown that it is protective against oxidative stress-induced gastrointestinal injury [27]. Taurine is one of the most abundant free amino acids in animal tissues and plays an important role in a variety of important physiological processes.…”

Section: Discussionmentioning

confidence: 99%

A metabolomics-binding network pharmacology study of Zuojin Pill intervention in chronic atrophic gastritis induced by Helicobacter pylori

Wu¹,

Chen²,

Liu³

et al. 2020

Preprint

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Background Zuojin Pill (ZJP) is widely used for the treatment of gastrointestinal diseases, while its specific mechanism has not been systematically investigated. The aim of this study was to explore the mechanism of intervention of ZJP in chronic atrophic gastritis (CAG) through metabolomics combined with network pharmacology.Materials and methods Potential metabolites and possible pathways for ZJP treatment of CAG were explored using a UPLC-Q-TOF/MS-based metabolomics technique. The key targeting mechanism of ZJP for CAG was explored by combining the analysis with network pharmacology.Results ZJP significantly reduced serum levels of IL-1β, IL-6, IL-10 and iNOS, and improved pathological characteristics. Metabolomic results indicated that the therapeutic effect of ZJP was mainly related to ten metabolites, including choline, L-threonine, hydroxypyruvic acid, creatine, taurine, succinic acid, cis-aconitic acid, citric acid, succinic acid semialdehyde and uric acid. Pathway analysis showed that the treatment of CAG by ZJP was associated with taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, glycerophospholipid metabolism, citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism, butanoate metabolism and purine metabolism. Validation of potential metabolic markers and key targets of network pharmacology by RT-PCR analysis showed that ZJP significantly down-regulated a series of inflammatory markers, such as MAPK1, PKIA, RB1, SCN5A, RXRA, E2F1, PTGS1, IGF2, ADRB1, ADRA1B, PTGS2, and GABRA1.Conclusion For the first time, a combination of metabolomics and network pharmacology has been used to clarify the therapeutic effects of ZJP on CAG and its relationship to the regulation of multiple metabolic pathways.

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Fructus Gardeniae-induced gastrointestinal injury was associated with the inflammatory response mediated by the disturbance of vitamin B6, phenylalanine, arachidonic acid, taurine and hypotaurine metabolism

Cited by 38 publications

References 38 publications

The Effects of a Weight-Loss Herbal Formula RCM-107 and Its Eight Individual Ingredients on Glucagon-Like Peptide-1 Secretion—An In Vitro and In Silico Study

The Effects of a Weight-Loss Herbal Formula RCM-107 and Its Eight Individual Ingredients on Glucagon-Like Peptide-1 Secretion—An In Vitro and In Silico Study

UPLC-Q-TOF/MS-Based Serum and Urine Metabonomics Study on the Ameliorative Effects of Palmatine on Helicobacter pylori–Induced Chronic Atrophic Gastritis

A metabolomics-binding network pharmacology study of Zuojin Pill intervention in chronic atrophic gastritis induced by Helicobacter pylori

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