Lysophosphatidic acid in medicinal herbs enhances prostaglandin E2 and protects against indomethacin-induced gastric cell damage in vivo and in vitro

Afroz, Sheuli; Yagi, Ayano; Fujikawa, Koki; Rahman, M Motiur; Morito, Katsuya; Fukuta, Tatsuya; Watanabe, Shiro; Kiyokage, Emi; Toida, Kazunori; Shimizu, Taro; Ishida, Tatsuhiro; Kogure, Kentaro; Tokumura, Akira; Tanaka, Tamotsu

doi:10.1016/j.prostaglandins.2018.01.003

Cited by 15 publications

(10 citation statements)

References 43 publications

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“…Our present data identify RP-1 as the highest potency specific nonlipid agonist of LPA 2 of the human and murine LPA 2 GPCR. The high potency and chemical structure of RP-1 make it a potential drug candidate for the treatment of conditions where LPA 2 activation has beneficial effects such as the prevention of apoptosis [40], prevention of stomach erosions caused by the NSAID family of drugs [42], attenuation of asthmatic reactions [43], and the inhibition of secretory diarrhea [44, 45].…”

Section: Discussionmentioning

confidence: 99%

The LPA2 receptor agonist Radioprotectin-1 spares Lgr5-positive intestinal stem cells from radiation injury in murine enteroids

Kuo

Szabó

Lee

et al. 2018

Cellular Signalling

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Rapidly proliferating cells are highly sensitive to ionizing radiation and can undergo apoptosis if the oxidative and genotoxic injury exceed the defensive and regenerative capacity of the cell. Our earlier work has established the antiapoptotic action of the growth factor-like lipid mediator lysophosphatidic acid (LPA). Activation of the LPA GPCR has been hypothesized to elicit antiapoptotic and regenerative actions of LPA. Based on this hypothesis we developed a novel nonlipid agonist of LPA, which we designated Radioprotectin-1 (RP-1). We tested RP-1 at the six murine LPA GPCR subtypes using the transforming growth factor alpha shedding assay and found that it had a 25 nM EC that is similar to that of LPA18:1 at 32 nM. RP-1 effectively reduced apoptosis induced by γ-irradiation and the radiomimetic drug Adriamycin only in cells that expressed LPA either endogenously or after transfection. RP-1 reduced γ-H2AX levels in irradiated mouse embryonic fibroblasts transduced with the human LPA GPCR but was ineffective in vector transduced MEF control cells and significantly increased clonogenic survival after γ-irradiation. γ-Irradiation induced the expression of lpar2 transcripts that was further enhanced by RP-1 exposure within 30 min after irradiation. RP-1 decreased the mortality of C57BL/6 mice in models of the hematopoietic and gastrointestinal acute radiation syndromes. Using Lgr5-EGFP-CreER;Tdtomato transgenic mice, we found that RP-1 increased the survival and growth of intestinal enteroids via the enhanced survival of Lgr5 intestinal stem cells. Taken together, our results suggest that the LPA-specific agonist RP-1 exerts its radioprotective and radiomitigative action through specific activation of the upregulated LPA GPCR in Lgr5 stem cells.

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Section: Discussionmentioning

confidence: 99%

The LPA2 receptor agonist Radioprotectin-1 spares Lgr5-positive intestinal stem cells from radiation injury in murine enteroids

Kuo

Szabó

Lee

et al. 2018

Cellular Signalling

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“…Therefore, the possible novel target for diarrhea therapy is the intestinal ion transporters. Some studies have reported that LPA, a form of phospholipids similar to growth factors, have been shown to prevent or restore gastrointestinal diseases, such as stomach ulcer and diarrhea in rats (Lin et al, 2010;Afroz et al, 2018). Diarrhea is caused by a decrease in the absorption of fluids and salts resulting from intestinal absorption and secretion disorders.…”

Section: Change Of Glycerophospholipid Metabolismmentioning

confidence: 99%

Pulsatilla Decoction Can Treat the Dampness-Heat Diarrhea Rat Model by Regulating Glycerinphospholipid Metabolism Based Lipidomics Approach

Hua

Ma²,

Zhang

et al. 2020

Front. Pharmacol.

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Ethnopharmacological Relevance: Diarrhea is a major medical problem in clinical practice. According to the theory of traditional Chinese medicine (TCM), different types of diarrhea should be treated with different TCM formulations based on the targeted medical condition. Dampness-heat diarrhea (DHD) is a serious diarrheal disease and Pulsatilla decoction (PD), a TCM, has been found effective against DHD. Objective: The aim of this study was to clarify the mechanism of action of PD in DHD using an untargeted lipidomics strategy. Materials and Methods: Wistar rats were randomized to four groups, including the control group, model group, PD groups and self-healing group. The PD groups were given a daily intragastric gavage of PD at doses of 3.76 g/kg. The rat model of DHD established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment, drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of DHD. Then the clinical symptoms and signs, blood routine, serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed to evaluate DHD model and therapeutic effect of PD. Lipid biomarkers of DHD were selected by comparing the control and model groups with the colon lipidomics technology and an ultra-high performance liquid chromatography (UHPLC) coupled with Q Exactive plus mass analyzer. Multivariate statistical analysis and pattern recognition were employed to examine different lipids within the colon of PD-treated rats. Results: The clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of DHD. After treatment with PD, the clinical symptoms and signs of the rats with DHD were improved; the indexes of blood routine and inflammatory cytokines levels tended to be normal. The lipidomics profile of the model group were

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“…LPA derived from cabbage leaves facilitated proliferation and motility of fibroblasts and gastric epithelial cells, which was inhibited by Ki16425 [101]. In addition, a number of studies have demonstrated the wound healing or anti-inflammatory effects of LPA derived from medicinal herbs [102,103,104,105]. On the other hand, oral administration of LPA to Apc Min mice, which are predisposed to intestinal adenoma formation due to a mutant allele of the Apc gene, increased the number of adenomas [36].…”

Section: Lpa1mentioning

confidence: 99%

Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer

Yun

2019

Cancers

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The intestinal epithelium interacts dynamically with the immune system to maintain its barrier function to protect the host, while performing the physiological roles in absorption of nutrients, electrolytes, water and minerals. The importance of lysophosphatidic acid (LPA) and its receptors in the gut has been progressively appreciated. LPA signaling modulates cell proliferation, invasion, adhesion, angiogenesis, and survival that can promote cancer growth and metastasis. These effects are equally important for the maintenance of the epithelial barrier in the gut, which forms the first line of defense against the milieu of potentially pathogenic stimuli. This review focuses on the LPA-mediated signaling that potentially contributes to inflammation and tumor formation in the gastrointestinal tract.

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Lysophosphatidic acid in medicinal herbs enhances prostaglandin E2 and protects against indomethacin-induced gastric cell damage in vivo and in vitro

Cited by 15 publications

References 43 publications

The LPA2 receptor agonist Radioprotectin-1 spares Lgr5-positive intestinal stem cells from radiation injury in murine enteroids

The LPA2 receptor agonist Radioprotectin-1 spares Lgr5-positive intestinal stem cells from radiation injury in murine enteroids

Pulsatilla Decoction Can Treat the Dampness-Heat Diarrhea Rat Model by Regulating Glycerinphospholipid Metabolism Based Lipidomics Approach

Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer

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