Protective mechanism of punicalagin against endoplasmic reticulum stress in the liver of mice with type 2 diabetes mellitus

Mo, Fangfang; Lv, Bohan; An, Tian; Miao, Jianan; Liu, Jia-Xian; Zhang, Jing; Zhang, Zhiyong; Ma, Meng-Hua; Yang, Xiuyan; Zhao, Dandan; Zhang, Dongwei; S, Gao; Jiang, Guiyan

doi:10.1016/j.jff.2019.03.006

Cited by 17 publications

(14 citation statements)

References 30 publications

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“…RA treatment alleviated weight loss, and abnormal food and water intake, suggesting that it could help improve the physical states of T2D rats. Effective control of the blood glucose level is a key step in preventing or reversing diabetic complications and improving the quality of life in T2D patients [22]. RA treatment resulted in a significant decrease in GLU, INS and HbAc1 level, and insulin resistance according to the HOMA-IR index, OGTT and ITT, indicating its significant hypoglycemic activity.…”

Section: Discussionmentioning

confidence: 99%

Rotundic Acid Protects against Metabolic Disturbance and Improves Gut Microbiota in Type 2 Diabetes Rats

Yan

Yao

et al. 2019

Nutrients

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Rotundic acid (RA) is a major triterpene constituent in the barks of Ilex rotunda Thunb, which have been widely used to make herbal tea for health care in southern China. RA has a variety of bioactivities such as anti-inflammation and lipid-lowering effect. However, little is known about the effects and mechanisms of RA on metabolic disturbance in type 2 diabetes (T2D) and its effect on gut microbiota. A T2D rat model induced by high fat diet (HFD) feeding and low-dose streptozotocin (STZ) injection was employed and RA showed multipronged effects on T2D and its complications, including improving glucolipid metabolism, lowering blood pressure, protecting against cardiovascular and hepatorenal injuries, and alleviating oxidative stress and inflammation. Furthermore, 16s rRNA gene sequencing was carried out on an Illumina HiSeq 2500 platform and RA treatment could restore the gut microbial dysbiosis in T2D rats to a certain extent. RA treatment significantly enhanced the richness and diversity of gut microbiota. At the genus level, beneficial or commensal bacteria Prevotella, Ruminococcus, Leuconostoc and Streptococcus were significantly increased by RA treatment, while RA-treated rats had a lower abundance of opportunistic pathogen Klebsiella and Proteus. Spearman’s correlation analysis showed that the abundances of these bacteria were strongly correlated with various biochemical parameters, suggesting that the improvement of gut microbiota might help to prevent or attenuate T2D and its complication. In conclusion, our findings support RA as a nutraceutical agent or plant foods rich in this compound might be helpful for the alleviation of T2D and its complications through improving gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Rotundic Acid Protects against Metabolic Disturbance and Improves Gut Microbiota in Type 2 Diabetes Rats

Yan

Yao

et al. 2019

Nutrients

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“…Increased expression of GRP78 and CHOP proteins are two important markers of ERS (Kratochvílová et al, 2016). Activation of PERK can phosphorylate eIF2a and phosphorylation of eIF2a can reduce the transcription and translation of cells, thereby reducing protein production (Mo et al, 2019). Therefore, activation of the PERK/p-eIF2a pathway can reduce protein synthesis in the ER and regulate endoplasmic reticulum homeostasis to reduce stress in the ER.…”

Section: Discussionmentioning

confidence: 99%

Effects of Lycium barbarum Polysaccharide on Endoplasmic Reticulum Stress and Oxidative Stress in Obese Mice

et al. 2020

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Background: The incidence of obesity-associated decline in male fertility has increased over the years. Lycium barbarum polysaccharide (LBP), a natural plant polysaccharide extracted from the Chinese herb L. barbarum has shown promising therapeutic effects in overcoming the same.Aim: This study aimed to investigate the protective effect of LBP on the testes of obese mice.Methods: Following administration of LBP to high-fat diet-induced obese mice for 35 days, serum, sperm, and testis samples were obtained for subsequent experiments. Biochemical analysis and sex hormone content determination were performed to observe changes in glycolipid metabolism and testosterone levels, respectively, in the blood. Hematoxylin and eosin staining were carried out to assess the pathological changes in the testicular tissue. Oxidative stress levels were detected using enzyme-linked immunosorbent assay and expression levels of endoplasmic reticulum stress markers were determined using western blot in the testicular tissue.Results: Our results suggested that LBP reduced glucose levels and insulin resistance, increased testosterone levels and insulin sensitivity, and decreased testicular oxidative stress and pathological damage in obese mice. In addition, LBP down-regulated the expression of p-eIF2a, GRP78, and CHOP in the testicular tissues of obese mice. Conclusion:Our results show that LBP is a potential novel drug for preventing male infertility caused by obesity.

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“…intraperitoneal for 4 weeks; Althunibat et al, 2010). Antioxidant action was found to be mediated via multiple mechanisms, including upregulation of antioxidant enzymes activities, that is, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and (glutathione reductase) GR, concurrent with the reduction of malondialdehyde (MDA) levels (Althunibat et al, 2010) and lipid peroxidation (Al-Gubory et al, 2016) as depicted in Table 1 and Figure Colombo et al, 2013;Cooper et al, 2018;Dey et al, 2015;Howell & D'Souza, 2013;Naseri et al, 2018) Anti-osteoporosis Punicalagin ↑Osteoblastic activity, ↑Calcium deposition ↑ALP, collagen 1a1 and 2a1, BSP, osteocalcin, OPG, DDR2, β-catenin, and LRP5 ↓Osteoclast differentiation ↓Bone resorption ↓NFATc1expression ↓Akt-and JNK dependent pathways ↓Inflammation and oxidative stress (Iwatake et al, 2015;Mélanie Spilmont et al, 2014;Mélanie Spilmont et al, 2015) Effect on lipid metabolism and obesity prevention Ellagic acid, punicalagin, urolithin A, anthocyanins ↓Serum TG, cholesterol, LDL ↓Lipase, FAS ↑LXRα, PPARα, PPARγ, ABCA1 (Wu et al, 2013;Fabroni et al, 2016;Les et al, 2018;Lv et al, 2016;Liu et al, 2015) Antidiabetic Punicalagin, ellagic acid, gallic acid, and valoneic acid dilactone ↓α-Glucosidase, α-amylase, recombinant human maltase-glucoamylase ↑Insulin sensitivity (Al-Muammar & Khan, 2012;Mo et al, 2019;Jain et al, 2012;Kam et al, 2013;Nankar & Doble, 2015) Anti-atherosclerosis Ellagic acid, punicalagin, punicalin, and gallic acid ↓Ox-LDL internalization, foam cell formation, platelet aggregation ↑ABCA1 and LXRα (Hou et al, 2019;Lutz et al, 2019;Park et al, 2011;Zhao et al, 2016) Hepatoprotective Polysaccharides, punicalagin, ellagic acid ↓Liver fibrosis (↓TGF-β1, collagen synthesis) ↑ LXLα ↑ABCA1 ↑PPAR-γ ↑Nrf2-ARE pathway ↓Oxidative stress ↓ Inflammation ↓NFκB pathway ↓Apoptosis ↑Bcl-2…”

Section: Antioxidant Activitymentioning

confidence: 99%

“…Many studies have proved the anti-hyperglycemic and antidiabetic effects of PPE and its main bioactive constituents such as punicalagin (Mo et al, 2019), ellagic acid (Nankar & Doble, 2015), gallic acid (Kam et al, 2013), and valoneic acid dilactone (Jain et al, 2012).…”

Section: Antidiabeticmentioning

confidence: 99%

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Ongoing and potential novel trends of pomegranate fruit peel; a comprehensive review of its health benefits and future perspectives as nutraceutical

Fahmy

Farag

2021

Journal of Food Biochemistry

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Pomegranate is an ancient shrub, globally distributed nowadays. It has been used in the middle east as a medicinal food and traditional medicine for thousands of years.Pomegranate peel (PP) constitutes about 50% of the total fruit, however, it has been previously regarded as a waste. Recent research points to PP as a rich source of phenolics (e.g., ellagitannins, flavonoids, and anthocyanins), polysaccharides, in addition to its biotransformed metabolites viz. urolithins making it a valuable waste with promising pharmacological actions.Compared to the pulp and the juice, PP exhibited stronger antioxidant and antimicrobial activities. Besides, it inhibited inflammation in several conditions, including colitis, arthritis, hepatitis, contact dermatitis, and lung inflammation. Moreover, it displayed anti-osteoporosis, anti-hyperglycemic, antidiabetic, antihypertensive, vasculoprotective, hepatoprotective, neuroprotective, and immunomodulatory effects. Additionally, it was effective as a prebiotic and in obesity control, besides it promoted wound healing. Furthermore, PP demonstrated anticancer effects against different cancer types, for example, colon, liver, thyroid, uterine, breast, bladder, prostate, leukemia, and osteosarcoma. Despite PP safety, it may interfere with the metabolism of other drugs because it inhibits cytochromes (CYP) changing their bioavailability, effectiveness, and toxicity. PP biowaste valorization not only avoids against its environmental and economic burden but can also provide a promising platform to produce novel or improved nutraceuticals. This study provides a comprehensive overview of PP biological activities with the reported action mechanisms related to its phytochemicals and further biotransformed metabolites inside the body. Future research prospects to unravel the merits of such waste and optimize its use are discussed.Practical application: Pomegranate is widely distributed throughout the world.Although its peel was previously considered a waste, recent research regards it as a rich source of bioactive compounds with promising biological activities. Its recycling not only overcomes the bio-waste problems, but also provides a source of valuable compounds with several health benefits.

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Protective mechanism of punicalagin against endoplasmic reticulum stress in the liver of mice with type 2 diabetes mellitus

Cited by 17 publications

References 30 publications

Rotundic Acid Protects against Metabolic Disturbance and Improves Gut Microbiota in Type 2 Diabetes Rats

Rotundic Acid Protects against Metabolic Disturbance and Improves Gut Microbiota in Type 2 Diabetes Rats

Effects of Lycium barbarum Polysaccharide on Endoplasmic Reticulum Stress and Oxidative Stress in Obese Mice

Ongoing and potential novel trends of pomegranate fruit peel; a comprehensive review of its health benefits and future perspectives as nutraceutical

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