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Syzygium cumini Leaf Extract Reverts Hypertriglyceridemia via Downregulation of the Hepatic XBP-1s/PDI/MTP Axis in Monosodium L-Glutamate-Induced Obese Rats.

ABSTRACT: Syzygium cumini is used worldwide for the treatment of metabolic syndrome-associated outcomes. Previously, we described the antihypertriglyceridemic effect of the hydroethanolic extract of S. cumini leaf (HESc) in monosodium L-glutamate- (MSG-) induced obese rats. This study sought to investigate the molecular mechanisms underlying the antihypertriglyceridemic effect of HESc in MSG-obese rats. Newborn male Wistar rats were injected subcutaneously with MSG (4.0 g/kg/day, obese group) or saline 1.25% (1.0 mL/kg/day, lean group), from 2nd through 10th postnatal day. At 8 weeks old, obese rats started to be orally treated with HESc (0.5 or 1.0 g/kg/day, n = 7) or saline 0.9% (1 mL/kg/day, n = 7). Lean rats received saline solution (1 mL/kg/day, n = 7). Upon 8-week treatment, animals were euthanized for blood and tissue collection. Another set of adult nonobese Wistar rats was used for the assessment of HESc acute effects on Triton WR1339-induced hypertriglyceridemia. HESc reduced weight gain, as well as adipose tissue fat pads, without altering food intake of obese rats. HESc restored fasting serum glucose, triglycerides, total cholesterol, and free fatty acids, as well as insulin sensitivity, to levels similar to lean rats. Additionally, HESc halved the triglyceride content into very low-density lipoprotein particles, as well as healed liver steatosis, in obese rats. Hepatic protein expression of the endoplasmic reticulum chaperone GRP94 was decreased by HESc, which also downregulated the hepatic triglyceride secretion pathway by reducing the splicing of X-box binding protein 1 (XBP-1s), as well as protein disulfide isomerase (PDI) and microsomal triglyceride transfer protein (MTP) translational levels. This action was further corroborated by the acute inhibitory effect of HESc on triglyceride accumulation on Triton WR1339-treated rats. Our data support the downregulation of the XBP-1s/PDI/MTP axis in the liver of MSG-obese rats as a novel feasible mechanism for the antihypertriglyceridemic effect promoted by the polyphenolic phytocomplex present in S. cumini leaf.

SUBMITTER: Franca LM

PROVIDER: S-EPMC6446099 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc) on lean and monosodium L-glutamate (MSG)-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg) or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a twofold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10-1000 ?g/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E ?-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating ?-cell insulin release, which was associated with improvements in metabolic outcomes in MSG-induced obese rats.

Project description:The emergence of bacterial strains resistant to different antibiotics has prompted the search for new sources of antimicrobial compounds. Studies have shown that jambolan [Syzygium cumini (L.) Skeels], a tropical fruit from the Mirtaceae family, contains a great variety of phytochemical compounds with high antioxidant and antimicrobial activity. This study aimed to determine the centesimal composition and physicochemical characteristics of the pulp and seed of S. cumini (L.) Skeels, as well as the content of total phenolic compounds and the antioxidant, antibacterial, antibiofilm and anti-quorum sensing (QS) activities of the phenolic extracts obtained from the pulp and the seeds of this fruit. The in vitro antibacterial and anti-QS activities of active films incorporating phenolic extracts were also evaluated. Additionally, we performed molecular docking of phenolic compounds present in jambolan with the CviR QS regulator of Chromobacterium violaceum. The composition and physicochemical characteristics of the samples presented similar values to those found for the species. However, the seed phenolic extract had a higher content of phenolic compounds and antioxidant activity than the pulp. Both phenolic extracts presented antibacterial activity against Aeromonas hydrophila, C. violaceum, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium, Serratia marcescens, Listeria monocytogenes, and Staphylococcus aureus. The seed phenolic extract was particularly inhibitory against S. aureus. The pulp phenolic extract inhibited swarming motility and biofilm formation of A. hydrophila, E. coli, and S. marcescens in sub-MIC concentrations. The pulp and seed phenolic extracts inhibited violacein production in C. violaceum. Films incorporating both phenolic extracts inhibited the growth of bacteria, particularly Pseudomonas fluorescens, L. monocytogenes, and S. aureus, as well as QS in C. violaceum. Molecular docking showed that a variety of compounds found in pulp and seed extracts of jambolan, particularly chlorogenic acid and dihydroquercetin, potentially bind CviR protein and may interfere with QS. Our results indicate that pulp and seed of jambolan are good sources of antibacterial, antibiofilm, and anti-QS compounds that can be used in the development of natural preservatives and for application in antibacterial active films.

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Syzygium cumini Leaf Extract Reverts Hypertriglyceridemia via Downregulation of the Hepatic XBP-1s/PDI/MTP Axis in Monosodium L-Glutamate-Induced Obese Rats.

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