PMID: 

J Food Biochem. 2019 Apr ;43(4):e12803. Epub 2019 Feb 11. PMID: 31353600

Abstract Title: 

Phenolic profiles, antihyperglycemic, antihyperlipidemic, and antioxidant properties of pomegranate (Punica granatum) peel extract.

Abstract: 

This work is aimed to evaluate phenolics composition, and in vitro antioxidant activities of hydro-methanol pomegranate (Punica granatum L.) peel extract (MPE). In addition, the antihyperglycemic, hypolipidemic, and hepatoprotective effect of MPE in Wister albino rats was compared with standard drugs (glibenclamide and atorvastatin). Total phenolic content and total flavonoid contents in MPE (mg g) accounted for 188.9 as GAE and 13.95 as QE, respectively. Phenolic and flavonoids compounds in MPE analyzed by HPLC and revealed the presence of 23 phenolic compounds and 20 flavonoid compounds. For in vivo experiment, 56 rats were distributed into 8 groups. Group 1 was the normal control, while group 2 contained rats orally administrated with 200 mg kgMPE daily. Group 3 contained diabetic rats (induced with a single dose of 100 mg/kg b.w. alloxan). Group 4 contained diabetic rats administered daily with 200 mg/kg MPE. Group 5 contained diabetic rats administered orally with a glibenclamide (standard drug for diabetic) at 10 mg/kg daily. Group 6 fed with high fat diet (HFD). Group 7 contained HFD-rats administered orally with 200 mg/kg MPE daily. Group 8 contained HFD-rats administered orally with atorvastatin (used to lower LDL-cholesterol (LDL-C) and fats and to raise HDL-cholesterol (HDL-C) in the blood) at 10 mg/kg daily. The study lasted for 56 days. Administration with MPE 200 mg/kg to both diabetic andhyperlipidemic rats significantly decreased blood glucose, HbA, total lipid, total cholesterol, LDL-C, and very low density lipoprotein cholesterol levels, while increased high density lipoprotein cholesterol levels, as well as improved liver and kidney functions, compared with glibenclamide and atorvastatin effects. PRACTICAL APPLICATIONS: Pomegranate peel, constituted about 50% of fruit fresh weight, is rich in bioactive compounds with potent health-promoting activities. The results of the current study stated that MPE is rich in phenolics and flavonoids with powerful antioxidant potential. In addition, MPE showed antihyperglycemic and antihyperlipidemic activities due to the strong antiradical action via its antioxidant compounds. MPE enhanced liver and kidney functions when compared to standard drugs in diabetic and hyperlipidemic rats. MPC could be used as a natural material to develop diabetic and hyperlipidemic drugs.

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PMID: 

J Food Biochem. 2019 Aug ;43(8):e12959. Epub 2019 Jun 17. PMID: 31368549

Abstract Title: 

Pomegranate supplementation attenuates inflammation, joint dysfunction via inhibition of NF-κB signaling pathway in experimental models of rheumatoid arthritis.

Abstract: 

Incisive search of innovative compounds for regulating pain, inflammation, and bone damage, with nominal side effects has focused on nutritional supplements. The endeavor of this research work was to investigate, for first time, the inhibitory effect of pomegranate rind extract in established models of nociception and inflammation. Pomegranate (50, 100, and 200 mg/kg) and indomethacin (3 mg/kg) was assessed in eddy's hot plate-induced algesia, carrageenan, and Complete Freund's adjuvant-induced models in Wistar rats. Results of study conclude that pomegranate at a dose of 200 mg/kg showed significant (p 

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PMID: 

J Med Food. 2019 Aug 9. Epub 2019 Aug 9. PMID: 31397609

Abstract Title: 

Potential Hypoglycemic Effect of Pomegranate Juice and Its Mechanism of Action: A Systematic Review.

Abstract: 

Pomegranate juice (PJ) has gained popularity attributed to its phenolic compounds and their medicinal properties. Its potential hypoglycemic effect has been related to enzymatic inhibition, insulin release, and the protection of pancreatic tissue. These effects depend on several aspects, such as the content and composition of phenols in pomegranate and characteristics of the organism that consumes the juice. The objective of this study was to systematically review scientific evidence investigating the hypoglycemic effect of PJ; the factors that affect bioactive compounds; and the mechanisms of action attributed to this effect. Human and rodentandstudies were retrieved from PubMed, Scopus, and ScienceDirect databases. After reviewing the articles, it was identified that the methodologies and results among the scientific evidence were quite heterogeneous. Despite these limitations, many of theandstudies found important hypoglycemic effects from PJ, as well as an increase in the function of-cell, insulin secretion, a significantly lower activity of-amylase enzyme, an inhibition of the enzyme-glucosidase and dipeptidyl peptidase-4 (DPP-4), and the protection against DNA damage. Determining the potential health benefits of polyphenols contained in the pomegranate is limited for multiple factors that could affect the efficacy of PJ. Overall, the results of this review suggest the need for further experimentation, using controlled variable factors and testing the effect of PJ under similar experimental conditions.

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PMID: 

Colloids Surf B Biointerfaces. 2019 Sep 1 ;181:927-934. Epub 2019 Jun 4. PMID: 31382342

Abstract Title: 

Nanoemulsion improves hypoglycemic efficacy of berberine by overcoming its gastrointestinal challenge.

Abstract: 

Berberine (BBR) is an important natural product with poor gastrointestinal behavior includes low permeability, P-glycoprotein efflux, and mass elimination in the intestine. The aim of this study was to develop a novel nanoemulsion (NE) to improve the hypoglycemic efficacy of BBR. NE was prepared and characterized by morphology and droplet size detection, stored stability, in vitro intestinal lipolysis and metabolism, Caco-2 cells transport, in situ single-pass intestinal perfusion, oral bioavailability in rats, and hypoglycemic efficacy in high-fat diet and streptozocin-induced mice. BBR-loaded NE exhibits small droplet size (30.56 ± 0.35 nm) and good stability. NE could remain intact after lipolysis and protect BBR against the intestinal metabolism mediated by CYP2D6 and CYP3A4. Cells transport and intestinal perfusion studies revealed that NE decreases the P-glycoprotein efflux of BBR by 2-fold and enhances its permeability by 5.5-fold. Consequently, NE increased the oral bioavailability of BBR in rats by 212.02%. Compared to BBR control, blood glucose level of diabetic mice by NE was decreased by 3-fold. This novel NE provides a promising carrier to improve the hypoglycemic efficacy of BBR by overcoming its gastrointestinal deficiency, which may offer a product for the therapy of diabetes.

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PMID: 

Pharmacol Res. 2019 Aug 7:104385. Epub 2019 Aug 7. PMID: 31400402

Abstract Title: 

Berberine protects against ischemia-reperfusion injury: a review of evidence from animal models and clinical studies.

Abstract: 

Ischemia-reperfusion (I/R) injury is accompanied with high morbidity and mortality and has seriously negative social and economic influences. Unfortunately, few effective therapeutic strategies are available to improve its outcome. Berberine is a natural medicine possessing multiple beneficial biological activities. Emerging evidence indicates that berberine has potential protective effects against I/R injury in brain, heart, kidney, liver, intestine and testis. However, up-to-date review focusing on the beneficial role of berberine against I/R injury is not yet available. In this paper, results from animal models and clinical studies are concisely presented and its mechanisms are discussed. We found that berberine ameliorates I/R injury in animal models via its anti-oxidant, anti-apoptotic and anti-inflammatory effects. Moreover, berberine also attenuates I/R injury by suppressing endoplasmic reticulum stress and promoting autophagy. Additionally, regulation of periphery immune system may also contributes to the beneficial effect of berberine against I/R injury. Although clinical evidence is limited, the current studies indicate that berberine may attenuate I/R injury via inhibiting excessive inflammatory response in patients. Collectively, berberine might be used as an alternative therapeutic strategy for the management of I/R injury.

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PMID: 

Exp Ther Med. 2019 Sep ;18(3):2122-2130. Epub 2019 Jul 12. PMID: 31410167

Abstract Title: 

Berberine exhibits antioxidative effects and reduces apoptosis of the vaginal epithelium in bacterial vaginosis.

Abstract: 

Bacterial vaginosis (BV) is a common type of vaginitis. Berberine is a natural alkaline product that reduces oxidative stress and apoptosis in cells. The aim of the present study was to investigate the effects of berberine on oxidative stress and apoptotic rates of BV. Vaginal epithelial and discharge samples were obtained from 60 healthy individuals and 180 patients with BV before and after one month of berberine treatment. Clinical observation was documented for all patients before and after treatment for comparison. Additionally, anstudy was performed; the samples were divided into groups the following groups: Control, model (HO-treated), LT (low-dose berberine), MT (medium-dose berberine) and HT (high-dose berberine). Expression levels of the oxidative stress related proteins were detected by western blotting. Clinical symptoms of patients with BV significantly improved following berberine treatment. Oxidative stress in vaginal discharge was significantly lower following treatment, indicated by the increased activity of superoxide dismutase (SOD) and catalase, as well as the reduced levels of malondialdehyde and HO. Apoptosis of the vaginal epithelial cells was also reduced, which was indicated by the reduced expression of apoptosis proteins caspase-3, cytochrome C, capase-12 and Bax, and increased expression of Bcl-2. The results of theexperiments demonstrated a dose-dependent decrease in apoptosis with berberine treatment compared with levels before treatment. Oxidative stress relief was demonstrated by the reduced reactive oxygen species level and increased SOD and endothelial nitric oxide synthase levels, whereas suppression of apoptosis was further supported by the reduction in apoptotic proteins, as well as a decreased Bax/Bcl-2 ratio. Berberine exhibited effects on lowering oxidative stress in vaginal discharge and reducing oxidative damage, as well as apoptosis of the vaginal epithelium, which are beneficial to patients with bacterial vaginosis.

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PMID: 

BMC Complement Altern Med. 2019 Aug 14 ;19(1):216. Epub 2019 Aug 14. PMID: 31412862

Abstract Title: 

Berberine inhibits NLRP3 Inflammasome pathway in human triple-negative breast cancer MDA-MB-231 cell.

Abstract: 

BACKGROUND: Breast cancer is still the most common malignant tumor that threatens the female's life in the world, especially triple-negative breast cancer (TNBC), one of the most difficult subtypes. Lack of targeted therapies brings about urgent demand for novel treatments. In this study we aim to investigate the anti-tumor activity of Berberine (BBR), a Chinese plant-derived alkaloid, against the TNBC cell line MDA-MB-231 and elucidate its mechanism referring to anti-inflammation.METHODS: Cell inhibition rate was measured by Cell Proliferation Assay, the cytotoxic effects was detected by Lactate dehydrogenase (LDH) leakage assay, the colony formation and migration potential were evaluated by colony formation assay and wound healing assay, the release of inflammatory cytokines was detected by EMD multifactor detection, and alterations of proteins and genes related to the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway were analyzed using western blotting and real-time Polymerase Chain Reaction (PCR).RESULTS: BBR reduce the viability of MDA-MB-231 cells and increased the release of LDH from the cells in a dose-dependent manner, with and inhibition of colony formation potential and migration of the cells. BBR also caused a marked reduction in the secretion of proinflammatory cytokines, Interleukin-1α (IL-1α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Besides, a down-regulated behavior was observed with the expression of P2X purinoceptor 7 (P2X7), NLRP3, pro-caspase-1, apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1 p20, Interleukin-18 (IL-18), IL-1β proteins and NLRP3, Caspase-1 and ASC mRNAs in the NLRP3 inflammasome cascade.CONCLUSIONS: Our results confirmed that BBR can effectively affect both tumor outgrowth and spontaneous metastasis in TNBC, and that we identified a new mechanism associated with inhibition the NLRP3 inflammasome pathway, suggesting its potential therapeutic relevance in clinical use.

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PMID: 

World J Gastroenterol. 2019 Aug 7 ;25(29):3956-3971. PMID: 31413530

Abstract Title: 

Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats.

Abstract: 

BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility.AIM: To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility.METHODS: IBS was induced in ratswater avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of C-kit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophicfactor (BDNF) and its receptor TrkB.RESULTS: WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group.CONCLUSION: BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.

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PMID: 

Sci Rep. 2019 Jul 12 ;9(1):10145. Epub 2019 Jul 12. PMID: 31300670

Abstract Title: 

Microplastic contamination of table salts from Taiwan, including a global review.

Abstract: 

Plastic pollution is a rapidly worsening environmental problem, especially in oceanic habitats. Environmental pollution with microplastic particles is also causing food consumed by humans to be increasingly polluted, including table salts. Therefore, we present the first study which focuses only on table salt products purchased in Taiwan which we examined for the presence of microplastics. We used Fourier transform infrared spectroscopy to identify the polymer type of each particle. Within 4.4 kg of salt, we detected 43 microplastic particles which averages to 9.77 microplastic particles/kg. The identified polymer types were, in descending abundance, polypropylene, polyethylene, polystyrene, polyester, polyetherimide, polyethylene terephthalate, and polyoxymethylene. We combined our novel results with those of previous studies to provide the first global review of microplastic contamination of table salts. We found that 94% of salt products tested worldwide contained microplastics, with 3 out of 27 polymer types (polyethylene terephthalate, polypropylene, polyethylene) accountingfor the majority of all particles. Averaging over seven separate studies, table salts contain a mean of 140.2 microplastic particles/kg. With a mean annual salt consumption of ~3.75 kg/year, humans therefore annually ingest several hundred microplastic particles from salt alone.

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PMID: 

Chemosphere. 2019 Jul 10 ;236:124334. Epub 2019 Jul 10. PMID: 31310986

Abstract Title: 

Accumulation of different shapes of microplastics initiates intestinal injury and gut microbiota dysbiosis in the gut of zebrafish.

Abstract: 

Different shapes of microplastics are widely detected in the environment and organisms and most of them remain in the gut. However, the influences of shapes on the bioaccumulation and toxicity of microplastics in the gut are largely unknown. Three shapes (bead, fragment, and fiber) of microplastics of comparable size in one dimension were prepared to exposure to zebrafish. The accumulation and toxicities of microplastics in the gut were detected. Shape-dependent accumulation in the gut was observed with the order of fibers (8.0 μg/mg) > fragments (1.7 μg/mg) > beads (0.5 μg/mg). The accumulation of microplastics caused multiple toxic effects in fish intestine, including mucosal damage, and increased permeability, inflammation and metabolism disruption. Based on these toxic effects, microplastic fibers resulted in more severe intestinal toxicity thanmicroplastic fragments and beads did. Furthermore, microplastics also induced gut microbiota dysbiosis and specific bacteria alterations, which will provide novel insights into the potential mechanism of microplastics causing intestinal toxicities in fish. Our results also suggested that shape-depended effects should not be ignored in the health risk assessment of microplastics.

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