PMID: 

Mol Divers. 2020 May 14. Epub 2020 May 14. PMID: 32410114

Abstract Title: 

Ellagic acid and human cancers: a systems pharmacology and docking study to identify principal hub genes and main mechanisms of action.

Abstract: 

Research on anticancer properties of natural compounds, as effective materials that are available while causing minimal side effects, is growing. Ellagic acid (EA) is a well-known polyphenolic compound, which has been found in both free and complex modes in several medicinal plants such as pomegranate, walnut, and berries. Although many articles have reported anticancer properties for this compound, its mechanism of action has not been fully elucidated. In this study, we used several online and offline bioinformatics tools and databases to identify the mechanism of action of EA on various types of human malignancies including bladder, blood, breast, cervical, colorectal, liver, pancreas, and prostate cancers. In this context, after identifying and extracting EA-affected human genes/proteins that have been reported in various references, we built the related gene networks and determined functional hub genes. In addition, docking was performed to recognize target proteins that react directly with EA and are in fact most affected by this compound. Our findings revealed that EA exerts its anticancer effects by influencing specific hub genes in various types of cancers. Moreover, different cellular signaling pathways are affected by this natural compound. Generally, it turned out that EA probably exerts most of its anticancer activities, through induction of apoptosis, as well as P53 and WNT signaling pathways, and also by affecting the expression of several hub genes such as CDKN1A, CDK4, CDK2, CDK6, TP53, JUN, CCNA2, MAPK14, CDK1, and CCNB1 and especially interactions with some related proteins including P53, CDK6, and MAPK14.

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PMID: 

Molecules. 2020 May 11 ;25(9). Epub 2020 May 11. PMID: 32403241

Abstract Title: 

A Herbal Mixture from Propolis, Pomegranate, and Grape Pomace Endowed with Anti-Inflammatory Activity in an In Vivo Rheumatoid Arthritis Model.

Abstract: 

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by the production of inflammatory factors. In order to overcome the side effects of currently used anti-inflammatory drugs, several attempts have been made to identify natural products capable of relieving RA symptoms. In this work, a herbal preparation consisting of propolis, pomegranate peel, and Aglianico grape pomace (PPP) extracts (4:1:1) was designed and evaluated for its effect on a murine collagen-induced arthritis (CIA) model. Firstly, the chemical contents of four different Italian propolis collected in the Campania region (Italy) were here reported for the first time. LC-MS analyses showed the presence of 38 constituents, identified in all propolis extracts, belonging to flavonoids and phenolic acids classes. The Pietradefusi extract was the richest one and thus was selected to design the PPP preparation for the in vivo assay. Our results highlight the impact of PPP on RA onset and progression. By using in vivo CIA models, the treatment with PPP resulted in a delayed onset of the disease and alleviated the severity of the clinical symptoms. Furthermore, we demonstrated that early PPP treatment was associated with a reduction in serum levels of IL-17, IL-1b, and IL-17-triggering cytokines.

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Don’t pity this year’s crop of graduates because this COVID-19 pandemic caused them to miss out on graduation. Pity them because they have spent their entire lives in a state of emergency

PMID: 

Planta Med. 2020 May 19. Epub 2020 May 19. PMID: 32428937

Abstract Title: 

Phenolic-rich Pomegranate Peel Extract: In Vitro, Cellular, and In Vivo Activities for Skin Hyperpigmentation Treatment.

Abstract: 

The pomegranate phenolics are reported to have cutaneous benefits and to be effective in treating skin disorders, including hyperpigmentation. In this context, a preparation method was developed by which to obtain phenolic-rich pomegranate peel extract. Sinapic acid was presented as the major pomegranate peel phenolics, followed by gallic and ellagic acids, and 4 additional phenolics. The extract exhibited strong antioxidant activity with antyrosinase inhibitory effect. The skin hyperpigmentation treating potency was confirmed by the suppression of cellular melanogenesis through tyrosinase and TRP-2 inhibitions as examined in the B16F10 melanoma cells. Cellular antioxidant and proliferative activities of the extract toward human dermal fibroblasts were evidenced, as well as an inhibitory effect against MMP-2. The extract was developed into the stable serum and mask. The products were proved to be non-irritated in 30 Thai volunteers participating in a single application closed patch test. A split-face, randomized, double-blind, placebo-controlled test of the skin lightening effect was evaluated in the 30 volunteers over 28 consecutive daily treatments and monitored by the Mexameter MX 18. The active serum and mask were better in facial skin lightening efficacy than the placebo (p 

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PMID: 

BMC Immunol. 2020 May 19 ;21(1):28. Epub 2020 May 19. PMID: 32429849

Abstract Title: 

Anti-inflammatory activity of berberine in non-alcoholic fatty liver disease via the Angptl2 pathway.

Abstract: 

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. Recent studies have shown that the Angptl2 pathway mediated hepatic inflammatory response plays an important role in the progression of nonalcoholic fatty liver disease. Our study investigated the possible molecular mechanisms of berberine (BBR) in the treatment of the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD via the Angptl2 pathway.RESULTS: At the end of 12 weeks, compared with the control group rats, the high-fat- diet group rats showed obvious pathological and biochemical changes. The levels of pro-infalmmatory cytokines (CCL2, TNF-α) were increased, the infiltration of inflammatory cells (CCR2) was elevated, and the hepatic mRNA and protein levels of Angptl2, NF-κB and Foxo1 were increased to different degrees. Nevertheless, following treatment with BBR, liver tissue pathology, biochemical data, and Angptl2 pathway-related genes expression were significantly ameliorated.CONCLUSIONS: Our findings demonstrate that BBR might attenuate the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD through the regulation of the Angptl2 pathway.

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PMID: 

J Nat Prod. 2020 May 20. Epub 2020 May 20. PMID: 32432470

Abstract Title: 

Anti-inflammatory Efficacy of Combined Natural Alkaloid Berberine and S1PR Modulator Fingolimod at Low Doses in Ulcerative Colitis Preclinical Models.

Abstract: 

The natural alkaloid berberine is being studied as a drug candidate for the treatment of ulcerative colitis (UC). Fingolimod is an immunomodulator approved for the treatment of multiple sclerosis. Whether fingolimod use can be extended to UC and how it interacts with berberine remain unclear. In the present study, the anti-inflammatory efficacies of berberine, fingolimod, and a combination of half-doses of them was examined in mice with dextran sulfate sodium-induced colitis. In mice with subchronic colitis, 14-day oral administration of fingolimod had greater efficacy than berberine in ameliorating the disease clinical severity and colon shortening. However, in mice with chronic colitis, 30-day oral administration of berberine was more effective than fingolimod except on splenic swelling. Notably, the combination of half-doses of each drug was equally effective as the superior single drugs for two models and resulted in reduced splenic swelling in the chronic colitis model. The inhibition of cytokine expression and STAT3 activation, as well as binding to the sphingosine 1-phosphate receptor by both drugs, contributed to the combination efficacy. Our findings suggest that fingolimod in combination with berberine at reduced doses represents a novel therapy for UC that attains satisfactory efficacy with reduced potentials for adverse effects.

PMID: 

Nanomaterials (Basel). 2020 May 25 ;10(5). Epub 2020 May 25. PMID: 32466299

Abstract Title: 

The Antibacterial Effect of Silver Nanoparticles on Staphylococcus epidermidis Strains with Different Biofilm-Forming Ability.

Abstract: 

Among many infectious diseases, infections caused by pathogens ofspecies exert a substantial influence upon human health, mainly due to their continuous presence on human skin and mucous membranes. For that reason, an intensive search for new, effective anistaphyloccocal agents can currently be observed worldwide. In recent years, there has been growing interest in nanoparticles, as compounds with potential antibacterial effect. The antibacterial activity of silver containing substances has been well recognized, but thoughtful studies focused on the effect of silver nanoparticles on bacterial biofilm are scarce. The aim of this study was to assess the influence of silver nanoparticles (AgNPs) with particle sizes in the range between 10 and 100 nm, and a concentration range from 1 to 10µg/mL, uponstrains with different biofilm-forming abilities (BFAs). The studies revealed the highest level of antimicrobial activity for AgNPs in relation tostrains with BFA, and what is more, the observed effect was proportional to the increasing particles' size, and strains not forming biofilm were more susceptible to silver nanoparticles with the smallest examined size, which was 10 nm.

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PMID: 

Curr Pharm Des. 2020 May 23. Epub 2020 May 23. PMID: 32445451

Abstract Title: 

AMPK and its activator Berberine in the Treatment of Neurodegenerative Diseases.

Abstract: 

Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration, causing the loss of neurons and axons in the central nervous system (CNS), showing high morbidity and mortality, and there are few effective therapies. Here we summarized the energy sensor adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and its agonist berberine can combat the common underlying pathological events of neurodegeneration including oxidative stress, neuroinflammation, mitochondrial disorder, glutamate excitotoxicity, apoptosis, autophagy disorder and neurovascular units disruption. The above actions of berberine may mainly depend on activating AMPK and its downstream targets such as mammalian target of rapamycin (mTOR), sirtuin1 (SIRT1) , nuclear factor erythroid-2 related factor-2 (Nrf2), nuclear factor-κB (NF-κB), phosphoinositide 3-kinase / protein kinase B (PI3K/Akt), nicotinamide adenine dinucleotide (NAD+ ), and p38 mitogen-activated protein kinase (p38 MAPK). It is hoped that this review will provide a powerful basis for further scientific exploration and development of berberine's therapeutic potential against neurodegeneration.

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PMID: 

Nutrients. 2019 Nov 15 ;11(11). Epub 2019 Nov 15. PMID: 31731808

Abstract Title: 

Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway.

Abstract: 

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

PMID: 

Pharmacol Res. 2020 01 ;151:104584. Epub 2019 Dec 3. PMID: 31809853

Abstract Title: 

Advances on Natural Polyphenols as Anticancer Agents for Skin Cancer.

Abstract: 

Polyphenols are one of most important phytochemicals distributing in herb plants, vegetables and fruits, which known as important anticancer agents. Given the high incidence and mortality of skin cancer, this study aimed to uncover the chemopreventive effects of polyphenols against skin cancer metastasis. Electronic databases including Scopus, PubMed, and Cochrane library were used to compile the literature from 2000 to August 2019. Only in vivo mechanistic studies with English full-texts were chosen for this review. Polyphenols were included in this study if they were administered in purified form; while total extract and fractions were excluded. Among the 8254 primarily selected papers, only a final number of 34 studies were included. The chemopreventive effects of polyphenols as anthocyanins, ellagitanins, EGCG, oleuropeindihydroxy phenyl, punicalagin, quercetin, resveratrol and theaflavin, were mainly examined in treatment of melanoma as the highly metastatic form of this cutaneous cancer. Those properties are mediated by modulation of angiogenesis, apoptosis, inflammation, metastasis, proliferation, pathways such as EGFR/MAPK, mTOR/PI3K/Akt, JAK/STAT, FAK/RTK2, PGE-2/VEGF, PGE-1/ERK/HIIF-1α, and modulation of related signals including NF-κB, P21, Bim, Bax, Bcl2, Bclx, Bim, Puma, Noxa, ILs and MMPs. Chemopreventive effects of polyphenols are mediated by several signaling pathways against skin carcinogenesis and metastasis, implying the importance of polyphenols to open up new horizons in development of anti-skin cancer therapeutic strategies.

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