Health Time

Pomegranate-derived anthocyanin regulates MORs-cAMP/CREB-BDNF pathways in opioid-dependent models and improves cognitive impairments.

PMID:

J Ayurveda Integr Med. 2020 May 16. Epub 2020 May 16. PMID: 32430240

Abstract Title:

Pomegranate-derived anthocyanin regulates MORs-cAMP/CREB-BDNF pathways in opioid-dependent models and improves cognitive impairments.

Abstract:

BACKGROUND: Pomegranate (Punica granatum) is one of the oldest known edible fruit. Recently, there has been an increased interest in this fruit as a functional food for health benefits due to its use in disease prevention and promotion of overall health wellness.OBJECTIVE: This study aims to investigate the effects of pomegranate extract for the development of non-opioid substitution therapy for in-vitro and in-vivo studies.MATERIALS AND METHODS: Anthocyanin contents consisting of cyanidin 3-glucoside, diglucoside, and pelargonidin 3-glucoside, diglucoside were detected and quantified in pomegranate extract using high-performance liquid chromatography. The optimum dosage of the extract was determined based on the regulation of MORs and cAMP proteins in U-87 cells. Co-treatment of the extract with morphine was performed to evaluate its potency in reducing the concentration levels of MORs and cAMP. For animal studies, rats were divided into two major groups representing both acute and chronic morphine-induced treatments and the Morris water maze (MWM)study was employed after treatment for each rat. The rats were sacrificed after the treatments and serum samples were collected to evaluate the levels of CREB and BDNF.RESULTS: The results indicated that each of the anthocyanin content tested in the study was present in the pomegranate extract. Additionally, in-vitro studies using pomegranate extract treatment showed that the extract was effective in decreasing the MORs and cAMP protein levels in U-87 cells at a concentration of 0.125 mg/mL. The memory impairment based on the MWM study in rats was also subsequently improved after treatment with pomegranate extract as compared to treatment with morphine. The blood serum derived from the rats treated with pomegranate extract also showed a significant decrease in CREB level and an increase in BDNF as compared to rats treated with morphine.CONCLUSION: In conclusion, this study substantiates the potency of pomegranate extract as a non-opioid substitution therapy for in-vitro and in-vivo studies.

Punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages.

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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.

Advances on natural polyphenols as anticancer agents for skin cancer.

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.

Pomegranate as a aource of bioactive constituents: a review on their characterization, properties and applications.

PMID:

Crit Rev Food Sci Nutr. 2020 Apr 21:1-18. Epub 2020 Apr 21. PMID: 32314615

Abstract Title:

Pomegranate as a source of bioactive constituents: a review on their characterization, properties and applications.

Abstract:

Increasing awareness about the use of compounds obtained from natural sources exerting health-beneficial properties, including antimicrobial and antioxidant effects, led to increased number of research papers focusing on the study of functional properties of target compounds to be used as functional foods or in preventive medicine. Pomegranate has shown positive health properties due to the presence of bioactive constituents such as polyphenols, tannins, and anthocyanins. Punicalagin is the major antioxidant, abundantly found in pomegranate's peel. Research has shown that pomegranate polyphenols not only have a strong antioxidant capacity but they also inhibit the growth of pathogenic bacteria like,and,andfactor, and inhibits fungi such as, and. Compounds of natural origin inhibit the growth of various pathogens by extending the shelf life of foodstuffs and assuring their safety. Therefore, the need to find compounds to be used in combination with antibiotics or as new antimicrobial sources, such as plant extracts. On the basis of the above discussion, this review focuses on the health benefits of pomegranate, by summarizing the current body of research focusing on pomegranate bioactive constituents and their therapeutic potential against some pathogenic microbes.

Punicalagin inhibits the viability, migration, invasion, and EMT by regulating GOLPH3 in breast cancer cells.

PMID:

J Recept Signal Transduct Res. 2020 Apr ;40(2):173-180. Epub 2020 Feb 6. PMID: 32024401

Abstract Title:

Punicalagin inhibits the viability, migration, invasion, and EMT by regulating GOLPH3 in breast cancer cells.

Abstract:

Breast cancer (BC) is one of the most common malignancies worldwide. Punicalagin (PN), which is a type of polyphenol, has been reported to act as a tumor suppressor. This study aimed to investigate the effects of PN on cellular process in BC and its molecular mechanism. The effects of various doses of PN on cell viability, migration, and invasion capacities of MCF-7 and MDA-MB-231 cells were detected by CCK-8, wound-healing, and Transwell assays. Golgi phosphoprotein 3 (GOLPH3) was then transfected into the cells with or without PN treatment, and GPLPH3 expression level was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, and expressions of epithelial-mesenchymal transition (EMT)-related protein matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-Cadherin, and N-Cadherin were measured by Western blot. High dose of PN treatment (50 μM or higher) significantly inhibited viability, migration, and invasion of MCF-7 and MDA-MB-231 cells, while overexpressed GOLPH3 promoted cell viability, migration, and invasion, and partially reversed the effects of PN treatment on the BC cells. PN inhibited the expressions of GOLPH3, MMP-2,MMP-9, and N-Cadherin, and promoted E-Cadherin expression, while overexpression of GOLPH3 partly reversed above effects attributing to PN. Thus, PN suppresses cell viability and metastasisregulating GOLPH3 in BC, which provides a possible therapeutic direction to the treatment of BC.

Punicalagin promotes the apoptosis in human cervical cancer.

PMID:

Saudi J Biol Sci. 2020 Apr ;27(4):1100-1106. Epub 2020 Mar 4. PMID: 32256171

Abstract Title:

Punicalagin promotes the apoptosis in human cervical cancer (ME-180) cells through mitochondrial pathway and by inhibiting the NF-kB signaling pathway.

Abstract:

Increasing attention of plant derived therapeutic agents against cancer, investigating the anti-proliferative efficiency of plant derived chemicals have achieved increasing momentum for the design of anticancer drug. Punicalagin, dietary phytochemical altered the various cell signal transduction pathways associated with cell apoptosis and proliferation. This investigation was intended to examine the efficiency of punicalagin lying on cell viability so as to examine the molecular based punicalagin mechanism stimulated apoptosis via exploring the expression of Bcl-2 family proteins, and caspases also the cell cycle regulatory proteins p53 and NF-κB signaling in human cervical cancer cells. We also analyzed the morphological characteristic changes through mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, TUNEL assay, AO/EtBr analysis in cervical cancer cells. Our findings demonstrated that punicalagin repressed the viability of cervical cancer cells in a dosereliant mode via stimulating mitochondrial mediated apoptosis. Moreover, our this study demonstrated that punicalagin blocked cervical cancer cell proliferation and stimulated cell apoptosis by suppressing NF-kappa B activity. Hence our study suggested that punicalagin exhibits opposing actions on NF-kappa B signaling networks to block cancer cell progression acts as a classical candidate for anticancer drug designing.

Pomegranate-derived anthocyanin regulates MORs-cAMP/CREB-BDNF pathways in opioid-dependent models and improves cognitive impairments.

PMID:

J Ayurveda Integr Med. 2020 May 16. Epub 2020 May 16. PMID: 32430240

Abstract Title:

Pomegranate-derived anthocyanin regulates MORs-cAMP/CREB-BDNF pathways in opioid-dependent models and improves cognitive impairments.

Abstract:

Punicalagin protects diabetic nephropathy.

PMID:

Nutrients. 2020 May 22 ;12(5). Epub 2020 May 22. PMID: 32456088

Abstract Title:

Punicalagin Protects Diabetic Nephropathy by Inhibiting Pyroptosis Based on TXNIP/NLRP3 Pathway.

Abstract:

Diabetic nephropathy is a diabetic complication caused by chronic inflammation. As the primary polyphenol in pomegranate, punicalagin is believed to have significant anti-inflammatory properties. In this study, we established a mice model for diabetes induced by high-fat diet (HFD)/ streptozotocin (STZ) to verify the protective effect of punicalagin in vivo. The results show that the blood urea nitrogen (BUN), serum creatinine (CREA), and the urine albumin to creatinine ratio (UACR) were significantly decreased in diabetic mice after punicalagin intervention, and the symptoms of glomerular interstitial hyperplasia and glomerular hypertrophy were alleviated. Pyroptosis is an essential manner of programmed cell death in the inflammatory response; the expression of pyroptosis-related proteins such as interleukin-1 (IL-1β), cysteinyl aspartate-specific protease-1 (caspase-1), gasdermin D (GSDMD), and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) was decreased in our study, which proved that the administration of punicalagin for eight weeks can significantly inhibit pyroptosis in mice. In addition, punicalagin reduced high glucose-mediated protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and alleviated mitochondria damage. Low expression of NOX4 inhibits the dissociation of thioredoxin (Trx) and thioredoxin-interacting protein (TXNIP) and the suppression of NLRP3 inflammasome activation. To summarize, our study provided evidence that punicalagin can alleviate diabetic nephropathy, and the effect is associated with downregulating the expression of NOX4, inhibiting TXNIP/NLRP3 pathway-mediated pyroptosis, suggesting its therapeutic implications for complications of diabetes.

Natural plant extract berbamine is a potent inhibitor of cell growth and survival of human tenon’s fibroblasts.

PMID:

Ophthalmic Res. 2020 Feb 20. Epub 2020 Feb 20. PMID: 32079013

Abstract Title:

Natural plant extract Berbamine is a potent inhibitor of cell growth and survival of human Tenon's fibroblasts.

Abstract:

INTRODUCTION: Post-trabeculectomy scaring due to excessive proliferation of human Tenon's fibroblasts (HTFs) often led to operation failure. Developing a new anti-fibrosis drug with high efficacy to inhibit HTFs' cell growth will greatly improve the effectiveness of trabeculectomy.OBJECTIVE: This study aims to investigate the effect of berbamine (BBM) treatment on the cell growth and survival of HTFs.METHODS: Cultured human fetal Tenon's fibroblasts (HFTFs) were treated with or without different concentrations of BBM. Cell morphology was observed with a phase contrast microscope. A CCK-8 method and Ki67 immunofluorescence were used to determine cell viability and cell proliferation. A scratch test was used to study cell migration. Flow cytometry and TUNEL staining were performed to detect cell apoptosis. The expression of BAX/BCL-2, ERK and AKT/mTOR pathway components was determined by western blotting.RESULTS: BBM treatment disrupted HFTF's normal morphology and inhibited its cell growth in a dose-dependent manner. Ki67 immunofluorescence and scratch assay showed BBM suppressed HFTF's cell proliferation and migration. Importantly, BBM dose-dependently increased the BAX/BCL-2 ratio and induced apoptosis in HFTF cells. Western blotting showed BBM significantly inhibited the ERK and AKT/mTOR pathway, and PTEN inhibition ameliorates the inhibitory effect of BBM on cell viability and survival in HFTFs.CONCLUSIONS: BBM potently inhibits the cell growth and survival of HTFs through AKT/mTOR and has the potential to serve as an anti-fibrosis drug after trabeculectomy.

Berbamine ameliorates ethanol-induced liver injury by inhibition of hepatic inflammation.

PMID:

Chin J Nat Med. 2020 Mar ;18(3):186-195. PMID: 32245588

Abstract Title:

Berbamine ameliorates ethanol-induced liver injury by inhibition of hepatic inflammation in mice.

Abstract:

Alcoholic liver disease (ALD) has become one of the leading causes of death in the world. Berbamine (BM), a natural product mainly derived from Berberis vulgaris L, possesses multiple bioactivities as a traditional medicine. However, the protective effect of BM on ALD remains unknown. In this study, we investigated the effect of BM on ethanol-induced hepatic injury in mice and its underlying mechanism. It was shown that BM at 0.3125-40μmol·Lhad no effect on macrophages and hepatocytes proliferation. BM at 5-20μmol·Lsignificantly inhibited lipopolysaccharide (LPS) or acetate-induced IL-1β and IL-6 mRNA expression in RAW264.7 cells. Moreover, BM treatment significantly inhibited LPS-induced p65 and STAT3 phosphorylation in RAW264.7 cells. Hepatic histopathology analysis showed that inflammatory cells infiltration and lipid accumulation were suppressed by 25 and 50 mg·kgBM administration in ethanol-induced hepatic injury mouse model. Meanwhile, BM treatment significantly inhibited serum ALT and AST levels in ethanol-fed mice. Oil red O staining results showed that BM administration ameliorated hepatic lipid accumulation in ethanol-fed mice. Preventions of ethanol-induced hepatic injury by BM were reflected by markedly decreased serum and hepatic triglyceride (TG) and total cholesterol (TC) contents. Real-time PCR results showed that BM treatment significantly inhibited pro-inflammatory cytokines mRNA expression in ethanol-fed mouse liver. Remarkably, the mechanism of action of BM was related to the reduction of ethanol-induced NF-κB and STAT3 phosphorylation levels in liver. In addition, BM treatment significantly inhibited ERK phosphorylation but not JNK and p38 of MAPK pathway. Taken together, our results demonstrate a beneficial effect of BM on ethanol-induced liver injury via a mechanism associated with inactivation ofNF-κB, STAT3 and ERK pathway, which gives insight into the further evaluation of the therapeutic potential of BM for ALD.