PMID: 

Antioxidants (Basel). 2020 Jan 6 ;9(1). Epub 2020 Jan 6. PMID: 31935828

Abstract Title: 

Neuroprotective Mechanisms of Three Natural Antioxidants on a Rat Model of Parkinson's Disease: A Comparative Study.

Abstract: 

We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA),α-lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson's disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals were divided into five groups: the sham-operated (SO) control group; striatal 6-OHDA-lesioned control group; and three groups of 6-OHDA-lesioned rats pre-treated for five days with EA, LA, and Myrt (50 mg/kg; intraperitoneally- i.p.), respectively. On the 2nd and the 3rd week post lesion, the animals were subjected to several behavioral tests: apomorphine-induced rotation; rotarod; and the passive avoidance test. Biochemical evaluation included assessment of main oxidative stress parameters as well as dopamine (DA) levels in brain homogenates. The results showed that all three test compounds improved learning and memory performance as well as neuromuscular coordination. Biochemicalassays showed that all three compounds substantially decreased lipid peroxidation (LPO) levels, and restored catalase (CAT) activity and DA levels that were impaired by the challenge with 6-OHDA. Based on these results, we can conclude that the studied AOs demonstrate properties that are consistentwith significant antiparkinsonian effects. The most powerful neuroprotective effect was observed with Myrt, and this work represents the first demonstration of its anti-Parkinsonian impact.

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PMID: 

Antioxidants (Basel). 2020 Jan 7 ;9(1). Epub 2020 Jan 7. PMID: 31936058

Abstract Title: 

Gamma Tocopherol Reduced Chemotherapeutic-Induced ROS in an Ovarian Granulosa Cell Line, But Not in Breast Cancer Cell Lines In Vitro.

Abstract: 

Doxorubicin and cyclophosphamide are used to treat breast cancer, but they also cause infertility through off-target cytotoxicity towards proliferating granulosa cells that surround eggs. Each chemotherapeutic generates reactive oxygen species (ROS) but the effects of the combination, or the antioxidants alpha (αToc) and gamma tocopherol (γToc) on ROS in breast cancer or ovarian cells are unknown. Human breast cancer (MCF7, T47D) and ovarian cancer (OVCAR, COV434) cells were loaded with DCDFA and exposed (1, 2, 3, 24 h) to the MCF7-derived EC25 values of individual agents, or to combinations of these. ROS were quantified and viable cells enumerated using crystal violet or DAPI. Each chemotherapeutic killed ~25% of MCF7, T47D and OVCAR cells, but 57 ± 2% (doxorubicin) and 66 ± 2% (cyclophosphamide) of the COV434 granulosa cells. The combined chemotherapeutics decreased COV434 cell viability to 34± 5% of control whereas doxorubicin + cyclophosphamide + γToc reduced ROS within 3 h (

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PMID: 

Antioxidants (Basel). 2020 Jan 13 ;9(1). Epub 2020 Jan 13. PMID: 31941067

Abstract Title: 

Oxidative Stress and Cancer: Chemopreventive and Therapeutic Role of Triphala.

Abstract: 

Oxidative stress, caused by the overproduction of free radicals, leads to the development of many chronic diseases including cancer. Free radicals are known to damage cellular biomolecules like lipids, proteins, and DNA that results in activation of multiple signaling pathways, growth factors, transcription factors, kinases, inflammatory and cell cycle regulatory molecules. Antioxidants, which are classified as exogenous and endogenous, are responsible for the removal of free radicals and consequently the reduction in oxidative stress-mediated diseases. Diet and medicinal herbs are the major source of antioxidants. Triphala, which is a traditional Ayurvedic formulation that has been used for centuries, has been shown to have immense potential to boost antioxidant activity. It scavenges free radicals, restores antioxidant enzymes and non-enzyme levels, and decreases lipid peroxidation. In addition, Triphala is revered as a chemopreventive, chemotherapeutic, immunomodulatory, and radioprotective agent. Accumulated evidence has revealed that Triphala modulates multiple cell signaling pathways including, ERK, MAPK, NF-κB, Akt, c-Myc, VEGFR, mTOR, tubulin, p53, cyclin D1, anti-apoptotic and pro-apoptotic proteins. The present review focuses on the comprehensive appraisal of Triphala in oxidative stress and cancer.

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PMID: 

Sci Rep. 2020 Feb 14 ;10(1):2687. Epub 2020 Feb 14. PMID: 32060308

Abstract Title: 

Inhibition of autophagic flux differently modulates cannabidiol-induced death in 2D and 3D glioblastoma cell cultures.

Abstract: 

Radiotherapy combined with chemotherapy is the major treatment modality for human glioblastoma multiforme (GBM). GBMs eventually relapse after treatment and the average survival of GBM patients is less than two years. There is some evidence that cannabidiol (CBD) can induce cell death and increases the radiosensitivity of GBM by enhancing apoptosis. Beside initiation of death, CBD has been demonstrated as an inducer of autophagy. In the present study, we address the question whether CBD simultaneously induces a protective effect in GBM by upregulating autophagy. Addition of chloroquine that suppressed autophagic flux to 2D GBM cultures increased CBD-induced cell death, presenting proof for the protective autophagy. Blockage of autophagy upregulated radiation-induced cytotoxicity but only modestly affected the levels of cell death in CBD- or CBD/γ-irradiated 3D GBM cultures. Furthermore, CBD enhanced the pro-apoptotic activities of JNK1/2 and MAPK p38 signaling cascades while partially downregulated the pro-survival PI3K-AKT cascade, thereby changing a balance between cell death and survival. Suppression of JNK activation partially reducedCBD-induced cell death in 3D GBM cultures. In contrast, co-treatment of CBD-targeted cells with inhibitors of PI3K-AKT-NF-κB, IKK-NF-κB or JAK2-STAT3 pathways killed surviving GBM cells in both 2D and 3D cultures, potentially improving the therapeutic ratio of GBM.

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PMID: 

Biomed Pharmacother. 2017 Nov ;95:1765-1776. Epub 2017 Oct 6. PMID: 28962082

Abstract Title: 

Protective effect of Schisandra chinensis bee pollen extract on liver and kidney injury induced by cisplatin in rats.

Abstract: 

Cisplatin (CP) has been used to cure numerous forms of cancers effectively in clinics, however, it could induce some toxic effects. Bee pollen is a natural compound, produced by honey bees. It is obtained from collected flower pollen and nectar, mixed with bee saliva. Bee pollen produced from Schisandra chinensis plants is described to exert potent antioxidant effects and to be a free radical scavenger. The purpose of this study was to investigate the effects of therapeutic treatment with Schisandra chinensis bee pollen extract (SCBPE) on liver and kidney injury induced by CP. The rats were intragastrically administrated with different doses of SCBPE (400mg/kg/day, 800mg/kg/day, 1200mg/kg/day) and vitamin C (400mg/kg/day, positive control group) for 12days, and the liver and kidney injury models were established by single intraperitoneal injection of CP (8mg/kg) at seventh day. The effect of SCBPE on CP toxicity was evaluated by measuring markers of liver and kidney injury in serum, levels of lipid peroxidation and antioxidants in liver and kidney, observing pathological changes of tissue, and quantified expression of NFκB, IL-1β, IL-6, cytochrome C, caspase3, caspase9, p53 and Bax in liver and kidney. Compared with the model group, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the content of blood urea nitrogen (BUN), creatinine (Cr) in serum all decreased in SCBPE high dose group. Meanwhile, the activities of superoxide dismutase (SOD), catalase (CAT) and the content of reduced glutathione (GSH) in liver and kidney increased, and the content of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) decreased. In addition, the histopathologic aspects showed that the pathological changes of liver and kidney were found in the model group, and SCBPE group reduced to varying degrees. Moreover, the expression of NFκB, IL-1β, IL-6, cytochrome C, caspase3, caspase9, p53 and Bax in liver and kidney decreased. Therefore, SCBPE could reduce the damage of liver and kidney caused by CP by reducing the level of oxidative stress, and improving the antioxidant, anti-inflammatory and anti-apoptotic capacity of the body.

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PMID: 

Brain Sci. 2019 Oct 15 ;9(10). Epub 2019 Oct 15. PMID: 31618942

Abstract Title: 

Neuroprotective and Antioxidant Effect of Naringenin-Loaded Nanoparticles for Nose-to-Brain Delivery.

Abstract: 

Parkinson's disease (PD) is a neurodegenerative disorder resulting in a decreased nigrostriatal availability of dopamine. Oxidative stress is one factor contributing to PD. Naringenin (NAR), a flavonoid, is a potent antioxidant shown to be beneficial in experimental PD. The clinical development of NAR has been hampered due to its low bioavailability resulting from gastrointestinal degradation, inefficient permeability, and low aqueous solubility. The objective of the present research was to formulate and characterize naringenin-loaded chitosan nanoparticles (NAR NPs) for nose-to-brain delivery. The cellular uptake, cytotoxicity, and neuroprotective effects of NAR NPs were determined using the SH-SY5Y cell line in vitro. NAR NPs were prepared using the ionic gelation method and characterized by zetasizer, transmission electron microscopy (TEM), and field emission microscopy (FESEM). The average particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and 24 h in vitro release profile were 87.6± 8.47 nm, 0.31 ± 0.04, 15.36 ± 2.05 mV, 91.12 ± 2.99%, and 54.80 ± 4.22%, respectively. The percentage NAR permeation through nasal mucosa from NPs was found to be 67.90 ± 0.72%. Cellular uptake of prepared NPs was confirmed by fluorescence microscopy. Neuroprotective activity of NAR NPs wasevaluated through viability assays and by estimating reactive oxygen species (ROS) levels. NAR NPs showed enhanced neuroprotective ability and antioxidant effect against 6-OHDA-induced neurotoxicity in SH-SY5Y cells. However, animal studies are necessary to establish the potential of NAR NPs to be an effective carrier for the treatment of PD for nose-to-brain delivery.

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PMID: 

Exp Ther Med. 2020 Feb ;19(2):1313-1321. Epub 2019 Dec 19. PMID: 32010304

Abstract Title: 

Antioxidant, anti-inflammatory and anti-fibrotic effects ofgum resin in CCl-induced hepatotoxicity.

Abstract: 

The present study aims to investigate the potential antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate (BS) gum resin against carbon tetrachloride (CCl)-induced liver damage. Four groups consisting of eight rats each were designated: Group I, normal healthy control; group II, CCl-induced liver fibrosis; group III, CCl-induced liver fibrosis followed by BS treatment daily for two weeks; and group IV, CCl-induced liver fibrosis followed by silymarin treatment daily for two weeks. Expression of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB), interleukin-6 (IL-6), transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) were assessed, in addition to histopathological and fibrotic changes in liver tissues isolated from the rats. BS significantly ameliorated CCl-induced increases in serum aspartate (AST) and alanine transaminase (ALT) levels, reduced lactate dehydrogenase (LDH) activities in addition to restoring total bilirubin, triglyceride and albumin levels. BS treatment also alleviated oxidative stress and improved total antioxidant capacity in the liver, and reduced the expression of TNF-α, NF-κB, TGF-β, IL-6 and COX-2. On a histopathological level, BS treatment also exhibited antifibrotic activity. In conclusion, these findings suggest that BS contains potentially hepatoprotective effects against CCl4-induced liver injury via its antioxidant, anti-inflammatory and antifibrotic characteristics.

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PMID: 

Pharmacol Rep. 2020 Feb ;72(1):199-207. Epub 2020 Jan 8. PMID: 32016841

Abstract Title: 

Silymarin suppresses HepG2 hepatocarcinoma cell progression through downregulation of Slit-2/Robo-1 pathway.

Abstract: 

BACKGROUND: 14 million people are diagnosed with new cancer and approximately 8 million people die from cancer every year. Hepatocellular carcinoma is the most common type of liver cancer and covers almost 5-6% of cancer deaths worldwide. Silybum marianum, a plant that contains silymarin, has been used traditionally in the treatment of liver diseases for centuries. The antioxidant, anti-inflammatory and anti-fibrotic anti-cancer properties of silymarin have been demonstrated in several studies in vivo and in vitro. The Slit/Robo signaling pathway plays a role in many processes such as neurogenesis, angiogenesis, cell proliferation, cell movement, cancer progression, cell invasion, migration and metastasis. In this study, we aimed to investigate the effects of silymarin on HepG2 Hepatocellular carcinoma cells on Slit-2/Robo-1 signaling pathway and CXCR-4 which plays a role in the metastasis process.METHODS: HepG2 Hepatocellular carcinoma cells were used in the study. Different doses of silymarin's effect on HepG2 cells were observed by hematoxylin and eosin staining. Immunoblotting techniques were used to test the expression of Slit-2/Robo-1 and CXCR4 protein level. Immunocytochemistry was used to visualize the localization of Slit-2/Robo-1 and CXCR4 protein within the cells.RESULTS: Silymarin caused apoptosis in HepG2 cells, decreased the level of CXCR-4 protein dose-dependently, and decreased the Slit-2/Robo-1 protein level at low doses and increased it at high doses.CONCLUSIONS: Silymarin doses showed anti-carcinogenic, anti-metastatic and apoptotic effects in a dose-dependent manner on HepG2 cells through the Slit-2/Robo-1 pathway.

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PMID: 

J Pharm Pharmacol. 2020 Jan 10. Epub 2020 Jan 10. PMID: 31922618

Abstract Title: 

Natural polyphenols prevent indomethacin-induced and diclofenac-induced Caco-2 cell death by reducing endoplasmic reticulum stress regardless of their direct reactive oxygen species scavenging capacity.

Abstract: 

OBJECTIVES: Indomethacin (INDO) and diclofenac (DIC) can induce intestinal cell death through induction of oxidative stress-mediated ER stress and mitochondrial dysfunction. This study investigated the cytoprotective potential of 11 polyphenols, namely caffeic acid (CAF), curcumin (CUR), epigallocatechin gallate (EGCG), gallic acid (GAL), hypophyllanthin (HYPO), naringenin (NAR), phyllanthin (PHY), piperine (PIP), quercetin (QUE), rutin (RUT) and silymarin (SLY) against these two NSAIDs in Caco-2 cells.METHODS: Reactive oxygen species (ROS) production was determined with fluorescence spectroscopy using specific probes (DHE, DCFH-DA, HPF). Cell viability and mitochondrial function were assessed by MTT and TMRE assays. The mRNA levels of Bax, Bcl-2 and CHOP proteins were determined by quantitative real-time polymerase chain reaction technique.KEY FINDINGS: All test polyphenols reduced NSAIDs-mediated ROS production. Only EGCG, QUE and RUT protected INDO-/DIC-induced cell death. These three polyphenols suppressed Bax/Bcl-2 mRNA ratio, CHOP up-regulation and MMP disruption in NSAIDs-treated cells. CAF and NAR prevented cytotoxicity from INDO, but not DIC. The cytoprotective effect of NAR, but not CAF, involved alteration of Bax/Bcl-2 mRNA ratio or MMP disruption, but not CHOP transcription.CONCLUSION: The cytoprotective activity of polyphenols against NSAIDs-induced toxicity stemmed from either suppression of CHOP-related ER and mitochondria stresses or other CHOP-independent pathways, but not from the intrinsic ROS scavenging capacity.

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PMID: 

Res Pharm Sci. 2019 Dec ;14(6):566-573. Epub 2019 Dec 11. PMID: 32038736

Abstract Title: 

Naringenin potentiatedβ-sitosterol healing effect on the scratch wound assay.

Abstract: 

In the present investigation scratch wound assay was used to study the ability of several combinations of each flavonoid (chrysin, naringenin or resveratrol) withβ-sitosterol to heal wounds. MTT test was performed to determine if the combination of flavonoid withβ-sitosterol was toxic to fibroblasts or not. Also, superoxide dismutase (SOD) activity and interleukin-1β (IL-1β) concentrations were measured. The best closure rates were obtained with β-sitosterol combined with naringenin and β-sitosterol combined with resveratrol. The combination that produced the best closure rate namely β-sitosterol with naringenin increased SOD activity significantly. However, this combination was not better than naringenin or β-sitosterol alone in reducing IL-β concentration. The results of MTT test indicated that the combination as well as β-sitosterol aloneor naringenin alone has no toxic effect on fibroblasts. In conclusion, the combination of β-sitosterol and naringenin exerted a synergistic effect on wound closure without decreasing the viability of fibroblasts, increased antioxidant defense mechanism and decreased IL-β.

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