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17 pages, 5025 KiB

Open AccessArticle

Nanoparticulated Honokiol Mitigates Cisplatin-Induced Chronic Kidney Injury by Maintaining Mitochondria Antioxidant Capacity and Reducing Caspase 3-Associated Cellular Apoptosis

by Hung-Ting Liu, Tse-En Wang, Yu-Ting Hsu, Chi-Chung Chou, Kai-Hung Huang, Cheng-Chih Hsu, Hong-Jen Liang, Hui-Wen Chang, Tzong-Huei Lee and Pei-Shiue Tsai

Antioxidants 2019, 8(10), 466; https://doi.org/10.3390/antiox8100466 - 09 Oct 2019

Cited by 22 | Viewed by 4642

Abstract

Cisplatin is a potent anti-cancer drug, however, its accompanied organ-toxicity hampers its clinical applications. Cisplatin-associated kidney injury is known to result from its accumulation in the renal tubule with excessive generation of reactive oxygen species. In this study, we encapsulated honokiol, a natural [...] Read more.

Cisplatin is a potent anti-cancer drug, however, its accompanied organ-toxicity hampers its clinical applications. Cisplatin-associated kidney injury is known to result from its accumulation in the renal tubule with excessive generation of reactive oxygen species. In this study, we encapsulated honokiol, a natural lipophilic polyphenol constituent extracted from Magnolia officinalis into nano-sized liposomes (nanosome honokiol) and examined the in vivo countering effects on cisplatin-induced renal injury. We observed that 5 mg/kg body weight. nanosome honokiol was the lowest effective dosage to efficiently restore renal functions of cisplatin-treated animals. The improvement is likely due the maintenance of cellular localization of cytochrome c and thus preserves mitochondria integrity and their redox activity, which as a consequence, reduced cellular oxidative stress and caspase 3-associated apoptosis. These improvements at the cellular level are later reflected on the observed reduction of kidney inflammation and fibrosis. In agreement with our earlier in vitro study showing protective effects of honokiol on kidney cell lines, we demonstrated further in the current study, that nanosuspension-formulated honokiol provides protective effects against cisplatin-induced chronic kidney damages in vivo. Our findings not only benefit cisplatin-receiving patients with reduced renal side effects, but also provide potential alternative and synergic solutions to improve clinical safety and efficacy of cisplatin treatment on cancer patients. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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23 pages, 3719 KiB

Open AccessArticle

Anthocyanins Protect Hepatocytes against CCl₄-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells

by Dejan Popović, Gordana Kocić, Vuka Katić, Aleksandra Zarubica, Ljubinka Janković Veličković, Vanja P. Ničković, Andrija Jović, Andrej Veljković, Vladimir Petrović, Violeta Rakić, Zorica Jović, Nataša Poklar Ulrih, Danka Sokolović, Marko Stojanović, Marko Stanković, Goran Radenković, Gordana R. Nikolić, Аzra Lukač, Aleksandar Milosavljević and Dušan Sokolović

Antioxidants 2019, 8(10), 451; https://doi.org/10.3390/antiox8100451 - 04 Oct 2019

Cited by 34 | Viewed by 5707

Abstract

This study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from Vaccinim myrtillus (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl₄ (3 mL/kg, i.p.). The preventive treatment of the bilberry extract (200 mg anthocyanins/kg, orally, 7 days) prior [...] Read more.

This study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from Vaccinim myrtillus (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl₄ (3 mL/kg, i.p.). The preventive treatment of the bilberry extract (200 mg anthocyanins/kg, orally, 7 days) prior to the exposure to the CCl₄ resulted in an evident decrease in markers of liver damage (glutamate dehydrogenase, sorbitol dehydrogenase, malate dehydrogenase), and reduced pro-oxidative (conjugated dienes, lipid hydroperoxide, thiobarbituric acid reactive substances, advanced oxidation protein products, NADPH oxidase, hydrogen peroxide, oxidized glutathione), and pro-inflammatory markers (tumor necrosis factor-alpha, interleukin-6, nitrite, myeloperoxidase, inducible nitric oxide synthase, cyclooxygenase-2, CD68, lipocalin-2), and also caused a significant decrease in the dissipation of the liver antioxidative defence capacities (reduced glutathione, glutathione S-transferase, and quinone reductase) in comparison to the results detected in the animals treated with CCl₄ exclusively. The administration of the anthocyanins prevented the arginine metabolism’s diversion towards the citrulline, decreased the catabolism of polyamines (the activity of putrescine oxidase and spermine oxidase), and significantly reduced the excessive activation and hyperplasia of the Kupffer cells. There was also an absence of necrosis, in regard to the toxic effect of CCl₄ alone. The hepatoprotective mechanisms of bilberry extract are based on the inhibition of pro-oxidative mediators, strong anti-inflammatory properties, inducing of hepatic phase II antioxidant enzymes (glutathione S-transferase, quinone reductase) and reduced glutathione, hypoplasia of Kupffer cells, and a decrease in the catabolism of polyamines. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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19 pages, 5110 KiB

Open AccessArticle

A Delphinidin-Enriched Maqui Berry Extract Improves Bone Metabolism and Protects against Bone Loss in Osteopenic Mouse Models

by Masahiro Nagaoka, Toyonobu Maeda, Masahiro Chatani, Kazuaki Handa, Tomoyuki Yamakawa, Shuichi Kiyohara, Takako Negishi-Koga, Yasumasa Kato, Masamichi Takami, Shumpei Niida, Stefanie C. Lang, Marlena C. Kruger and Keiko Suzuki

Antioxidants 2019, 8(9), 386; https://doi.org/10.3390/antiox8090386 - 10 Sep 2019

Cited by 17 | Viewed by 5739

Abstract

In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui [...] Read more.

In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol^®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. MBE stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased alkaline phosphatase activity, through the upregulation of bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), Osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA expression. Immunostaining and immunoprecipitation assays demonstrated that MBE suppressed NF-κB transnucleation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, MBE inhibited both osteoclastogenesis in primary bone marrow macrophages and pit formation by maturated osteoclasts on dentine slices. Microcomputed tomography (micro-CT) and bone histomorphometry analyses of femurs demonstrated that the daily ingestion of MBE significantly increased BV/TV (ratio of bone volume to tissue volume), Tb.Th (trabecular thickness), Tb.N (trabecular number), N.Nd/N.Tm (node to terminus ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (bone formation rate per tissue volume), and significantly decreased Tb.Sp (trabecular separation), ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclast per unit of bone surface), compared to vehicle controls in osteopenic mouse models. These findings suggest that MBE can be a promising natural agent for the prevention of bone loss in osteopenic conditions by not only inhibiting bone resorption, but also stimulating bone formation. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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11 pages, 1691 KiB

Open AccessArticle

Evaluation of Antioxidant and Antiproliferative Properties of Cornus mas L. Fruit Juice

by Angeliki Tiptiri-Kourpeti, Eleni Fitsiou, Katerina Spyridopoulou, Stavros Vasileiadis, Christos Iliopoulos, Alex Galanis, Stavroula Vekiari, Aglaia Pappa and Katerina Chlichlia

Antioxidants 2019, 8(9), 377; https://doi.org/10.3390/antiox8090377 - 05 Sep 2019

Cited by 35 | Viewed by 3563

Abstract

Cornus mas L. (Cornelian cherry) is a flowering plant indigenous to Europe and parts of Asia, mostly studied for the antimicrobial activity of its juice. In this report, we investigated the composition and the in vitro antioxidant capacity of Cornus mas L. fruit [...] Read more.

Cornus mas L. (Cornelian cherry) is a flowering plant indigenous to Europe and parts of Asia, mostly studied for the antimicrobial activity of its juice. In this report, we investigated the composition and the in vitro antioxidant capacity of Cornus mas L. fruit juice from Greece, as well as its antiproliferative properties in vitro and in vivo. The fruits showed a high content of citric, malic, and succinic acid, in contrast to their juice, which had a low concentration of organic acids. The juice demonstrated significant antioxidant activity against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and modest antiproliferative potential against four human cancer cells lines and one murine: mammary adenocarcinoma MCF-7, hepatocellular carcinoma HepG2 and colon adenocarcinomas Caco2, HT-29, as well as murine colon carcinoma CT26. Cell viability was reduced by 40–50% following incubation of the cells with the highest concentration of the juice. Although Cornelian cherry juice exhibited in vitro growth inhibitory effects against colon carcinoma cells, no tumor growth inhibition was observed in an in vivo experimental colon carcinoma model in mice following prophylactic oral administration of a daily dose of 100 μL juice for a period of 10 days. Thus, our findings raise interesting questions for further research on Cornus mas L. fruit juice, and in parallel, the strong antioxidant potential implies that the plant could be further explored and exploited for its protective effect against oxidative damage. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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15 pages, 3983 KiB

Open AccessArticle

Inhibitory Effect of Nelumbo nucifera Leaf Extract on 2-Acetylaminofluorene-induced Hepatocarcinogenesis Through Enhancing Antioxidative Potential and Alleviating Inflammation in Rats

by Mon-Yuan Yang, Tung-Wei Hung, Chau-Jong Wang and Tsui-Hwa Tseng

Antioxidants 2019, 8(9), 329; https://doi.org/10.3390/antiox8090329 - 22 Aug 2019

Cited by 12 | Viewed by 3451

Abstract

Leaf extract of Nelumbo nucifera (NLE) has been demonstrated to possess anti-atherosclerosis, improve alcohol-induced steatohepatitis, prevent high-fat diet-induced obesity, and inhibit the proliferation and metastasis of human breast cancer cells. This study determines the chemopreventive role of NLE against 2-acetylaminofluorene (AAF)-induced hepatocellular carcinoma [...] Read more.

Leaf extract of Nelumbo nucifera (NLE) has been demonstrated to possess anti-atherosclerosis, improve alcohol-induced steatohepatitis, prevent high-fat diet-induced obesity, and inhibit the proliferation and metastasis of human breast cancer cells. This study determines the chemopreventive role of NLE against 2-acetylaminofluorene (AAF)-induced hepatocellular carcinoma (HCC) in rats. AAF was used to induce hepatocarcinogenesis in rats through genetic and nongenetic effects. After administration for 12 weeks, NLE (0.5–2%) supplementation orally inhibited AAF (0.03%)-induced hepatic fibrosis which appears during the development of premalignant lesions in rats. After the 6-month experiment, NLE supplementation resulted in decreasing AAF-induced serum parameters of hepatic injury, including the level of triglycerides, total cholesterol, alpha-fetoprotein (AFP), and inflammatory mediator interleukin (IL)-6 and tumor necrosis factor (TNF)-α as well as the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (γGT). NLE supplementation also reduced AAF-induced lipid peroxidation and 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation in the rat liver. Hepatic histopathological investigation revealed that NLE supplementation attenuated the AAF-induced HCC and glutathione S-transferase-Pi (GST-Pi) expression. Furthermore, NLE supplementation increased the expression of transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets, including catalase, glutathion peroxidase (GPx), and superoxide dismutase 1 (SOD-1) in the rat liver. Our findings indicate that NLE supplementation inhibited AAF-induced hepatocarcinogenesis by enhancing antioxidative potential and alleviating inflammation in rats. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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14 pages, 1537 KiB

Open AccessArticle

Induction of G2/M Cell Cycle Arrest and Apoptosis by Genistein in Human Bladder Cancer T24 Cells through Inhibition of the ROS-Dependent PI3k/Akt Signal Transduction Pathway

by Cheol Park, Hee-Jae Cha, Hyesook Lee, Hyun Hwang-Bo, Seon Yeong Ji, Min Yeong Kim, Su Hyun Hong, Jin-Woo Jeong, Min Ho Han, Sung Hyun Choi, Cheng-Yun Jin, Gi-Young Kim and Yung Hyun Choi

Antioxidants 2019, 8(9), 327; https://doi.org/10.3390/antiox8090327 - 21 Aug 2019

Cited by 69 | Viewed by 6049

Abstract

We examined the anti-cancer effect of genistein, a soy-derived isoflavone, in human bladder transitional cell carcinoma T24 cells. According to our data, genistein induced G2/M phase arrest of the cell cycle and apoptosis. Genistein down-regulated the levels of cyclin A and cyclin B1, [...] Read more.

We examined the anti-cancer effect of genistein, a soy-derived isoflavone, in human bladder transitional cell carcinoma T24 cells. According to our data, genistein induced G2/M phase arrest of the cell cycle and apoptosis. Genistein down-regulated the levels of cyclin A and cyclin B1, but up-regulated the levels of p21WAF1/CIP1, cyclin-dependent kinase (Cdk) inhibitor, that was complexed with Cdc2 and Cdk2. Furthermore, genistein induced the activation of caspases (caspase-3, -8 and -9), and cleavage of poly (ADP-ribose) polymerase cleavage. However, genistein-induced apoptosis was significantly inhibited by a pan-caspase inhibitor, indicating that the induction of apoptosis by genestein was caspase-dependent. In addition, genistein increased the cytosolic release of cytochrome c by increasing the Bax/Bcl-2 ratio and destroying mitochondria integrity. Moreover, genistein inactivated the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, while LY294002, a PI3K/Akt inhibitor, increased the apoptosis-inducing effect of genistein. Genistein further increased the accumulation of reactive oxygen species (ROS), which was significantly suppressed by N-acetyl cysteine (NAC), a ROS scavenger, and in particular, NAC prevented genistein-mediated inactivation of PI3K/Akt signaling, G2/M arrest and apoptosis. Therefore, the present results indicated that genistein promoted apoptosis induction in human bladder cancer T24 cells, which was associated with G2/M phase cell cycle arrest via regulation of ROS-dependent PI3K/Akt signaling pathway. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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14 pages, 1711 KiB

Open AccessArticle

Protective Effects of Melon Extracts on Bone Strength, Mineralization, and Metabolism in Rats with Ovariectomy-Induced Osteoporosis

by Bongju Kim, Sung-Ho Lee, Su-Jin Song, Won Hyeon Kim, Eun-Sung Song, Jae-Chang Lee, Sung-Jae Lee, Dong-Wook Han and Jong-Ho Lee

Antioxidants 2019, 8(8), 306; https://doi.org/10.3390/antiox8080306 - 14 Aug 2019

Cited by 12 | Viewed by 3602

Abstract

A polyphenolic extract from melon (Cucumis melo L.), as a potential source of natural antioxidants, has been reported to have a positive effect on osteoblast activity. In this study, the protective effects of heat-treated melon extract (ECO-A) on bone strength, mineralization, and [...] Read more.

A polyphenolic extract from melon (Cucumis melo L.), as a potential source of natural antioxidants, has been reported to have a positive effect on osteoblast activity. In this study, the protective effects of heat-treated melon extract (ECO-A) on bone strength, mineralization, and metabolism were examined in osteoporotic rat models. Osteoporosis was induced by ovariectomy (OVX) in female rats and then maintained for 8 weeks, along with the ingestion of phosphate-buffered saline (PBS, OVXP) or ECO-A (OVXE) for an additional 4 weeks. At a pre-determined timepoint, bone strengths, as well as bone mineral contents (BMC) and the density (BMD) of femurs and/or lumbar spines extracted from each animal, were measured by a mechanical test and dual-energy X-ray absorptiometry, respectively. Moreover, several biochemical markers for bone turnover were analyzed by respective colorimetric assay kits in addition to clinical analyses. The maximum load and stiffness of femurs from the OVXE group were found to be significantly higher than the other groups. Furthermore, the OVXE group showed significantly higher BMC, BMD, and bone volume than the OVX and OVXP groups, which were comparable to the non-OVX (sham) group. The levels of bone formation and resorption markers in the OVXE group were similar to the sham group, but significantly different from other groups. In conclusion, these results suggest that ECO-A can play potentially positive roles in the protection of bone loss in rats with OVX-induced osteoporosis. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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19 pages, 1892 KiB

Open AccessArticle

Carnosine Decreases PMA-Induced Oxidative Stress and Inflammation in Murine Macrophages

by Giuseppe Caruso, Claudia G. Fresta, Annamaria Fidilio, Fergal O’Donnell, Nicolò Musso, Giacomo Lazzarino, Margherita Grasso, Angela M. Amorini, Fabio Tascedda, Claudio Bucolo, Filippo Drago, Barbara Tavazzi, Giuseppe Lazzarino, Susan M. Lunte and Filippo Caraci

Antioxidants 2019, 8(8), 281; https://doi.org/10.3390/antiox8080281 - 06 Aug 2019

Cited by 59 | Viewed by 4970

Abstract

Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine. This naturally occurring molecule is present at high concentrations in several mammalian excitable tissues such as muscles and brain, while it can be found at low concentrations in a few invertebrates. Carnosine has [...] Read more.

Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine. This naturally occurring molecule is present at high concentrations in several mammalian excitable tissues such as muscles and brain, while it can be found at low concentrations in a few invertebrates. Carnosine has been shown to be involved in different cellular defense mechanisms including the inhibition of protein cross-linking, reactive oxygen and nitrogen species detoxification as well as the counteraction of inflammation. As a part of the immune response, macrophages are the primary cell type that is activated. These cells play a crucial role in many diseases associated with oxidative stress and inflammation, including atherosclerosis, diabetes, and neurodegenerative diseases. In the present study, carnosine was first tested for its ability to counteract oxidative stress. In our experimental model, represented by RAW 264.7 macrophages challenged with phorbol 12-myristate 13-acetate (PMA) and superoxide dismutase (SOD) inhibitors, carnosine was able to decrease the intracellular concentration of superoxide anions (O₂⁻•) as well as the expression of Nox1 and Nox2 enzyme genes. This carnosine antioxidant activity was accompanied by the attenuation of the PMA-induced Akt phosphorylation, the down-regulation of TNF-α and IL-6 mRNAs, and the up-regulation of the expression of the anti-inflammatory mediators IL-4, IL-10, and TGF-β1. Additionally, when carnosine was used at the highest dose (20 mM), there was a generalized amelioration of the macrophage energy state, evaluated through the increase both in the total nucleoside triphosphate concentrations and the sum of the pool of intracellular nicotinic coenzymes. Finally, carnosine was able to decrease the oxidized (NADP⁺)/reduced (NADPH) ratio of nicotinamide adenine dinucleotide phosphate in a concentration dependent manner, indicating a strong inhibitory effect of this molecule towards the main source of reactive oxygen species in macrophages. Our data suggest a multimodal mechanism of action of carnosine underlying its beneficial effects on macrophage cells under oxidative stress and inflammation conditions. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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22 pages, 2312 KiB

Open AccessArticle

Effect of Propolis on Diet-Induced Hyperlipidemia and Atherogenic Indices in Mice

by Nada Oršolić, Irena Landeka Jurčević, Domagoj Đikić, Dunja Rogić, Dyana Odeh, Vedran Balta, Eleonora Perak Junaković, Svjetlana Terzić and David Jutrić

Antioxidants 2019, 8(6), 156; https://doi.org/10.3390/antiox8060156 - 03 Jun 2019

Cited by 56 | Viewed by 5856

Abstract

Obesity, a major health problem worldwide, is associated with increased cardiovascular risk factors, such as dyslipidemia, glucose intolerance, and hypertension. We investigated the antioxidative capacity of the ethanol extract of propolis (EEP) and its effect on the lipid profile, the hepatorenal function, and [...] Read more.

Obesity, a major health problem worldwide, is associated with increased cardiovascular risk factors, such as dyslipidemia, glucose intolerance, and hypertension. We investigated the antioxidative capacity of the ethanol extract of propolis (EEP) and its effect on the lipid profile, the hepatorenal function, and the atherogenic indices in mice fed with a high-fat diet (HFD). EEP (50 mg/kg) was given orally to mice for 30 days. After the treatments, levels of the serum total triglyceride and cholesterol, the high density lipoprotein (HDL-c) and low density lipoprotein (LDL-c) cholesterols, the serum enzymes, and the metabolites were measured, and atherogenic indices [atherogenic index of plasma (AIP); cardiac risk ratio (CRR); cardioprotective index (CPI); atherogenic coefficient (AC)] were calculated and compared with the antioxidant, the reducing power, the radical-scavenging, and the chelating activity of EEP. The HFD diet with EEP significantly reduced the negative lipid profile and lowered AIP, CRR, and AC and increased CPI in animals on a HFD. In addition, EEP reduced the weight of mice and lipid accumulation in the liver, and it had significant in vitro antioxidative activities. The EEP possesses anti-hyperlipidemic and antioxidant activity and exhibits protective action on the cardiovascular system and hepatorenal functions. Our results contribute towards the validation of the traditional use of propolis as a food supplement in aiding hyperlipidemic disorders. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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20 pages, 5265 KiB

Open AccessArticle

Propolis Extracts Inhibit UV-Induced Photodamage in Human Experimental In Vitro Skin Models

by Athanasios Karapetsas, Georgia-Persephoni Voulgaridou, Manolis Konialis, Ilias Tsochantaridis, Spyridon Kynigopoulos, Maria Lambropoulou, Maria-Ioanna Stavropoulou, Konstantina Stathopoulou, Nektarios Aligiannis, Petros Bozidis, Anna Goussia, Konstantinos Gardikis, Mihalis I. Panayiotidis and Aglaia Pappa

Antioxidants 2019, 8(5), 125; https://doi.org/10.3390/antiox8050125 - 09 May 2019

Cited by 37 | Viewed by 5911

Abstract

The aim of this study was to assess the antioxidant, photoprotective, and antiaging effects of Greek propolis. Propolis was subjected to n-heptane or methanol extraction. Total phenolic/flavonoid content and antioxidant potential were determined in the extracts. Promising extracts were evaluated for their cytoprotective [...] Read more.

The aim of this study was to assess the antioxidant, photoprotective, and antiaging effects of Greek propolis. Propolis was subjected to n-heptane or methanol extraction. Total phenolic/flavonoid content and antioxidant potential were determined in the extracts. Promising extracts were evaluated for their cytoprotective properties using human immortalized keratinocyte (HaCaT) or reconstituted human skin tissue following exposure to UVB. Assessment of cytotoxicity, DNA damage, oxidative status, and gene/protein expression levels of various matrix metalloproteinases (MMPs) were performed. The propolis methanolic fractions exhibited higher total phenolic and flavonoid contents and significant in vitro antioxidant activity. Incubation of HaCaT cells with certain methanolic extracts significantly decreased the formation of DNA strand breaks following exposure to UVB and attenuated UVB-induced decrease in cell viability. The extracts had no remarkable effect on the total antioxidant status, but significantly lowered total protein carbonyl content used as a marker for protein oxidation in HaCaT cells. MMP-1, -3, -7, and -9, monitored as endpoints of antiaging efficacy, were significantly reduced by propolis following UVB exposure in a model of reconstituted skin tissue. In conclusion, propolis protects against the oxidative and photodamaging effects of UVB and could be further explored as a promising agent for developing natural antiaging strategies. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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11 pages, 11467 KiB

Open AccessArticle

Flavonoid Analysis and Antioxidant Activities of the Bryonia alba L. Aerial Parts

by Irina Ielciu, Michel Frédérich, Daniela Hanganu, Luc Angenot, Neli-Kinga Olah, Allison Ledoux, Gianina Crișan and Ramona Păltinean

Antioxidants 2019, 8(4), 108; https://doi.org/10.3390/antiox8040108 - 20 Apr 2019

Cited by 16 | Viewed by 5114

Abstract

Bryonia alba L. is the only Bryonia species found in Romanian flora, being known as a remedy for inflammatory pathologies or for its hepatoprotective and adaptogen activities. The present investigation studied the flavonoid composition and antioxidant activities of the aerial parts of this [...] Read more.

Bryonia alba L. is the only Bryonia species found in Romanian flora, being known as a remedy for inflammatory pathologies or for its hepatoprotective and adaptogen activities. The present investigation studied the flavonoid composition and antioxidant activities of the aerial parts of this species. Flavonoid profile was evaluated by HPLC coupled with Diode Array Detection (DAD), while antioxidant capacity was assessed by various methods, testing different antioxidant mechanisms: DPPH (2,2-diphenyl-1-picrylhydrazyl), CUPRAC (cupric reducing antioxidant capacity), FRAP (ferric reducing ability of plasma), TEAC (Trolox equivalent antioxidant capacity), EPR (electron paramagnetic resonance method) and SNPAC (silver nanoparticles antioxidant capacity). Cytotoxicity was tested on human cancerous and healthy cell lines. Anti-plasmodial tests were performed on two strains of Plasmodium falciparum. Whole organism toxicity was assessed on zebrafish larvae. The HPLC-DAD analysis proved the presence of lutonarin, saponarin, isoorientin, and isovitexin as the major flavonoids in the composition of tested samples. Significant results were obtained for all antioxidant capacity assays. The cytotoxicity tests proved the absence of cellular and parasitic toxicity and these results were confirmed by the lack of toxicity on the zebrafish larvae model. This study proves a promising potential of the aerial parts of Bryonia alba L. as antioxidant agents. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

14 pages, 1362 KiB

Open AccessArticle

Effects of Extra Virgin Olive Oil and Apples Enriched-Dark Chocolate on Endothelial Progenitor Cells in Patients with Cardiovascular Risk Factors: A Randomized Cross-Over Trial

by Francesca Felice, Alessandra Francini, Valentina Domenici, Mario Cifelli, Ester Belardinelli, Luca Sebastiani, Claudio Cantini and Rossella Di Stefano

Antioxidants 2019, 8(4), 88; https://doi.org/10.3390/antiox8040088 - 04 Apr 2019

Cited by 7 | Viewed by 4420

Abstract

Background: Endothelial dysfunction has been associated to cardiovascular outcomes in patients with cardiovascular risk factors. Circulating endothelial progenitor cells (EPCs) play an important physiological role for their reparative potential of vascular integrity, but are numerically reduced and functionally impaired in patients with cardiovascular [...] Read more.

Background: Endothelial dysfunction has been associated to cardiovascular outcomes in patients with cardiovascular risk factors. Circulating endothelial progenitor cells (EPCs) play an important physiological role for their reparative potential of vascular integrity, but are numerically reduced and functionally impaired in patients with cardiovascular risks. This study assesses the effects of Extra Virgin Olive Oil (EVOO) and apple-enriched dark chocolate intake on the blood levels of EPCs. Methods: Thirty volunteers with cardiovascular risk factors, enrolled in a randomised, crossover, four-weeks trial, received a solid dark chocolate bar (40 g/day) containing 10% EVOO or 2.5% dry apples. Urine samples were analyzed for endogenous metabolites. Circulating EPCs levels, clinical data and anthropometric examinations were collected. Results: 26 volunteers (M/F:14/12, 51 ± 9 years of age) completed the study. Comparison of pre-post intervention revealed a significant increase in EPCs levels associated with EVOO-dark chocolate consumption. Most biochemical parameters were not significantly modified by both chocolates. Conclusions: This study shows that a daily consumption of a non fattening dose of dark chocolate enriched with EVOO improves blood levels of EPCs, a well known surrogate biologic marker for endothelial function. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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16 pages, 1519 KiB

Open AccessArticle

Resveratrol Anti-Obesity Effects: Rapid Inhibition of Adipocyte Glucose Utilization

by Christian Carpéné, Francisco Les, Guillermo Cásedas, Cécile Peiro, Jessica Fontaine, Alice Chaplin, Josep Mercader and Víctor López

Antioxidants 2019, 8(3), 74; https://doi.org/10.3390/antiox8030074 - 26 Mar 2019

Cited by 43 | Viewed by 6940

Abstract

Studies in animal models of diabetes and obesity have shown that resveratrol mitigates complications of metabolic diseases, beyond those resulting from oxidative stress. Furthermore, results obtained with cultured preadipocytes have also revealed that prolonged resveratrol treatment impairs adipogenesis. Considering the role of adipocytes [...] Read more.

Studies in animal models of diabetes and obesity have shown that resveratrol mitigates complications of metabolic diseases, beyond those resulting from oxidative stress. Furthermore, results obtained with cultured preadipocytes have also revealed that prolonged resveratrol treatment impairs adipogenesis. Considering the role of adipocytes in the hypertrophy of fat stores, and keeping in mind that insulin is the main trigger of excessive energy storage during post-prandial periods, the present study aimed to investigate how short-term effects of resveratrol can limit glucose disposal in a gut-adipose tissue axis. We found that resveratrol exhibits a more potent inhibitory capacity towards α-glucosidase than pancreatic lipase activity. Resveratrol also rapidly blunts glucose transport in mature fat cells by counteracting the effect of insulin and insulin-like lipogenic agents. Within two hours, resveratrol also inhibited the incorporation of glucose into lipids of adipocytes, which was unaffected by membrane cholesterol depletion. Moreover, the comparison between adipocytes with invalidated semicarbazide-sensitive amine oxidase activity and their control, or between resveratrol and several inhibitors, did not indicate that the recently described interaction of resveratrol with amine oxidases was involved in its antilipogenic effect. Caffeine and piceatannol, previously said to interact with glucose carriers, also inhibit lipogenesis in adipocytes, whereas other antioxidant phytochemicals do not reproduce such an antilipogenic effect. This study highlights the diverse first steps by which resveratrol impairs excessive fat accumulation, indicating that this natural molecule and its derivatives deserve further studies to develop their potential anti-obesity properties. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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10 pages, 246 KiB

Open AccessArticle

Production of a Novel Functional Fruit Beverage Consisting of Cornelian Cherry Juice and Probiotic Bacteria

by Ioanna Mantzourani, Chryssa Nouska, Antonia Terpou, Athanasios Alexopoulos, Eugenia Bezirtzoglou, Mihalis I. Panayiotidis, Alexis Galanis and Stavros Plessas

Antioxidants 2018, 7(11), 163; https://doi.org/10.3390/antiox7110163 - 12 Nov 2018

Cited by 59 | Viewed by 5261

Abstract

The present study describes the development of a novel functional beverage through the application of probiotic Lactobacillus plantarum ATCC (American Type Culture Collection) 14917 in Cornelian cherry juice fermentation. The probiotic was employed in free and immobilized in a delignified wheat bran carrier [...] Read more.

The present study describes the development of a novel functional beverage through the application of probiotic Lactobacillus plantarum ATCC (American Type Culture Collection) 14917 in Cornelian cherry juice fermentation. The probiotic was employed in free and immobilized in a delignified wheat bran carrier (DWB) form. Cornelian cherry juice was fermented for 24 h and then it was stored at 4 °C for 4 weeks. Several parameters were evaluated such as residual sugar, organic acid and alcohol levels, total phenolics content, and cell viability as well as consumers acceptance. Regarding sugar and organic acids analyses, it was proved that the probiotic free or immobilized biocatalyst was effective. The concentration of ethanol was maintained at low levels (0.3–0.9% v/v). The total phenolic content of fermented Cornelian cherry juice with immobilized cells was recorded in higher levels (214–264 mg GAE/100 mL) for all the cold storage time compared to fermented juice with free cells (165–199 mg GAE/100 mL) and non-fermented juice (135–169 mg GAE/100 mL). Immobilized cells retained their viability in higher levels (9.95 log cfu/mL at the 4th week) compared to free cells (7.36 log cfu/mL at the 4th week). No significant sensory differences were observed among the fermented and the non-fermented samples. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

11 pages, 1503 KiB

Open AccessArticle

Bark of Passiflora edulis Treatment Stimulates Antioxidant Capacity, and Reduces Dyslipidemia and Body Fat in db/db Mice

by Marielle Fernanda Panelli, Damiana Tortolero Pierine, Sérgio Luiz Borges De Souza, Artur Júnio Togneri Ferron, Jéssica Leite Garcia, Klinsmann Carolo dos Santos, Matheus Antônio Filiol Belin, Giuseppina Pace Pereira Lima, Milena Galhardo Borguini, Igor Otávio Minatel, Antônio Carlos Cicogna, Fabiane Valentini Francisqueti and Camila Renata Corrêa

Antioxidants 2018, 7(9), 120; https://doi.org/10.3390/antiox7090120 - 08 Sep 2018

Cited by 30 | Viewed by 5091

Abstract

Obesity is considered an important risk factor for several disorders, such as diabetes mellitus, systemic arterial hypertension, dyslipidemia, and atherosclerosis, which are associated with inflammation and oxidative stress as a trigger factor. Passiflora edulis contains important bioactive compounds, such as phenolics, carotenoids, vitamin [...] Read more.

Obesity is considered an important risk factor for several disorders, such as diabetes mellitus, systemic arterial hypertension, dyslipidemia, and atherosclerosis, which are associated with inflammation and oxidative stress as a trigger factor. Passiflora edulis contains important bioactive compounds, such as phenolics, carotenoids, vitamin C, and polyamines in pulp, leaves, seeds, and bark. Aim: To evaluate the effect of bark of Passiflora edulis (BPe) on body composition, and metabolic and oxidative stress parameters in genetically obese mice. Methods: Obese male db/db mice (n = 14 animals) received normal feeds and water ad libitum for 8 weeks. Then, animals were randomly divided to continue either receiving standard chow (obese, n = 7 (OB)) or feed with standard chow plus bark Passiflora edulis (BPe) (obese + BPe, n = 7 (OB + BPe)) for 8 more weeks, totaling 16 weeks. BPe was added to chow (7 g of BPe/kg of chow corresponding to 1.5 g/kg of body weight). The parameters evaluated in animals included food and caloric intake, body weight, body fat, plasma glucose, triglycerides, and total cholesterol. Malondialdehyde and antioxidant capacity were evaluated in plasma and organs. Groups were compared by Student t-test, with p < 0.05. Results: BPe reduced visceral and subcutaneous fat deposit and adiposity index, cholesterol and triglyceride levels, ameliorated the antioxidant capacity, and reduced malondialdehyde (MDA) levels. Conclusion: the bark of Passiflora edulis was effective in improving body composition, and metabolic and antioxidant parameters in obese mice. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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Review

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15 pages, 915 KiB

Open AccessReview

Curcumin as a Therapeutic Option in Retinal Diseases

by Daniel López-Malo, Carlos Alberto Villarón-Casares, Jorge Alarcón-Jiménez, Maria Miranda, Manuel Díaz-Llopis, Francisco J. Romero and Vincent M. Villar

Antioxidants 2020, 9(1), 48; https://doi.org/10.3390/antiox9010048 - 06 Jan 2020

Cited by 39 | Viewed by 6211

Abstract

The retina is subjected to oxidative stress due to its high vascularization, long time light exposition and a high density of mitochondria. Oxidative stress can lead to pathological processes, like cell apoptosis, angiogenesis and inflammation ending in retinal pathologies. Curcumin, a major bioactive [...] Read more.

The retina is subjected to oxidative stress due to its high vascularization, long time light exposition and a high density of mitochondria. Oxidative stress can lead to pathological processes, like cell apoptosis, angiogenesis and inflammation ending in retinal pathologies. Curcumin, a major bioactive component obtained from the spice turmeric (Curcuma longa) rhizome has been used for centuries in Asian countries for cooking and for curing all kinds of diseases like dysentery, chest congestion and pain in general, due to its antioxidant effects. Curcumin prevents the formation of reactive oxygen species and so it is a good protective agent. Curcumin has shown also anti-inflammatory, and antitumor properties. Curcumin is a natural product, which can be a therapeutic option in a variety of retinal diseases due to its pleiotropic properties. Some drawbacks are its poor solubility, bioavailability and lack of stability at physiological conditions; which have been shown in curcumin skeptical publications. In this review, we provide some lights and shadows on curcumin administration on the major retinal pathologies. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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25 pages, 1809 KiB

Open AccessReview

Carotenoids of Capsicum Fruits: Pigment Profile and Health-Promoting Functional Attributes

by Norazian Mohd Hassan, Nurul Asyiqin Yusof, Amirah Fareeza Yahaya, Nurul Nasyitah Mohd Rozali and Rashidi Othman

Antioxidants 2019, 8(10), 469; https://doi.org/10.3390/antiox8100469 - 09 Oct 2019

Cited by 92 | Viewed by 11892

Abstract

Pepper of the Capsicum species is a common ingredient in various food preparations by different cultures worldwide. The Capsicum is recognised by its five main domesticated species, namely Capsicum annuum, C. baccatum, C. chinense, C. frutescens and C. pubescens. The genetic diversity [...] Read more.

Pepper of the Capsicum species is a common ingredient in various food preparations by different cultures worldwide. The Capsicum is recognised by its five main domesticated species, namely Capsicum annuum, C. baccatum, C. chinense, C. frutescens and C. pubescens. The genetic diversity in Capsicum offers fruits in wide ranges of morphology and carotenoid profile. Carotenoids enhance the value of pepper from a nutritional standpoint, despite being commonly prized for the pharmacologically active pungent capsaicinoids. Carotenoids of pepper comprise mainly of the unique, powerful and highly stable capsanthin and capsoroubin, together with β-carotene, β-cryptoxanthin, lutein, zeaxanthin, antheraxanthin and violaxanthin. These carotenoids are present at diverse profile and varying levels, biosynthetically connected to the fruit maturity stages. This review describes the health-promoting functional attributes of the carotenoids that are mainly associated with their excellent role as lipophilic antioxidants. Capsicum as a great source of carotenoids is discussed in the aspects of main domesticated species, biosynthesis, pigment profile, antioxidant activity and safety. Findings from a number of in vitro, in vivo and clinical studies provided appreciable evidence on the protective effects of pepper’s carotenoids against degenerative diseases. Hence, pepper with its functional carotenoids might be recommended in health-promoting and disease preventing strategies. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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18 pages, 650 KiB

Open AccessReview

Anticancer Activity of Essential Oils and Other Extracts from Aromatic Plants Grown in Greece

by Eleni Fitsiou and Aglaia Pappa

Antioxidants 2019, 8(8), 290; https://doi.org/10.3390/antiox8080290 - 07 Aug 2019

Cited by 37 | Viewed by 5041

Abstract

Aromatic plants have a long and significant history in the traditional medicine of many countries. Nowadays, there is an increasing interest in investigating the biological properties of aromatic plant extracts mainly due to their diversity, high availability, and low toxicity. Greece is abundant [...] Read more.

Aromatic plants have a long and significant history in the traditional medicine of many countries. Nowadays, there is an increasing interest in investigating the biological properties of aromatic plant extracts mainly due to their diversity, high availability, and low toxicity. Greece is abundant in aromatic plants, which can be attributed to the country’s geographical position, the morphology of its landscape, and its numerous mountainous and insular areas. In the past 15 years, a number of aromatic plant extracts of Greek origin have been studied for their bioactivities, including their antiproliferative potential against different types of cancer. Although the pharmacological activities of specific species of Greek origin have been reviewed before, no gathered information on explicitly Greek species exist. In this review, we summarize existing data on the antiproliferative activity of extracts isolated from Greek aromatic plants and discuss their molecular mode(s) of action, where available, in order to identify promising extracts for future research and link chemical constituents responsible for their activity. We conclude that essentials oils are the most frequently studied plant extracts exhibiting high diversity in their composition and anticancer potential, but also other extracts appear to be worthy of further investigation for cancer chemoprevention. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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35 pages, 788 KiB

Open AccessReview

The Role of Isothiocyanates as Cancer Chemo-Preventive, Chemo-Therapeutic and Anti-Melanoma Agents

by Melina Mitsiogianni, Georgios Koutsidis, Nikos Mavroudis, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Vasilis Zoumpourlis, Tom Amery, Alex Galanis, Aglaia Pappa and Mihalis I. Panayiotidis

Antioxidants 2019, 8(4), 106; https://doi.org/10.3390/antiox8040106 - 18 Apr 2019

Cited by 83 | Viewed by 9728

Abstract

Many studies have shown evidence in support of the beneficial effects of phytochemicals in preventing chronic diseases, including cancer. Among such phytochemicals, sulphur-containing compounds (e.g., isothiocyanates (ITCs)) have raised scientific interest by exerting unique chemo-preventive properties against cancer pathogenesis. ITCs are the major [...] Read more.

Many studies have shown evidence in support of the beneficial effects of phytochemicals in preventing chronic diseases, including cancer. Among such phytochemicals, sulphur-containing compounds (e.g., isothiocyanates (ITCs)) have raised scientific interest by exerting unique chemo-preventive properties against cancer pathogenesis. ITCs are the major biologically active compounds capable of mediating the anticancer effect of cruciferous vegetables. Recently, many studies have shown that a higher intake of cruciferous vegetables is associated with reduced risk of developing various forms of cancers primarily due to a plurality of effects, including (i) metabolic activation and detoxification, (ii) inflammation, (iii) angiogenesis, (iv) metastasis and (v) regulation of the epigenetic machinery. In the context of human malignant melanoma, a number of studies suggest that ITCs can cause cell cycle growth arrest and also induce apoptosis in human malignant melanoma cells. On such basis, ITCs could serve as promising chemo-therapeutic agents that could be used in the clinical setting to potentiate the efficacy of existing therapies. Full article

(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)

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