PMID: 

J Integr Med. 2017 03 ;15(2):158-164. PMID: 28285621

Abstract Title: 

Antidiarrheal activity of hexane extract of Citrus limon peel in an experimental animal model.

Abstract: 

OBJECTIVE: Acute diarrhea is one of the major illnesses that cause death in children, despite clinical interventions and the use of oral rehydration therapy. Thus, there is need to discover other effective, affordable and accessible treatments for this disease. Therefore, this study was carried out to investigate the effects of hexane extract of Citrus limon peel (HECLP) on castor oil-induced diarrhea in rats.METHODS: Diarrhea was induced in male albino Wistar rats weighing 100-150 g. The antidiarrheal activity of HECLP at different oral dosages (5, 10 and 20 mg/kg) was investigated by counting the number of wet fecal pellets. Animals were further treated with propranolol, prazosin, nifedipine and atropine to assess the effects of receptor blockers on the activities of the extract. The effects of HECLP on castor oil-induced enteropooling and the intestinal transit time of activated charcoal were also evaluated.RESULTS: Each of the 3 doses of C. limon significantly reduced (P

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PMID: 

Appl Physiol Nutr Metab. 2017 May ;42(5):479-486. Epub 2016 Dec 15. PMID: 28177735

Abstract Title: 

Protective effects of essential oil of Citrus limon against aspirin-induced toxicity in IEC-6 cells.

Abstract: 

Aspirin, one of the widely used nonsteroidal anti-inflammatory drugs, is the most highly consumed pharmaceutical product in the world. However, it has several side effects in cells. This study was designed to investigate the antioxidative activity and cytoprotective effects of essential oil of Citrus limon (EOC) extracted from leaves against aspirin-induced damages in the rat small intestine epithelial cells (IEC-6). Biochemical indicators were used to assess cytotoxicity and oxidative damages caused by aspirin treatment on IEC-6. Our results showed that the chemical characterization of EOC identified 25 compounds representing 98.19% of the total oil. The major compounds from this oil were z-citral (53.21%), neryl acetate (13.06%), geranyl acetate (10.33%), and limonene (4.23%). Aspirin induced a decrease in cell viability as well as an increase in superoxide dismutase (SOD) and catalase (CAT) activities. Contrariwise, the co-exposure of cells to aspirin and EOC alleviated every above syndrome by an increase in cell survival and decrease in SOD and CAT activities. In conclusion, the essential oil of C. limon has a potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

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PMID: 

Biomed Pharmacother. 2016 Oct ;83:1327-1334. Epub 2016 Aug 27. PMID: 27571876

Abstract Title: 

The protective effect of Citrus limon essential oil on hepatotoxicity and nephrotoxicity induced by aspirin in rats.

Abstract: 

Citrus limon is a member of the large Rutaceae family characterized by its therapeutic proprieties and has been widely used in traditional medicine to treat various diseases. This study investigates the protective effect of Citrus limon essential oil against a high dose of aspirin-induced acute liver and kidney damage in female Wistar albino rats. Twenty-eight adult female Wistar rats were divided into 4 groups of 7 each: (1) a control group; (2) a group of rats which was kept untreated for 56days then treated with aspirin (A) (600mg/kg) for 4 days; (3) a group fed with essential oil of Citrus limon for 56days then (A) for 4 days; and (4) a group of rats receiving essential oil of Citrus limon for 56 days, then given NaCl for 4 days. Estimations of biochemical parameters in blood were determined. Lipid peroxidation levels (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidas (GPx) activities in liver and kidney was determined. A histopathological study was done. Under our experimental conditions, aspirin induced an increase of serum biochemical parameters and it resulted in an oxidative stress in both liver and kidney. This was evidenced by significant increase in TBARS in liver and kidney by 108% and 55%, respectively, compared to control. On the other hand, a decrease in the activities of SOD by 78% and 53%, CAT by 53% and 78%, and GPx by 78% and 51% in liver and kidney, respectively. Administration of EOC to rats attenuated the induced an effect of the high dose of aspirin induced in the afore mentioned serum biochemical parameters. In conclusion, our data suggest that treatment with essential oil of Citrus limon prevented the liver and kidney damage induced by aspirin.

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PMID: 

Biomed Res Int. 2018 ;2018:6251546. Epub 2018 Jan 15. PMID: 29568760

Abstract Title: 

from Tunisia: Phytochemical and Physicochemical Properties and Biological Activities.

Abstract: 

Natural plant extracts contain a variety of phenolic compounds which are assigned various biological activities. Our work aims to make a quantitative and qualitative characterization of the Zest (ZL) and the Flesh (FL) of lemon, to valorize the pharmacological uses of lemon, by evaluatingactivities (DPPH, free radical scavenging and reducing power). The antibacterial, antifungal, and antiproliferative activities were sought in the ability ofextracts to protect DNA and protein. We found that the ZL contains high amounts of phenolics responsible for the important antioxidant properties of the extract. However, the FL is richer in flavonoids than the ZL. The FL extract was also found to be more effective than the ZL in protecting plasmid DNA against the strand breakage induced by hydroxyl radicals. We also concluded that the FL extract exhibited potent antibacterial activity unlike ZL. Analysis by LC/MS-MS identified 6 compounds (Caffeoyl N-Tryptophan, Hydroxycinnamoyl-Oglucoside acid, Vicenin 2, Eriocitrin, Kaempferol-3-O- rutinoside, and Quercetin-3-rutinoside). These preliminary results showed thathas antibacterial and antioxidant activity. It would be interesting to conduct further studies to evaluate thepotential in an animal model.

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PMID: 

J Nat Med. 2017 Oct ;71(4):735-744. Epub 2017 Jul 11. PMID: 28699128

Abstract Title: 

Structures of antimutagenic constituents in the peels of Citrus limon.

Abstract: 

The methanolic extracts from the peels of Citrus limon were found to show antimutagenic effects against 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the Ames test. From the methanolic extracts, four new coumarins (wakayamalimonol A-D) and a new furanocoumarin (wakayamalimonol E) were isolated together with fifteen known compounds. The absolute stereostructures of the new compounds were determined by chemical synthesis and the modified Mosher's method. Among the isolated constituents, coumarins, furanocoumarins, and limonoids showed antimutagenic effects in the Ames test. One of the major constituent, limonin, showed significant antimutagenic effects against mitomycinC and PhIP in the micronucleus test in vivo.

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Merck has received the FDA’s fast-tracked approval of a live, genetically modified Ebola vaccine which, according to its vaccine insert, can cause a novel new form of Ebola-type infection, resulting in immunosuppression and possible shedding of live virus to others.

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PMID: 

Curr Pharm Biotechnol. 2018 ;19(11):877-885. PMID: 30332948

Abstract Title: 

Exosome-like Nanovesicles Isolated from Citrus limon L. Exert Antioxidative Effect.

Abstract: 

BACKGROUND: Exosome-like nanovesicles are biological nanostructures mediating cell-tocell communication and capable to load selected cargos also in the interaction among different species.OBJECTIVE: We aimed to explore the content of exosome-like nanovesicles derived from Citrus limon L. and to analyze the effects of their uptake on human cells.METHOD: We isolated exosome-like nanovesicles from Citrus limon L. juice (EXO-CLs) by differential centrifugation. EXO-CLs were analyzed for short RNA content by advanced sequencing technologies, and for ascorbic acid (vitamin C) and citrate content by enzymatic assays. EXO-CLs anti-oxidant and pro-differentiative potential was evaluated in vitro on mesenchymal stromal cells (MSC), a common tool for regenerative strategies for several human tissues.RESULTS: We showed that EXO-CLs carry detectable amounts of citrate and vitamin C and, although it was not possible to identify specific miRNAs, we detected short RNA sequences (20-30 bp) with unknown functions and with different distribution size in respect to whole Citrus limon L. juice. In vitro, EXO-CLs were uptaken by MSC and had a significant protective effect against oxidative stress. Furthermore, regarding the potential benefit for human bone health, we found that EXO-CLs modulate MSC differentiation versus the osteogenic lineage.CONCLUSION: We demonstrated that incubation with EXO-CLs exert antioxidant activity in human cells. This is most likely due to the direct delivery and uptake of micronutrients by human cells that are well preserved inside the nanovesicle membrane, including the unstable vitamin C. Based on our results, we speculate that fruit-derived nanovesicles have the potential to mediate interspecies influence after food intake.

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PMID: 

Oncotarget. 2015 Aug 14 ;6(23):19514-27. PMID: 26098775

Abstract Title: 

Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death.

Abstract: 

Nanosized vesicles are considered key players in cell to cell communication, thus influencing physiological and pathological processes, including cancer. Nanovesicles have also been found in edible-plants and have shown therapeutic activity in inflammatory bowel diseases; however information on their role in affecting cancer progression is missing.Our study identify for the first time a fraction of vesicles from lemon juice (Citrus limon L.), obtained as a result of different ultracentrifugation, with density ranging from 1,15 to 1,19 g/ml and specific proteomic profile. By using an in vitro approach, we show that isolated nanovesicles inhibit cancer cell proliferation in different tumor cell lines, by activating a TRAIL-mediated apoptotic cell death. Furthermore, we demonstrate that lemon nanovesicles suppress CML tumor growth in vivo by specifically reaching tumor site and by activating TRAIL-mediated apoptotic cell processes. Overall, this study suggests the possible use of plant-edible nanovesicles as a feasible approach in cancer treatment.

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PMID: 

Biomolecules. 2019 Dec 5 ;9(12). Epub 2019 Dec 5. PMID: 31817563

Abstract Title: 

Lemon Peel Polyphenol Extract Reduces Interleukin-6-Induced Cell Migration, Invasiveness, and Matrix Metalloproteinase-9/2 Expression in Human Gastric Adenocarcinoma MKN-28 and AGS Cell Lines.

Abstract: 

Among plant polyphenols, lemon peels extract (LPE) from the residues of the industrial processing of lemon (shows anti-proliferative properties in cancer cells and anticholinesterase activity. In this study, we analyze the anti-cancer properties of LPE on migration and invasiveness in MKN-28 and AGS human gastric cancer cell lines either in the absence or presence of the pro-inflammatory cytokine IL-6. We find that the pretreatment with non-cytotoxic concentrations (0.5-1μg/ml of gallic acid equivalent) of LPE inhibits interleukin-6 (IL-6)-induced cell migration and invasiveness in MKN-28 and AGS cells, as analyzed by wound and matrigel assays. Pretreatment with LPE is able to prevent either IL-6-induced matrix metalloproteinases (MMP)-9/2 activity, as assessed bygel zymography, or mRNA and protein MMP-9/2 expression, as evaluated by qPCR and Western blotting analysis, respectively. These LPE effects are associated with an IL-6-dependent STAT3 signaling pathway in MKN-28 and AGS cells. Furthermore, LPE shows acetylcholinesterase inhibitory activity when assayed by the Ellman method. In conclusion, our results demonstrate that LPE reduces the invasiveness of gastric MKN-28 and AGS cancer cells through the reduction of IL-6-induced MMP-9/2 up-regulation. Therefore, these data suggest that LPE exerts a protective role against the metastatic process in gastric cancer.

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PMID: 

Molecules. 2019 Dec 13 ;24(24). Epub 2019 Dec 13. PMID: 31847295

Abstract Title: 

Polyphenols, Antioxidant, Antibacterial, and Biofilm Inhibitory Activities of Peel and Pulp ofL.,, andcv. Salò Cultivated in Southern Italy.

Abstract: 

The aim of this paper was to study the polyphenols of peel and pulp of threetaxa-, andcv. Salò-cultivated in the Cosenza province, Southern Italy, and to evaluate their antioxidant and antibacterial activity, performed against,,,, and. Furthermore, we assessed the inhibitory effect of the extracts on bacterial capacity to form biofilm, and on the metabolic activity of the cells present therein. The results indicated that such extracts could find new potential applications in the field of natural antioxidant and anti-bacterial agents in pharmaceutics, agriculture, and food fields.

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