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PMID: 

Molecules. 2019 Feb 12 ;24(3). Epub 2019 Feb 12. PMID: 30759846

Abstract Title: 

Korean Thistle (var.(Maxim.) Matsum.): A Potential Dietary Supplement against Diabetes and Alzheimer's Disease.

Abstract: 

In the search for natural products having a dual inhibitory action on diabetes and Alzheimer's disease, this study investigated the activity of different parts of Korean thistle (var.(Maxim.) Matsum), and its fractional constituents by in vitro enzymatic and in silico molecular docking studies.has been used as a traditional medicine for the treatment of several diseases. The ethyl acetate and dichloromethane fractions of a leaf extract showedα-glucosidase and BACE1 inhibitory activity, respectively. Furthermore, the isolated compound, luteolin, exhibited concentration-dependent non-competitive inhibition against both α-glucosidase and BACE1 (IC= 51.27± 1.23 and 13.75 ± 0.26 μM;value = 52.04 and 14.76μM, respectively). Moreover, docking studies showed that luteolin formed a strong hydrogen bond with the peripheral binding amino acid residues, and hydrophobic interactions with the α-glucosidase and BACE1 enzymes. Therefore, Korean thistle may act as an important dietary supplement against diabetes and Alzheimer's disease, especially the leaves, because of the preponderance of the active component, luteolin, making Korean thistle a promising candidate for more detailed in vitro and in vivo studies.

PMID: 

Plant Foods Hum Nutr. 2019 Dec 14. Epub 2019 Dec 14. PMID: 31838616

Abstract Title: 

Pomegranate Juice and Peel Extracts are Able to Inhibit Proliferation, Migration and Colony Formation of Prostate Cancer Cell Lines and Modulate the Akt/mTOR/S6K Signaling Pathway.

Abstract: 

Pomegranate (Punica granatum) is known to contain polyphenols with many potential health benefits, including anti-tumoral, anti-inflammatory, and anti-microbial properties. It has been used in popular medicine for cancer treatment, which still represents the major cause of cancer-related deaths in men worldwide. Importantly, pomegranate peels are valuable by-products of the food industry that are rich in polyphenols. Here we report a comparison between juice and peel aqueous extracts in prostate cancer DU-145 and PC-3 cell lines. Both extracts were able to inhibit the proliferation, migration and colony formation of those cells, although peel extracts presented more robust effects compared to juice. Besides, the growth-related mTOR/S6K signaling pathway presented strong inhibition after pomegranate extracts treatment. This study presents evidence that both juice and isolated peel extracts from promegate fruit have important anti-cancer effects against prostate cancer cells, modulating the mTOR/S6K signaling pathway.

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PMID: 

Biosci Biotechnol Biochem. 2019 Dec 22:1-7. Epub 2019 Dec 22. PMID: 31868102

Abstract Title: 

Ellagitannins fromleaves suppress microsomal prostaglandin E synthase-1 expression and induce lung cancer cells to undergo apoptosis.

Abstract: 

Prostaglandin E(PGE), which is a potent pro-inflammatory lipid mediator, is biosynthesized from arachidonic acid by cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Non-steroidal anti-inflammatory drugs (NSAIDs) are used clinically as COX inhibitors, but they have gastrointestinal and cardiovascular side-effects. Thus, the terminal enzyme mPGES-1 holds promise as the next therapeutic target. In this study, we found that the ellagitannins granatin A and granatin B isolated from pomegranate leaves, and geraniin, which is their structural analog, selectively suppressed mPGES-1 expression without affecting COX-2 in non-small cell lung carcinoma A549 cells. The ellagitannins also down-regulated tumor necrosis factorα, inducible nitric oxide synthase, and anti-apoptotic factor B-cell chronic lymphocytic leukemia/lymphoma 2, and induced A549 cells to undergo apoptosis. These findings indicate that the ellagitannins have anti-inflammatory and anti-carcinogenic effects, due to their specific suppression of mPGES-1.: Bcl-2: B-cell chronic lymphocytic leukemia/lymphoma 2; COX: cyclooxygenase; CRE: cAMP response element; DHHDP: dehydrohexahydroxydiphenoyl; EtO: diethyl ether; EtOAc: ethyl acetate; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; iNOS: inducible nitric oxide synthase; mPGES-1: microsomal prostaglandin E synthase-1;-BuOH: water-saturated-butanol; NSAIDs: non-steroidal anti-inflammatory drugs; NF-κB: nuclear factor-κB; PG: prostaglandin; TNF: tumor necrosis factor; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling.

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PMID: 

Pharm Biol. 2017 Dec ;55(1):1780-1786. PMID: 28524774

Abstract Title: 

Cytotoxicity and anti-Leishmania amazonensis activity of Citrus sinensis leaf extracts.

Abstract: 

CONTEXT: Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease characterized by lesional polymorphism and the commitment of skin surface. Previous reports demonstrated that the Citrus genus possess antimicrobial activity.OBJECTIVE: This study evaluated the anti-L. amazonensis activity of Citrus sinensis (L.) Osbeck (Rutaceae) extracts.MATERIALS AND METHODS: Citrus sinensis dried leaves were subjected to maceration with hexane (CH), ethyl acetate (CEA), dichloromethane/ethanol (CD/Et – 1:1) or ethanol/water (CEt/W – 7:3). Leishmania amazonensis promastigotes were treated with C. sinensis extracts (1-525 μg/mL) for 120 h at 27 °C. Ultrastructure alterations of treated parasites were evaluated by transmission electron microscopy. Cytotoxicity of the extracts was assessed on RAW 264.7 and J774.G8 macrophages after 48-h treatment at 37 °C using the tetrazolium assay. In addition, Leishmania-infected macrophages were treated with CH and CD/Et (10-80 μg/mL).RESULTS: CH, CD/Et and CEA displayed antileishmanial activity with 50% inhibitory activity (IC) of 25.91 ± 4.87, 54.23 ± 3.78 and 62.74 ± 5.04 μg/mL, respectively. Parasites treated with CD/Et (131.2 μg/mL) presented severe alterations including mitochondrial swelling, lipid body formation and intense cytoplasmic vacuolization. CH and CD/Et demonstrated cytotoxic effects similar to that of amphotericin B in the anti-amastigote assays (SI of 2.16, 1.98 and 1.35, respectively). Triterpene amyrins were the main substances in CH and CD/Et extracts. In addition, 80 μg/mL of CD/Et reduced the number of intracellular amastigotes and the percentage of infected macrophages in 63%and 36%, respectively.CONCLUSION: The results presented here highlight C. sinensis as a promising source of antileishmanial agents.

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PMID: 

J Basic Clin Physiol Pharmacol. 2015 Sep ;26(5):471-7. PMID: 26030791

Abstract Title: 

Inhibition of metalloproteinase and proteasome activities in colon cancer cells by citrus peel extracts.

Abstract: 

BACKGROUND: Citrus peels are consumed in the form of infusions, candy or wine, based on their well-documented nutritional and medicinal properties. This study sought to investigate the effect of some citrus peels' [grapefruit (Citrus paradisii), orange (Citrus sinensis) and shaddock (Citrus maxima)] extracts on matrix metalloproteinase (MMP) and proteasome activities in primary human colonic tumor (Caco-2) and the metastatic cell lines (LoVo and LoVo/ADR) in a bid to explain the possible mechanism by which the peels could manage/prevent colon cancer.METHODS: The inhibition of MMP and proteasome activities in the cells by the peel extracts, as well as the identification of phenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD), was determined.RESULTS: Orange peel extracts had the strongest inhibition of MMP in Caco-2 and LoVo cells, while shaddock had the least. Shaddock peel extracts also had the least MMP inhibition in LoVo/ADR lysates. Grapefruit had the least proteasome inhibition in Caco-2 and LoVo lysates, while there was no significant (p>0.05) difference in the proteasome inhibition of the peel extracts in LoVo/ADR lysates. The extracts inhibited proteasome activity in extract-treated cells, and HPLC fingerprinting of the extracts revealed the presence of some phenolic compounds such as quercetin, caffeic acid, kaempferol, catechin and naringin.CONCLUSIONS: The inhibition of MMP and proteasome activities in colon cancer cell lines suggests the potential use of citrus peels as functional food in the management and/or prevention of colon cancer.

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PMID: 

Nutrients. 2014 Apr 21 ;6(4):1618-34. Epub 2014 Apr 21. PMID: 24763109

Abstract Title: 

Selected activities of Citrus maxima Merr. fruits on human endothelial cells: enhancing cell migration and delaying cellular aging.

Abstract: 

Endothelial injury and damage as well as accumulated reactive oxygen species (ROS) in aging play a significant role in the development of cardiovascular disease (CVD). Recent studies show an association of high citrus fruit intake with a lower risk of CVD and stroke but the mechanisms involved are not fully understood. This study investigated the effects of pummelo (Citrus maxima Merr. var. Tubtim Siam, CM) fruit extract on human umbilical vein endothelial cell (HUVECs) migration and aging. The freeze-dried powder of fruit extract was characterized for antioxidant capacity (FRAP assay) and certain natural antioxidants, including ascorbic acid, gallic acid, hesperidin, and naringin (HPLC). Short-term (48 h) co-cultivation of HUVECs with CM enhanced cell migration as evaluated by a scratch wound assay and Boyden chamber assay. A long-term treatment with CM for 35 days significantly increased HUVEC proliferation capability as indicated by population doubling level (PDL). CM also delayed the onset of aging phenotype shown by senescence-associatedβ-galactosidase (SA-β-gal) staining. Furthermore, CM was able to attenuate increased ROS levels in aged cells when determined by 2',7'-dichlorodihydrofluorescein diacetate (DCDHF) while eNOS mRNA expression was increased but the eNOS protein level was not changed. Thus, further in vivo and clinical studies are warranted to support the use of pummelo as a functional fruit for endothelial health and CVD risk reduction.

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PMID: 

Biomed Pharmacother. 2018 Feb ;98:338-346. Epub 2017 Dec 27. PMID: 29274591

Abstract Title: 

Extract of Citrus maxima (pummelo) leaves improve hepatoprotective activity in Wistar rats submitted to the induction of non-alcoholic hepatic steatosis.

Abstract: 

Non-alcoholic fatty liver disease is a spectrum of liver changes, ranging from hepatic steatosis to hepatocellular carcinoma. The Citrus maxima (CM) has been shown to be beneficial to the organism, and these activities are attributed to the presence of phytochemical compounds. The objective of this study was to evaluate the n vitro antioxidant potential of the CM leaves extract and on Wistar rats submitted to hepatic steatosis induction by fructose-associated hyperlipid diet (FHD). For the evaluation of in vivo effects, the animals were distributed in G1 (normal diet – ND), G2 (FHD), G3 (ND + extract 50mg/kg) and G4 (FHD + extract 50 mg/kg). All the parameters were determined through classical methodologies. The extract showed a significant antioxidant potential in vitro. In the in vivo analysis, the diet used was able to induce the development of metabolic abnormalities that favored the formation of hepatic steatosis (G2). Changes in inflammatory markers, increase in markers of oxidative damage, and reduction of antioxidant defenses were also observed. In addition, the extract did not cause changes in the animals' weight gain and acted as an anti-inflammatory, since G4 animals exhibited significantly reduced levels of the inflammatory markers. In the liver, the extract significantly decreased the content of fat, cholesterol and triglycerides compared to G2. The extract also showed antioxidant activity (G4) when compared to G2. The results suggest that the extract of CM leaf showed hepatoprotective, hypolipidemic, anti-inflammatory and antioxidant activities and the presence of phenolic compounds is a probable cause for such activities.

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PMID: 

Diabetes Metab Syndr. 2011 Jul-Sep;5(3):148-52. Epub 2012 Mar 15. PMID: 22813568

Abstract Title: 

Shaddock peels (Citrus maxima) phenolic extracts inhibitα-amylase, α-glucosidase and angiotensin I-converting enzyme activities: a nutraceutical approach to diabetes management.

Abstract: 

In this study, the interactions of free and bound phenolic-rich extracts from shaddock peels (popular in folklore for the management of diabetes and hypertension) withα-amylase and α-glucosidase (key enzymes linked to type-2 diabetes) and angiotensin I-converting enzyme (ACE) (key enzyme linked to hypertension) were assessed. The free phenolics of shaddock (Citrus maxima) peels were extracted with 80% acetone, while the bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate; and their interaction with the enzymes were assessed. The phenolic extracts inhibited α-amylase, α-glucosidase and ACE enzyme activities in a dose-dependent manner; however, bound phenolics had significantly higher (P

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PMID: 

J Complement Integr Med. 2018 Aug 11 ;16(1). Epub 2018 Aug 11. PMID: 30099413

Abstract Title: 

Modulatory effect of some citrus (Citrus limon, Citrus reticulata, Citrus maxima) peels on monoamine oxidase, phosphodiesterase-5 and angiotensin-1 converting enzyme activities in rat heart homogenate.

Abstract: 

Background Citrus peels have been reported useful in folk medicine for the management of cardiovascular diseases, but there is dearth of information on the possible mechanisms for their therapeutic action. The aim of this study was to investigate the effect of methanolic extracts from some citrus [lime (Citrus limon), tangerine (Citrus reticulata), shaddock (Citrus maxima)] peels on some enzymes relevant to the management of cardiovascular diseases [monoamine oxidase (MAO), phosphodiesterase-5 (PDE-5) and angiotensin-1-converting enzyme (ACE)]. Methods Effect of methanolic extracts of lime, tangerine and shaddock peels on MAO, PDE-5 and ACE were carried out using standard methods. In addition, the ability of the extracts to prevent oxidative damage in rat heart homogenates was also investigated. Finally, the total polyphenol content of extracts was determined. Results The results revealed that methanolic extracts of lime, tangerine and shaddock peels inhibited MAO, PDE-5, ACE and pro-oxidants induced lipid peroxidation in rat heart homogenate in a concentration-dependent manner. Conclusions Findings in this study revealed citrus peel methanolic extracts as natural inhibitor of enzymes (MAO, PDE-5 and ACE) implicated in cardiovascular diseases. Therefore, citrus peels could help in the management of cardiovascular diseases possibly through inhibition of these enzymes.

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PMID: 

Metab Brain Dis. 2017 02 ;32(1):123-131. Epub 2016 Aug 11. PMID: 27510713

Abstract Title: 

Behavioral effects of Citrus limon and Punica granatum combinations in rats.

Abstract: 

Dietary supplements are becoming more influential as viable treatment for common chronic diseases and to promote normal development and functions of all system including brain. Disorders like anxiety and depression may be managed through healthier variations is dietary pattern, since there are indications that diet rich in antioxidants and vitamins diminish anxiety and depression. Hence this investigation was planned to assess the behavioral effects of Citrus limon and Punica granatum in two combination doses i.e. 0.4 + 5 ml/kg and 0.2 + 8 ml/kg C. limon and P. granatum respectively in rats. Antidepressant and anxiolytic effects were explicitly judged twice during 15 days using forced swimming and open field tests and elevated plus maze. In open field test C. limon and P. granatum showed increase in distance travelled, number of central entries and number of rearing's at 0.4 + 5 ml/kg combination, in the elevated plus maze, number of open arm entries were found to be augmented and in forced swimming test, there was decline in duration of immobility and rise in duration of climbing at both combinations i.e. 0.4 + 5 ml/kg and 0.2 + 8 ml/kg C. limon and P. granatum. These results suggest that C. limon and P. granatum at 0.4 + 5 ml/kg combination have anxiolytic and antidepressant effect.

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