PMID: 

Food Funct. 2019 Oct 16 ;10(10):6459-6472. PMID: 31528975

Abstract Title: 

Antidiabetic effects of extracts of red and yellow fruits of cornelian cherries (Cornus mas L.) on rats with streptozotocin-induced diabetes mellitus.

Abstract: 

The effects of extracts of red and yellow fruits of cornelian cherries have been evaluated in rats with streptozotocin-induced diabetes mellitus. Cornus mas L. active compounds were analyzed by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-qTOF-MS/MS) in positive and negative ion modes and by HPLC-PDA, followed by the identification of iridoids, anthocyanins, phenolic acids and flavonols. Rats with type 1 diabetes mellitus were orally dosed with the extracts in amounts of 20 mg kg-1 of body weight for 14 days. The cornelian cherry extracts lowered blood glucose and improved glucose tolerance. The treatments significantly decreased the amount of glycated hemoglobin (by 25%) and increased erythrocyte resistance to acid hemolysis. Importantly, only treatment with the extract of yellow fruits of the cornelian cherry increased the level of reduced glutathione and mean cell hemoglobin in diabetic rats. The active compounds of Cornus mas L. demonstrated the antidiabetic and antioxidant effects via the attenuation of hyperglycemia and inhibition of oxidative modifications of proteins and lipids, advanced glycation and oxidation protein formation or accumulation. The results suppose that cornelian cherries can be considered as a food supplement to alleviate diabetes mellitus and its complications.

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PMID: 

Antioxidants (Basel). 2019 Sep 25 ;8(10). Epub 2019 Sep 25. PMID: 31557846

Abstract Title: 

Red-Osier Dogwood Extracts Prevent Inflammatory Responses in Caco-2 Cells and a Caco-2 BBe1/EA.hy926 Cell Co-Culture Model.

Abstract: 

Red-osier dogwood extracts (RDE) contain high levels of phenolic compounds which have been recognized as natural antioxidants. In this study, the potential of RDE to prevent cardiovascular diseases (CVDs) was evaluated using Caco-2 cells and a co-culture model of Caco-2 BBe1/EA.hy926 cells in Transwellplates. The results showed that RDE supplementation significantly prevented interleukin-8 (IL-8) production and suppressed the gene expression of IL-8, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and cyclooxygenase 2 (COX-2) in the TNF-α inflamed Caco-2 cells. Meanwhile, the polyphenols (quercetin-3-glucoside, quercetin-glucuronide, rutin, quercetin-3–malonylglucoside, and kaempferol-glucoside) in the RDE were validated to be absorbed by Caco-2 BBe1 cells and transported to the basal chamber where EA.hy926 cells were located during 12 h incubation. The transported polyphenols were able to prevent IL-8 production and suppress the gene expression of proinflammatory mediators (TNF-α, ICAM-1, VCAM-1, and COX-2) in the TNF-α or oxidized low-density lipoprotein (ox-LDL) treated EA.hy926 cells. These novel findings demonstrated that phenolic compounds in RDE can be transported to the cardiovascular system by intestinal absorption and mitigate the inflammatory responses of vascular endothelial cells, indicating that RDE could be a natural resource of polyphenols to prevent inflammation cytokine or oxidized lipid-induced CVDs.

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PMID: 

Environ Sci Pollut Res Int. 2019 Dec 29. Epub 2019 Dec 29. PMID: 31885062

Abstract Title: 

Ellagic acid ameliorates lung damage in rats via modulating antioxidant activities, inhibitory effects on inflammatory mediators and apoptosis-inducing activities.

Abstract: 

Phytochemicals is considered one of the most effective and safe alternative therapy against oxidative linked lung diseases. Ellagic acid (EA), an important component of fruits, nuts, and vegetables, are partly responsible for their beneficial health effects against oxidation-related diseases. In the present study, we investigated the ameliorative effect of EA on lung damage induced by carbon tetrachloride (CCl) in Wistar male albino rats. Thirty-six male rats (n = 36, 8-week old) were divided into 4 groups, each with 9 rats. The groups were: Control group: received standard diet; EA group: administered with EA (10 mg/kg body weight, intraperitoneal); CClgroup: administered with CCl(1.5 mg/kg body weight, intraperitoneal); EA+CClgroup: administered with EA and CCl. . The rats were decapitated at the end of experimental period of 8 weeks and the lung tissues were examined. CCl-induced rats showed elevation in the expressions of inflammatory proteins, nuclear factor kappa b (NF-κB), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α); and the indicator of lipid peroxidation, malondialdehyde (MDA). Intraperitoneal administration of EA significantly reduced the levels of these markers. EA administration increased the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2) and enhanced the activity of glutathione (GSH) and catalase enzyme (CAT). In addition, EA administration increased the expression levels of the executioner protein of apoptosis, caspase-3, and decreasing pro-survival protein, B cell lymphoma-2 (Bcl-2). In conclusion, these results establishes the protective role of EA in the treatment of lung damage and that in the future, this may have the potential to be used as a medication for the prevention or attenuation of lung diseases. Graphical abstract.

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PMID: 

Pharm Biol. 2013 Mar ;51(3):361-8. Epub 2012 Nov 8. PMID: 23137183

Abstract Title: 

In vitro inhibition of angiogenesis by hydroalcoholic extract of oak (Quercus infectoria) acorn shell via suppressing VEGF, MMP-2, and MMP-9 secretion.

Abstract: 

CONTEXT: Angiogenesis is an essential factor for cancer progression. Although more attention is paid in angiogenesis on its role in cancer biology, many other non-neoplastic diseases are also angiogenic-dependent. Recently, there is motivation to control cancer via inhibition of angiogenesis.OBJECTIVE: Quercus infectoria Olivier var (Fagaceae) (oak) is a plant whose different parts, such as its fruit shell, have been used extensively as a traditional drug in the west part of Iran. Although some biological properties of oak are determined, its effects on angiogenesis are unclear. So, we investigated the antiangiogenic effects of oak acorn shell.MATERIALS AND METHODS: Fresh oak acorns were collected, and after authentication; hydroalcoholic extract of acorn shells (5, 10, 20, 30, 40, 60, 80, and 100μg/ml) was used for evaluation of its cytotoxicity, antiproliferative, and antiangiogenic effects in vitro. Also, effects of the extract on vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and MMP-9 secretion were assayed using enzyme-linked immunosorbent assay (ELISA)and gelatin zymography.RESULTS: Treatment with hydroalcoholic extract in eight doses resulted in a significant decrease of endothelial cell proliferation and angiogenesis with an IC₅₀ value of ~20 μg/ml, without any toxic effect. At 40 μg/ml, the extract inhibited MMP-9 activity; however, a dose-dependent reduction (60-80 µg/ml) in MMP-2 activity was seen. VEGF secretion was decreased with increase in the concentration of the extract from 5 to 100 μg/ml.DISCUSSION AND CONCLUSION: This study indicated that hydroalcoholic extract of oak acorn shell acts as a potent antiangiogenic agent which exerts its inhibitory effect mainly through downregulation of essential mediators such as VEGF and MMPs.

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PMID: 

Biomolecules. 2019 Dec 29 ;10(1). Epub 2019 Dec 29. PMID: 31905797

Abstract Title: 

Anti-Atopic Effect of Acorn Shell Extract on Atopic Dermatitis-Like Lesions in Mice and Its Active Phytochemicals.

Abstract: 

To investigate the potential effects of acorn shells on atopic dermatitis (AD), we utilized oxazolone (OX)- or 2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesion mouse models. Our research demonstrates that Acorn shell extract (ASE) improved the progression of AD-like lesions, including swelling, which were induced by oxazolone on Balb/c mouse ears. Additionally, ASE significantly decreased the ear thickness (OX: 0.42± 0.01 mm, OX-ASE: 0.32 ± 0.02 mm) and epidermal thickness (OX: 75.3 ± 32.6 µm, OX-ASE: 46.1 ± 13.4 µm). The continuous DNCB-induced AD mouse model in SKH-1 hairless mice demonstrated that ASE improved AD-like symptoms, including the recovery of skin barrier dysfunction, Immunoglobulin E hyperproduction (DNCB: 340.1 ± 66.8 ng/mL, DNCB-ASE: 234.8 ± 32.9 ng/mL) and an increase in epidermal thickness (DNCB: 96.4 ± 21.9 µm, DNCB-ASE: 52.4 ± 16.3 µm). In addition, we found that ASE suppressed the levels of AD-involved cytokines, such as Tumor Necrosis Factor α, IL-1β, IL-25 and IL-33in both animal models. Furthermore, gallic acid and ellagic acid isolated from ASE suppressed β-hexosaminidase release and IL-4 expression in RBL-2H3 cells. The acorn shell and its active phytochemicals have potential as a new remedy for the improvement of atopic dermatitis and other inflammatory diseases.

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PMID: 

Phytother Res. 2020 Jan 7. Epub 2020 Jan 7. PMID: 31908068

Abstract Title: 

Anti-inflammatory and anti-cancer activities of pomegranate and its constituent, ellagic acid: Evidence from cellular, animal, and clinical studies.

Abstract: 

Inflammation is commonly characterized as a defensive and protective reaction of the body to various exogenous or endogenous stimuli, which aims to maintain the body health. Punica granatum (pomegranate) and its constituent ellagic acid (EA) are recently more taken into accounts since their promising pharmacological effects. Therefore, we aimed to obtain a comprehensive review regarding antiinflammatory, anticancer, and antioxidant activities of both pomegranate and EA and their possible involved mechanisms. In the procedure, scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar, were searched in the English language, until the end of January 2019. Pomegranate belonging to the Punicaceae has been used for medical purposes from ancient and in different cultures. Several studies have also supported that EA is the major active compound of pomegranate and possesses antimutagenic, antiinflammatory, antifibrosis, anticancer, and antiaging properties. It has been suggested that pomegranate and EA possess promising immunomodulatory effects in preclinical models as well as human studies through regulation of the T-cell function and suppressing humoral immunity. Hopefully, we wish that this review and information could be helpful for designing further experiments to investigate the potential protective effects of pomegranate and EA.

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PMID: 

J Ethnopharmacol. 2020 Feb 10 ;248:112322. Epub 2019 Oct 20. PMID: 31644942

Abstract Title: 

Healing effects of Cornus mas L. in experimentally induced ulcerative colitis in rats: From ethnobotany to pharmacology.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: The ethnobotanical studies conducted in Turkey and other countries have revealed that Cornus mas L., from the family Cornaceae have been used against stomachache, diarrhea and colitis.AIM OF THE STUDY: The objective the present study is to determine the possible activity of C. mas in experimentally induced ulcerative colitis in rats and to identify its phytochemical feature.MATERIALS AND METHODS: 2,4,6-Trinitrobenzene sulfonic acid-induced colitis model was induced in rats. The rats were orally treated with different doses (50, 100, 200 and 400 mg/kg) of C. mas 80% methanol extract for 14 days. Increase in body weight, consumed amount of feed, form of the stool, presence of rectal prolapse were followed every day. At the end of the experiment, colon tissues were removed and wet weights for each animal were measured and colon damages were scored. Total antioxidant and total oxidant status, cytokine (TNF-α and IL-1β) and protein levels of colon tissues were evaluated and histopathological analyses were carried out. After the detection of the effective dose as 400 mg/kg, the aqueous methanol extract was fractionated by using liquid-liquid fractionation technique and the sub-extracts were also tested for in vivo biological activities. High Performance Liquid Chromatography analyses were conducted to determine the phytochemical profile of the active crude extract and n-butanol sub-extract.RESULTS: Amount of feed consumed per day and increase in body weight were the lowest in the control group, while those values were determined to be the highest in 80% methanol extract (at 400 mg/kg dose), n-butanol sub-extract and reference groups. Following colitis induction, it was determined that the fecal form was yellow-slippery in all groups and returned to normal after the treatment with C. mas extracts. Rectal prolapse score was less in the extract (400 mg/kg) and n-butanolsub-extract treated groups. Total antioxidant, total oxidant status, cytokine and protein levels were found to be in parallel with macroscopic findings. 80% methanol extract (400 mg/kg) and n-butanol sub-extract provided the best healing according to the wet weight measurements and colon damage scoring performed on the removed colon tissues. These findings supported the results of histopathological analysis. According to the chromatographic analysis, ellagic acid was determined in both extracts and its amount was quantified.CONCLUSIONS: The present study has verified the ethnomedical use of C. mas for the treatment of ulcerative colitis.

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PMID: 

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2015 Sep ;35(9):1090-8. PMID: 26591365

Abstract Title: 

[Protective Effects of Cornus Officinalis Total Glycosides and Cornus Polysaccharides on Myocardial Mitochondria of Acute Myocardial Infarction Rats: an Experimental Study].

Abstract: 

OBJECTIVE: To observe the effect of Cornus Officinalis total glycosides (COTG) and Cornus polysaccharides (CP) on myocardial mitochondria and expression levels of glycogen synthase kinase-3β (GSK-3β) of acute myocardial infarction (AMI) rats.METHODS: The AMI rat model was established by ligating the left anterior descending branch of coronary artery. Rats were divided into 5 groups according to random digit table, i.e., the sham-operation group, the model group, the COTG prevention group, the CP treatment group, the COTG treatment group, 12 in each group. Normal saline was administered to rats in the normal control group and the model group by gastrogavage. Corresponding medication was respectively administered to rats in the rest 3 groups by gastrogavage. The cardiac function was detected by echocardiography and hemodynamics. The infarct size was determined by Masson trichrome staining. The expression of mitochondrial biogenesis genes such as a subunit of peroxisome proliferators-activated receptor-γ coactivator-1 (PGC-1α), PGC-1β, nuclear respiratory factor-1 (NRF-1), and GSK-3P mRNA were detected by Real-time PCR.RESULTS: Compared with the sham-operation group, the myocardial infarction size increased, cardiac function decreased, the expression of PGC-1α, PGC-1β, and NRF-1 mRNA decreased, and the expression of GSK-3β mRNA increased (all P

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PMID: 

BMC Complement Altern Med. 2016 Jul 8 ;16:196. Epub 2016 Jul 8. PMID: 27391600

Abstract Title: 

Antioxidant activities and oxidative stress inhibitory effects of ethanol extracts from Cornus officinalis on raw 264.7 cells.

Abstract: 

BACKGROUND: Cornus officinalis, is a deciduous tree native to the eastern Asia, distributes mainly in (e.g. Korea, as well as China, and Japan). It is used as folk medicine to backache, polyuria, hypertension and nervous breakdown. Pharmacological studies have demonstrated that C. officinalis possess anti-oxidant, anti-hyperglycemic, and immune regulatory effects. However, reports on the antioxidant activity of C. officinalis have been limited to in vitro radical scavenging studies. Its mechanism of action within the cell at the genetic level especially has not yet been clearly defined. Therefore, we investigated the anti-antioxidant activities of C. officinalis in RAW 264.7 cells.METHODS: The antioxidant activities and protective effects of C. officinalis ethanol extract on cell damage and the antioxidant enzyme system in lipopolysaccharide (LPS)-induced oxidative stress-damaged RAW 264.7 cells were assessed. To measure the effects of C. officinalis on antioxidant activities, we used the following methods: Total phenol and flavonoid contents, DPPH scavenging activity assay, ABTS scavenging activity assay, FRAP value measurement, xanthine oxidase activity assay, ROS generation measurement and real time PCR.RESULTS: The total phenol and flavonoid contents of C. officinalis extracts were 27.04 mg GAE/g and 3.70 mg QE/g, respectively. The antioxidant activities of C. officinalis extracts increased in a dose-dependent manner: the IC50 values for DPPH and ABTS radical scavenging activities of C. officinalis extracts were 99.32 μg/mL and 138.51 μg/mL, respectively. C. officinalis extracts inhibited xanthine oxidase activity and reactive oxygen species generation. The expression of antioxidant enzymes, Cu/ZnSOD, MnSOD, catalase, and glutathione peroxidase increased upon treatment with C. officinalis extracts at 100 μg/mL, compared to that in the LPS-treated group.CONCLUSIONS: These results suggest the therapeutic potential of C. officinalis extract as an anti-oxidant agent.

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PMID: 

Br J Pharmacol. 2017 04 ;174(7):580-590. Epub 2017 Feb 16. PMID: 28098360

Abstract Title: 

Morroniside, a secoiridoid glycoside from Cornus officinalis, attenuates neuropathic pain by activation of spinal glucagon-like peptide-1 receptors.

Abstract: 

BACKGROUND AND PURPOSE: Iridoid glycosides containing the double bond scaffold of cyclopentapyran are reversible and orthosteric agonists of glucagon-like peptide-1 (GLP-1) receptors and exert anti-nociceptive and neuroprotective actions. Morroniside, derived from the medicinal herb Cornus officinalis, is an atypical secoiridoid containing a six-membered cyclic inner ether fragment. Here we investigated whether morroniside was an orthosteric GLP-1 receptor agonist and had anti-hypersensitivity activities in a model of neuropathic pain.EXPERIMENTAL APPROACH: We used a model of neuropathic pain, induced by tight ligation of L5/L6 spinal nerves in rats. Hydrogen peroxide-induced oxidative damage was also assayed in N9 microglial cells and human HEK293 cells stably expressing GLP-1 receptors.KEY RESULTS: Morroniside protected against hydrogen peroxide-induced oxidative damage in N9 microglial and HEK293 cells that expressed mouse or human GLP-1 receptors, but not in HEK293T cells without GLP-1 receptors. The GLP-1 receptor orthosteric antagonist exendin(9-39) also concentration-dependently shifted the concentration-protective response curves of morroniside and exenatide to the right without affecting maximal protection, with similar pAvalues. Furthermore, morroniside given by oral gavage or intrathecally in neuropathic rats dose-dependently attenuated mechanical allodynia, with comparable Evalues and EDs of 335 mg·kgand 7.1 μg and completely blocked thermal hyperalgesia. Daily intrathecal injections of morroniside over 7 days did not induce anti-allodynic tolerance. Pretreatment with intrathecal exendin(9-39) completely blocked systemic and intrathecal morroniside-induced mechanical anti-allodynia.CONCLUSION AND IMPLICATIONS: Our data demonstrated that morroniside was an orthosteric agonist of GLP-1 receptors and produced antihypersensitivity in a neuropathic pain model by activation of spinal GLP-1 receptors.

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