Neuroprotective Effects of the Peel of <I>Citrus Kawachiensis</I>

Total Page:16

File Type:pdf, Size:1020Kb

Neuroprotective Effects of the Peel of <I>Citrus Kawachiensis</I> Proceedings for The 92nd Annual Meeting of the Japanese Pharmacological Society 3-S26-1 Symposium Neuroprotective effects of the peel of Citrus kawachiensis (Kawachi Bankan) and auraptene in the hippocampus of hyperglycemia mice and global cerebral ischemia/reperfusion injury mice. Satoshi Okuyama1, Atsushi Sawamoto1, Mitsunari Nakajima1, Yoshiko Furukawa1 1Dept. Pharm. Pharmacol., Col. Pharm. Sci., Matsuyama Univ. The peel of Citrus kawachiensis (Kawachi Bankan), a citrus species grown in Ehime, Japan, is abundant in auraptene. Hyperglycemia and brain ischemia induce inflammation and oxidative stress and cause massive damage in the brain; therefore, we examined the anti-inflammatory and other effects of the dried peel powder of C. kawachiensis in the type 2 diabetic db/db mice model and global cerebral ischemia mice. The C. kawachiensis treatment inhibited astroglial activation in the hippocampus and the hyperphosphorylation of tau protein in hippocampal neurons, and also relieved the suppression of neurogenesis in the dentate gyrus of the hippocampus in the db/db mice. The C. kawachiensis treatment inhibited microglial and astroglial activation, and neuronal cell death in the hippocampus of transient global cerebral ischemia mice. It was suggested that the dried peel powder of C. kawachiensis exerts anti- inflammatory and neuroprotective effects in the brain. Auraptene, a coumarin compound, have been shown to exert anti-inflammatory effects in peripheral tissues; therefore, we attempted to demonstrate the effect in the brains in streptozotocin-induced hyperglycemic mice and transient global cerebral ischemia mice. Auraptene administration showed the similar effects as the peel of C. kawachiensis in the hippocampus of these mice models. These results suggested that auraptene have potential effects as a neuroprotective agent in the peel of C. kawachiensis. Copyright ©2019 The Japanese Pharmacological Society.
Recommended publications
  • Leading-Edge Technologies & Sophisticated Techniques Leading
    Really The 2015-2016 Guidebook for the Database of Incredible! “SUGOWAZA” Manufacturing Companies in EHIME Database of“SUGOWAZA”Manufacturing Canpanies in EHIME Leading-edgeLeading-edge TechnologiesTechnologies& & SophisticatedSophisticated TechniquesTechniques, A Selection of 163 Companies! inEEHIMEHIME Leading-edge Technologies & Sophisticated Techniques in EEHIMEHIMAE Selection of 163 Companies! No.1 in Japan/ Only One is packed with information! There are many characteristic production companies accumulated in Ehime, varying in their regional history and culture. Information about the technology and products of these companies has been digitized in a database and publicized in this website. Complete with company search functions, and Ehime production industry introductions. Ehime Inquiries Prefecture ●Inquiries about "SUGOWAZA" database and registered companies Leading-edge Technologies & Sophisticated Techniques group, Industry Policy Division⦆Economy and Labor Department, Ehime Prefecture 4-4-2 Ichiban-cho, Matsuyama 790-8570 TEL: 089-912-2473 ⦆ FAX: 089-912-2259 E-mail:[email protected] http://www.sugowaza-ehime.com/ ehime sugowaza Search http://www.sugowaza-ehime.com/ 2015.07 m e s s a g e The industrial structure of Ehime Prefecture is defined by a balance rarely seen anywhere else in Japan, with each prefectural region having its own unique industrial concentrations: secondary industry is abundant in the Toyo Region (eastern area of the prefecture), tertiary industry thrives in the Chuyo Region (the central area of the prefecture around Total Value of Manufa ctured Goods Shipped Matsuyama City), and primary industry is dominant in the Nanyo Region (southwestern area of the prefecture). for Major Cities in Ehi me Prefecture Tokihiro Nakamura, There is a wide array of industrial cities in the Toyo Region, Governor of Ehime Prefecture which are home to numerous manufacturing companies boasting advanced technology unparalleled elsewhere in Japan and producing top-quality products.
    [Show full text]
  • Holdings of the University of California Citrus Variety Collection 41
    Holdings of the University of California Citrus Variety Collection Category Other identifiers CRC VI PI numbera Accession name or descriptionb numberc numberd Sourcee Datef 1. Citron and hybrid 0138-A Indian citron (ops) 539413 India 1912 0138-B Indian citron (ops) 539414 India 1912 0294 Ponderosa “lemon” (probable Citron ´ lemon hybrid) 409 539491 Fawcett’s #127, Florida collection 1914 0648 Orange-citron-hybrid 539238 Mr. Flippen, between Fullerton and Placentia CA 1915 0661 Indian sour citron (ops) (Zamburi) 31981 USDA, Chico Garden 1915 1795 Corsican citron 539415 W.T. Swingle, USDA 1924 2456 Citron or citron hybrid 539416 From CPB 1930 (Came in as Djerok which is Dutch word for “citrus” 2847 Yemen citron 105957 Bureau of Plant Introduction 3055 Bengal citron (ops) (citron hybrid?) 539417 Ed Pollock, NSW, Australia 1954 3174 Unnamed citron 230626 H. Chapot, Rabat, Morocco 1955 3190 Dabbe (ops) 539418 H. Chapot, Rabat, Morocco 1959 3241 Citrus megaloxycarpa (ops) (Bor-tenga) (hybrid) 539446 Fruit Research Station, Burnihat Assam, India 1957 3487 Kulu “lemon” (ops) 539207 A.G. Norman, Botanical Garden, Ann Arbor MI 1963 3518 Citron of Commerce (ops) 539419 John Carpenter, USDCS, Indio CA 1966 3519 Citron of Commerce (ops) 539420 John Carpenter, USDCS, Indio CA 1966 3520 Corsican citron (ops) 539421 John Carpenter, USDCS, Indio CA 1966 3521 Corsican citron (ops) 539422 John Carpenter, USDCS, Indio CA 1966 3522 Diamante citron (ops) 539423 John Carpenter, USDCS, Indio CA 1966 3523 Diamante citron (ops) 539424 John Carpenter, USDCS, Indio
    [Show full text]
  • Citrus Waste Reuse for Health Benefits and Pharma-/Neutraceutical Applications
    ERA’S JOURNAL OF MEDICAL RESEARCH VOL.3 NO.1 Review Article CITRUS WASTE REUSE FOR HEALTH BENEFITS AND PHARMA-/NEUTRACEUTICAL APPLICATIONS Neelima Mahato, Kavita Sharma, Fatema Nabybaccus & Moo Hwan Cho School of Chemical Engineering, Yeungnam University, Gyeongsan-si Gyongsanbuk-do, Republic of South Korea- 712 749 ABSTRACT Citrus are the largest fruit crops grown across the globe. It is one of the most profitable crops in terms of economy as well as popular for Address for correspondence nutritional benefits. The most interesting aspect about citrus is the Neelima Mahato availability of several varieties with attractive colours. Approximately 50 School of Chemical Engineering % of citrus remains unconsumed after processing as pith residue, peels Yeungnam University, Gyeongsan-Si, and seeds. Direct disposal of these wastes cause serious environmental Gyeongsanbuk-do, problems in terms of killing natural flora in the soil because of Republic of Korea- 712 749 antibacterial properties of limonene oils. Seepage to underground waters Ph: +82-010-2798-8476 Email:[email protected] or open water bodies affects water quality and aquatic life, respectively. Citrus waste reuse to obtain value added-phytochemicals and pectin is one of the popular topics in industrial research, food and synthetic chemistry. The present article reviews recent advances in exploring the effects of phytochemical compounds obtained from citrus wastes in view of various health aspects. Key words: Citrus waste, Phytochemical compounds, Hesperidin, Naringenin, Flavonoids, Polyphenols INTRODUCTION of the fruit is sedative and fruit and seed extracts are useful in palpitation and making cardiac tonics.(2-4) Citrus fruits have long been known for health benefits due to their nutrient contents and secondary metabolites, such Citrus belongs to family Rutaceae comprising 140 as ascorbic acid, citric acid, phenolics, flavanoids, pectin, genera and 1300 species.
    [Show full text]
  • The Ecology of the South African Citrus Thrips
    THE ECOLOGY OF THE SOUTH AFRICAN CITRUS THRIPS Seirtothrips aurantii Faure AND ITS ECONOMIC IMPLICATIONS THESIS Submitted in fulfillment of the requirements for the Degree of DOCTOR OF PHILOSOPHY of Rhodes University by MARTIN JEFFRAY GILBERT December 1992 ACKNOWLEDGMENTS I would like to thank the management of Letaba Estates and the Board of Directors of African Realty Trust for the financial support of this study. Thanks are also due to Dr. S.G. Compton, formerly of Rhodes University, for supervision of the study, editorial advice and constant encouragement, as well as to Professor R. Hepburn for final supervision. During the study, Dr. R. zur Strassen of the Senckenberg Museum, Frankfurt, Germany gave considerable help with the rapid identification of a large number of thrips specimens, which was most appreciated. A special word of thanks to the many people who made me welcome on my arrival in South Africa, of whom three deserve special mention; Mr. D.C. Lotter for providing me with the opportunity to come to this country; and Mr. F. Honiball and Dr. S.S. Kamburov who gave me the finest introduction to citrus entomology possible. Finally, this thesis is dedicated to my wife Mari, as well as to my parents, for their continual support throughout the years. i i ABSTRACT The South African Citrus Thrips, Scirtothrips aurantii Faure (Thysanoptera: Thripidae) has been a serious pest of the citrus industry of Southern Africa for over 70 years. It is indigenous to Africa and has no recorded parasitoids and, in most citrus-growing regions, predators are not economically effective.
    [Show full text]
  • Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants
    Int. J. Mol. Sci. 2012, 13, 1832-1845; doi:10.3390/ijms13021832 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants Yoshiko Furukawa 1,*, Satoshi Okuyama 1, Yoshiaki Amakura 2, Sono Watanabe 1, Takahiro Fukata 1, Mitsunari Nakajima 1, Morio Yoshimura 2 and Takashi Yoshida 2 1 Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan; E-Mails: [email protected] (S.O.); [email protected] (S.W.); [email protected] (T.F.); [email protected] (M.N.) 2 Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan; E-Mails: [email protected] (Y.A.); [email protected] (M.Y.); [email protected] (T.Y.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +81-89-925-7111; Fax: +81-89-926-7162. Received: 5 January 2012; in revised form: 24 January 2012 / Accepted: 31 January 2012 / Published: 9 February 2012 Abstract: Extracellular signal-regulated kinases 1/2 (ERK1/2), components of the mitogen-activated protein kinase (MAPK) signaling cascade, have been recently shown to be involved in synaptic plasticity and in the development of long-term memory in the central nervous system (CNS). We therefore examined the ability of Citrus compounds to activate ERK1/2 in cultured rat cortical neurons, whose activation might have a protective effect against neurodegenerative neurological disorders.
    [Show full text]
  • Home Site Map Privacy Policy Contact Ehime Mikan Harehime
    ●English ●中文(繁体語) ●日本語 Home Varieties of Citrus eat the whole fruit seedless easy to peel with hands with inner thin skin Ehime Mikan Harehime Dekopon Iyokan Ponkan Setoka Haruka Kiyomi Kara Kawachi-Bankan Beni-Madonna Kanpei Home │ Site map │ Privacy policy │ Contact Copyright © Ehime “Ai-Food” promotion Organaization All Rights Reserved. ●English ●中文(繁体語) ●日本語 Home Varieties of Citrus Ehime Mikan Easy to peel, Eat the whole fruit The reason of its high popularity is its easiness to eat. As easy to peel by When Japanese hear the word "Mandarin orange (mikan)", "Ehime" springs hand (so-called zipper skin) and seedless, you could eat a whole segment to their minds. Ehime is known as the Citrus Kingdom, and "Ehime Mikan" is even with inner skin. There is a good way to differentiate a delicious Mikan one of the best citrus fruits of Ehime. Raised by full of sunlight and the sea from others. Choose "Ehime Mikan" with more flatted head, smaller stem wind, "Ehime Mikan" has a fabulous taste with well-balanced sweetness and and deeper color. tartness. Everyone loves this cultivar. Note "Ehime Mikan" was widely cultivated around 1900, and its cultivation has been operated up to date. During this time, our predecessors have developed the technology of growing better mandarins. As result, Ehime boasts the top-class quality and high production of mandarins in Japan. *Reference from JA Standard 1・・・more than 5.0cm less than 6.1cm 2・・・more than6.1cm less than 7.3cm 3・・・more than 7.3cm less than 8.8cm 4・・・more than 8.8cm less than 10.2cm 5・・・more than 10.2cm less than 11.6cm Home │ Site map │ Privacy policy │ Contact Copyright © Ehime “Ai-Food” promotion Organaization All Rights Reserved.
    [Show full text]
  • Citrus Genetic Resources in California
    Citrus Genetic Resources in California Analysis and Recommendations for Long-Term Conservation Report of the Citrus Genetic Resources Assessment Task Force T.L. Kahn, R.R. Krueger, D.J. Gumpf, M.L. Roose, M.L. Arpaia, T.A. Batkin, J.A. Bash, O.J. Bier, M.T. Clegg, S.T. Cockerham, C.W. Coggins Jr., D. Durling, G. Elliott, P.A. Mauk, P.E. McGuire, C. Orman, C.O. Qualset, P.A. Roberts, R.K. Soost, J. Turco, S.G. Van Gundy, and B. Zuckerman Report No. 22 June 2001 Published by Genetic Resources Conservation Program Division of Agriculture and Natural Resources UNIVERSITY OF CALIFORNIA i This report is one of a series published by the University of California Genetic Resources Conservation Program (technical editor: P.E. McGuire) as part of the public information function of the Program. The Program sponsors projects in the collection, inventory, maintenance, preservation, and utilization of genetic resources important for the State of California as well as research and education in conservation biology. Further information about the Program may be obtained from: Genetic Resources Conservation Program University of California One Shields Avenue Davis, CA 95616 USA (530) 754-8501 FAX (530) 754-8505 e-mail: [email protected] Website: http://www.grcp.ucdavis.edu/ Additional copies of this report may be ordered from this address. Citation: Kahn TL, RR Krueger, DJ Gumpf, ML Roose, ML Arpaia, TA Batkin, JA Bash, OJ Bier, MT Clegg, ST Cockerham, CW Coggins Jr, D Durling, G Elliott, PA Mauk, PE McGuire, C Orman, CO Qualset, PA Roberts, RK Soost, J Turco, SG Van Gundy, and B Zuckerman.
    [Show full text]
  • Isolation and Characterization of Neuroprotective Components from Citrus Peel and Their Application As Functional Food
    ←確認用doi (左上Y座標:-17.647 pt) 2 Chem. Pharm. Bull. 69, 2–10 (2021) Vol. 69, No. 1 Current Topics Pharmaceutical Research for Quality Evaluation and Characterization of Foods and Natural Products Review Isolation and Characterization of Neuroprotective Components from Citrus Peel and Their Application as Functional Food Yoshiko Fur ukawa,*,a Satoshi Okuyama,a Yoshiaki Amakura,b Atsushi Sawamoto,a Mitsunari Nakajima,a Morio Yoshimura,b Michiya Igase,c Naohiro Fukuda,d Takahisa Tamai,d and Takashi Yoshidab,e a Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University; 4–2 Bunkyo-cho, Matsuyama, Ehime 790–8578, Japan: b Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University; 4–2 Bunkyo-cho, Matsuyama, Ehime 790–8578, Japan: c Department of Geriatric Medicine and Neurology, Ehime University Graduate School of Medicine; 454 Shizugawa, To-on, Ehime 791–0295, Japan: d Ehime Institute of Industrial Technology; 487–2 Kumekubota, Matsuyama, Ehime 791–1101, Japan: and e Department of Pharmaceutical Sciences, Okayama University; Okayama 701–1152, Japan. Received March 22, 2020 The elderly experience numerous physiological alterations. In the brain, aging causes degeneration or loss of distinct populations of neurons, resulting in declining cognitive function, locomotor capability, etc. The pathogenic factors of such neurodegeneration are oxidative stress, mitochondrial dysfunction, inflamma- tion, reduced energy homeostatis, decreased levels of neurotrophic factor, etc. On the other hand, numerous studies have investigated various biologically active substances in fruit and vegetables. We focused on the peel of citrus fruit to search for neuroprotective components and found that: 1) 3,5,6,7,8,3,4-heptamethoxy- flavone (HMF) and auraptene (AUR) in the peel of Kawachi Bankan (Citrus kawachiensis) exert neuroprotec- tive effects; 2) both HMF and AUR can pass through the blood–brain barrier, suggesting that they act di- rectly in the brain; 3) the content of AUR in the peel of K.
    [Show full text]
  • Relationship Between Sterility and Seedlessness in Citrus
    J. Japan. Soc. Hort. Sci. 64 (1) : 23-29. 1995. Relationship between Sterility and Seedlessness in Citrus Masashi Yamamoto, Ryoji Matsumoto and Yoshio Yamada* Kuchinotsu Branch, Fruit Tree Research Station, Kuchinotsu, Nagasaki 859 -25 Summary The relationship of female and male sterility, and self-incompatibility to seed content in citrus were investigated using 22 male sterile and fertile cultivars. The male fertile culti- vars were grouped into self-compatible and self-incompatible. Positive correlation (r = 0.927**, r2=0.859) existed between the average number of seeds per fruit obtained by hand pollination, which indicated the degree of female fertility, and that yielded by open pollination. This result indicates that the degree of female fertility and sterility can be estimated from seeds derived by open pollination. The difference between the average number of seeds per fruit by hand pollination and that by open pollination was greater in male sterile cultivars and in self-incompatible cultivars than it was in self-compatible cul- tivars. This indicates that self-incompatibility as well as male sterility is effective on the reduction of seediness. In open pollination, self-compatible cultivars produced very few seedless fruits, whereas male sterile and self-incompatible cultivars produced many seed- less fruits. Hanaori (1990) who investigated male sterility Introduction and fertility and seediness of progenies using Seedlessness is a desirable characteristic for satsuma mandarins, 'Kiyomi' and 'Sweet Spring' as both fresh and processed citrus market, thus, it is parents. These results suggest that not only male a major breeding objective. Among the breeding sterility but also female sterility and self-incom- methods for developing seedless cultivars (Spiegel- patibility play important roles in developing seed- Roy, 1988) are the production of triploid hybrid less cultivars.
    [Show full text]
  • Title Hybrid Origins of Citrus Varieties Inferred from DNA Marker Analysis
    Hybrid Origins of Citrus Varieties Inferred from DNA Marker Title Analysis of Nuclear and Organelle Genomes. Shimizu, Tokurou; Kitajima, Akira; Nonaka, Keisuke; Yoshioka, Terutaka; Ohta, Satoshi; Goto, Shingo; Toyoda, Author(s) Atsushi; Fujiyama, Asao; Mochizuki, Takako; Nagasaki, Hideki; Kaminuma, Eli; Nakamura, Yasukazu Citation PLOS ONE (2016), 11(11) Issue Date 2016-11-30 URL http://hdl.handle.net/2433/217793 © 2016 Shimizu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, Right which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Type Journal Article Textversion publisher Kyoto University RESEARCH ARTICLE Hybrid Origins of Citrus Varieties Inferred from DNA Marker Analysis of Nuclear and Organelle Genomes Tokurou Shimizu1*, Akira Kitajima2, Keisuke Nonaka1, Terutaka Yoshioka1, Satoshi Ohta1, Shingo Goto1, Atsushi Toyoda3, Asao Fujiyama3, Takako Mochizuki4, Hideki Nagasaki4¤, Eli Kaminuma4, Yasukazu Nakamura4 1 Division of Citrus Research, Institute of Fruit Tree and Tea Science, NARO, Shimizu, Shizuoka, Japan, 2 Experimental Farm, Graduate School of Agriculture, Kyoto University, Kizugawa, Kyoto, Japan, 3 National Institute of Genetics, Comparative Genomics laboratory, National Institute of Genetics, Mishima, Shizuoka, a11111 Japan, 4 National Institute of Genetics, Center for Information Biology, National Institute of Genetics, Mishima, Shizuoka, Japan ¤ Current address: Department of Frontier Research, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan * [email protected] OPEN ACCESS Abstract Citation: Shimizu T, Kitajima A, Nonaka K, Most indigenous citrus varieties are assumed to be natural hybrids, but their parentage has Yoshioka T, Ohta S, Goto S, et al. (2016) Hybrid Origins of Citrus Varieties Inferred from DNA so far been determined in only a few cases because of their wide genetic diversity and the Marker Analysis of Nuclear and Organelle low transferability of DNA markers.
    [Show full text]
  • Citrus Peel Polyphenols: Recent Updates and Perspectives
    Int. J. Biosci. 2020 International Journal of Biosciences | IJB | ISSN: 2220-6655 (Print), 2222-5234 (Online) http://www.innspub.net Vol. 16, No. 2, p. 53-70, 2020 RESEARCH PAPER OPEN ACCESS CITRUS PEEL POLYPHENOLS: RECENT UPDATES AND PERSPECTIVES Muhammad Imran, Shahnai Basharat, Sidra Khalid, Maria Aslam, Fatima Syed, Shaista Jabeen, Hafsa Kamran, Muhammad Zia Shahid*, Tabussam Tufail, Faiz-ul- Hassan Shah, Awais Raza University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, University of Lahore, Lahore-Pakistan Key words: Citrus peel, Polyphenols, Anti-oxidants, Health benefits, Toxicity. http://dx.doi.org/10.12692/ijb/16.2.53-70 Article published on February 05, 2020 Abstract Enormous amount of agro-wastes is producing annually during the processing of fruits and vegetables. These by- products are prominent and promising source of bioactive compounds which exhibits health endorsing perspectives such as prevention from cancer insurgence, diabetes preventive, and protection from cardiovascular complications, anti-aging, and prevention from oxidative stress due to their strong antioxidant potential. Among these agro-wastes,citrus peels are rich source of polyphenols as flavanones, flavones, flavonols and anthocyanins and have health protective effect and act as a potential nutraceutical in the treatment of various non- communicable diseases. These bioactive moieties act as antioxidant thereby scavenging free radical activity and reducing oxidative stress which is cause of burden of diseases. Polyphenols has been used as prebiotic in mitigating gut microbiome and a solution for gastrointestinal disorders. Citrus polyphenols exert health promoting effect in regulating lipid metabolism and treating neurodegenerative diseases. * Corresponding Author: Muhammad Zia Shahid [email protected] 53 Imran et al.
    [Show full text]
  • Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells
    International Journal of Molecular Sciences Article Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells Yoshiko Furukawa * , Ryu-ichi Hara, Makiko Nakaya, Satoshi Okuyama, Atsushi Sawamoto and Mitsunari Nakajima Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama 790-8578, Japan; [email protected] (R.-i.H.); [email protected] (M.N.); [email protected] (S.O.); [email protected] (A.S.); [email protected] (M.N.) * Correspondence: [email protected]; Tel.: +81-89-925-7111 Received: 13 November 2019; Accepted: 27 December 2019; Published: 30 December 2019 Abstract: We previously demonstrated that auraptene (AUR), a natural coumarin derived from citrus plants, exerts anti-inflammatory effects in the brain, resulting in neuroprotection in some mouse models of brain disorders. The present study showed that treatment with AUR significantly increased the release of glial cell line-derived neurotrophic factor (GDNF), in a dose- and time-dependent manner, by rat C6 glioma cells, which release was associated with increased expression of GDNF mRNA. These results suggest that AUR acted as a neuroprotective agent in the brain via not only its anti-inflammatory action but also its induction of neurotrophic factor. We also showed that (1) the AUR-induced GDNF production was inhibited by U0126, a specific inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) 1/2, and by H89, a specific inhibitor of protein kinase A (PKA); and (2) AUR induced the phosphorylation of cAMP response element-binding protein (CREB), a transcription factor located within the nucleus.
    [Show full text]