Anti-inflammatory effects of Lycium barbarum leaf extracts in lipopolysaccharide-induced RAW 264.7 macrophage cells and isolation of secondary metabolites

Anti-inflammatory effects of Lycium barbarum leaf extracts in lipopolysaccharide-induced RAW 264.7 macrophage cells and isolation of secondary metabolites

Lycium barbarum possesses many bioactivities such as antidiabetic, antioxidant, antitumor, and immunomodulatory activities. In the present study, the MeOH extract (1 mg/mL) prepared from the leaves of L. barbarum cultivated in Turkey exerted significant anti-inflammatory activity via reducing the release of nitric oxide (NO) in LPSstimulated RAW 264.7 macrophages comparable to positive control indomethacin. Then, the extract was partitioned against CH2Cl2 and EtOAc to yield CH2Cl2, EtOAc and H2O subextracts which were also submitted to the same tests. Among the tested extracts, EtOAc (0.25 and 0.5 mg/mL), and CH2Cl2 (0.25 mg/mL) subextracts showed significant NO production inhibitory activities. The tested extracts also inhibited the production of PGE2 slightly. Successive chromatographic studies on the EtOAc subextract led to the isolation of three secondary metabolites, including chlorogenic acid, hesperidin and rutin as the potential bioactive compounds that are responsible for the in vitro antiinflammatory activity of the EtOAc subextract. The structures were elucidated based on 1D and 2D NMR spectra. Although chlorogenic acid and rutin were previously reported from leaves of L. barbarum, this is the first report of hesperidin from L. barbarum to the best of our knowledge.

___

  • Davis PH, Flora of Turkey and the East Aegean Islands, sixth ed., Edinburgh University Press, Edinburgh, United Kingdom 1979.
  • Yao X, Peng Y, Xua LJ, Li L, Wu QL, Xiao PG. Phytochemical and biological studies of Lycium medicinal plants. Chem Biodivers. 2011; 8: 976-1010. [CrossRef]
  • Amagase H and Farnsworth NR. A review of botanical characteristics, phytochemistry, clinical relevance in efficacy and safety of Lycium barbarum fruit (Goji). Food Res Int. 2011; 44(7): 1702-1717. [CrossRef]
  • Cai H, Liu F, Zuo P, Huang G, Song Z, Wang T, Lu H, Guo F, Han C, Sun G. Practical application of antidiabetic efficacy of Lycium barbarum polysaccharide in patients with type 2 diabetes. Med Chem. 2015; 11: 383-390. [CrossRef]
  • Amagase H, Sun B, Nance DM. Immunomodulatory effects of a standardized Lycium barbarum fruit juice in Chinese older healthy human subjects. J Med Food. 2009; 12(5): 1159-1165. [CrossRef]
  • Amagase H, Sun B, Borek C. Lycium barbarum (goji) juice improves in vivo antioxidant biomarkers in serum of healthy adults. Nutr Res. 2009; 29(1): 19-25. [CrossRef]
  • Mocan A, Vlase L, Vodnar DC, Bischin C, Hanganu D, Gheldiu AM, Oprean R, Silaghi-Dumitrescu R, Crișan G. Polyphenolic content, antioxidant and antimicrobial activities of Lycium barbarum L. and Lycium chinense Mill. leaves. Molecules. 2014; 19(7): 10056-10073. [CrossRef]
  • Liu H, Fan Y, Wang W, Liu N, Zhang H, Zhu Z, Liu A. Polysaccharides from Lycium barbarum leaves: isolation, characterization and splenocyte proliferation activity. Int J Biol Macromol. 2012; 51(4): 417-22. [CrossRef]
  • Dong JZ, Lu DY, Wang Y. Analysis of flavonoids from leaves of cultivated Lycium barbarum L. Plant Foods Hum Nutr. 2009; 64(3): 199-204. [CrossRef]
  • Dong JZ, Gao WS, Lu DY, Wang Y. Simultaneous extraction and analysis of four polyphenols from leaves of Lycium barbarum L. J Food Biochem. 2011; 35(3): 914-931. [CrossRef] Wang, Y., Wang Y, Zhao B, Ma HR, Aisa HA. Two new sesquiterpenoid glycosides from the leaves of Lycium barbarum. J Asian Nat Prod Res. 2016; 18(9): 871-7. [CrossRef]
  • Kumar KP, Nicholls AJ, Wong CHY. Partners in crime: neutrophils and monocytes/macrophages in inflammation and disease. Cell Tissue Res. 2018; 371: 551–565. [CrossRef]
  • Phan AT, Goldrath AW, Glass CK. Metabolic and epigenetic coordination of T cell and Macrophage immunity. Immunity. 2017; 46(5): 714–729. [CrossRef]
  • Tsai HH, Lee WR, Wang PH, Cheng KT, Chen YC, Shen SC. Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-kB and AP-1 activation in macrophages. J Dermatol Sci. 2013; 69(2): 122-131. [CrossRef]
  • López-Martínez LM, Santacruz-Ortega H, Navarro RE, Sotelo-Mundo RR, González-Aguilar GA. A 1H NMR investigation of the interaction between phenolic acids found in mango (Manguifera indica cv Ataulfo) and papaya (Carica papaya cv Maradol) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) Free Radicals. PLoS ONE. 2015; 10(11): 1-11. [CrossRef]
  • Lahmer N, Belboukhari N, Cheriti A, Sekkoum K. Hesperidin and hesperitin preparation and purification from Citrus sinensis peels. Der Pharma Chemica. 2015; 7(2): 1-4.
  • Fathiazad F, Delazar A, Amiri R, Sarker SD. Extraction of flavonoids and quantification of rutin from waste tobacco leaves. 2006; 5(3): 222-227.
  • Medzhitov R. Inflammation 2010: New Adventures of an Old Flame. Cell. 2010; 140: 771-776. [CrossRef]
  • Nathan C and Ding A. Nonresolving inflammation. Cell. 2010; 140: 871–882. [CrossRef]
  • Handschin C and. Spiegelman BM. The role of exercise and PGC1α in inflammation and chronic disease. Nature. 2008; 454(7203): 463–469. [CrossRef]
  • Minihane AM, Vinoy S, Russell WR, Baka A, Roche HM, Tuohy KM, Teeling JL, Blaak EE, Fenech M, Vauzour D, McArdle HJ, Kremer BHA, Sterkman L, Vafeiadou K, Benedetti MM, Williams CM, Calder PC. Low-grade inflammation, diet composition and health: Current research evidence and its translation. Br J Nutr. 2015; 114: 999– 1012. [CrossRef]
  • Bogdan C. Nitric oxide synthase in innate and adaptive immunity: An update. Trends Immunol. 2015; 36(3): 161-178. [CrossRef]
  • Wang S, Suh JH, Hung WL, Zheng X, Wang Y, Ho CT. Use of UHPLC-TripleQ with synthetic standards to profile anti-inflammatory hydroxycinnamic acid amides in root barks and leaves of Lycium barbarum. J Food Drug Anal. 2018; 26: 572-582. [CrossRef]
  • Lopatriello A, Previtera R, Pace S, Werner M, Rubino L, Werz O, Taglialatela-Scafati O, Forino M. NMR-based identification of the major bioactive molecules from an Italian cultivar of Lycium barbarum. Phytochemistry. 2017; 144: 52-57. [CrossRef]
  • Mocan A, Vlase L, Vodnar DC, Bischin C, Hanganu D, Gheldiu AM, Oprean R, Silaghi-Dumitrescu R, Crișan G. Polyphenolic content, antioxidant and antimicrobial activities of Lycium barbarum L. and Lycium chinense Mill. leaves. Molecules. 2014; 19: 10056-10073. [CrossRef]
  • Mocan A, Vlase L, Vodnar DC, Gheldiu AM, Oprean R, Crișan G. Antioxidant, antimicrobial effects and phenolic profile of Lycium barbarum L. flowers. Molecules. 2015; 20: 15060-15071. [CrossRef]
  • Kazłowska K, Hsu T, Hou CC, Yang WC, Tsai GJ. Anti-inflammatory properties of phenolic compounds and crude extract from Porphyra dentate. J Ethnopharmacol. 2010; 128: 123–130. [CrossRef]
  • Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Il Farmaco. 2001; 56: 683–687. [CrossRef]
  • Liu CC, Zhang Y, Dai BL, Ma YJ, Zhang Q, Wang Y, Yang H. Chlorogenic acid prevents inflammatory responses in IL‑1β‑stimulated human SW‑1353 chondrocytes, a model for osteoarthritis. Mol Med Rep. 2017; 16: 1369-1375. [CrossRef]
  • Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M. Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: An updated review of their molecular mechanisms and experimental models. Phytother Res. 2015; 29: 323–331. [CrossRef]
Journal of research in pharmacy (online)-Cover
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: Marmara Üniversitesi
Sayıdaki Diğer Makaleler

Electrochemical detection of anticancer drug lumazine and DNA interaction by using carbon nanotube modified electrodes

Hakan KARADENİZ, Arzum ERDEM, Ece EKSİN

Morphology, myxocarpy, mineral content and in vitro antimicrobial and antiproliferative activities of mericarps of the vulnerable Turkish endemic Salvia pilifera

Mahmut ÜLGER, İbrahim BOZGEYİK, Özkan SARIKAYA, Sevda GÜZEL, Yusuf ÖZAY, Ahmet KAHRAMAN

Evaluation of enzyme inhibitory and antioxidant activity of some Lamiaceae plants

İlkay ERDOĞAN ORHAN, Didem DELİORMAN ORHAN, Nilüfer ORHAN, Mustafa ASLAN, Hasya Nazlı EKİN

Anti-inflammatory effects of Lycium barbarum leaf extracts in lipopolysaccharide-induced RAW 264.7 macrophage cells and isolation of secondary metabolites

Hande SİPAHİ, Hasan KIRMIZIBEKMEZ, Ozan ŞEN, Beril KADIOĞLU YAMAN, Aycan SALMA, Norbert KUSZ, Judit HOHMANN

Preparation of self-flocculated solid lipid nanoparticles

Ahmed GARDOUH, El-Sayed KHAFAGY, Mogamed ELKADY

Preparation and in vitro characterization of AL-Beads containing carbamazepine and/or levetiracetam

Meltem ÇETİN, Afife, Büşra KANDİLLİ, Fatma DEMİRKAYA

The ameliorating effect of silymarin against vancomycininduced apoptosis and inflammation in rat liver

Necmiye CANACA, Sevda GÜZEL, Gülsen BAYRAK, Şerife Efsun ANTMEN, Zuhal UÇKUN ŞAHİNOĞULLARI, Deniz KİBAR

Kojic acid derivatives as potential anticancer agents: Synthesis and cytotoxic evaluation on A375 human malignant melanoma cells

Ayşe ERCAN, Gülşah KARAKAYA, Selin ÖNCÜL, Mutlu Dilsiz AYTEMİR

Optimization of the conditions of the extraction and purification stages of the Shilajit substance

Fedor BUGAEV, Dmitriy KOMPANTSEV, Lyudmila POGRENYAK

Evaluation of the concurrent use of lidocaine and ketamine infusions as adjunctive analgesia in the intensive care unit

Alex EBIED, Abigail ANTIGUA