Inhibition of Proinflammatory Cytokine Release by Flavones and Flavanones from the Leaves of Dracaena steudneri Engl.

Vaderament-A Nchiozem-Ngnitedem; Leonidah Kerubo Omosa; Kibrom Gebreheiwot Bedane; Solomon Derese; Michael Spiteller

doi:10.1055/a-1306-1368

Planta Medica, Inhaltsverzeichnis

Planta Med 2021; 87(03): 209-217
DOI: 10.1055/a-1306-1368

Biological and Pharmacological Activity

Original Papers

Inhibition of Proinflammatory Cytokine Release by Flavones and Flavanones from the Leaves of Dracaena steudneri Engl.

Vaderament-A Nchiozem-Ngnitedem

¹Department of Chemistry, University of Nairobi, Nairobi, Kenya

³Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Dortmund, Germany

,

Leonidah Kerubo Omosa

¹Department of Chemistry, University of Nairobi, Nairobi, Kenya

,

Kibrom Gebreheiwot Bedane

²Department of Chemistry, Addis Ababa University, Addis Ababa, Ethiopia

,

Solomon Derese

¹Department of Chemistry, University of Nairobi, Nairobi, Kenya

,

Michael Spiteller

³Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Dortmund, Germany

› Institutsangaben

Abstract

The leaves of Dracaena steudneri yielded 6 new flavonoids–3,5,7-trihydroxy-6-methyl-3′,4′-methylenedioxyflavone (1), 5,7-dihydroxy-3-methoxy-6-methyl-3′,4′-methylenedioxyflavone (2), 3,5,7-trihydroxy-6-methoxy-3′,4′-methylenedioxyflavone (3), (2S,3S)-3,7-dihydroxy-6-methoxy-3′,4′-methylenedioxyflavanone (4), 4′,5,7-trihydroxy-3,3′,8-trimethoxy-6-methylflavone (5), (2R) 7-hydroxy-2′,8-dimethoxyflavanone (6)–together with 13 known congeners. Their structures were established using spectroscopic and spectrometric methods including NMR, CD, and HRMSⁿ measurements. The compounds were evaluated for their anti-inflammatory potential through measurement of the levels of cytokines IL-1β, IL-2, GM-CSF, and TNF-α in the supernatant of human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Flavones derivatives 1–4 with a C-3′/4′ methylenedioxy substituent led to a substantial increase in the production of IL-1β and GM-CSF out of 4 pro-inflammatory cytokines relative to LPS control. Quercetin derivatives 5, 11, and 13 with a hydroxyl group at C-4′ inhibited the production of IL-2, GM-CSF, and TNF-α. The presence of a C-2/C-3 double bond in 14 was pivotal to the significantly stronger (0.4 to 27.5% of LPS control) inhibitory effect compared to its dihydro derivative 8 (36.2 to 262.7% of LPS control) against all tested cytokines. It is important to note that the inhibitory activity of 14 was substantially higher than that of the standard drug used, ibuprofen.

Key words

Dracaena steudneri - Asparagaceae - flavonoids - anti-inflammatory effects - flavones - flavanones

Volltext

Referenzen

References
1 Lu PL, Morden C. Phylogenetics of the plant genera Dracaena and Pleomele (Asparagaceae). Bot Orient 2010; 7: 64-72
2 Beentje HJ. Kenya Trees, Shrubs, and Lianas, 6th edition. Nairobi: National Museums of Kenya; 1994: 1-722
3 Moshi MJ, Otieno DF, Weisheit A. Ethnomedicine of the Kagera Region, north western Tanzania. Part 3: Plants used in traditional medicine in Kikuku village, Muleba District. J Ethnobiol Ethnomed 2012; 8: 1-11
4 Mukazayire MJ, Minani V, Ruffo CK, Bizuru E, Stevigny C, Duez P. Traditional phytotherapy remedies used in Southern Rwanda for the treatment of liver diseases. J Ethnopharmacol 2011; 138: 415-431
5 Kokwaro JO. Medicinal Plant of East Africa. 3rd edition.. Nairobi: University of Nairobi Press; 2009: 1-478
6 Sun J, Liu JN, Fan B, Chen XN, Pang DR, Zheng J, Zhang Q, Zhao YF, Xiao W, Tu PF, Song YL, Li J. Phenolic constituents, pharmacological activities, quality control, and metabolism of Dracaena species: A review. J Ethnopharmacol 2019; 244: 112138 doi:10.1016/j.jep.2019.112138
7 Hu L, Wang FF, Wang XH, Wang XH, Yang QS, Xiong Y, Liu WX. Phytoconstituents from the leaves of Dracaena cochinchinensis (Lour.) S. C. Chen. Biochem Syst Ecol 2015; 63: 1-5
8 Nchiozem-Ngnitedem VA, Omosa LK, Derese S, Tane P, Heydenreich M, Spiteller M, Seo EJ, Efferth T. Two new flavonoids from Dracaena usambarensis Engl. Phytochem Lett 2020; 36: 80-85
9 Teponno RB, Dzoyem JP, Ngansop RN, Kauhl U, Sandjo LP, Tapondjou LA, Bakowsky U, Opatz T. Cytotoxicity of secondary metabolites from Dracaena viridiflora Engl & Krause and their semisynthetic analogues. Rec Nat Prod 2017; 5: 421-430
10 Lang GZ, Li CJ, Gaohu TY, Chuan L, Ma J, Yang JZ, Zhou TT, Yuan YH, Ye F, Wei JH, Zhang DM. Bioactive flavonoid dimers from Chinese dragonʼs blood, the red resin of Dracaena cochinchinensis . Bioorg Chem 2020; 97: 103659 doi:10.1016/j.bioorg.2020.103659
11 Tapondjou LA, Ponou KB, Teponno RB, Mbiantcha M, Djoukeng JD, Nguelefack TB, Park HJ. In vivo anti-inflammatory effect of a new steroidal saponin, mannioside A, and its derivatives isolated from Dracaena mannii . Arch Pharm Res 2008; 31: 653-658
12 Yang J, Jiang J, Huang G, Liu B, Liu Y, Zhan R, Chen Y. Two new flavanone glycosides from Sunipia scariosa . Biochem Syst Ecol 2014; 57: 317-321
13 Jeong SY, Sang HS, Jong HP, Kim YC. Flavonoids from Spatholobus suberectus . Arch Pharm Res 2004; 27: 589-592
14 Iinuma M, Ohyama M, Tanaka T, Mizuno M, Lang F. Two C-methylated flavonoid glycosides from the roots of Sophora leachiana . J Nat Prod 1991; 54: 1144-1146
15 Ezenyi IC, Salawu OA, Kulkarni R, Emeje M. Antiplasmodial activity-aided isolation and identification of quercetin-4′-methyl ether in Chromolaena odorata leaf fraction with high activity against chloroquine-resistant Plasmodium falciparum . Parasitol Res 2014; 113: 4415-4422
16 Pabuprapap W, Wassanatip Y, Khetkam P, Chaichompoo W, Kunkaewom S, Senabud P, Hata J, Chokchaisiri R, Svasti S, Suksamrarn A. Quercetin analogs with high fetal hemoglobin-inducing activity. Med Chem Res 2019; 28: 1755-1765
17 Park CH, Kim KH, Lee IK, Lee SY, Choi SU, Lee JH, Lee KR. Phenolic constituents of Acorus gramineus . Arch Pharm Res 2011; 34: 1289-1296
18 Huo CH, Li Y, Zhang ML, Wang YF, Zhang Q, Qin F, Shi QW, Kiyota H. Cytotoxic flavonoids from the flowers of Achillea millefolium . Chem Nat Compd 2013; 48: 958-962
19 Vibha P, Osamu S, Setsuko S, Yutaka H, Yusuke H, Tatsuo H, Takuma Y, Motoyoshi S. Antiandrogenic phenolic constituents from Dalbergia cochinchinensis . Phytochemistry 1997; 46: 1219-1223
20 Purusotam B, Shigetoshi K, Hase K, Namba T. Five new C-methyl flavonoids, the potent aldose reductase inhibitors from Matteuccia orientalis TREV. Chem Pharm Bull 1995; 43: 1558-1564
21 Fang JM, Chang CF, Cheng YS. Flavonoids from Pinus morrisonicola . Phytochemistry 1987; 26: 2559-2561
22 Yoshinori A. Chemical constituents of Alnus sieboldiana (Betulaceae) II. The isolation and structure of flavonoids and stilbenes. Bull Chem Soc Jpn 1971; 44: 2761-2766
23 Li F, Awale S, Tezuka Y, Shigetoshi K. Cytotoxic constituents from Brazilian red propolis and their structure-activity relationship. Bioorganic Med Chem 2008; 16: 5434-5440
24 Higa M, Imamura M, Ogihara K, Suzuka T. Isolation of five new flavonoids from Melicope triphylla . Chem Pharm Bull 2013; 61: 384-389
25 Quang TH, Cuong NX, Minh VC, Kiem PV. New flavonoids from Baeckea frutescens and their antioxidant activity. Nat Prod Commun 2008; 3: 755-758
26 Yang XD, Xu LZ, Yang SL. Xanthones from the stems of Securidaca inappendiculata . Phytochemistry 2001; 58: 1245-1249
27 Wu TS, Hsu MY, Kuo PC, Sreenivasulu B, Damu AG, Su CR, Li CY, Chang HC. Constituents from the leaves of Phellodendron amurense var. wilsonii and their bioactivity. J Nat Prod 2003; 66: 1207-1211
28 Slade D, Ferreira D, Marais JPJ. Circular dichroism, a powerful tool for the assessment of absolute configuration of flavonoids. Phytochemistry 2005; 66: 2177-2215
29 Cui L, Thuong PT, Lee HS, Ndinteh DT, Mbafor JT, Fomum ZT, Oh WK. Flavanones from the stem bark of Erythrina abyssinica . Bioorganic Med Chem 2008; 16: 10356-10362
30 OʼBryan MK, Schlatt S, Phillips DJ, David M, Kretser D, Hedger MP. Bacterial lipopolysaccharide-induced inflammation compromises testicular function at multiple levels in vivo. Endocrinology 2000; 141: 238-246
31 Li N, Ma Z, Li M, Xing Y, Hou Y. Natural potential therapeutic agents of neurodegenerative diseases from the traditional herbal medicine Chinese Dragon Blood. J Ethnopharmacol 2014; 152: 508-521
32 Hougee S, Sanders A, Faber J, Graus YM, Van WB, Garssen J, Hoijer MA. Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophages. Biochem Pharmacol 2005; 69: 241-248
33 Owor RO, Bedane KG, Zühlke S, Derese S, Otieno G, Ndakala A, Spiteller M. Anti-infl ammatory flavanones and flavones from Tephrosia linearis . J Nat Prod 2019; 83: 996-1004
34 Mukavi J, Omosa LK, Nchiozem-Ngnitedem VA, Nyaga J, Omole R, Bitchagno GTB, Spiteller M. Anti-inflammatory norhopanes from the root bark of Fagaropsis angolensis (Engl.) H.M. Gardner. Fitoterapia 2020; 146: 104690 doi:10.1016/j.fitote.2020.104690
35 Nchiozem-Ngnitedem VA, Omosa LK, Bedane KG, Derese S, Brieger L, Strohmann C, Spiteller M. Anti-inflammatory steroidal sapogenins and a conjugated chalcone-stilbene from Dracaena usambarensis Engl. Fitoterapia 2020; 146: 104717 doi:10.1016/j.fitote.2020.104717

Zusatzmaterial

Supporting Information