Planta Med 2025; 91(04): 208-221
DOI: 10.1055/a-2520-0013
Original Papers

Combating Inflammation and Oxidative Stress: Exploring the Cellular Effects of Lonicera caerulea var. kamtschatica Extract

1   Department of Physiology, Medical University of Gdańsk, Poland
2   AronPharma Ltd. R&D Department, Gdańsk, Poland
,
2   AronPharma Ltd. R&D Department, Gdańsk, Poland
,
3   Department of Forensic Medicine, Medical University of Gdańsk, Poland
,
2   AronPharma Ltd. R&D Department, Gdańsk, Poland
,
2   AronPharma Ltd. R&D Department, Gdańsk, Poland
,
2   AronPharma Ltd. R&D Department, Gdańsk, Poland
4   3P-Medicine Laboratory, Medical University of Gdańsk, Poland
› Author Affiliations
This study was supported by the European Union through the European Regional Development Fund under the Smart Growth Operational Programme. Project POIR.01.01.01 – 00 – 1206/20 is implemented under The National Centre for Research and Development (Narodowe Centrum Badań i Rozwoju) call for proposals: “Fast Track”.

Abstract

Lonicera caerulea var. kamtschatica, known as blue honeysuckle or haskap berry, is rich in bioactive compounds such as polyphenols, flavonoids, and anthocyanins, which are linked to various health benefits, including anti-inflammatory and antioxidant properties. The research specifically investigates the effects of an L. caerulea var. kamtschatica extract that has been standardized to contain a minimum of 15% anthocyanins on inflammation and oxidative stress at the cellular level.

In vitro studies using A549 human lung epithelial cells and peripheral blood mononuclear cells demonstrated the extractʼs anti-inflammatory and antioxidant properties. L. caerulea var. kamtschatica extract significantly inhibited the nuclear translocation of NF-κB p65 and reduced the production of IL-8 in A549 cells. It also downregulated the expression of proinflammatory genes (RELA and PTGS2) while upregulating antioxidant genes (CAT, HMOX1, and SOD2). In peripheral blood mononuclear cells, L. caerulea var. kamtschatica extract decreased the phosphorylation of NF-κB p65 and reduced the levels of proinflammatory cytokines IL-1β and IL-6 following lipopolysaccharide stimulation. Additionally, the extract inhibited reactive oxygen species formation and nitric oxide production, demonstrating its potential to modulate oxidative stress. Furthermore, in vitro assays indicated that L. caerulea var. kamtschatica extract could hinder the binding of SARS-CoV-2 spike protein to the hACE2 receptor, suggesting antiviral potential.

These findings suggest that L. caerulea var. kamtschatica extract exerts significant anti-inflammatory and antioxidant effects, indicating its potential as a functional food ingredient or dietary supplement to combat inflammation and oxidative stress.

Supporting Information



Publication History

Received: 22 May 2024

Accepted after revision: 19 January 2025

Accepted Manuscript online:
19 January 2025

Article published online:
11 February 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 
  • References

  • 1 Gerbrandt EM, Bors RH, Chibbar R, Bauman TE. Blue honeysuckle (Lonicera caerulea L.) vegetative growth cessation and leaf drop phenological adaptation to a temperate climate. Genet Resour Crop Evol 2018; 65: 1471-1484
  • 2 Guo L, Qiao J, Zhang L, Yan W, Zhang M, Lu Y, Wang Y, Ma H, Liu Y, Zhang Y, Li J, Qin D, Huo J. Critical review on anthocyanins in blue honeysuckle (Lonicera caerulea L.) and their function. Plant Physiol Biochem 2023; 204: 108090
  • 3 Oszmiański J, Kucharska AZ. Effect of pre-treatment of blue honeysuckle berries on bioactive iridoid content. Food Chem 2018; 240: 1087-1091
  • 4 Zhao L, Li S, Zhao L, Zhu Y, Tianyang H. Antioxidant activities and major bioactive components of consecutive extracts from blue honeysuckle (Lonicera Caerulea L.) cultivated in China. J Food Biochem 2015; 39: 653-662
  • 5 Rop O, Mlcek J, Jurikova T, Neugebauerova J, Vabkova J. Edible flowers–a new promising source of mineral elements in human nutrition. Molecules 2012; 17: 6672-6683
  • 6 Khattab R, Brooks MSL, Ghanem A. Phenolic analyses of haskap berries (Lonicera caerulea L.): spectrophotometry versus high performance liquid chromatography. Int J Food Prop 2016; 19: 1708-1725
  • 7 Rupasinghe H, Boehm M, Sekhon-Loodu S, Parmar I, Bors B, Jamieson AR. Anti-inflammatory activity of haskap cultivars is polyphenols-dependent. Biomolecules 2015; 5: 1079-1098
  • 8 Zdarilová A, Svobodová AR, Chytilová K, Simánek V, Ulrichová J. Polyphenolic fraction of Lonicera caerulea L. fruits reduces oxidative stress and inflammatory markers induced by lipopolysaccharide in gingival fibroblasts. Food Chem Toxicol 2010; 48: 1555-1561
  • 9 Wang Y, Li B, Zhu J, Zhang Q, Zhang X, Li L, Ma Y, Meng X. Lonicera caerulea berry extract suppresses lipopolysaccharide-induced inflammation via Toll-like receptor and oxidative stress-associated mitogen-activated protein kinase signaling. Food Funct 2016; 7: 4267-4277
  • 10 Jin XH, Ohgami K, Shiratori K, Suzuki Y, Koyama Y, Yoshida K, Ilieva I, Tanaka T, Onoe K, Ohno S. Effects of blue honeysuckle (Lonicera caerulea L.) extract on lipopolysaccharide-induced inflammation in vitro and in vivo . Exp Eye Res 2006; 82: 860-867
  • 11 Gołba M, Sokół-Łętowska A, Kucharska AZ. Health properties and composition of honeysuckle berry Lonicera caerulea L. an update on recent studies. Molecules 2020; 25: 749
  • 12 Celli GB, Ghanem A, Brooks MSL. Haskap berries (Lonicera caerulea L.)–a critical review of antioxidant capacity and health-related studies for potential value-added products. Food Bioproc Tech 2014; 7: 1541-1554
  • 13 Croge CP, Cuquel FL, Pintro PTM, Biasi LA, De Bona CM. Antioxidant capacity and polyphenolic compounds of blackberries produced in different climates. HortScience 2019; 54: 2209-2213
  • 14 Mansour KA, Moustafa SF, Abdelkhalik SM. High-resolution UPLC-MS profiling of anthocyanins and flavonols of red cabbage (Brassica oleracea L. var. capitata f. rubra DC.) cultivated in Egypt and evaluation of their biological activity. Molecules 2021; 26: 7567
  • 15 Pachulicz RJ, Yu L, Jovcevski B, Bulone V, Pukala TL. Structural analysis and identity confirmation of anthocyanins in Brassica oleracea extracts by direct injection ion mobility-mass spectrometry. ACS Meas Sci Au 2023; 3: 200-207
  • 16 Ishibashi M, Zaitsu K, Yoshikawa I, Otagaki S, Matsumoto S, Oikawa A, Shiratake K. High-throughput analysis of anthocyanins in horticultural crops using probe electrospray ionization tandem mass spectrometry (PESI/MS/MS). Hortic Res 2023; 10: uhad039
  • 17 Brahmi F, Vejux A, Ghzaiel I, Ksila M, Zarrouk A, Ghrairi T, Essadek S, Mandard S, Leoni V, Poli G, Vervandier-Fasseur D, Kharoubi O, El Midaoui A, Atanasov AG, Meziane S, Latruffe N, Nasser B, Bouhaouala-Zahar B, Masmoudi-Kouki O, Madani K, Boulekbache-Makhlouf L, Lizard G. Role of diet and nutrients in SARS-CoV-2 infection: Incidence on oxidative stress, inflammatory status and viral production. Nutrients 2022; 14: 2194
  • 18 Messaoudi O, Gouzi H, El-Hoshoudy AN, Benaceur F, Patel C, Goswami D, Boukerouis D, Bendahou M. Berries anthocyanins as potential SARS-CoV–2 inhibitors targeting the viral attachment and replication; molecular docking simulation. Egypt J Pet 2021; 30: 33-43
  • 19 Pitsillou E, Liang J, Ververis K, Hung A, Karagiannis TC. Interaction of small molecules with the SARS-CoV-2 papain-like protease: In silico studies and in vitro validation of protease activity inhibition using an enzymatic inhibition assay. J Mol Graph Model 2021; 104: 107851
  • 20 Kim GY, Lee JW, Ryu HC, Wei JD, Seong CM, Kim JH. Proinflammatory cytokine IL-1β stimulates IL-8 synthesis in mast cells via a leukotriene B4 receptor 2-linked pathway, contributing to angiogenesis. J Immunol 2010; 184: 3946-3954
  • 21 Liu Y, Biarnés Costa M, Gerhardinger C. IL-1β is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1β autostimulation. PLoS One 2012; 7: e36949
  • 22 Malkova A, Orlova R, Zhukova N, Kaledina E, Demchenkova A, Naymushina P, Sharayko V. Clinical and pathogenetic relationship between IL-1β and IL-8 in melanoma. 15 March 2022, PREPRINT (Version 1), Research Square. Accessed on 2024;
  • 23 Huang B, Lang X, Li X. The role of IL-6/JAK2/STAT3 signaling pathway in cancers. Front Oncol 2022; 12: 2013177
  • 24 Khan YM, Kirkham P, Barnes PJ, Adcock IM. Brd4 is essential for IL-1β-induced inflammation in human airway epithelial cells. PLoS One 2014; 9: e95051
  • 25 Neuschäfer-Rube F, Pathe-Neuschäfer-Rube A, Hippenstiel S, Kracht M, Püschel GP. NF‐κB‐dependent IL‐8 induction by prostaglandin E(2) receptors EP(1) and EP(4). Br J Pharmacol 2013; 168: 704-717
  • 26 Ghosh CC, Ramaswami S, Juvekar A, Vu HY, Galdieri L, Davidson D, Vancurova I. Gene-specific repression of proinflammatory cytokines in stimulated human macrophages by nuclear IκBα . J Immunol 2010; 185: 3685-3693
  • 27 Liu W, Liu B, Liu S, Zhang J, Lin S. Sphingosine-1-phosphate receptor 2 mediates endothelial cells dysfunction by PI3K-Akt pathway under high glucose condition. Eur J Pharmacol 2016; 776: 19-25
  • 28 Hartman ZC, Poage GM, den Hollander P, Tsimelzon A, Hill J, Panupinthu N, Zhang Y, Mazumdar A, Hilsenbeck SG, Mills GB, Brown PH. Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8. Cancer Res 2013; 73: 3470-3480
  • 29 Zdařilová A, Svobodová AR, Chytilová K, Simánek V, Ulrichová J. Polyphenolic fraction of Lonicera caerulea L. fruits reduces oxidative stress and inflammatory markers induced by lipopolysaccharide in gingival fibroblasts. Food Chem Toxicol 2010; 48: 1555-1561
  • 30 Tsuda T, Horio F, Osawa T. Cyanidin 3-O-beta-D-glucoside suppresses nitric oxide production during a zymosan treatment in rats. J Nutr Sci Vitaminol (Tokyo) 2002; 48: 305-310
  • 31 Saeidi A, Zandi K, Cheok YY, Saeidi H, Wong WF, Lee CYQ, Cheong HC, Yong YK, Larsson M, Shankar EM. T-cell exhaustion in chronic infections: Reversing the state of exhaustion and reinvigorating optimal protective immune responses. Front Immunol 2018; 9: 2569
  • 32 Dustin LB. Innate and adaptive immune responses in chronic HCV infection. Curr Drug Targets 2017; 18: 826-843
  • 33 Jin XH, Ohgami K, Shiratori K, Suzuki Y, Koyama Y, Yoshida K, Ilieva I, Tanaka T, Onoe K, Ohno S. Effects of blue honeysuckle (Lonicera caerulea L.) extract on lipopolysaccharide-induced inflammation in vitro and in vivo . Exp Eye Res 2006; 82: 860-867
  • 34 Tran QK, Firkins R, Giles J, Francis S, Matnishian V, Tran P, VerMeer M, Jasurda J, Burgard MA, Gebert-Oberle B. Estrogen enhances linkage in the vascular endothelial calmodulin network via a feedforward mechanism at the G protein-coupled estrogen receptor 1. J Biol Chem 2016; 291: 10805-10823
  • 35 Furuuchi R, Shimizu I, Yoshida Y, Hayashi Y, Ikegami R, Suda M, Katsuumi G, Wakasugi T, Nakao M, Minamino T. Boysenberry polyphenol inhibits endothelial dysfunction and improves vascular health. PLoS One 2018; 13: e0202051
  • 36 Akaberi D, Krambrich J, Ling J, Luni C, Hedenstierna G, Järhult JD, Lennerstrand J, Lundkvist Å. Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro . Redox Biol 2020; 37: 101734
  • 37 Adusumilli NC, Zhang D, Friedman JM, Friedman AJ. Harnessing nitric oxide for preventing, limiting and treating the severe pulmonary consequences of COVID-19. Nitric Oxide 2020; 103: 4-8
  • 38 Martel J, Ko YF, Young JD, Ojcius DM. Could nasal nitric oxide help to mitigate the severity of COVID-19?. Microbes Infect 2020; 22: 168-171
  • 39 Zhao J, Xie Y, Meng Z, Liu C, Wu Y, Zhao F, Ma X, Christopher TA, Lopez BJ, Wang Y. COVID-19 and cardiovascular complications: Updates of emergency medicine. Emerg Crit Care Med 2023; 3: 104-114
  • 40 Yu R, Chen L, Xin X. Comparative assessment of chemical compositions, antioxidant and antimicrobial activity in ten berries grown in China. Flavour Fragr J 2020; 35: 197-208
  • 41 Wang Y, Li B, Ma Y, Wang X, Zhang Z, Zhang Q, Meng X. Lonicera caerulea berry extract attenuates lipopolysaccharide induced inflammation in BRL-3A cells: Oxidative stress, energy metabolism, hepatic function. Food Funct 2016; 24: 1-10
  • 42 Yeung AWK, Solka M, Jóźwik A, Ksepka N, Matin M, Wang D, Zielińska A, Mohanasundaram A, Vejux A, Zarrouk A, Tewari D, Horbańczuk JO, Lucarini M, Durazzo A, Ghzaiel I, Michalczuk M, Rezig L, Tzvetkovn NT, Matin FB, Lizard G, Bishayee A, Devkota HP, El-Demerdash A, Brnčićm. Santini A, Mickael ME, Horbańczuk O, Charuta A, Szafrańska K, Małachowska E, Wieczorek M, Siddiquea BHN, Hrg D, Frazzini S, Rossi L, Singla RK, Wieczorek A, Łysek-Gładysinska MW, Chandragiri SS, Adamska O, Stolarczyk A, Klusek J, Szymańska-Czerwińska M, Niemczuk K, Hejna M, Sztandarski P, Jaszczyk A, Michnowska H, Tomasik C, Zima-Kulisiewicz B, Marchewka J, Ławiński M, Atanasov AG. Anthocyanins-dietary natural products with a variety of bioactivities for the promotion of human and animal health. Anim Sci Pap Rep 2024; 42: 5-33
  • 43 Bulent Arman A, Pınar A, Megan W, Luini A, Legnaro MLM, Raisini E, Ferrari M, Marino F. PBMC isolation from buffy coat V.2. 2018. Accessed on 2024-12-11 at https://www.protocols.io/view/pbmc-isolation-from-buffy-coat-qu2dwye.pdf
  • 44 Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012; 9: 671-675