Effects of 20-hydroxyecdysone, Leuzea carthamoides extracts, dexamethasone and their combinations on the NF-κ B activation in HeLa cells
Abstract
OBJECTIVES: The plant steroid 20-hydroxyecdysterone (20E) and 20E-containing extracts from Leuzea carthamoides (Willd.) DC are sold with claims of anabolic and immunomodulatory effects. Yet their effect on the activation of nuclear factor kappa B (NF-κB), a key player in immune response and cell fate, and their influence on the NF-κB-inhibiting activity of steroidal anti-inflammatory drugs is still unknown. METHODS: The ability of 20E, Leuzea extracts and selected steroidal/non-steroidal anti-inflammatory drugs to influence the activation of NF-κB was explored using, as the experimental model, human cervical cancer HeLa-IL-6 cells stably transfected with an IL-6-bound reporter gene. Effects on cell viability and proliferation were monitored (MTT assay). HPLC-DAD was used to establish links between chemical patterns of Leuzea extracts and their bioactivities. KEY FINDINGS: 20E inhibited NF-κB activation (IC50 31.8 µm) but was less active than other plant metabolites (xanthohumol 3.8 µm, withaferin A 1.4 µm). Leuzea extracts with high content in 20E had a fair activating effect, but in contrast, some extracts with low 20E content significantly inhibited NF-κB activation at IC50s ranging from 3.5 to 6.2 µg/ml. Combination tests confirmed that 20E does not explain the NF-κB modulation achieved by Leuzea extracts. The extracts but not 20E itself showed a significant modulation of the NF-κB inhibitory effect of dexamethasone. CONCLUSIONS: 20E is unlikely a major player in the NF-κB inhibitory effects displayed by some Leuzea extracts in vitro. If confirmed in vivo, caution should prevail towards marketed Leuzea extracts that are non-standardised or standardised on 20E only, since different starting materials and extracts may even cause opposite effects. More importantly, our results indicate the interaction potential of Leuzea with steroidal anti-inflammatory drugs.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
20E inhibited NFκB activation similar to dexamethasone, but it did not modulate the effect of dexamethasone in HeLa cells.
“Moreover, 20E inhibited NFκB activation similar to this drug; however, it has not been found to modulate the effect of dexamethasone in HeLa cells [34].”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [34]
Investigations into Rhaponticum carthamoides revealed that its extracts are low in toxicity.
“The investigations into R. carthamoides revealed that its extracts are low in toxicity [69,121,122,123,124,125,126,127,128,129,130,131,132].”
From Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition (2024) · cites this paper as [125]
Extracts from Rhaponticum carthamoides show antibacterial, cytotoxic, anti-adipogenic, and antioxidant activities.
“Extracts from R. carthamoides show a variety of activities, including antibacterial, cytotoxic, anti-adipogenic, and antioxidant [69,121,122,123,124,125,126,127,128,129,130,131,132].”
From Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition (2024) · cites this paper as [125]
Beta-ecdysone is reported to promote muscle cell growth via insulin and PI3K/Akt signaling.
“Mechanistically, βEcd is reported to promote muscle cell growth via insulin and PI3K/Akt signaling and is reported to inhibit NF-kB activation in a cancer cell line [21, 25, 27, 61].”
From Prevention of glucocorticoid induced bone changes with beta-ecdysone (2015) · cites this paper as [61]
Beta-ecdysone is reported to inhibit NF-kB activation in a cancer cell line.
“Mechanistically, βEcd is reported to promote muscle cell growth via insulin and PI3K/Akt signaling and is reported to inhibit NF-kB activation in a cancer cell line [21, 25, 27, 61].”
From Prevention of glucocorticoid induced bone changes with beta-ecdysone (2015) · cites this paper as [61]
Cites
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104 · see citing works
NF-κB regulation in the immune system
Li, Q., & Verma, I. M. (2002) · Nature Reviews Immunology · doi:10.1038/nri910 · Cited by 4,007 · see citing works
Activation of interleukin-6 gene expression through the NF-kappa B transcription factor.
Libermann, T. A., & Baltimore, D. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.5.2327 · Cited by 1,372 · see citing works
Scheinman, R. I., Gualberto, A., Jewell, C. M., Cidlowski, J. A., & Baldwin, A. S. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.2.943 · Cited by 819 · see citing works
McKay, L. I., & Cidlowski, J. A. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.4.0375 · Cited by 805 · see citing works
McKay, L. I., & Cidlowski, J. A. (1997) · Molecular Endocrinology · doi:10.1210/mend.12.1.0044 · Cited by 410 · see citing works
Plant adaptogens III. Earlier and more recent aspects and concepts on their mode of action
Panossian, A., Wikman, G., & Wagner, H. (1999) · Phytomedicine · doi:10.1016/s0944-7113(99)80023-3 · Cited by 211 · see citing works
The IKK‐NF‐κB pathway: a source for novel molecular drug targets in pain therapy?
Niederberger, E., & Geißlinger, G. (2008) · The FASEB Journal · doi:10.1096/fj.08-109355 · Cited by 205 · see citing works
Practical uses for ecdysteroids in mammals including humans: and update
Lafont, R., & Dinan, L. (2003) · Journal of Insect Science · doi:10.1093/jis/3.1.7 · Cited by 196 · see citing works
Practical uses for ecdysteroids in mammals including humans: And update
Lafont, R., & Dinan, L. (2003) · Journal of Insect Science · doi:10.1673/031.003.0701 · Cited by 196 · see citing works
Chromatographic procedures for the isolation of plant steroids
Dinan, L. N., Harmatha, J., & Lafont, R. (2001) · Journal of Chromatography A · doi:10.1016/s0021-9673(01)00992-x · Cited by 165 · see citing works
Exploiting semiochemicals in insect control
Agelopoulos, N. G., Birkett, M. A., Hick, A. J., Hooper, A. M., Pickett, J. A., Pow, E. M., Smart, L. E., Smiley, D. W. M., Wadhams, L. J., & Woodcock, C. M. (1999) · Pesticide Science · doi:10.1002/(sici)1096-9063(199903)55:3 · Cited by 161 · see citing works
Biological activities of lignans and stilbenoids associated with plant-insect chemical interactions
Harmatha, J., & Dinan, L. N. (2003) · Phytochemistry Reviews · doi:10.1023/b:phyt.0000045494.98645.a3 · Cited by 160 · see citing works
Plaisance, S., Berghe, W. V., Boone, E., Fiers, W., & Haegeman, G. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.7.3733 · Cited by 139 · see citing works
Garside, H., Stevens, A., Farrow, S. N., Normand, C., Houle, B., Berry, A., Maschera, B., & Ray, D. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407309200 · Cited by 115 · see citing works
Chemistry and Pharmacology of Rhaponticum carthamoides: A Review
Kokoska, L., & Janovska, D. (2009) · Phytochemistry · doi:10.1016/j.phytochem.2009.04.008 · Cited by 112 · see citing works
Cucurbitacins are insect steroid hormone antagonists acting at the ecdysteroid receptor
Dinan, L. N., Whiting, P., Girault, J., Lafont, R., DHADIALLA, S. T., CRESS, E. D., Mugat, B., Antoniewski, C., & Lepesant, J. (1997) · Biochemical Journal · doi:10.1042/bj3270643 · Cited by 106 · see citing works
Mango leafhoppers (Homoptera: Cicadellidae) - a review.
Sohi, A. S. (1990) · Journal of insect science/Journal of Insect Science · Cited by 96 · see citing works
Ecdysteroids from the Roots of Leuzea carthamoides
Píš, J., Buděšínsky̌, M., Vokáč, K., Laudová, V., & Harmatha, J. (1994) · Phytochemistry · doi:10.1016/s0031-9422(00)90343-1 · Cited by 81 · see citing works
Insect hormones in vertebrates: Anabolic effects of 20-hydroxyecdysone in Japanese quail
Sláma, K., Koudela, K., Tenora, J., & Maťhová, A. (1996) · Cellular and Molecular Life Sciences · doi:10.1007/bf01925578 · Cited by 73 · see citing works
Dvořák, Z., Vrzal, R., Maurel, P., & Jitka Ulrichová, A. (2005) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2005.10.105 · Cited by 72 · see citing works
New anti-inflammatory ergostane-type ecdysteroids from the sclerotium of Polyporus umbellatus
Sun, Y., & Yasukawa, K. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.04.008 · Cited by 69 · see citing works
Boehlk, S., Fessele, S., Mojaat, A., Miyamoto, N. G., Werner, T., Nelson, E. L., Schlöndorff, D., & Nelson, P. J. (2000) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(200004)30:4 · Cited by 65 · see citing works
Ecdysteroids from Leuzea Carthamoides
Girault, J.-P., Lafont, R., Varga, E., Hajdu, Z., Herke, I., & Szendrei, K. (1988) · Phytochemistry · doi:10.1016/0031-9422(88)84085-8 · Cited by 62 · see citing works
Kormosh, N., Лактионов, К. К., & Antoshechkina, M. (2006) · Phytotherapy Research · doi:10.1002/ptr.1889 · Cited by 52 · see citing works
Oehme, I., Bösser, S., & Zörnig, M. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401730 · Cited by 48 · see citing works
Castro‐Caldas, M., Mendes, A. F., Carvalho, A. P., Duarte, C. B., & Lopes, M. C. (2003) · Mediators of Inflammation · doi:10.1080/0962935031000096953 · Cited by 36 · see citing works
20-hydroxyecdysone as a human lymphocyte and neutrophil modulator: In vitro evaluation
Trenin, D. S., & Володин, В. В. (1999) · Archives of Insect Biochemistry and Physiology · doi:10.1002/(sici)1520-6327(1999)41:3 · Cited by 33 · see citing works
Donjerković, D., Mueller, C. M., & Scott, D. W. (2000) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(200004)30:04 · Cited by 29 · see citing works
A Stilbene from the Roots of Leuzea carthamoides
Hajdú, Z., Varga, E., Hohmann, J., Kálmán, A., Argay, G., & Günther, G. V. (1998) · Journal of Natural Products · doi:10.1021/np980128i · Cited by 23 · see citing works
Effect of Pfaffia iresinoides on the experimental inflammatory process in rats
Taniguchi, S. F., Bersani‐Amado, C. A., Sudo, L. S., Caparroz‐Assef, S. M., & Oga, S. (1997) · Phytotherapy Research · doi:10.1002/(sici)1099-1573(199712)11:8 · Cited by 22 · see citing works
Inhibition of the 53BP2S‐mediated apoptosis by nuclear factor κB and Bcl‐2 family proteins
Takahashi, N., Kobayashi, S., Kajino, S., Imai, K., Tomoda, K., Shimizu, S., & Okamoto, T. (2005) · Genes to Cells · doi:10.1111/j.1365-2443.2005.00878.x · Cited by 19 · see citing works
Thiophene acetylenes from Leuzea roots
Szendrei, K., Reisch, J., & Varga, E. (1984) · Phytochemistry · doi:10.1016/s0031-9422(00)85055-4 · Cited by 18 · see citing works
Phototoxic activity of a thiophene polyacetylene from Leuzea carthamoides
Chobot, V., Vytlačilová, J., Kubicová, L., Opletal, L., Jahodář, L., Laakso, I., & Vuorela, P. M. (2006) · Fitoterapia · doi:10.1016/j.fitote.2006.01.001 · Cited by 17 · see citing works
Rm, G., Николаевич, П. С., Vv, P., & Kondrat'eva, I. I. (1995) · PubMed · Cited by 17 · see citing works
Two Flavonol 5-O-Glycosides from the Roots of Leuzea carthamoides
Sharaf, M., Skiba, A., Weglarz, Z., & El-Ansari, M. A. (2001) · Fitoterapia · doi:10.1016/s0367-326x(01)00316-1 · Cited by 16 · see citing works
Sesquiterpene lactones. XXXIV. Guaianolides in the genus Leuzea DC.
Nowak, G., Holub, M., & Buděšı́nský, M. (2014) · Acta Societatis Botanicorum Poloniae · doi:10.5586/asbp.1988.015 · Cited by 15 · see citing works
Evaluation of biological activities of Rhaponticum carthamoides extracts.
Biskup, E., & Łojkowska, E. (2009) · doi:10.5897/jmpr.9000619 · Cited by 15 · see citing works
Gaube, F., Wölfl, S., Pusch, L., Werner, U., Kroll, T., Schrenk, D., Hartmann, R., & Hamburger, M. (2008) · Planta Medica · doi:10.1055/s-0028-1088316 · Cited by 14 · see citing works
Sesquiterpene lactones. XXX. Cynaropicrin in species of the subtribe Centaureanae Dumort.
Nowak, G., Drożdż, B., Kroszczyński, W., & Holub, M. (2014) · Acta Societatis Botanicorum Poloniae · doi:10.5586/asbp.1986.003 · Cited by 14 · see citing works
Harmatha, J., Vokáč, K., Kmonı́čková, E., & Zı́dek, Z. (2008) · Steroids · doi:10.1016/j.steroids.2007.12.014 · Cited by 14 · see citing works
Effects of extracts from medicinal plants on the development of metastatic process
Гольдберг, Е. Д., Амосова, Е. Н., Зуева, Е. П., Разина, Т. Г., Крылова, С. Г., & Владимирович, Р. Д. (2004) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-005-0023-x · Cited by 5 · see citing works
Gadzhieva, R. M., Portugalov, S. N., Panyushkin, V. V., et al. (1995) · Cited by 3 · see citing works
Castro‐Caldas, M., Mendes, A. F., Carvalho, A. P., Duarte, C. B., & Lopes, M. C. (2003) · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Molecular insight in the multifunctional activities of Withaferin A
Berghe, W. V., Sabbe, L., Kaileh, M., Haegeman, G., & Heyninck, K. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.08.027 · Cited by 242 · see citing works
Medicinal plants from the 14th edition of the Russian Pharmacopoeia, recent updates
Shikov, A. N., Наркевич, И. А., Флисюк, Е. В., Luzhanin, V. G., & Pozharitskaya, O. N. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.113685 · Cited by 192 · see citing works
Peschel, W., & Politi, M. (2015) · Talanta · doi:10.1016/j.talanta.2015.02.040 · Cited by 77 · see citing works
Self-citationWithaferin A: From Ancient Remedy to Potential Drug Candidate
Sultana, T., Okla, M. K., Ahmed, M., Akhtar, N., Al-Hashimi, A., AbdElgawad, H., & Haq, I. (2021) · Molecules · doi:10.3390/molecules26247696 · Cited by 59 · see citing works
Sun, L., Li, W., Lin, Z., Duan, X., Li, X., Yang, N., Lan, T., Li, M., Sun, Y. N., Yu, M., et al. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356669 · Cited by 58 · see citing works
Withanolides: Promising candidates for cancer therapy
Zhang, Q., Yuan, Y., Cao, S., Kang, N., & Qiu, F. (2024) · Phytotherapy Research · doi:10.1002/ptr.8090 · Cited by 34 · see citing works
Potential Anticancer Properties and Mechanisms of Action of Withanolides
Samadi, A. K. (2015) · The Enzymes · doi:10.1016/bs.enz.2015.05.002 · Cited by 32 · see citing works
Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition
Todorova, V., Ivanova, S., Chakarov, D., Kraev, K., & Ivanov, K. (2024) · Nutrients · doi:10.3390/nu16091382 · Cited by 31 · see citing works
“[125] Table 3.”
Prevention of glucocorticoid induced bone changes with beta-ecdysone
Dai, W., Jiang, L., Lay, Y.-A. E., Chen, H., Jin, G., Zhang, H., Kot, A., Ritchie, R. O., Lane, N. E., & Yao, W. (2015) · Bone · doi:10.1016/j.bone.2015.01.001 · Cited by 30 · see citing works
Dushkin, M., Khrapova, M., Kovshik, G., Chasovskikh, M., Menshchikova, E., Trufakin, V., Shurlygina, A., & Vereschagin, E. (2014) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-14-33 · Cited by 25 · see citing works
Sun, L., Li, W., Lin, Z., Duan, X., Xing, E., Jiang, M., Yang, N., Qi, H.-H., Sun, Y. N., Li, M., et al. (2015) · Cell and Tissue Research · doi:10.1007/s00441-014-2083-6 · Cited by 17 · see citing works
Sida tuberculata reduces oxidative stress and pain caused by the knee osteoarthritis
Yamada, E. F., Olin, L. C., Pontel, C. L., da Rosa, H. S., Folmer, V., & da Silva, M. D. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.112277 · Cited by 15 · see citing works
Park, M. N., Choi, J., Fahim, M. M. H., Asevedo, E. A., Nurkolis, F., Ribeiro, R. I. M. D. A., Kang, H. N., Kang, S., Syahputra, R. A., & Kim, B. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1504618 · Cited by 14 · see citing works
Phytoecdysteroids as modulators of the Toxoplasma gondii growth rate in human and mouse cells
Dzitko, K., Grzybowski, M. M., Pawełczyk, J., Dziadek, B. R., Gatkowska, J. M., Stączek, P., & Długońska, H. (2015) · Parasites & Vectors · doi:10.1186/s13071-015-1019-7 · Cited by 13 · see citing works
Park, I., Park, K., Lee, H.-S., Hong, S.-M., Sriramulu, D. K., Hwang, H., Song, S., Baek, J. G., Kim, D. H., Kim, S. Y., et al. (2023) · ACS Omega · doi:10.1021/acsomega.3c02421 · Cited by 11 · see citing works
Zádor, E. (2025) · Cells · doi:10.3390/cells14060431 · Cited by 9 · see citing works
“Moreover, 20E inhibited NF κ B activation similar to this drug; however, it has not been found to modulate the effect of dexamethasone in HeLa cells [34].”
Biskup, E., Szynklarz, B., Gołębiowski, M., Borsuk, K., Stepnowski, P., & Łojkowska, E. (2013) · Journal of Medicinal Plants Research · Cited by 7 · see citing works
KKh, B. I. O., & Тимофеев, Н. П. (2023) · Sel skokhozyaistvennaya Biologiya · doi:10.15389/agrobiology.2023.1.114rus · Cited by 6 · see citing works
Sriraman, N., Sarkar, A., Naskar, S., Mahajan, N., Mukherjee, O., Pradeep, R., George, M., & Sarkar, K. (2024) · Medical Oncology · doi:10.1007/s12032-024-02331-7 · Cited by 3 · see citing works
Sida tuberculata: In vitro cytotoxicity and in vivo anti-inflammatory effect
da Rosa, H. S., Santos, M. C., Costa, M. T., Salgueiro, A. C. F., da Silva, M. D., Nogueira-Librelotto, D. R., Jessé, C. R., Machado, M. M., de Oliveira, L. F. S., Folmer, V., et al. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114956 · Cited by 3 · see citing works
Тимофеев, Н. П. (2022) · Agricultural science Euro-North-East · doi:10.30766/2072-9081.2022.23.4.480-495 · Cited by 2 · see citing works
Three novel constituents from the roots of Rhaponticum carthamoides
Zomborszki, Z. P., Kúsz, N., Hohmann, J., & Csupor, D. (2023) · Acta Pharmaceutica Hungarica · doi:10.33892/aph.2023.93.9-14 · Cited by 1 · see citing works
NF-κB inhibitors from terrestrial plants reported in 2011
Schumacher, M. M., Dicato, M. A., & Diederich, M. F. (2020) · Journal of Food and Drug Analysis · doi:10.38212/2224-6614.2111
- Authors
- Peschel, W., Kump, A., & Prieto, J. M.
- Affiliations
- University of London (GB)
- Botanische Arbeitsgemeinschaft am Oberösterreichischen Landesmuseum , Biologiezentrum, Linz,
- Corresponding author
- Peschel, Wieland
- ORCID
- Prieto, José Maria
- Venue
- Journal of Pharmacy and Pharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-11-01
- Volume
- 63
- Issue
- 11
- Pages
- 1483-1495
- ISSN
- 0022-3573 (ISSN-L)
- 2042-7158
- OpenAlex
- W2119673735
- Cited by
- 24
- References
- 42
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2015: 5 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Pharmacy and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical Studies and Bioactivities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- 20-hydroxyecdysone, Leuzea carthamoides, NF-κB activation, dexamethasone, plant steroids, xanthohumol, withaferin A, HeLa cells, combined effects, immunomodulation
- MeSH terms
- Anti-Inflammatory Agents, Non-Steroidal, Dexamethasone, Drug Combinations, Ecdysterone, HeLa Cells, Humans, NF-kappa B, Plant Preparations, Leuzea
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
