The inhibition of pathological IgE in allergic diseases by natural compounds

doi:10.1007/s13659-026-00596-1

Abstract

Abstract: IgE-mediated allergic diseases are common and greatly affect quality of life. Current therapeutic strategies include avoidance, which is unreliable, and unspecific symptom management, which causes adverse effects and are expensive. This urges the need for safe, effective, and affordable treatment options for infants, children, adolescents, and adults. This narrative review discusses naturally occurring compounds that have been researched in animal models, in vitro cell lines, and clinical trials to inhibit pathological IgE. These include Food Allergy Herbal Formula (FAHF)-1 and -2 and the derivatives B-FAHF-2, EBF-2, and berberine; Rubia cordifolia and its isolate xanthopurpurin; arctigenin; Anti-Asthma Herbal Medicine Intervention and its isolate formononetin; apigenin; luteolin; resveratrol; pterostilbene; and ginsenoside Rh1. Natural compounds largely work through reduction of IgE production of B cells through modulation of genes involved in B cell activation, differentiation and proliferation, and cell cycle. There is a resulting reduction of Th2 responses and mast cell degranulation, and hence allergic disease pathology and symptomology. There are rich resources of natural compounds, including those with the capacity to restore immunity to that seen in non-allergic individuals. Natural compounds are promising, novel treatment strategies for the vast sufferers of food allergy, allergic asthma, allergic rhinitis, and allergic eczema.

Key words: Natural compounds, IgE, Allergy, Th2 response, Traditional Chinese medicine

摘要： IgE-mediated allergic diseases are common and greatly affect quality of life. Current therapeutic strategies include avoidance, which is unreliable, and unspecific symptom management, which causes adverse effects and are expensive. This urges the need for safe, effective, and affordable treatment options for infants, children, adolescents, and adults. This narrative review discusses naturally occurring compounds that have been researched in animal models, in vitro cell lines, and clinical trials to inhibit pathological IgE. These include Food Allergy Herbal Formula (FAHF)-1 and -2 and the derivatives B-FAHF-2, EBF-2, and berberine; Rubia cordifolia and its isolate xanthopurpurin; arctigenin; Anti-Asthma Herbal Medicine Intervention and its isolate formononetin; apigenin; luteolin; resveratrol; pterostilbene; and ginsenoside Rh1. Natural compounds largely work through reduction of IgE production of B cells through modulation of genes involved in B cell activation, differentiation and proliferation, and cell cycle. There is a resulting reduction of Th2 responses and mast cell degranulation, and hence allergic disease pathology and symptomology. There are rich resources of natural compounds, including those with the capacity to restore immunity to that seen in non-allergic individuals. Natural compounds are promising, novel treatment strategies for the vast sufferers of food allergy, allergic asthma, allergic rhinitis, and allergic eczema.

关键词: Natural compounds, IgE, Allergy, Th2 response, Traditional Chinese medicine

Michelle Carnazza, Morgan Begley, Raj K. Tiwari, Jan Geliebter, Nan Yang, Jixun Zhan, Xiu-Min Li. The inhibition of pathological IgE in allergic diseases by natural compounds[J]. Natural Products and Bioprospecting, 2026, 16(5): 77-77.

References

[1] Carnazza M, Werner R, Tiwari RK, Geliebter J, Li XM, Yang N. The etiology of IgE-mediated food allergy: potential therapeutics and challenges. Int J Mol Sci. 2025. https://doi.org/10.3390/ijms26041563.
[2] Michelson KA, Dribin TE, Vyles D, Neuman MI. Trends in emergency care for anaphylaxis. J Allergy Clin Immunol. 2020;8:767-8. https://doi.org/10.1016/j.jaip.2019.07.018.
[3] Lafuente I, Mazon A, Nieto M, Uixera S, Pina R, Nieto A. Possible recurrence of symptoms after discontinuation of omalizumab in anti-IgE-assisted desensitization to egg. Pediatr Allergy Immunol. 2014;25:717-9. https://doi.org/10.1111/pai.12259.
[4] Cildag S, Senturk T. The effect of omalizumab treatment on IgE and other immunoglobulin levels in patients with chronic spontaneous urticaria and its association with treatment response. Postepy Dermatol Alergol. 2018;35:516-9. https://doi.org/10.5114/ada.2017.71422.
[5] Sampson H, Shreffler W, Yang WH, Sussman G, Brown-Whitehorn T, Nadeau K, et al. Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity. JAMA. 2017;318:1798-809. https://doi.org/10.1001/jama.2017.16591.
[6] Patel VH, Thannir S, Dhanani M, Augustine I, Sandeep SL, Mehadi A, et al. Current limitations and recent advances in the management of asthma. Dis Mon. 2023;69:101483. https://doi.org/10.1016/j.disamonth.2022.101483.
[7] Chapman KR, Boulet LP, Rea RM, Franssen E. Suboptimal asthma control: prevalence, detection and consequences in general practice. Eur Respir J. 2008;31:320-5. https://doi.org/10.1183/09031936.00039707.
[8] Krouse JH. Allergic rhinitis—current pharmacotherapy. Otolaryngol Clin North Am. 2008;41:347-58. https://doi.org/10.1016/j.otc.2007.11.014.
[9] Rollema C, van Roon EN, Ekhart C, van Hunsel F, de Vries TW. Adverse drug reactions of intranasal corticosteroids in the Netherlands: an analysis from the Netherlands pharmacovigilance center. Drugs Real World Outcomes. 2022;9:321-31. https://doi.org/10.1007/s40801-022-00301-x.
[10] Fowler J, Sowerby LJ. Using intranasal corticosteroids. CMAJ. 2021;193:E47. https://doi.org/10.1503/cmaj.201266.
[11] Wise SK, Damask C, Roland LT, Ebert C, Levy JM, Lin S, et al. International consensus statement on allergy and rhinology: allergic rhinitis - 2023. Int Forum Allergy Rhinol. 2023;13:293-859. https://doi.org/10.1002/alr.23090.
[12] Kouzegaran S, Zamani MA, Faridhosseini R, Rafatpanah H, Rezaee A, Yousefzadeh H, et al. Immunotherapy in allergic rhinitis: it’s effect on the immune system and clinical symptoms. Open Access Maced J Med Sci. 2018;6:1248-52. https://doi.org/10.3889/oamjms.2018.264.
[13] Scadding GW, Calderon MA, Shamji MH, Eifan AO, Penagos M, Dumitru F, et al. Effect of 2 years of treatment with sublingual grass pollen immunotherapy on nasal response to allergen challenge at 3 years among patients with moderate to severe seasonal allergic rhinitis: the GRASS randomized clinical trial. JAMA. 2017;317:615-25. https://doi.org/10.1001/jama.2016.21040.
[14] InformedHealth.org. Hay fever: Learn More—Allergen-specific immunotherapy (desensitization) in the treatment of hay fever. https://www.ncbi.nlm.nih.gov/books/NBK279487/. Accessed 11 Mar.
[15] De Carli M, Capezzali E, Tonon S, Frossi B. Mechanism and clinical evidence of immunotherapy in allergic rhinitis. Front Allergy. 2023;4:1217388. https://doi.org/10.3389/falgy.2023.1217388.
[16] Lazor JE, Bozsoki BA, Bharadwaj P. Cure for the itch: current clinical standards and therapies in allergic eczema. Front Allergy. 2025;6:1569292. https://doi.org/10.3389/falgy.2025.1569292.
[17] Lam M, Zhu JW, Tadrous M, Drucker AM. Association between topical calcineurin inhibitor use and risk of cancer, including lymphoma, keratinocyte carcinoma, and melanoma: a systematic review and meta-analysis. JAMA Dermatol. 2021;157:549-58. https://doi.org/10.1001/jamadermatol.2021.0345.
[18] Ahuja K, Lio P. Pediatric topical steroid withdrawal syndrome: what is known, what is unknown. Pediatr Dermatol. 2025;42:311-7. https://doi.org/10.1111/pde.15799.
[19] Sciences D. Vtama (tapinof) cream 1%. https://vtama.com/eczema/. Accessed 5 Apr.
[20] Sun Y, Liu H, Gao Y, Sang H, Kong Q. Effects of dupilumab on quality of life in patients with atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials. Front Pharmacol. 2025;16:1587977. https://doi.org/10.3389/fphar.2025.1587977.
[21] MayoClinic. Atopic dermatitis (eczema). https://www.mayoclinic.org/diseases-conditions/atopic-dermatitis-eczema/diagnosis-treatment/drc-20353279. Accessed 13 Mar.
[22] Ahad T, Wang EY, Liu YA, Lee TK, Lui H, Crawford RI, et al. Incidence of skin cancers in patients with eczema treated with ultraviolet phototherapy. J Am Acad Dermatol. 2022;87:387-9. https://doi.org/10.1016/j.jaad.2021.11.048.
[23] Kokubo K, Onodera A, Kiuchi M, Tsuji K, Hirahara K, Nakayama T. Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis. Front Immunol. 2022;13:945063. https://doi.org/10.3389/fimmu.2022.945063.
[24] Pajulas A, Fu Y, Cheung CCL, Chu M, Cannon A, Alakhras N, et al. Interleukin-9 promotes mast cell progenitor proliferation and CCR2-dependent mast cell migration in allergic airway inflammation. Mucosal Immunol. 2023;16:432-45. https://doi.org/10.1016/j.mucimm.2023.05.002.
[25] Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature. 2008;454:445-54. https://doi.org/10.1038/nature07204.
[26] Li XM. Complementary and alternative medicine for treatment of food allergy. Immunol Allergy Clin North Am. 2018;38:103-24. https://doi.org/10.1016/j.iac.2017.09.012.
[27] Wang J. Treatment of food anaphylaxis with traditional Chinese herbal remedies: from mouse model to human clinical trials. Curr Opin Allergy Clin Immunol. 2013;13:386-91. https://doi.org/10.1097/ACI.0b013e3283615bc4.
[28] Patil SP, Wang J, Song Y, Noone S, Yang N, Wallenstein S, et al. Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: extended phase I study. J Allergy Clin Immunol. 2011;128:1259-1265.e1252. https://doi.org/10.1016/j.jaci.2011.06.015.
[29] Wang J, Patil SP, Yang N, Ko J, Lee J, Noone S, et al. Safety, tolerability, and immunologic effects of a food allergy herbal formula in food allergic individuals: a randomized, double-blinded, placebo-controlled, dose escalation, phase 1 study. Ann Allergy Asthma Immunol. 2010;105:75-84. https://doi.org/10.1016/j.anai.2010.05.00.
[30] Srivastava K, Yang N, Chen Y, Lopez-Exposito I, Song Y, Goldfarb J, et al. Efficacy, safety and immunological actions of butanol-extracted Food Allergy Herbal Formula-2 on peanut anaphylaxis. Clin Exp Allergy. 2011;41:582-91. https://doi.org/10.1111/j.1365-2222.2010.03643.x.
[31] Chen X, Lai J, Song Y, Yang N, Gnjatic S, Gillespie V, et al. Butanol purified food allergy herbal formula-2 has an immunomodulating effect ex-vivo in pediatric Crohn’s disease subjects. Front Med. 2021;8:782859. https://doi.org/10.3389/fmed.2021.782859.
[32] Li XM, Zhang TF, Huang CK, Srivastava K, Teper AA, Zhang L, et al. Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a murine model. J Allergy Clin Immunol. 2001;108:639-46. https://doi.org/10.1067/mai.2001.118787.
[33] Srivastava KD, Kattan JD, Zou ZM, Li JH, Zhang L, Wallenstein S, et al. The Chinese herbal medicine formula FAHF-2 completely blocks anaphylactic reactions in a murine model of peanut allergy. J Allergy Clin Immunol. 2005;115:171-8. https://doi.org/10.1016/j.jaci.2004.10.003.
[34] Qu C, Srivastava K, Ko J, Zhang TF, Sampson HA, Li XM. Induction of tolerance after establishment of peanut allergy by the food allergy herbal formula-2 is associated with up-regulation of interferon-gamma. Clin Exp Allergy. 2007;37:846-55. https://doi.org/10.1111/j.1365-2222.2007.02718.x.
[35] Srivastava KD, Qu C, Zhang T, Goldfarb J, Sampson H, Li X-M. Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-γ-producing CD8+ T cells. J Allergy Clin Immunol. 2009;123(2):443-51. https://doi.org/10.1016/j.jaci.2008.12.1107.
[36] Srivastava KD, Bardina L, Sampson H, Li X-M. Efficacy and immunological actions of FAHF-2 in a murine model of multiple food allergies. Ann Allergy Asthma Immunol. 2012;108:351-8. https://doi.org/10.1016/j.anai.2012.03.008.
[37] Kattan JD, Srinivasan KD, Zou ZM, Goldfarb J, Sampson HA, Li XM. Pharmacological and immunological effects of individual herbs in the Food Allergy Herbal Formula-2 (FAHF-2) on peanut allergy. Phytother Res. 2008;22:651-9. https://doi.org/10.1002/ptr.2357.
[38] Wang J, Jones SM, Pongracic J, Song Y, Yang N, Sicherer SH, et al. Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy. J Allergy Clin Immunol. 2015;136:962-70. https://doi.org/10.1016/j.jaci.2015.04.029.
[39] Srivastava K, Song Y, Yang N, Liu C, Goldberg IE, Nowak-Wegrzyn A, et al. B-FAHF-2 plus oral immunotherapy (OIT) is safer and more effective than OIT alone in a murine model of concurrent peanut/tree nut allergy. Clin Exp Allergy. 2017;47:1038-49. https://doi.org/10.1111/cea.12936.
[40] Song Y, Qu C, Srivastava KD, Yang N, Busse P, Zhao W, et al. Food allergy herbal formula -2 protection against peanut anaphylactic reaction is via inhibition of mast cells and basophils. J Allergy Clin Immunol. 2011;126:1208-17. https://doi.org/10.1016/j.jaci.2010.09.013.
[41] Song Y, Dunkin D, Dahan S, Iuga A, Ceballos C, Hoffstadter-Thal K, et al. Anti-inflammatory effects of the Chinese herbal formula FAHF-2 in experimental and human IBD. Inflamm Bowel Dis. 2014;20:144-53. https://doi.org/10.1097/01.MIB.0000436467.37566.48.
[42] Wang J, Wood RA, Raymond S, Suarez-Farinas M, Yang N, Sicherer SH, et al. Double-blind, placebo-controlled study of E-B-FAHF-2 in combination with omalizumab-facilitated multiallergen oral immunotherapy. J Allergy Clin Immunol Pract. 2023;11:2208-16. https://doi.org/10.1016/j.jaip.2023.03.051.
[43] Carnazza M, Werner R, Begley M, Yang N, Tiwari RK, Geliebter J, et al. Traditional Chinese medicine for pediatric allergic diseases. Curr Allergy Asthma Rep. 2025. https://doi.org/10.1007/s11882-025-01208-7.
[44] Yang N, Srivastava K, Song Y, Liu C, Cho S, Chen Y, et al. Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2. Int Immunopharmacol. 2017;45:120-7. https://doi.org/10.1016/j.intimp.2017.01.009.
[45] Nie Q, Li M, Huang C, Yuan Y, Liang Q, Ma X, et al. The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review. J Transl Med. 2024;22:225. https://doi.org/10.1186/s12967-024-05011-2.
[46] Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015;161:69-81. https://doi.org/10.1016/j.jep.2014.09.049.
[47] Ye Y, Liu X, Wu N, Han Y, Wang J, Yu Y, et al. Efficacy and safety of berberine alone for several metabolic disorders: a systematic review and meta-analysis of randomized clinical trials. Front Pharmacol. 2021;12:653887. https://doi.org/10.3389/fphar.2021.653887.
[48] Yang N, Wang J, Liu C, Song Y, Zhang S, Zi J, et al. Berberine and limonin suppress IgE production by human B cells and peripheral blood mononuclear cells from food-allergic patients. Ann Allergy Asthma Immunol. 2014;113:556-64. https://doi.org/10.1016/j.anai.2014.07.021.
[49] Yang N, Maskey AR, Srivastava KD, Kim M, Wang Z, Musa I, et al. Inhibition of pathologic immunoglobulin E in food allergy by EBF-2 and active compound berberine associated with immunometabolism regulation. Front Immunol. 2023. https://doi.org/10.3389/fimmu.2023.1081121.
[50] Maskey AR, Carnazza M, Spears M, Hemmindinger S, Kopulos D, Yang N, et al. Berberine suppression of human IgE but not IgG production via inhibition of STAT6 binding activity at IgE promoter by BCL6. Cells. 2025. https://doi.org/10.3390/cells14080591.
[51] Carnazza M, Spears M, Tiwari RK, Geliebter J, Yang N, Li XM. A small molecule compound, berberine reduces IgE but not IgG production via promoting miRNA-34a-p53 axis. Cells. 2025. https://doi.org/10.3390/cells14221799.
[52] Srivastava KD, Cao M, Fidan O, Shi Y, Yang N, Nowak-Wegrzyn A, et al. Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature. Front Immunol. 2023;14:1174907. https://doi.org/10.3389/fimmu.2023.1174907.
[53] Ma J, Chan CC, Huang WC, Kuo ML. Berberine inhibits pro-inflammatory cytokine-induced IL-6 and CCL11 production via modulation of STAT6 pathway in human bronchial epithelial cells. Int J Med Sci. 2020;17:1464-73. https://doi.org/10.7150/ijms.45400.
[54] Kim BY, Park HR, Jeong HG, Kim SW. Berberine reduce allergic inflammation in a house dust mite allergic rhinitis mouse model. Rhinology. 2015;53:353-8. https://doi.org/10.4193/Rhino15.02.
[55] Sakat MS, Kilic K, Kandemir FM, Yildirim S, Sahin A, Kucukler S, et al. The ameliorative effect of berberine and coenzyme Q10 in an ovalbumin-induced allergic rhinitis model. Eur Arch Otorhinolaryngol. 2018;275:2495-505. https://doi.org/10.1007/s00405-018-5104-3.
[56] Luo G, Gao M, Lin Q. Integration of bioinformatics analysis, molecular docking and animal experiments to study the therapeutic mechanisms of berberine against allergic rhinitis. Sci Rep. 2024;14:11999. https://doi.org/10.1038/s41598-024-60871-4.
[57] Li Z, Zheng J, Zhang N, Li C. Berberine improves airway inflammation and inhibits NF-κB signaling pathway in an ovalbumin-induced rat model of asthma. J Asthma. 2016;53:999-1005. https://doi.org/10.1080/02770903.2016.1180530.
[58] Andoh T, Yoshihisa Y, Rehman MU, Tabuchi Y, Shimizu T. Berberine induces anti-atopic dermatitis effects through the downregulation of cutaneous EIF3F and MALT1 in NC/Nga mice with atopy-like dermatitis. Biochem Pharmacol. 2021;185:114439. https://doi.org/10.1016/j.bcp.2021.114439.
[59] Maskey AR, Kopulos D, Kwan M, Reyes N, Figueroa C, Mo X, et al. Berberine inhibits the inflammatory response induced by Staphylococcus aureus isolated from atopic E. Cells. 2024;13:1639. https://doi.org/10.3390/cells13191639.
[60] Ai X, Yu P, Peng L, Luo L, Liu J, Li S, et al. Berberine: a review of its pharmacokinetics properties and therapeutic potentials in diverse vascular diseases. Front Pharmacol. 2021;12:762654. https://doi.org/10.3389/fphar.2021.762654.
[61] Jin H, Li J, Zhang M, Luo R, Lu P, Zhang W, et al. Berberine-loaded biomimetic nanoparticles attenuate inflammation of experimental allergic asthma via enhancing IL-12 expression. Front Pharmacol. 2021;12:724525. https://doi.org/10.3389/fphar.2021.724525.
[62] Wen M, Chen Q, Chen W, Yang J, Zhou X, Zhang C, et al. A comprehensive review of Rubia cordifolia L.: traditional uses, phytochemistry, pharmacological activities, and clinical applications. Front Pharmacol. 2022;13:965390. https://doi.org/10.3389/fphar.2022.965390.
[63] Lopez-Exposito I, Castillo A, Yang N, Liang B, Li XM. Chinese herbal extracts of Rubia cordifolia and Dianthus superbus suppress IgE production and prevent peanut-induced anaphylaxis. Chin Med. 2011. https://doi.org/10.1186/1749-8546-6-35.
[64] Yang N, Srivastava KD, Chen Y, Li H, Maskey AR, Yoo P, et al. Sustained silencing peanut allergy by xanthopurpurin is associated with suppression of peripheral and bone marrow IgE-producing B cell. Front Immunol. 2024;15:1299484. https://doi.org/10.3389/fimmu.2024.1299484.
[65] Bhowmik R, Shaharyar MA, Kanakal MM, Sarkar A, Farhana SA, Hussain SM, et al. Ayurvedic herbal formulations Haridra Khanda and Manjisthadi Kwath (brihat) in the management of allergic rhinitis: a pharmacological study. Heliyon. 2024;10:e31937. https://doi.org/10.1016/j.heliyon.2024.e31937.
[66] Li X, Hou R, Ding H, Gao X, Wei Z, Qi T, et al. Mollugin ameliorates murine allergic airway inflammation by inhibiting Th2 response and M2 macrophage activation. Eur J Pharmacol. 2023;946:175630. https://doi.org/10.1016/j.ejphar.2023.175630.
[67] Kim SM, Park HS, Jun DY, Woo HJ, Woo MH, Yang CH, et al. Mollugin induces apoptosis in human Jurkat T cells through endoplasmic reticulum stress-mediated activation of JNK and caspase-12 and subsequent activation of mitochondria-dependent caspase cascade regulated by Bcl-xL. Toxicol Appl Pharmacol. 2009;241:210-20. https://doi.org/10.1016/j.taap.2009.08.024.
[68] Gao M, Yang J, Wang Z, Yang B, Kuang H, Liu L, et al. Simultaneous determination of purpurin, munjistin and mollugin in rat plasma by ultra high performance liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study after oral administration of Rubia cordifolia L. extract. Molecules. 2016. https://doi.org/10.3390/molecules21060717.
[69] Zheng Z, Li S, Zhong Y, Zhan R, Yan Y, Pan H, et al. UPLC-QTOF-MS identification of the chemical constituents in rat plasma and urine after oral administration of Rubia cordifolia L. extract. Molecules. 2017. https://doi.org/10.3390/molecules22081327.
[70] Han DE, Shi Y, Tian P, Wei H, Miao M, Li XM. Development of an ultra-performance liquid chromatography-electrospray ionization-Orbitrap mass spectrometry method for determination of xanthopurpurin in rat plasma and its application to pharmacokinetic study. Biomed Chromatogr. 2020;34:e4838. https://doi.org/10.1002/bmc.4838.
[71] George TA, Chen MM, Czosseck A, Chen HP, Huang HS, Lundy DJ. Liposome-encapsulated anthraquinone improves efficacy and safety in triple negative breast cancer. J Control Release. 2022;342:31-43. https://doi.org/10.1016/j.jconrel.2021.12.001.
[72] Han HS, Koo SY, Choi KY. Emerging nanoformulation strategies for phytocompounds and applications from drug delivery to phototherapy to imaging. Bioact Mater. 2022;14:182-205. https://doi.org/10.1016/j.bioactmat.2021.11.027.
[73] Bok SH, Cho SS, Bae CS, Park DH, Park KM. Safety of 8-weeks oral administration of Arctium lappa L. Lab Anim Res. 2017;33:251-5. https://doi.org/10.5625/lar.2017.33.3.251.
[74] Lyu YR, Jung SK, Lee S, Yang W, Kim S, Jung IC, et al. Efficacy and safety of CAEC (Canavalia gladiata arctium lappa extract complex) on immune function enhancement: An 8 week, randomised, double-blind, placebo-controlled clinical trial. J Funct Foods. 2020;75:104259. https://doi.org/10.1016/j.jff.2020.104259.
[75] Li J, Lv YG, Pan LH, Yao FF, Peng T, Tan YJ, et al. Toxicity study of 28-day subcutaneous injection of arctigenin in Beagle Dogs. Front Pharmacol. 2019;10:1218. https://doi.org/10.3389/fphar.2019.01218.
[76] Cao M, Liu C, Srivastava K, Lin A, Lazarski C, Wang L, et al. Anti-IgE effect of small-molecule-compound arctigenin on food allergy in association with a distinct transcriptome profile. Clin Exp Allergy. 2022;52:250-64. https://doi.org/10.1111/cea.14048.
[77] Mei J, Li X, Xu Z, Zhao H, Zhang J, Xu Q, et al. Acute and chronic toxicity in Sprague-Dawley rats of orally-administered total lignans from Arctii Fructus, a potential therapeutic drug for diabetes. Regul Toxicol Pharmacol. 2024;146:105542. https://doi.org/10.1016/j.yrtph.2023.105542.
[78] Han YH, Mun JG, Jeon HD, Yoon DH, Choi BM, Kee JY, et al. The extract of Arctium lappa L. fruit (Arctii Fructus) improves cancer-induced cachexia by inhibiting weight loss of skeletal muscle and adipose tissue. Nutrients. 2020. https://doi.org/10.3390/nu12103195.
[79] Pellegrini G, Starkey Lewis PJ, Palmer L, Hetzel U, Goldring CE, Park BK, et al. Intraperitoneal administration of high doses of polyethylene glycol (PEG) causes hepatic subcapsular necrosis and low-grade peritonitis with a rise in hepatic biomarkers. Toxicology. 2013;314:262-6. https://doi.org/10.1016/j.tox.2013.06.003.
[80] Zhao M, Wang P, Sun X, Yang D, Zhang S, Meng X, et al. Detrimental impacts of pharmaceutical excipient PEG400 on gut microbiota and metabolome in healthy mice. Molecules. 2023. https://doi.org/10.3390/molecules28227562.
[81] Tan YJ, Ren YS, Gao L, Li LF, Cui LJ, Li B, et al. 28-day oral chronic toxicity study of arctigenin in Rats. Front Pharmacol. 2018;9:1077. https://doi.org/10.3389/fphar.2018.01077.
[82] Ikeda M, Sato A, Mochizuki N, Toyosaki K, Miyoshi C, Fujioka R, et al. Phase I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabine. Cancer Sci. 2016;107:1818-24. https://doi.org/10.1111/cas.13086.
[83] Yoo J, Yang J, Yang HJ, Cho W, Ma JY. Inhibitory effect of fermented Arctium lappa fruit extract on the IgE-mediated allergic response in RBL-2H3 cells. Int J Mol Med. 2016;37:501-8. https://doi.org/10.3892/ijmm.2015.2447.
[84] Wang Y, Xue D, Liu M, Zhou Z, Shang J. A novel arctigenin-containing latex glove prevents latex allergy by inhibiting type I/IV allergic reactions. Chin J Nat Med. 2016;14:185-95. https://doi.org/10.1016/S1875-5364(16)30015-2.
[85] Kee J, Hong S. Inhibition of mast cell-mediated allergic responses by Arctii Fructus extracts and its main compound arctigenin. J Agric Food Chem. 2017;65:9443-52. https://doi.org/10.1021/acs.jafc.7b02965.
[86] He B, Zhang HJ, Yang WH, Shao ZY, Wu LJ, Chen XB, et al. Pharmacokinetics of arctigenin and Fructus Arctii powder in piglets. Front Vet Sci. 2019;6:235. https://doi.org/10.3389/fvets.2019.00235.
[87] Li J, Li X, Ren YS, Lv YY, Zhang JS, Xu XL, et al. Elucidation of Arctigenin pharmacokinetics and tissue distribution after intravenous, oral, hypodermic and sublingual administration in rats and beagle dogs: integration of in vitro and in vivo findings. Front Pharmacol. 2017;8:376. https://doi.org/10.3389/fphar.2017.00376.
[88] Zeng XY, Dong S, He NN, Jiang CJ, Dai Y, Xia YF. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration. Fitoterapia. 2015;105:119-26. https://doi.org/10.1016/j.fitote.2015.06.014.
[89] Liu C, Jiang X, Liang L, Liu H, Li L, Shan Q. Intramyocardial delivery of injectable hydrogel with arctigenin alleviated myocardial ischemia-reperfusion injury in rats. Biotechnol Appl Biochem. 2024;71:501-11. https://doi.org/10.1002/bab.2554.
[90] Liu S, He Y, Feng M, Huang Y, Wu W, Wang J. Targeted delivery of arctigenin using sialic acid conjugate-modified liposomes for the treatment of breast cancer. Molecules. 2024. https://doi.org/10.3390/molecules29010278.
[91] Wang P, Wang B, Chung S, Wu Y, Henning SM, Vadgama JV. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells. RSC Adv. 2014;4:35242-50. https://doi.org/10.1039/c4ra06616b.
[92] Hao Q, Henning SM, Magyar CE, Said J, Zhong J, Rettig MB, Vadgama JV, Wang P. Correction: Hao et al. Enhanced chemoprevention of prostate cancer by combining arctigenin with green tea and quercetin in prostate-specific phosphatase and tensin homolog knockout mice. Biomolecules 2024, 14, 105. Biomolecules. 2025;15. https://doi.org/10.3390/biom15020160.
[93] Li XM, Huang CK, Zhang TF, Teper AA, Srivastava K, Schofield BH, et al. The chinese herbal medicine formula MSSM-002 suppresses allergic airway hyperreactivity and modulates TH1/TH2 responses in a murine model of allergic asthma. J Allergy Clin Immunol. 2000;106:660-8. https://doi.org/10.1067/mai.2000.110102.
[94] Srivastava KD, Teper AA, Zhang T, Li S, Walsh MJ, Huang C, et al. Immunomodulatory effect of the antiasthma Chinese herbal formula MSSM-002 on TH2 cells. J Allergy Clin Immunol. 2004;113:268-76. https://doi.org/10.1016/j.jaci.2003.10.062.
[95] Li XM, Zhang TF, Sampson H, Zou ZM, Beyer K, Wen MC, et al. The potential use of Chinese herbal medicines in treating allergic asthma. Ann Allergy Asthma Immunol. 2004;93:S35-44. https://doi.org/10.1016/s1081-1206(10)61485-8.
[96] Wen M, Wei C, Hu Z, Srivastava K, Ko J, Xi S, et al. Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma. J Allergy Clin Immunol. 2005;116:517-24. https://doi.org/10.1016/j.jaci.2005.05.029.
[97] Zhou W, Chen Z, Li W, Wang Y, Li X-M, Yu H, et al. Systems pharmacology uncovers the mechanisms of anti-asthma herbal medicine intervention (ASHMI) for the prevention of asthma. J Funct Foods. 2019;52:611-9. https://doi.org/10.1016/j.jff.2018.11.048.
[98] Ko J, Busse PJ, Shek LP, Noone S, Sampson HA, Li X. Effect of Chinese herbal formulas on T cell responses in patients with peanut allergy or asthma. J Allergy Clin Immunol. 2005;115:S34.
[99] Kelly-Pieper K, Patil SP, Busse P, Yang N, Sampson HA, Li X, et al. Safety and tolerability of an antiasthma herbal Formula (ASHMI) in adult subjects with asthma: a randomized, double-blinded, placebo-controlled, dose-escalation phase I study. J Altern Complement Med. 2009;15:735-43. https://doi.org/10.1089/acm.2008.0543.
[100] Busse PJ, Schofield B, Birmingham N, Yang N, Wen M, Zhang T, et al. The traditional Chinese herbal formula ASHMI inhibits allergic lung inflammation in antigen-sensitized and antigen-challenged aged mice. Ann Allergy Asthma Immunol. 2010;104:236-46. https://doi.org/10.1016/j.anai.2009.12.006.
[101] Srivastava K, Zhang T, Yang N, Sampson HA, Li X. Anti-asthma simplified herbal medicine intervention-induced long-lasting tolerance to allergen exposure in an asthma model is interferon-γ, but not transforming growth factor-β dependent. Clin Exp Allergy. 2010;40:1678-88. https://doi.org/10.1111/j.1365-2222.2010.03545.x.
[102] Lopez-Exposito I, Srivastava KD, Birmingham N, Castillo A, Miller RL, Li X. Maternal antiasthma simplified herbal medicine intervention therapy prevents airway inflammation and modulates pulmonary innate immune responses in young offspring mice. Ann Allergy Asthma Immunol. 2015;114:43-51. https://doi.org/10.1016/j.anai.2014.10.018.
[103] Jayaprakasam B, Yang N, Wen M, Wang R, Goldfarb J, Sampson HA, et al. Constituents of the anti-asthma herbal formula ASHMI(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro. J Integr Med. 2013;11:195-205. https://doi.org/10.3736/jintegrmed2013029.
[104] Zhang T, Srivastava K, Wen M, Yang N, Cao J, Busse P, et al. Pharmacology and immunological actions of a herbal medicine ASHMI on allergic asthma. Phytother Res. 2010;24:1047-55. https://doi.org/10.1002/ptr.3077.
[105] Srivastava K, Sampson HA, Emala CW, Li X. The anti-asthma herbal medicine ASHMI acutely inhibits airway smooth muscle contraction via prostaglandin E2 activation of EP2/EP4 receptors. Am J Physiol Lung Cell Mol Physiol. 2013;305:L1002-1010. https://doi.org/10.1152/ajplung.00423.2012.
[106] Yang N, Liang B, Srivastava K, Zeng J, Zhan J, Brown L, et al. The Sophora flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction. Phytochem. 2013;95:259-67. https://doi.org/10.1016/j.phytochem.2013.07.023.
[107] Song Y, Wang Z, Wang L, Faybusovich P, Srivastava KD, Liu C, et al. Sophora flavescens alkaloids and corticosteroid synergistically augment IL-10/IL-5 ratio with Foxp3-gene-epigenetic modification in asthma PBMCs. J Asthma Allergy. 2021;14:1559-71. https://doi.org/10.2147/JAA.S321616.
[108] Srivastava KD, Dunkin D, Liu C, Yang N, Miller RL, Sampson HA, et al. Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil predominant airway inflammation in a ragweed sensitized murine asthma model. Ann Allergy Asthma Immunol. 2014;112:339-47. https://doi.org/10.1016/j.anai.2014.01.021.
[109] Wang Z, Li H, Maskey AR, Srivastava KD, Liu C, Yang N, et al. The efficacy & molecular mechanisms of a terpenoid compound Ganoderic acid C1 on corticosteroid-resistant neutrophilic airway inflammation: in vivo and in vitro validation. J Inflamm Res. 2024;17:2547-61. https://doi.org/10.2147/JIR.S433430.
[110] Liu C, Yang N, Song Y, Wang L, Zi J, Zhang S, et al. Ganoderic acid C1 isolated from the anti-asthma formula, ASHMI^TM suppresses TNF-α production by mouse macrophages and peripheral blood mononuclear cells from asthma patients. Int Immunopharmacol. 2015;27:224-31. https://doi.org/10.1016/j.intimp.2015.05.018.
[111] Liu C, Cao M, Yang N, Reid-Adam J, Tversky J, Zhan J, et al. Time-dependent dual beneficial modulation of interferon-γ, interleukin 5, and Treg cytokines in asthma patient peripheral blood mononuclear cells by ganoderic acid B. Phytother Res. 2022;36:1231-40. https://doi.org/10.1002/ptr.7266.
[112] Yang N, Patil S, Zhuge J, Wen M, Wen M, Jayaprakasam B, et al. Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI^TM, inhibit memory Th2 responses in vitro and in vivo. Phytother Res. 2013;27:1381-91. https://doi.org/10.1002/ptr.4862.
[113] Maskey AR, Wang ZZ, Chen X, Dunkin D, Soffer G, Yuan Q, et al. A Flavonoid compound 7, 4 dihydroxy flavone as a potential therapeutic for the treatment and management of EoE. FASEB. 2022. https://doi.org/10.1096/fasebj.2022.36.S1.R4598.
[114] Maskey AR, Wang ZZ, Chen X, Dunkin D, Yang N, Soffer G, et al. Computational analysis to define efficacy & molecular mechanisms of 7, 4'-dihydroxyflavone on eosinophilic esophagitis: ex-vivo validation in human esophagus biopsies. Front Immunol. 2022. https://doi.org/10.3389/fimmu.2022.1015437.
[115] Yu H, Zhang G, Xu J, Wang X, Wang Y, Yang J, et al. Pharmacokinetic and tissue distribution analysis of sporoderm-removed Ganoderma lucidum spore powder in rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2025;1259:124626. https://doi.org/10.1016/j.jchromb.2025.124626.
[116] Cao M, Zhan M, Wang Z, Wang Z, Li XM, Miao M. Development of an orally bioavailable Isoliquiritigenin self-nanoemulsifying drug delivery system to effectively treat ovalbumin-induced asthma. Int J Nanomed. 2020;15:8945-61. https://doi.org/10.2147/ijn.S269982.
[117] Tian J, Wang XQ, Tian Z. Focusing on formononetin: recent perspectives for its neuroprotective potentials. Front Pharmacol. 2022;13:905898. https://doi.org/10.3389/fphar.2022.905898.
[118] Zhang L, Wu Q, Huang Y, Zheng J, Guo S, He L. Formononetin ameliorates airway inflammation by suppressing ESR1/NLRP3/Caspase-1 signaling in asthma. Biomed Pharmacother. 2023;168:115799. https://doi.org/10.1016/j.biopha.2023.115799.
[119] Huang J, Chen X, Xie A. Formononetin ameliorates IL-13-induced inflammation and mucus formation in human nasal epithelial cells by activating the SIRT1/Nrf2 signaling pathway. Mol Med Rep. 2021;24:832. https://doi.org/10.3892/mmr.2021.12472.
[120] Yang N, Musa I, Maskey AR, Li K, Wang Z, Liang B, et al. Formononetin isolated from Sophorae flavescentis inhibits B cell-IgE production by regulating ER-stress transcription factor XBP-1. Front Allergy. 2023;3:1056203. https://doi.org/10.3389/falgy.2022.1056203.
[121] Musa I, Wang Z, Yang N, Li X. Formononetin inhibits IgE by huPlasma/PBMCs and mast cells/basophil activation via JAK/STAT/PI3-Akt pathways. Front Immunol. 2024. https://doi.org/10.3389/fimmu.2024.1427563.
[122] Zhou Z, Ji K, Zhu X, wu X, Lin R, Xie C, et al. Natural isoflavone formononetin inhibits IgE-mediated mast cell activation and allergic inflammation by increasing IgE receptor degradation. Food Funct. 2023;14:2857-69. https://doi.org/10.1039/d2fo03997d.
[123] Li L, Wang Y, Wang X, Tao Y, Bao K, Hua Y, et al. Formononetin attenuated allergic diseases through inhibition of epithelial-derived cytokines by regulating E-cadherin. Clin Immunol. 2018;195:67-76. https://doi.org/10.1016/j.clim.2018.07.018.
[124] Yuan W, Chen Y, Zhou Y, Bao K, Yu X, Xu Y, et al. Formononetin attenuates atopic dermatitis by upregulating A20 expression via activation of G protein-coupled estrogen receptor. J Ethnopharmacol. 2021;266:113397. https://doi.org/10.1016/j.jep.2020.113397.