Song Y, Wang ZZ, Wang L, Faybusovich P, Srivastava K, Liu C, Tversky J, Dunkin D, Busse P, Ren X, Miller R, Miao M, and Li XM
Background: It has been demonstrated that ASHMI (antiasthma-simplified herbal medicine intervention) can improve airway function and reduce inflammation in human asthmatic patients with high safety and tolerability. In addition, ASHMI significantly suppresses Th2 cytokine production and increases Th1 cytokine production in treating asthma., Objective: Allergic asthma is associated with dysregulation of cytokines. We focused on IL-5 and IL-10 as signature Th2 and Treg cytokines to characterize ASHMI immunomodulatory components., Methods: The effects of ASHMI and individual herbal constituents on IL-5 and IL-10 production by PBMCs from asthmatic subjects were determined ex vivo. Sophora flavescens (SF)-F2, containing alkaloid compounds, effects on PBMC IL-10 and IL-5 production in the presence or absence of dexamethasone (Dex), and on DNA methylation levels at the foxp3 gene promoter were determined., Results: The ratio of anti-CD3/CD28 stimulated IL-10/IL-5 production by PBMCs from asthmatic subjects was significantly reduced compared to healthy subjects. In PBMCs from asthmatic subjects, ASHMI significantly reduced IL-5 production and increased IL-10 secretion in a dose-dependent manner (p < 0.05-0.01). SF-F2 was most effective in increasing IL-10, whereas SF-F4 (flavonoid compounds) was most effective in suppressing IL-5 production. Dex-treated PBMCs from asthma subjects showed a trend of increasing ratio of IL-10/IL-5 while demonstrating reduced levels in both IL-5 and IL-10 (p < 0.05). Co-culture with Dex and SF-F2 significantly prevented Dex suppression of IL-10, while retained Dex-suppression of IL-5 production, and increased IL-10/IL-5 ratio by Dex. Co-culture with SF-F2 and Dex significantly reduced DNA methylation levels at the foxp3 gene promoter at CpG -126 ., Conclusion: The SF alkaloid-rich fraction may be responsible for ASHMI induction of IL-10 production by PBMCs and plays a synergistic effect with Dex for augmenting IL-10/IL-5 ratio., Competing Interests: Xiu-Min Li received research support from the National Institutes of Health (NIH)/National Center for Complementary and Alternative Medicine (NCCAM); Food Allergy Research and Education (FARE) and Winston Wolkoff Integrative Medicine Fund for Allergies and Wellness, the Parker Foundation and Henan University of Chinese Medicine; received consultancy fees from FARE and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Bayer Global Health LLC; received royalties from UpToDate; is an Honorary Professor of Chinese Medical University, Taichung, Taiwan, and Henan University of Chinese Medicine; received travel expenses from the NCCAM, FARE and Henan University of Chinese Medicine and China Allergy Asthma College (Conference); share US patent PCT/US05/008417, PCT 14/875, 772, PCT/US2014/012306, PCT/US14/68396; PCT/US2017/056822) (pending); received practice compensation from the Integrative Health and Acupuncture P, US Times Technology Inc is managed by the related party; is a member of Herbs Springs, LLC, General Nutraceutical Technology, and Health Freedom LLC; Nan Yang shares US patent PCT/US14/68396, PCT 14/875, 772, PCT/US2014/012306, PCT/US14/68396, and is a member of Health Freedom LLC. Kamal Srivastava share PCT/US2017/056822) (pending). The other authors have declared that they have no conflict of interest., (© 2021 Song et al.)