PMID- 38380329 OWN - NLM STAT- MEDLINE DCOM- 20240222 LR - 20240401 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 15 DP - 2024 TI - Sustained silencing peanut allergy by xanthopurpurin is associated with suppression of peripheral and bone marrow IgE-producing B cell. PG - 1299484 LID - 10.3389/fimmu.2024.1299484 [doi] LID - 1299484 AB - INTRODUCTION: Peanut allergy is an immunoglobulin E (IgE) mediated food allergy. Rubia cordifolia L. (R. cordifolia), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production in vivo. This study aims to identify IgE-inhibitory compounds from the water extract of R. cordifolia and investigate the underlying mechanisms using in vitro and in vivo models. METHODS: Compounds were isolated from R. cordifolia water extract and their bioactivity on IgE production was assessed using a human myeloma U266 cell line. The purified active compound, xanthopurpurin (XPP), was identified by LC-MS and NMR. Peanut-allergic C3H/HeJ mice were orally administered with or without XPP at 200microg or 400microg per mouse per day for 4 weeks. Serum peanut-specific IgE levels, symptom scores, body temperatures, and plasma histamine levels were measured at challenge. Cytokines in splenocyte cultures were determined by ELISA, and IgE (+) B cells were analyzed by flow cytometry. Acute and sub-chronic toxicity were evaluated. IL-4 promoter DNA methylation, RNA-Seq, and qPCR analysis were performed to determine the regulatory mechanisms of XPP. RESULTS: XPP significantly and dose-dependently suppressed the IgE production in U266 cells. XPP significantly reduced peanut-specific IgE (>80%, p <0.01), and plasma histamine levels and protected the mice against peanut-allergic reactions in both early and late treatment experiments (p < 0.05, n=9). XPP showed a strong protective effect even 5 weeks after discontinuing the treatment. XPP significantly reduced the IL-4 level without affecting IgG or IgA and IFN-gamma production. Flow cytometry data showed that XPP reduced peripheral and bone marrow IgE (+) B cells compared to the untreated group. XPP increased IL-4 promoter methylation. RNA-Seq and RT-PCR experiments revealed that XPP regulated the gene expression of CCND1, DUSP4, SDC1, ETS1, PTPRC, and IL6R, which are related to plasma cell IgE production. All safety testing results were in the normal range. CONCLUSIONS: XPP successfully protected peanut-allergic mice against peanut anaphylaxis by suppressing IgE production. XPP suppresses murine IgE-producing B cell numbers and inhibits IgE production and associated genes in human plasma cells. XPP may be a potential therapy for IgE-mediated food allergy. CI - Copyright (c) 2024 Yang, Srivastava, Chen, Li, Maskey, Yoo, Liu, Tiwari, Geliebter, Nowak-Wegrzyn, Zhan and Li. FAU - Yang, Nan AU - Yang N AD - R & D Division, General Nutraceutical Technology, LLC, Elmsford, NY, United States. FAU - Srivastava, Kamal AU - Srivastava K AD - R & D Division, General Nutraceutical Technology, LLC, Elmsford, NY, United States. FAU - Chen, Yujuan AU - Chen Y AD - School of Life Science and Technology, Changchun University of Science and Technology, Changchun, Jilin, China. FAU - Li, Hang AU - Li H AD - Central Lab, Shenzhen Bao'an Chinese Medicine Hospital, Shenzhen, China. FAU - Maskey, Anish AU - Maskey A AD - Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States. FAU - Yoo, Patrick AU - Yoo P AD - Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States. FAU - Liu, Xiaohong AU - Liu X AD - Department of Respiratory, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Tiwari, Raj K AU - Tiwari RK AD - Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States. FAU - Geliebter, Jan AU - Geliebter J AD - Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States. FAU - Nowak-Wegrzyn, Anna AU - Nowak-Wegrzyn A AD - Department of Pediatrics, Hassenfeld Children's Hospital, NYU Grossman School of Medicine, New York, NY, United States. FAU - Zhan, Jixun AU - Zhan J AD - Department of Biological Engineering, Utah State University, Logan, UT, United States. FAU - Li, Xiu-Min AU - Li XM AD - Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240206 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 820484N8I3 (Histamine) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) RN - 059QF0KO0R (Water) SB - IM MH - Mice MH - Humans MH - Animals MH - *Peanut Hypersensitivity/therapy MH - *Anaphylaxis/prevention & control MH - Histamine MH - Interleukin-4 MH - Bone Marrow MH - Mice, Inbred C3H MH - *Food Hypersensitivity MH - Immunoglobulin E MH - Water PMC - PMC10876879 OTO - NOTNLM OT - IgE OT - RNA-Seq OT - Rubia cordifolia L. OT - food allergy OT - transcriptome COIS- X-ML received research support to her institution from the National Institutes of Health (NIH)/National Center for Complementary and Alternative Medicine (NCCAM) # 1P01 AT002644725-01 "Center for Chinese Herbal Therapy (CHT) for Asthma", and grant #1R01AT001495-01A1 and 2R01 AT001495-05A2, NIH/NIAID R43AI148039, NIH/NIAID 1R21AI176061-01, NIH/NIAID 1R44AI177183-01, NIH/NIAID 1R41AI172572-01A1, Food Allergy Research and Education (FARE), 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; received travel expenses from the NCCAM and FARE; share US patent US7820175B2 (FAHF-2), US10500169B2 (XPP), US10406191B2 (S. Flavescens), US10028985B2 (WL); US11351157B2 (nanoBBR): take compensation from her practice at Center for Integrative Health and Acupuncture PC; US Times Technology Inc is managed by her related party; is a member of General Nutraceutical Technology LLC and Health Freedom LLC. NY received research support from the National Institutes of Health (NIH)/National Center for Complementary and Alternative Medicine (NCCAM), NIH/NIAID R43AI148039, NIH/NIAID 1R21AI176061-01, NIH/NIAID 1R44AI177183-01, NIH/NIAID 1R41AI172572-01A1; shares US patent: US10500169B2 (XPP), US10406191B2 (S. Flavescens), US10028985B2 (WL); and is a member of General Nutraceutical Technology, LLC and Health Freedom LLC; receives a salary from General Nutraceutical Technology, LLC. KS shares US patent: US11351157B2 (nanoBBR). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2024/02/21 11:15 MHDA- 2024/02/22 06:43 PMCR- 2024/01/01 CRDT- 2024/02/21 04:08 PHST- 2023/09/22 00:00 [received] PHST- 2024/01/11 00:00 [accepted] PHST- 2024/02/22 06:43 [medline] PHST- 2024/02/21 11:15 [pubmed] PHST- 2024/02/21 04:08 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2024.1299484 [doi] PST - epublish SO - Front Immunol. 2024 Feb 6;15:1299484. doi: 10.3389/fimmu.2024.1299484. eCollection 2024.