دورية أكاديمية
Withaferin-A alleviates acute graft versus host disease without compromising graft versus leukemia effect.
| العنوان: | Withaferin-A alleviates acute graft versus host disease without compromising graft versus leukemia effect. |
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| المؤلفون: | Kumar Gupta S; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Gohil D; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Dutta D; Cell and Tumor Biology Group, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Panigrahi GC; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Gupta P; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India., Dalvi K; Hematopathology Laboratory, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India., Khanka T; Hematopathology Laboratory, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India., Yadav S; Department of Pathology, Tata Memorial Hospital, Parel, Mumbai 400012, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Kumar Kaushal R; Department of Pathology, Tata Memorial Hospital, Parel, Mumbai 400012, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Chichra A; Department of Medical Oncology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Punatar S; Department of Medical Oncology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Gokarn A; Department of Medical Oncology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Mirgh S; Department of Medical Oncology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Jindal N; Department of Medical Oncology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Nayak L; Department of Medical Oncology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Tembhare PR; Hematopathology Laboratory, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Khizer Hasan S; Cell and Tumor Biology Group, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Kumar Sandur S; Radiation Biology and Health Science Division, Bio-science Group, Bhabha Atomic Research Centre, Mumbai 400094, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Hingorani L; Pharmanza Herbal Pvt. Ltd., Anand 388435, Gujarat, India., Khattry N; Department of Medical Oncology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Gota V; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India. Electronic address: vgota76@gmail.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2023 Aug; Vol. 121, pp. 110437. Date of Electronic Publication: 2023 Jun 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Graft vs Host Disease* , Hematopoietic Stem Cell Transplantation* , Leukemia*/drug therapy, Humans ; Animals ; Mice ; Graft vs Leukemia Effect ; Leukocytes, Mononuclear ; Cytokines/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; Acute Disease |
| مستخلص: | Acute graft versus host disease (aGvHD) contributes to a significant proportion of non-relapse mortality and morbidity in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Withaferin-A (WA), a phytomolecule obtained from Withania somnifera (Ashwagandha), is known to have anti-inflammatory, anti-proliferative and immunomodulatory properties. The efficacy of WA for the prevention and treatment of aGvHD was evaluated using a murine model of alloHSCT. Prophylactic administration of WA to mice mitigated the clinical symptoms of aGvHD and improved survival significantly compared to the GvHD control [HR = 0.07 (0.01-0.35); P < 0.001]. Furthermore, WA group had better overall survival compared to standard prophylactic regimen of CSA + MTX [HR = 0.19 (0.03-1.1), P < 0.05]. At the same time, WA did not compromise the beneficial GvL effect. In addition, WA administered to animals after the onset of aGvHD could reverse the clinical severity and improved survival, thus establishing its therapeutic potential. Our findings suggest that WA reduced the systemic levels of Th1, Th2 and Th17 inflammatory cytokine and increased the anti-inflammatory cytokine IL-10 levels significantly (P < 0.05). WA also inhibited lymphocytes migration to gut, liver, skin and lung and protected these organs from damage. Ex-vivo, WA inhibited proliferation of human peripheral blood mononuclear cells (hPBMCs), modulated immune cell phenotype and decreased cytokine release. In addition, WA inhibited pJAK2 and pSTAT3 protein levels in mouse splenocytes and hPBMCs. In conclusion, our study demonstrates the utility of WA for the prevention and treatment of aGvHD, which should be further evaluated in a clinical setting. Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Dr. Lal Hingorani is the managing director of Pharmza Herbal Pvt. Ltd., which manufactures Witahferin-A containing nutraceuticals for human use. He had no role in the design or conduct of the study nor in the interpretation of results. Other authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.’ (Copyright © 2023 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Acute graft versus host disease (aGvHD); Allogeneic hematopoietic stem cell transplantation (alloHSCT); Graft versus Leukemia (GvL); JAK2-STAT3 signaling; Prophylaxis; Treatment; Withaferin-A (WA) |
| المشرفين على المادة: | 0 (Cytokines) 0 (Anti-Inflammatory Agents) |
| تواريخ الأحداث: | Date Created: 20230613 Date Completed: 20231023 Latest Revision: 20231023 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.intimp.2023.110437 |
| PMID: | 37311352 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2023.110437 |