PMID- 38258793
OWN - NLM
STAT- MEDLINE
DCOM- 20240124
LR  - 20240201
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Print)
IS  - 0963-6897 (Linking)
VI  - 33
DP  - 2024 Jan-Dec
TI  - Withania Somnifera Extract Mitigates Experimental Acute Graft versus Host Disease 
      Without Abrogating Graft Versus Leukemia Effect.
PG  - 9636897241226573
LID - 10.1177/09636897241226573 [doi]
LID - 09636897241226573
AB  - Acute graft versus host disease (aGvHD) is the major contributor of nonrelapse 
      mortality in alloHSCT. It is associated with an inflammatory immune response 
      manifesting as cytokine storm with ensuing damage to target organs such as liver, 
      gut, and skin. Prevention of aGvHD while retaining the beneficial graft versus 
      leukemia (GvL) effect remains a major challenge. Withania somnifera extract (WSE) 
      is known for its anti-inflammatory, immune-modulatory, and anticancer properties, 
      which are appealing in the context of aGvHD. Herein, we demonstrated that 
      prophylactic and therapeutic use of WSE in experimental model of alloHSCT 
      mitigates aGvHD-associated morbidity and mortality. In the prophylaxis study, a 
      dose of 75 mg/kg of WSE offered greatest protection against death due to aGvHD 
      (hazard ratio [HR] = 0.15 [0.03-0.68], P </= .01), whereas 250 mg/kg was most 
      effective for the treatment of aGvHD (HR = 0.16 [0.05-0.5], P </= .01). WSE 
      treatment protected liver, gut, and skin from damage by inhibiting cytokine storm 
      and lymphocytic infiltration to aGvHD target organs. In addition, WSE did not 
      compromise the GvL effect, as alloHSCT with or without WSE did not allow the 
      leukemic A20 cells to grow. In fact, WSE showed marginal antileukemic effect in 
      vivo. WSE is currently under clinical investigation for the prevention and 
      treatment of aGvHD.
FAU - Gupta, Saurabh Kumar
AU  - Gupta SK
AD  - Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
AD  - Homi Bhabha National Institute, Mumbai, India.
FAU - Gohil, Dievya
AU  - Gohil D
AD  - Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
AD  - Homi Bhabha National Institute, Mumbai, India.
FAU - Momin, Mohd Bashar
AU  - Momin MB
AD  - Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
FAU - Yadav, Subhash
AU  - Yadav S
AD  - Homi Bhabha National Institute, Mumbai, India.
AD  - Department of Pathology, Tata Memorial Hospital, Mumbai, India.
FAU - Chichra, Akanksha
AU  - Chichra A
AD  - Homi Bhabha National Institute, Mumbai, India.
AD  - Department of Medical Oncology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
FAU - Punatar, Sachin
AU  - Punatar S
AD  - Homi Bhabha National Institute, Mumbai, India.
AD  - Department of Medical Oncology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
FAU - Gokarn, Anant
AU  - Gokarn A
AD  - Homi Bhabha National Institute, Mumbai, India.
AD  - Department of Medical Oncology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
FAU - Mirgh, Sumeet
AU  - Mirgh S
AD  - Homi Bhabha National Institute, Mumbai, India.
AD  - Department of Medical Oncology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
FAU - Jindal, Nishant
AU  - Jindal N
AD  - Homi Bhabha National Institute, Mumbai, India.
AD  - Department of Medical Oncology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
FAU - Nayak, Lingaraj
AU  - Nayak L
AD  - Homi Bhabha National Institute, Mumbai, India.
AD  - Department of Medical Oncology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
FAU - Hingorani, Lal
AU  - Hingorani L
AD  - Pharmanza Herbal Pvt. Ltd., Anand, India.
FAU - Khattry, Navin
AU  - Khattry N
AD  - Homi Bhabha National Institute, Mumbai, India.
AD  - Department of Medical Oncology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
FAU - Gota, Vikram
AU  - Gota V
AUID- ORCID: 0000-0001-6348-6667
AD  - Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and 
      Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
AD  - Homi Bhabha National Institute, Mumbai, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Plant Extracts)
SB  - IM
MH  - *Withania
MH  - Cytokine Release Syndrome
MH  - *Graft vs Host Disease/drug therapy/prevention & control
MH  - *Leukemia/drug therapy
MH  - Plant Extracts/pharmacology/therapeutic use
PMC - PMC10807391
OTO - NOTNLM
OT  - Withania somnifera extract (WSE)
OT  - aGvHD prophylaxis
OT  - aGvHD treatment
OT  - acute graft versus host disease (aGvHD)
OT  - graft versus leukemia (GvL)
COIS- Declaration of Conflicting InterestsThe author(s) declared the following 
      potential conflicts of interest with respect to the research, authorship, and/or 
      publication of this article: LH is the managing director of Pharmanza Herbal Pvt. 
      Ltd. which is licensed to manufacture WSE for human use as a nutraceutical. 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.
EDAT- 2024/01/23 12:44
MHDA- 2024/01/24 06:43
PMCR- 2024/01/23
CRDT- 2024/01/23 08:09
PHST- 2024/01/24 06:43 [medline]
PHST- 2024/01/23 12:44 [pubmed]
PHST- 2024/01/23 08:09 [entrez]
PHST- 2024/01/23 00:00 [pmc-release]
AID - 10.1177_09636897241226573 [pii]
AID - 10.1177/09636897241226573 [doi]
PST - ppublish
SO  - Cell Transplant. 2024 Jan-Dec;33:9636897241226573. doi: 
      10.1177/09636897241226573.