NDLI: Ayurvedic formulations Guduchi and Madhuyashti triggers JNK signaling mediated immune response and adversely affects Huntington phenotype

Content Provider	Springer Nature : BioMed Central
Author	Singh, Surabhi Tapadia, Madhu G.
Abstract	Background Huntington’s disease manifests due to abnormal CAG trinucleotide expansion, in the first exon of the Huntingtin gene and disease progression involves genetic, immune, and environmental components. The pathogenesis is characterized by the formation of Inclusion Bodies, disruption of neuronal circuitry, cellular machinery, and apoptosis, resulting in gradual and progressive loss of neuronal cells, ultimately leading to nervous system dysfunction. Thus, the present study was conducted to assess the effect of two Ayurvedic formulations, Guduchi and Madhuyashti, on Huntington’s phenotype, using Drosophila as a model system. Method The Huntington phenotype was ectopically induced in the Drosophila eye using the UAS-GAL4 binary system and the effect of the two Ayurvedic formulations were assessed by feeding the progenies on them. Degeneration was observed microscopically and Real Time-PCR was done to assay the alterations in the different transcripts of the innate immune pathways and JNK signaling pathway. Immunostaining was performed to assay different gene expression patterns. Result The present study shows that Guduchi and Madhuyashti, endowed with immunomodulatory and intellect promoting properties, aggravates polyQ mediated neurodegeneration. We provide evidence that these formulations enhance JNK signaling by activating the MAP 3 K, dTAK1, which regulates the expression of Drosophila homologue for JNK. Sustained, rather than a transient expression of JNK leads to excessive production of Anti-Microbial Peptides without involving the canonical transcription factors of the Toll or IMD pathways, NF-κB. Enhanced JNK expression also increases caspase levels, with a concomitant reduction in cell proliferation, which may further contribute to increased degeneration. Conclusion This is a report linking the functional relevance of Guduchi and Madhuyashti with molecular pathways, which can be important for understanding their use in therapeutic applications and holds promise for mechanistic insight into the mammalian counterpart.
Related Links	https://bmccomplementmedtherapies.biomedcentral.com/counter/pdf/10.1186/s12906-022-03724-9.pdf
Ending Page	15
Page Count	15
Starting Page	1
File Format	HTM / HTML
ISSN	26627671
DOI	10.1186/s12906-022-03724-9
Journal	BMC Complementary Medicine and Therapies
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2022-10-12
Access Restriction	Open
Subject Keyword	Complementary & Alternative Medicine Internal Medicine Chiropractic Medicine Guduchi Madhuyashti Ayurveda Immune response Neurodegeneration JNK signaling
Content Type	Text
Resource Type	Article
Subject	Complementary and Alternative Medicine
Journal Impact Factor	3.3/2023
5-Year Journal Impact Factor	3.6/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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