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Exploring the immunomodulatory potential of Brahmi (Bacopa monnieri) in the treatment of invasive ductal carcinoma

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Abstract

Bacopa monnieri (L) Wettst, commonly known as Brahmi, stands as a medicinal plant integral to India’s traditional medical system, Ayurveda, where it is recognized as a “medhya rasayana”—a botanical entity believed to enhance intellect and mental clarity. Its significant role in numerous Ayurvedic formulations designed to address conditions such as anxiety, memory loss, impaired cognition, and diminished concentration underscores its prominence. Beyond its application in cognitive health, Brahmi has historically been employed in Ayurvedic practices for the treatment of inflammatory diseases, including arthritis. In contemporary biomedical research, Bacopa monnieri can attenuate the release of pro-inflammatory cytokines TNF-α and IL-6 in animal models. However, there remains a paucity of information regarding Bacopa’s potential as an anticancer agent, warranting further investigation in this domain. Based on previous findings with Brahmi (Bacopa monnieri), the current study aims to find out the role of Brahmi plant preparation (BPP) in immunomodulatory actions on IDC. Employing a specific BPP concentration, we conducted a comprehensive study using MTT assay, ELISA, DNA methylation analysis, Western blotting, ChIP, and mRNA profiling to assess BPP’s immunomodulatory properties. Our research finding showed the role of BPP in augmenting the action of T helper 1 (TH1) cells which secreted interferon-γ (IFN-γ) which in turn activated cytotoxic T-lymphocytes (CTL) to kill the cells of IDC (*p < 0.05). Moreover, we found out that treatment with BPP not only increased the activities of tumor-suppressor genes (p53 and BRCA1) but also decreased the activities of oncogenes (Notch1 and DNAPKcs) in IDC (*p < 0.05). BPP had an immense significance in controlling the epigenetic dysregulation in IDC through the downregulation of Histone demethylation & Histone deacetylation and upregulation of Histone methylation and Histone acetylation (*p < 0.05). Our Chromatin immunoprecipitation (ChIP)-qPCR data showed BPP treatment increased percentage enrichment of STAT1 & BRCA1 (*p < 0.05) and decreased percentage enrichment of STAT3, STAT5 & NF ΚB (*p < 0.05) on both TBX21 and BRCA1 gene loci in IDC. In addition, BPP treatment reduced the hypermethylation of the BRCA1-associated-DNA, which is believed to be a major factor in IDC (*p < 0.05). BPP not only escalates the secretion of type 1 specific cytokines but also escalates tumor suppression and harmonizes various epigenetic regulators and transcription factors associated with Signal Transducer and Activator of Transcription (STAT) to evoke tumor protective immunity in IDC.

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Data availability

The raw data supporting the conclusion of this article will be made available by the authors without undue reservation. The data that has been used is confidential.

Abbreviations

IDC:

Invasive ductal carcinoma

BPP:

Brahmi plant preparation

TH :

T helper cell

IFN:

Interferon

CTL:

Cytotoxic T lymphocytes

ChIP-qPCR:

Chromatin immunoprecipitation-quantitative real time polymerase chain reaction

PBMCs:

Peripheral blood mononuclear cells

PBS:

Phosphate buffered saline

RPMI 1640:

Rosewell Park Memorial Institute Media

Con A:

Concanavalin A

DMSO:

Dimethyl sulfoxide

ELISA:

Enzyme-linked immunosorbent assay

BSA:

Bovine serum albumin

TMB:

Tetramethyl benzidine

OD:

Optical density

LDH:

Lactate dehydrogenase

SEM:

Standard error of mean

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Funding

This work has been supported by Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Govt. of India (Sanction order No. “ECR/2016/000965”).

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Authors and Affiliations

  1. Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India

    Sohini Roy, Geetha Shanmugam, Sudeshna Rakshit, R. Pradeep & Koustav Sarkar

  2. Department of Clinical Pharmacology, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India

    Melvin George

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  1. Sohini Roy
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Contributions

SR: Formal analysis, Investigation, Data curation, Writing—original draft. GS: Writing—review & editing, Supervision. SR: Writing—review & editing, Supervision. MG: Resources. KS: Conceptualization, Methodology, Software, Validation, Writing—review & editing, Supervision, Project administration, Funding acquisition.

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Correspondence to Koustav Sarkar.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

The study involving human participants was reviewed and approved by the Ethics Committee of SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu 603203, India. All human participants gave their written informed consent to participate in the study as per the Institutional Ethical Committee guidelines (Ethics Clearance Number: 2997/IEC/2021).

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Roy, S., Shanmugam, G., Rakshit, S. et al. Exploring the immunomodulatory potential of Brahmi (Bacopa monnieri) in the treatment of invasive ductal carcinoma. Med Oncol 41, 115 (2024). https://doi.org/10.1007/s12032-024-02365-x

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