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 (T_H1) 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.

Graphical abstract

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中文翻译：

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探索 Brahmi（假马齿苋）治疗浸润性导管癌的免疫调节潜力

摘要

Bacopa monnieri (L) Wettst，俗称 Brahmi，是印度传统医学体系阿育吠陀中不可或缺的药用植物，被认为是“medhya rasayana”——一种被认为可以增强智力和思维清晰度的植物实体。它在许多旨在解决焦虑、记忆丧失、认知受损和注意力不集中等问题的阿育吠陀配方中发挥着重要作用，凸显了它的重要性。除了在认知健康方面的应用之外，婆罗米历史上还被用于阿育吠陀疗法中，用于治疗包括关节炎在内的炎症性疾病。在当代生物医学研究中，假马齿苋可以减弱动物模型中促炎细胞因子 TNF-α 和 IL-6 的释放。然而，关于假马齿苋作为抗癌药物的潜力的信息仍然很少，需要在这一领域进行进一步的研究。基于先前对 Brahmi ( Bacopa monnieri ) 的研究结果，本研究旨在找出 Brahmi 植物制剂 (BPP) 在 IDC 免疫调节作用中的作用。采用特定的 BPP 浓度，我们使用 MTT 测定、ELISA、DNA 甲基化分析、蛋白质印迹、ChIP 和 mRNA 分析进行了全面研究，以评估 BPP 的免疫调节特性。我们的研究结果表明，BPP 在增强 T 辅助细胞 1 ( _TH 1) 细胞的作用中发挥作用，该细胞分泌干扰素-γ (IFN-γ)，进而激活细胞毒性 T 淋巴细胞 (CTL) 以杀死 IDC 细胞。 * p  < 0.05）。此外，我们发现，BPP 治疗不仅增加了 IDC 中肿瘤抑制基因（p53 和 BRCA1）的活性，而且还降低了癌基因（​​Notch1 和 DNAPKcs）的活性 (* p  < 0.05)。 BPP 通过下调组蛋白去甲基化和组蛋白去乙酰化以及上调组蛋白甲基化和组蛋白乙酰化来控制 IDC 的表观遗传失调具有巨大意义 (* p  < 0.05)。我们的染色质免疫沉淀 (ChIP)-qPCR 数据显示，BPP 处理增加了 TBX21 和 BRCA1 基因位点上STAT1 和 BRCA1 的富集百分比 (* p <  0.05)，并降低了 STAT3、STAT5 和 NF κB 的富集百分比 (* p < 0.05)。国际数据中心。此外，BPP 治疗减少了 BRCA1 相关 DNA 的高甲基化，这被认为是 IDC 的主要因素 (* p  < 0.05)。 BPP不仅能增强1型特异性细胞因子的分泌，还能增强肿瘤抑制作用，并协调与信号转导器和转录激活器（STAT）相关的各种表观遗传调节因子和转录因子，以激发IDC中的肿瘤保护性免疫。

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