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Transcriptome-wide miRNA identification of Bacopa monnieri: a cross-kingdom approach.

ABSTRACT: Bacopa monnieri known as 'Brahmi' is a well-known medicinal plant belonging to Scrophulariaceae family for its nootropic properties. To the best of our knowledge, no characterization data is available on the potential role of micro RNAs (miRNAs) from this plant till date. We present here the first report of computational characterizations of miRNAs from B. monnieri. Owing to the high conservation of miRNAs in nature, new and potential miRNAs can be identified in plants using in silico techniques. Using the plant miRNA sequences present in the miRBase repository, a total of 12 miRNAs were identified from B. monnieri which pertained to 11 miRNA families from the shoot and root transcriptome data. Furthermore, gene ontology analysis of the identiﬁed 68 human target genes exhibited significance in various biological processes. These human target genes were associated with signaling pathways like NF-kB and MAPK with TRAF2, CBX1, IL1B, ITGA4 and ITGB1BP1 as the top five hub nodes. This cross-kingdom study provides initial insights about the potential of miRNA-mediated cross-kingdom regulation and unravels the essential target genes of human with implications in numerous human diseases including cancer.

SUBMITTER: Gadhavi H

PROVIDER: S-EPMC7012157 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Bacopa monnieri (L) Wettst (common name, bacopa) is a medicinal plant used in Ayurveda, the traditional system of medicine of India, as a nootropic. It is considered to be a "medhya rasayana", an herb that sharpens the mind and the intellect. Bacopa is an important ingredient in many Ayurvedic herbal formulations designed to treat conditions such as memory loss, anxiety, poor cognition and loss of concentration. It has also been used in Ayurveda to treat inflammatory conditions such as arthritis. In modern biomedical studies, bacopa has been shown in animal models to inhibit the release of the pro-inflammatory cytokines TNF-? and IL-6. However, less is known regarding the anti-inflammatory activity of Bacopa in the brain.The current study examines the ability of Bacopa to inhibit the release of pro-inflammatory cytokines from microglial cells, the immune cells of the brain that participate in inflammation in the CNS. The effect of Bacopa on signaling enzymes associated with CNS inflammatory pathways was also studied.Various extracts of Bacopa were prepared and examined in the N9 microglial cell line in order to determine if they inhibited the release of the proinflammatory cytokines TNF-? and IL-6. Extracts were also tested in cell free assays as inhibitors of caspase-1 and matrix metalloproteinase-3 (enzymes associated with inflammation) and caspase-3, which has been shown to cleave protein Tau, an early event in the development of Alzheimer's disease.The tea, infusion, and alkaloid extracts of bacopa, as well as Bacoside A significantly inhibited the release of TNF-? and IL-6 from activated N9 microglial cells in vitro. In addition, the tea, infusion, and alkaloid extracts of Bacopa effectively inhibited caspase 1 and 3, and matrix metalloproteinase-3 in the cell free assay.Bacopa inhibits the release of inflammatory cytokines from microglial cells and inhibits enzymes associated with inflammation in the brain. Thus, Bacopa can limit inflammation in the CNS, and offers a promising source of novel therapeutics for the treatment of many CNS disorders.

Project description:BackgroundBacopa monnieri commonly known as Brahmi is utilized in Ayurveda to improve memory and many other human health benefits. Bacosides enriched standardized extract of Bacopa monnieri is being marketed as a memory enhancing agent. In spite of its well known pharmacological properties it is not much studied in terms of transcripts involved in biosynthetic pathway and its regulation that controls the secondary metabolic pathway in this plant. The aim of this study was to identify the potential transcripts and provide a framework of identified transcripts involved in bacosides production through transcriptome assembly.ResultsWe performed comparative transcriptome analysis of shoot and root tissue of Bacopa monnieri in two independent biological replicate and obtained 22.48 million and 22.0 million high quality processed reads in shoot and root respectively. After de novo assembly and quantitative assessment total 26,412 genes got annotated in root and 18,500 genes annotated in shoot sample. Quality of raw reads was determined by using SeqQC-V2.2. Assembled sequences were annotated using BLASTX against public database such as NR or UniProt. Searching against the KEGG pathway database indicated that 37,918 unigenes from root and 35,130 unigenes from shoot were mapped to 133 KEGG pathways. Based on the DGE data we found that most of the transcript related to CYP450s and UDP-glucosyltransferases were specifically upregulated in shoot tissue as compared to root tissue. Finally, we have selected 43 transcripts related to secondary metabolism including transcription factor families which are differentially expressed in shoot and root tissues were validated by qRT-PCR and their expression level were monitored after MeJA treatment and wounding for 1, 3 and 5 h.ConclusionsThis study not only represents the first de novo transcriptome analysis of Bacopa monnieri but also provides information about the identification, expression and differential tissues specific distribution of transcripts related to triterpenoid sapogenin which is one of the most important pharmacologically active secondary metabolite present in Bacopa monnieri. The identified transcripts in this study will establish a foundation for future studies related to carrying out the metabolic engineering for increasing the bacosides biosynthesis and its regulation for human health benefits.

Project description:Neurological diseases (NDs), especially Alzheimer's and Spinocerebellar ataxia (SCA), can severely cause biochemical abnormalities in the brain, spinal cord and other nerves of human beings. Their ever-increasing prevalence has led to a demand for new drug development. Indian traditional and Ayurvedic medicine used to combat the complex diseases from a holistic and integrative point of view has shown efficiency and effectiveness in the treatment of NDs. Bacopa monnieri is a potent Indian medicinal herb used for multiple ailments, but is significantly known as a nootropic or brain tonic and memory enhancer. This annual herb has various active compounds and acts as an alternative and complementary medicine in various countries. However, system-level insights of the molecular mechanism of a multiscale treatment strategy for NDs is still a bottleneck. Considering its prominence, we used cheminformatics and system pharmacological approaches, with the aim to unravel the various molecular mechanisms represented by Bacopa-derived compounds in identifying the active human targets when treating NDs. First, using cheminformatics analysis combined with the drug target mining process, 52 active compounds and their corresponding 780 direct receptors were retrieved and computationally validated. Based on the molecular properties, bioactive scores and comparative analysis with commercially available drugs, novel and active compounds such as asiatic acid (ASTA) and loliolide (LLD) to treat the Alzheimer's and SCA were identified. According to the interactions among the active compounds, the targets and diseases were further analyzed to decipher the deeper pharmacological actions of the drug. NDs consist of complex regulatory modules that are integrated to dissect the therapeutic effects of compounds derived from Bacopa in various pathological features and their encoding biological processes. All these revealed that Bacopa compounds have several curative activities in regulating the various biological processes of NDs and also pave the way for the treatment of various diseases in modern medicine.

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Transcriptome-wide miRNA identification of Bacopa monnieri: a cross-kingdom approach.

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