Regulatory effects of berberine on microRNome in Cancer and other conditions
Section snippets
Berberine: source and structure
Berberine (BBR) is a phytochemical compound found in different plant families such as Berberidaceae, Ranunculaceae, and Papaveraceae families (Singh and Mahajan, 2013). It is primary isolated from roots, rhizome, and stem bark of barberry (Berberis vulgaris), tree turmeric (Berberis aristata), goldenseal (Hydrastis canadensis), Coptis (Coptis chinensis) and Oregon grape (Berberis aquifolium) (Singh and Mahajan, 2013, Srivastava et al., 2015). Chemically, BBR is an isoquinoline alkaloid
Berberine: bioavailability and pharmacokinetic data
Due to poor water solubility, the BBR intestinal absorption is scarce (Godugu et al., 2014) with an oral bioavailability less than 5% (Pan et al., 2003). However, changing the BBR structure or coadministering BBR with an absorption enhancer can improve the BBR bioavailability (Chen et al., 2011). Dihydroberberine (dhBBR) is one of the absorbable structurally modified compounds of BBR. BBR converts to dhBBR in the intestine via a reduction reaction. Some studies showed that bacterial
Berberine: tolerability and safety
In animal models, orally administered highly purified BBR sulfate has a LD50 (lethal dose for the 50% of treated animals) of 25 mg/kg (Ye et al., 2009). BBR does not have any genotoxic, cytotoxic and mutagenic activity, however it can cause dose-dependent gastrointestinal/abdominal discomfort (till 34.5% events) on the middle-term use (Yina et al., 2008). On the other hand, BBR strongly interacts with macrolides potentially causing dangerous arrhythmias (Caliceti et al., 2015, Ji and Shen, 2011
Berberine: pharmacological effects
Pharmacological effects of BBR were the subject of extensive in vitro, in vivo and clinical researches (Imanshahidi and Hosseinzadeh, 2008). It is a wildly used natural product that showed multiple pharmacological activities in modern and traditional medicine (Li et al., 2014). Plants rich in BBR were largely employed in traditional eastern medicine for their anti-inflammatory, anticancer, anti-diabetic, antibacterial, antiparasitic, anti-diarrheal and fungicide activities (Imanshahidi and
Berberine: molecular targets
Beyond the above-described metabolic effect on PCSK9, several mechanistic investigations have demonstrated that BBR can also inhibit inflammation both in vitro and in vivo (Kuo et al., 2004, Küpeli et al., 2002) and suppress the growth of a wide variety of tumor cells with different mechanisms (Pandey et al., 2008, Sun et al., 2009).
BBR can inhibit transcription of proinflammatory genes such as IL-1β, TNF-α, IL-6 and monocyte chemoattractant protein 1 (MCP-1) (Jeong et al., 2009). On the other
MicroRNA
MicroRNAs (miRs) are single stranded, evolutionary conserved, small non-coding RNA molecules with 19–23 nucleotides. miRs are involved in RNA silencing and post-transcriptional regulation of gene expression by binding to 3′ untranslated region (3′UTR) of target mRNA (Ambros, 2004, Bartel, 2004, Filipowicz et al., 2008). More than 60% of human protein coding genes are regulated by miRs through post-transcriptional operation (Lewis et al., 2005).
MiRs play a key role in almost every biological
Role of miRs in tumorigenesis
Development of high throughput strategies for miR profiling like miR microarrays (Liu et al., 2004), bead-based flow cytometric miR expression profiling (Lu et al., 2005) and quantitative polymerase chain reaction (qPCR) (Chen et al., 2005) makes it easier to study miR pattern changes in different disease (Aravin and Tuschl, 2005, Creighton et al., 2009, Meyer et al., 2010). Recent studies shown that miR expression is different in cancer versus normal cells and also among different tumors, and
Multiple myeloma
BBR decreases both mRNA and protein of IL-6, that is an important factor in the expansion of multiple myeloma (MM) cells (Kim et al., 2008, Lin et al., 2006, Yu et al., 2007). Different miRs including miR-21, miR-155, miR–17 ∼ 92, mir-99a ∼ 125b and miR–106 ∼ 25 function as OncomiRs in MM (Luo et al., 2014). miR-21 increases cell proliferation, apoptosis and tumor invasiveness via targeting various proteins such as Bcl-2 (Xu et al., 2014). Hu and coworkers evaluated the effect of various
Anti-diabetic effect
As mentioned above, BBR increases AMPK activity and reduces lipid accumulation in diabetic and obese patients (Lee et al., 2006). Aberrant overexpression of miR-21 was detected in diabetic rats and results in insulin resistance in 3T3-L1 adipocytes (He et al., 2007). Zhao et al. indicated that BBR-containing herbs exert antidiabetic effects through modulation of hepatic gene expression via down-regulation of miR29-b. They treated 3 groups of proved Zucker Diabetic fatty [ZDF] rats with an oral
Conclusion
BBR is a natural compound with well-known metabolic effects and a high safety profile. However, BBR also exerts anticancer and anti-inflammatory effects via regulation of different types of miRs. BBR plays anticancer role through regulating the expression of oncomiRs and tumor-suppressive miRs in various cancer cells. This isoquinoline alkaloid induces cytotoxicity and apoptosis through down-regulating different miRs including miR-21, miR–17 ∼ 92, mir-99a ∼ 125b and miR–106 ∼ 25 that have oncogenic
Conflict of interests
None.
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Alkaloids: Their relevance in cancer treatment
2023, New Insights into Glioblastoma: Diagnosis, Therapeutics and TheranosticsCoptis chinensis and dried ginger herb combination inhibits gastric tumor growth by interfering with glucose metabolism via LDHA and SLC2A1
2022, Journal of EthnopharmacologyCitation Excerpt :It decreases the cell viability and proliferation of gastric cancer cells and induces apoptosis (Chen et al., 2015; Hesari et al., 2018). Berberine exhibits an anti-gastric cancer effect via many regulatory pathways including Notch, MAPK, and NF-κB signaling using specific circRNAs (Ayati et al., 2017; Wang et al., 2021). In addition, It was shown to inhibit the growth of human gastric cancer cells by inhibiting MAPK/mTOR/p70S6K axis and inducing inhibitory autophagy by Akt both in vitro and in vivo (Zhang et al., 2020).
Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent
2022, Journal of Integrative MedicineThe protective impact of berberine against doxorubicin-induced nephrotoxicity in rats
2021, Tissue and CellCitation Excerpt :Berberine (BEB), a quaternary amine-iso-quinoline alkaloid, is the main potent component of a Chinese herb “Berberis species”, also known as Coptis rhizome, is traditionally used for treating several disorders (Tillhon et al., 2012; Liu et al., 2019). BEB is characterized by exhibiting anti-inflammatory, anti-oxidative, and anti-apoptotic potentials (Moghaddam et al., 2014; Ayati et al., 2017), that are reflected in its neuroprotective, hepatoprotective and cardioprotective potentials (Liu et al., 2016; Eissa et al., 2018; Fang et al., 2020). The very low concentration of BEB is maintained for 36 h in plasma; moreover, BEB exhibits a good distribution-manner in organs such as liver and kidney (Ahmad et al., 2019).
Berberine attenuates uric acid-induced cell injury by inhibiting NLRP3 signaling pathway in HK-2 cells
2023, Naunyn-Schmiedeberg's Archives of Pharmacology