**2.10** β**-Sitosterol-d-glucoside**

β-Sitosterol-d-glucoside is bioactive compounds that has been isolated from *Agave angustifolia* and sweet potato [88, 89]. Pharmacological activity of β-Sitosterold-glucoside has been reported including immunomodulatory, anti-inflammatory, cytotoxic, and antiparasitic activities [88]. β-Sitosterol-d-glucoside exhibited cytotoxic effect in breast cancer cells by up-regulated miR-10a expression and decreased the PI3K/Akt signaling pathway [89]. Treatment of β-Sitosterol-d-glucoside can down-regulate miR-322-5p, miR-301a-3p, miR-129-5p, miR-322-3p, and miR-129-2-3p in neural stem cell and their targets are related to the regulation of proliferation [90]. Therefore, β-Sitosterol-d-glucoside could be developed for further therapeutic applications.

## **2.11 Sulforaphane**

Sulforaphane is dietary compounds in broccoli (*Brassica oleracea*) and cruciferous plants. It has been demonstrated the capability of sulforaphane for anti-inflammatory, antiaging, antidiabetic, antioxidant, anti-tumor, hepatoprotective and cardioprotective effects [91]. Plant-derived phytochemicals including sulforaphane are potentially affected miRNAs expression. Sulforaphane inhibited breast cancer cell cycle arrest and senescence via down-regulation of miR-23b, miR-92b, miR-381 and miR-382 [92]. Anti-tumor effect of sulforaphane also reported in non-small cell lung cancer by down-regulation of miR-616-5p and targeting GSK3β/β-catenin signaling pathway [93]. Sulforaphane inhibited the progression of pancreatic cancer through down-regulated miR30a-3p with the increasing of its target, Cx43 expression and upregulated miR-135b-5p mediated RASAL2 expression [94, 95]. In addition, sulforaphane treatment significantly increased the expression of tumor suppressor miRNA, miR-200c, resulted in inhibited the cancer stemness and tumorinitiating properties in oral squamous cell carcinomas and cancer stem cells both in vitro and in vivo [96]. Anti-proliferative and apoptotic effects of sulforaphane have been reported in gastric cancer cells, which leading to alter the expression of miR-9 and miR-326 [97]. Up-regulation of miR-124-3p and inhibition of its target, STAT3 by sulforaphane treatment were observed and thereby induced apoptosis, inhibited proliferation and decreased the stemness of nasopharyngeal cancer cell [98].

Sulforaphane has potential to inhibit hepatic fibrosis by downregulating miR-423-5p in hepatic stellate cell [99]. Sulforaphane showed the protective effect in microglia-mediated neurotoxicity by inhibited LPS-induced expression of inflammatory miRNA, miR-155 [100].

## **3. Dietary miRNA and human gene regulation**

Several evidences demonstrated the direct modulation of cellular signaling pathways by dietary compounds could decrease the risk of chronic diseases [101]. Interestingly, it has been reported that small non-coding RNA including miRNAs can be transferred across Kingdoms, for example dietary miRNAs have been found in human body fluids and these circulating miRNAs are likely to regulate human gene

#### *The Impact of Dietary Compounds in Functional Foods on MicroRNAs Expression DOI: http://dx.doi.org/10.5772/intechopen.96746*

expression [15, 102–107]. The uptake of plant derived miRNAs could be in the form of raw and cooked plants in capable of stability forms [107, 108]. Due to high temperature cooking process, low pH and enzymes in digestive tract as well as enzymes in blood circulation, miRNAs might be destroyed before their functions with target mRNAs [15]. Strikingly, GC base content, 2'-O-methylation on the 3′-terminal, unique nucleotide sequence of dietary miRNAs and extracellular vesicles (exosome and microvesicle) are preventive features of plant derived miRNAs in harmful conditions [109–114].

There are numerous studies to support the functional roles of dietary miRNAs in cross kingdom gene regulation. Rice miR156a and miR168a were detected in human serum and miR168a down-regulated low-density lipoprotein receptor adapter protein 1 (LDLRAP1) expression, resulted in an increase of plasma LDL cholesterol level, **Table 2** [105]. miR2910 from *Populus euphratica* was identified in human plasma and targeting Sprouty RTK Signaling Antagonist 4 (SPRY4) gene of the Janus kinase/ signal transducers and activators of transcription (JAK–STAT) signaling pathway [115]. Based on the computationally predicted miRNAs from *Camptotheca acuminate,* 14 potential miRNAs were found to be regulated 152 target human genes such as miR4723–3p, miR5780d, and miR548d-3p targeting discs large MAGUK scaffoldprotein 2 (DLG2), NUMB endocytic adaptor protein (NUMB) and glycogen synthase kinase-3B (GSK3B) genes which were related to cancers such as breast cancer, lung cancer and leukemia [116]. *Ocimum basilicum* is a medicinal plant and its bioactive compounds have potential for therapeutic approaches. miRNA target prediction analysis revealed the target of *O. basilicum* miRNAs, miR156, miR531, miR160, miR529b, and miR1118 were 87 human target genes associated with the Ras-mitogenactivated protein kinase (Ras-MAPK) signaling pathway, Alzheimer disease, breast cancer, cardiomyopathy, HIV, lung cancer, and several neurological disorders [117].


#### **Table 2.**

*Dietary miRNAs and human gene regulation.*

The abundantly expressed miRNA in dietary green vegetable, miR156a which was detected in human serum and targeted the junction adhesion molecule-A (JAM-A) [118]. The JAM-A was up-regulated in atherosclerotic lesions from cardiovascular disease patients and miR156a could suppressed inflammatory cytokine-induced monocytes adhesion by targeting JAM-A [118]. The very recently report using a computational approach to predict the potential target of rice miRNAs including miR156-5p, miR164-5p, miR168-5p, miR395-3p, miR396-3p, miR396-5p, miR444-3p, miR529-3p, miR1846-3p, miR2907-3p, which can bind to the human mRNA [119]. Most of these target genes were associated with cancer, cardiovascular and neurodegenerative diseases [119]. miR14 derived from *Curcuma longa* was detected and remarkably stable in human serum for 48 h. The potential targets of miR14 were associated with inflammation in rheumatoid arthritis such as Phosphotidylinositol-specific-phospholipase C (PLCXD3), Adenylate cyclase 9 (ADCY9), and 3′ (2′), 5′-bisphosphate nucleotidase (BPNT1) [120].
