**2.4 Curcumin**

Curcumin[(1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptane-3,5-dione] is well known as natural polyphenol and derived from the rhizome of turmeric or *Curcuma longa* Linn [34, 35]. Curcumin has been shown to possess of several medicinal properties such as anti-inflammation, antioxidant, pro-apoptosis, chemoprevention, anti-proliferation, wound healing, anti-nociception, anti-parasite, anti-malaria, anti-diabetes, neuroprotection and anti-tumor [34, 36]. Numerous studies have been focused on curcumin as a novel anti-cancer drug due to the inhibition of NF-kB, Akt/PI3K, and MAPK pathways and enhancement of p53 by curcumin, thereby inhibited several cancer cells proliferation, migration, invasion and induced apoptosis [35, 37]. Emerging data suggest that curcumin dysregulate oncogenic miRNAs and tumor suppressor miRNAs expression in various type of cancers such as lung cancer, prostate cancer, breast cancer, colorectal cancer, nasopharyngeal carcinoma, pancreatic cancer, ovarian cancer and etc. [35]. Curcumin have been shown to up-regulation of miR-15a, miR-16, miR-34a, miR-146b-5p and miR-181b and down-regulation of miR-19a and miR-19b upon treatment of several breast cancer cell lines with curcumin [38]. Curcumin but not 5-fluorouracil, upregulated the expression of miR-101, miR-200b, miR-200c, miR-141 and miR-429 and downregulated oncogenic miR-21 in colorectal cancer cells [39, 40]. In addition, miR-21 was down-regulated in gastric cancer with curcumin treatment, resulting in inhibition of cell migration and invasion by regulation of the PTEN/PI3K/AKT pathway [41]. Lui et al. showed that curcumin up-regulated 6 miRNAs (miR-145, miR-1275, miR-1908, miR-3127, miR-3178, and miR-3198), whereas 8 miRNAs (miR-23b\*, miR-183, miR-193b\* miR-210, miR-222\*, miR-494, miR-664\*, miR-671-5p) were down-regulated when treated with curcumin in human prostate cancer stem cells (HuPCaSCs) [42]. Experimental confirmed of miR-145 function in HuPCaSCs revealed that miR-145 inhibited cell proliferation by targeting transcription factors Oct4 [42]. Another study also reported that miR-181b was up-regulated by curcumin and inhibited breast cancer cell proliferation, invasion and induced cell apoptosis by targeting CXCL1 and CXCL2 [43]. Inhibitory effect of curcumin on glioblastoma cell growth was observed and curcumin also up-regulated miR-378 expression and p38 was the target of miR-378 [44]. Curcumin and Pioglitazone combination have a potential as therapeutic applications for neurodegenerative disorders by increasing of miR-124 and miR-155 expression, thereby inhibiting the inflammatory cytokines TNF-α, IL-1β and IL-6 production and inflammation-associated enzymes COX-2, iNOS through inhibition of NF-κB activity in animal model [45].
