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Karthikeyan et al. Nanocurcumin: A Promising Candidate for Therapeutic Applications allergic rat model of asthma caused by ovalbumin. Experimental results revealed that airway hyperresponsiveness and inflammatory cell infiltration suppressed by C-SLNs. Also, C- SLNs mainly obstructed the expression of T-helper-2-type cytokines (interleukin-4 and 13) in bronchoalveolar lavage fluid (Wang et al., 2012). Milano et al. found that nanocurcumin is effective against esophageal adenocarcinoma (EAC) cell lines, OE33 and OE19. It sensitizes EAC cells to T cell-induced cytotoxicity and decreases the pro-inflammatory signals from T cells (Milano et al., 2013). CUR-SLNs has enhanced solubility compared to its native form and significantly downregulated LPS-induced pro- inflammatory mediators (i.e., NO, PGE2, and IL-6) through obstructing the activation of NF-kB in RAW 264.7 murine macrophage (Nahar et al., 2015). Similarly, nanocurcumin enhances oral bioavailability and thus increases effectiveness over to native form in the prevention of streptozotocin (ST) induced diabetes in rats, at least partly, by the suppression of inflammation and pancreatic beta-cell apoptosis (Ganugula et al., 2017). In another report, it was seen that loss of NF-kb activation leads to the down-regulation of COX-2 and iNOS expression, obstructing the inflammatory response and tumorigenesis. The experimental study demonstrated that the curcumin-loaded PLGA nanoparticles (CUR-NP) decrease the pro-inflammatory mediators in Staphylococcus aureus affected mammary tissues via increasing NF-kb signaling. Also, over to native curcumin, CUR- NP seems to be a good substitute against murine mastitis (Suresh et al., 2018). Hosseini et al. showed that the encapsulation of curcumin in nanomicelle had more anti-inflammation activity than curcumin to prevent the development of paraquat (PQ) induced lung injury (Hosseini et al., 2019). A recent investigation from Sinjari et al. gave evidence that the anti-inflammatory effect of curcumin liposomal formulations (CurLIP) in response to 2- hydroxyethyl methacrylate (HEMA) treatment in human dental pulp stem cells improved the quality of dental care with a major human community impact (Sinjari et al., 2019). Anticancer Effects Many researchers have demonstrated the anticancer activity of curcumin on humans. It acts as a potential agent against human lung, breast, prostate, colorectal, liver, carcinoma, pancreatic, myeloma, and melanoma cancers due to the capability of inducing apoptosis, preventing cancer cell growth and suppression of cell cycle development (Shishodia et al., 2005). It was seen that curcumin prevents the growth of metastasis of cancer cells. Curcumin averts the attack of cancer cells in the normal tissue by obstructing the activity of matrix metalloproteinases that regulate the process. Curcumin suppresses the expression of genes cyclin D1, c-myc, bcl-2, Bcl- xL that are involved in tumor growth, proliferation, and apoptosis. For instance, the inhibition of nuclear factor-kappa (NF-kB) is important in carcinogenesis and proliferation. Curcumin deters the NF-kB activity that can increase the expression of genes related to proliferation (e.g., cyclin D1, c-myc), invasion (e.g., matrix metalloproteinases) and antiapoptotic (Tan and Norhaizan, 2019). Over to native curcumin, curcumin encapsulated in monomethoxy poly (ethylene glycol)-poly(3-caprolactone) (MPEG-PCL) micelles hindered the proliferation of 26 colon carcinoma at in vivo condition (Gou et al., 2011). Chen et al. synthesized the curcumin-loaded liposomes nanoparticles (CLNP) and then examined for the anticancer activity in B16BL6 melanoma cells. It revealed that the proliferation activity of the B16BL6 melanoma cells severely hindered by CLNP. It was mainly due to better drug delivery enabled by the fusion of particles and cell membranes of the lipids in the intracellular region. It also inhibits the PI3 K/AKT pathway that had a major role in skin carcinogenesis (Chen et al., 2012). Basniwal et al. studied the effect of anticancer properties of curcumin nanoparticles in the lung (A549), liver (HepG2), and skin (A431) cancer cell lines. It was seen that curcumin nanoparticles showed a much better effect on the cancer cells compared to native curcumin at aqueous conditions (Basniwal et al., 2014). In another research, it has been demonstrated that PLGA-curcumin nanoparticles enhanced the lysosomal activity, apoptosis, inhibition of androgen receptor (AR), and nuclear b- catenin activity that resulted from a growth obstruction in prostate cancer cells (Yallapu et al., 2015). Triple-negative breast cancer (TNBC) is one of the most important histological subtypes of breast cancers having a metastatic phenotype. It has been demonstrated that dendrosomal nanocurcumin and exogenous p53 can act together to produce anticancer effects against TNBC cells (Baghi et al., 2018). HIF-1 and NF-kB are both indispensable for the improvement of cancer cell progression. PLGA nanoparticles (NP), loaded with curcumin (cur-PLGA-NP) elevated the HIF-1 and NF-kB subunits (HIF- 1a and nuclear p65 (Rel A) expression in breast and lung cancer cells at the hypoxic microenvironment (Khan et al., 2018). Antiamyloid Effects Amyloid beta (Ab) is an important component associated with Alzheimer’s disease (AD). Thus, inhibition of the amyloid b‐ peptide (Ab) activities such as amyloid b‐peptide (Ab) accretion, development of b‐amyloid fibrils (fAb) from Ab and the weakening of particular fAb in the central nervous system offers probable targets for the treatment of AD. Several studies showed that curcumin regulated Ab metabolism and inhibits Ab aggregation in many ways to produce strong anti‐amyloidogenic effects against AD (Ohno et al., 2004). Cheng et al. developed a highly stabilized curcumin nanoparticle and orally administered to Alzheimer’s disease model, Tg2576 mice for 3 months. In comparison to native curcumin, nanocurcumin showed potent anti‐amyloidogenic effects in Tg2576 with reduced amyloid plaque density and improved bioavailability (Cheng et al., 2010). Apolipoprotein E3-mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin (ApoE3-C-PBCA) effectiveness examined against b-amyloid SH-SY5Y neuroblastoma cells under in vitro condition. It revealed that ApoE3-C-PBCA had potent anti-amyloidogenic activity over the free form of curcumin and possible in the treatment of b- amyloid-induced cytotoxicity (Mulik et al., 2009). An investigation conducted by Mathew et al. described that conjugation of Tet-1 peptide to curcumin-PLGA nanoparticles showed the anti-amyloid effect against AD. It was seen that Frontiers in Pharmacology | www.frontiersin.org 12 May 2020 | Volume 11 | Article 487PDF Image | Nanocurcumin Promising Candidate for Therapeutic Applications
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