Curcumin-Based Nanomedicines in the Treatment of Inflammatory and Immunomodulated Diseases: An Evidence-Based Comprehensive Review

Abstract

Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Despite CUR's numerous beneficial effects on human health, it has limitations, such as poor absorption. Nano-based drug delivery systems have recently been applied to improve CUR's solubility and bioavailability and potentialize its health effects. This review investigated the effects of different CUR-based nanomedicines on inflammatory and immunomodulated diseases. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR databases were searched, and the Scale for Assessment of Narrative Review Articles (SANRA) was used for quality assessment and PRISMA guidelines. Overall, 66 studies were included comprising atherosclerosis, rheumatoid arthritis (RA), Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), inflammatory bowel diseases (IBD), psoriasis, liver fibrosis, epilepsy, and COVID-19. The available scientific studies show that there are many known nanoformulations with curcumin. They can be found in nanosuspensions, nanoparticles, nanoemulsions, solid lipid particles, nanocapsules, nanospheres, and liposomes. These formulations can improve CUR bioavailability and can effectively be used as adjuvants in several inflammatory and immune-mediated diseases such as atheroma plaque formation, RA, dementia, AD, PD, MS, IBD, psoriasis, epilepsy, COVID-19, and can be used as potent anti-fibrotic adjuvants in fibrotic liver disease.

Keywords: auto-immune diseases; autoimmunity; curcumin; curcumin-based nanomedicines; delivery systems; inflammation; inflammatory diseases; nanomedicines.

Figure 1

Possible mechanisms associated with CUR’s protective effects against atheroma formation. Atherosclerosis is a phenomenon that depends highly on modified LDL in the arterial vessels. CUR protects against atherosclerosis via anti-inflammatory and immunomodulating effects, as well as exerting antilipidemic actions and promoting MMP expression down-regulation. ↑, increase; Ap2, apetala type 2; AT1R; angiotensin 1 receptor; CD36R, CD36 receptor; COX-2, ciclooxigensase 2; ERK, extracellular signal-regulated kinases; ICAM-1, intercellular adhesion molecule 1; IkBa, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; IKKs, IκB kinases; IL, interleukin; IRAK, interleukin-1 receptor-associated kinases; JNK, N-terminal kinase; iNOS, inducible nitric oxide synthase; LDL-c, low-density lipoprotein cholesterol; LOX-1R, lysyl oxidase type 1; LPS, lipopolysaccharides; MAPK, mitogen-activated protein kinase; MyD88, myeloid differentiation primary response 88; NF-kB, nuclear factor kappa b; P38, p38 signaling transduction pathway; P50, NF-kB P50 heterodimer; P65, NF-kB P65 heterodimer; PPARγ, peroxisome proliferator-activated receptor γ; SR-AR, scavenger receptor type A; TLR4, tool-like receptor 4; TNF-α, tumor factor necrosis alfa; VCAM-1, vascular cell adhesion molecule 1.

Figure 2

Most important pro-inflammatory vias involved in the occurrence of inflammatory bowel diseases that are inhibited by CUR. This bioactive compound diminishes inflammation and promotes antioxidant effects during in vivo, in vitro, and human studies regarding its use against IBD. The inhibition of NF-kB activation by CUR is highlighted. Ap1, apetala type 1; ARE, antioxidant redox element; ASC, apoptosis-associated speck-like protein; C-FOX, forkhead box protein C; C-JUN, transcription factor Jun C; ERK, extracellular signal-regulated kinases; IkB, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor; IKK a, IκB kinases α; JAK, Janus kinase; JNK, N-terminal kinase; Keap1, kelch-like ECH-associated protein 1; Maf, MAF BZIP Transcription Factor; MAPK, mitogen-activated protein kinase; NF-kB, nuclear factor kappa b; NLRP2, NLR family pyrin domain containing 3; Nrf2, nuclear factor erythroid 2–related factor 2; P38, p38 signaling transduction pathway; P50, NF-kB P50 heterodimer; P65, NF-kB P65 heterodimer; PPARγ, peroxisome proliferator-activated receptor γ; P-STAT, phosphorylated STAT; STAT, signal transducer and activator of transcription; TAK1, transforming growth factor beta-activated kinase 1; TLRs, tool-like receptors; TRAF6, TNF receptor-associated factor 6.

Figure 3

Effects of CUR not only on the inflammatory vias associated with COVID-19, but also with SARS-CoV-2 viral processing and release processes. CUR exerts principally anti-inflammatory and antioxidant effects against COVID-19, but also conducts immunomodulatory effects by controlling the expression of immunological genes. Regarding its use, CUR can also promote symptoms-relief during COVID-19 infection. ACE1, angiotensin-converting enzyme 1; ACE2, angiotensin-converting enzyme 2; ADAM17, disintegrin and metalloprotease 17; Ang 1, angiotensin 1; Ang 2, angiotensin 2; AKT, Alpha serine/threonine protein kinase; ATR1, angiotensin 1 receptor; DAMPs, damage-associated molecular patterns; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; GP130, glycoprotein 130; Ikβ, inhibitor of nuclear factor kappa β; IL, interleukin; IL-6R, interleukin 6 receptor; Mpro, main protease; mTOR, mammalian-target of rapamycin; NF-kB, nuclear factor kappa B; P50, the nuclear factor kappa B p50 heterodimer; P65, the nuclear factor kappa B p65 heterodimer; PAMPs, pathogen-associated molecular patterns; PI3K, phosphatidylinositol-3 kinase; sIL-6R, soluble form of the interleukin 6 receptor; TMPRSS2, transmembrane protease serine 2.