A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin

Abstract

Curcuma longa Linn. (C. longa), popularly known as turmeric, belongs to the Zingiberaceae family and has a long historical background of having healing properties against many diseases. In Unani and Ayurveda medicine, C. longa has been used for liver obstruction and jaundice, and has been applied externally for ulcers and inflammation. Additionally, it is employed in several other ailments such as cough, cold, dental issues, indigestion, skin infections, blood purification, asthma, piles, bronchitis, tumor, wounds, and hepatic disorders, and is used as an antiseptic. Curcumin, a major constituent of C. longa, is well known for its therapeutic potential in numerous disorders. However, there is a lack of literature on the therapeutic potential of C. longa in contrast to curcumin. Hence, the present review aimed to provide in-depth information by highlighting knowledge gaps in traditional and scientific evidence about C. longa in relation to curcumin. The relationship to one another in terms of biological action includes their antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, cardioprotective, immunomodulatory, antifertility, antimicrobial, antiallergic, antidermatophytic, and antidepressant properties. Furthermore, in-depth discussion of C. longa on its taxonomic categorization, traditional uses, botanical description, phytochemical ingredients, pharmacology, toxicity, and safety aspects in relation to its major compound curcumin is needed to explore the trends and perspectives for future research. Considering all of the promising evidence to date, there is still a lack of supportive evidence especially from clinical trials on the adjunct use of C. longa and curcumin. This prompts further preclinical and clinical investigations on curcumin.

Keywords: Curcuma longa; curcumin; pharmacology; phytochemical; toxicology.

FIGURE 1

Important parts of C. longa. (A) C. longa in natural habitat, (B) medicinally important part of C. longa (rhizome), and (C) powder of dried rhizome of C. longa (used as a coloring agent in food).

FIGURE 2

The taxonomic classification and nutritional profile of C. longa.

FIGURE 3

Benefits of curcumin in various conditions.

FIGURE 4

Chemical structure of phytoconstituents present in C. longa.

FIGURE 5

Modulation of antibodies by curcumin. Curcumin assists in the modulation of antibodies that react with endothelium and causes hyperacute graft rejection. Blocking the expression of pro-inflammatory cytokines and transcription factors linked to inflammation and fibrosis may help to prevent dead grafts.

FIGURE 6

Curcumin’s mechanism of action in reducing inflammation, anabolism, and apoptosis. By inhibiting the pro-inflammatory transcription factor (NF-κB), and activation of PPAR-γ, curcumin aids in anabolism and apoptosis, suppression of pro-inflammatory cytokines, as well as the expression and release of TNF-α. Abbreviations: TLR, Toll-like receptors; TNFR, Tumor necrosis factor receptor; ROS, Reactive oxygen species; TRADD, Tumor necrosis factor receptor type 1-associated death domain protein; CYLD, CYLD lysine 63 deubiquitinase; cIAP1/2, Cellular inhibitor of apoptosis protein 1/2; TRAF 2/5, Tumor necrosis factor receptor-associated factor 2/5; RIPK1, Receptor-interacting serine/threonine-protein kinase 1; LUBAC, Linear ubiquitin chain assembly complex; SPATA2, Spermatogenesis-associated protein 2; NEMO, NF-κB essential modulator; TAB2/3, TGF-beta activated kinase 1 (MAP3K7) binding protein 2; TAK1, Transforming growth factor-β-activated kinase 1; IKKα, IKKβ, and IKKγ, Inhibitory kappa b kinase alpha, beta, and gamma; IkB, Inhibitor of nuclear factor kappa Bv; PPAR-γ, Peroxisome proliferator-activated receptor gamma; P13K, Phosphoinositide 3-kinases; Akt, Ak strain transforming; ERK, Extracellular-signal-regulated kinase; JNK, Jun N-terminal kinase; Bax, Bcl-2-associated X-protein; AP-1, Activated protein-1; MMP-9, Matrix metallopeptidase 9; COX-2, Cyclooxygenase 2; IL-6 and 1β, Interleukin 6 and 1 beta; TNF-α, Tumor necrosis factor alpha; MCP-1, Monocyte chemoattractant protein-1.

FIGURE 7

Mechanism of curcumin in regulation of cancer proliferation. TGF-β1/smad3, IGF, PI3K/Akt, Wnt/β-catenin, and vascular endothelial growth factor (VEGF) are some of the signaling pathways and molecular targets that curcumin modulates to inhibit cancer. Blocking these receptors has the potential to reduce chronic inflammation and oxidative damage. DSH and AXIN are recruited once the WNT binds to LRP 5/6, producing the β-catenin destruction complex. β-catenin that has escaped into the nucleus promotes the transcription of genes including cyclin D1 and P13k, which promote cell proliferation and growth. IGF-1R, Insulin-like growth factor 1 receptor; TGF-β1, Transforming growth factor beta 1; WNT, Wingless/integrated; LRP 5/6, Low-density lipoprotein receptor-related protein 5/6; Smad, small mothers against decapentaplegic; Ras, Rat sarcoma virus; Raf, Rapidly Accelerated Fibrosarcoma; MEK 1/2, Mitogen-activated protein kinase 1/2; ERK ½, Extracellular-signal-regulated kinase ½; P13K, Phosphoinositide 3-kinases; Akt, Ak strain transforming; mTOR, mammalian target of rapamycin; TCF/LEF, T-cell factor/lymphoid enhancer factor; FZD, Frizzled; DSH, Dishevelled; AXIN, Axis Inhibitor; APC, Adenomatous polyposis coli; GSK-3β, Glycogen synthase kinase-3 beta; CK-1, casein kinase 1.

FIGURE 8

Curcumin must be modified/improved prior to future research due to its extremely low bioavailability. Due to the quick elimination of curcumin in the systemic circulation as a result of enzyme metabolism, conjugating curcumin to adjuvants or other delivery systems may be beneficial in order to increase its half-life and bioavailability.

FIGURE 9

Curcumin safety, toxicity profiles, and solution to overcome it. Curcumin safety, toxicity profiles, and a way to circumvent it. Despite its recognized safety, certain investigations have highlighted unprecedented side effects of curcumin, including gastrointestinal problems, chronic inflammations, and others. To address this issue, fewer additives should be utilized, and curcumin microencapsulation should be tailored.

FIGURE 10

Future perspective of curcumin-loaded gold nanoparticles functionalized with Ty1 and bevacizumab in a patient infected with SARS-CoV-2 (COVID-19).