Curcumin: Getting Back to the Roots

TLDR: Interestingly, 6‐gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that ofCurcumin, which is now being used to treat cancer, arthritis, diabetes, Crohn's Disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies.

Abstract: The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."

Figures

FIGURE 1. Disease targets of curcumin.

TABLE 1. Relative potency of curcumin and its synthetic analogs

FIGURE 3. Structure of various analogs of curcumin. Hydrazinocurcumin,25 hydrazinodemethoxycurcumin,25 hydrazinobisdemethoxycurcumin,25 hydrazinobenzoyldemethoxycurcumin,25 dihydrocurcumin,50 hexahydrocurcumin,51 octahydrocurcumin,51 bisdemethoxycurcumin,52 diacetylcurcumin,51 salicylcurcuminoid,30 monomethylcurcumin,53 trimethylcurcumin,53 and 7–bis(3,-4-dihydroxyphenyl)11,6-heptadiene-3,5dione.53

TABLE 2. Sources and site of action of natural analogs of curcumina

FIGURE 2. Molecular targets of curcumin.

Frequently asked questions

Q1. What is the role of NF-B in prostate cancer?

Curcumin suppresses a number of protein kinases including mitogen-activated protein kinases, JNK, PKA, PKC, src tyrosine kinase, phosphorylase kinase, IκBα kinase, JAK kinase, and the growth factor receptor protein tyrosine kinases. 

Q2. What is the role of the aromatic ring in the inhibition of breast cancer?

A 3-hydroxy group of the aromatic ring is essential for the inhibition, and a free carboxyl group at the end opposite the aromatic ring interferes with the inhibitory effect. 

Q3. What is the role of the phenolic group in apoptosis?

The phenolic group is essential for free radical scavenging activity, and the presence of the methoxy group further increases the activity. 

Q4. What is the effect of curcumin on NF-B?

curcumin induced G0/G1 and/or G2/M phase cell cycle arrest, upregulated CDKIs, p21WAF1/CIP1, p27KIP1, and p53, and slightly downregulated cyclin B1 and cdc2. 

Q5. What is the role of curcumin in the prevention of atherosclerosis?

Dietary curcumin also partially reversed the abnormalities in plasma albumin, urea, creatine, and inorganic phosphorus in diabetic animals. 

Q6. What is the name of the compound?

The aromatic enone and dienone analogs of curcumin were demonstrated to have potent antiangiogenic properties in an in vitro SVR assay. 

Q7. What is the effect of curcumin on PPAR-?

Xu et al.13 demonstrated that curcumin dramatically induced the gene expression of PPAR-γ and activated PPAR-γ. AP-1, another transcription factor that has been closely linked with proliferation and transformation of tumor cells, has been shown to be suppressed by curcumin. 

Q8. What is the role of the diketone in the inhibition of cancer cells?

Synthetic cassumunins also show stronger protective activity than curcumin against oxidative cell death induced by hydrogen peroxide. 

Q9. What is the effect of curcumin on the body?

In fact, curcumin has been found to be at least 10 times more active as an antioxidant than even vitamin E.4 Curcumin prevents the oxidation of hemoglobin and inhibits lipid peroxidation (for references see Ref. 1). 

Q10. What is the common use of curcumin in traditional Indian medicine?

It is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. 

Q11. What is the peptide that inhibits oxidative stress?

38Analogs more potent than curcuminTHC: lipid peroxidation under aqueous condition by pulse radiolysis technique17HC: preventing nitrite-induced oxidation of haemoglobin 18NaC: carrageenin-induced rat hind paw edema 19HMBME: inhibition of prostate cancer 20BJC005, CHC011, and CHC007: formation of Fos-/Jun- DNA complex21Tocopheryl curcumin: inhibiting Tat transactivation of HIV-LTR 224,4′-DAC : histamine blocking activity 23 Copper chelates of 2-hydroxynapthyl curcumin: antitumor activity 24Hydrazinocurcumin: BAECs proliferation 25o-hydroxy substituted analog: inhibiting alcohol and PUFA induced oxidative stress26Di-O-glycinoyl curcumin and 2′-deoxy-2'-curcuminyl uridine: antiviral activity27Pyrazole and isoxazole analogs: Cox-2 inhibitory activity 281,7-bis-(2-hydroxy-4-methoxyphenyl)-1,6-heptadiene-3,5-dione): AL activity29Salicylcurcuminoid: antioxidantAnalogs less potent than curcuminTHC: lipid peroxidation under aerated condition by pulse radiolysis technique17THC: TPA-induced mouse ear edema and skin carcinogenesis 30Analogs as potent as curcumin5-hydroxy-1,7-diphenyl-1,4,6-heptatriene-3-one: Scavenge hydroxyl radicals31Manganese complexes of curcumin and diacetylcurcumin: Scavenge hydroxyl radicals32ABBREVIATIONS: THC, tetrahydrocurcumin; NaC, sodium curcuminate; HMBME, 4-hydroxy3-methoxybenzoic acid methyl ester; DAC, diacetylcurcumin; BAEC, bovine aortic endothelial cells; PUFA, thermally oxidized sunflower oil; Cox-2, cyclooxygenase-2; AL, anti-leishmanial. 

Q12. What did they show that curcumin inhibited?

Bharti et al.12 demonstrated that curcumin inhibited IL-6–induced STAT3 phosphorylationand consequent STAT3 nuclear translocation. 

Q13. How long did curcumin help with diarrhea?

Pretreatment of mice with curcumin for 10 days significantly ameliorated the appearance of diarrhea and the disruption of the colonic architecture.