Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

The Essential Medicinal Chemistry of Curcumin

Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells In addition, spermidine administration potently inhibited oxidative stress in ageing mice In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity

Induction of autophagy by spermidine promotes longevity

Curcumin, a pigment from turmeric, is one of the very few promising natural products that has been extensively investigated by researchers from both the biological and chemical point of view. While there are several reviews on the biological and pharmacological effects of curcumin, chemistry reviews are comparatively scarcer. In this article, an overview of different aspects of the unique chemistry research on curcumin will be discussed. These include methods for the extraction from turmeric, laboratory synthesis methods, chemical and photochemical degradation and the chemistry behind its metabolism. Additionally other chemical reactions that have biological relevance like nucleophilic addition reactions, and metal chelation will be discussed. Recent advances in the preparation of new curcumin nanoconjugates with metal and metal oxide nanoparticles will also be mentioned. Directions for future investigations to be undertaken in the chemistry of curcumin have also been suggested.

/pdf/the-chemistry-of-curcumin-from-extraction-to-therapeutic-3i2ua7g7ok.pdf

The Chemistry of Curcumin: From Extraction to Therapeutic Agent

For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury.

https://cyberleninka.org/article/n/470093.pdf

Renoprotective effect of the antioxidant curcumin: Recent findings

The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update.

Curcumin is a secondary plant metabolite present in Curcuma longa L. Since curcumin is widely used as a food colorant in thermally processed food it may undergo substantial chemical changes which in turn could affect its biological activity. In the current study, curcumin was roasted at 180 °C up to 70 minutes and its kinetic of degradation was analyzed by means of HPLC-PDA and LC-MS, respectively. Roasting of curcumin resulted in the formation of the degradation products vanillin, ferulic acid, and 4-vinyl guaiacol. In cultured hepatocytes roasted curcumin as well as 4-vinyl guaiacol enhanced the transactivation of the redox-regulated transcription factor Nrf2, known to be centrally involved in cellular stress response and antioxidant defense mechanisms. The antioxidant enzyme paraoxonase 1 was induced by roasted curcumin and 4-vinyl guaiacol. Furthermore, roasted curcumin and 4-vinyl guaiacol decreased interleukin-6 gene expression in lipopolysaccharide stimulated murine macrophages. Current data suggest that curcumin undergoes degradation due to roasting and its degradation product exhibit significant biological activity in cultured cells.

/pdf/thermal-stability-antioxidant-and-anti-inflammatory-activity-2vz7ryk7cb.pdf

Thermal stability, antioxidant, and anti-inflammatory activity of curcumin and its degradation product 4-vinyl guaiacol

In this study, we analyzed eight phenolic compounds (tyrosol, hydroxytyrosol, oleuropein, pinoresinol, and caffeic, ferulic, vanillic, and p-coumaric acid) in 55 mono- and multivarietal extra virgin olive oil samples by high performance liquid chromatography (HPLC) coupled to a coulometric electrochemical array detector (ECD). The phenolic profile of olive oil samples differed depending on the geographical origin and olive variety. The total reducing capacity (total phenolics) of olive oils ranged from about 40 to 530 mg gallic acid equivalents/kg oil. Tyrosol, hydroxytyrosol and pinoresinol were the most abundant phenolic compounds in olive oils. The antioxidant capacity of the olive oil extracts was determined by ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays. Total reducing capacity was significatly correlated with FRAP (R
 2
  = 0.91, p < 0.001) and TEAC (R
 2
  = 0.92, p < 0.001) values. Total reducing capacity, TEAC and FRAP values were significantly correlated with tyrosol, hydroxytyrosol as well as oleuropein concentrations. Hydroxytyrosol, comprising over 40 % of total olive oil phenolics, mainly contributed to the antioxidant activity of olive oils. The present study provides a comprehensive database of polyphenols in olive oils from 9 different countries and four continents.

Comprehensive Analysis of Polyphenols in 55 Extra Virgin Olive Oils by HPLC-ECD and Their Correlation with Antioxidant Activities

Turmeric is traditionally used as a spice and coloring in foods. It is an important ingredient in curry and gives curry powder its characteristic yellow color. As a consequence of its intense yellow color, turmeric, or curcumin (food additive E100), is used as a food coloring (e.g. mustard). Turmeric contains the curcuminoids curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Recently, the health properties (neuroprotection, chemo-, and cancer prevention) of curcuminoids have gained increasing attention. Curcuminoids induce endogenous antioxidant defense mechanisms in the organism and have anti-inflammatory activity. Curcuminoids influence gene expression as well as epigenetic mechanisms. Synthetic curcumin analogues also exhibit biological activity. This Review describes the development of curcumin from a "traditional" spice and food coloring to a "modern" biological regulator.

Curcumin — From Molecule to Biological Function

The aim of this review is to summarize the relevant literature about the use of canthaxanthin in food science and nutrition research. Canthaxanthin is a red-orange carotenoid that belongs to the xanthophyll group. This naturally occurring pigment is present in bacteria, algae and some fungi. Canthaxanthin is also responsible for the color of flamingo feathers, koi carp skin and crustacean shells. Canthaxanthin is widely used in poultry (broiler, laying hens) as a feed additive. Canthaxanthin can be obtained by total synthesis. The canthaxanthin-mediated color of foods is an important quality criterion for consumers. Recently, the potential health-promoting effects of canthaxanthin have been discussed. Canthaxanthin enrichment of LDL has the potential to protect cholesterol from oxidation. In addition to its free radical scavenging and antioxidant properties (e.g., the induction of catalase and superoxide dismutase), canthaxanthin's immunomodulatory activity (e.g., enhancing the proliferation and function of immune competent cells) and its important role in gap junction communication (e.g., induction of the transmembrane protein connexin 43) have been reported. Many studies regarding the potential health benefits of canthaxanthin have been conducted in vitro and should be validated in appropriate in vivo models.

Tuba Esatbeyoglu

Papers

Thermal stability, antioxidant, and anti-inflammatory activity of curcumin and its degradation product 4-vinyl guaiacol

Comprehensive Analysis of Polyphenols in 55 Extra Virgin Olive Oils by HPLC-ECD and Their Correlation with Antioxidant Activities

Curcumin — From Molecule to Biological Function

Canthaxanthin: From molecule to function

Fractionation, enzyme inhibitory and cellular antioxidant activity of bioactives from purple sweet potato (Ipomoea batatas).