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.

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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.

The GC-MS analysis of tea tree oil (TTO) revealed 38 volatile components with sesquiterpene hydrocarbons (43.56%) and alcohols (41.03%) as major detected classes. TTO efficacy is masked by its hydrophobicity; nanoencapsulation can address this drawback. The results showed that TTO-loaded solid lipid nanoparticles (SLN1), composed of glyceryl monostearate (2% w/w) and Poloxamer188 (5% w/w), was spherical in shape with a core-shell microstructure. TTO-SLN1 showed a high entrapment efficiency (96.26 ± 2.3%), small particle size (235.0 ± 20.4 nm), low polydispersity index (0.31 ± 0.01), and high negative Zeta potential (−32 mV). Moreover, it exhibited a faster active agent release (almost complete within 4 h) compared to other formulated TTO-SLNs as well as the plain oil. TTO-SLN1 was then incorporated into cellulose nanofibers gel, isolated from sugarcane bagasse, to form the ‘TTO-loaded nanolipogel’ which had a shear-thinning behavior. Second-degree thermal injuries were induced in Wistar rats, then the burned skin areas were treated daily for 7 days with the TTO-loaded nanolipogel compared to the unmedicated nanolipogel, the TTO-loaded conventional gel, and the normal saline (control). The measurement of burn contraction proved that TTO-loaded nanolipogel exhibited a significantly accelerated skin healing, this was confirmed by histopathological examination as well as quantitative assessment of inflammatory infiltrate. This study highlighted the success of the proposed nanotechnology approach in improving the efficacy of TTO used for the repair of skin damage induced by burns.

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Nanolipogel Loaded with Tea Tree Oil for the Management of Burn: GC-MS Analysis, In Vitro and In Vivo Evaluation

In this study, the in vitro bioavailability of rosehip infusion phenolics, mainly catechin, as a response to conventional and non-thermal treatments by combining gastrointestinal digestion and a Caco-2 cell culture model, was investigated. After application of thermal treatment (TT, 85 °C/10 min), high pressure (HPP, 600 MPa/5 min) or pulsed electric field (PEF, 15 kJ/kg) processing, all samples were subjected to simulated gastrointestinal digestion. Then, the amount of maximum non-toxic digest ratio was determined by the cytotoxicity sulforhodamine B (SRB) assay. Next, Caco-2 cells were exposed to 1:5 (v/v) times diluted digests in order to simulate the transepithelial transportation of catechin. Results showed that non-thermally processed samples (5.19 and 4.62% for HPP and PEF, respectively) exhibited greater transportation across the epithelial cell layer compared to than that of the TT-treated sample (3.42%). The present study highlighted that HPP and PEF, as non-thermal treatments at optimized conditions for infusions or beverages, can be utilized in order to enhance the nutritional quality of the final products.

/pdf/bioavailability-of-rosehip-rosa-canina-l-infusion-phenolics-3pia4w40.pdf

Bioavailability of Rosehip (Rosa canina L.) Infusion Phenolics Prepared by Thermal, Pulsed Electric Field and High Pressure Processing

Antioxidative activity, total polyphenols, monomeric index, monomeric anthocyanins, chlorogenic acids, quercetin derivatives, and polymeric procyanidins were evaluated in eight different chokeberry juices. All juices show a high antioxidant activity (26.8-34.2 mmol TE/I) and a high content of polyphenols (3911-5812 mg GAE/I) using the TEAC and Folin-Ciocalteu assay, respectively. The monomeric index ranged from 2.6 to 21.7. According to the HPLC results it is apparent that chokeberry juices show high monomeric anthocyanin contents (341-1163 mg/l). The anthocyanin composition of all juices consists of the two major pigments cyanidin 3-galactoside and cyanidin 3-arabinoside, as well as the minor anthocyanins cyanidin 3-glucoside and cyanidin 3-xyloside, respectively. Chokeberry juices are also a rich source of hydroxycinnamic acid derivatives mainly represented by 5-caffeoylquinic acid (chlorogenic acid) and 3-caffeoylquinic acid (neochlorogenic acid). The total content of chlorogenic acids varied from 490 to 1412 mg/l. The main flavanol glycosides of chokeberry are quercetin 3-glycosides. The analyzed juices contain high contents of quercetin 3-galactoside, quercetin 3-glucoside, and quercetin 3-rutinoside. The total amount of quercetin 3-glycosides ranged from 204 mg/l to 656 mg/l. High concentrations of polymeric procyanidins were found (up to 1693,3 mg/100 g Tr). With regard to the composition of the polymers, degradation with phloroglucinolysis revealed that they almost exclusively consist of (-)-epicatechin units.

Analysis of phenolic components of black chokeberries (Aronia melanocarpa).

An estimated 450 species of Dryopteris in the Dryoperidaceae family grow in Japan, North and South Korea, China, Pakistan, and Kashmir. This genus has been reported to have biological capabilities; however, research has been conducted on Dryopteris juxtapostia. Therefore, with the present study, we aimed to exploring the biological potential of D. juxtapostia root and shoot extracts. We extracted dichloromethane and methanol separately from the roots and shoots of D. juxtapostia. Antioxidant activity was determined using DPPH, FRAP, and H2O2 assays, and anti-inflammatory activities were evaluated using both in vitro (antiurease activity) and in vivo (carrageenan- and formaldehyde-induced paw edema) studies. Toxicity was evaluated by adopting a brine shrimp lethality assay followed by determination of cytotoxic activity using an MTT assay. Hepatoprotective effects of active crude extracts were examined in rats. Activity-bearing compounds were tentatively identified using LC-ESI-MS/MS analysis. Results suggested that D. juxtapostia root dichloromethane extract exhibited better antioxidant (DPPH, IC50 of 42.0 µg/mL; FRAP, 46.2 mmol/g; H2O2, 71% inhibition), anti-inflammatory (urease inhibition, 56.7% at 50 µg/mL; carrageenan-induced edema inhibition, 61.7% at 200 µg/mL; formaldehyde-induced edema inhibition, 67.3% at 200 µg/mL), brine shrimp % mortality (100% at 1000 µg/mL), and cytotoxic (HeLa cancer, IC50 of 17.1 µg/mL; prostate cancer (PC3), IC50 of 45.2 µg/mL) effects than D. juxtapostia root methanol extract. D. juxtapostia shoot dichloromethane and methanol extracts exhibited non-influential activity in all biological assays and were not selected for hepatoprotective study. D. juxtapostia root methanol extract showed improvement in hepatic cell structure and low cellular infiltration but, in contrast the dichloromethane extract, did not show any significant improvement in hepatocyte morphology, cellular infiltration, or necrosis of hepatocytes in comparison to the positive control, i.e., paracetamol. LC-ESI-MS/MS analysis showed the presence of albaspidin PP, 3-methylbutyryl-phloroglucinol, flavaspidic acid AB and BB, filixic acid ABA and ABB, tris-desaspidin BBB, tris-paraaspidin BBB, tetra-flavaspidic BBBB, tetra-albaspidin BBBB, and kaempferol-3-O-glucoside in the dichloromethane extract, whereas kaempferol, catechin, epicatechin, quinic acid, liquitrigenin, and quercetin 7-O-galactoside in were detected in the methanol extract, along with all the compounds detected in the dichloromethane extract. Hence, D. juxtapostia is safe, alongside other species of this genus, although detailed safety assessment of each isolated compound is obligatory during drug discovery.

/pdf/dryopteris-juxtapostia-root-and-shoot-determination-of-2smni030.pdf

Dryopteris juxtapostia Root and Shoot: Determination of Phytochemicals; Antioxidant, Anti-Inflammatory, and Hepatoprotective Effects; and Toxicity Assessment

Differences between seven authentic samples of Citrus sinensis var. Valencia peel (albedo and flavedo) and juices from Spain and Uruguay, in addition to a concentrate obtained from Brazil, were investigated by untargeted metabolic profiling. Sixty-six metabolites were detected by nano-liquid chromatography coupled to a high-resolution electrospray-ionization quadrupole time-of-flight mass spectrometer (nLC-ESI-qTOF-MS) belonging to phenolic acids, coumarins, flavonoid glycosides, limonoids, terpenes, and fatty acids. Eleven metabolites were detected for the first time in Citrus sinensis and identified as citroside A, sinapic acid pentoside, apigenin-C-hexosyl-O-pentoside, chrysoeriol-C-hexoside, di-hexosyl-diosmetin, perilloside A, gingerol, ionone epoxide hydroxy-sphingenine, xanthomicrol, and coumaryl alcohol-O-hexoside. Some flavonoids were completely absent from the juice, while present most prominently in the Citrus peel, conveying more industrial and economic prospects to the latter. Multivariate data analyses clarified that the differences among orange parts overweighed the geographical source. PCA analysis of ESI-(−)-mode data revealed for hydroxylinoleic acid abundance in flavedo peel from Uruguay the most distant cluster from all others. The PCA analysis of ESI-(+)-mode data provided a clear segregation of the different Citrus sinensis parts primarily due to the large diversity of flavonoids and coumarins among the studied samples.

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Comparative Untargeted Metabolic Profiling of Different Parts of Citrus sinensis Fruits via Liquid Chromatography–Mass Spectrometry Coupled with Multivariate Data Analyses to Unravel Authenticity

Tuba Esatbeyoglu

Papers

Nanolipogel Loaded with Tea Tree Oil for the Management of Burn: GC-MS Analysis, In Vitro and In Vivo Evaluation

Bioavailability of Rosehip (Rosa canina L.) Infusion Phenolics Prepared by Thermal, Pulsed Electric Field and High Pressure Processing

Analysis of phenolic components of black chokeberries (Aronia melanocarpa).

Dryopteris juxtapostia Root and Shoot: Determination of Phytochemicals; Antioxidant, Anti-Inflammatory, and Hepatoprotective Effects; and Toxicity Assessment

Comparative Untargeted Metabolic Profiling of Different Parts of Citrus sinensis Fruits via Liquid Chromatography–Mass Spectrometry Coupled with Multivariate Data Analyses to Unravel Authenticity