Curcumin: novel treatment in neonatal hypoxic-ischaemic brain injury

Hypoxic-ischaemic encephalopathy (HIE) is a major cause of mortality and morbidity in neonates, with an estimated global incidence of 3/1000 live births. HIE brain damage is associated with an inflammatory response and oxidative stress, resulting in the activation of cell death pathways. At present, therapeutic hypothermia is the only clinically approved treatment available for HIE. This approach, however, is only partially effective. There is therefore an unmet clinical need for the development of novel therapeutic interventions for the treatment of HIE. Curcumin is an antioxidant reactive oxygen species scavenger, with reported anti-tumour and anti-inflammatory activity. Curcumin has been shown to attenuate mitochondrial dysfunction, stabilise the cell membrane, stimulate proliferation, and reduce injury severity in adult models of spinal cord injury, cancer, and cardiovascular disease. The role of curcumin in neonatal HIE has not been widely studied due to its low bioavailability and limited aqueous solubility. The aim of this study was to investigate the effect of curcumin treatment in neonatal HIE, including time of administration and dose-dependent effects. Our results indicate that curcumin administration prior to HIE in neonatal mice elevated cell and tissue loss, as well as glial activation compared to HI alone. However, immediate post-treatment with curcumin was significantly neuroprotective, reducing grey and white matter tissue loss, TUNEL+ cell death, microglia activation, reactive astrogliosis and iNOS oxidative stress when compared to vehicle-treated littermates. This effect was dose-dependent, with 200µg/g body weight as the optimal dose-regimen, and was maintained when curcumin treatment was delayed by 60min or 120min post-HI. Cell proliferation measurements showed no changes between curcumin and HI alone, suggesting that the protective effects of curcumin on the neonatal brain following HI are most likely due to curcumin’s anti-inflammatory and antioxidant properties, as seen in the reduced glial and iNOS activity. In conclusion, this study suggests curcumin as a potent neuroprotective agent with potential for the treatment of HIE. The delayed application of curcumin further increases its clinical relevance

Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling

In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance in vitro and the adverse effect ototoxicity in vivo

Effect of Aromatic Substitution of Curcumin Nanoformulations on Their Stability

Curcumin, a poorly water-soluble bioactive compound, was successfully loaded into three different aromatic contents of hydroxypropylmethacrylamide (HPMA)-based polymeric micelles in order to develop water-soluble curcumin nanoformulations (Cur-Nano). The stability study of Cur-Nano was done by keeping the formulations at 4, 30, and 40 °C for 90 days. The physical appearance, curcumin remaining, and particle size of Cur-Nano were examined by visual inspection, high-performance liquid chromatography, and dynamic light scattering, respectively. After the storage period, the Cur-Nano composed of 100% aromatic-substituted polymer exhibited the highest stability of curcumin (80% of curcumin remaining) with a similar particle size as measured on the first day (50–60 nm) in all storage conditions. Curcumin in Cur-Nano composed of 25% and 0% aromatic-substituted polymer was significantly less stable accordingly. The results suggested that aromatic substitution to HPMA-based polymeric micelles can significantly enhance the stability of the loaded curcumin, considerably due to the π-π stacking interactions between the aromatic groups of curcumin and the polymer. It is concluded that curcumin-loaded polymeric micelles with high substituted aromatic content can be promising candidates with good storage stability for further clinical evaluations

Potential and Alternative Bioactive Compounds from Brown <i>Agaricus bisporus</i> Mushroom Extracts for Xerosis Treatment

This study aimed to investigate the ability of brown Agaricus bisporus extracts to enhance xerosis treatment via their biological activities, including their antioxidant, anti-aging, and anti-inflammation. Brown A. bisporus ethanol extract (EE) and brown A. bisporus water extract (WE) contained ergothioneine and gallic acid as their major compounds, as detected by HPLC, respectively. The WE exhibited the highest total polysaccharide content (734.04 ± 0.03 mg glucose/g extract) and total phenolic content (190.90 ± 0.07 mg gallic acid/g extract). The WE exhibited an inhibitory effect of 83.34 ± 18.66% on a collagenase enzyme, whereas the EE inhibited the elastase enzymes by 81.26 ± 4.37%. In addition, the EE also demonstrated strong activities against DPPH, with an IC50 0.30 ± 0.04 mg/mL, ABTS with a TEAC value of 8.06 ± 0.08 µM Trolox/g extract, and a FRAP assay with a FRAP value of 390.50 ± 0.32 mM FeSO4/g. In addition, all extracts were non-cytotoxic and could decrease the secretion of IL-6 and TNF-α in HaCaT cells. Therefore, brown A. bisporus extracts might be a potential natural raw material that can be further used in cosmeceutical products for xerosis treatment due to their good efficacy

Potential and Alternative Bioactive Compounds from Brown Agaricus bisporus Mushroom Extracts for Xerosis Treatment

This study aimed to investigate the ability of brown Agaricus bisporus extracts to enhance xerosis treatment via their biological activities, including their antioxidant, anti-aging, and anti-inflammation. Brown A. bisporus ethanol extract (EE) and brown A. bisporus water extract (WE) contained ergothioneine and gallic acid as their major compounds, as detected by HPLC, respectively. The WE exhibited the highest total polysaccharide content (734.04 &plusmn; 0.03 mg glucose/g extract) and total phenolic content (190.90 &plusmn; 0.07 mg gallic acid/g extract). The WE exhibited an inhibitory effect of 83.34 &plusmn; 18.66% on a collagenase enzyme, whereas the EE inhibited the elastase enzymes by 81.26 &plusmn; 4.37%. In addition, the EE also demonstrated strong activities against DPPH, with an IC50 0.30 &plusmn; 0.04 mg/mL, ABTS with a TEAC value of 8.06 &plusmn; 0.08 &micro;M Trolox/g extract, and a FRAP assay with a FRAP value of 390.50 &plusmn; 0.32&thinsp;mM FeSO4/g. In addition, all extracts were non-cytotoxic and could decrease the secretion of IL-6 and TNF-&alpha; in HaCaT cells. Therefore, brown A. bisporus extracts might be a potential natural raw material that can be further used in cosmeceutical products for xerosis treatment due to their good efficacy

Curcumin nanoformulations : A review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment

Curcumin, a natural yellow phenolic compound, is present in many kinds of herbs, particularly in Curcuma longa Linn. (turmeric). It is a natural antioxidant and has shown many pharmacological activities such as anti-inflammatory, anti-microbial, anti-cancer, and anti-Alzheimer in both preclinical and clinical studies. Moreover, curcumin has hepatoprotective, nephroprotective, cardioprotective, neuroprotective, hypoglycemic, antirheumatic, and antidiabetic activities and it also suppresses thrombosis and protects against myocardial infarction. Particularly, curcumin has demonstrated efficacy as an anticancer agent, but a limiting factor is its extremely low aqueous solubility which hampers its use as therapeutic agent. Therefore, many technologies have been developed and applied to overcome this limitation. In this review, we summarize the recent works on the design and development of nano-sized delivery systems for curcumin, including liposomes, polymeric nanoparticles and micelles, conjugates, peptide carriers, cyclodextrins, solid dispersions, lipid nanoparticles and emulsions. Efficacy studies of curcumin nanoformulations using cancer cell lines and in vivo models as well as up-to-date human clinical trials are also discussed

Optimization of Semha-Pinas Extract Orodispersible Tablets Using Response Surface Methodology

The original dosage form of the Semha-Pinas herbal formula, an expectorant in Thai traditional medicine, is in a pill form. However, it is inconvenient to use because it must be powdered and dissolved in hot water or juice of Citrus x aurantium L. before use. The development of a new dosage form presents a challenging prospect. This work aimed to develop Semha-Pinas extract orodispersible tablets based on the response surface methodology using the Box-Behnken design. Firstly, Semha-Pinas extract was tested for its safety in HepG2 cells. The safe extract was further developed as orodispersible tablets. Four levels of three factors — compressional force (500–2,000 psi), the quantity of microcrystalline cellulose (0–15%), and the quantity of croscarmellose sodium and sodium starch glycolate (0:8–6:2%) — were screened using the one factor at a time technique. The Box-Behnken design has three levels for each factor: 1,000–2,000 psi, 5–15%, and 2:6–6:2%, respectively. Tablet thickness, hardness, friability, and disintegration time were the four responses that were monitored. The results indicated the safety of the Semha-Pinas extract, even at a concentration of 5 mg/mL. The optimal orodispersible tablet formulation had a compressional force of 1,500 psi, microcrystalline cellulose of 10%, and croscarmellose sodium to sodium starch glycolate of 4:4%. In summary, this study successfully fabricated Semha-Pinas extract orodispersible tablets using response surface methodology, achieving the desired property of fast disintegration. Moreover, these findings can serve as a valuable reference for pilot scale and industrial scale production

Hydrolyzed Flavonoids from Cyrtosperma johnstonii with Superior Antioxidant, Antiproliferative, and Anti-Inflammatory Potential for Cancer Prevention

Cyrtosperma johnstonii is one of the most interesting traditional medicines for cancer treatment. This study aimed to compare and combine the biological activities related to cancer prevention of the flavonoid glycosides rutin (RT) and isorhamnetin-3-o-rutinoside (IRR) and their hydrolysis products quercetin (QT) and isorhamnetin (IR) from C.johnstonii extract. ABTS and MTT assays were used to determine antioxidant activity and cytotoxicity against various cancer cells, as well as normal cells. Anti-inflammatory activities were measured by ELISA. The results showed that the antioxidant activities of the compounds decreased in the order of QT &gt; IR &gt; RT &gt; IRR, while most leukemia cell lines were sensitive to QT and IR with low toxicity towards PBMCs. The reduction of IL-6 and IL-10 secretion by QT and IR was higher than that induced by RT and IRR. The combination of hydrolysis products (QT and IR) possessed a strong synergism in antioxidant, antiproliferative and anti-inflammatory effects, whereas the combination of flavonoid glycosides and their hydrolysis products revealed antagonism. These results suggest that the potential of the combination of hydrolyzed flavonoids from C. johnstonii can be considered as natural compounds for the prevention of cancer

A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles

Curcumin, a phenolic compound, possesses many pharmacological activities and is under clinical evaluation to treat different diseases. However, conflicting data about its stability have been reported. In this study, the kinetic degradation of curcumin from a natural curcuminoid mixture under various conditions (pH, temperature, and dielectric constant of the medium) was investigated. Moreover, the degradation of pure curcumin at some selected conditions was also determined. To fully solubilize curcumin and to prevent precipitation of curcumin that occurs when low concentrations of co–solvent are present, a 50:50 (v/v) aqueous buffer/methanol mixture was used as standard medium to study its degradation kinetics. The results showed that degradation of curcumin both as pure compound and present in the curcuminoid mixture followed first order kinetic reaction. It was further shown that an increasing pH, temperature, and dielectric constant of the medium resulted in an increase in the degradation rate. Curcumin showed rapid degradation due to autoxidation in aqueous buffer pH = 8.0 with a rate constant of 280 × 10-3h-1, corresponding with a half–life (t1/2) of 2.5 h. Dioxygenated bicyclopentadione was identified as the final degradation product. Importantly, curcumin loaded as curcuminoid mixture in ω–methoxy poly (ethylene glycol)–b–(N–(2–benzoyloxypropyl) methacrylamide) (mPEG–HPMA–Bz) polymeric micelles and in Triton X–100 micelles was about 300–500 times more stable than in aqueous buffer. Therefore, loading of curcumin into polymeric micelles is a promising approach to stabilize this compound and develop formulations suitable for further pharmaceutical and clinical studies