Influence of different preparation techniques on the composition and antioxidant action of curcumin and curcuminoids / Influencia de diferentes técnicas de preparación en la composición y acción antioxidante de la curcumina y los curcuminoides

Epidemiological evidence indicates that plant antioxidants activity can treat or help to prevent the development of various diseases. One species with great potential as an antioxidant is Curcuma longa. However, different extraction techniquescan influence isolated chemical compounds. This study investigated chemical composition and antioxidant activity of two rhizome extracts of C. longa: hydroethanolic, obtained by exhaustion (HECLex); and dried by a spray dryer (HECLsd). The phytochemical composition was evaluated by GC/MS. Antioxidant activity was evaluated using DPPH and FRAP assays. Total phenolic compounds and soil analyses were performed. The main components of HECLex were ar-turmerone, γ-curcumene, α-turmerone, and ß-sesquiphellandrene. The main components of HECLsd were 9,12,15-octadecatrienoic acid, 2, 3-bis([trimethylsilyl]oxy) propyl ester, verrucarol, and 1-monolinoleoylglycerol trimethylsilyl ether. HECLsd had significantly higher levels of phenolic compounds and higher antioxidant capacity compared with HECLex. In conclusion, processes of the preparation of C. longarhizomes alter the chemical components and consequently their biological activity.

La evidencia epidemiológica indica que la actividad de los antioxidantes de las plantas pueden tratar o ayudar a prevenir el desarrollo de diversas enfermedades. Una especie con gran potencial como antioxidante es Curcuma longa. Sin embargo, diferentes técnicas de extracción pueden influir en los compuestos químicos aislados. Este estudio investigó la composición química y la actividad antioxidante de dos extractos de rizoma de C. longa: hidroetanólico, obtenido por agotamiento (HECLex); y se seca con un secador por pulverización (HECLsd). La composición fitoquímica se evaluó mediante GC/MS. La actividad antioxidante se evaluó mediante ensayos DPPH y FRAP. Se realizaron análisis de suelos y compuestos fenólicos totales. Los componentes principales de HECLex fueron ar-turmerona, γ-curcumene, α-turmerone y ß-sesquiphellandrene. Los componentes principales de HECLsd fueron ácido 9,12,15-octadecatrienoico, éster 2,3-bis ([trimetilsilil] oxi) propílico, verrucarol y éter 1-monolinoleoilglicerol trimetilsilil. HECLsd tenía niveles significativamente más altos de compuestos fenólicos y mayor capacidad antioxidante en comparación con HECLex. En conclusión, los procesos de preparación de los rizomas de C. longa alteran los componentes químicos y consecuentemente su actividad biológica.

Research progresses in the biosynthesis of curcuminoids / 生物工程学报

Curcuminoids are rare diketone compounds in plants and can be found in the rhizome of Curcuma longa as well as other Zingiberaceae and Araceae. Curcuminoids have been widely used in food and medical area owing to the yellow colors, as well as the antioxidant and many other pharmacological activities. Curcuminoids are a mixture of compounds containing curcumin, demethoxycurcumin and bisdemethoxycurcumin, which have distinct benzene ring substituents. Currently, curcuminoids are exclusively produced through plant extraction, which do not satisfy the meeting of the market demand. Empowered with new synthetic biology tools and metabolic engineering strategies, there is renewed interest in production of curcuminoids using microorganisms. Heterologous production of curcuminoids has been achieved using Escherichia coli, Yarrowia lipolytica, Pseudomonas putida and Aspergillus oryzae via engineering of curcuminoids biosynthesis pathway. In this review, we first describe the biological activities and various applications of curcuminoids. Next, we summarize the biosynthetic pathway of curcuminoids in Curcuma longa and discuss the catalytic mechanisms of curcumin synthases. Then, we thoroughly explore recent advances in the use of distinct microorganisms for the production of curcuminoids with a special focus on metabolic engineering strategies. Finally, we prospect the microbial production of curcuminoids by highlighting some promising techniques and approaches.

Biological effects of formulation containing curcuminoids and Bidens Pilosa L. in oral carcinoma cell line

Abstract: FITOPROT, which contains curcuminoids and Bidens pilosa L. extract, is an innovative mucoadhesive formulation indicated for the topical treatment of chemoradiotherapy-induced oral mucositis (OM) in patients with advanced and visible oral squamous cell carcinoma. The formulation is used as a mouthwash directly on tumor tissue of patients with advanced neoplasms, without triggering cancer cell proliferation or tumor invasiveness. Thus, the aim of this study was to evaluate the biological effects of FITOPROT on an oral squamous cell carcinoma cell line (SCC-4). The viability of SCC-4 cells was assessed after exposure to FITOPROT using MTT reduction assay. The effects of the mucoadhesive formulation on cell cycle progression and cell death parameters were evaluated using flow cytometry. In addition, the inflammatory profile of the tumor cells was evaluated using the cytometric bead array (CBA) assay. FITOPROT promoted a concentration-dependent decrease in cell viability and cell cycle arrest at the G2/M phase (p < 0.05). Mitochondrial membrane potential was also altered after exposure to the formulation (p < 0.05), in parallel with a reduction in VEGF and IL-8 production (p = 0.01 and p = 0.05, respectively). In summary, the results indicate that FITOPROT reduces SCC-4 cell viability, promotes cell cycle arrest, modulates mitochondrial membrane potential, and exhibits antiangiogenic and anti-inflammatory properties, thus indicating its potential for topical use in patients with OM and visible tumors in the mouth.

Breeding of a new cultivar "Chuanjianghuang 1" of Sichuan Dao-di herbs Curcumae Longae Rhizoma and Curcumae Radix / 中国中药杂志

The systematic breeding method was adopted to breed a new good cultivar of Curcuma longa, named "Chuanjianghuang 1". From 2014 to 2015, two consecutive years of multi-point test were carried out in Shuangliu, Chongzhou and Wenjiang. The biological characters, phenology, agronomic characters, yield and quality indexes of "Chuanjianghuang 1" were comprehensively evaluated. The results showed that compared with local traditional species, the rhizome yield of the new cultivar "Chuanjianghuang 1" increased by 20.61%.The average content of volatile oil was higher than 24.17% and the average content of curcumin in root tuber was higher than 26.62%. The yield of root tuber increased by 54.59%.The average content of volatile oil is higher than 36.28% and the average content of curcuminoids is higher than 25.31%. Compared with "Huangsi Yujin 1", "Chuanjianghuang 1" increased the average yield of rhizome by 123.68%,the volatile oil increased by an average of 7.69%and the curcumin content increased by an average of 58.23%. The average content of volatile oil is higher than 52.82% and the average content of curcuminoids in root tuber was higher than 38.34%. The new variety "Chuanjianghuang 1" has better yield than the local traditional species, and the internal quality of rhizome and root tuber is better. Compared with "Huangsi Yujin 1", the yield of rhizome is significantly increased, and the internal quality of rhizome and root tuber is better, especially the content of curcumin in rhizome and curcuminoids in root tuber is significantly higher than that of "Huangsi Yujin 1". "Chuanjianghuang 1" is high yield, good quality, good stability and strong adaptability, which is suitable for cultivation and promotion in Chengdu Jinma River Basin, such as Shuangliu, Chongzhou, Wenjiang.

Efeito de análogos de curcumina, irradiados ou não por LED, como agentes antimicrobianos e indutores de proliferação e migração celular / Effect of curcumin analogues, irradiated or not by LED, as antimicrobial agents and inducers of cell proliferation and migration

O tratamento endodôntico de dentes permanentes jovens com infecções pulpares/periapicais antes de completar a rizogênese ainda é um desafio para a Endodontia e a Odontopediatria. Relatos científicos têm mostrado que a curcumina (CUR), um fitoquímico polifenólico, apresenta diversas propriedades terapêuticas, entre as quais, amplo espectro de ação antimicrobiana e a capacidade de induzir a proliferação e migração celular. Além disso, devido à sua capacidade excitatória na presença de luz, a CUR também tem sido utilizada como fotossensibilizante em terapia fotodinâmica associada ao LED (light emitting diode), promovendo aumento dos seus efeitos biológicos. Uma forma de aumentar seu potencial terapêutico e reduzir algumas limitações do uso da CUR é a síntese de análogos a partir de pequenas modificações químicas na estrutura original, entretanto, mantendo sua capacidade fotossensibilizante. O objetivo desse estudo foi avaliar a ação antimicrobiana e antibiofilme de análogos de curcumina sob a influência ou não do LED sobre microrganismos de interesse endodôntico e sua influência sobre a viabilidade, proliferação e migração de fibroblastos da linhagem L-929. Uma série de compostos análogos de CUR (PCR-4 H, PCR-3 OH, PCR-4 OH, PCR-3 OCH3, PCR-4 OCH3, PCR-3 acetil, PCR-4 acetil) foram sintetizados pela metodologia de Pabon. A atividade antimicrobiana da CUR e seus análogos foi determinada pelo ensaio de Concentração Inibitória Mínima (CIM) e Concentração Bactericida Mínima (CBM) sobre Streptococcus mutans, Lactobacillus casei, Actinomyces israelii, Enterococcus faecalis e Fusobacterium nucleatum, sob a ação ou não do LED InGaN (nitreto de gálio e índio, com potência de saída de 100 mW/cm², ponta do LED com área de 0,78 cm², 60 s). A curcumina e seu análogo com melhor efeito antimicrobiano (PCR-3 OH) foi avaliado sobre o biofilme inicial (72h) e maduro (1 semana) dessas espécies em microplacas e sobre biofilmes multiespécies formados em túbulos dentinários por contagem das UFC/mL e por microscopia confocal, respectivamente, sob ação ou não do LED. Também foram avaliados quanto à citotoxicidade e a capacidade de induzir proliferação e migração em fibroblastos, por meio de ensaios de metiltetrazólio, azul de tripan e azul de Coomassie, respectivamente. Os dados foram avaliados estatisticamente (p<0,05). Dos 7 análogos de curcumina sintetizados, PCR-3 OH foi o único composto que apresentou atividade bactericida quando testado sobre as bactérias de interesse endodôntico selecionadas. Seu efeito foi potencializado na presença do LED, variando entre as espécies bacterianas. A curcumina teve efeito bactericida para as espécies S. mutans, A. israelii, L. casei e F. nucleatum, e em algumas delas, foi independente do LED. Ambos os compostos reduziram o crescimento dos biofilmes iniciais ou maduros, independente do LED. Entretanto, quando irradiados, o efeito dos compostos variou de acordo com a espécie bacteriana, sendo que A. israelii e S. mutans foram os mais afetados. Ambos os compostos reduziram significativamente os biofilmes multiespécies quando comparados ao controle sem tratamento, sendo que melhor efeito foi observado para PCR-3 OH. A curcumina foi considerada citocompatível a partir de 0,039µg/mL e PCR-3 OH a partir de 0,019 µg/mL. Houve redução significativa na viabilidade celular quando os compostos foram irradiados com LED nas concentrações 0,039 e 0,019 µg/mL. O LED, dentro dos parâmetros testados, reduziu significativamente a viabilidade, a proliferação e a migração celular, independente do composto ou tempo de exposição. Conclui-se que PCR-3 OH apresentou atividade bactericida e sobre biofilmes simples e multiespécies de bactérias de interesse endodôntico superior à CUR, principalmente sob ação do LED. Entretanto, sua citocompatiblidade foi inferior à da CUR. A presença do LED afetou a viabilidade, proliferação e migração dos fibroblastos, mostrando que os parâmetros utilizados para fins antimicrobianos não foram adequados para aplicação em células eucarióticas(AU)

Endodontic treatment of young permanent teeth with pulp / periapical infections before completing rhizogenesis is still a challenge for Endodontics and Pediatric Dentistry. Scientific reports have shown that curcumin (CUR), a polyphenolic phytochemical, has several therapeutic properties, including a broad spectrum of antimicrobial action and the ability to induce cell proliferation and migration. In addition, due to its excitatory capacity in the presence of light, CUR has also been used as a photosensitizer in photodynamic therapy associated with LED (light emitting diode), promoting an increase in its biological effects. One way to increase its therapeutic potential and reduce some limitations of the use of CUR is the synthesis of analogues from small chemical modifications in the original structure, however, maintaining its photosensitizing capacity. The aim of this study was to evaluate the antimicrobial and antibiofilm action of curcumin analogues under the influence or not of LED on microorganisms of endodontic interest and their influence on the viability, proliferation and migration of L-929 fibroblasts. A series of CUR analog compounds (PCR-4 H, PCR-3 OH, PCR-4 OH, PCR-3 OCH3, PCR-4 OCH3, PCR-3 acetyl, PCR-4 acetyl) were synthesized by Pabon's methodology. The antimicrobial activity of CUR and its analogs was determined by the Minimum Concentration Inhibitory (CIM) and Minimum Bactericidal Concentration (CBM) assay on Streptococcus mutans, Lactobacillus casei, Actinomyces israelii, Enterococcus faecalis and Fusobacterium nucleatum, with or without the InGaN LED (gallium and indium nitride, with output power of 100 mW / cm², LED tip with an area of 0.78 cm², 60 sec). Curcumin and its analog with the best antimicrobial effect (PCR-3 OH) were evaluated on the initial (72h) and mature (1 week) biofilm of these species in microplates and on multispecies biofilms formed in dentinal tubules by counting CFU / mL and by confocal microscopy, respectively, under the action or not of the LED. They were also evaluated for cytotoxicity and the ability to induce proliferation and migration in fibroblasts, using methyltetrazolium, trypan blue and Coomassie blue assays, respectively. The data were evaluated statistically (p <0.05). Of the 7 curcumin analogues synthesized, PCR-3 OH was the only compound that showed bactericidal activity when tested on selected bacteria of endodontic interest. Its effect was enhanced in the presence of LED, varying between bacterial species. Curcumin had a bactericidal effect for the species S. mutans, A. israelii, L. casei and F. nucleatum, and in some of them, it was independent of the LED. Both compounds reduced the growth of the initial or mature biofilms, regardless of the LED. However, when irradiated, the effect of the compounds varied according to the bacterial species, with A. israelii and S. mutans being the most affected. Both compounds significantly reduced multispecies biofilms when compared to the untreated control, with the best effect being observed for PCR-3 OH. Curcumin was considered cytocompatible from 0.039 µg / mL and PCR-3 OH from 0.019 µg / mL. There was a significant reduction in cell viability when the compounds were irradiated with LED at concentrations of 0.039 and 0.019 µg / mL. The LED, within the parameters tested, significantly reduced cell viability, proliferation and migration, regardless of the compound or time of exposure. It is concluded that PCR-3 OH showed bactericidal activity and on simple and multispecies biofilms of bacteria of endodontic interest superior to CUR, mainly under the action of LED. However, its cytocompatibility was lower than that of the CUR. The presence of the LED affected the viability, proliferation and migration of fibroblasts, showing that the parameters used for antimicrobial purposes were not suitable for application in eukariotic cells(AU)

The Cytotoxic Constituents of Betula platyphylla and their Effects on Human Lung A549 Cancer Cells

During the screening for cytotoxic compounds from plants grown in Korea, Betula platyphylla (BP) showed potent activity against the adenocarcinomic human alveolar basal epithelial A549 cell line. To identify the cytotoxic components from BP, the CH₂Cl₂ fraction with the most significant cytotoxic effect was applied to the column chromatographies. Seven compounds were isolated: lupeol (1), betulinic acid (2), (−)-rhododendrol (3), platyphyllenone (4), platyphyllone (5), (−)-centrolobol (6), and oleanolic acid (7). Among them, three diarylheptanoids (4 – 6) exhibited cytotoxicity toward A549 cells. Especially, 50 µM of 4 reduced A549 cell viability to 18.93 ± 0.82% compared to control (100.00 ± 21.48%). Lactate dehydrogenase (LDH) leakage and intracellular reactive oxygen species (ROS) production were also induced by 50 µM 4. This is the first report on the cytotoxic effect of BP-derived diarylheptanoids 4–6 against A549 cells. The compound 4 may be useful for the development of early hit compounds for non-small cell lung carcinoma, but the consideration about selectivity of 4 is required since 4 also showed the cytotoxicity in the human normal lung epithelial BEAS-2B cell line.

Identification and characterization of major constituents in Juglans mandshurica using ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-ESI-Q-TOF/MS) / 中国天然药物

The present study was designed to identify and characterize the major constituents in Juglans mandshurica Maxim. A simple, efficient and sensitive ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-ESI-Q-TOF/MS) method was established and validated under positive and negative ion modes. The separation was performed on a Waters ACQUITY UPLC BEH C column (2.1 mm × 100 mm, 1.7 μm) by gradient elution with a mobile phase (Phase A: 0.1% aqueous formic acid solution, Phase B: 0.1% formic acid acetonitrile solution). A total of 165 compounds were rapidly selected by Targeted and Non-Targeted Peak Finding approaches, and then tentatively identifled by comparing with reference substances or inferred through mass spectrometry fragment ion analysis and literature data. These compounds included 68 naphthalenequinones, 20 diarylheptanoids, 29 flavonoids, 20 triterpenes, and 28 phenolic acids. In conclusion, the present study provided an effective approach to identifying components in complex matrices of herbal medicines such as Juglans mandshurica Maxim.

Identification and characterization of major constituents in Juglans mandshurica using ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-ESI-Q-TOF/MS) / 中国天然药物

The present study was designed to identify and characterize the major constituents in Juglans mandshurica Maxim. A simple, efficient and sensitive ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-ESI-Q-TOF/MS) method was established and validated under positive and negative ion modes. The separation was performed on a Waters ACQUITY UPLC BEH C column (2.1 mm × 100 mm, 1.7 μm) by gradient elution with a mobile phase (Phase A: 0.1% aqueous formic acid solution, Phase B: 0.1% formic acid acetonitrile solution). A total of 165 compounds were rapidly selected by Targeted and Non-Targeted Peak Finding approaches, and then tentatively identifled by comparing with reference substances or inferred through mass spectrometry fragment ion analysis and literature data. These compounds included 68 naphthalenequinones, 20 diarylheptanoids, 29 flavonoids, 20 triterpenes, and 28 phenolic acids. In conclusion, the present study provided an effective approach to identifying components in complex matrices of herbal medicines such as Juglans mandshurica Maxim.

Nanopartículas lipídicas sólidas encapsulando curcuminoides (NLS-CT): estudos in vitro e in vivo / Solid lipid nanoparticles encapsulating curcuminoids (SLN-TC): in vitro and in vivo studies

Objetivos: Etapa 1 - avaliar características organolépticas e físico-químicas de formulações tópicas contendo nanopartículas lipídicas sólidas encapsulando curcuminoides; Etapa 2 - avaliar a citotoxicidade das nanopartículas lipídicas sólidas e dos curcuminoides encapsulados em nanopartículas lipídicas sólidas ou não em cultura de células de fibroblastos e queratinócitos com ou sem serem submetidos a RI; avaliar a atividade alergênica dos curcuminoides encapsulados em nanopartículas lipídicas sólidas ou não encapsulados; Etapa 3 - avaliar a toxicidade aguda de uma formulação contendo curcuminoides encapsulados em nanopartículas lipídicas sólidas na pele e em órgãos-alvo de camundongos BALB após 21 dias de aplicação tópica; induzir radiodermite em camundongos BALB; avaliar o efeito de formulações tópicas contendo curcuminoides encapsulados em nanopartículas lipídicas sólidas na prevenção e no tratamento de radiodermite, em camundongos BALB. Método: Etapa 1 - inspeção visual, cor, sensibilidade ao tato e odor, quantificação do pH, análise do comportamento reológico e quantificação de ativo (curcuminoides) das formulações; Etapa 2 - avaliação da viabilidade celular de queratinócitos, fibroblastos e mastócitos, quantificação da % de liberação da enzima ?-hexosaminidade em mastócitos; Etapa 3 - avaliação do peso, consumo alimentar e comportamento dos animais; quantificação de marcadores sanguíneos de toxicidade renal (ureia e creatinina) e hepática (TGP, FA e proteínas totais); análises histológicas qualitativas do coração, fígado, rim, pulmão e pele; quantificação de colágeno na pele; analisar a probabilidade de desenvolvimento de radiodermite, em grupos independentes, após crescentes doses de radiação ionizante; quantificação de citocinas (IL-1?, IL-6, IL-10, KC e FNT-?) avaliação do grau de radiodermite. Resultados: Etapa 1 - as formulações permaneceram estáveis por três meses, sem alteração de características organolépticas e físico-químicas; aos seis meses a formulação mais concentrada ficou mais opaca e observou-se aumento do pH e da perda de curcumina e curcuminoides totais; Etapa 2 - os resultados mostraram que as nanopartículas lipídicas sólidas são mais citotóxicas para os queratinócitos do que para os fibroblastos nas doses avaliadas, apesar de serem menos citotóxicas que os curcuminoides não encapsulados; não se observou diferença na viabilidade destas células sem ou após radiação ionizante (2 Gy); as nanopartículas lipídicas sólidas contendo curcuminoides e os curcuminoides não encapsulados não estimularam a liberação de ?-hexosaminidase em mastócitos, sugerindo que a formulação com nanopartículas não possui propriedades alergênicas. Etapa 3 - a formulação tópica contendo nanopartículas lipídicas sólidas com 30 mg de curcuminoides não conferiu toxicidade local e nem aos órgãos-alvo; os animais não apresentaram perda ponderal, alterações comportamentais ou mudanças na ingestão alimentar ou hídrica; foi possível a indução de radiodermite a partir de 25 Gy, sendo 30 Gy a que apresentou maior probabilidade de desenvolvimento; os animais não apresentaram perda ponderal, redução do consumo alimentar e hídrico significativos; o painel de citocinas avaliado evidenciou que a pele responde ao tratamento de forma diferente do controle da radiação; não foi observado infiltrado inflamatório; a quantificação do colágeno mostrou grande variabilidade. Conclusões: Devido a uma toxicidade mínima do sistema nanocarreador desenvolvido, somos encorajados a realizar testes futuros para aplicações clínicas em dermocosmética e na prevenção e tratamento de lesões cutâneas ou osteoarticulares

Aims: Step 1 - to evaluate organoleptic and physicochemical characteristics of topical formulations containing solid lipid nanoparticles encapsulating curcuminoids; Step 2 - to evaluate the cytotoxicity of solid lipid nanoparticles and curcuminoids encapsulated in solid lipid nanoparticles or not in culture of fibroblast and keratinocytes cells without and after being submitted to IR; to evaluate the allergenic activity of encapsulated curcuminoids in solid or non-encapsulated lipid nanoparticles; Step 3 - to evaluate the acute toxicity of a formulation containing encapsulated curcuminoids in solid lipid nanoparticles on the skin and target organs of BALB mice after 21 days of topical application; to induce radiodermatitis in BALB mice; to evaluate the effect of topical formulations containing encapsulated curcuminoids in solid lipid nanoparticles in the prevention and treatment of radiodermatitis in BALB mice. Method: Step 1 - visual inspection, color, sensitivity to touch and odor, pH quantification, rheological behavior analysis and quantification of active (curcuminoids) of the formulations; Step 2 - evaluation of the cellular viability of keratinocytes, fibroblasts and mast cells, quantification of the release % of ?-hexosaminase enzyme in mast cells; Step 3 - evaluation of weight, food consumption and behavior of the animals, quantification of markers of renal toxicity (urea and creatinine) and hepatic (TGP, FA and total proteins), qualitative histological analysis of the skin, heart, liver, kidney and lung and quantitative analysis of collagen in the skin; analysis of the probability to developing radiodermatitis in independent groups after increasing doses of ionizing radiation; quantification of the cytokines (IL-1?, IL-6, IL-10, KC and TNF-?) and collagen, qualitative histological analyzis of the skin, and the degree of radiodermatitis. Results: Step 1 - the formulations remained stable for three months, without alteration of organoleptic and physicochemical characteristics; at six months the more concentrated formulation became more opaque and there was an increase in pH and loss of curcumin and total curcuminoids; Step 2 - the results showed that solid lipid nanoparticles are more cytotoxic for keratinocytes than for fibroblasts at the doses evaluated, although they were less cytotoxic than non-encapsulated curcuminoids; no significant difference was observed in the viability of these cells without or after ionizing radiation (2 Gy); the solid lipid nanoparticles containing curcuminoids and non-encapsulated curcuminoids did not estimulated ?-hexosaminidase release in mast cells, suggesting that the nanoparticle formulation does not have allergenic properties. Stage 3 - the topical formulation containing solid lipid nanoparticles with 30 mg curcuminoids did not confer local toxicity and nor to the target organs the animals did not showed any weight loss, behavioral changes or changes in food or water ingestion; the radiodermatitis induction was possible from 25 Gy, with the dose of 30 Gy being the most likely to develop; the animals had no significant weight loss, nor reduction in food and water ingestion, the cytokine panel evaluated showed that skin responds to treatment differently from radiation control, no inflammatory infiltrate was evident and the quantification of collagen showed great variability. Conclusions: Due to the minimal toxicity of the developed nanocarrier system, we are encouraged to perform future tests for clinical applications in dermocosmetic and in the prevention and treatment of cutaneous or osteoarticular lesions

Diagnostic ion filtering strategy for chemical characterization of Guge Fengtong Tablet with high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry / 中国天然药物

The present study was designed to characterize the chemical constituents of Guge Fengtong Tablet (GGFTT). Based on the chromatographic retention behavior, fragmentation pathways of chemical components and the published literatures, a diagnostic ion filtering strategy with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q-TOF/MS) was established to identify the multiple bioactive constituents of GGFTT. The rapid identification of forty-seven components, including 18 phenolic acids, 8 saponins, 14 gingerol-related compounds, and 7 diarylhepatonoids, was accomplished using this newly developed method. The coupling of HPLC-ESI-Q-TOF/MS with the diagnostic ion filtering strategy was useful and efficient for the in-depth structural elucidation of chemical compounds of GGFTT.

A new cyclic diarylheptanoid from the bark of Myrica rubra / 药学学报

To study the chemical constituents from the bark of Myrica rubra, fourteen compounds were isolated from the methanolic extract using various chromatographic techniques, including silica gel, Sephadex LH-20 and preparative HPLC. Their structures were identified on the basis of chemical properties and spectroscopic data, as 3, 5-dimethoxy-4-hydroxymyricanol (1), myricanol (2), myricanone (3), myricanol 11-sulfate (4), myricitrin (5), quercetin (6), quercetin-3-rhamnoside (7), tamarixol (8), uvaol (9), ursolic acid (10), taraxerol (11), myricadiol (12), β-sitosterol (13) and β-daucosterol (14). Among them, compound 1 is a new compound, named as 3, 5-dimethoxy-4-hydroxymyricanol, compounds 8, 9 were isolated from the genus Myrica for the first time.

A new dimeric diarylheptanoid from the rhizomes of Alpinia officinarum / 中国天然药物

AIM@#To study the chemical constituents of the rhizomes of Alpinia officinarum Hance.@*METHOD@#Compounds were isolated by repeated column chromatography, and their structures were elucidated on the basis of spectral analysis. The cytotoxic activities of these compounds were evaluated with the T98G and B16F10 cell lines by the MTT assay.@*RESULTS@#A dimeric diarylheptanoid, named alpinin B (1), along with three known diarylheptanoids were obtained, and their structures were identified as alpinin B (1), 1, 7-diphenyl-3,5-heptanedione (2), (4E)-1, 7-diphenylhept-4-en-3-one (3) and (4E)-7- (4-hydroxyphenyl)-1-phenylhept-4-en-3-one (4).@*CONCLUSION@#Compound 1 is a new dimeric diarylheptanoid. The biosynthetic pathway of 1 was speculated to originate from a Michael reaction between compounds 2 and 3. Compound 3 showed cytotoxicity against the human glioblastoma T98G cell line with IC50 of 27 μmol·L(-1).

Benzylideneacetophenone derivatives attenuate IFN-gamma-induced IP-10/CXCL10 production in orbital fibroblasts of patients with thyroid-associated ophthalmopathy through STAT-1 inhibition

The aim of the present study was to identify a new candidate anti-inflammatory compound for use in the active stage of thyroid-associated ophthalmopathy (TAO). Benzylideneacetophenone compound JC3 [(2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one] was synthesized based on a structural modification of yakuchinone B, a constituent of the seeds of Alpinia oxyphylla, which belongs to the ginger family (Zingiberaceae), has been widely used in folk medicine as an anti-inflammatory phytochemical. Orbital fibroblasts were primarily cultured from patients with TAO, and the potential of JC3 to suppress the interferon (IFN)-gamma-induced protein (IP)-10/CXCL10 production in these cells was determined. IFN-gamma strongly increased the level of IP-10/CXCL10 in orbital fibroblasts from patients with TAO. JC3 exerted a significant inhibitory effect on the IFN-gamma-induced increase in IP-10/CXCL10 in a dose-dependent manner; its potency was greater than that of an identical concentration of yakuchinone B with no toxicity to cells at the concentration range used. Moreover, the constructed dimer and trimer polystructures of JC3, showed greater potency than JC3 in suppressing the IFN-gamma-induced production of IP-10/CXCL10. JC3 significantly attenuated the IP-10/CXCL10 mRNA expression induced by IFN-gamma, and a gel-shift assay showed that JC3 suppressed IFN-gamma-induced DNA binding of signal transducer and activator of transcription-1 (STAT-1) in TAO orbital fibroblasts. Our results provide initial evidence that the JC3 compound reduces the levels of IP-10/CXCL10 protein and mRNA induced by IFN-gamma in orbital fibroblasts of TAO patients. Therefore, JC3 might be considered as a future candidate for therapeutic application in TAO that exerts its effects by modulating the pathogenic mechanisms in orbital fibroblasts.

A pair of sulfonated diarylheptanoid epimers from Kaempferia galanga / 中国天然药物

AIM@#To discover new bioactive constituents from Kaempferia galanga L. (Zingiberaceae).@*METHODS@#The extract of K. galanga was divided into the chloroform and water-soluble portions. The latter fraction was successively subjected to column chromatography over a D101 macroporous adsorption resin, MCI, Sephadex LH-20, and preparative HPLC to obtain two compounds.@*RESULTS@#Two novel sulfonated diarylheptanoid epimers, namely kaempsulfonic acids A (1) and B (2), were isolated from the rhizomes of K. galanga. Their structures were established by analysis of spectroscopic data. The absolute configurations of 1 and 2 were determined by the comparison of experimental electronic circular dichroism (ECD) spectroscopy and the computational calculation method, combined with Mo2(OAc)4 induced circular dichroism (ICD).@*CONCLUSION@#The isolates 1 and 2 are new compounds and their absolute configurations were determined for the first time.

Diarylheptanoid-myricanone isolated from ethanolic extract of Myrica cerifera shows anticancer effects on HeLa and PC3 cell lines: signalling pathway and drug-DNA interaction / 中西医结合学报

<p><b>OBJECTIVE</b>To test if myricanone (C21H24O5), a cyclic diarylheptanoid, has anticancer effects on two different cancer cell lines HeLa and PC3. The present study was conducted with a note on the drug-DNA interaction and apoptotic signalling pathway.</p><p><b>METHODS</b>Several studies like cytotoxicity, nuclear damage, annexin-V-fluorescein isothiocyanate (FITC)/propidium iodide (PI)-labelled apoptotic assay and cell cycle arrest, immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) were used following standard protocols. Circular dichroism (CD) spectroscopy was also done to evaluate whether myricanone effectively interacted with DNA to bring about conformational changes that could strongly inhibit the cancer cell proliferation.</p><p><b>RESULTS</b>Myricanone showed a greater cytotoxic effect on PC3 cells than on HeLa cells. Myricanone promoted G0/G1 arrest in HeLa cells and S phase arrest in PC3 cells. Nuclear condensation and annexin V-FITC/PI studies revealed that myricanone promoted apoptotic cell death. CD spectroscopic data indicated that myricanone had an interaction with calf thymus DNA that changed DNA structural conformation. RT-PCR and immunoblot studies revealed that myricanone activated the apoptotic signalling cascades through down-regulation of transcription factors like nuclear factor-κB (NF-κB) (p65), and signal transducers and activators of transcription 3 (STAT3); cell cycle regulators like cyclin D1, and survivin and other signal proteins like Bcl-2 and up-regulation of Bax, caspase-9 and caspase-3.</p><p><b>CONCLUSION</b>Myricanone induced apoptosis in both types of cancer cells by triggering caspase activation, and suppression of cell proliferation by down-regulation of NF-κB and STAT3 signalling cascades, which makes it a suitable candidate for possible use in the formulation of therapeutic agent for combating cancer.</p>

Antioxidative and cytotoxic properties of diarylheptanoids isolated from Zingiber officinale / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the antioxidant and cytotoxic properties of five diarylheptanoids (1-5) isolated from the rhizomes of Zingiber officinale.</p><p><b>METHOD</b>Various models such as scavenging superoxide anions and 1,1-diphenyl-2- picrylhydrazyl (DPPH) radicals, inhibiting lipid peroxidation, as well as protecting of rat pheochromocytoma (PC12) cells induced by hydrogen peroxide (H2O2) were employed to assay the antioxidative effects of the diarylheptanoids. The cytotoxicities of compounds 1-5 were measured with MTT assays.</p><p><b>RESULT</b>The test compounds (1-5) showed promising DPPH inhibitory activities, and compound 5 exhibited the strongest DPPH scavenging activity with an IC50 value of (22.6+/-2.4) micromol x L(-1). Compounds 1, 3 and 4 showed potential anti-peroxidative effects with inhibitory rates of (66.3+/-15.4)%, (68.7+/-15.8)% and (72.2+/-10.6)%, respectively, at 100 microg x mL(-1). It could be observed that compounds 1, 3 and 4 demonstrated significant neuroprotective activities in a dose-dependent manner. Moreover, compound 3 exhibited certain cytotoxicities against human chronic myelogenous leukemia cells (K562) and its adriamycin-resistant cells (K562/ADR) with IC50 values of (34.9+/-0.6), (50.6+/-23.5) micromol x L(-1), respectively.</p><p><b>CONCLUSION</b>In vitro results demonstrated that five diarylheptanoids (1-5) isolated from the roots of Z. officinale were capable of scavenging radicals, inhibiting lipid peroxidation and protecting PC12 cells against the insult by H2O2. Additionally, compound 3 could inhibit the growth of K562 and K562/ADR cells.</p>

Studies on chemical constituents in fruit of Alpinia oxyphylla / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents in fruit of Alpinia oxyphylla and their cytotoxicities on cancer cell lines.</p><p><b>METHOD</b>Compounds were isolated and purified by various column chromatographic methods. Their structures were determined by physico-chemical properties and spectral analyses. Compound cytotoxicity was assessed by the sulforhodamine B (SRB) assay.</p><p><b>RESULT</b>Eight compounds were obtained from Me2CO-H2O (70%) extract of the fruit of A. oxyphylla and their structures were identified as: (9E)-humulene-2, 3; 6, 7-diepoxide (1), 3(12), 7(13), 9(E)-humulatriene-2, 6-diol (2), (-)-oplopanone (3), yakuchinone A (4), yakuchinone B (5), tectochrysin (6), isovanillin (7), (2E, 4E)-6-hydroxy-2, 6-dimethylhepta-2, 4-dienal (8), and the cytotoxicities of compounds 1, 3-5 on cancer cell lines, A549, HT-29 and SGC-7901, were also investigated.</p><p><b>CONCLUSION</b>Compounds 1-3, 7, 8 were isolated for the first time from this genus and compounds 1, 3-5 exhibited no cytotoxicity against three cancer cell lines at a concentration of 10 mg x L(-1).</p>

Estudo de compostos diarílicos como potenciais agentes leishmanicidas: avaliação do efeito na biossíntese de esteróides / Study of diarylic compounds as potents leishmanicidal agents: evaluation of the effect in biosynthesis of steroids

Compostos diarílicos derivados da curcumina vêm sendo estudados pelo nosso grupo contra algumas espécies de Leishmania com resultados bastante promissores. Dando continuidade a este projeto, no presente trabalho foram estudados in vitro e in vivo derivados diarílicos sintéticos: diarilheptanóides e diarilpentanóides, contra contra promastigotas de L. braziliensis, L. chagasi e L. amazonensis e amastigotas axênicas de L. amazonensis. Nossos resultados in vitro mostraram que de uma maneira geral, os diarilheptanóides foram mais ativos que os diarilheptanóides contra as três espécies de Leishmania estudadas, e que funções oxigenadas nos anéis e uma cadeia alifática de maior número de carbonos são importantes para a atividade leishmanicida. O diarilheptanóide l (5-hidroxi-7-(4-hidroxi-3-metoxifenil)-1-4-metoxifenil)-1,4,6-heptatrien-3-ona), que foi o mais ativo nos experimentos in vitro, foi escolhido para dar continuidades aos experimentos. Nos ensaios de toxicidade in vitro utilizando-se macrófagos peritoniais de camundongos Balb/c, este composto não se mostrou deletério paras as células do hospedeiro, mesmo em concentrações 10 vezes maior que o equivalente ao seu IC50/24h=0,514mM. O efeito sobre a infecção de macrófagos por L. amazonensis, sugere uma toxicidade seletiva contra as amastigotas intracelulares. Além disto, foi observado um efeito no processo de interiorização dos parasitas nos macrófagos, possivelmente indicando alterações em moléculas de superfície do parasita. O estudo in vivo, mostrou que o composto foi eficaz, diminuindo o tamanho das patas dos camundongos Balb/c tratados experimentalmente com até três doses, quando comparados aos animais que não receberam tratamento ou que foram tratados com a Pentamidina, que foi a droga de referência em todos os experimentos. A análise do efeito do composto no metabolismo de ergosterol de L. amazonensis, mostrou mudanças significativas na biossíntese deste esteLmetilados e a inibição completa de sua síntese, permitindo supor ser esta via metabólica um potencial alvo para os compostos diarílicos.