中国姜黄属植物根茎中姜黄素类化合物的含量测定

在硅胶G板上,以正丁醉-26%氨水-无水乙醇(30:3:1)为展开剂,用薄层扫描法分离测定了中国姜黄属植物毛郁金Curcuma aromatica Salisb.,温郁金C. wenyujin Y. H. Chen et C.Ling(or C. aromatica cv. Wenyujin),莪术C. aeruginosa Roxb.,黄莪术C. zedoaria (Christm.)Rosc.,桂莪术C. kwangsiensis S. G. Lee et C. F. Liang,川郁金C. chuanyujin C. K. Hsich et H.Zhang,姜黄C. longa L.根茎中姜黄素(curcumin),去甲氧基姜黄素(demethoxycurcumin),双去甲氧基姜黄素(bisdemethoxycurcumin)和总姜黄素(curcuminoids)的含量,回收率97.07%～102.0%(n=6),变异系数为3.1%～5.0%。     

Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzheimer's disease

Curcuminoids (a mixture of curcumin, bisdemethoxycurcumin and demethoxycurcumin) share vital pharmacological properties possessed by turmeric, a well known curry spice, considered useful in Alzheimer's disease (AD). The aim of this study was to evaluate if curcuminoids possess acetylcholinesterase (AChE) inhibitory and memory enhancing activities. The in-vitro and ex-vivo models of AChE inhibitory activity were used along with Morris water maze test to study the effect on memory in rats. Curcuminoids inhibited AChE in the in-vitro assay with IC₅₀ value of 19.67, bisdemethoxycurcumin 16.84, demethoxycurcumin 33.14 and curcumin 67.69 µM. In the ex-vivo AChE assay, curcuminoids and its individual components except curcumin showed dose-dependent (3-10 mg/kg) inhibition in frontal cortex and hippocampus. When studied for their effect on memory at a fixed dose (10 mg/kg), all compounds showed significant (p < 0.001) and comparable effect in scopolamine-induced amnesia. These data indicate that curcuminoids and all individual components except curcumin possess pronounced AChE inhibitory activity. Curcumin was relatively weak in the in-vitro assay and without effect in the ex-vivo AChE model, while equally effective in memory enhancing effect, suggestive of additional mechanism(s) involved. Thus curcuminoids mixture might possess better therapeutic profile than curcumin for its medicinal use in AD.     

正交试验法优选姜黄的醇提工艺

目的优选和验证姜黄的醇提取工艺。方法以提取物中姜黄素的量、总姜黄素含量和干膏得率为评价指标,采用L9(34)正交试验,考察乙醇浓度、用量、提取时间、提取次数对姜黄中有效成分提取率的影响。结果最佳提取工艺为:用10倍量80%的乙醇提取,提取三次,每次1.5h。结论优选的提取工艺操作简单,重复性好,姜黄素及总姜黄素的提取率高。     

Reversed-phase High-performance Liquid Chromatography Method for Analysis of Curcuminoids and Curcuminoid-loaded Liposome Formulation

A simple, sensitive, precise and specific method for the determination of curcuminoids and curcuminoid-loaded liposome formulation was developed using reverse-phase high-performance liquid chromatography method. The analysis was performed isocratically on Zorbax Eclipse XDB-C18 column (150×4 mm, 5 μm), analytical column using UV detector and mobile phase consisting of 0.1% orthophosphoric acid and acetonitrile. The proposed method for curcuminoids was validated for linearity in the range from 50 to 300 ΅g/ml with correlation coefficient above 0.997. Intraday and interday precision studies showed the relative standard deviation less than 2%. The limit of detection and limit of quantitation values were 2.5 and 8.25 ΅g/ml, respectively. Forced degradation study for curcuminoids and liposomal curcuminoids sample was carried out and observed that proposed method was also suitable for finding degradation products in the sample. Proposed method was successfully applied to estimate curcuminoids content without any interference of other excipients from liposomal formulation. Therefore, the method developed is well suited for curcuminoids and its liposome estimation.     

Multi-layer polymeric implants for sustained release of chemopreventives

Poor oral bioavailability limits the use of many chemopreventives in the prevention and treatment of cancer. To overcome this limitation, we report an improvised implant formulation (“coated” implants) using curcumin, individual curcuminoids, withaferin A and oltipraz. This method involves the coating of blank polycaprolactone implants with 20–30 layers of 10–20% polycaprolactone solution in dichloromethane containing 0.5–2% of the test agent. The in vitro release showed that while oltipraz was released with almost zero-order kinetics over 8 weeks, curcumin, individual curcuminoids and withaferin A were released with some initial burst. The in vivo release was determined by grafting implants subcutaneously in A/J mice. When delivered by coated implants, oltipraz significantly diminished lung DNA adducts in mice treated with dibenzo[a,l]pyrene compared with sham treatment (28 ± 7 versus 54 ± 17 adducts/10⁹ nucleotides). Withaferin A also diminished DNA adducts, but it was insignificant. Curcumin and individual curcuminoids were ineffective. Analysis of lung, liver and brain by UPLC-fluorescence showed the presence of the three test curcuminoids indicating effectiveness of the implant delivery system. Further, based on its known antitumor activity in vivo, withaferin A given via the implants significantly inhibited human lung cancer A549 xenograft in athymic nude mice, while it was ineffective when the same total dose was administered i.p. and required over 2-fold higher dose to elicit effectiveness. Together, our data suggest that coated polymeric implants can accommodate heat-labile compounds, can furnish sustained release for long duration, and elicit DNA damage-inhibiting and anti-tumor activities.     

Demethoxycurcumin from Curcuma longa Rhizome Suppresses iNOS Induction in an in vitro Inflamed Human Intestinal Mucosa Model

Background: It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integralrole during intestinal inflammation, an important factor for colon cancer development. Natural compoundsfrom Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with variousbeneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has beenshown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microgliacells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinalmucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NOproduction of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitoryeffects on NO production of DMC at 65 μM for 24-96 h were assessed by monitoring nitrite levels. Expressionof iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in ourinflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS atmRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanismof action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest thatDMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.     

Curcumin analogs as potent aldose reductase inhibitors

In the present study, curcuminoids isolated from curcuma longa were demonstrated to possess inhibitory activities on bovine lens aldose reductase. In order to find more potent aldose reductase inhibitor, curcumin analogs were synthesized and evaluated for their ability to inhibit bovine lens aldose reductase enzyme. The results indicated that the compounds with tetrahydroxyl groups, 2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone (A(2)), 2,5-bis(3,4-dihydroxybenzylidene)cyclopentanone (B(2)), 1,5-bis(3,4-dihydroxyphenyl)-1,4-pentadiene-3-one (C(2)), and 3,5-bis(3,4-dihydroxybenzylidene)-4-piperidone (D(2)) showed remarkably potent inhibitory effects on aldose reductase with IC(50) of 2.9 microM, 2.6 microM, 3.4 microM, and 4.9 microM, respectively. The structure-activity relationship revealed that the curcumin analogs with ortho-dihydroxyl groups could form a more tight affinity with aldose reductase to exert more potential inhibitory activities.     

Revisiting curcumin chemistry part I: a new strategy for the synthesis of curcuminoids

A new strategy for the synthesis of curcuminoids is described involving the reaction of acetylacetone difluroboronite with an aromatic aldehyde in the presence of n-butylamine as catalyst. The new intermediate products, curcuminoid difluroboronites, of symmetrically substituted curcuminoids like curcumin and bisdemethoxycurcumin are stable, can be isolated and hydrolysed with aq. methanol at pH 5.8 to get the curcuminoids of high purity. The method is applicable for unsymmetrical curcuminoids like demethoxycurcumin also with some modification involving column chromatography. The intermediate curcuminoid difluroboronites, as also the natural β-diketone pongamol difluroboronite, prepared for the first time were characterized on the basis of physical and chemical properties and spectroscopic data. The advantage of using borontrifluoride to protect the enol group in acetylacetone over the generally used boric oxide is brought out. The importance of conducting biological activity studies using pure curcuminoids is explained.     

Curcuma increasing antitumor effect of Rhizoma paridis saponins through absorptive enhancement of paridis saponins

Rhizoma paridis saponins (RPS) played a good antitumor role in many clinical applications. However, low oral bioavailability limited its application. In this research, water extract of Curcuma (CW) significantly increased antitumor effect of Rhizoma paridis saponins (RPS). GC–MS was used to identify its polar composition. HPLC was applied for determination of the content of curcuminoids in CW. As a result, 47 analytes with 0.65% of curcuminoids were identified in CW. According to the in vivo anti-tumor data, the best proportion of curcuminoids in CW with RPS was 16:500 (w/w). Using this ratio, curcuminoids significantly increased absorption of RPS in the everted rat duodenum sac system. In addition, curcuminoids decreased the promotion of RPS on rhodamine 123 efflux. The effect of curcuminoids was similar to that of the P-gp inhibitor, cyclosporin A in combination with RPS. In conclusion, drug combination of water extract of Curcuma with RPS was a good method to increase the antitumor effect of RPS. This combination would be a potent anticancer agent used in the prospective application.     

姜黄地下部分的形态发育动态与药材品质形成的初步研究

目的：阐明药材郁金－姜黄的复杂关系,为优质高产栽培生育调控和制定科学合理的采收制度提供依据。方法：采用生长分析法考察姜黄,地下部分的形态发育和重量变化动态,及其与主要化学成分挥发油和总姜黄素含量的相关性。结果：将黄丝郁金的地下器官形态发育划分为五个时期,即根系发育期,根茎形成期,根茎膨大－块根形成期,根茎干物质积累－块根膨大期,块根干物质积累期。结论：药材黄丝郁金采挖的最佳时间可订为１２月中旬。