Effect of curcumin on regulatory B cells in chronic colitis mice involving TLR/MyD88 signaling pathway

Curcumin (Cur) is a natural active phenolic compound extracted from the root of Curcuma Longa L. It has anti-inflammatory, anti-tumor and other pharmacological activities, and is commonly used to treat ulcerative colitis (UC). However, it is not clear whether curcumin regulates the function and differentiation of Breg cells to treat UC. In this study, mice with chronic colitis were induced by dextran sulfate sodium (DSS), and treated with curcumin for 12 days. Curcumin effectively improved the body weight, colonic weight, colonic length, decreased colonic weight index and pathological injury score under colonoscopy in mice with chronic colitis, and significantly inhibited the production of IL-1β, IL-6, IL-33, CCL-2, IFN-γ, TNF-α, and promoted the secretion of IL-4, IL-10, IL-13 and IgA. Importantly, curcumin markedly upregulated CD3⁻CD19⁺CD1d⁺, CD3⁻CD19⁺CD25⁺, CD3⁻CD19⁺Foxp3⁺Breg cells level and significantly down-regulated CD3⁻CD19⁺PD-L1⁺, CD3⁻CD19⁺tim-1⁺, CD3⁻CD19⁺ CD27⁺ Breg cells level. In addition, our results also showed that curcumin observably inhibited TLR2, TLR4, TLR5, MyD88, IRAK4, p-IRAK4, NF-κB P65, IRAK1, TRAF6, TAB1, TAB2, TAK1, MKK3, MKK6, p38MAPK, p-p38MAPK and CREB expression in TLR/MyD88 signaling pathway. These results suggest that curcumin can regulate the differentiation and function of Breg cell to alleviate DSS-induced colitis, which may be realized by inhibiting TLR/MyD88 pathway.     

Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II, and III purified from Turmeric powder

P-glycoprotein (Pgp, ABCB1) is an ATP-dependent drug efflux pump linked to development of multidrug resistance (MDR) in cancer cells. Previously [Biochem Pharmacol 2002;64:573-82], we reported that a curcumin mixture could modulate both function and expression of Pgp. This study focuses on the effect of three major curcuminoids--curcumin I, II and III purified from a curcumin mixture--on modulation of Pgp function in a multidrug resistant human cervical carcinoma cell line (KB-V1). The similar IC(50) values for cytotoxicity of curcuminoids of KB-V1, and KB-3-1 (parental drug sensitive cell line) suggest that these curcuminoids may not be substrates for Pgp. Treating the cells with non-toxic doses of curcuminoids increased their sensitivity to vinblastine only in the Pgp expressing drug resistant cell line, KB-V1, and curcumin I retained the drug in KB-V1 cells more effectively than curcumin II and III, respectively. Effects of each curcuminoid on rhodamine123, calcein-AM, and bodipy-FL-vinblastine accumulation confirmed these findings. Curcumin I, II and III increased the accumulation of fluorescent substrates in a dose-dependent manner, and at 15 microM, curcumin I was the most effective. The inhibitory effect in a concentration-dependent manner of curcuminoids on verapamil-stimulated ATPase activity and photoaffinity labeling of Pgp with the [(125)I]-iodoarylazidoprazosin offered additional support; curcumin I was the most potent modulator. Taken together, these results indicate that curcumin I is the most effective MDR modulator among curcuminoids, and may be used in combination with conventional chemotherapeutic drugs to reverse MDR in cancer cells.     

Mitochondrial metals as a potential therapeutic target in neurodegeneration

Transition metals are critical for enzyme function and protein folding, but in excess can mediate neurotoxic oxidative processes. As mitochondria are particularly vulnerable to oxidative damage due to radicals generated during ATP production, mitochondrial biometal homeostasis must therefore be tightly controlled to safely harness the redox potential of metal enzyme cofactors. Dysregulation of metal functions is evident in numerous neurological disorders including Alzheimer''s disease, stroke, Parkinson''s disease, Huntington''s disease, amyotrophic lateral sclerosis and Friedrich''s ataxia. This review describes the mitochondrial metal defects in these disorders and highlights novel metal-based therapeutic approaches that target mitochondrial metal homeostasis in neurological disorders.

Linked Articles

This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8     

注射用姜黄素脂质体过敏现象的初步研究

目的 比较3种不同粒径注射用姜黄素脂质体（CLI）引起的过敏反应,并判断可能的过敏反应类型。方法 将平均粒径约为70、100、130 nm的CLI （剂量为20 mg/kg,以姜黄素计）分别尾iv给予大鼠,分别于注射前,注射后10 min、7 d,眼眶采血,分离血清,ELISA法检测注射前后血清中过敏相关因子——补体C3a、C3b和C5a,组胺和抗体IgE、IgG、IgM的含量变化。将平均粒径约为100 nm的CLI和抗过敏药地塞米松（预处理2 h,2 mg/kg）联用给予大鼠,观察血清中补体C3a、C5a和组胺的含量变化。结果 给予3种粒径的CLI,血清中补体C3a、C3b、C5a和组胺含量均明显升高,与给药前比较差异具有统计学意义（P<0.01）;血清中抗体IgE、IgG、IgM的含量均无明显变化。预先给予地塞米松,在注射CLI前后C3a和C5a的含量无明显变化,组胺含量极低。结论 3种不同粒径CLI在体内引起的过敏反应一致,且可能是补体激活相关的假性过敏反应。     

Native and β-cyclodextrin-enclosed curcumin: entrapment within liposomes and their in vitro cytotoxicity in lung and colon cancer

With a view to improving the solubility and delivery characteristics of poorly water-soluble drugs, we prepared β-cyclodextrin-curcumin (βCD-C) inclusion complexes (hydrophilic curcumin) and entrapped both native curcumin (hydrophobic) and the complexes separately into liposomes; these were then assessed for in vitro cytotoxicity in lung and colon cancer cell lines. Optimization of curcumin entrapment within βCD was achieved, with the resultant βCD-C complexes prepared by methanol reflux. Inclusion complexes were confirmed using UV spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction. The water solubility of βCD-C complexes improved markedly (c.f. native curcumin) and successful entrapment of complexes into liposomes, prepared using a thin-film hydration approach, was also achieved. All the liposomal formulations were characterized for curcumin and βCD-C complex entrapment efficiency, particle size, polydispersity and stability at 2–8°C. Curcumin, βCD-C complex and their optimized liposomal formulations were evaluated for anticancer activity in lung (A-459) and colon (SW-620) cancer cell lines. All curcumin-containing formulations tested were effective in inhibiting cell proliferation, as determined via an MTT assay. The median effective dose (EC₅₀) for all curcumin formulations was found to be in the low µM range for both lung and colon cancer cell lines tested. Our results confirm that βCD inclusion complexes of poorly water soluble drugs, such as curcumin can be entrapped within biocompatible vesicles such as liposomes, and this does not preclude their anticancer activity.     

Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies

Sepsis is a complex disease that begins with an infectious disorder and causes excessive immune responses. Curcumin is considered as an active component of turmeric that can improve the condition in sepsis due to its anti‐inflammatory and antioxidant properties. PubMed, Embase, Google Scholar, Web of Science, and Scopus databases were searched. Searching was not limited to a specific publication period. Only English‐language original articles, which had examined the effect of curcumin on sepsis, were included. At first, 1,098 articles were totally found, and 209 articles were selected after excluding duplicated data; 46 articles were remained due to the curcumin effects on sepsis. These included 23 in vitro studies and 23 animal studies. Our results showed that curcumin and various analogs of curcumin can have an inhibitory effect on sepsis‐induced complications. Curcumin has the ability to inhibit the inflammatory, oxidative coagulation factors, and regulation of immune responses in sepsis. Despite the promising evidence of the therapeutic effects of curcumin on the sepsis complication, further studies seem necessary to investigate its effect and possible mechanisms of action in human studies.     

姜黄素的药理作用及其在眼科的应用研究进展

姜黄素是从姜黄中提取的活性单体成分，具有抗纤维化、抗肿瘤、抗炎症及抗微生物等多种药理作用．且无明显毒副作用。目前，姜黄素在眼科的应用也取得了一定的进展，包括抑制翼状胬肉成纤维细胞增生，抑制角膜和视网膜新生血管生成．抑制晶状体上皮细胞增殖，抑制视网膜色素上皮细胞增殖，预防白内障及防治增殖性玻璃体视网膜病变等。     

Diet-Induced Cognitive Deficits: The Role of Fat and Sugar,Potential Mechanisms and Nutritional Interventions

It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments.     

姜黄素对5-Fu化疗大鼠肠黏膜屏障保护作用的实验研究

目的：观察姜黄素在利用5-Fu化疗期间对大鼠肠黏膜屏障的保护功能的研究。方法：健康Wister大鼠60只随机分成Control组（20只）,5-Fu组（20只,5-氟尿嘧啶）,5-Fu＋Cur.组（20只,5-氟尿嘧啶＋姜黄素）,在实验的第2、4、6天监测各组大鼠的体重、内毒素、DAO、D-乳酸水平,第7天处死大鼠后取出大鼠回肠,并在光镜下观察肠黏膜组织结构病理变化。结果：与正常组相比,化疗组的体重明显下降（P〈0.05）;内毒素、血浆DAO、D-乳酸水平明显增高（P〈0.05）;肠组织病理学观察可见：肠黏膜明显萎缩,绒毛脱落,并伴有大量炎性细胞浸润。结论：姜黄素对5-Fu化疗期间肠黏膜屏障具有保护作用。     

Therapeutic Potential of Turmeric in Alzheimer's Disease: Curcumin or Curcuminoids?

Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple‐site‐targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.