Curcumin Encapsulated into Biocompatible Co-Polymer PLGA Nanoparticle Enhanced Anti-Gastric Cancer and Anti-Helicobacter Pylori Effect

Background: The current disadvantages (high cost, toxicity, resistance) of chemotherapy for gastric cancer opted people for alternative therapy from natural source. Curcumin (natural product) possess multiple biological activities but low bio-availability limits their uses as therapeutic. The Nano-formulation of curcumin increased the bioavailability and productivity of anti-cancer and anti-bacterial properties. The present study was initiated to determine the anti-cancer and anti-bacterial effect of Nano curcumin against gastric cancer and H. pylori. Methods: Curcumin loaded PLGA nanoparticles (CUR-NPs) was prepared by single emulsion solvent evaporation method. The MIC were determined using agar dilution method to find the anti-H. Pylori activity of Nano curcumin. The cytotoxicity of Nano curcumin was evaluated by MTT assay and the apoptotic effect (cell cycle arrest and morphology change) was shown by PI staining and microscopy. Results: The MIC of nanocurcumin and curcumin for all four H. pylori strains were 8 µg/ml and 16 µg/ml respectively. The inhibition rate of gastric cancer cells after treatment with curcumin was increased from 6% to 67% for 24h, from 8% to 75% for 48h, from 10% to 83% for 72h. In case of nanocurcumin, the inhibition rate increased from 7% to 69% for 24h, 11% to 87% for 48h and 16% to 97% for 72h. The IC50 of curcumin and Nano-curcumin were 24.20 µM and 18.78 µM respectively for 72 h. The population of cells in sub-G0 population increased from 4.1% in the control group to 24.5% and 57.8% when treated with curcumin and nanocurcumin respectively. After 72h of treatment with nanocurcumin, the apoptotic cells population increased as compared to native curcumin treated cells. Conclusion: The Nano curcumin might be used as a potential therapeutics against gastric cancer and H. Pylori. There is need of further in vivo study in order to validate CUR-NPs activity.     

Efficacy of Curcumin in Combination with Intralesional Dexamethasone with Hyaluronidase in the Treatment of Oral Submucous Fibrosis: A Randomized Controlled Trial

Objective: The objective of this study was to determine the efficacy of curcumin in combination with  intralesional dexamethasone with hyaluronidase in the treatment of oral submucous fibrosis (OSF). Methods: This randomized, double blind, parallel design, clinical trial was conducted at B.P. Koirala Institute of Health Sciences, Nepal. Thirty-four patients with clinically diagnosed OSF were randomized into two groups (17 participants in each) with baseline treatment of intralesional dexamethasone with hyaluronidase for 6 weeks for the both. Curcumin (2gm/day) was provided to Group A (Test) and Group B (Control) received placebo. Interincisal mouth opening, tongue protrusion, cheek flexibility and visual analogue scale (VAS) scoring of burning sensation of oral mucosa was recorded at baseline, 6, 8 and 12 weeks follow-up and independent t-test was used to compare the improvements in two groups. Results: On comparing the 6 weeks and baseline values, in Group A and B the mean difference in mouth opening was 8.82±1.33 mm and 5.53±1.17 mm respectively (p<0.001), in cheek flexibility was 2.94±1.02 mm and 1.94±1.24 mm respectively (p=0.02) and in tongue protrusion was 6.23±1.48 and 3.65±1.37 mm respectively (p<0.001). The findings were consistent in the 8 weeks follow-up. In 12 weeks follow-up, on comparing with the baseline values, in Group A and B, the mean difference in mouth opening was 8.71±1.16 mm and 5.35±1.22 mm respectively (<0.001), ), in cheek flexibility was 2.81±1.01 mm and 1.76±1.35 mm respectively (p=0.02) and in tongue protrusion was 6.06±1.48 and 3.35±1.50 mm respectively (p<0.001). Both the arms showed 100% improvement in burning sensation in 6, 8 and 12 weeks follow-up. Conclusion: Curcumin in combination with intralesional dexamethasone with hyaluronidase is efficacious in the treatment of OSF.     

姜黄素促进高糖环境下骨髓间充质干细胞成骨分化的作用及机制研究

目的研究姜黄素对高糖环境下骨髓间充质干细胞(BMSCs)成骨分化的影响及可能机制。方法原代分离培养大鼠骨髓间充质干细胞,分为正常组、高糖组和高糖+姜黄素组。CCK-8检测细胞增殖;免疫荧光染色检测细胞NF-κB p65核转位; Western blot检测NF-κB p65核蛋白表达。成骨能力检测分为正常糖浓度成骨诱导组、高糖浓度成骨诱导组、高糖+姜黄素成骨诱导组,其中成骨诱导培养为每100 m Lα-MEM培养基中加入2 mmol/L谷氨酰胺、10 mmol/Lβ-甘油磷酸钠、10 nmol/L地塞米松、50 mg/L抗坏血酸。茜素红染色检测细胞钙结节形成,荧光定量PCR检测成骨相关基因Runx2和OCN mRNA表达。结果接种培养7 d,倒置显微镜下可见骨髓间充质干细胞集落,呈克隆性生长;传代培养以后细胞伸展为长梭形。CCK-8结果表明,与正常组比较,高糖组细胞1 d、3 d时增殖能力无显著性差异(P0.05); 5 d时与正常组比较,高糖组细胞增殖能力显著降低(P0.05); 1 d、3 d、5 d时姜黄素组与高糖组比较细胞增殖能力差异均无统计学意义(P0.05)。与正常组比较,高糖组细胞NF-κB p65活化入核增多,姜黄素组则抑制高糖浓度下细胞NF-κB p65核转位,Western blot显示姜黄素可抑制NF-κB p65核蛋白表达。各组细胞成骨诱导14 d后茜素红染色,正常组可见大量矿化结节,高糖组仅见少量矿化结节,而姜黄素处理可以明显促进高糖浓度下钙结节形成。PCR结果显示,各组细胞成骨诱导14 d后,与正常组比较,高糖组成骨分化相关基因Runx2、OCN mRNA表达显著降低,差异有统计学意义(P0.05);高糖+姜黄素组则可以促进高糖环境下骨髓间充质干细胞成骨分化相关基因Runx2、OCN mRNA表达,差异有统计学意义(P0.05)。结论姜黄素能促进高糖环境下骨髓间充质干细胞成骨分化,其机制可能与抑制高糖浓度下细胞NF-κB p65活化相关。     

Anti-Cancer Effects of Traditional Medicinal Herbs on Oral Squamous Cell Carcinoma

Backgrounds: Oral squamous cell carcinoma (OSCC) is among the most frequent oral cancers in individuals under 40. Documents have endorsed that a diet enriched with fruit and vegetables can banish the risk of developing major cancers. This study aimed to evaluate the effects of different concentrations of four medicinal herbs including saffron, ginger, cinnamon and curcumin on OSCC cell line. Methods: Having obtained the aqueous extract of the four herbs, they were administered on OSCC cell lines per se and in dual, triple, and quadruple combinations. Their effects were measured in different concentrations and in 24 and 48 hours by using MTT assay. Results: The minimum and maximum effective concentrations were respectively 108 and 217 mg/ml for curcumin with IC30 of 77mg/ml, 108 and 270 mg/ml for ginger with IC30 of 58 mg/ml, 2 and 10 mg/ml for saffron with IC30 of 1.9 mg/ml, and 5 and 40 mg/ml for cinnamon with IC30 of 3.3 mg/ml. The best effect of the combinations was seen for cinnamon-saffron after both 24 and 48 hours and the four herbs combination after 48 hours. Conclusion: Although all the four herbs were effective on OSCC cell line, the strongest extract was saffron, followed by cinnamon. Combination of cinnamon-saffron and combination of the four herbs showed maximum effects. These findings suggest that traditional medicinal herbs may potentially contribute to oral cancer treatment; providing new windows for the development of new therapeutic strategies for OSCC.     

Comparison of the protective effects of curcumin and caffeic acid phenethyl ester against doxorubicin-induced testicular toxicity

Whether testicular toxicity is mediated by matrix metalloproteinases (MMPs) is an important question that has not been examined. This study investigated the suppressive effect of curcumin and caffeic acid phenethyl ester (CAPE) on oxidative stress, apoptosis, and whether MMPs mediate doxorubicin (DOX)-induced testicular injury. Male rats were randomly divided into eight groups (n = 8 per group). The groups were as follows: sham, dimethyl sulphoxide (100 µL), DOX (3 mg/kg), CAPE (2.68 mg/kg), curcumin (30 mg/kg), DOX+CAPE (3 mg/kg DOX and 2.68 mg/kg CAPE), DOX+curcumin (3 mg/kg DOX and 30 mg/kg curcumin) and DOX+CAPE+curcumin (3 mg/kg DOX, 2.68 mg/kg CAPE and 30 mg/kg curcumin). Injections were administered daily for 21 days. The oxidative stress, MMPs, proinflammatory cytokines and apoptotic markers in the DOX group were higher than the sham group (p < .05); these measures were lower in the groups treated with CAPE and curcumin together with DOX compared with the DOX group (p < .05). The results showed that MMPs mediated DOX-induced testicular injury, but CAPE and especially curcumin suppressed testis injury and cell apoptosis by suppressing DOX-induced increases in MMPs, oxidative stress and proinflammatory cytokines. However, curcumin exhibited more pronounced effects than CAPE in terms of all studied parameters.     

基于传统性效及现代研究的姜黄质量标志物分析

姜黄为我国传统中药,味辛、苦,性温,具有破血行气、通经止痛之功效,其用药历史悠久,最早收载于《新修本草》。对姜黄化学成分及主要药理活性进行总结,并基于传统性效及现代研究两方面对姜黄质量标志物进行预测分析。建议对姜黄的芳姜黄酮、α-姜黄酮、β-姜黄酮、姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素及黄酮类等成分进行定性、定量分析,进一步开展其所含的萜类和甾醇类等成分化学物质组的深入研究,为明确姜黄的质量标志物和姜黄质量评价研究提供科学依据。     

The effects of curcumin supplementation on body mass index,body weight,and waist circumference in patients with nonalcoholic fatty liver disease: A systematic review and dose–response meta‐analysis of randomized controlled trials

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver‐related morbidity; its prevalence is elevating due to the rising epidemic of obesity. Several clinical trials have examined the effects of curcumin supplementation on anthropometric variables in NAFLD patients with inconclusive results. This dose–response meta‐analysis aimed to evaluate the impact of curcumin supplementation on body mass index (BMI), body weight, and waist circumference (WC) in patients with NAFLD. A systematic review of the literature was conducted using PubMed/Medline, ISI Web of Science, Scopus, Cochrane Library, EMBASE, Google Scholar, Sid.ir, and Magiran.com to identify eligible studies up to March 2019. A meta‐analysis of eligible studies was performed using the random‐effects model to estimate the pooled effect size. Eight randomized controlled trials with 520 participants (curcumin group = 265 and placebo group = 255) were included. Supplementation dose and duration ranged from 70 to 3,000 mg/day and 8 to 12 weeks, respectively. Curcumin supplementation significantly reduced BMI (weighted mean difference [WMD] = ?0.34 kg/m², 95% CI [?0.64, ?0.04], p < .05) and WC (WMD = ?2.12 cm, 95% CI [?3.26, ?0.98], p < .001). However, no significant effects of curcumin supplementation on body weight were found. These results suggest that curcumin supplementation might have a positive effect on visceral fat and abdominal obesity that have been associated with NAFLD.     

姜黄色素-共聚维酮共研磨粉体性质及溶出度研究

目的 以姜黄色素为模型药物，考察辅料共聚维酮在共研磨过程中的应用特性及共研磨产物提高难溶性药物姜黄色素体外溶出方面的可行性。方法 采用共研磨法，在姜黄色素粉末中分别加入0%、1%、3%共聚维酮，制成不同比例的共研磨物，通过激光粒度仪及扫描电子显微镜（SEM）对其粒径形态进行考察；运用差示扫描量热法（DSC）、SEM和X射线粉末衍射法（XRPD）鉴别药物在共研磨物中的物相状态；测定姜黄色素原料药、物理混合物和共研磨物在2种溶出介质中的体外溶出度，并考察其加速稳定性。结果 与原料药相比，共聚维酮共研磨物粉末粒径减小，吸湿性和DSC无明显变化；XRPD中姜黄色素主要峰强度有所减弱，结晶度降低；共研磨物中姜黄色素的主要成分溶出度显著提高，在加速条件下放置3个月后溶出未发生变化，稳定性较好。结论 共聚维酮作为新型辅料，其与姜黄色素共研磨后得到的产物能有效改善难溶性药物姜黄色素的溶出度，且稳定性较好；为提高难溶性药物的溶解度和口服生物利用度提供了一种可行的策略。     

Effect of new curcumin‐containing nanostructured lipid dispersions on human keratinocytes proliferative responses

This study describes the production and characterization of nanostructured lipid dispersions (NLDs) containing curcumin (CUR) as new tools for curcumin topical delivery. Four types of NLDs based on monoolein in association with different emulsifiers were produced: Na cholate and poloxamer 407 (NLD1), poloxamer alone (NLD2), the mixture of Na cholate and Na caseinate (NLD3) and Na cholate alone (NLD4). Morphology and dimensional distribution of lipid dispersions were investigated by cryo‐TEM and photon correlation spectroscopy (PCS). In vitro studies based on Franz cell, membrane nylon and stratum corneum–epidermis (SCE) were carried out to compare the four NLDs in terms of cytotoxicity in human keratinocytes and CUR diffusion. Our PCS studies showed differences in particles diameter among the different NLDs. In addition, cytotoxicity results in HaCaT cells evidenced that NLD1 and NLD2 were toxic at doses over 1 μm . Therefore, cryo‐TEM was determined only for NLD3 and NLD4 showing that CUR did not affect their structure. Diffusion measurement in SCE and nylon membrane evidenced that CUR had a time‐delayed release for NLD4. The ‘wound healing’ effect of NLD3 and NLD4 with and without CUR analysed keratinocytes in vitro, and a clear inhibition of cell proliferation/migration by CUR was observed. This effect was mediated by the inhibition of cyclin D1 expression as a consequence of the impaired NFkB activation. This study confirms the antiproliferative properties of CUR and evidenced a new possible model of CUR topical delivery for hyperproliferative cutaneous diseases such as psoriasis.     

Assessment of antibacterial and antifungal potential of Curcuma longa and synthesized nanoparticles: A comparative study

Curcumin nanoparticles were most recently considered in medical research because of their antibacterial properties. The main objective of the study was to develop the green synthesis and antibacterial activity of curcumin nanoparticles using Curcuma longa. The processing of curcumin nanoparticles was carried out after the collection, identification, and extraction of curcumin. The effect of a sample on the synthesis of nanoparticles, such as curcumin aqueous concentrations (5, 10, and 20 mg/ml) and curcumin nanoparticles (5, 10, and 20 mg/ml), and the antibacterial effect of these nanoparticles on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and the fungal strain Aspergillus niger. For examining antibacterial and anti-fungal activity disc diffusion method was performed, followed by the zone of inhibition. According to X-ray diffraction and scanning electron microscope analysis, nanoparticles have spherical shapes and size of 42.64 nm. Results showed that a high dose of 20 mg/ml curcumin nanoparticles have more antibacterial activity than curcumin extracts in E. coli as it showed the largest diameter of zone of inhibition as compared to other doses. Other bacterial and fungal strains also showed significant results but E. coli was most prominent. The biosynthesis of curcumin nanoparticles using an aqueous extract of C. longa is a clean, inexpensive, and safe method that has not been used any toxic substance and consequently does not have side effects. Since several pathogenic species have acquired antibiotic resistance, the combination of curcumin with various nanoparticles would be beneficial in the cure of pathogenic diseases.