Elucidating the molecular targets of Curcuma longa for breast cancer treatment using network pharmacology,molecular docking and molecular dynamics simulation

Background:To elucidate the molecular mechanisms of Curcuma longa(C.longa)in breast cancer treatment.Methods:Phytocompounds of C.longa were obtained from Dr.Duke’s Phytochemical and Ethnobotanical Database.Potential active targets were retrieved from Bindingdb,SEA and Swiss Target Prediction databases.Breast cancer targets were retrieved from the Therapeutic Target Database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were done using DAVID and KOBAS3.0 databases respectively.The Cytoscape software was used to construct the phytocompound-target-pathway network.The PyRx and Desmond software were utilized for molecular docking and molecular dynamics simulation respectively.Results:Out of one hundred and fifty-six phytocompounds,fifty-four modulated proteins involved in breast cancer.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated C.longa exerts its therapeutic effect through regulating several key pathways.Molecular docking analysis revealed that most phytocompounds of C.longa had a good affinity with the key targets.Molecular dynamics simulation showed that ethinylestradiol formed stable ligand-protein complexes.Conclusion:The results of this study will enhance our understanding of the potential molecular mechanisms by which C.longa inhibits breast cancer and lay a foundation for future experimental studies.

Zea-longa评分与改良Garcia评分应用于针刺治疗CIRI大鼠神经功能缺损评估的研究

目的比较Zea-longa评分与改良Garcia评分用于针刺治疗脑缺血再灌注损伤(cerebral ischemia reperfusion injury,CIRI)大鼠的神经功能缺损评估的稳定性、准确性。方法将60只SPF级SD大鼠随机分为假手术组、模型组、针刺组,每组20只。采用线栓法制备大鼠大脑中动脉闭塞模型,2 h后,将线栓拔出1 cm左右,建立CIRI模型。针刺组针刺“大椎”“百会”“水沟”,每12 h进行1次,共治疗7次。72 h后,分别采用Zea-longa评分与改良Garcia评分进行评价,每组选取10只大鼠行TTC染色,并测定脑梗死面积;分别分析和比较Zea-longa评分和改良Garcia评分与脑梗死面积的相关性。结果CIRI术后,大鼠均表现有一定程度神经功能的缺损症状,脑组织TTC染色可见脑梗死病灶。针刺治疗能显著减少脑梗死面积(P<0.05),并改善神经功能(P<0.05,P<0.01)。相关性分析发现,改良Garcia评分与脑梗死面积的r值为-0.647(P<0.01),而Zea-longa评分与脑梗死面积的r值为0.575(P<0.01);针刺与改良Garcia评分及脑梗死面积三者相关性分析r值为-0.522(P<0.05);而针刺与Zea-longa评分及脑梗死面积r值为0.495(P<0.05)。结论改良Garcia评分与Zea-longa评分均可用于CIRI评价研究及针刺疗效评估。在对CIRI大鼠进行感觉功能相关研究时可优先采用改良Garcia评分,偏向运动功能评估时可考虑与Zea-longa评分联合使用,能够比较全面地反映模型大鼠神经功能损伤的严重程度和治疗后的神经功能的恢复程度。

Hepatoprotective and immunomodulatory properties of aqueous extract of Curcuma longa in carbon tetra chloride intoxicated Swiss albino mice

Objective:To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl_4 intoxicated Swiss albino mice.Methods:first group of mice(n=5) received CCl_4 treatment at a dose of 0.5 mL/kg bw(i.p.) for 7 days.Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for IS days.The third group was given both the turmeric extract(for 15 days,orally) and CCl_4(for last 7 days,i.p.).The fourth group was kept as a control.To study the liver function,the transaminase enzymes(SGOT and SGPT) and bilirubin level were measured in the serum of respective groups.For assaying the immunotherapeutic action of Curcuma longa(C.longa),non specific host response parameters like morphological alteration,phagocytosis,nitric oxide release,myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups.Results:The result of present study suggested that CCl_4 administration increased the level of SCOT and SGPT and bilirubin level in serum.However,the aqueous extract of turmeric reduced the level of SGOT, SCFT and bilirubin in CCl_4 intoxicated mice.Apart from damaging the liver system,CCl_4 also reduced non specific host response parameters like morphological alteration,phagocytosis, nitric oxide release,myeloperoxidase release and intracellular killing capacity of peritoneal macrophages.Administration of aqueous extract of C.longa offered significant protection from these damaging actions of CCl_4 on the non specific host response in the peritoneal macrophages of CCl_4 intoxicated mice.Conclusions:In conclusion,the present study suggests that C.longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.

眼虫Astasia longa类核纤层蛋白基因的初步研究

利用PCR和克隆测序技术 ,对眼虫Astasialonga的核纤层蛋白 (lamin)基因进行了研究。参考多种相对较低等多细胞动物的已知序列 ,设计出扩增lamin基因尾部区的引物 ,扩增获得两个主要片段 :序列Ⅰ(6 5 0bp)和序列Ⅱ (797bp)。测序分析表明 ,序列Ⅱ包含序列Ⅰ ,并具有lamin基因尾部特征 (编码“CaaX”序列的四种密码子 +终止密码子 )

TC指数在改良LONGA线栓法局灶性脑缺血/再灌注动物模型制备中的应用

目的观察TC指数定位血管线栓法对大鼠局灶性脑缺血模型制备的影响。方法300只雄性SD大鼠随机分为预试验组30只、原始方法组120只(按LONGA氏血管线栓法)、改良方法组150只(按动物门齿根部T点距颈总动脉分叉点C点长短而定,简称TC指数定位法)；比较两种不同造模法对血管线栓局灶性脑缺血/再灌注实验大鼠的成功率及形态学的变化。结果TC指数定位法改良的LONGA氏血管线栓再灌注制模法,比原始的LONGA氏血管线栓法大鼠脑缺血/再灌注模型成功率高,直线相关分析及统计学上均具有显著性意义；形态学表现差异无显著性。结论TC指数定位法的LONGA氏血管线栓法大鼠脑缺血/再灌注模型是一种较好的制模方法,值得实验研究中推广应用。

Contraceptive effect of Curcuma longa (L.) in male albino rat

Aim:To study the contraceptive effect of the crude extracts of Curcuma longa in male albino rats.Methods:Rats were fed orally with Curcuma longa aqueous and 70% alcoholic extract for 60 days (500 mg·kg^-1·day^-1).Results:A reduction in sperm motility and density was observed in both the treated groups.Conclusion:Curcuma longa may have affected the androgen synthesis either by inhibiting the Leydig cell function or the hypothalamus pituitary axis and as a result,spermatogenesis is arrested.(Asian J Androl 2004 Mar;6:71-74)

Use of Support Vector Regression Based on Mean Impact Value Model to Identify Active Compounds in a Combination of Curcuma longa L.and Glycyrrhiza extracts

A support vector regression based on the mean impact value (MIV) model was constructed to identify the bioactive compounds inhibiting proliferation of He La cells in a combination of turmeric (Curcuma longa L.)and liquorice (Glycyrrhiza) extracts.The quantitative chemical fingerprint from 50 batches of turmeric and liquorice extracts was established using high performance liquid chromatography hyphenated to an ultraviolet visible detector.Qualitative results were obtained using ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.A total of 46 peaks (peaks 1–15 from turmeric and 16–46 from liquorice) were selected as "common peaks" for analysis.The inhibitory effect of the combined extracts on He La cells was measured by MTT (3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.It was found that 15 compounds (peaks:8,12,30,24,46,11,14,9,3,1,44,18,7,45 and 43)possessing high absolute MIV exhibited a significant correlation with the cytotoxicity against He La cells; most of these have already been confirmed with potential cytotoxicity in previous research.The important potential application of the present model can be extended to help discover active compounds from complex herbal medicine prior to traditional bioassay-guided separation.It is considered that this could be a useful tool for redeveloping herbal medicine based on the use of these active compounds.

Isolated Endophytic Fungi from the Plant <i>Curcuma longa</i>and Their Potential Bioactivity—A Review

Endophytes (both fungi and bacteria) represent a treasure house for bioactive compounds such as anticancer, immunomodulatory, antioxidant, antiparasitic, insecticidal etc. for use in the pharmaceutical and agrochemical industries. Endophytic population is greatly influenced by climatic conditions and location where the host plant grows. Curcuma longa L. (Turmeric) is a medicinal plant belonging to the Zingiberaceae family that is usually used as spice and preservative. Traditionally it is used to treat various conditions and symptoms such as digestive disorders, arthritis, cardiovascular conditions, cancer, bacterial infections etc. In recent times, there have been different discoveries on endophytic fungi and their biological activity from C. longa. But there is no comprehensive review on endophytic fungi of C. longa. The aim of this review is to analyze the published report based on the endophytic fungi to provide for the first time an updated information about their isolation from different tissues, their biological activities including the phytochemistry of C. longa. This will lead the way to forecast the missing link for future research work.

腐生型眼虫Astasia longa两种TIM同工酶cDNA的克隆和分析

利用 3′ RACE和 5′ RACE技术 ,从腐生型眼虫长变胞藻 (Astasialonga)克隆了磷酸丙糖异构酶(TIM)的两个同工酶cDNA全序列。分析表明 :它们分别编码定位于细胞质的胞质型TIM (cTIM)和定位于质体的质体型TIM (pTIM) ;后者的N端具有引导该酶定位到质体中去的典型“前导序列”。根据这些事实我们推测腐生型眼虫A .longa质体中可能存在功能性的TIM ,并进一步认为该质体可能不只是一般意义上的“叶绿体退化的残迹” 。

Difference of Curcumin Content in Curcuma longa L. (Zingiberaceae) Caused by Hybridization with Other Curcuma Species

Curcumin, which is traditionally known to have effects on various types of diseases in humans, is found in Curcuma longa L. Previous reports have indicated that the curcumin content varies between the different lines of this species. To clarify the differences in the amounts of curcumin between the lines, we investigated the outcomes of cultivation ex-periments with the hybridization or introgression between C. longa and other Curcuma species using the matK gene of chloroplast DNA (cpDNA) and the external transcribed spacer (ETS) of nuclear DNA (nrDNA). The results show that there is heterogeneity of the ETS and incongruence between the matK and the ETS phylogenetic trees, suggesting that hybridization and introgression had taken place in the diversification of the various lines of C. longa. Moreover, al-though all of the lines had the same cpDNA haplotype of C. longa, the lines of homogeneous C. longa had a high con-tent of curcumin, whereas the lines created by hybridization and introgression with other Curcuma species had a me-dium or low level. These results suggest that the difference of curcumin content among the various lines of C. longa was caused by hybridization and introgression with other Curcuma species.

Chronic Administration of <i>Curcuma longa </i>Extract Improves Spatial Memory-Related Learning Ability in Aged Rats by Inhibiting Brain Cortico-Hippocampal Oxidative Stress and TNF<i>&alpha;</i>

We studied on the effect of Curcuma longa extract on spatial learning-related memory ability of old rats in eight-arm radial maze task. Rats were randomly divided into two groups: one group was orally administered 100 mg/KgBW/day C. longa extract (CLE) dissolved in deionized water and the other group was administered the vehicle alone for 10 weeks. The rats were tested with the partially baited eight-arm radial maze to evaluate two types of spatial memory-related learning ability displayed by reference memory errors (RMEs) and working memory errors (WMEs). Chronic administration of CLE significantly decreased the number of RMEs and WMEs, concurrently with the decreases in the cortico-hippocampal levels of lipid peroxides (LPO) and tumor necrosis factor alpha (TNF-α). In a parallel set of experiments, CLE-pretreated rats of the same age group were subjected to hypoxia-reperfusion injury by carotid artery occlusion to induce oxidative stress in the brains in order to examine whether such an in vivo hypoxia-induced oxidative stress could be ameliorated by the extract. Again, the levels of LPO were significantly decreased in the cortico-hippocampal tissues of the CLE-fed hypoxic rats. The histology of the brains also revealed that the CLE-pretreated rats had retained improved cellular integrity. Finally, our results provide the evidence that oral administration of C. longa extract increases the defense against oxidative stress and proinflammatory TNF-α, concurrently with the improvement of memory-related brain cognitive ability of the aged rats.

Curcuma longa normalized cimetidine-induced pituitarytesticular dysfunction: Relevance in nutraceutical therapy

Background:The increasing incidence of chemically induced infertility is both a social threat and a threat to the continuation of life itself.Treatment or management therapy is often expensive.This study investigated the effects of acetone extract of a local plant(Curcuma longa)in a Wistar rat model of cimetidine‐induced pituitarytesticular dysfunction.Methods:Thirty‐five male Wistar rats were divided into 7 groups of 5 rats.After a phytochemical screening of an acetone extract of C.Longa,cimetidine and the extract at three doses,200,400 and 600 mg/kg,were orally co‐administered to the rats for 28 consecutive days.Comparisons were made(at P<0.05)against a control(2 mL/kg distilled water),a standard treatment group(cimetidine+50 mg/kg vitamin C),a toxic group(60 mg/kg cimetidine)and a group receiving extract alone.Results:Cimetidine administration was associated with deleterious alterations to sperm motility,sperm count and sperm viability,as well as derangements in the plasma levels of FSH,LH and testosterone(P<0.05).Both brain and testicular GSH and TBARS levels were significantly altered following cimetidine administration,and distortions were seen in the pituitary and testicular histoarchitecture.These changes were significantly normalized by co‐administration of graded doses of the extract,with an associated improvement of both pituitary and testicular histology.Conclusion:Acetone extract of C.Longa normalized cimetidine‐induced pituitarytesticular dysfunction in Wistar rats.This presents the extract as a potential nutraceutical choice against chemically induced reproductive toxicity.

Protective effects of Aristolochia longa and Aquilaria malaccensis against lead induced acute liver injury in rats

Objective: To investigate the protective effects of Aristolochia longa (A. longa) and Aquilaria malaccensis (A. malaccensis) on acute hepatotoxicity induced by lead in female albino rats. Methods: Twenty five (25) apparently healthy female Wistar rats were randomly divided into five groups of five rats in each: control, Pb, Pb + A. longa (Ar), Pb+ A. malaccensis (Aq), and Pb+ A. longa (Ar) + A. malaccensis (Aq) lead (100 mg/kg b.w.) as Pb (C2H3O2)2 added in their drinking water for 75 days. A. longa (rhizome powder at a dose of 10 g/kg of diet ) and A. malaccensis (heartwood powder at a dose 10 g/kg of diet) were added to the feed during the last 15 days of lead exposed in the animals. Results: Obtained results revealed that lead treatment caused a significant increase in serum GOT, GPT and ALP activities and in liver of MDA level and CAT activity. In contrast, it led to an decrease in the liver GOT, GPT and GST activities and in GSH level in rats. Also, the results clearly showed that lead causes alterations of hepatic tissue in comparison with controls. Our results showed that treatment with A. malaccensis and A. longa a partial correction of the previous parameters. The histological observations confirmed the hepatoprotection results by the biochemical parameters. Conclusions: Results demonstrated beneficial effects of A. longa and A. malaccensis treatment in Pb-induced oxidative stress and tissue damage in liver.

Development of a Molecular Marker to Identify a Candidate Line of Turmeric (Curcuma longa L.) with a High Curcumin Content

Dried and fresh rhizomes of the spice turmeric (Curcuma longa L.) are well known in traditional medicine, and curcu- min is widely used in various geographic regions. Although there are differences in the amount of curcumin within this species, identification of the candidate line by rhizome is difficult because of the relative simplicity of its morphological characteristics. To accurately identify lines of C. longa with a high content of curcumin, we analysed several sequences of chloroplast DNA. First, to determine the appropriate outgroup taxa in which to conduct infras-pecific analyses of C. longa, we reconstructed the molecular phylogenetic tree of C. longa and its allied species. The results showed that C. aromatica and C. zedoaria are closely related to C. longa. Next, to develop a molecular marker for identifying lines of C. longa with a high content of curcumin, a network analysis using chloroplast microsatellite regions was performed. Results showed that a unique haplotype within C. longa corresponds to the high curcumin content line. Therefore, the chloroplast microsatellite regions used for the analysis allowed us to determine the lines of this species with high cur- cumin content.

Determination of Cinnamic Acid in Stephania longa Lour. by HPLC

[Objectives] To establish a HPLC method for the quantitative determination of cinnamic acid in Stephania longa Lour. [Methods]The chromatographic column: Thermo BDS HYPERSIL C_(18)( 4. 6 mm × 250 mm,5 μm); mobile phase: acetonitrile-0. 1% phosphoric acid( 24∶ 76); flow rate: 1 mL/min; column temperature: 30℃; wavelength: 285 nm. [Results]The cinnamic acid was in a good linear relationship in the range of 0. 021 7-0. 076 μg,the sample recovery rate was 100. 46%,the RSD was 2. 20%,and the content was in the range of 0. 004%-0. 022%. [Conclusions] The method is simple,accurate and reproducible,and can be used for the quality control of S. longa Lour.

In Vitro Antioxidant and Free Radical Scavenging Activity of Curcuma longa, Acorus calamus and Camellia sinensis

The purpose of the current study was to determine the total phenolic and flavonoid content and total antioxidant activity of the Curcuma longa, Acorus calamus, and Camellia sinensis ethanolic extracts and their free radical scavenging activity. The study concluded that the Curcuma longa, Acorus calamus, and Camellia sinensis ethanolic extracts have a good source of phenolics, flavonoids, and antioxidant sources in turn which opens the high possibility of the extracts being used as food preservatives. The DPPH assay for scavenging free radicals showed that the IC50 value was above 123% of Curcuma longa ethanolic extract, 129.9% μg/ml of Acorus calamus ethanolic extract and 25% of Camellia sinensis ethanolic extracts shows very strong inhibition of the free radicals. Thus, comparing the DPPH assay for scavenging free radicals of Curcuma longa, Acorus calamus and Camellia sinensis ethanolic extracts with the positive control ascorbic acid, Curcuma longa and Camellia sinensis ethanolic extracts showed strong inhibition of the free radicals.

Evaluation of the Nutritional Status and Phytomedicinal Properties of Dried Rhizomes of Turmeric (<i>Curcuma longa</i>)

Turmeric (Curcuma longa) belongs to the family Zingiberaceae and has long been used traditionally for centuries as a spice and medicinal elixir. Hence, the present study aimed to profile the nutritional and phytomedicinal properties of the plant in order to justify its relevance in traditional phytomedicine and advocate its application in novel pharmacological products. Using standard methods (High Performance Liquid Chromatography, Gas Chromatography-Mass Spectroscopy and Atomic Absorption Spectrophotometry), the dried rhizomes were washed, pulverized and ethanol extracts subjected to proximate, phytochemical, vitamins, amino acid and mineral determinations. Data obtained were analyzed using student’s t-test in Statistical Package for the Social Sciences version 21. Determined proximate indices indicated moisture content of 9.55%, carbohydrate (57.30%), ash (24.70%), crude fiber (1.12%), proteins (2.15%) and fat (5.32%). Mineral composition analyses showed that C. longa rhizomes had higher contents of calcium, magnesium, potassium and sodium in parts per million (ppm) at 38.68 ± 0.114, 19.75 ± 0.001, 9.20 ± 0.002 and 7.06 ± 0.014 respectively. Amino acid profile revealed the presence of both essential and non-essential types with aspartate and glutamate in higher contents at 9.78 g/100 g and 9.65 g/100 g, respectively. Findings showed also the presence of vitamins A, C and D at 254.5 ± 2.19 mg/kg, 19.47 ± 0.16 mg/kg and 10.92 ± 0.92 mg/kg, respectively. Phytochemical analyses showed the presence of phenolic compounds with high retention times. This study thus revealed that C. longa possesses various nutritional and pharmacological/medicinal components in considerable quantities and can provide the body with basic nutrients for its therapeutic needs as well as secondary compounds with tremendous phytomedicinal potentials.

Growing <i>Curcuma longa</i>for Rhizome Production on Diverse Arable Soil Types in Cameroon: Agronomic and Microbial Parameters

The aim of this work is to assess soil types’ effect on the growth and production of Curcuma longa rhizomes. The Rhizome of Curcuma longa was grown in a greenhouse in pots for seven months on different soil types. Physico-chemical analyses of the different soils were carried out. Collar diameter, the height of the plants, and yield of rhizome were measured. Total microbial density, number of spores, and root colonization of arbuscular mycorrhizal fungi (AMF) from these soils were assessed. Results show that soils are sandy clay loam, clay sandy, clay, acidic (pH 4.16 to 6.62), and have a C/N ratio from 6.10 to 19.83. Nitrogen (N) is between 0.49 to 2.41 g/kg, available phosphorus (P) between 2 to 16 ppm, Organic matter (OM) from 14.6 to 51.4 g/kg. Total microbial density is between 2 to 16 × 106 Cell/mm3, number of AMF spores in situ between 4 to 67 spores/g of soil. The frequency of root colonization is between 47% to 78%. The average growth and rhizome production are between 5 to 15 g/plant. All the results obtained show that the soils with clay to sandy clayey loam texture, medium acidity (pH 5.5 - 6.6), low C content (7.3 - 9.6 g/kg), low N content (0.49 - 1.13 g/kg), good C/N ratio (<14), low to medium AMF sporulation (28 - 41 spores/g) and AMF root colonization between 55% to 78% are the most suitable for the cultivation and rhizome production of Curcuma longa in Cameroon.

Study of the Knowledge of Turmeric <i>Curcuma longa</i>) and Ginger (<i>Zingiber officinale</i>) in the Region of Daloa (Côte D’Ivoire)

Ginger and turmeric are two plants of the Zingiberaceaes family. They are used as spices and in the treatment of many diseases. Despite their importance, data on their knowledge and their uses are scarce. The objective of this work was to assess the knowledge and different uses of ginger and turmeric. A survey was carried out among saleswomen and consumers. The survey reveals that 100% of those surveyed knew about ginger, but fewer people (17.5%) knew about turmeric. The survey identified that ginger tastes more pungent (82.65%) than bitter (17.35%), whilst turmeric’s taste is bitterer (53.47%) rather than pungent (46.53%). Consumption differed between the two rhizomes, with ginger consumed fresh (90.22%) and turmeric dry (84.25%). Differences were also noted in their medicinal (40.66% for ginger and 32.15% for turmeric), nutritional (50.82% for ginger and 11.65% for turmeric) and cosmetic (8.63% properties for ginger and 56.2% for turmeric) uses. The vernacular names of the two rhizomes varied from one ethnic group to another.

Effect of Dietary Incorporation of <i>Curcuma longa</i>Powder on Haematology and Serological Properties of Guinea Pigs (<i>Cavia porcellus</i>)

The reduced efficiency of antibiotic growth promoters in livestock, and the unavoidable residual effects on livestock products such as egg, meat and milk have pushed researchers to rush towards the use of phytobiotics in animal feed. This study was conducted at the Teaching and Research Farm of the University of Dschang to evaluate the Effect of Cucurma longa powder as feed additive on hemato-serological parameters in Guinea pigs. A total of 120 three weeks old Guinea pigs (60 males and 60 females), with an average weight of 150 ± 20 g were used. The animals were randomly distributed into four treatments in a completely randomized design with 30 animals per treatment (15 males and 15 females). Four experimental treatments were used by adding 0%, 0.25%, 0.5% and 1% C. longa in the diet corresponding to R0, R0.25%, R0.5% and R1% respectively. At the 8th week of age, 12 Guinea pigs (6 males and 6 females) per treatment were fasted for 12 hours and sacrificed by cervical dislocation. Blood was rapidly collected from the jugular vein for the evaluation of haematological and biochemical parameters. Results revealed that the inclusion of Curcuma longa at 0.25% significantly (p < 0.05) increased the concentration of hematocrit, lymphocytes, monocytes, granulocytes and platelets. A significant decrease (p < 0.05) was observed in hemoglobin, red blood cells, white blood cells, serum lipids, globulin, AST, ALT, and urea. It was concluded that the use of Curcuma longa powder at 0.25% as feed additive positively regulates blood serum parameters of Guinea pigs.