Exploring dynamic biomedical algorithm of Eurycoma longifolia Jack and its bioactive phytochemicals: A review of pharmacokinetic and pharmacodynamic implications and future prospects

Eurycoma longifolia Jack(E.longifolia) is a well-recognized traditional herbal medicine that offers a wide dynamic range of biomedical applications including anti-osteoporotic, anticancer, anti-proliferative, anti-malarial, antimicrobial, antioxidant, aphrodisiac, antiinflammatory, anxiolytic, anti-diabetic, anti-rheumatism and anti-ulcer properties.This review aims to overview the pharmacokinetic and a pharmacodynamic algorithm of E.longifolia and its bioactive components.Analysis of pharmacokinetic profile revealed that E.longifolia exhibit higher bioavailability, high volume of distribution, slow elimination rate, and does not show inhibitory effects on cytochrome P450 isoenzymes.E.longifolia has been used, alone or in combination with other pharmacological agents, in the form of crude extracts, standard extracts, or decoctions of different plant parts(i.e., herbs, shrubs, stem, leaves, and roots) for the treatment of various ailments in animals and humans.Among various bioactive constituents, eurycomanone has been found to be the most remarkable, super-stable, versatile, and most potent phytochemical(isolated or extracted from root extracts) against various types of animals and human diseases.Based on its well-established pharmacokinetic and pharmacodynamic profiles, we suggested that E.longifolia can be a well-accepted complementary and alternative medicine for the treatment of different types of human ailments.

Effect of Eurycoma longifolia stem extract on uric acid excretion in hyperuricemia mice

OBJECTIVE Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia.The aim of this study is to explore the effect and mechanism of E.longifolia stem 70%ethanol extract(EL)and its active com⁃poundson uric acid excretion.METHODS Potassium oxonate(PO)induced hyperuricemia rats and adenine-PO induced hyperuricemia mouse model were used to evaluate the effects of EL.Ultra Performance Liquid Chromatography was used to determine the levels of plasma or serum uric acid and creatinine.Hematoxylin-eosin staining was applied to observe kidney pathological changes,Western blot⁃ting was applied to detect protein expression levels of uric acid transporters.Effects of constituents on urate uptake were tested in hU⁃RAT1-expressing HEK293T cells.RESULTS EL significantly reduced serum and plasma uric acid levels at dosages of 100,200 and 400 mg·kg^-1 in hyperuricemia rats and mice,and increased the clearance rate of uric acid and creatinine,improved therenal pathological injury.The protein expression levels of urate reabsorption transporter 1(URAT1)and glucose transporter 9 were down-regulated while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treat⁃ment.The diterpenes(50μmol·L^-1)isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells,and the effect of eurycomanol was further confirmed in vivo.CONCLUSION EL significantly reduced blood uric acid levels and prevented pathological changes of kidney in PO induced hyperuricemia animal model,improved renal urate transports.We partly clarified the mechanism was related to suppressing effect of URAT1 by diterpene in EL.This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.

Factors affecting the accumulation of 9-methoxycanthin-6-one in callus cultures of Eurycoma longifolia

A study was conducted to improve 9-methoxycanthin-6-one productivity （potential anti-tumour compound） from callus cultures of Emycorna longifolia （Tongkat All）. Several factors affecting 9-methoxycanthin-6-one production in callus cultures such as different medium compositions and physical factors were investigated and analyzed. Results show that a higher production of 9-methoxycanthin-6-one （3.84 mg-g-1 DW （Dry Weight）） is obtained from callus cultured in 1/4 MS basal media. At fructose of 2% （w/v）, the production of 9-methoxycanthin-6-one （4.59 mgg-1DW） is promoted to gain the highest yield, compared to other carbon sources tested. The addition of 2.0-mg·L^-1 dicamba also increases 9-methoxycanthin-6-one production （12.3 mg·g^-1 DW）. Higher production of 9-methoxycanthin-6-one was obtained at pH 5.5 （1.53 mg·g^-1 DW）. Production of 9-methoxycanthin-6-one （2.34 mg-g^-1 DW） in callus cultures is also increased when the medium is added with 1×10 ^-1μM phenylalanine. This study suggests that the successful production of 9-methoxycanthin-6-one in vitro cultures has a potential in large-scale production using bioreactor technology.

Anti-inflammatory effects of alkaloid enriched extract from roots of Eurycoma longifolia Jack

Objective: To examine the in vitro and in vivo anti-inflammatory effects of the alkaloid enriched extract(ELA) from the roots of Eurycoma longifolia. Methods: The in vitro antiinflammatory effects of ELA were evaluated by examining its inhibitory activities against nitric oxide(NO) production and inducible nitric oxide synthase(iN OS) and cyclooxygenase2(COX-2) expressions in lipopolysaccharide(LPS)-stimulated RAW264.7 cells. The level of NO produced in the culture media was determined by Griess method. The i NOS and COX-2 protein expressions were analyzed by Western blot. The in vivo effect of ELA was evaluated on LPS-induced septic shock in mice model. Mice mortality was monitored for5 days after injection of LPS. The chemical contents of the ELA were determined by using various chromatographic and spectroscopic techniques. Results: The ELA was found to exhibit a significant anti-inflammatory effect in both in vitro and in vivo models. The results demonstrated that ELA dose-dependently inhibited LPS-induced NO production as well as the protein iN OS and COX-2 expressions. In the septic shock model, ELA dose-dependently protected mice from LPS-induced mortality. Further study on the isolated components of ELA indicated that 9,10-dimethoxycanthin-6-one may contribute significantly to the antiinflammatory effects of the extract. Conclusions: These results suggest that ELA exhibits the anti-inflammatory activity via suppression of pro-inflammatory mediators such as NO, iN OS,and COX-2 and protects mice from LPS-induced mortality in septic shock model.

Methanol extracts of Brachystegia eurycoma and Detarium microcarpum seeds flours inhibit some key enzymes linked to the pathology and complications of type 2 diabetes in vitro

The inhibitory effect of methanol extracts of Brachystegia eurycoma and Detarium microcarpum seeds flours on some key enzymes[α-amylase,α-glucosidase and aldose reductase(AR)]linked to the pathology and complications of type 2 diabetes(T2D);and their antioxidant properties were evaluated.The antioxidant properties evaluated were DPPH•and ABTS•^+scavenging abilities,reducing power,and antioxidant phytochemicals(total phenolics,tannins,total flavonoids and total saponins).Extracts of both flours inhibitedα-amylase,α-glucosidase and AR in a dose-dependent manner.The half-maximal inhibitory concentrations(IC50)of B.eurycoma onα-amylase,α-glucosidase,AR and lipid peroxidation were lower than those of D.microcarpum,indicating that it had stronger inhibitory potency than D.microcarpum.B.eurycoma also had significantly(P<0.05)higher DPPH•and ABTS•^+scavenging abilities,and reducing power than D.microcarpum.The antioxidant phytochemicals(total phenolics,tannins,total flavonoids and total saponins)were also significantly(P<0.05)higher in B.eurycoma than D.microcarpum.The inhibitory effect of B.eurycoma and D.microcarpum extracts onα-amylase,α-glucosidase and AR activities may be attributed to the combined action of their polyphenols and total saponins,and this may be a possible mechanism of action providing support for their use in managing hyperglycemia and the complications of T2D.

The Effect of Mixture of Alpinia Galanga, Eurycoma Longifolia Jack and Syzygium Aromaticum Crude Extract on the Growth of Saccharomyces Cerevisiae and Escherichia Coli

Alpinia galanga, Eurycoma longifolia Jack and Syzygium aromaticum have been widely used in traditional medicine for decades. Antimicrobial activities for individual crude extract were well established. Crude methanolic extracts of Alpinia galanga, Eurycoma longifolia Jack and Syzygium aromaticum and the combination for all extracts were tested using well diffusion techniques against Saccharomyces cerevisiae （ATCC 9763） and Escherichia coli （ATCC 25922）. The mixed extracts were prepared based on the concentration ratio of 50 μg/μL which are 1：1, 1：1：1 and 1：2：2. Single Syzygium aromaticum extract showed higher inhibition zone on Saccharomyces cerevisiae compared to Escherichia coli. There is reduction in diameter of inhibition zone for single extract and mixture extracts either in combination of two or three extracts tested on Saccharomyces cerevisiae and Escherichia coli growth but they are not significant. In conclusion, Syzygium aromaticum showed highest activity against Saccharomyces cerevisiae and Escherichia coli. Reduction in diameter of inhibition zone indicated that Alpinia galanga and Eurycoma longifolia Jack extracts had antagonistic effect with Syzygium aromaticum.

The potential of standardized quassinoid-rich extract of Eurycoma longifolia in the regulation of the oestrous cycle of rats

Objective: To evaluate the effects of Eurycoma longifolia(E. longifolia) standardized extract on the oestrous cycle, levels of reproductive hormones and histology of the ovaries of Sprague-Dawley rats.Methods: Female rats were orally treated with E. longifolia standardized extract at the dose levels of 2.5, 5.0, 10.0, 25.0, 50.0 and 100.0 mg/kg of body weight over 5 days.Vaginal smears were monitored daily within the duration and after withdrawal of the treatment before being sacrificed. The body weights of the females were recorded before and after the 5 days treatment. At the end of the experiments, blood samples were collected for determination of testosterone, oestradiol and progesterone levels. Ovaries were removed, weighed and examined for histomorphological changes.Results: The administration of E. longifolia standardized extract did not significantly alter the oestrous cycle of the rats during the 5 days treatment and after withdrawal of the treatments. This was supported by normal testosterone, oestradiol and progesterone levels as well as normal morphology of the ovaries.Conclusions: The data obtained showed that E. longifolia standardized extract did not exhibit any toxic effect on reproductive activities of female rats suggesting potential use in the management of infertility.

东革阿里提取物对红火蚁工蚁的生物活性研究

为明确东革阿里Eurycoma longifolia提取物对红火蚁Solenopsis invicta工蚁的防治效果,本研究采用水试管喂毒法测定了其主要成分苦木苦味素对红火蚁工蚁的毒杀活性和行为能力的影响。结果表明,喂毒后1~10 d,苦木苦味素化合物ep6对红火蚁工蚁的毒杀活性与处理时间和浓度呈正相关,20 mg/L浓度下处理10 d后的死亡率为77.78%。ep6对红火蚁工蚁的聚集率、抓附率、行走率、爬杆率和食物识别率有显著抑制活性,但对红火蚁食物消耗率基本没有显著影响。20 mg/L浓度下处理10 d的聚集率、抓附率、爬杆率、行走率、食物识别率和食物消耗率与对照相比分别降低了73.86、50.27、44.99、27.78、6.67和10.81百分点。苦木苦味素化合物对红火蚁工蚁具有良好的毒杀和抑制行为活性。

Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies

Eurycoma longifolia(EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, Bio Med Central, Hindawi, Web of Knowledge, Pub Med Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders.

Advances in Studies on Chemistry,Pharmacological Effect,and Pharmacokinetics of Eurycoma longifolia

Eurycoma longifolia,also known as Tongkat Ali in Malaysia,as one of traditional herbal medicines,is used for centuries in South-East Asia.With the discovery of anticancer and anti-HIV properties,this herbal medicine has attracted great attention recently.In this review,the following information on E.longifolia,including chemistry,bioactivities,pharmacokinetics,clinical studies,and side effects and safety,was introduced.Our results,to a certain extent,will provide scientific base for commercial utilization and clearance of the Tongkat Ali products with regard to consumers’ safety.

Physical properties of Brachystegia Eurycoma seeds as affected by moisture content

Some physical,frictional and thermal properties of Brachystegia eurycoma seed were studied at different moisture contents in order to explore the possibility of mechanizing the handling and processing techniques.Results showed that the seed could be considered an oval disc in shape.In the moisture range of 2.79%to 27.13%(d.b.),the major,intermediate and minor axial dimensions increased with increase in moisture content from 2.29 mm to 2.45 mm,1.65 mm to 1.91 mm and 0.34 mm to 0.52 mm,respectively.In the above moisture range,one thousand seed weight,particle density,porosity,roundness,sphericity,surface area and angle of repose increased linearly from 0.901 kg to 1.252 kg,2270 kg/m^(3) to 2520 kg/m^(3),11.23%to 15.46%,35%to 47%,67%to 82%,7.67 cm^(2) to 8.48 cm^(2) and 16.8°to 29.2°respectively,while bulk density decreased from 745.4 kg/m^(3) to 613.6 kg/m^(3).Static coefficient of friction on different structural surfaces increased linearly with moisture content and had the highest values on galvanized steel sheet(0.445-0.639),and the lowest values on fiber glass(0.287-0.404).Kinetic coefficient of friction increased linearly with moisture content on different structural surfaces except on galvanized steel sheet where it decreased linearly with increase in moisture content in the above moisture range.It had the highest values on hessian bag material(0.266-0.389),and the lowest values on plywood with wood grains perpendicular to the direction of movement(0.204-0.271).Specific heat ranged from 1474 to 5992.7 J/kgK,and increased with increase in moisture content and temperature.Regression equations were used to express the relationships existing between the seed properties and moisture content.

东革阿里抗炎的物质基础及其作用机制:基于UPLC-Q-TOFMS/MS和网络药理学方法

目的阐明东革阿里抗炎活性的物质基础及作用机制。方法利用二甲苯致耳肿胀和脂多糖致急性肺炎模型筛选东革阿里的活性部位;采用UPLC-Q-TOF-MS/MS技术鉴定活性部位的化学组成,结合SwissADME、SwissTargetPrediction、Genecards等数据库筛选东革阿里抗炎的潜在作用靶点,String数据库绘制蛋白互作(PPI)网络图,Cytoscape软件做网络拓扑分析并筛选核心靶点,通过Metascape数据库对核心靶点进行富集分析,使用Autodock软件进行核心成分和靶点进行分子对接,Pymol软件将对接结果可视化;采用脂多糖诱导的RAW264.7细胞炎症模型验证东革阿里抗炎作用机制,通过Griess试剂法检测NO的水平,Western blot法检测MAPK1、JAK2及STAT3蛋白的表达水平。结果东革阿里75%提取物(ELE)为活性部位,该部位共鉴定出37个化学成分,化合物和疾病共有靶点541个,涉及JAK/STAT3、cAMP等信号通路,筛选出12个指标性成分,指标性成分与涉及信号通路上的2个核心靶点进行分子对接,对接结果良好;细胞验证实验显示ELE的低、中、高剂量组均能显著降低细胞NO的释放量,中剂量可以显著降低JAK2和STAT3的表达。结论东革阿里抗炎活性的物质基础为苦木素及生物碱类成分,其抗炎作用的机制可能与靶向JAK2、STAT3调控JAK/STAT3信号通路有关。

东革阿里对运动训练大鼠睾酮含量、物质代谢及抗运动疲劳能力的影响

本实验以大强度耐力训练大鼠为模型,研究东革阿里对运动训练大鼠睾酮含量、物质代谢及抗运动疲劳能力的影响。试验中分别以0.4、0.8、2.4 g/(kg·d)的剂量给大鼠灌胃49 d,并进行负重游泳实验、血睾酮等生化指标测定。结果显示,东革阿里各剂量组力竭游泳时间长于运动对照组(T组)(P<0.01);血清睾酮高于T组(P<0.01);血清皮质酮低于T组,促黄体生成素、促卵泡刺激素高于T组,与T组比较均不具有显著性差异;各组间血清睾酮与皮质酮比值变化与睾酮变化较为一致;肝糖原、肌糖原(P<0.05)高于T组;血尿素氮低于T组(P<0.05);血红蛋白高于T组(P<0.05)。从而表明补充东革阿里可以减轻大鼠血睾酮、皮质酮受高强度运动量的影响,维持在正常生理水平;促进蛋白质合成,抑制氨基酸和蛋白质分解,提高血红蛋白含量和糖原的储备,增强抗疲劳能力,具有多靶点、多途径的显著特点。

东革阿里树皮的化学成分研究

利用溶剂提取和正、反相色谱法、Sephadex LH-20凝胶柱色谱等技术对泰国产东革阿里（Eurycoma longifolia）树皮的化学成分进行分离纯化.采用核磁共振、质谱等波谱技术鉴定化合物的结构.从泰国产东革阿里树皮提取物中分离得到8个化合物,分别鉴定为铁屎米酮（1）,铁屎米酮-N（3）-氧化物（2）,9-羟基铁屎米酮（3）,9-甲氧基铁屎米酮（4）,9,10-二甲氧基铁屎米酮（5）,东哥内酯（6）,宽缨酮（7）,豆甾-4,22-二烯-3-酮（8）.化合物1~5为β-咔巴啉类生物碱,化合物6~7为苦木萜类成分,化合物8为甾体化合物,除化合物5和6外,其他6个化合物均为首次从该植物树皮中分离得到.

HPLC法测定东革阿里中宽缨酮的含量

目的:测定东革阿里中宽缨酮含量。方法:采用Waters Sunfire C18(4.6×250mm,5μm)色谱柱,乙腈-0.1%甲酸为流动相梯度洗脱,流速1.0mL/min,检测波长:238nm,柱温40℃。结果:宽缨酮在线性范围1.272~101.72μg·mL^-1(r=0.9998)内具有良好的线性关系,平均回收率分别为98.87%(n=9),日内精密度RSD为0.46%。结论:本法操作简便,结果稳定,重现性好,可作为东革阿里中宽缨酮的质量控制方法。

超高效液相色谱-串联四极杆飞行时间质谱法快速分析东革阿里化学成分

应用超高效液相色谱-串联四极杆飞行时间质谱法(UPLC-Q-TOF-MS)对东革阿里提取物的化学成分进行定性分析。采用Agilent Eclipse Plus-C18 RRHD色谱柱(2.1 mm×100 mm,1.8μm),以乙腈-0.1%甲酸水为流动相进行梯度洗脱。质谱分析采用电喷雾正离子模式采集,通过对照品比对及高分辨质谱数据解析,鉴定了49种化学成分,包括29种苦木素二萜、4种β-咔巴啉类生物碱、12种铁屎米-6-酮类生物碱、3种联苯新木脂素类及1种角鲨烯型三萜。该方法快速、可靠、高效,能较全面地反映东革阿里的化学成分,可为深入阐明东革阿里的药效物质基础及质量标准研究提供参考。

药用植物东革阿里的研究进展

东革阿里广泛分布于东南亚,是具有抗癌、抗疟疾、改善男性性功能障碍等作用的药用植物。文章主要从植物生物学和生态学特征、化学成分、药理作用、繁殖技术、次生代谢产物的生产等5个方面对其近年来的研究进展进行了综述,并对今后的研究方向进行了展望。

东革阿里多糖制备工艺研究

在单因素试验中考察提取温度、提取次数、提取时间和液料比对东革阿里多糖提取率的影响,并运用响应面分析方法进行优化,最终确定了东革阿里多糖的最佳提取工艺,液料比30∶1 (mL/g)、提取温度100℃,提取时间2 h、提取次数3次。采用此工艺,多糖提取率达到4.18%。

Tabletting Characteristics of the Selected Malaysian Herbs

This work describes a study of tabletting of selected Malaysian herbs such as Eurycoma longifolia Jack, Ficus deltoidea and Morinda citrifolia. These herbs are famous for their therapeutic properties and are used as herbal medicine or as medicinal food. A cylindrical uniaxial die of 13 mm was used to compress the herb powders into tablets. Pressures ranging from 7.5 MPa to 75 MPa were applied using a universal testing machine. Two feed weights, 0.5 g and 1.0 g, were used to produce the tablets. A binder, the microcrystalline cellulose known as Avicel, was used to investigate its effect on tabletting. Properties associated with both the binder and the compounds were studied, and binary mixtures with compositions ranging from 10% to 60% were examined. The strength of the herb tablets was then tested using an indirect tensile strength test. Upon compression, the Morinda citrifolia powder showed the highest density compared to that of Avicel. However, due to its high elasticity, the tensile strength of the Morinda citrifolia tablet was the lowest. The experimental data were also verified using an established model for compression property development. The results indicated that this simple approach can be used to understand the tabletting characteristics of these herbs.

东革阿里多糖对红细胞氧化溶血的保护作用

采用超声结合水提的方法提取东革阿里的多糖,通过L9(34)正交试验确定最佳提取条件。利用柱层析纯化得到一种含糖醛酸的新型多糖组分Ali-1;通过分子量检测和单糖组成分析对Ali-1进行基本结构表征;采用氧自由基吸收能力(ORAC)和人血红细胞溶血模型测定多糖的抗氧化活性,并同时测定红细胞内活性氧物质(ROS)、丙二醛(MDA)水平和过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)抗氧化酶活力的变化。结果表明:东革阿里多糖最佳提取条件为料液比1:40、浸提温度95℃、超声波破碎功率300W、浸提时间2h,最适条件下东革阿里的粗多糖得率为10.09%;Ali-1的平均分子量为14.3ku,主要由木糖、阿拉伯糖、葡萄糖醛酸和半乳糖醛酸组成,其摩尔比为:4.43:1.10:1:1.14;Ali-1的QRAC值为302.48±2.71μmol Trolox/g,且Ali-1的预处理使得AAPH损伤的人血红细胞内的ROS和MDA水平降低,使红细胞恢复到正常状态;虽SOD、GSH-Px和CAT平均酶活力降低,但结果表明较弱的红细胞也受到了保护。综上所述,经分离纯化后的东革阿里多糖组分Ali-1可以保护人血红细胞免受AAPH的损伤,具有较好的抗氧化活性。