Anticancer,Anti-inflammatory and Antibacterial Effects of Aloin and Its Molecular Mechanism

Aloin is the main medicinal component extracted from Aloe vera.It is a natural anthraquinone compound,with anticancer,anti-inflammatory and antibacterial and other biological functions.This paper reviews the pharmacological action and related mechanisms of aloin,in order to provide a theoretical basis for the development and utilization of aloin.

Relationship Between Leaf Structure and Aloin Content in Six Species of Aloe L.

The leaf structure, content and the storage location of aloin in the leaves of six species of Aloe L. were studied by means of semi-thin section, high performance liquid chromatography (HPLC) and fluorescent microscope. Results showed that all leaves consisted of epidermis, chlorenchyma, aquiferous tissue and vascular bundles. The leaves had the xeromorphic characteristics, including thickened epidermal cell wall, thickened cuticle, sunken stomata and well-developed aquiferous tissue. With the exception of thus, there were remarkable differences in leaf structure among the six species. The chlorenchyma cells were similar to palisade tissues in Aloe arborescens Mill. and A. mutabilis Pillans, but isodiametric in A. vera L., A. vera L. var. chinensis Berg., A. saponaria Hawer and A. greenii Bali. A. arborescens, A. mutabilis, A. very and A. vera var. chinensis included large parenchymatous cells at the vascular bundles, whereas no such cells were observed at the vascular bundles of A. saponaria and A. greenii. In A. arborescens, A. mutabilis and A. vera, the aquiferous tissue sheaths were present and composed of a layer of small parenchymatous cells without chloroplasts around the aquiferous tissue. While there were no aquiferous tissue sheaths in A. vera var. chinensis, A. saponaria and A. greenii. The HPLC revealed that the content of aloin was high in A. arborescens, low in A. vera, and very low in A. saponaria among the six species. The fluorescent microscopy showed that the yellow-green globule only appeared in the large parenchymatous cells of vascular bundles, vascular bundle sheath and aquiferous tissue sheath, but not in the chlorenchyma and aquiferous tissue. Consequently, the large parenchymatous cells of vascular bundles, vascular bundle sheath and aquiferous tissue sheath were the storage location of aloin. They were positively correlated with the content of aloin.

Anti-diabetic effect of aloin via JNK-IRS1/PI3K pathways and regulation of gut microbiota

This research aimed to investigate the antidiabetic activity,underlying mechanisms,and gut microbiota regulation of aloin.The insulin-resistant HepG2(IR-HepG2)cell model and the type 2 diabetic(T2D)mouse model were successfully established using dexamethasone and a high-fat high-sucrose diet with low-dose streptozotocin,respectively.Aloin intervention increased glucose consumption and stimulated the activity of hexokinase and pyruvate dehydrogenase in IR-HepG2 cells.Additionally,it diminished the weight loss,reduced fasting blood glucose levels and hemoglobin A1c activity,and promoted glucose tolerance and fasting serum insulin activity in T2D mice.Histopathological analysis of the liver indicated hepatic protection by aloin.Additionally,aloin treatment inhibited the protein expression of c-Jun N-terminal kinases and activated that of IRS1/PI3K/Akt in the liver.Moreover,aloin modulated the bacterial community in the gut by raising the abundance of Bacteroidota and reducing the richness of Firmicutes,Proteobacteria,and Actinobacteriota.Thus,aloin ameliorated IR via activating IRS1/PI3K/Akt signaling pathway and regulating the gut microbiota,and it may be promising candidate as functional food for diabetic therapy.

Aloin attenuates chronic constriction injury-induced neuropathic pain in rats by inhibiting inflammatory cytokines and oxidative stress

Objective:To investigate the effect of aloin against chronic constriction injury(CCI)-induced neuropathic pain in rats.Methods:Rats were randomly divided into 7 groups:GroupⅠ(normal control),GroupⅡ(sham-operated),GroupⅢ(CCI control)and GroupⅣ,Ⅴ,Ⅵ,andⅦ,which underwent CCI surgery and then were administered with aloin(5 mg/kg,p.o.;25 mg/kg,p.o.;125 mg/kg,p.o.)and gabapentin(50 mg/kg,p.o.),respectively for 14 days.Peripheral neuropathy was induced by silk ligatures(4-0)loosely placed around the sciatic nerve.Nociceptive thresholds against mechanical stimuli(Von-Frey filaments)and thermal stimuli(12℃and 40℃)were measured at midplantar paw region ipsilateral to the compressed nerve on day-3,7,11,and 14.The concentration of cytokines including tumor necrosis factor-α(TNF-α),interleukin-6,and interleukin-1βwas estimated at day-7.At day 14,motor nerve conduction velocity was determined under urethane anesthesia(1.25 g/kg).Oxidative stress parameters(malondiadehyde,glutathione,catalase,and superoxide dismutase)were estimated in sciatic nerve homogenates at day 14.Representative nerve samples were processed for histological investigations.Results:Aloin significantly reduced CCI-induced mechanical and thermal allodynia.It also improved motor nerve conduction velocity and decreased oxidative stress in nerve tissues.In addition,it decreased pro-inflammatory cytokine levels and restored the histoarchitecture of compressed sciatic nerve.Conclusions:Aloin mitigates CCI-induced neuropathic pain in rats by inhibiting oxidative stress and pro-inflammatory cytokines in the afflicted sciatic nerve.

Quantitative Detection of Aloin and Related Compounds Present in Herbal Products and Aloe vera Plant Extract Using HPLC Method

We have developed a novel methodology for the determination of Aloins A and B in Aloe vera plant extract and commercial Aloe vera product formulations using HPLC method. The result shows good sensitivity and accuracy which can be utilized for the scientific validation of bioactive compounds present in the commercial formulations.

不同来源芦荟药材品质评价研究

目的:对不同来源的24份芦荟药材品质进行分析及评价,为芦荟后期开发利用提供参考。方法:参照2020年版《中华人民共和国药典》的检测方法和含量要求及相关文献,测定不同来源的24份芦荟药材的性状、杂质、水分、总灰分、浸出物以及芦荟苷、芦荟大黄素含量。结果:进口芦荟药材性状主要是不规则块状,少部分粉末状;表面棕褐色,较粗糙,较有光泽;断面棕褐色,较光滑,较有光泽。国产芦荟药材性状主要是圆饼状,表面较粗糙,呈黑褐色,略有光泽,断面粗糙,呈黑褐色,略有光泽。杂质含量在0.00%~0.05%之间。水分含量均符合规定,达标率为100.00%。总灰分含量只有9份符合规定,达标率为37.50%(9/24)。浸出物含量范围在2.82%~93.57%之间。大部分芦荟苷含量测定未达到2020年版《中华人民共和国药典》中的标准(芦荟苷含量库拉索芦荟不得少于16.00%,好望角芦荟不得少于6.00%),仅有7份芦荟苷含量符合规定,达标率为29.17%(7/24)。13份无法检出芦荟大黄素,11份芦荟大黄素含量范围为0.07%~0.63%。结论:当前药材市场上芦荟主要为进口芦荟和国产芦荟,质量参差不齐,进口芦荟药材品质较为优良,在以后的生产、销售过程中应注意加强产地初加工监督管理,进一步提高药材品质。

芦荟素减轻大鼠心肌细胞缺氧损伤:抑制氧化应激和铁死亡

背景:心肌细胞缺氧损伤与氧化应激和铁死亡密切有关。既往研究表明芦荟素具有抗氧化、抗炎、抗肿瘤等多种作用。目的:探讨芦荟素对缺氧诱导的H9C2细胞氧化应激及铁死亡的影响。方法:利用H9C2细胞构建缺氧模型,首先通过检测细胞活性,确定芦荟素无细胞毒性及最佳干预浓度。随后,利用试剂盒、超氧化物阴离子荧光探针及MitoSOX^(TM)Red荧光探针,分别评估芦荟素对缺氧诱导的H9C2细胞乳酸脱氢酶释放、活性氧产生以及线粒体氧化应激的影响。为了验证芦荟素对铁死亡的影响,采用荧光染色和流式细胞术,分别检测细胞内Fe^(2+)的含量和脂质过氧化程度。接着,利用蛋白免疫印迹和实时荧光定量PCR技术,检测铁死亡调节因子(谷胱甘肽过氧化物酶4、酰基辅酶A合成酶长链家族成员4和核因子E2相关因子2)的表达。最后,通过运用铁死亡诱导剂Erastin,进一步确认铁死亡在芦荟素介导心肌保护过程中的重要作用。结果与结论:(1)与对照组相比,缺氧组H9C2细胞活力显著降低,乳酸脱氢酶释放、活性氧水平、线粒体氧化应激程度、Fe^(2+)含量及脂质过氧化程度显著上升,谷胱甘肽过氧化物酶4、核因子E2相关因子2的mRNA和蛋白表达明显降低,酰基辅酶A合成酶长链家族成员4的mRNA和蛋白表达显著升高(均P<0.05);(2)与缺氧组比较,芦荟素低、高剂量组逆转了上述指标变化(均P<0.05);(3)与缺氧+芦荟素组相比,缺氧+芦荟素+Erastin组H9C2细胞活力明显下降,乳酸脱氢酶释放显著升高(均P<0.01)。结果表明,芦荟素对缺氧处理的H9C2细胞具有保护作用,且呈剂量依赖性,主要通过抑制氧化应激和铁死亡实现的。

Isolation and Purification of Isoaloeresin D and Aloin from Aloe vera by High-speed Counter-current Chromatography

Objective To develop an efficient method to isolate and purify the main components isoaloeresin D and aloin from Aloe vera for its industrial production.Methods High-speed counter-current chromatography was used to isolate isoaloeresin D and aloin in a one-step separation from dried crude extract of A.vera.The biphasic solvent system composed of hexane-ethyl acetate-acetone-water(0.2:5:1.5:5) was used at a flow rate of 1.0 mL/min,while the lipophilic phase was selected as the mobile phase and the apparatus was rotated at 840 r/min.The effluent was detected at 254 nm.Results Isoaloeresin D(53.1 mg) and aloin(106.9 mg) were separated from the crude extract(384.7 mg) with the purities of 98.6% and 99.5%,respectively.Conclusion HSCCC is a powerful technique for isolation and separation of chemical composition from aloe.

Aloin Protects Against Blood-Brain Barrier Damage After Traumatic Brain Injury in Mice

Aloin is a small-molecule drug well known for its protective actions in various models of damage.Traumatic brain injury(TBI)-induced cerebral edema from secondary damage caused by disruption of the blood-brain barrier(BBB) often leads to an adverse prognosis.Since the role of aloin in maintaining the integrity of the BBB after TBI remains unclear,we explored the protective effects of aloin on the BBB using in vivo and in vitro TBI models.Adult male C57 BL/6 mice underwent controlled cortical impact injury,and mouse brain capillary endothelial bEnd.3 cells underwent biaxial stretch injury,then both received aloin treatment.In the animal experiments,we found 20 mg/kg aloin to be the optimum concentration to decrease cerebral edema,decrease disruption of the BBB,and improve neurobehavioral performance after cortical impact injury.In the cellular studies,the optimum concentration of 40 μg/mL aloin reduced apoptosis and reversed the loss of tight junctions by reducing the reactive oxygen species levels and changes in mitochondrial membrane potential after stretch injury.The mechanisms may be that aloin downregulates the phosphorylation of p38 mitogen-activated protein kinase,the activation of p65 nuclear factor-kappa B,and the ratios of B cell lymphoma(Bcl)-2-associated X protein/Bcl-2 and cleaved caspase-3/caspase-3.We conclude that aloin exhibits these protective effects on the BBB after TBI through its anti-oxidative stress and anti-apoptotic properties in mouse brain capillary endothelial cells.Aloin may thus be a promising therapeutic drug for TBI.

Valorization of Aloe barbadensis Miller. (Aloe vera) Processing Waste

Aloe vera plant is known worldwide for its medicinal properties and application in gel-based products such as shampoo,soap,and sunscreen.However,the demand for these gel-based products has led to a surplus production of Aloe vera processing waste.An Aloe vera gel processing facility could generate up to 4000 kg of Aloe vera waste per month.Currently the Aloe vera waste is being disposed to the landfill or used as fertilizer.A sustainable management system for the Aloe vera processing waste should be considered,due to the negative societal and environmental impacts of the currents waste disposal methods.Therefore,this review focuses on various approaches that can be used to valorize Aloe vera waste into value-added products,such as animal and aquaculture feeds,biosorbents,biofuel and natural polymers.Researchers have reported Aloe vera waste for environmental applications biosorbents used for wastewater treatment of various pollutants.Several studies have also reported on the valorization of Aloe vera waste for production of biofuels such as bioethanol,mixed alcohol fuels,biogas and syngas.Aloe vera waste could also be valorized through isolation and synthesis of natural polymers for application in wound dressing,tissue engineering and drug delivery systems.Aloe vera waste valorization was also reviewed through extraction of value-added bioactive compounds such as aloe-emodin,aloin and aloeresin.These value-added bioactive compounds have various applications in the cosmetics(non-steroidal anti-inflammatory,tyrosinase inhibitors)and pharmaceutical(anticancer agent and COVID 19 inhibitors)industry.

芦荟苷可抑制胃癌细胞的增殖和迁移:基于下调STAT3/HMGB1信号通路

目的通过体内外实验探讨芦荟苷抑制胃癌细胞增殖和迁移的分子机制。方法胃癌MGC-803细胞分为对照组、不同浓度芦荟苷(100、200和300μg/mL)处理组。CCK-8、EdU和Transwell实验分别检测细胞活力、细胞增殖和迁移能力;RT-qPCR检测HMGB1 mRNA的表达水平;Western blot检测HMGB1,Cyclin B1/E1,E-cadherin,MMP-2/9的表达以及STAT3的磷酸化。JASPAR数据库预测STAT3与HMGB1启动子的结合。MGC-803细胞(2×106/只)注射于BALB/c-Nu小鼠腋下进行皮下植瘤,裸鼠随机分为对照组和芦荟苷组(n=5)。实验组使用芦荟苷50 mg/kg/d腹腔注射,对照组注射等量PBS。每日测量瘤体大小和小鼠质量;提取肿瘤组织蛋白,Western blot检测HMGB1,Cyclin B1/E1,E-cadherin,MMP-2/9和p-STAT3的表达。HE染色检测肝、肺组织中肿瘤转移情况。结果芦荟苷能够浓度依赖性的抑制胃癌细胞活力(P<0.05),不同浓度芦荟苷处理组EdU阳性染色细胞与对照组相比显著减少(P<0.01),芦荟苷处理的胃癌细胞转移能力明显较对照组减弱(P<0.01)。芦荟苷能够浓度依赖性的下调HMGB1 mRNA和蛋白表达(P<0.01),下调Cyclin B1,E1,MMP-2/9,上调E-cadherin,明显抑制p-STAT3。JASPAR数据库预测STAT3能够与HMGB1启动子区域相结合。芦荟苷处理组瘤体大小和质量明显低于对照组(P<0.01)。芦荟苷处理组Cyclin B1/E1,MMP-2/9,HMGB1和p-STAT3的表达与对照组相比明显降低,E-cadherin的表达则显著增强(P<0.01)。结论芦荟苷通过抑制p-STAT3/HMGB1信号途径,抑制胃癌细胞的增殖和迁移。

芦荟素通过激活Nrf2改善TGF-β诱导的肾小管上皮细胞纤维化作用机制

目的探讨芦荟提取物芦荟素(aloin)对TGF-β诱导的肾小管上皮细胞(HK-2)纤维化发生的作用和分子机制。方法实验分为对照组、TGF-β诱导组、芦荟素50μmol·L^(-1)+TGF-β诱导组、芦荟素100μmol·L^(-1)+TGF-β诱导组。通过CCK-8细胞毒性实验检测芦荟素对细胞活力的影响。Western blot、细胞免疫荧光检测纤维化相关蛋白及抗氧化应激相关蛋白表达水平。流式细胞术检测ROS,SOD活性和MDA脂质氧化试剂盒检测氧化应激相关指标。ELISA检测炎症因子水平。结果芦荟素处理HK-2细胞后无显著性影响细胞活性。芦荟素减低TGF-β诱导的HK-2细胞α-SMA、E-Cadherin、Collagen I、Fibronectin纤维化相关蛋白表达水平。芦荟素上调Nrf2、HO-1、NQO1等抗氧化应激分子表达水平,减轻ROS、MDA含量,升高SOD酶活性。同时,芦荟素还能抑制IL-1β、IL-6炎症因子释放。结论芦荟素通过上调Nrf2蛋白表达,改善TGF-β诱导的HK-2细胞氧化应激和纤维化,并抑制其炎症因子释放。

芦荟主要生物学功能及其在动物生产中的应用

百合科芦荟属植物库拉索芦荟作为可饲用天然植物,具有提高机体免疫力、预防疫病、提高成活率、改善繁殖性能等作用。芦荟代谢产物类型主要为多糖、蒽醌和色原酮,其主要功能成分为芦荟多糖、芦荟苷、芦荟大黄素、芦荟苦素。芦荟主要成分具有抗菌、消炎、抗氧化、免疫调节等作用。文章综述了芦荟主要活性成分、生物学功能及其在动物生产中的应用,以期为芦荟在动物生产中的合理应用提供参考。

不同品种芦荟中芦荟苷的抗氧化活性研究

目的:比较木立芦荟、中华芦荟和库拉索芦荟3种鲜品芦荟中芦荟苷的抗氧化活性。方法:以芦荟苷含量为评价指标,利用超声提取法获得芦荟苷乙醇提取液,采用体外测试法考察不同品种中芦荟苷的抗氧化活性。结果:木立芦荟苷提取物(ALMs)中芦荟苷含量最高(9.02 mg/g)。中华芦荟苷提取物(ALZs)在清除DPPH自由基、ABTS自由基、羟基自由基方面均有一定的优势,其EC50值分别为0.78 mg/mL、0.24 mg/mL和1.35 mg/mL。结论:不同品种芦荟中芦荟苷有不同的抗氧化活性,本研究可为芦荟的进一步开发利用提供研究依据。

Simultaneous determination of four active compounds in Dangguilonghui tablet by high-performance liquid chromatography

A high-performance liquid chromatography （HPLC） method has been developed for the first time to simultaneously quantify the four active ingredients, namely aloha, baicalein, aloe-emodin and wogonin, in Dangguilonghui tablet. The marker compotmds were separated on the Diamonsil C18 column at a flow rate of 1.0 mL/min with a mobile phase of methanol-acetonitrile-0.3% aqueous phosphoric acid （220： 4： 200, v/v/v） and while the detection wavelength was set at 225 nm. The assay was linear over the range of 1.450 - 29.00 ug/mL （r = 0.9992） for aloin, 0.4050 - 8.100ug/mL （r = 0.9994） for baicalein, 0.1100 - 2.200 ug/mL （r = 0.9997） for aloe-emodin, 0.2160 - 4.320 ug/mL （r = 0.9991） for wogonin, respectively. The average sample recoveries at three concentration levels were 100.7% （RSD = 0.88%）, 101.0% （RSD = 0.89%）, 100.0% （RSD = 1.3%） and 100.1% （RSD = 1.1%） for these constituents, respectively. This method is suitable for the quality control of Dangguilonghui tablet.

芦荟抗菌作用与蒽醌化合物的关系

目的 :分析芦荟抗菌作用与蒽醌化合物含量的关系 ,比较芦荟大黄素和芦荟苷的抗菌作用 ,探讨糖基取代结构对芦荟苷抗菌活性的影响。方法 :利用琼脂扩散法分析皂质芦荟叶皮提取物、芦荟大黄素和芦荟苷对 3种革兰氏阴性菌、2种革兰氏阳性菌的抑菌活性 ,利用扫描电镜技术分析了芦荟苷对大肠杆菌的作用。结果 :芦荟的抗菌作用与蒽醌化合物的含量呈正相关性。芦荟苷 (1g·L- 1)具有较强的抗菌活性 [抑菌直径大于 (7.1± 0 .15)mm] ,对革兰氏阳性菌的抗性高于革兰氏阴性菌。芦荟大黄素的抗菌活性较弱。芦荟苷能够改变细胞的形态 ,破坏细胞结构。结论 :蒽醌化合物是芦荟中的抗菌成分 ,芦荟苷是主要抗菌有效成分之一 。

国内外芦荟应用研究进展

神奇植物芦荟可广泛应用于医药、化妆品、化工冶金、食品、美容保健等领域，其功效十分显著。本文详细介绍了国内外的芦荟应用研究进展，并就目前我国芦荟产业化过程中存在的问题进行了分析。

遮荫对库拉索芦荟细胞超微结构和芦荟素含量的影响

分别用透射电子显微镜技术、高效液相色谱法研究了生长在遮荫和自然光照条件下库拉索芦荟叶片的超微结构和芦荟素含量.电镜观察结果表明,遮荫处理6个月后,库拉索芦荟叶片细胞中叶绿体基粒数量减少,类囊体片层数目减少且排列疏松,质体中原来积累的淀粉粒逐渐减少直至消失;内质网、高尔基体等内膜系统不发达.高效液相色谱分析结果显示,生长在遮荫条件下的库拉索芦荟叶片,芦荟素含量明显低于生长在自然光照下的含量.其中,遮荫下幼叶芦荟素的含量是自然光照下的63.33%,而成熟叶芦荟素含量仅有自然光照下的23.77%.无论自然光下还是遮荫条件下生长的芦荟,芦荟素的含量与叶龄有显著的负相关性,遮荫对成熟叶的影响更大.综合两方面的实验结果认为,遮荫首先影响芦荟叶片细胞内膜系统的发育,进而限制了芦荟素的合成和运输,使芦荟叶片中芦荟素含量降低.

高效液相色谱法同时测定芦荟中芦荟苷和芦荟大黄素的含量

目的：建立用高效液相色谱法同时测定芦荟中芦荟苷和芦荟大黄素含量的方法。方法：采用ZORBAX—SA—C18柱（5μm，200nm×4．6mm），以甲醇-水（体积比60：40）溶液为流动相，在360nm处测定芦荟苷的含量，在430nm处测定芦荟大黄素的含量。结果：芦荟苷在线性范围0．002～0．050mmol／L内线性关系良好（r=0．99974），精密度良好（RSD=0.24％），平均加样回收率为102．5％（RSD=1．1％）；芦荟大黄素在线性范围0．001～0．040mmo1／L内线性关系良好（r=0．99977），精密度良好（RSD=0．39％），平均加样回收率为101.4％（RSD=1．0％）。结论：该方法快速、简便、准确，能同时测定芦荟苷和芦荟大黄素的含量。

反相高效液相色谱法测定芦荟中芦荟苷及芦荟大黄素

目的 :建立以高效液相色谱法测定芦荟鲜汁及复方芦荟胶囊中的芦荟苷及芦荟大黄素的方法。方法 :A法以甲醇 水(4 5∶5 5 )为流动相 ,于 3 5 4nm波长处以外标法直接测定样品中芦荟苷 ;B法先将样品加三氯化铁和盐酸水浴加热回流使芦荟苷水解为芦荟大黄素后在 2 87nm波长处 ,以甲醇 水 (70∶3 0 )为流动相 ,以外标法测定。结果 :芦荟苷及芦荟大黄素线性范围均为0 .0 4～ 0 .4μg。在此范围内浓度与峰面积线性关系良好 (r =0 .9999)。芦荟苷的平均回收率为 10 2 .1% (复方芦荟胶囊 ) ,RSD为 1.3 7% ;芦荟大黄素平均回收率为 10 2 .5 % (复方芦荟胶囊 ) ,RSD为 3 .6%。结论 :该两种方法均比较灵敏、准确 ,而A法直接测定芦荟苷更为简便、快捷。