Emodin: A Review of its Pharmacology,Toxicity and Pharmacokinetics

Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum. Emodin has been used as a traditional Chinese medicine for over 2000 years and is still present in various herbal preparations. Emerging evidence indicates that emodin possesses a wide spectrum of pharmacological properties, including anticancer, hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities. However, emodin could also lead to hepatotoxicity, kidney toxicity and reproductive toxicity, particularly in high doses and with long‐term use. Pharmacokinetic studies have demonstrated that emodin has poor oral bioavailability in rats because of its extensive glucuronidation. This review aims to comprehensively summarize the pharmacology, toxicity and pharmacokinetics of emodin reported to date with an emphasis on its biological properties and mechanisms of action. Copyright © 2016 John Wiley & Sons, Ltd.     

Aloe‐emodin Induces Apoptosis in Human Liver HL‐7702 Cells through Fas Death Pathway and the Mitochondrial Pathway by Generating Reactive Oxygen Species

Aloe‐emodin (1,8‐dihydroxy‐3‐hydroxymethyl‐anthraquinone) is one of the primary active compounds in total rhubarb anthraquinones isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. Thus, the aim of this study was to determine the potential cytotoxic effects and the underlying mechanism of aloe‐emodin on human normal liver HL‐7702 cells. The CCK‐8 assays demonstrated that aloe‐emodin decreased the viability of HL‐7702 cells in a dose‐dependent and time‐dependent manner. Aloe‐emodin induced S and G2/M phase cell cycle arrest in HL‐7702 cells. This apoptosis was further investigated by flow cytometry and nuclear morphological changes by DAPI staining, respectively. Moreover, aloe‐emodin provoked the production of intracellular reactive oxygen species and the depolarization of mitochondrial membrane potential (MMP). Further studies by western blot indicated that aloe‐emodin dose‐dependently up‐regulated the levels of Fas, p53, p21, Bax/Bcl‐2 ratio, and cleaved caspase‐3, ‐8, ‐9, and subsequent cleavage of poly(ADP‐ribose)polymerase (PARP). Taken together, these results suggest that aloe‐emodin inhibits cell proliferation of HL‐7702 cells and induces cell cycle arrest and caspase‐dependent apoptosis via both Fas death pathway and the mitochondrial pathway by generating reactive oxygen species, indicating that aloe‐emodin should be taken into account in the risk assessment for human exposure. Copyright © 2017 John Wiley & Sons, Ltd.     

A Biochemical and Cellular Approach to Explore the Antiproliferative and Prodifferentiative Activity of Aloe Arborescens Leaf Extract

Aloe arborescens Miller, belonging to the Aloe genus (Liliaceae family), is one of the main varieties of Aloe used worldwide. Although less characterized than the commonest Aloe vera, Aloe arborescens is known to be richer in beneficial phytotherapeutic, anticancer, and radio‐protective properties. It is commonly used as a pharmaceutical ingredient for its effect in burn treatment and ability to increase skin wound healing properties. However, very few studies have addressed the biological effects of Aloe at molecular level. The aim of the research is to provide evidences for the antiproliferative properties of Aloe arborescens crude leaf extract using an integrated proteomic and cellular biological approach. We analysed the composition of an Aloe arborescens leaf extract by gas chromatography‐mass spectrometry analysis. We found it rich in Aloe‐emodin, a hydroxylanthraquinone with known antitumoral activity and in several compounds with anti‐oxidant properties. Accordingly, we show that the Aloe extract has antiproliferative effects on several human transformed cell lines and exhibits prodifferentiative effects on both primary and immortalized human keratinocyte. Proteomic analysis of whole cell extracts revealed the presence of proteins with a strong antiproliferative and antimicrobial activity specifically induced in human keratinocytes by Aloe treatment supporting its application as a therapeutical agent. Copyright © 2013 John Wiley & Sons, Ltd.     

The anti‐hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera

Although the approved hepatitis B virus (HBV)‐polymerase inhibitors (e.g., lamivudine) often lead to drug‐resistance, several natural products have shown promising efficacies. Though Aloe vera (AV) gel and its constituents are shown inhibitors of many viruses, their anti‐HBV activity still remains elusive. We therefore, tested the anti‐HBV potential of AV extract and its anthraquinones in hepatoma cells, including molecular docking, high‐performance thin layer chromatography (HPTLC), and cytochrome P450 (CYP3A4) activation analyses. Our anti‐HBV assays (HBsAg/HBeAg Elisa) showed maximal inhibition of viral antigens production by aloe‐emodin (~83%) > chrysophanol (~62%) > aloin B (~61%) > AV extract (~37%) in HepG2.2.15 cells. Interestingly, the effect of aloe‐emodin was comparable with lamivudine (~86%). Moreover, sequential treatment with lamivudine (pulse) followed by aloe‐emodin (chase) enhanced the efficacy of monotherapy by ~12%. Docking (AutoDock Vina) of the anthraquinones indicated strong interactions with HBV‐polymerase residues that formed stable complexes with high Gibbs's free energy. Further, identification of aloe‐emodin and aloin B by validated HPTLC in AV extract strongly endorsed its anti‐HBV potential. In addition, our luciferase‐reporter gene assay of transfected HepG2 cells showed moderate induction of CYP3A4 by aloe‐emodin. In conclusion, this is the first report on anti‐HBV potential of AV–derived anthraquinones, possibly via HBV‐polymerase inhibition. Of these, although aloin B exhibits novel antiviral effect, aloe‐emodin appears as the most promising anti‐HBV natural drug with CYP3A4 activating property towards its enhanced therapeutic efficacy.     

Review of Clinical Pharmacology of Aloe vera L. in the Treatment of Psoriasis

Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune‐mediated chronic inflammatory disease, involving mainly the skin, affects about the 2–3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions. Copyright © 2015 John Wiley & Sons, Ltd.     

A Comparative Study of Baby Immature and Adult Shoots of Aloe Vera on UVB‐Induced Skin Photoaging in vitro

Ultraviolet (UV) irradiation induces photo‐damage of the skin, which in turn causes depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkle formations are associated with collagen synthesis and matrix metalloproteinase (MMP) expression. The production of type I procollagen is regulated by transforming growth factor‐β1 (TGF‐β1) expression; the activation of MMP is also correlated with an increase of interleukin‐6 (IL‐6). Aloe barbadensis M. (Aloe vera) is widely used in cosmetic and pharmaceutical products. In this study, we examined whether baby aloe shoot extract (BAE, immature aloe extract), which is from the one‐month‐old shoots of Aloe vera, and adult aloe shoot extract (AE), which is from the four‐month‐old shoots of Aloe vera, have a protective effect on UVB‐induced skin photoaging in normal human dermal fibroblasts (NHDFs). The effects of BAE and AE on UVB‐induced photoaging were tested by measuring the levels of reactive oxygen species, MMP‐1, MMP‐3, IL‐6, type I procollagen, and TGF‐β1 after UVB irradiation. We found that NHDF cells treated with BAE after UVB‐irradiation suppressed MMP‐1, MMP‐3, and IL‐6 levels compared to the AE‐treated cells. Furthermore, BAE treatment elevated type I procollagen and TGF‐β1 levels. Our results suggest that BAE may potentially protect the skin from UVB‐induced damage more than AE. Copyright © 2013 John Wiley & Sons, Ltd.     

A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology,toxicology, and some pharmaceutical aspects

Beneficial therapeutic effects of phenolic acids have been proven in various research projects including in vivo and in vitro studies. Gentisic acid (GA) is a phenolic acid that has been associated with useful effects on human health, such as antiinflammatory, antigenotoxic, hepatoprotective, neuroprotective, antimicrobial, and especially antioxidant activities. It is an important metabolite of aspirin and also widely distributed in plants as a secondary plant product such as Gentiana spp., Citrus spp., Vitis vinifera, Pterocarpus santalinus, Helianthus tuberosus, Hibiscus rosa‐sinensis, Olea europaea, and Sesamum indicum and in fruits such as avocados, batoko plum, kiwi fruits, apple, bitter melon, black berries, pears, and some mushrooms. This study was undertaken to review the pharmacological effects, pharmacokinetic properties as well as toxicity and pharmaceutical applications of GA.     

Comparative Pharmacokinetics of Five Rhubarb Anthraquinones in Normal and Thrombotic Focal Cerebral Ischemia‐Induced Rats

A comparative oral pharmacokinetic study of five anthraquinones (aloe‐emodin, emodin, rhein, chrysophanol and physcion) from the extract of Rheum palmatum L. was performed in normal and thrombotic focal cerebral ischemia (TFCI)‐induced rats. The plasma samples were clarified through solid phase extraction prior to simultaneous determination of the anthraquinones with a validated high‐performance liquid chromatography ‐fluorescence system. The results indicated that the C_max, t_1/2 and AUC_0‐t, of aloe‐emodin, rhein, emodin and chrysophanol in TFCI‐induced rats were nearly double, whereas the CL values were remarkably decreased (p < 0.05) over those of the normal rats. The plasma drug concentration–time data of five anthraquinones to rats fitted a two‐compartment open model. The five anthraquinones in rat plasma were absorbed quickly and eliminated slowly in both groups. The obtained results could be helpful for evaluating the impact of the efficacy and safety of the drug in clinical applications. Copyright © 2012 John Wiley & Sons, Ltd.     

Screening of Kit inhibitors: suppression of Kit signaling and melanogenesis by emodin

In search of novel antipigmentation agents, a set of 3,840 compounds with natural‐like synthetic or natural origin were screened against Kit (stem cell factor receptor). Emodin from the seed of Cassia tora and baicalin from Scutellariae radix showed potent inhibitory effects (IC₅₀ = 4.9 and 9.0 mm, respectively) on the phosphorylation of Kit. Emodin also blocked other receptor tyrosine kinase activities, such as epithelial growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR‐2), fibroblast growth factor receptor 1 (FGFR‐1), platelet‐derived growth factor receptor b (PDGFR‐b). In contrast to emodin, aloe‐emodin did not inhibit Kit activity at all. Emodin also blocked the cellular kinase activities of Kit and its down‐stream p44/42 mitogen activated protein kinase (MAPK) in MO7e cells and human primary melanocytes. Emodin strongly suppressed the melanin synthesis triggered by stem cell factor (SCF) treatment. Also, emodin showed almost no toxicity up to 10 mm on cultured melanocytes as reported previously by other researchers. The results indicate that emodin is a good candidate for the development of antipigmentation agents since it can radically block the differentiation and proliferation of pigment cells by reducing Kit signaling. Copyright © 2009 John Wiley & Sons, Ltd.     

Aloe vera as an herbal medicine in the treatment of metabolic syndrome: A review

Metabolic syndrome (MS) is a highly prevalent health problem worldwide and is associated with different risk factors, including hyperglycemia, dyslipidemia, hypertension, and obesity. This condition increases the risk of developing type II diabetes mellitus and cardiovascular problems. The MS is one of the most important health concerns in industrialized countries and mainly results from a sedentary lifestyle, high levels of subjective stress, and unhealthy diets. Nowadays, the identification of appropriate health care approaches, such as herbal medicines, with fewer side effects is more favorable, especially with regard to the adverse effects of chemical drugs. Aloe barbadensis Miller known as Aloe vera is a useful plant with two major parts, including leaves that contain high concentrations of anthraquinone compounds and a clear gel. The gel is used as a food with several beneficial properties, such as antiinflammatory, antioxidant, antiviral, antibacterial, and wound‐healing features. Other effects of A. vera, such as its lipid‐lowering, antihypertensive, antidiabetic, antiobesity, and cardioprotective impacts, have been demonstrated in several studies. The present study was conducted to review the evidence on the pharmacological effects of A. vera on the different components of MS.     

A Review: The Pharmacology of Isoliquiritigenin

Isoliquiritigenin (ISL) is one of the bioactive ingredients isolated from the roots of plants belonging to licorice, including Glycyrrhiza uralensis, Mongolian glycyrrhiza, Glycyrrhiza glabra, and so forth. Liquiritigenin is available in common foods and alternative medicine, and its derivative‐ISL is applied into food additives and disease treatment like cancer therapy, antibiotic therapy, and so on. This review aims at providing a comprehensive summary of the pharmacological activities of ISL. The information published between 1972 and 2014 from a number of reliable sources including PubMed, ScienceDirect, Springer, and Wiley‐Blackwell. The practical application of ISL on the various disease prevention and treatments may stem from its numerous pharmacological properties such as antiinflammatory, anti‐microbial, anti‐oxidative, anticancer activities, immunoregulatory, hepatoprotective, and cardioprotective effects. However, further studies are needed to verify the target‐organ toxicity or side effects investigation. Copyright © 2015 John Wiley & Sons, Ltd.     

Antiviral Activity of Aloe Extracts against Cytomegalovirus

Substances extracted from the leaves of aloe plants have been reported to have antiviral effects against enveloped viruses in in vitro test systems. In the present studies, we have assessed the antiviral activity of partially purified extracts prepared from the gel portion of leaves of Aloe barbadensis Miller against human cytomegalovirus (CMV) by plaque inhibition tests (PIT), flow cytometry and morphometry assays. Six test extracts of gel filet portions of aloe leaves were prepared; i.e. R1 from immature leaves harvested in the early summer, S1 from mature leaves harvested in the autumn, F1 from S1 after freezing at −20°C, and R2, S2 and F2 which were ethanol treated extracts of R1, S1 and F1, respectively. When test aloe extracts were added at various concentrations during the course of infection with CMV, R1, S1 and F2 at concentrations of 10⁻¹ inhibited plaque formation. The addition of S1 to the medium between 12 and 36 h after initiation of CMV infection, a time of high DNA synthesis, caused the most effective plaque inhibition. Flow cytometric and morphometric analyses revealed no significant differences in aloe extract treated, CMV infected cells compared with non-aloe treated CMV infected control cells. The results suggest that a major mechanism of inhibition of CMV infection by aloe extracts is through interference with DNA synthesis.     

高效毛细管电泳法分析库拉索芦荟中的多种成分

目的 建立分离芦荟苷同分异构体及同时测定不同库拉索芦荟样品中芦荟苷、异芦荟色苷D、芦荟大黄素含量的毛细管区带电泳法(CZE),并对各种影响电泳分离的因素进行了探讨.方法 以芦丁为内标,采用未涂层弹性熔融石英毛细管柱(57 cm×75 μm,有效长度50 cm),以20 mmol·L-1 硼砂+2 mmol·L-1β-环糊精(pH=9.65)为背景电解质溶液,分离电压为18 kV,重力进样5 s(高度15 cm),检测波长365 nm.结果 芦荟苷的一对同分异构体能够达到良好的分离,以芦丁为内标,库拉索芦荟样品中的芦荟苷、异芦荟色苷D、芦荟大黄素3种成分在7 min内得到良好的分离测定.结论 此方法简便,快速,成本低,可用于芦荟样品的质量控制.     

大黄及其活性成分抗炎作用及机制的研究进展

大黄为蓼科植物掌叶大黄Rheum palmatum、唐古特大黄R.tanguticum或药用大黄R.officinale的干燥根和根茎,具有泻下攻积、清热泻火、凉血解毒、逐瘀通经、利湿退黄之功。近年来研究发现大黄及其活性成分大黄素、大黄酸、大黄酚、芦荟大黄素等具有良好的抗炎、解热镇痛、抗肿瘤等活性。对大黄及其活性成分在治疗急性胰腺炎、脓毒症、关节炎等炎症性疾病的作用及机制的研究进展进行综述,以期为其在防治炎症疾病中的深入研究及开发应用提供参考。     

Influence of aloe vera on the healing of dermal wounds in diabetic rats

The positive influence of Aloe vera, a tropical cactus, on the healing of full-thickness wounds in diabetic rats is reported. Full-thickness excision/incision wounds were created on the back of rats, and treated either by topical application on the wound surface or by oral administration of the Aloe vera gel to the rat. Wound granulation tissues were removed on various days and the collagen, hexosamine, total protein and DNA contents were determined, in addition to the rates of wound contraction and period of epithelialization. Measurements of tensile strength were made on treated/untreated incision wounds. The results indicated that Aloe vera treatment of wounds in diabetic rats may enhance the process of wound healing by influencing phases such as inflammation, fibroplasia, collagen synthesis and maturation, and wound contraction. These effects may be due to the reported hypoglycemic effects of the aloe gel.     

大黄素对肝脏疾病的防治作用与安全性研究进展

大黄素是一种蒽醌类衍生物,是从何首乌、大黄等中药中提取得到的主要活性单体.现代药理研究证明,大黄素具有广泛的药理活性,其中对于肝脏疾病如肝脏炎症、肝癌、肝纤维化以及对各类肝损伤等均有良好的防治作用.然而在研究过程中,大黄素对肝细胞的潜在毒性作用也逐渐显现.因此,本研究综合近年来大黄素在肝脏上的研究,对其药理作用、机制及...     

泽泻调血脂活性成分及其药理和临床应用研究进展

泽泻是一味具有多种用途的中药,在中国已有很长的应用历史。早期的临床研究已初步证明泽泻提取物可能是良好的调血脂药物,现代药理学研究发现其可能具有抗动脉粥样硬化作用,已有的安全性评价实验发现泽泻提取物肝肾毒性小,适合长期用药。从已发表的泽泻有关调血脂药效的文献出发,对泽泻的作用机制、药效成分、药动学、临床疗效以及安全性进行综述。泽泻原萜烷三萜类成分泽泻醇A、泽泻醇A 24-乙酸酯等是其调血脂活性物质基础。     

Antimicrobial,anti-inflammatory and mutagenic investigation of the South African tree aloe (Aloe barberae)

Ethnopharmacology relevance

In recent times, many products ranging from aloe drinks to aloe gels, powders, capsules, and creams have appeared on the commercial market prepared from different aloe species including Aloe barberae. These products are used in ethnomedicine to treat various conditions including gastrointestinal disorders, insect bites, skin burns and other skin injuries by traditional communities.

Aim of the study

This study was aimed at evaluating the antibacterial, antifungal and anti-inflammatory activities as well as genotoxic effects of different extracts of Aloe barberae.

Materials and methods

Organic and water extracts of the upper stem, young bark, mature bark, leaves and roots of the South African tree aloe (Aloe barberae) were evaluated for their antimicrobial [Gram-positive (Bacillus subtilis and Staphylococcus aureus), Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria as well as the fungus Candida albicans], anti-inflammatory (COX-1 and COX-2) and mutagenic properties (Ames test). Thin layer chromatography (TLC) was used to compare the phytochemical profiles of different extracts of Aloe barberae.

Results

The petroleum ether (PE) and dichloromethane (DCM) extracts of the mature bark, leaves and roots exhibited good activity against all the bacteria and fungus Candida albicans with minimum inhibitory concentrations (MIC) ranging from 0.195 to 1.56 mg/ml. All the PE extracts evaluated showed a high activity (>70%) in both COX-1 and COX-2 assays. Apart from the organic extracts of the root with consistently good activity (>70%), all the remaining extracts showed moderate activity (40–69%) in COX-1 assay. The PE extracts also showed a dose dependent increase in activity. Ultraviolet (UV) spectrum of the leaves and root EtOH extracts indicated the presence of compounds that could absorb UV light (wavelength: 190–820 nm). None of the extracts had a mutagenic effect in the Salmonella/microsome assay against a tester strain, TA98.

Conclusion

Activity observed in the bark, leaves and roots of Aloe barberae validates its use in commercial herbal products, ethnobotany and ethnoveterinary medicine by South African communities and small scale farmers to treat various conditions.     

L02肝脂肪变性细胞膜快速筛选大黄调血脂活性成分

目的 构建L02肝脂肪变性细胞膜固相色谱耦合脂肪变性模型,并将其应用于大黄调血脂活性成分的快速筛选.方法 利用L02肝脂肪变性细胞膜作为固定相选择性地吸附大黄30％乙醇提取液中的活性成分,采用高效液相色谱(HPLC)测定吸附前后的化学成分;根据对照品的保留时间及紫外光谱信息,对比鉴定各亲和活性成分;并将筛选出的活性成分...     

Herbal medicines and phytochemicals for obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) is a relatively prevalent mental disorder that poses significant health burdens on the community. Although current conventional medications have good efficacy for many patients, they can elicit a range of associated adverse effects. Plant‐based compounds have been evaluated for different mental disorders, with a range of anxiolytic properties revealed. To determine the current evidence in the area, we conducted a systematic review using the electronic databases including PubMed, Scopus, and the Cochrane Library up to June 12, 2019, for pharmacological and clinical evidence of herbal medicines and phytochemicals with antiobsessive–compulsive effects. Additional search criteria were employed for locating research on the underpinning mechanisms of action. Results revealed that tentative low‐quality evidence exists for several plant medicines, including Crocus sativus, Silybum marianum, Echium amoenum, Hypericum perforatum, and Withania somnifera, along with several natural molecules, including crocin, cannabidiol, and curcumin. Although more research is needed to confirm effectiveness, present preclinical studies indicate that monoamine pathway modulation (in particular serotonin reuptake inhibition) may be the most important anti‐OCD mechanism among the studied natural compounds.