An evaluation of the RNase H inhibitory effects of Vietnamese medicinal plant extracts and natural compounds

Context: Acquired immune deficiency syndrome (AIDS) is a severe pandemic disease especially prevalent in poor and developing countries. Thus, developing specific, potent antiviral drugs that restrain infection by human immunodeficiency virus type 1 (HIV-1), a major cause of AIDS, remains an urgent priority.

Objective: This study evaluated 32 extracts and 23 compounds from Vietnamese medicinal plants for their inhibitory effects against HIV-1 ribonuclease H (RNase H) and their role in reversing the cytopathic effects of HIV.

Materials and methods: The plants were air-dried and extracted in different solvent systems to produce plant extracts. Natural compounds were obtained as previously published. Samples were screened for RNase H inhibition followed by a cytopathic assay. Data were analyzed using the Microsoft Excel.

Results and discussion: At 50?μg/mL, 11 plant extracts and five compounds inhibited over 90% of RNase H enzymatic activity. Methanol extracts from Phyllanthus reticulatus and Aglaia aphanamixis leaves inhibited RNase H activity by 99 and 98%, respectively, whereas four extracts showed modest protection against the cytopathic effects of HIV.

Conclusion: The screening results demonstrated that the butanol (BuOH) extract of Celastrus orbiculata leaves, methanol (MeOH) extracts of Glycosmis stenocarpa stems, Eurya ciliata leaves, and especially P. reticulatus leaves showed potential RNase H inhibition and protection against the viral cytopathic effects of HIV-1. Further chemical investigations should be carried out to find the active components of these extracts and compounds as potential anti-HIV drug candidates.     

化疗药物靶向肿瘤相关免疫抑制性细胞的研究进展

肿瘤相关免疫抑制性细胞在肿瘤的发生、发展过程中发挥重要的免疫抑制作用,肿瘤的发展和转移常伴有这些细胞的异常聚集。调节性T细胞(regulatory T cells,Treg)和髓系来源的抑制性细胞(myeloid-derived suppressor cells,MDSC)是免疫抑制性细胞网络的主要成分,它们通过直接或间接作用负向调节其他免疫细胞,抑制抗肿瘤的免疫反应。最新研究显示,有些常规化疗药物除可直接杀伤肿瘤细胞外,还可降低Treg和MDSC的数量,抑制其功能,从而增强抗肿瘤免疫功能。因此,将化疗药物作为预处理方案,凭借其免疫调节作用联合后续的过继性细胞免疫治疗可有效增强抗肿瘤免疫应答。化学免疫治疗策略将改变人们对传统化疗抗肿瘤地位的认识,继而更加合理地应用化疗药物。     

The effect of sixteen medicinal plants used in the Brazilian pharmacopoeia on the expression and activity of glutathione S-transferase in hepatocytes and leukemia cells

Glutathione S-transferase (GST) is a family of enzymes involved in the detoxification of electrophilic compounds. Different classes of GST are expressed in various organs, such as liver, lungs, stomach and others. Expression of GST can be modulated by diet components and plant-derived compounds. The importance of controlling GST expression is twofold: increasing levels of GST are beneficial to prevent deleterious effects of toxic and carcinogenic compounds, while inhibition of GST in tumor cells may help overcoming tumor resistance to chemotherapy. A screening of 16 plants used in the Brazilian pharmacopoeia tested their effects on GST expression in hepatocytes and Jurkat (leukemia) T-cells. The methanol extracts of five plants inhibited GST expression in hepatocytes. Three plants significantly inhibited and four others induced GST expression in Jurkat cells. Among these, the extracts of Bauhinia forficata Link. (Leguminosae) and Cecropia pachystachya Tréc. (Urticaceae) inhibited GST expression at relatively low concentrations. With the exception of B. forficata, all plants were cytotoxic when administered to Jurkat cells at high doses (1?mg/mL) and some extracts were considerably cytotoxic even at lower concentrations.     

Therapeutic applications of medicinal plants in the treatment of breast cancer: a review of their pharmacology, efficacy and tolerability

Various active compounds (or their semi-synthetic derivatives) derived from medicinal plants have been assessed for their efficacy and tolerability in the treatment of breast cancer. Some of these plant species, including Taxus baccata (paclitaxel, docetaxel), Podophyllum peltatum (etoposide), Camptotheca acuminata (camptothecin) and Vinca rosea (vinblastine, vinorelbine) have well recognized antitumour activity in breast cancer, and have been evaluated in clinical trials. For example, results from recent Phase II/III trials have established docetaxel as the most active single agent in the treatment (first or second-line) of advanced metastatic breast cancer. For other plant species such as Panax ginseng and Allium sativum, antitumour activity has been evaluated in experimental studies using cultured cells and animal models, but the therapeutic potential in patients remains to be determined. Antitumour activity derived from medicinal plants may produce results via a number of mechanisms, including effects on cytoskeletal proteins which play a key role in mitosis (paclitaxel), inhibition of activity of topoisomerase enzymes I (camptothecin) or II (etoposide), stimulation of the immune system (Viscum album), or antiprotease-antioxidant activity. Medicinal plant-derived antineoplastic agents may be used in single agent or in combinational therapies, and have been used in first-line or second-line (including anthracycline-refractory patients) treatment of localized or metastatic breast cancer. Adverse effects resulting from the use of these agents include neutropenia and peripheral neuropathies.     

Studies on the antiplasmodial properties of some South African medicinal plants used as antimalarial remedies in Zulu folk medicine

The parasite lactate dehydrogenase (pLDH) assay method, a recently developed in vitro enzymatic method for evaluating antimalarial compounds, was used to examine the antiplasmodial activities of the aqueous leaf, stem-bark and fruit extracts of some plants used for the treatment and/or prophylaxis of malaria in KwaZulu-Natal province of South Africa. The in vitro antiplasmodial assay was carried out using a chloroquine-sensitive strain of malarial parasite, Plasmodium falciparum D10. A preliminary phytochemical analysis of the plant extracts was carried out using UV spectral analysis and thin-layer chromatography (TLC) to separate the chemical constituents of the extracts. Their chemical components were subsequently identified by treating the TLC plates with various spray reagents. Of the 14 plant extracts investigated, only 10 were found to have IC50 values of 10-50 micrograms/ml. The two most active extracts were Psidium guajava stem-bark extract and Vangueria infausta leaf extract, both of which showed IC50 values of 10-20 micrograms/ml. Phytochemical analysis of these two active plant extracts revealed the presence of anthraquinones, flavonoids, seccoirridoids and terpenoids.     

Cell‐line‐based assay for the toxicity/benefit analysis of lipopolysaccharides in plants

There are many immune‐boosting medicinal plants that can potently activate innate immune cells. Recent studies indicate that the active factors of some immune‐boosting plants are lipopolysaccharides (LPSs) of plant‐associated bacteria. However, little is currently known about the potential risk and benefit of LPSs in medicinal plants. To facilitate their characterization, we established a simple cell‐line‐based assay that can be used to screen the toxicity and benefit of LPSs in medicinal plants. The assay can distinguish endotoxic diphosphoryl lipid A (DPL) from beneficial monophosphoryl lipid A (MPL), which is a clinically used immunological adjuvant for vaccines. The established assay was used to characterize commercial supplements of Ashwagandha, which was shown to contain immunostimulatory LPSs. The study revealed that Ashwagandha activates macrophages in a manner similar to MPL. The current finding underscores the importance of further studies to characterize the LPSs in immune‐boosting medicinal plants.     

天然植物成分抗真菌研究新进展

查阅近年来有关天然植物成分抗真菌研究的国内外文献,并对其进行分析、归纳和总结,综述了天然植物成分抗真菌研究的新进展。天然植物以提取物和活性成分的形式发挥抗真菌作用,或作为抗真菌药物的增效剂和增敏剂,与抗真菌药物联合应用。研究的深入为筛选天然植物抗真菌活性成分和先导化合物提供了有利条件。     

Screening of Panamanian Medicinal Plants for Brine Shrimp Toxicity,Crown Gall Tumor Inhibition,Cytotoxicity and DNA Intercalation

Crude extracts from 20 Panamanian plants used in traditional medicine have been screened for brine shrimp toxicity, tumor inhibition, DNA-intercalation and cytotoxicity tests in a clonogenic assay in V79 suspension culture gassed with air or nitrogen. Of the 20 plant extracts, 8 (40%) proved active in DNA intercalation. The most active were the methanol extracts of Bidens pilosa (root), Jatropha curcas (leaf), Pereskia bleo (whole plant), Isertia hypoleuca (leaf), Cyperus luzulae (root), Vernonia patens (leaf and stem), Alibertia edulis (stem) and Justicia graciliflora (aerial parts). Sixteen (80%) of the 20 methanol plant extracts were active in potato disc tumor inhibition assay; Cyperus luzulae (root), Justicia graciliflora (aerial parts), Pereskia bleo (whole plant) and Vernonia patens (leaf and stem) being the most active. Cytotoxicity in the clonogenic assay was observed only in three plant extracts: Cyperus luzulae, Piper auritum and Psychotria correae, whereas high brine shrimp toxicity (LC 50 <100 p.p.m.) was observed in 13(65%) of the 20 plant extracts tested. These results appear to show a good correlation between the three bioassays: brine shrimp toxicity, tumor inhibition and DNA intercalation. The latter bioassay is rapid, economical, and can be used in activity guided fractionation of plant extracts.     

Metabolomics in research of phytotherapeutics

Pharmaceutical and food industries are increasingly focused on the great potential of plant secondary metabolites or natural substances which can be used as therapeutics or model compounds for development of new drugs. The paper is devoted to the use of metabolomics, metabolic profiling and metabolic "fingerprint" for the identification of individual active phyto-substances in plant extracts, in profiling of unique groups of plant secondary metabolites that can be used to improve the classification of several species of medicinal plants as well as for a better characterization and quality control of medicinal extracts, tinctures and phytotherapeutic products prepared from these plants. Combined analytical methods and multivariate statistical analysis are used for metabolite identification. Using this approach, medicinal plants are evaluated not only on the basis of a limited number of pharmacologically important metabolites but also based on the fingerprints of minor metabolites and bioactive molecules.     

植物成分对肠道微生物的影响

植物的成分复杂多样。有些植物提取成分如各种寡聚糖、黄豆苷元、大豆蛋白肽等,能加强有益菌的功能,抑制有害菌的生长,从而改善动物消化道微生物区系平衡,促进动物的生长。该文综述了各种植物中起作用的主要成分及其对肠道微生物的影响研究进展。     

Ability of some plant extracts, traditionally used to treat ciguatera fish poisoning, to prevent the in vitro neurotoxicity produced by sodium channel activators.

The effects of 31 plant extracts, which most are traditionally used to treat ciguatera fish poisoning in the Pacific area, were studied on the cytotoxicity of mouse neuroblastoma cells produced by ouabain, veratridine and/or brevetoxin-3 or Pacific ciguatoxin-1. The cell viability was determined using a quantitative colorimetric method. A marked cytotoxicity of seven of the 31 plant extracts studied, was observed. Despite this, these plant extracts were suspected to contain active compound(s) against the cytotoxicity produced by brevetoxin (2 extracts), brevetoxin, ouabain and/or veratridine (3 extracts), or only against that of ouabain and/or veratridine (2 extracts). Among the 24 plant extracts that exhibited by themselves no cytotoxicity, 22 were active against the effect of brevetoxin or against that of both veratridine and brevetoxin. Similar results were obtained when the seven most active plant extracts were reassayed using ciguatoxin instead of brevetoxin. In conclusion, the present work reports the first activity assessment of some plant extracts, achieved in vitro on a quite large scale. The fact that 27 plant extracts were found to exert, in vitro, a protective effect against the action of ciguatoxin and/or brevetoxin, paves the way for finding new active compounds to treat ciguatera fish poisoning, provided these compounds also reverse the effects of sodium channel activators.     

Adverse and beneficial effects of plant extracts on skin and skin disorders

Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for primary health care. Approximately one-third of all traditional medicines are for treatment of wounds or skin disorders, compared to only 1-3% of modern drugs. The use of such medicinal plant extracts for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence, since there has been relatively little data available in the scientific literature, particularly with regard to the efficacy of plant extracts in controlled clinical trials. In this article therefore, adverse and beneficial aspects of medicinal plants relating to skin and skin disorders have been reviewed, based on recently available information from the peer-reviewed scientific literature. Beneficial aspects of medicinal plants on skin include: healing of wounds and burn injuries (especially Aloe vera); antifungal, antiviral, antibacterial and acaricidal activity against skin infections such as acne, herpes and scabies (especially tea tree (Melaleuca alternifolia) oil); activity against inflammatory/immune disorders affecting skin (e.g. psoriasis); and anti-tumour promoting activity against skin cancer (identified using chemically-induced two-stage carcinogenesis in mice). Adverse effects of plants on skin reviewed include: irritant contact dermatitis caused mechanically (spines, irritant hairs) or by irritant chemicals in plant sap (especially members of the Ranunculaceae, Euphorbiaceae and Compositae plant families); phytophotodermatitis resulting from skin contamination by plants containing furocoumarins, and subsequent exposure to UV light (notably members of the Umbelliferae and Rutaceae plant families); and immediate (type I) or delayed hypersensitivity contact reactions mediated by the immune system in individuals sensitized to plants or plant products (e.g. peanut allergy, poison ivy (Toxicodendron) poisoning).     

Metabolic profiling of the Mexican anxiolytic and sedative plant Galphimia glauca using nuclear magnetic resonance spectroscopy and multivariate data analysis

Galphimia glauca is popularly employed in Mexico for the treatment of central nervous system disorders. Pharmacological and phytochemical studies have resulted in the identification of the anxiolytic and sedative principle consisting of a mixture of nor-secofriedelanes, named the galphimine series (1 - 9). These active constituents were found in plants collected in the vicinity of a restricted region in Central Mexico, where this species is abundant. A metabolic profiling carried out by means of 1H-NMR spectroscopy and multivariate data analysis was applied to crude extracts from wild plant populations, collected from six different locations as a quality control assessment, in order to differentiate their chemical profile. Principal component analysis (PCA) of the 1H-NMR spectra revealed clear variations among the populations, with two populations out of the six studied manifesting differences, when the principal components PC-1 and PC-2 were analyzed. These two PCs permitted the differentiation of the various sample populations, depending on the presence of galphimines. This information consistently correlated with the corresponding HPLC analysis. The neuropharmacological effects of the crude extracts were evaluated by using ICR mice in the elevated plus maze, as well as the sodium pentobarbital-induced hypnosis models. Both assays demonstrated anxiolytic and sedative responses only among those sample populations which had previously been differentiated by PC-1. Partial least square regression-discriminant analysis (PLS-DA) also confirmed a strong correlation between the observed effects and the metabolic profiles of the plants. The overall results of this study confirm the benefits of using metabolic profiling for the in silico analysis of active principles in medicinal plants.     

Neuroprotective effects of resveratrol derivatives from the roots of Vitis thunbergii var. sinuate against glutamate-induced neurotoxicity in primary cultured rat cortical cells

We observed that an aqueous extract of this medicinal plant exhibited significant neuroprotection against glutamate-induced toxicity in primary cultured rat cortical cells from methanol extracts of the roots of Vitis thunbergii var. sinuate (Vitaceae). To further clarify the underlying neuroprotective mechanisms of this observed effect, we isolated and identified various active fractions and components. By using such fractionation procedures, five resveratrol derivatives - vitisinols A (1), B (2), C (3), (+)-vitisin A (4), and (+)-vitisin C (5) - were isolated from the methanol extracts from the roots of V. thunbergii var. sinuate. Among these five resveratrol derivatives, 3 exhibited most significant neuroprotective activity against glutamate-induced neurotoxicity, as indicated by a cell viability of approximately 75%-85%, at concentrations ranging from 0.1 μM to 10 μM. These findings indicate that the neuroprotective effects of V. thunbergii var. sinuate might be due to the inhibition of glutamate-induced toxicity by resveratrol derivatives present in the plant.     

Synthetic and natural coumarins as antioxidants

Coumarins, an old class of compounds, are naturally occurring benzopyrene derivatives. A lot of coumarins have been identified from natural sources, especially green plants. These natural compounds have served as valuable leads for further design and synthesis of more active analogs. The pharmacological and biochemical properties and therapeutic applications of simple coumarins depend upon the pattern of substitution. Coumarins have attracted intense interest in recent years because of their diverse pharmacological properties. Among these properties, their antioxidant effects were extensively examined. In this review, plant derived coumarins and their synthetic analogs will be systematically evaluated based on their plant origin, structure-activity relationship and antioxidant efficacy. Owing their diverse effects and inconclusive results from different in vitro studies, the mechanism of their action has not yet been fully understood and the correlation of effects with chemical structure is not conclusive at the moment. It is the objective of this review will be to summarize experimental data for different coumarins used as antioxidant agents, because promising data have been reported for a series of these agents. In addition, their ability to bind metal ions represents an additional means of modulating their pharmacological responses.     

甘草提取物及有效成分抗代谢相关脂肪性肝病的药理作用及机制研究进展

甘草是最常用的药用植物,广泛应用于食品及制药行业。甘草的化学成分主要有三萜皂苷类、黄酮类和多糖类等,具有抗氧化、免疫调节、抗病毒及抗炎保肝等多种药理作用。现代研究发现甘草提取物及有效成分（甘草酸、甘草次酸、甘草查尔酮A、甘草总黄酮等）能通过调节糖脂代谢、减轻氧化应激、改变肠道菌群、保护肠道屏障等机制达到改善及治疗代谢相关脂肪性肝病（MAFLD）的目的。综述近年来甘草提取物及有效成分抗MAFLD的药理作用及机制研究进展,旨在为该类药物的临床合理应用及新药研发提供理论依据。     

Evaluation of the antibacterial activity of Chilean plants traditionally used for wound healing therapy against multidrug-resistant Staphylococcus aureus

Anti-staphylococcal activity of Chilean medicinal plants traditionally used by the Huilliche people for wound healing therapy was evaluated against nine Staphylococcus aureus strains. Three extracts of 26 plant samples (20 species) were evaluated by agar overlay bioautography and MIC determination. Total phenolics and tannins were determined, and the antibacterial contribution of the latter was evaluated. The diffusion assay showed that 17 species were active against susceptible S. AUREUS and that 15 species were active against resistant S. aureus. Removal of tannins from extracts rendered only six species active. MIC-determination showed that 20 extracts had antibacterial activity on all eight strains, and the most potent MIC value was 64?μg/mL. Remarkably, 37 extracts were active against the otherwise multidrug-resistant vanthida strain. Our findings support the wound healing properties of Huilliche medicinal plants and the hypothesis that these plants are promising sources of potential anti-staphylococcal agents towards multidrug-resistant strains.     

蒿属植物在胃肠道疾病防治中的药理作用及其机制研究进展

蒿属植物在世界各国胃肠道疾病传统防治中有广泛应用,现代药理研究验证了蒿属植物提取物及其活性成分异泽兰黄素、dehydryleucodine等的临床前及临床治疗效果。艾蒿、茵陈等蒿属植物是传统中药,具有广泛的药理活性;然而,国内对其在胃肠道疾病防治中的应用及现代研究相对滞后。主要综述了蒿属植物在胃肠道疾病防治中的药理作用及其机制研究进展,以期为蒿属植物的创新应用及中药现代化研究提供借鉴。