Journal of Ethnopharmacology

Published by Elsevier
Print ISSN: 0378-8741
The Amazon Indians Waiãpi living in the West of Amapá State of Brazil, treat malaria with an inhalation of vapor obtained from leaves of Viola surinamensis. The essential oil obtained from adult and plantlet leaves was analyzed by GC/MS and 11 monoterpenes, 11 sesquiterpenes and three phenylpropanoids were identified. Plantlet essential oil caused 100% of growth inhibition after 48 h in the development of the young trophozoite to schizont stage and the sesquiterpene nerolidol (100 microg/ml) was identified as one of the active constituents (100% of growth inhibition was obtained). In addition, examination of [U14C]-glucose incorporation showed that activity of nerolidol is related to the inhibition of glycoprotein biosynthesis.
Panax notoginseng is used as a therapeutic agent to stop haemorrhages and a tonic to promote health in Chinese medicine. Currently saponins of P. notoginseng (PNS) are especially given attentions for their hemorheological properties. The pharmacokinetic profiles of the main PNS are still not accurately investigated. Therefore, our preliminary aim is to elucidate the pharmacokinetic features of ginsenoside Rb(1) (Rb(1)) and ginsenoside Rg(1) (Rg(1)), two of the main PNS in rats. Firstly, quantitive analysis of Rb(1) and Rg(1) in saponins of P. notoginseng was studied and the most suitable assay method by HPLC for blood sample were established. Then Rb(1) and Rg(1) in the same serum were determined after administering PNS to rats. The decline of Rb(1) in serum could be described by a two-compartment model. The half-life of alpha phase was 23.40 min and that of beta phase was 17.96 h. Rb(1) was absorbed from the digestive tract and the bioavailability via P.O. was 4.35%. The pharmacokinetics of Rg(1) in rats also could be described by a two-compartment model. The half-lives of Rg(1) were 24.23 min for alpha phase and 14.13 h for beta phase. Rg(1) could be absorbed in the digestive tract and the oral bioavailability was 18.40%. Both of the low oral bioavailability of Rb(1) and rapid reduction of Rg(1) in blood indicated that formula modification is necessary.
HD-03 is a polyherbal formulation containing plant drugs which are known for their hepatoprotective properties in the Ayurvedic system of medicine. In the present study, the formulation was evaluated for its protective effect against diverse hepatotoxic agents viz., paracetamol, thioacetamide and isoniazid. Treatment with HD-03 led to significant amelioration of toxin-induced changes in the biochemical parameters. Since the protective effect of HD-03 was observed in all three types of intoxication, which are different in their primary mechanism of inducing hepatotoxicity, a protective mode of action of HD-03, not specific to the hepatotoxin, is suggested.
The biochemical effect of coriander seeds on lipid parameters in 1,2-dimethyl hydrazine (DMH) induced colon cancer in rats were studied. The study shows that the concentrations of cholesterol and cholesterol to phospholipid ratio decreased while the level of phospholipid increased significantly in the DMH control group compared to the spice administered group. Fecal dry weight, fecal neutral sterols and bile acids showed a sharp increase in the coriander-fed group compared with the DMH administered group. Thus, coriander plays a protective role against the deleterious effects in lipid metabolism in experimental colon cancer.
Although many studies have been performed to elucidate the molecular consequences of ultraviolet irradiation, little is known about the effect of natural products. Ultraviolet irradiation is widely considered to be an environmental stress. Here we investigated the effect of erythrodiol-3-acetate on the expressions of MMP-1,2 in cultured human skin fibroblasts. Erythrodiol-3-acetate was isolated from the stems of Styrax japonica (Styracaceae). Erythrodiol-3-acetate reduced the expression of MMP-1 but not MMP-2, at the mRNA and protein levels in a dose-dependent manner by ultraviolet irradiation. Taken together, our results suggest that erythrodiol-3-acetate an important role in the reduction of MMP-1 induction by ultraviolet irradiation.
Prunus persica L. BATSCH seed-water extract (PPE) has been used in the treatment of the degenerative disorders, such as hypermenorrhea and dysmenorrhea, in Taiwan, China, Japan and Korea. In this study, the effects of oral administration of PPE on the extracellular acetylcholine concentration in the hippocampus of rats were evaluated, and compared to that of tacrine (9-amino-1,2,3,4-tetrahydroacridine hydrochloride), a well-known and centrally acting acetylcholinesterase (AChE) inhibitor, which had been developed for the treatment of Alzheimer's disease. We measured the inhibition of brain AChE. PPE at 2.5g/kg and tacrine at 5mg/kg showed significant effects for more than 6h. At these doses, the maximum increases were observed at about 1.5h after administration of PPE, and at about 2h with tacrine, and were 454 and 412% of the pre-level, respectively. The results suggest that oral administration of PPE and tacrine increases acetylcholine concentration in the synaptic cleft of the hippocampus mostly through AChE inhibition, and that PPE has a potent and long-lasting effect on the central cholinergic system.
Dangguijakyak-san protects dopamine neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity under postmenopausal conditions. Dangguijakyak-san (DJS), a famous traditional herbal formula, has long been used to treat gynecological disorders, including postmenopausal symptoms. This study evaluated the effects and mechanism of DJS on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a postmenopausal mouse model induced by ovariectomy. Three weeks after ovariectomy, C57bl/6 female mice were divided randomly into (1) control, (2) MPTP (30 mg/kg/day, i.p., 5 days), (3) MPTP+estrogen (50 μg/kg/day, i.p., 5 days), and (4) MPTP+DJS (50 mg/kg/day, p.o., 5 days) groups. We investigated the behavioral recovery and dopamine neuron protection of DJS using the pole test and tyrosine hydroxylase (TH) immunohistochemistry. We also explored the mechanism by assessing the protein expression of Bax, Bcl-2, cytochrome c, and cleaved caspase-3. DJS treatment restored the movement behavior impaired by MPTP, showing a similar or better effect than estrogen. DJS protected TH-immunoreactive cells and fibers in the nigrostriatal region from MPTP toxicity. In addition, DJS inhibited the Bcl-2 decrease and Bax increase in mitochondria, cytochrome c release to the cytosol, and caspase-3 activation induced by MPTP. DJS showed behavior recovery and dopamine neuron protection against MPTP-induced toxicity via anti-apoptotic activities in ovariectomized female mice. These results suggest that DJS treatment is effective for postmenopausal neurodegenerative diseases.
Ethnopharmacological relevance: Cyperi Rhizoma has commonly been used for the treatment of gynecological and neuropsychiatric disorders in traditional medicine. The aim of this study was to evaluate the estrogenic properties and neuroprotective effects of Cyperi Rhizoma under estrogen-deprived condition in female mice. Materials and methods: To determine the estrogen-like effect of Cyperi Rhizoma extract (CRE), we measured luciferase expression after transfection of a promoter construct containing an estrogen response element (ERE) and treatment of CRE. To evaluate the neuroprotective effect of CRE, we measured striatal dopamine, movement ability, tyrosine hydroxylase (TH) immunoreactivity, and apoptosis-related protein expression levels after treatment of CRE either with or without 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in ovariectomized female mice. Results: CRE significantly induced the luciferase expression driven by an ERE in PC12 cells, a dopaminergic cell line, in a dose-dependent manner. In mice, MPTP significantly decreased the levels of dopamine in the striatum and behavior performance; in contrast, both CRE and 17β-estradiol benzoate (EB) recovered these parameters to normal levels. CRE and EB treatment also recovered TH immunopositive fibers and cells, respectively, from MPTP toxicity. Additionally, MPTP significantly down-regulated Bcl-2 expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in Bax expression, cytochrome C translocation to the cytosol, and cleaved-caspase-3 expression, whereas these were inhibited by CRE or EB treatment. Conclusions: These findings provide the first evidence that CRE has estrogen-like and neuroprotective effects on dopaminergic neurons in estrogen-deprived mice treated with MPTP-toxin.
Ethnopharmacological relevance: Acorus gramineus Solander (Acoraceae, AG), is a widely distributed plant in Asian countries. Rhizome part of this plant has long been used as a traditional medicine for treating various symptoms including central nervous system (CNS) disorders. Aim of study: The anti-neuroinflammatory effect of AG aqueous extract was investigated using in vitro cellular and in vivo Parkinson's disease (PD) mouse model. Materials and methods: Lipopolysaccharide (LPS) is used to stimulate BV-2 microglial cells in vitro and the changes in neuroinflammatory expressional levels were measured using ELISA, Western blotting, RT-PCR and immunofluorescence techniques. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD was developed followed by immunohistochemical analysis of specific brain tissues. Results: LPS-stimulation to BV-2 cells increased the production of nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β. Pretreatment with AG extract inhibited the increased levels of NO and pro-inflammatory cytokines in LPS-stimulated BV-2 cells. Mechanistic study revealed that AG acts via the regulation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs) and TRIF-dependent signaling pathways. Further, AG protected MPTP-induced neuronal cell death and inhibited neuroinflammation in vivo. Conclusion: Our results indicated that AG extract exerted anti-neuroinflammatory effects against activated microglia mediated insults through multiple signaling pathways and prevented in vivo neuronal cell death in mouse model of PD substantiating the traditional claims for its use in CNS disorders.
Phyllanthus urinaria Linnea (Euphorbiaceae) is a widely used traditional medicinal plant by oriental countries and has been reported to possess various biological activities. Previously, the acetone extract from Phyllanthus urinaria was found to inhibit herpes simplex virus (HSV) infection. In this study, geraniin and 1,3,4,6-tetra-O-galloyl-beta-D-glucose (1346TOGDG), both of which were isolated from the acetone extract of Phyllanthus urinaria, were examined for their activity against HSV-1 and HSV-2 in vitro. Results showed that geraniin actively suppressed HSV-2 infection, whereas 1346TOGDG effectively inhibited HSV-1 infection. The 50% inhibitory concentration (IC(50)) was 18.4+/-2.0 microM for geraniin against HSV-2 infection, and 19.2+/-4.0 microM for 1346TOGDG against HSV-1. No toxic effect towards the host cell was observed at the antiviral concentrations. In conclusion, geraniin and 1346TOGDG were found to inhibit HSV-1 and HSV-2 multiplication at different magnitudes of potency.
1,7-Dihydroxy-3,4-dimethoxyxanthone (XAN) is an antirheumatic agent isolated from traditional Chinese medicine Securidaca inappendiculata Hassk. This study was designed to investigate its anti-proliferative and anti-inflammatory activities on rheumatoid arthritis derived fibroblast-like synoviocyte cell line MH7A, and explore the underlying mechanism. The anti-proliferative activity of XAN on MH7A cells was assessed by MTT method. Its pro-apoptotic and cell cycle arrest activities were analyzed by flow cytometry. W-B method was employed to investigate hallmark kinases involved in the course. Pro-inflammatory cytokines in culture supernatant of MH7A cells was determined by ELISA method. The results showed XAN efficiently suppressed the proliferation and secretion of IL-1β and IL-6 of MH7A cells in a concentration-dependent manner. Co-treatment with MAPKs inhibitors U0126, SB202190 and SP600125 indicated JNK and p38 pathways were involved in the course. Up-regulation of p-p38, p-ERK, bax and p21, and down-regulation of p-JNK, cyclin D1 and bcl-2 were observed upon the treatment with XAN. SB202190 partly reversed the modulatory effects. The results suggested XAN inhibited the proliferation of MH7A cells mainly via cell cycle arrest at G1/S phase, and the activity was due to the up-regulation of p-p38, which led to the modulation of p21 and cyclin D1. The down-regulation of p-JNK by XAN suppressed the secretion of pro-inflammatory cytokines, which was beneficial to the anti-proliferative activity of MH7A cells. XAN selectively modulated MAPKs signaling, and exerted the subsequent anti-proliferative and anti-inflammatory activities on MH7A cells. Copyright © 2015. Published by Elsevier Ireland Ltd.
Effect of RCM-101 (1–100 ␮ g/ml) on endothelium-independent (SNP- 0.001-1 ␮ M) relaxations in PE-precontracted endothelium-denuded aorta. Data are means ± S.E.M. ( n = 6). P > 0.05, two-way ANOVA. 
The herbal constituents of RCM-101 (% of granulated herbs by weight) a
Half-inhibition concentration (IC 50 ) values of the extract of individual herb included in the herbal formula RCM-101
Inhibition of LPS/IFN- ␥ -stimulated NO production in Raw 264.7 cells by RCM-101 (1–100 ␮ g/ml; determined as the stable metabolite nitrite). Data plotted are means percentage of control NO production ( ± S.E.M.; n = 6). * P < 0.05, one-way ANOVA and Dunnet’s test. 
Inhibition of LPS/IFN-induced iNOS protein in RAW 264.7 cells. PC = positive control (iNOS lysate), VC = vehicle control, Dex = dexamethasone. Cells were treated by LPS (1 g/ml) and IFN-(10 ng/ml) in the presence or absence of RCM-101 (100 g/ml) for 24 h. Results are expressed as mean ± S.E.M. (n = 3). *P < 0.05, one-way ANOVA and Dunnet's test.
A Chinese herbal formula (RCM-101) has shown to be effective in reducing symptoms of seasonal allergic rhinitis (SAR) in a randomised, placebo-controlled clinical trial. The aim of this study is to investigate the effects of RCM-101 on the actions and synthesis of nitric oxide (NO). l-Arginine-induced endothelium-independent relaxations were studied in rat isolated aorta which was pre-treated with lipopolysaccharide (LPS). NO production and inducible nitric oxide synthase (iNOS) protein expression were studied in LPS and interferon gamma-stimulated murine macrophages (Raw 264.7), measured by NO sensors and Western blotting. In rat aortic preparations, RCM-101 significantly inhibited endothelium-independent relaxations to l-arginine, but not affected those to sodium nitroprusside (SNP). In Raw 264.7 cells, RCM-101 and some of its individual ingredients (e.g., Radix glycyrrhizae, Radix bupleuri, Radix saposhnikoviae and Atractylodis rhizome macrocephalae) significantly inhibited the NO production and iNOS protein expression. The findings indicate that RCM-101 may inhibit inducible NO production by suppressing iNOS. In addition, its inhibitory action of iNOS is likely to be mediated by several key herbal ingredients.
Korean ginseng tea (KGT), prepared from the roots of Panax ginseng, is widely used by Korean people for antistress, antifatigue, and endurance promoting effects. In the present study we evaluated neuroprotective/cerebroprotective actions of KGT in stroke, using rat global and focal models of ischemia. Varied biochemical/enzymatic alterations, produced subsequent to the application of middle cerebral artery (MCAO) and bilateral carotid artery occlusion (BCAO) followed by reperfusion viz. increase in lipid peroxidation (LPO) and decrease in glutathione (GSH), glutathione reductase (GR), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD), were markedly reversed and restored to near normal levels in the groups pre-treated with KGT (350 mg/kg given orally for 10 days). It is concluded that the protective action, exhibited by KGT against hypoperfusion/reperfusion induced brain injury, suggests its therapeutic potential in cerebrovascular diseases (CVD) including stroke. These findings are important because: (a) the present treatment strategies for CVD are far from adequate and (b) KGT with wide usage is known to be a safe natural product.
Sesuvium portulacastrum has long been used as a remedy for fever and scurvy. Hydrodistillation was used to extract the essential oil from the fresh leaves of Sesuvium portulacastrum. The essential oil yield obtained was 0.15%. Using GC-MS analysis, alpha-pinene, camphene, beta-pinene, alpha-terpinene, O-cymene, limonene, 1,8-cineole, alpha-terpinene, bornyl acetate, tridecane, trans-caryophyllene and alpha-humulene were identified. The hole plate diffusion method was used for antibacterial testing. The essential oil exhibited antibacterial activity against Acetobacter calcoacetica, Bacillus subtillis, Clostridium sporogenes, Clostridium perfringens, Escherichia coli, Salmonella typhii, Staphylococcus aureus and Yersinia enterocolitica. The mycelium growth inhibition method was used for the antifungal testing. The oil exhibited antifungal activity against Candida albicans, Aspergillus niger, Aspergillus flavus and Penicillium notatum. Using the beta-carotene, acetone and linoleic acid method for the antioxidant testing, the essential oil showed antioxidant activity threshold of 15.9 mm mean zone of color retention.
Rhodiola rosea is a medicinal plant having stimulating and adaptogenic properties, and some reports also indicate its anticancer and antimutagenic effect. However, the mechanism of its anticancer effect is unknown as there have been no cytological studies regarding cytostatics, cell cycle, induction of apoptosis or the mitotic activity of healthy and cancerous cells. In the present paper, those parameters were investigated using HL-60 cells, with flow cytometry and fluorescence microscopy. It has been found that the extract of Rhodiola rosea rhizomes inhibits division of HL-60 cells, which is preceded by an accumulation of cells at the prophase stage. This leads to induction of apoptosis and necrosis in HL-60 cells, and to marked reduction of their survival. The cells enter apoptosis from phase G2/M of the cell cycle. After treatment with the extract, no chromosome aberrations or micronuclei were observed, which indicates the mild action of the extract. The cytostatic and antiproliferative effect of the Rhodiola rosea rhizome extract, and its mild action, raises hope for its use in anticancer therapy by enhancing the effectiveness of cytostatics.
A special ethanolic-aqueous extract from seven traditional medicinal plants (BNO 1030) has been used for several decades to treat recurrent infections of the respiratory tract. Considering the potential role of interleukin-8 (IL-8) and human beta defensin-2 (hBD-2) in inflammation, we investigated the effect of BNO 1030 on lipopolysaccharide (LPS) from Pseudomonas aeruginosa or IL-1β-induced inflammatory mediators in A549 human type II alveolar epithelial cells. A549 cells were stimulated with LPS (100 μg/ml) or IL-1β (50 ng/ml) in the presence of the preparation and the secretion of IL-8 and hBD-2 were measured after 18 h and 24h in cell free supernatants using enzyme-linked immunosorbent assays (ELISA). Cell viability and cell growth was investigated by propidium iodide uptake and WST-1 assay, respectively. BNO 1030 inhibited the secretion of IL-8 and hBD-2 at non-cytotoxic concentrations (0.1-100 μg/ml; cell growth inhibitory concentration, 50% (IC(50))=678 ± 87.6 μg/ml). Stimulation by IL-1β led to a 7-fold activation of IL-8 secretion, which was reduced by 37.7 ± 4.1% (p<0.05) after incubation with 100 μg/ml BNO 1030. Inducible hBD-2 was suppressed by 91.8 ± 15.6% (p<0.01) at the same concentration of BNO 1030 (IC(50)=0.7 ± 0.1 μg/ml). The 2-fold increase of IL-8 secretion by LPS-stimulated cells was completely abolished at concentration of 50 μg/ml BNO 1030 (IC(50)=5.7±3.6 μg/ml). BNO 1030 suppressed the secretion of IL-8 and hBD-2 in cultured epithelial A549 cells. These results support its use as a phytotherapeutic product prepared from traditional remedies in inflammatory diseases, especially those affecting the respiratory tract.
Certain Lamiaceous and Asteraceous plants have long histories of use as restoratives of lost or declining cognitive functions in western European systems of traditional medicine. Investigations were carried out to evaluate human CNS cholinergic receptor binding activity in extracts of those European medicinal plants reputed to enhance or restore mental functions including memory. Ethanolic extracts were prepared from accessions of these plants and a number of other species related by genus. Amongst the plant extracts screened for contents able to displace [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic receptors and muscarinic receptors, respectively in homogenates of human cerebral cortical cell membranes, the most potent extracts, prepared from one accession of Melissa officinalis, three Salvia species and Artemisia absinthium had IC50 concentrations of < 1 mg/ml. The displacement curves of some extracts were comparable with that of carbamylcholine chloride, a potent acetylcholine analogue. Choline, a weak nicotinic ligand (IC50 = 3 x 10(-4) M) was found in extracts of all plants studied at concentrations of 10(-6)-10(-5) M. These concentrations could not account for not more than 5% of the displacement activity observed. Some extracts displayed differential displacement at nicotinic and muscarinic acetylcholine receptors, with M. officinalis 0033 having the highest [3H]-(N)-nicotine displacement value and Salvia elegans with the highest [3H]-(N)-scopolamine displacement value. There was also considerable variation in cholinoreceptor interactions between different accessions of a single plant species. Although most plant extracts screened showed some nicotinic and muscarinic activity, only some showed dose-dependent receptor activity typical of materials with genuine cholinergic activity.
The aqueous extract obtained from Stichaster striatus Müller & Troschel (Asteroidea, Stichasteridae) has been shown to possess activity as an alcohol appetite inhibitor after oral administration in a rat model with a genetically established excessive appetite for alcohol (Wistar rats, lineage UChB). A significant decrease in the consumption of ethanol was observed (unrelated to a possible disulfiram effect) without a change in the normal food or water intake during the experimentation period. A bio-guided fractionation of the extract was carried out in order to identify the most active fraction, in which the presence of a group of natural endogenous polyamines in undetermined proportions is suspected. Our hypothesis was to relate the activity obtained for the original ME-3451-106 extract with the presence of these polyamines in the extract in question. The activity shown by a series of commercially available polyamines (putrescine (Pu), spermidine (SPD) and spermine (SP)) in inhibiting voluntary ethanol intake lends support to our hypothesis. The extract was selected on the basis of oral tradition, which claimed that the consumption of a "soup" obtained by boiling starfish, later identified as Stichaster striatus, prevented the appearance of alcoholism in laborers on properties entrusted to the Jesuit order during the middle period of the Spanish conquest of America (17-18th century).
This work aimed to elucidate the anti-inflammatory mechanism of the n-BuOH subfraction (PL) prepared from fruiting bodies of Phellinus linteus. PL induced heme oxygenase-1 (HO-1) of the RAW264.7 macrophages in concentration- and time-dependent manner. It suppressed induction of inducible nitric oxide synthase (iNOS) and subsequent production of nitric oxide (NO) through down-regulation of iNOS promoter activity in lipopolysaccharide (LPS)-stimulated macrophages. Zn(II) protoporphyrin IX (ZnPP), a specific inhibitor of HO-1, partly blocked suppression by PL on iNOS promoter activity and NO production, which were elevated in LPS-stimulated macrophages. LPS was able to enhance NO production via reactive oxygen species (ROS) generation, c-Jun NH(2)-terminal kinase (JNK) and c-Jun induction. ZnPP prevented PL from down-regulating ROS generation and JNK activation in LPS-stimulated macrophages. Taken together, PL shows its anti-inflammatory activity via mediation of HO-1 in an in vitro inflammation model.
Effect of plant extracts and the positive control, metformin (M) on glucose utilisation (top) and toxicity (bottom) in Chang liver cells. Cells were exposed to 12.5 g/ml extract or 1 M metformin for 48 h, where after glucose utilisation was measured in the presence of 8 mM glucose and 50 g/ml extract or 1 M metformin for 3 h. Organic extracts were prepared with dichloromethane:methanol (1:1). B = bark; FL = flowers; L = leaves; R = roots; S = stems; T = twigs; W = whole plant. The first letters of genus and species names of each plant were used to abbreviate plant names; refer to Table 2 for full names. Data points represent mean ± S.E.M.; N = 8 (glucose utilisation) or 4 (cell viability) wells in a 96-well plate. 
Aim: To investigate the traditional antidiabetic uses of indigenous or naturalised South African plants using an optimised screening and scoring method. Materials and methods: Eleven plant specieswere screened against Chang liver, 3T3-L1 adipose and C2C12 muscle cells measuring glucose utilisation in all three cell lines and toxicity in the hepatocytes and adipocytes only. A scoring system was devised to aid interpretation of results. Results: Catharanthus roseus results correlated with previously reported in vivo results, with best stimulation of glucose utilisation in hepatocytes. Momordica foetida and Momordica balsamina extracts were active in myocytes but only the latter stimulated glucose utilisation in hepatocytes. Brachylaena discolor gave the best overall results, with all plant parts giving high activity scores and negligible toxicity. In vitro toxicity results for Catharanthus roseus, Vinca major, Momordica balsamina and some Sclerocarya birrea extracts raise concern for chronic use. Conclusion: This screening system increases the likelihood of identifying drug candidates using in vitro antidiabetic screening of crude plant extracts, whilst the scoring system aids data interpretation. Ethnopharmacological relevance: The multitude of metabolic steps affected by Type II diabetes offer many drug targets but they complicate in vitro screening to validate traditional uses or find new drug leads from plants.
The importance of the Genizah for the research of the medieval Mediterranean communities, supplying information on almost every aspect of life, is well known among historian. Less known is that pharmacy was the most popular of all branches of the healing art in the medieval Jewish community of Cairo, according to the Genizah manuscripts. Sources for study of medieval practical drugs are extremely rare since most records naturally vanish over the years, and only some medical books, which contained theoretical pharmacology, have survived to the present day. Drugs lists enable us to understand medieval practical pharmacy and to reconstruct their inventories. This study reports on 71 original drugs lists that were found in the Genizah; they are different from merchants' letters dealing with commerce in drugs and give no instructions for the use or preparation of formulas as usually found in prescriptions. Twenty-six lists are written in Judeo-Arabic and 45 in Arabic, none of the lists is written in Hebrew. The longest list contains 63 identified substances. These lists were apparently used by pharmacists for professional and business purposes as inventories of drugs, records, orders, or even receipts. Two hundred and six different drugs are mentioned in the drugs lists of which 167 are of plant origin, 16 are of animal origin, and the remaining 23 are inorganic. The lists point directly to the place they occupied on the shelves of the pharmacies that could be found in the lanes and alleys of the Jewish quarter of Cairo. The most frequently mentioned substance were myrobalan (27), pepper and saffron (21), lentisk (15), almond, basil, rose, rosemary (14), cattle products, camphor and spikenard (13).
Current study was designed to explore the analgesic and anti-inflammatory effects of a constituent isolated from Mallotus philippinensis, in order to validate its folk use. 11-O-galloylbergenin was isolated from ethanolic extract of Mallotus philippinensis. Analgesic and anti-inflammatory activities of the test compound were assessed using formalin test and carrageenan-induced paw edema models. 11-O-galloylbergenin showed significant analgesic activity at doses of 20 and 40 mg/kg against formalin test in rats. Similarly, 11-O-galloylbergenin exhibited significant anti-inflammatory activity in carrageenan-induced paw edema model at doses of 10, 20 and 30 mg/kg. 11-O-galloylbergenin has demonstrated its significant potential to be further investigated for its discovery as a new lead compound for management of pain and inflammation.
Extracts of Andrographis paniculata Nees are used for various ethnomedical conditions including hyperglycemia and hypertension complications. The purpose of this study is to evaluate the anti-diabetic nephropathy effect of diterpene lactones andrographolide (AP1) and 14-deoxy-11,12-didehydroandrographolide (AP2) from Andrographis paniculata. MES-13, a SV40-transformed murine glomerular mesangial cell line, was cultured in high concentration of glucose to induce diabetic nephropathy phenotypes, which include secretion of extracellular matrix protein fibronectin, cytokine TGF-β, states of oxidative stress, and apoptosis marker caspase-3. Our data suggest that addition of compounds AP1 or AP2 reduces the phenotypes indicating diabetic nephropathy in MES-13 cells. The compound AP2 showed potent activity than AP1 in the reduction of apoptosis marker caspase-3, fibrosis marker TGF-β, and PAI-1. Furthermore, AP1 and AP2 do not have antioxidant ability in acellular environment; however, addition of AP1 and AP2 reduced intracellular oxidative states in high glucose cultured MES-13 cells. This is the first report on anti-diabetic nephropathy effect of AP1 and AP2 in part due to the regulation of intracellular signaling transduction, not mere clearance of reactive oxygen species. Thus, this study may be useful for drug development or food supplement for diabetes and nephropathy from Andrographis paniculata.
Aim of this study: Gochnatia polymorpha ssp. floccosa (Asteraceae), popularly known as "cambará", is well recognized in Brazilian traditional medicine to treat the respiratory tract inflammatory diseases and rheumatism. However, no scientific data have been published to support this ethnopharmacological use. This work aimed to evaluate the anti-inflammatory action of its ethanol (EEGP) extract, ethyl acetate (EA), dichloromethane (DCM), petroleum ether (PE) butanolic (BT) fractions, and the isolated compounds bauerenyl acetate (GPC1) and 11,13-dihydrozaluzanin C (GPC2). Materials and methods: The anti-inflammatory activities were evaluated in mice subjected to paw oedema and carrageenan-induced air pouch inflammation models. Results: The oral administration of EEGP (30, 100 and 300 mg/kg), DCM (50 mg/kg), BT (20 mg/kg) and GPC2 (10 and 30 mg/kg), but not EP and EA fractions (both at 30 mg/kg) and GPC1 (1 and 10 mg/kg), significantly inhibited the paw oedema induced by carrageenan (41±13, 39±5 and 60±10% for EEGP at the three doses, respectively; 44,47±12.8 and 70.19±11.52% for DCM and BT, respectively; and 29.52±4.8 and 31.67±5.4%, for 11,13-dihydrozaluzanin C at 10 and 30mg/kg, respectively) compared to control group. The oral administration of EEGP (30, 100 and 300 mg/kg) inhibited the carrageenan-induced leukocyte migration in the air pouch model (37.2±12.5, 62.6±5.0 and 54.3±6.8%, respectively), as well as protein extravasation (47.9±12.5, 51.7±15.2 and 60.9±13.7%, respectively) compared to control group. In a similar way, DCM (50 mg/kg) or GPC2 (10 mg/kg), but not BT (20 mg/kg) given by oral route inhibited leukocyte infiltration into the pouch (29.5±10.6 and 54.4±21.8%, respectively). Also DCM and GPC2 significantly reduced the protein levels in the supernatants (52.4±15.0 and 51.83±16.9%, respectively). Conclusion: The results suggest that EEGP, and BT and DCM fractions from G. polymorpha possess anti-inflammatory activity and probably the compound 11,13-dihydrozaluzanin C was responsible, at least in part, for this action.
Fruiting bodies of Phellinus linteus were extracted with 70% ethanol at room temperature. The Phellinus linteus extract (PL) showed strong anti-angiogenic activity, which was detected using the chick embryo chorioallantoic membrane (CAM) assay. The in vitro antioxidant activities of PL were evaluated using two different bioassays. PL was comparable to Vitamin C in scavenging the stable free radical 1,1-diphenyl-2-picrylhyrazyl (DPPH). It also inhibited lipid peroxidation (LPO) in a concentration-dependent manner. These results suggest that antioxidant and anti-angiogenic activities of Phellinus linteus would be partly responsible for its anti-tumor effect.
Dangnyohwan (DNH) has been used for treatment of diabetes mellitus. However, the exact cellular and molecular mechanisms underlying the beneficial effects of DNH are not well understood. Therefore, we investigated how DNH improves hyperglycemia and insulin resistance in obese-type diabetes model. We examined the effect of DNH on the expression of glucose transporter 4 (GLUT4), GLUT4 translocation, and glucose transport activity in muscle and adipose tissues from Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats. DNH ameliorated hyperglycemia and impaired glucose tolerance (IGT) observed in 26- and 42-week-old male OLETF rats. The basal and insulin-stimulated [14C]2-Deoxyglucose (2DG) uptake was significantly increased in adipocytes from DNH-treated OLETF rats, as compared with untreated OLETF rats. The expression level of GLUT4 was markedly decreased (by 90-95%) in the adipose tissue of OLETF rats, whereas DNH treatment drastically increased the expression of GLUT4 within 8 weeks. DNH improved GLUT4 recruitment stimulated by insulin in both the 26- and 42-week-old OLETF rat adipocytes. These results suggest that DNH could exert the beneficial effects on hyperglycemia and insulin resistance by increasing the expression and insulin-stimulated translocation of GLUT4 in OLETF rat adipocytes.
Phellinus linteus and Panax ginseng have been widely used as traditional herbal medicines to treat various diseases including cancer in East Asia. The present study sought to investigate the possible mechanism in anti-proliferative effect of Phellinus linteus that was grown on Panax ginseng (PGP) on B16F10 melanoma cells. The anti-proliferative effect of PGP on B16F10 was evaluated by CCK-8 assays. Apoptotic cells were detected by flow cytometry analysis. The proteins involved in apoptosis and cellular differentiation were assessed by immunoblot analysis. Ginsenosides contents of PG or PGP were analyzed using HPLC. The ethyl acetate fraction (EtOAc) of PGP exhibited the strongest anti-proliferative activity among PGP fractions (butanol or water) on B16F10 cells. PGP EtOAc extract showed stronger inhibitory effect than Panax ginseng (PG) or Phellinus linteus (PL) EtOAc extract on B16F10 melanoma cell proliferation. PGP EtOAc extract induced the dendrite-like structures and the melanin production in B16F10 cells. PGP EtOAc extract increased a sub-G1 cell population through inducing p53/p21 and activated caspase-8 protein expression in B16F10 cells. Notably, PGP EtOAc extract contained ginsenosides Rd, Rg3, Rb2, Rg1 and Rb1 more than PG EtOAc extract. Rd and Rg3 significantly inhibited B16F10 cell proliferation. Our data suggest that PGP EtOAc extract inhibits B16F10 cell proliferation through inducing apoptosis and cellular differentiation.
Ulmus davidiana Nakai (UDN) has been used in folk medicine for its anti-inflammatory activity. In the present study, we investigated the antiapoptotic effect of UDN glycoprotein in glucose/glucose oxidase (G/GO)-induced BNL CL.2 cells. To evaluate the antiapoptotic effect of UDN glycoprotein, experiments were carried out using Western blot analysis for nuclear factor-kappa B (NF-kappaB), caspase-3, and poly(ADP-ribose) polymerase (PARP). We also examined nitric oxide (NO) production and nuclear staining. When BNL CL.2 cells were treated with G/GO (50 mU/ml), viability of the cells was 54.1%. However, the number of living cells after the addition of UDN glycoprotein in the presence of G/GO increased. UDN glycoprotein protected from cell damage caused by G/GO. Interestingly, UDN glycoprotein decreased NF-kappaB activation and stimulated NO production in G/GO-induced BNL CL.2 cells. In apoptotic parameters, UDN glycoprotein inhibited activations of caspase-3 and PARP cleavage in G/GO-induced BNL CL.2 cells. The results of nuclear staining indicated that UDN glycoprotein (50 microg/ml) has a protective ability from apoptotic cell death caused G/GO (50 mU/ml). In conclusion, UDN glycoprotein has a protective effect on apoptosis induced by G/GO through the inhibition of NF-kappaB, caspase-3, and PARP activity, and the stimulation of NO production in BNL CL.2 cells.
Coptidis rhizoma (huanglian) and its major component, berberine, have drawn extensive attention toward their antineoplastic effects in the recent years. The antineoplastic effects are related to the Chinese Medicine (CM) properties of huanglian in treating diseases by removing damp-heat and purging fire and counteracting toxicity. To trace the long history of the traditional use of huanglian from folk medicines, especially from Chinese medicine, to recent pharmacological studies of huanglian and berberine, with an emphasis on their antineoplastic effects and the promise as novel antineoplastic agents. A total of seven databases were extensively searched for literature research. The terms and keywords for searching included huanglian, berberine, Coptis, Coptidis rhizoma, anticancer, anti-invasion, antimatastasis and mechanism. The papers including ours with studies on anticancer and mechanism, pharmacology and toxicology of huanglian and/or berberine were focused. In view of traditional use, the anticancer effects of huanglian can be ascribed to its CM trait by removing damp-heat, fire and toxicity. From modern biomedical studies, anticancer effects have been demonstrated in both huanglian and berberine. The underlying molecular mechanisms involve cell-cycle arrest, apoptosis induction and anti-inflammation. Berberine is an essential anticancer compound in huanglian. In some studies, the use of huanglian was shown to be more effective and beneficial than the use of berberine alone. The presence of other protoberberine-type alkaloids in huanglian might give synergistic effects for the anticancer effects. Berberine also demonstrates effects of antiangiogenesis, anti-invasion and anti-metastasis in some cancer cell lines, however, more investigations are required to unravel the underlying mechanisms involved. The modern evidences of treating cancer with huanglian and berberine have a strong linkage with traditional concept and rules of using huanglian in CM practice. As anticancer candidates with low toxicity, berberine and its altered structure, as well as huanglian and its formulae, will attract scientists to pursue the potential anticancer effects and the mechanisms by using technologies of genomics, proteomics and other advanced approaches. On the other hand, relatively few in vivo studies have been conducted on anticancer effects of huanglian and berberine. The clinical application of berberine or huanglian as novel cancer therapeutic agents requires in vivo validations and further investigations of their anticancer mechanisms.
Brazil is a country of interest to ethnopharmacology because of its great wealth of cultural and biological diversity. This paper describes relevant research activities in the areas of botany, chemistry, basic and clinical pharmacology, and discusses the key factors that shaped ethnopharmacology development in the country. Specific attention is given to analyzing ongoing attempts to include medicinal plant based formulations in the official health care system.
Ethnopharmacological relevance: The scientific study of natural products traditionally used in anticancer preparations has yielded several therapeutically relevant compounds. One of these traditional preparations with potentially beneficial properties is aqueous extracts of Sutherlandia frutescens, a shrub indigenous to the Western Cape region of South Africa. The aims of this study were to evaluate in vitro efficacy of these preparations on the MCF-7 breast adenocarcinoma and MCF-12A non-tumorigenic cell lines in terms of cell proliferation, cell morphology and possible induction of cell death. Materials and methods: Crystal violet staining was used to evaluate cell proliferation, light-and fluorescence microscopy were used to investigate both intracellular and extracellular morphological features of apoptosis and autophagy (e.g. membrane blebbing, condensed chromatin and intracellular lysosomes), while flow cytometry quantified cell cycle changes and induction of apoptosis through analysis of the flip-flop translocation of phosphatidylserine. Results: Crystal violet staining showed a time- and dose specific response to aqueous Sutherlandia frutescens extracts, revealing exposure to 1mg/ml aqueous extract for 48h to be ideal for comparing the differential effects of Sutherlandia frutescens in the MCF-7 and MCF-12A cell lines. Microscopy showed distinct morphological changes with hallmarks of apoptosis being observed in both cell lines. Flow cytometry revealed a decrease in actively cycling cells in both cell lines, and a 4.36% increase in phosphatidylserine translocation in the MCF-7 cell line, indicative of apoptosis induction, while fluorescence microscopy showed evidence of the induction of autophagy. Conclusions: Analyses revealed the carcinogenic MCF-7 cell line to be more susceptible to the cytostatic and cytotoxic effects of aqueous extracts of Sutherlandia frutescens when compared to the non-tumorigenic MCF-12A cell line, thus warranting further research into the exact cellular mechanisms involved and the possible synergistic activities of Sutherlandia frutescens ingredients.
The aim of this study was to evaluate the antiplasmodial properties of 13 plants used against malaria in traditional medicine in Burkina Faso. In vitro antiplasmodial activity of dichloromethane, methanol and aqueous crude extracts obtained from vegetal samples collected in Burkina Faso was first evaluated on the Plasmodium falciparum 3D7 chloroquine-sensitive strain using a colorimetric method. Thirteen extracts obtained from 8 different species were found to exhibit antiplasmodial activity (IC(50)<50 microg/ml). Five species demonstrated a moderate activity (15 microg/ml<IC(50)<50 microg/ml): Boswellia dalzielii (leaves), Waltheria indica (roots and aerial parts), Bergia suffruticosa (whole plant), Vitellaria paradoxa (bark) and Jatropha gossypiifolia (leaves). The best results were obtained with extracts from the Dicoma tomentosa whole plant, from Psorospermum senegalense leaves and from Gardenia sokotensis leaves. These extracts found to display promising antiplasmodial activity, with IC(50) values ranging from 7.0 to 14.0 microg/ml. The most active plant extracts were then tested for in vitro activity on the Plasmodium falciparum W2 chloroquine-resistant strain and also for in vitro cytotoxicity on normal human fibroblasts (WI-38) in order to determine the selectivity index. Dicoma tomentosa (Asteraceae) and Psorospermum senegalense (Clusiaceae) appeared to be the best candidates for further investigation of their antiplasmodial properties, reported for the first time by this study.
The Leonuri Herba has been traditionally used for women's disease in Asian countries. The objective of the present study was to evaluate the subchronic toxicity of Leonuri Herba aqueous extract in male and female F344 rats. Leonuri Herba aqueous extract was administered orally once daily at dose levels of 0, 125, 250, 500, 1000 and 2000mg/kg/day for 13 weeks. Toxicological assessment was performed including mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. There were no treatment related differences in clinical signs, urinalysis, hematology and serum chemistry, except for a histopathologic examination. The squamous cell hyperplasia in the forestomach was observed in both sexes of rats given 2000mg/kg/day of Leonuri Herba aqueous extract. In conclusion, the NOAEL (No Observed Adverse Effect Level) for Leonuri Herba aqueous extract was determined as 1000mg/kg/day in both sexes of rats under the present experimental conditions. And the acceptable daily intake value for Leonuri Herba aqueous extract was calculated to be 10mg/kg body weight per day using a safety factor of 100 to the NOAEL.
Cortex Phellodendri is derived from the dried bark of Phellodendron chinense Schneid. or Phellodendron amurense Rupr. Traditionally, Cortex Phellodendron Chinensis (CPC) and Cortex Phellodendron Amurensis (CPA) are used interchangeably under the name "Huang Bai" for the treatment of gastroenteritis, abdominal pain or diarrhea. The present study aims to compare the anti-inflammatory effect of ethanol extracts of Cortex Phellodendri Chinensis (ECPC) and Cortex Phellodendri Amurensis (ECPA) in a mouse model of inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA). The anti-inflammatory effect was evaluated by measuring the ear thickness, activity of myeloperoxidase (MPO) and the production reactive oxygen species (ROS). The anti-inflammatory mechanism was explored by determining the protein and mRNA levels of cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. The results showed that both ECPC and ECPA significantly decreased the ear thickness, MPO activity and the ROS level in mouse model of inflammation induced by TPA. In addition, ECPC and ECPA also remarkably inhibited the protein and mRNA levels of TNF-α, IL-1β, IL-6 and COX-2. Interestingly, ECPC has better anti-inflammatory effect than that of ECPA. These results indicate that both ECPC and ECPA have potential anti-inflammatory effect on TPA-induced inflammatory in mice, and ECPC is more effective than ECPA. The anti-inflammatory effect of the herbal drugs may be mediated, at least in part, by down-regulating the mRNA expression of a panel of inflammatory mediators including TNF-α, IL-1β, IL-6 and COX-2.
Ethnopharmacological relevance: Acupoint application of cold asthma recipe (CAR) was a traditional Chinese medicine (TCM) method, widely used as an alternative medicine for clinical prevention of the common winter diseases of asthma and bronchitis. Tetrahydropalmatine (THP) was a main active ingredient of CAR extract. The aim of this study is to compare plasma pharmacokinetics and lung distribution of THP between Feishu (FS) acupoint (BL 13) and Non-Feishu (NFS) acupoint application of CAR extract by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Materials and methods: The extract of CAR was topically administrated in FS and NFS acupoint of rats for plasma pharmacokinetics, and topically administrated in FS and NFS acupoint of mice for lung distribution. The plasma and lung homogenates were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on an ACQUITY UPLC BEH C18 column with a mobile phase consisted of 0.1% formic acid in acetonitrile and 0.1% formic acid in water. The detection was accomplished by multiple-reaction monitoring (MRM) scanning in the positive electrospray ionization (ESI(+)) mode. All pharmacokinetic parameters were estimated by non-compartmental analysis. Results: A sensitive, accurate and precise UPLC-MS/MS method was successfully established for determination of THP in 100 μL plasma and lung homogenate. The lower limit of quantification (LLOQ) of THP was 0.05 ng/mL and 0.072 ng/mL, respectively. The pharmacokinetic results manifested that THP was absorbed and eliminated slowly in plasma. Additionally, it was found that there was significantly higher amount of THP absorbed into blood and lung after FS acupoint application compared to NFS acupoint application. Conclusions: Both of the rat plasma pharmacokinetics and mice lung distribution of THP could support that FS acupoint application of CAR extract has greater advantages of absorption into the blood circulation and distribution in target tissue over NFS acupoint application. The results might be helpful in providing a rational explanation for why the TCM chose the acupoint application and elucidating the underlying mechanism of this treatment.
Ethnopharmacological relevance: 12-Deoxyphorbol 13-palmitate (G) is one toxic compound isolated from Euphorbia fischeriana, an Asian spice used for cancer treatment as a folk remedy. However, whether 12-deoxyphorbol 13-palmitate affects angiogenesis remains unclear. Aim of the study: To explore the in vitro and in vivo antiangiogenic effects of 12-deoxyphorbol 13-palmitate and its underlying mechanisms. Materials and methods: We explored antigenic functions in human umbilical vein endothelial cells (HUVEC) by 12-deoxyphorbol 13-palmitate, including proliferation, migration and metastasis through matrigel plug assay, chorioallantoic membrane assay, in vitro migration assay, tube formation assay, motility assay. Antibody chip was applied to screen differentially expressed proteins modulated by 12-deoxyphorbol 13-palmitate, and was further confirmed by RT-PCR and western blot analysis. Tumor xenograft mice were applied to investigate whether 12-deoxyphorbol 13-palmitate could inhibit microvessel density in vivo. Results: 12-Deoxyphorbol 13-palmitate inhibited vascular endothelial growth factor (VEGF)-induced angiogenic processes in vitro, such as proliferation, in vitro migration, and tube formation of HUVEC. In chorioallantoic membrane assay, 12-deoxyphorbol 13-palmitate significantly inhibited neovessel formation. Antibody chip technology demonstrated decreased expression of TIMP-1, TIMP-2, VEGF, basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP)-2, VEGFR-2 and VEGFR-3 proteins in HUVEC after 24h. In addition, 12-deoyphorbol 13-palmitate inhibited the in vivo growth of MCF-7 cells in grafted mouse model. Immunohistochemistry staining showed decreased microvessel density (CD31) and attenuated VEGFR-2 signaling pathways by 12-deoxyphorbol 13-palmitate. Conclusion: 12-Deoxyphorbol 13-palmitate may be utilized to target active angiogenesis through VEGF/VEGFR2 signal pathway for cancer.
The cholesterol lowering effect of SG-GN3, the extract of salted and fermented small shrimps, Acetes japonicus, was investigated in hypercholesterolemic animal models. Hypercholesterolemia was induced with Triton WR-1339 (nonionic detergent) or high cholesterol (HC)-diet. SG-GN3 significantly decreased total cholesterol (TC) in Triton WR-1339 model at 30 post-treatment hour (549.80 +/- 152.46 mg/dl) compared to the control which induced by only Triton WR-1339 (798.84 +/- 94.98 mg/dl), whereas high-density lipoprotein (HDL) content did not decrease (P < 0.05). In HC-diet model, TC content significantly decreased by SG-GN3 treatment at 3 post-treatment day (P < 0.05). These results suggest that SG-GN3 effectively decreased serum TC level in hypercholesterolemic animal models.
In the present study, an aqueous extract from Erica multiflora L. (Ericaceae) flowers was evaluated for its hypocholesterolaemic and hypotriglyceridaemic activities using Triton WR-1339 induced hyperlipemic rats as experimental model. Hyperlipideamia was developed by intraperitonial injection of Triton (200mg/kg body weight). The animals were divided into control (CG), hyperlipidaemic (HG), hyperlipidaemic plus herb extract (HG+EmE) and hyperlipidaemic plus fenofibrate (HG+FF) treated groups. Intragastric administration of Erica multiflora extract (0.25 g/100g body weight) to the rats caused a significant decrease on their plasma lipid levels (quantified using enzymatic kits). At 7h after treatment, plasma total cholesterol, triglycerides and LDL-cholesterol were decreased by 47%, 95% and 67%, respectively, but the change of HDL-cholesterol level was not significant. However, the hypolipidaemic effect of fenofibrate was limited to triglycerides and LDL-cholesterol, which were lowered by about 92% and 41%, respectively. At 24h after treatment, Erica multiflora extract reduced plasma total cholesterol by 68.5% and triglycerides by 91%. HDL-cholesterol was not significantly increased and LDL-cholesterol was lowered by 80.5%. In fenofibrate treated rats, only plasma triglyceride concentrations were lowered by 82%, while the other lipid parameters were not significantly changed indicating that this aqueous herb extract may contain products that lower plasma lipid concentrations and might be beneficial in treatment of hyperlipideamia.
Indications and preliminary studies of Rhizoma Sparganii (RS) suggest its pharmacological mechanism is involved with endocrine/angiogenesis functions. We therefore studied its potential toxicity on reproduction in mice. Reproductive toxicity of 100, 200 and 400 mg/kg RS extract were studied in pregnant ICR mice and its offspring. The embryos' fibroblast growth factor-1 (FGF-1), vascular endothelial growth factor (VEGF) and estrogen receptor-α (ER-α) were evaluated as targets of endocrine/angiogenesis by immunohistochemical test. The offspring of treated mice (100, 200 and 400 mg/kg RS extract) during their pregnancy had various pathological conditions, suggesting an abnormal FGF signaling phenomenon during pregnancy. Embryos from the 400 mg/kg group had significantly depressed levels of FGF-1 (P < 0.01) and VEGF (P < 0.05) expression levels as compared to controls by immunohistochemical test. Dysplasia in the heart (12.9%), craniofacial region (18.3%) and vertebrae (32.5%) presented in embryos of the 400 mg/kg group. Furthermore, the ER-α expression was inversely proportional to FGF-1 levels in the same embryo (P < 0.01). These results implicate a FGF signaling abnormality in vivo and indicate that RS has anti-angiogenesis and anti-estrogen toxicity effects in pregnant rodents.
The bioactive components extracted from Scutellaria baicalensis Georgi (SB) have been widely used for anti-cancer, anti-oxidation, anti-inflammation and modulating the immune response. The purpose of this study is to verify the inhibitory effect and the underlying mechanisms of Scutellaria baicalensis ethanol extract (SBEE) on activated hepatic stellate cells which play a central role in liver fibrogenesis. Dimethylnitrosamine (DMN)-administrated rat model was applied to evaluate the anti-fibrotic effect of SBEE in vivo. Flow cytometric analysis and immunoblotting were then used to further investigate the molecular mechanisms by which Scutellaria baicalensis extract induces HSC-T6 cell death. Hepatic collagen contents and alpha-smooth muscle actin levels were remarkably reduced by treating with SBEE. 100 μg/mL SBEE-induced apoptosis of HSC-T6 cell was characterized with elevated levels of activated caspase-3, poly-(ADP-ribose) polymerase (PARP) cleavage, and release of cytochrome c into the cytosol in a time-dependent manner. A 24h treatment of SBEE induced G(2)/M cell cycle arrest with increased expression of p21 and downregulation of cdc2 and cyclin B1 protein levels. Again, SBEE induced bax expression with concomitant decrease of bcl-2 and upregulated the p53 and MAPK signaling in HSC-T6 cells. These findings demonstrated that SBEE could prevent hepatic fibrosis by promoting ERK-p53 pathways which may in turn cause G(2)/M cell cycle arrest and activate caspase system resulting in final apoptosis of HSC-T6 cells.
To dissect the mechanism of the protection of staurosporin-induced apoptosis on rat chondrocytes by a purified extract from Clematis mandshurica. Primary cultured rat articular chondrocytes as well as RCJ3.1C.18 cells were incubated with 1 microM staurosporin and 300 microg/ml purified extract from Clematis mandshurica. Western blot assay, silencing 14-3-3 gene and immunoprecipitation were conducted. Clematis mandshurica prevented staurosporin-induced downregulation of several antiapoptotic bcl-2 family proteins Bcl-xL and Bcl-2, and staurosporin-induced upregulation of an apoptotic bcl-2 family protein Bax. Clematis mandshurica also prevented staurosporin-induced downregulation of a premitochondrial antiapoptotic protein 14-3-3. It is noticeable that siRNA to 14-3-3 abolished the prevention of caspase-3 activation by Clematis mandshurica. Furthermore viability assay corroborated that silencing of 14-3-3 gene abolished this apoptosis protection efficacy by Clematis mandshurica. Immunoprecipitation assay elucidated that Clematis mandshurica prevented the staurosporin-induced reduction of the interactions between 14-3-3 with phospho-ser112-Bad and Bcl-xL to phospho-ser155-Bad. Clematis mandshurica prevents staurosporin-induced apoptosis of rat chondrocytes via 14-3-3.
The aim of the present study is to determine in a procedurally uniform manner the mescaline concentrations in stem tissue of 14 taxa/cultivars of the subgenus Trichocereus of the genus Echinopsis (Cactaceae) and to evaluate the relationship (if any) between mescaline concentration and actual shamanic use of these plants. Columnar cacti of the genus Echinopsis, some of which are used for diagnostic and therapeutic purposes by South American shamans in traditional medicine, were selected for analysis because they were vegetative clones of plants of documented geographic origin and/or because they were known to be used by practitioners of shamanism. Mescaline content of the cortical stem chlorenchyma of each cactus was determined by Soxhlet extraction with methanol, followed by acid-base extraction with water and dichloromethane, and high-pressure liquid chromatography (HPLC). By virtue of the consistent analytical procedures used, comparable alkaloid concentrations were obtained that facilitated the ranking of the various selected species and cultivars of Echinopsis, all of which exhibited positive mescaline contents. The range of mescaline concentrations across the 14 taxa/cultivars spanned two orders of magnitude, from 0.053% to 4.7% by dry weight. The mescaline concentrations reported here largely support the hypothesis that plants with the highest mescaline concentrations - particularly E. pachanoi from Peru - are most associated with documented shamanic use.
Seventy five medicinal plants of the traditional Ayurvedic pharmacopoeia of Sri Lanka have been screened chemically for alkaloids and pyrrolizidine alkaloids. Of these, Crotolaria juncea L. was found to contain pyrrolizidine alkaloids with biological effects consistent with pyrrolizidine alkaloid toxicity. Feeding trials in rats with three plants lacking pyrrolizidine alkaloids, namely Aegle marmelos (L.) Corr., Hemidesmus indicus (L.) Ait. F. and Terminalia chebula Retz. produced hepatic lesions which included central vein abnormalities while Terminalia chebula and Withania somnifera (L.) dunal produced marked renal lesions.
Further to a systematic chemotaxonomic study of Uzbek Haplophyllum A. Juss. plants selected on ethnopharmacological data, 14 alkaloids were screened for their cytotoxic properties. As a first selection for interesting compounds, each alkaloid was tested against two human cancer cell lines (HeLa and HCT-116), using WST-1 reagent. Of the 14 alkaloids, 5 were cytotoxic when tested against the HeLa line with an IC50 < 100 microM. These five compounds consisted of three furoquinolines: skimmianine; haplopine and gamma-fagarine and two pyranoquinolones: flindersine and haplamine. Only haplamine was active against the HCT-116 line. The cytotoxic properties of these five alkaloids were further investigated against five additional human cancer cell lines. Their structure-activity relationships will be discussed. Of these five pre-selected alkaloids, only haplamine showed significant cytotoxic activity against all the tested cell lines. This is the first report of the cytotoxic activity of haplamine. Finally, this pyranoquinolone alkaloid was tested here against 14 different cancer cell lines and against normal skin fibroblasts.
Top-cited authors
Erdem Yesilada
  • Yeditepe University
Arnold J Vlietinck
  • University of Antwerp
Anna K Jäger
Michael Heinrich
  • The School of Pharmacy
Peter Houghton