Antioxidant and 15-lipoxygenase inhibitory activities of the Malian medicinal plants Diospyros abyssinica (Hiern) F. White (Ebenaceae), Lannea velutina A. Rich (Anacardiaceae) and Crossopteryx febrifuga (Afzel) Benth. (Rubiaceae)

The African flora contains numerous medicinal plants whose biological and chemical properties are incompletely known. Antioxidant and radical scavenging properties of plants are subject to intensive research. In the work described here, we have investigated the antioxidant activity of the plants Diospyros abyssinica (root bark), Lannea velutina (root bark and stem bark) and Crossopteryx febrifuga (seeds). Extracts of different polarity were assayed for radical scavenging activity, using the stable free radical diphenylpicrylhydrazyl, and for inhibition of enzymatic lipid peroxidation mediated by soybean 15-lipoxygenase. All plants investigated showed activity, but there were large differences between plants and between extracts. In general, Diospyros abyssinica and Lannea velutina were richer in antioxidants than Crossopteryx febrifuga. Lipophilic extracts were not active as radical scavengers, but did inhibit 15-lipoxygenase. Semipolar extracts (80% aqueous ethanol and methanol) of Diospyros abyssinica and Lannea velutina showed the highest activity both as radical scavengers and lipoxygenase inhibitors, and also gave the highest extract yields. These plants therefore appear to be excellent sources of antioxidants.     

Studies on the anti-inflammatory and analgesic properties of Tithonia diversifolia leaf extract

A methanol extract of the dried leaves of Tithonia diversifolia was investigated for anti-inflammatory and analgesic activities. The extract (50–200 mg/kg, p.o.) produced dose-related inhibition of carrageenan-induced paw oedema and cotton pellet-induced granuloma in rats. At the same doses, analgesic effect was also observed with hot plate latency assays maintained at (55 °C) as well as on the early and late phases of formalin-induced paw licking in rats. The results of the present study further confirm the use of Tithonia diversifolia traditionally for the treatment of painful inflammatory conditions.     

The antiinflammatory and liver protective effect of Tithonia diversifolia (Hemsl.) gray and Dicliptera chinensis Juss. Extracts in rats

The antiinflammatory and liver protective effect of water extracts of Tithonia diversifolia (Hemsl.) Gray (aerial part), T. diversifolia (stem) and Dicliptera chinensis Juss. (aerial part) against paw oedema induced by carrageenan and acute hepatic damage induced by CCI₄ were determined in rats. The results indicated that treatment with a water extract of the aerial part of T. diversifolia decreased the paw oedema induced by carrageenan (p < 0.001) and the GOT, GPT level elevation caused by CCI₄ were reduced (p < 0.01). The pathological changes of hepatic lesions caused by CCI₄ were improved by treatment with the drug extracts mentioned above.     

Anticancer and antiviral activities of Youngia japonica (L.) DC (Asteraceae, Compositae)

Aqueous and ethanol extracts of Youngia japonica (also known as Oriental hawksbeard) were tested in vitro for anti-tumor activity against three cell lines, human promyelocytic leukaemia (HL-60), human myelogenous leukaemia (chronic K-562) and mouse Sarcoma 180 (S-180), and for antiviral activity against respiratory syncytial virus (RSV), influenza A virus (Flu A) and herpes simplex virus type 1 (HSV-1) by cytopathic effect (CPE) reduction assay. Hot water extract of Youngia japonica inhibited cell proliferation and growth of all cancer cell lines to various extent. K-562 cells were the most sensitive to the extract whereas S-180 cells were the least. It did not show any significant cytotoxic effects on normal mammalian Vero cells up to the concentration of 450 microg/mL. The ethanol extract of whole plant of Youngia japonica exhibited antiviral activity against RSV cultured in HEp-2 cells, but did not have any activity against Flu A and HSV-1. Two partially purified fractions (Fr.10 and Fr.11) from the 95% ethanol extract exhibited significant anti-RSV with 50% inhibitory concentration (IC50) in the range of 3.0-6.0 microg/mL. The ratio of the viral titer reduction in the absence (viral control) and presence of the maximal non-cytotoxic concentration (MNCC) of the Fr.10 and Fr.11 was both estimated to be 1 x 10(4) (RF, viral titer reduction factors), indicating that their anti-RSV activity was high enough to justify for further analysis. Our preliminary analysis showed that the antiviral ingredients were likely to contain phenolic compounds including tannins by chemical tests.     

In vivo anti-inflammatory activities of Ocimum suave in mice

Ethnopharmacological relevance

Ocimum suave has been used in the Ethiopian traditional medicine to relieve pain, fever, inflammation and other disease conditions.

Aim of the study

The aim of the present study was to investigate the anti-inflammatory activities of the aqueous and ethanol leaf extracts and some fractions of Ocimum suave in mice.

Materials and methods

The crude extracts were screened for their anti-inflammatory activities on carrageenan-induced mouse paw edema at three dose levels. The butanol and aqueous fractions of the aqueous extract were also evaluated for their anti-inflammatory activities using carrageenan, histamine and serotonin-induced mouse paw edema at three dose levels. Normal saline and aspirin were employed as negative and positive control groups, respectively.

Results

Both ethanol and aqueous extracts significantly decreased carrageenan-induced inflammation at all the three doses used. However, greater paw edema inhibition was observed with the aqueous extract. The two fractions also showed significant reduction of inflammation against inflammatory models in which the aqueous residue exhibited the highest inhibition.

Conclusions

From the present findings, it can be concluded that the ethanol and aqueous leaf extracts as well as butanol and aqueous fractions of Ocimum suave have shown anti-inflammatory properties.     

Effects of three Mexican medicinal plants (Asteraceae) on blood glucose levels in healthy mice and rabbits

The effects of Psacalium decompositum, Psacalium peltatum and Acourtia thurberi (Asteraceae) on blood glucose levels were investigated in fasting mice and temporally hyperglycemic rabbits. The root decoction of P. decompositum reduced the blood glucose of normal mice from 49.1 ± 3.8 to 35.7 ± 2.0 mg/dl after intraperitoneal administration (P ≤ 0.005) and significantly lowered the hyperglycemic peak (17.1%) in rabbits with temporal hyperglycemia. P. peltatum and A. thurberi decoctions also diminished fasting glycemia in mice and hyperglycemia in rabbits, but the effects were minor. A preliminary phytochemical study using thin layer chromatography showed that water decoctions of the three roots contained alkaloids and sugars. P. decompositum and P. peltatum showed the presence of maturine. However, other furoeremophylanes, such as cacalol and cacalone were only present in P. decompositum. A. thurberi root water decoction showed the presence of the benzoquinone perezone, and its derivative pipitzol.     

Antiviral activities of purified compounds from Youngia japonica (L.) DC (Asteraceae, Compositae)

The ethanol extract of a biannual medicinal herb, Youngia japonica (commonly known as Oriental hawk's beard) was reported previously to have potent antiviral activity against respiratory syncytial virus (RSV) cultured in HEp-2 cells. Three anti-microbial agents, namely 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, and luteolin-7-O-glucoside were subsequently purified and chemically characterized from the ethanol extract of Youngia japonica. The two dicaffeoylquinic acids exhibited prominent anti-RSV with 50% inhibitory concentration (IC50) of 0.5 microg/ml in vitro. Luteolin-7-O-glucoside together with the two dicaffeoylquinic acids were also manifested to have some antibacterial activity towards the causal agents of food-borne disease, namely Vibrio cholerae and Vibrio parahaemolyticus at the concentration of 2mg/ml. Bacillus cereus was sensitive to 3,4-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid only, but not to luteolin-7-O-glucoside.     

黄芪对动物在体胃肠运动的影响

观察黄芪对在体小鼠胃排空和肠推进的作用．并初步探讨其作用机制。结果发现黄芪可抑制正常小鼠的胃排空，对阿托品所致的胃排空减缓具有一定的拮抗作用。黄芪可明显促进正常小鼠的肠推进作用，对阿托品和异丙肾上腺素所致的小肠推进抑制具有拮抗作用。     

Antimalarial activity of Bidens pilosa L. (Asteraceae) ethanol extracts from wild plants collected in various localities or plants cultivated in humus soil

Bidens pilosa (Asteraceae), a medicinal plant used worldwide, has antimalarial activity as shown in previous work. This study tested ethanol extracts from wild plants collected in three different regions of Brazil and from plants cultivated in various soil conditions. The extracts were active in mice infected with P. berghei: doses of < or =500 mg/kg administered by oral route reduced malaria parasitaemia and mouse mortality; higher doses were found to be less effective. Tested in vitro against three P. falciparum isolates, two chloroquine resistant and one mefloquine resistant, the plants cultivated under standard conditions, and in humus enriched soil, were active; but the wild plants were the most active. Analysis using thin layer chromatography demonstrated the presence of flavonoids (compounds considered responsible for the antimalarial activity) in all plants tested, even though at different profiles. Because B. pilosa is proven to be active against P. falciparum drug-resistant parasites in vitro, and in rodent malaria in vivo, it is a good candidate for pre-clinical tests as a phytotherapeutic agent or for chemical isolation of the active compounds with the aim of finding new antimalarial drugs.     

荨麻属植物大蝎子草化学成分及质量标准研究

 目的 研究荨麻属植物大蝎子草的化学成分及药材质量控制标准。方法 采用硅胶柱色谱、薄层色谱等手段进行分离纯化,并通过波谱数据鉴定结构;采用TLC鉴别大蝎子草中东莨菪内酯,采用HPLC测定东莨菪内酯含量,以东莨菪内酯为对照,采用 RP-HPLC,岛津-C₁₈色谱柱(4.6 mm ×250 mm,5 μm) ,乙腈（A）-0.2%磷酸（B）梯度洗脱：洗脱程序 0～5 min,A-B（25∶75）线性变化至A-B（20∶80）;5～10 min,线性变化至A-B（15 ∶85）;10～18 min,保持A-B （15∶85）;18～19 min,A-B（50∶50）;19 ～ 25 min,A-B（25∶75）。流速1 mL·min^-1,检测波长 298 nm,柱温 30 ℃。结果 分离鉴定了3个化合物,东莨菪内酯 (1) ,山柰素（2）,β-谷甾醇（3）;定性鉴别薄层色谱特征明显,东莨菪内酯含量测定的线性范围为 0.022 ～0.352μg(r=0.999 9),平均回收率(n=6)为92.93%(RSD 1.86%) 。结论 化合物东莨菪内酯、山柰素为首次从该植物中分离;建立的质量标准可准确地定性、定量,有效地控制大蝎子草药材的质量。     

Toxicity,antimicrobial and anthelmintic activities of Vernonia guineensis Benth. (Asteraceae) crude extracts

Ethnopharmacological relevance

This study examined the antibacterial, antifungal, and anthelmintic properties of extracts obtained from the plant Vernonia guineensis, a plant commonly used in traditional Cameroonian medicine.

Materials and methods

For in vitro studies, 10 g of leaf and tuber powder from V. guineensis was extracted separately using dichloromethane, methanol and distilled water. The extracts were dried in vacuo and used for antimicrobial and anthelmintic activity studies. In the antimicrobial assay, extracts were tested against bacterial and fungal organisms including; Staphylococcus aureus, Staphylococcus epidermidis, Acinetobacter baumannii, Aspergillus fumigatus, Candida albicans and Trichophyton mentagrophytes. In the anthelmintic assay, larval and adult stages of the hookworm Ancylostoma ceylanicum and the mouse nematode Trichuris muris were used. For the acute toxicity test, male and female rats of 150–200 g body weight were used in the experiment. The aqueous extract of V. guineensis tubers was administered in 4 doses of 500, 1000, 2000 and 4000 mg/kg per group (n=6), respectively, and the control group received distilled water.

Results

The crude extracts exhibited weak antibacterial and antifungal activity except for the dichloromethane extract, which showed moderate activity against A. fumigatus (MIC=200 μg/ml). In the anthelmintic assay, the organic extracts of the tubers had 100% killing efficacy against T. muris at 2 mg/ml in 48 h, while the aqueous extract showed no activity. The organic leaf extracts demonstrated potent activity killing 100% of the adult worms 1 mg/ml in 24 h. The aqueous leaf extract was active at 2 mg/ml in 72 h, killing 100% of the adult worms. In the acute toxicity test, V. guineensis did not produce any toxic signs or death at the maximum concentration of 4000 mg/kg.

Conclusion

Crude extracts from V. guineensis possess anthelmintic activity against T. muris with only weak antibiotic activity. Acute administration of aqueous extract from V. guineensis tubers did not produce toxic effects in rats. The absence of acute toxicity at the highest concentration tested indicates that the tea decoction from V. guineensis extract is safe at concentrations ≤4000 mg/kg.     

Absence of alkaloids in Psychotria carthagenensis Jacq. (Rubiaceae)

Psychotria viridis and P. carthagenensis are often discussed in relation to the hallucinogenic beverage Ayahuasca, used for religious, medicinal and social purposes. The significance of including Psychotria species in this beverage has been understood on the basis of substantial amounts of tryptamine alkaloids detected on leaves of both P. viridis and P. carthagenensis. Nevertheless, there is a long lasting debate over the identification of which Psychotria species are actually traditionally employed. We here report that a P. carthagenensis leaf ethanol extract was found to be devoid of alkaloids. The extract significantly decreased mice body temperature (350 and 500 mg/kg). Toxicity assessment revealed that the extract induced sedation and slight ptoses (75% of animals treated with 1000 mg/kg). Lethality was not observed within 48 h. The data indicate that P. carthagenensis does have bioactive compound(s), possibly active at the central nervous system, but unlikely to be tryptamine alkaloids as in the case of P. viridis. Therefore, if P. carthagenensis is indeed used by ayahuasqueros, its chemical and pharmacological significance have yet to be elucidated.     

In vivo antimalarial activities of Quassia amara and Quassia undulata plant extracts in mice

Extracts obtained from two Nigerian Simaroubaceae plants, Quassia amara L. and Quassia undulata (Giull and Perr) D. Dietr were screened for antimalarial properties using a total of six extracts. The plant extracts showed significant antimalarial activities in the 4 day suppressive in vivo antimalarial assay in mice inoculated with red blood cells parasitized with Plasmodium berghei berghei. Plant extracts were studied at 100 mg and 200 mg per kg body weight mouse per day, respectively. At a concentration of 100 mg/kg of mouse, Q. amara leaf hexane extract had the highest suppressive activity with a parasite density of 0.16 +/- 0.001%. Q. amara leaf methanol extract had an outstanding activity; of 0.05 +/- 0.03% at 200 mg/kg. Chloroquine (10 mg/kg, positive control) had a suppressive activity of 0.34 +/- 0.02 in the same assay on day 4.     

The in vitro antioxidant and antimicrobial activities of the essential oil and methanol extracts of Achillea biebersteini Afan. (Asteraceae)

The essential oil and methanol extracts from A. biebersteinii Afan. (Asteraceae) were evaluated for their antimicrobial and antioxidant activities in vitro. The oil showed stronger antimicrobial activity than the extracts. Their antioxidant features were also evaluated using diphenyl-1-picrylhydrazyl (DPPH), inhibition of superoxide and hydroxyl radicals and inhibition of the lipid peroxidation assays. Particularly, polar subfraction of the methanol extract showed antioxidant activity. The GC-MS analysis of the oil has resulted in the identification of 23 components; piperitone, eucalyptol, camphor, chrysanthenone and borneol were the main components. Antimicrobial activity tests carried out with the fractions of the oil showed that the activity was mainly observed in those containing eucalyptol and camphor, in particular, followed by borneol and piperitone.     

In vivo anti-inflammatory activities of leaf extracts of Ocimum lamiifolium in mice model

Aim of the study

Ocimum lamiifolium Hochst. ex Benth. (Lamiaceae) has been used in Ethiopian traditional medicine for the treatment of different inflammatory disorders such as oropharyngitis, wound, pain, fever, and others. However, its use has mainly been based on empirical findings. Thus the objective of this study was therefore to evaluate the antiinflammatory effects and acute oral toxicities of the leaf extracts of Ocimum lamiifolium in mice.

Materials and methods

Aqueous and ethanol crude extracts were screened for their antiinflammatory activities in mice using carrageenin induced paw edema. And then the aqueous extract, the most active extract, was further fractionated and the fractions were tested for their anti-inflammatory activities using carrageenin, histamine and serotonin induced mice paw edema. Distilled water and aspirin were employed as negative and positive controls, respectively. Acute oral toxicity of both extracts and fractions were also determined after giving graded doses.

Results

The aqueous and ethanol extracts were able to reduce inflammation significantly, but greater anti-inflammatory activity was observed for the aqueous extract at all dose levels. Of all fractions the water residue showed highly significant anti-inflammatory activity.

Conclusions

Ocimum lamiifolium leaf extracts exhibited significant anti-inflammatory activities with less acute toxicity.     

In vitro anti-prostate cancer and ex vivo antiangiogenic activity of Vernonia guineensis Benth. (Asteraceae) tuber extracts

Ethnopharmacological relevance

Prostate cancer is a major problem worldwide and affects most men above the age of forty-five. Vernonia guineensis Benth. (Asteraceae) root decoction is used in folk medicine in Cameroon to treat a number of ailments including prostate cancer. The aim of this study was to provide a preliminary validation of the use of Vernonia guineensis Benth. extracts to treat prostate cancer by evaluating the in vitro activity of its crude extracts and isolated molecules on prostate cancer cells lines and effect on angiogenesis which is essential for growth and metastases of prostate cancer.

Materials and methods

Aqueous, dichloromethane and methanol extracts of Vernonia guineensis Benth. tubers were tested for activity against three prostate cancer cell lines (PC-3, DU-145 and AT3B-1). The dichloromethane extract was subjected to bioactivity guided fractionation. Anti-proliferation, clonogenic and antiangiogenic activity of the crude extracts and isolated compound were tested. The WST-1 assay was used for the anti-proliferation activity meanwhile the standard clonogenic test and the rat ring aorta assay were carried out to determine the clonogenic and antiangiogenic activity of tested products respectively.

Results

The aqueous and methanol extracts of Vernonia guineensis Benth. demonstrated weak activity against prostate cancer cell lines in vitro with IC₅₀ > 100 μg/mL. The dichloromethane extract was more potent with IC₅₀ of 56.233 ± 3.630 μg/ml and 67.316 ± 2.452 μg/ml against the DU-145 and PC-3 cell lines respectively. Activity guided fractionation of this extract yielded a Pentaisovalerylsucrose (1) isolated for the first time from a natural source to the best of our knowledge. Compound 1 demonstrated in vitro activity against the human prostate cancer cell lines PC-3 and DU-145 with IC₅₀ of 5.701 ± 0.142 μM and 4.275 ± 0.710 μM, respectively. The IC₅₀ of the compound was 5.763 ± 0.425 μM against AT3B-1, a rat prostate cancer cell line expressing P-glycoprotein which is linked to drug resistance in most metastatic cancers. Compared to compound 1, Paclitaxel and Docetaxel were active against AT3B-1 at 2.641 ± 1.253 μM and 0.613 ± 0.251 μM. Paclitaxel showed IC₅₀ values of 0.004 ± 0.002 μM and 0.003 ± 0.001 μM against DU-145 and PC-3 prostate cancer cell lines respectively. Docetaxel showed IC₅₀ values of 0.002 ± 0.001 μM and 0.004 ± 0.001 μM against DU-145 and PC-3 prostate cancer cell lines respectively.

Conclusion

The in vitro anti-prostate cancer and the antiangiogenic activity of Vernonia guineensis Benth. extracts and isolated compound support the use of the tubers of this plant for the treatment of prostate cancer.     

Anti-inflammatory activities of flavonoids of Baphia nitida Lodd. (Leguminosae) on mice and rats

Leaves of Baphia nitida are used in folk medicine for the treatment of inflamed and infected umbilical cords in Nigeria. Phytochemical analysis of the leaves detected tannins, flavonoids and saponin glycosides. Flavonoid rich fraction of the leaf, obtained by a chromatographic process, was formulated into an ointment and tested at 3 dose levels for anti-inflammatory activity against croton oil and heat induced inflammation on ears of mice and depilated backs of rats, respectively. Both provide evidence for the ability of this fraction to inhibit the inflammatory condition on the rodents. The activity was found to be dose related, and the mouse ear model was found to be the more sensitive of the two tests used. Hydrocortisyl cream used as a positive control reference was significantly active in both systems. These results provide a scientific basis for the traditional use of the leaves of Baphia nitida as an anti-inflammatory agent.     

Immunostimulatory effects of Uncaria perrottetii (A. Rich.) Merr. (Rubiaceae) vinebark aqueous extract in Balb/C mice

Aims of the study

Crude extract of Uncaria perrottetii (A. Rich.) Merr. vinebark was evaluated for its immunomodulating activity in Balb/C mice. Initially, the immunomodulatory potential of the plant extract was evaluated using in vitro immune response assays at different concentrations of the plant extract (10 μg/mL, 20 μg/mL, 50 μg/mL and 100 μg/mL). Using the optimum concentration determined in the in vitro assays, the protective effect of the plant extract was assessed against drug-induced immunosuppression in vivo.

Materials and Methods

For the in vivo experiment, thirty-six (36) mice were divided into 3 groups of 12 mice each: (1) cyclophosphamide drug-induced (30 mg/kg BW) immunosuppressed mice (Cy group) served as the positive control; (2) Uncaria perrottetii extract and Cy-treated mice (U + Cy); and (3) PBS-injected mice as the negative control group [(−) CTRL].

Results

The optimum concentration was determined to be 50 μg/mL in the in vitro assays. At this concentration, Uncaria perrottetii extract stimulated peritoneal phagocyte activation, produced a significant increase in the activity of phagocytic cells from the spleen and promoted splenic cellular proliferation with or without lipopolysaccharide (LPS) when compared with the PBS-treated cells (negative control). Moreover, cells treated with 50 μg/mL of Uncaria perrottetii increased macrophage respiratory burst activity that was comparable to that of the phorbol myristate acetate-stimulated splenic macrophages.In all immune assays undertaken in the in vivo experiment, the Cy-treated mice showed significantly lower response when compared with the PBS-treated mice. Significant improvement in peritoneal cell activation, phagocytic activity and cellular proliferation was exhibited by the U + Cy-treated mice when compared with Cy-injected mice. The extract from Uncaria perrottetii also significantly enhanced respiratory burst and plasma lysozyme activity compared with the Cy-injected mice.

Conclusions

Based on the results of both in vitro and in vivo trials, Uncaria perrottetii extract has immunopotentiating activities on the innate immunity of Balb/C mice and the extract could potentially reverse the immunosuppressive effects of Cy. However, the potential of the plant as source of bioactive products and metabolites for drug development still has to be fully investigated.     

Antimalarial and cytotoxic activities of ethnopharmacologically selected medicinal plants from South Vietnam

Malaria is a major global public health problem and the alarming spread of drug resistance and limited number of effective drugs now available underline how important it is to discover new antimalarial compounds. An ethnopharmacological investigation was undertaken of medicinal plants traditionally used to treat malaria in the South Vietnam. Forty-nine plants were identified, 228 extracts were prepared and tested for their in vitro activity against Plasmodium falciparum, and assessed for any cytotoxicity against the human cancer cell line HeLa and the embryonic lung MRC5 cell line. In a first screening at a concentration of 10 microg/ml, 92 extracts from 46 plants showed antiplasmodial activity (parasite growth inhibition >30%). The IC(50) values of the most active extracts were determined as well as their selectivity towards Plasmodium falciparum in comparison to their cytotoxic effects against the human cell lines. Six plants showed interesting antiplasmodial activity (IC(50) ranging from 0.4 to 8.6 microg/ml) with a good selectivity: two Menispermaceae, Arcangelisia flava (L.) Merr. and Fibraurea tinctoria Lour., and also Harrisonia perforata (Blanco) Merr. (Simaroubaceae), Irvingia malayana Oliv. ex Benn. (Irvingiaceae), Elaeocarpus kontumensis Gagn. (Elaeocarpaceae) and Anneslea fragrans Wall. (Theaceae).     

Screening for in vivo (anti)estrogenic and (anti)androgenic activities of Tropaeolum majus L. and its effect on uterine contractility

Ethnopharmacological relevance

Tropaeolum majus L. (Tropaeolaceae) is a medicinal herb popularly used in Brazil for treatment of inflammatory and cardiovascular diseases. Despite some published data on its efficacy, there are still few toxicological data describing the safety of this plant. The aim of this study was to evaluate the (anti)estrogenic and (anti)androgenic activity of the hydroethanolic extract obtained from Tropaeolum majus L. (HETM), as well as its possible effects on uterine contractility.

Materials and methods

Three experimental protocols were performed, (a) uterotrophic assay, (b) Hershberger assay and (c) an ex vivo test to investigate the effects of maternal administration of HETM on uterine contractility at the end of pregnancy. In all protocols three doses of the HETM were administered to Wistar rats: 3, 30 and 300 mg/kg.

Results

In vivo tests for detection of (anti)androgenic and (anti)estrogenic activities did not show any significant alterations. Similarly, no alterations were observed on uterine contractility induced by oxytocin and arachidonic acid.

Conclusions

HETM was unable to produce (anti)estrogenic or (anti)androgenic activities in the short-term in vivo screening assays performed. In addition, there was no evidence that HETM can affect uterine contractility following gestational exposure of rats.