Labisia pumila var. alata reduces bacterial load by inducing uroepithelial cell apoptosis

Ethnopharmacological relevance

Labisia pumila var. alata (LPva) is a traditional medicinal herb used by Malaysian women to treat many ailments of the genitourinary tract. Its phytoestrogenic properties suggest potential to prevent recurrent urinary tract infection (UTI) in women post menopause. The aim of this study was therefore to investigate the mechanisms of action of LPva in an in vitro model of UTI.

Materials and methods

Bladder epithelial cell lines T24 and 5637 and uropathogenic Escherichia coli (UPEC) strain CFT073 were used to model uroepithelial infection. The ability of LPva to induce programmed cell death was tested using the Annexin-V-FLUOS and TUNEL assays. Expression of caveolin-1, β1 integrin and antimicrobial peptides HBD-2 and LL-37 in response to LPva treatment and/or infection, was assessed using RT real-time PCR. Effects on protein expression were confirmed by Western blot analysis. Sensitivity and yeast agglutination assays were employed to determine if LPva had antimicrobial activities and/or interacted with type 1 fimbriae, respectively. Finally, bacterial adherence and invasion to cells treated with LPva was examined.

Results

LPva induced uroepithelial apoptosis which was coupled with upregulated expression of caveolin-1 and downregulation of β1 integrin. LPva did not exhibit direct antimicrobial properties and did not influence antimicrobial peptide levels in cells. Additionally, LPva did not interact with type 1 fimbriae and did not affect adherence in comparison to non-treated control cells. However, LPva significantly reduced the number of intracellular UPEC in bladder epithelial cells.

Conclusions

Our findings suggest that LPva has beneficial applications against UPEC infection due to its ability to induce programmed cell death and reduce bacterial invasion of the uroepithelium.     

Inhibitory effects of alkaline extract of Citrus reticulata on pulmonary fibrosis

Ethnopharmacological relevance

The pericarp of Citrus reticulata possesses medical functions of regulating Qi and expelling phlegm, and has been clinically used for the treatment of lung related diseases in traditional Chinese medicine for a long time. Our previous research revealed that Citrus reticulata exhibited inhibitory effects on pulmonary fibrosis; however, its active principles are still unclear.

Aim of the study

To investigate the inhibitory effects on pulmonary fibrosis of alkaline extract from ethanol extract of Citrus reticulata and clarify its possible mechanism.

Materials and methods

The citrus alkaline extract (CAE) was prepared from ethanol extract of Citrus reticulata and MRC-5 cells were used for the evaluation of inhibitory activity in vitro. CAE was further orally administrated to bleomycin (BLM)-induced pulmonary fibrosis rats. The rat body weight, hydroxyproline levels in serum and lung, pathological changes of lung, as well as mRNA and protein expressions of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and tumor necrosis factor-α (TNF-α) in rat lung tissues were analyzed.

Results

CAE dose-dependently inhibited the proliferation of MRC-5 cells, and the LDH assay clearly revealed that the inhibitory activity of CAE was not due to its cytotoxicity. CAE treatment significantly increased rat weight gain, ameliorated alveolitis and pulmonary fibrosis degree, and lowered hydroxyproline contents in both serum and lung tissues. RT-PCR and western blot revealed that mRNA and protein expressions of MMP-9 were significantly elevated, while mRNA and protein levels of TIMP-1 and TNF-α were markedly decreased in lung tissues of CAE treated rats.

Conclusions

The results collectively demonstrated that CAE possessed an inhibitory activity on the proliferation of MRC-5 and a preventive effect on BLM-induced pulmonary fibrosis in rats. The preliminary mechanisms of the effects may be through upregulation of MMP-9 expression and inhibition of the expressions of TNF-α and TIMP-1.     

In vitro activity of Tridax procumbens against promastigotes of Leishmania mexicana

Ethnopharmacological relevance

Tridax procumbens is an active herb against leishmaniasis.

Aim of the study

Leishmaniasis is a group of diseases caused by Leishmania protozoa. We investigated the antileishmanial activity of Tridax procumbens extracts and a pure compound against promastigotes of Leishmania mexicana, the causative agent of cutaneous leishmaniasis in the New World.

Materials and methods

Extracts and (3S)-16,17-didehydrofalcarinol (1) were obtained by chromatographic methods from Tridax procumbens, and the latter identified by spectroscopic analysis. The effect of these extracts and 1 on the growth inhibition of promastigotes of Leishmania mexicana was evaluated. In order to test the safety of extracts and 1, mammalian cells were treated with them, and cell viability was assessed using trypan blue and MTT.

Results

We demonstrated that extracts of Tridax procumbens and 1 showed a pronounced activity against Leishmania mexicana. The methanol extract inhibited promastigotes growth of Leishmania mexicana with a 50% inhibitory concentration (IC₅₀) of 3 μg/ml, while oxylipin 1 exhibited the highest inhibition at IC₅₀ = 0.478 μg/ml.

Conclusions

In this study we report the biological activity of extracts and (3S)-16,17-didehydrofalcarinol (1), obtained from Tridax procumbens, on the promastigote form of Leishmania mexicana, with no effect upon mammalian cells.     

Inhibitory effects of citrus extracts on the experimental pulmonary fibrosis

Aim of the study

A Chinese herbal formula, Hu-qi-yin possessed an anti-pulmonary fibrosis effect. Pericarp of Citrus reticulata, one of the herbal drugs contained in this formula showed the most potent inhibitory activity on the proliferation of human embryonic lung fibroblasts (HELF). The present study was designed to clarify the active principles responsible for the activity and further explore the anti-pulmonary fibrosis effect in vivo.

Materials and methods

The water, 75% ethanol and flavonoids-enriched extracts of Citrus reticulata were prepared and screened for their anti-proliferation activity using HELF culture system. The ethanol extract was further administered orally at doses of 100 and 200 mg/(kg day) to bleomycin (BLM)-induced pulmonary fibrosis rats. The analyses of the rat body weight, hydroxyproline levels in serum and lung, scores of alveolitis and fibrosis, as well as the expression of transforming growth factor-β₁ (TGF-β₁) at the protein and the messenger ribonucleic acid (mRNA) levels in lung were performed.

Results

The ethanol extract showed the strongest inhibitory activity on HELF proliferation. Further research using BLM-induced rat model revealed that the ethanol extract at the doses of 100 and 200 mg/(kg day) caused a marked increase of body weight at first 7 days, significantly lowered the hydroxyproline levels in lung, greatly improved the pathologic scores, as well as inhibited the overexpressions of TGF-β₁ protein and mRNA.

Conclusions

The results suggest that the ethanol extract of Citrus reticulata has anti-pulmonary fibrosis effects and might have a great potential for the treatment of fibrosis of lung.     

The effect of Dodonaea viscosa var. angustifolia on Candida albicans proteinase and phospholipase production and adherence to oral epithelial cells

Aim of the study

This study investigated effect of a crude extract of Dodonaea viscosa on the proteinase and phospholipase production and adherence to epithelial cells by Candida albicans isolated from HIV positive and HIV negative patients.

Materials and methods

Twenty Candida albicans strains isolated from HIV positive and 20 from HIV negative patients were investigated. The isolates were exposed to subinhibitory concentration of crude plant extract and adherence, proteinase and phospholipase production were assessed. The results were analysed using Student's t-test and a two-way ANOVA.

Results

Dodonaea viscosa var. angustifolia inhibited the adherence of Candida albicans to oral epithelial cells (p = <0.01) but no significant effect of the plant extract on proteinase and phospholipase production was observed. Results from Candida albicans strains isolated from HIV positive and HIV negative patients were similar.

Conclusions

Dodonaea viscosa var. angustifolia inhibited the adherence of Candida albicans to oral epithelial cells, which is the initial step of colonization in the infection process. This plant has a therapeutic potential at subinhibitory concentration.     

Drosera rotundifolia and Drosera tokaiensis suppress the activation of HMC-1 human mast cells

Ethnopharmacological relevance

Several Northern Hemisphere Drosera species have been used in the therapy of respiratory tract infections as the traditional medicine Droserae Herba.

Aim of the study

To determine the anti-inflammatory effects of Drosera species and to investigate a substitute material for Droserae Herba, we examined the effect of extracts of Drosera rotundifolia, Drosera tokaiensis and Drosera spatulata on activated T cell membrane (aTc-m)-induced inflammatory gene expression in HMC-1 human mast cells.

Materials and methods

Drosera rotundifolia, Drosera spatulata and Drosera tokaiensis were collected in Japan. Herbs were extracted with 80% EtOH, and subsequently applied to OASIS HLB column. HMC-1 cells were treated with each Drosera column-adsorbed fraction for 15 min, and subsequently added to aTc-m and incubated for 16 h. Inflammatory gene and protein expressions were determined by DNA microarray, RT-PCR and Western blotting.

Results

Drosera rotundifolia and Drosera tokaiensis fractions, but not the Drosera spatulata fraction, suppressed inflammatory gene expression induced by aTc-m in HMC-1 cells.

Conclusions

Drosera rotundifolia and Drosera tokaiensis suppressed activation of HMC-1 cells induced by aTc-m. Since the Drosera tokaiensis fraction was more effective than the traditionally used Drosera rotundifolia, Drosera tokaiensis is a likely substitute as a source of Droserae Herba.     

Screening of the topical anti-inflammatory activity of the bark of Acacia cornigera Willdenow, Byrsonima crassifolia Kunth, Sweetia panamensis Yakovlev and the leaves of Sphagneticola trilobata Hitchcock

Ethnopharmacological relevance

An investigation of topical anti-inflammatory activity was undertaken on plants used in Central America traditional medicine.

Aim of study

Four herbal drugs used in the folk medicine of Central America to treat inflammatory skin affections (Acacia cornigera bark, Byrsonima crassifolia bark, Sphagneticola trilobata leaves and Sweetia panamensis bark) were evaluated for their topical anti-inflammatory activity.

Materials and methods

Petroleum ether, chloroform and methanol extracts were obtained for herbal medicines and then extracts were tested on Croton oil-induced ear dermatitis model in mice.

Results

Almost all the extracts reduced the Croton oil-induced ear dermatitis in mice and the chloroform ones showed the highest activity, with ID₅₀ (dose giving 50% oedema inhibition) values ranging from 112 μg/cm² (Byrsonima crassifolia) to 183 μg/cm² (Sphagneticola trilobata). As reference, ID₅₀ of the non-steroidal anti-inflammatory drug indomethacin was 93 μg/cm².

Conclusions

Lipophilic extracts from these species can be regarded as potential sources of anti-inflammatory principles.     

Ginseng treatment reverses obesity and related disorders by inhibiting angiogenesis in female db/db mice

Ethnopharmacological relevance

Korean red ginseng (ginseng, Panax ginseng C.A. Meyer) has traditionally been used in the treatment of most ageing-related diseases, such as obesity, diabetes, and dyslipidemia, but the mechanism of the effects is unclear. The aim of this study was to determine the effects of ginseng on obesity in a mouse model of female obesity (obese female db/db mouse) and to investigate the mechanism of anti-obesity effects.

Materials and methods

After female db/db (B6.Cg-m Lepr^db/++/J) mice were treated with 5% (w/w) ginseng for 13 weeks, variables and parameters of obesity and disorders related to obesity were examined. Blood vessel density and the expression of genes involved in angiogenesis were also measured.

Results

Mice treated with ginseng for 13 weeks had less body weight and lower adipose tissue mass compared to control, untreated mice. The size of adipocytes was smaller in visceral adipose tissues of ginseng-treated mice. Obesity-related complications, such as hepatic steatosis, hypertriglyceridemia, and hyperglycemia, were markedly improved in treated mice. Blood vessel density was lower in visceral adipose tissue sections from treated mice than those from control mice. Concomitantly, mRNA levels for VEGF-A and FGF-2 were lower in both visceral adipose tissue from treated mice and treated 3T3-L1 cells compared to those from untreated controls. Protein levels for VEGF were also lower in visceral adipose tissue from treated mice. In contrast, ginseng increased mRNA expression of genes responsible for energy expenditure and fatty acid β-oxidation in visceral adipose tissue during ginseng-induced weight reduction.

Conclusions

These results suggest that ginseng may effectively treat female obesity and related disorders in part by inhibition of angiogenesis.     

Citrus limetta leaves extract antagonizes the hypertensive effect of angiotensin II

Ethnopharmacological relevance

Citrus limetta Risso (Rutaceae) is widely used in Mexico for healing purposes, among them as antihypertensive treatment.

Aim of the study

To assess the antihypertensive effect of C. limetta leaves as one of its ethnomedical uses.

Materials and methods

The acute response of blood pressure to angiotensin II administration was measured in mice. Additionally, the acute oral toxicity profiles were determined.

Results

The findings of the current investigation showed that different concentrations of the aqueous extract prevented the raise of systolic blood pressure (p ≤ 0.001 vs. vehicle), diastolic blood pressure (p ≤ 0.0002 vs. vehicle) and mean blood pressure (p ≤ 0.0000 vs. vehicle); with a dose dependent effect for diastolic pressures at 125–500 mg/kg dosages. The 500 and 1000 mg/kg doses inhibited the action of Ang II in similar extent to telmisartan. Toxic signs or deaths were not observed in mice treated at 2000 mg/kg of C. limetta extract.

Conclusions

All doses of C. limetta aqueous extract, used in this assay, were safe and effective.     

Anti-nociceptive activity of Pereskia bleo Kunth. (Cactaceae) leaves extracts

Ethnopharmacological relevance

Local communities in Malaysia consume Pereskia bleo Kunth. (Cactaceae) leaves as raw vegetables or as a concoction and drink as a tea to treat diabetes, hypertension, rheumatism, cancer-related diseases, inflammation, gastric pain, ulcers, and for revitalizing the body.

Aim of the study

To evaluate anti-nociceptive activity of the extracts and vitexin, isolated for the first time in this species, in two analgesic models; formalin-induced licking and acetic acid-induced abdominal writhing.

Materials and methods

Three and a half kilos of P. bleo leaves were extracted using Soxhlet apparatus with ethanol for 72 h. The crude ethanol extract was treated with activated charcoal overnight and subjected to a liquid–liquid partition yielding hexane, dichloromethane, ethyl acetate and butanol extracts. All extracts, including the crude ethanol and vitexin isolated from the ethyl acetate partition were tested for peripheral anti-nociceptive activity using formalin test and acetic acid-induced abdominal writhing, besides having their acute toxicity assays performed.

Results

The phytochemical analyses resulted in the isolation of vitexin (1), β-sitosterol glucoside (2) and β-sitosterol (3) isolated from the ethyl acetate, dichloromethane and hexane extracts, respectively. This is the first time vitexin and β-sitosterol glucoside are isolated from this species. The anti-nociceptive activities for all extracts were only moderate. Vitexin, which was isolated from the ethyl acetate extract did not show any activity in all models tested when used alone at the same concentration as it appears in the extract.

Conclusion

This study showed that all the extracts possess moderate anti-nociceptive activity. Vitexin is not the compound responsible for the anti-nociceptive effect in the ethyl acetate extract. Further investigations are needed to identify the compound(s) that might be responsible for the anti-nociceptive activity in this plant.     

Acanthopanax senticosus extracts have a protective effect on Drosophila gut immunity

Ethnopharmacological relevance

Aanthopanax senticosus (A. senticosus) Harms is a classical adaptogenic agent used in China. It has been applied as an analeptic aid to improve weakened physical status. However, little is known about the effects of A. senticosus on inflammatory disease processes.

Materials and methods

Flies fed with standard cornmeal–yeast medium were used as controls, and the treatment groups contained 10% of A. senticosus aqueous extracts (root or fruit) in standard medium. Survival rate was performed by feeding a vial containing five layers of filter paper hydrated with 5% sucrose solution contaminated with pathogenic or toxic compounds. Imaging of the guts was viewed under the microscope. Death cells were detected by 7-AAD staining.

Results

The A. senticosus extract improved the survival rate, attenuated the death of intestinal epithelial cells, promoted the expression of antimicrobial peptide genes, and decreased the formation of melanotic masses. Moreover, our results indicated that the protective effect of fruit is much higher than that of root extracts.

Conclusions

A. senticosus extracts have a protective effect on Drosophila gut immunity and stress response, and may contribute to the prevention of inflammatory diseases induced by pathogenic and toxic compounds.     

Zanthoxylum capense constituents with antimycobacterial activity against Mycobacterium tuberculosis in vitro and ex vivo within human macrophages

Ethnopharmacological relevance

Zanthoxylum capense Thunb. (Rutaceae) is a medicinal plant traditionally used in Mozambique to treat tuberculosis.

Aims of the study

The main aim of the study was to find antimycobacterial lead compounds from Zanthoxylum capense. Another goal was to provide scientific validation for the use of this plant in traditional medicine.

Methods and materials

By bioassay-guided fractionation, 16 compounds were isolated and screened for their in vitro antimycobacterial activity against two different strains of Mycobacterium tuberculosis. Their in vitro cytotoxicity to human THP-1 macrophages was also assessed. The compounds with favourable selectivity index values (SI>10) were further investigated for their ability to inhibit the growth of Mycobacterium tuberculosis H37Rv in an intracellular macrophage model of infection.

Results

The best results were obtained for a benzophenanthridine alkaloid, decarine (1), and an N-isobutylamide, N-isobutyl-(2E,4E)-2,4-tetradecadienamide (15), which showed high activity against Mycobacterium tuberculosis H37Rv (MIC of 1.6 μg/ml), and a low macrophage cytotoxicity (IC₅₀>60 μg/ml), indicating considerable selective activity. The benzophenanthridine alkaloid 6-acetonyldihydronitidine (6) revealed cytotoxicity (IC₅₀ 1.7 μg/ml), despite the determined MIC of 6.2–12.5 μg/ml. In infected macrophages, decarine (1) was able to reduce bacterial survival by almost two log units at a concentration of 6.2 μg/ml 5 days post-drug exposure. Compound 15 exhibited an intermediate activity at drug concentrations ranging from 6.2 to 25 μg/ml.

Conclusions

The high antimycobacterial activity of decarine found, both in vitro and ex vivo against mycobacteria, and the low cytotoxicity towards human macrophages indicate that it may be valuable as a lead scaffold for the development of anti-TB drugs.     

Effect of Brazilian copaiba oils on Leishmania amazonensis

Ethnopharmacological relevance

Copaiba oil has been used in folk medicine since the 19th century. The use of copaiba oils to treat leishmaniasis is cited in several ethnopharmacological studies. Nevertheless, the potential antileishmania of copaiba oils had not been studied.

Aim of the study

Eight different kinds of Brazilian copaiba oils were screened for antileishmanial activity.

Materials and methods

The antiproliferative effect of copaiba oil on promastigote and amastigote axenic were determined. To determine the survival index peritoneal macrophage were infected with promastigotes of Leishmania amazonensis and treated with copaiba oil. The cytotoxic effect of copaiba oil was assessed on macrophage strain J774G8 by assay of sulforhodamine B.

Results

Copaiba oils showed variable levels of activity against promastigote forms with IC₅₀ values in the range between 5 and 22 μg/mL. The most active oil was that from Copaifera reticulata (collected in Pará State, Brazil) with IC₅₀ values of 5, 15, and 20 μg/mL for promastigote, axenic amastigote and intracellular amastigote forms, respectively. Amphotericin B showed IC₅₀ of 0.058 and 0.231 μg/mL against promastigote and amastigote forms, respectively. Cytotoxicity assay showed that this copaiba oil obtained from Copaifera reticulata showed low cytotoxicity against J774G8 macrophages.

Conclusion

Copaiba oils showed significant activity against the parasite Leishmania amazonensis.     

Rehmannia glutinosa ameliorates the progressive renal failure induced by 5/6 nephrectomy

Aim of the study

Rehmannia glutinosa, the steamed root of the Scrophulariaceae family, has been widely used in Asian countries for the treatment of renal diseases. In this study, we evaluated the renoprotective effect of aqueous extract of Rehmannia glutinosa in progressive renal failure.

Materials and methods

The effects of Rehmannia glutinosa on renal function, 24-h proteinuria, and the expression of angiotensin II, angiotensin II type 1 (AT₁) receptor, TGF-β1, and type IV collagen in renal cortex were analyzed in progressive renal failure rats induced by 5/6 nephrectomy.

Results

Rehmannia glutinosa reduced the serum creatinine level, 24-h urinary protein excretion, and glomerulosclerosis, and it also inhibited the expression of angiotensin II, AT₁ receptor, TGF-β1 and type IV collagen in the renal cortex.

Conclusions

These results suggest that the renoprotective effect of Rehmannia glutinosa might be mediated by suppressing the expression of angiotensin II and AT₁ receptor and by regulating TGF-β1 and type IV collagen expression.     

Prophylactic and curative activities of extracts from Warburgia ugandensis Sprague (Canellaceae) and Zanthoxylum usambarense (Engl.) Kokwaro (Rutaceae) against Plasmodium knowlesi and Plasmodium berghei

Ethnopharmacological relevance

This work reports the anti-plasmodial activities of Warburgia ugandensis and Zanthoxylum usambarense commonly used as phytomedicines against malaria by some Kenyan communities.

Aim of study

To determine the anti-plasmodial activities of extracts from Warburgia ugandensis and Zanthoxylum usambarense against Plasmodium knowlesi and Plasmodium berghei.

Materials and methods

Eight plant extracts were screened for in vitro anti-plasmodial activity against Plasmodium knowlesi, in a 96-well plate incubated at 37 °C on a RPMI culture medium supplemented with baboon serum. Of the eight, three were investigated for prophylactic and curative activities in BALB/c mice against drug-sensitive Plasmodium berghei in a 4-day test at a dose rate of 200 mg/kg/day.

Results

Inhibitory concentrations (IC₅₀) values of between 3.14 and 75 μg/ml, up to 69% chemosuppression of parasites growth and over 80% survivorship of treated mice were observed.

Conclusion

The two medicinal plants, Warburgia ugandensis and Zanthoxylum usambarense possess bioactive compounds against malaria parasites and could be exploited for further development into malaria therapy.     

In vivo antimalarial activities of Enantia polycarpa stem bark against Plasmodium berghei berghei in mice

Ethnopharmacological relevance

Enantia polycarpa (PC) Engl. Et Diels (Annonaceae) is used in traditional medicine as an antimalarial remedy in Southern Nigeria.

Aim of the study

The antimalarial activities of ethanolic stem bark extracts of Enantia polycarpa was studied in vivo, in mice infected with Plasmodium berghei berghei.

Materials and methods

The ethanolic stem bark extract of Enantia polycarpa was administered at doses ranging from 200 to 600 mg/kg/day to Plasmodium berghei infected mice in both early and established models of antiplasmodial studies.

Results

The extract of Enantia polycarpa exhibited promising antimalarial activity against both early and established infections. At a dose of 600 mg/kg the extract achieved a 75.8% and 72% chemosuppression of parasitaemia in the study of acute and established infections, respectively. The extract also prolonged mean survival time of Plasmodium berghei infected mice during the study of established infection. The mean survival time of mice administered Enantia polycarpa extract at 600 mg/kg/day (27 days) was significantly longer than infected/untreated control (12 days). For the acute toxicity study the extract had an intraperitoneal LD₅₀ of 186 mg/kg but caused no mortality when administered orally at doses as high as 2,000 and 4,000 mg/kg.

Conclusions

Collectively, the results indicate that Enantia polycarpa is safe when administered orally and possesses promising antimalarial activity, thus supporting its use in traditional medicine for the treatment of malaria.     

The anti-cancer activity of Antrodia camphorata against human ovarian carcinoma (SKOV-3) cells via modulation of HER-2/neu signaling pathway

Ethnopharmacological relevance

Antrodia camphorata (AC) is well known in Taiwan as a traditional Chinese medicinal fungus. However, the anticancer activity of AC against human HER-2/neu-overexpressing ovarian cancers is poorly understood.

Materials and methods

The aim of this study is to investigate whether a submerged fermentation culture of AC can inhibit human ovarian carcinoma cell (SKOV-3) proliferation by suppressing the HER-2/neu signaling pathway. Cell viability, colony formation, DCFH-DA fluorescence microscopy, western blotting, HER-2/neu immunofluorescence imaging, flow cytometry, and TUNEL assays were carried out to determine the anti-cancer effects of AC.

Results

MTT and colony formation assays showed that AC induced a dose-dependent reduction in SKOV-3 cell growth. Immunoblot analysis demonstrated that HER-2/neu activity and tyrosine phosphorylation were significantly inhibited by AC. Furthermore, AC treatment significantly inhibited the activation of PI3K/Akt and their downstream effector β-catenin. We also observed that AC caused G₂/M arrest mediated by down-regulation of cyclin D1, cyclin A, cyclin B1, and Cdk1 and increased p27 expression. Notably, AC induced apoptosis, which was associated with DNA fragmentation, cytochrome c release, caspase-9/-3 activation, PARP degradation, and Bcl-2/Bax dysregulation. An increase in intracellular reactive oxygen species (ROS) was observed in AC-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented AC-induced cell death, HER-2/neu depletion, PI3K/Akt inactivation, and Bcl-2/Bax dysregulation, indicating that AC-induced cell death was mediated by ROS generation.

Conclusions

These results suggest that AC may exert anti-tumor activity against human ovarian carcinoma by suppressing HER-2/neu signaling pathways.     

Davilla elliptica and Davilla nitida: Gastroprotective,anti-inflammatory immunomodulatory and anti-Helicobacter pylori action

Ethnopharmacological relevance

Davilla elliptica and Davilla nitida are species commonly found in the Brazilian Cerrado biome.

Aim of the study

Based on ethnopharmacological and phytochemical analyses, methanolic extracts from leaves of Davilla elliptica (EDE) and Davilla nitida (EDN) were evaluated for their anti-ulcer, anti-inflammatory, immunological and anti-Helicobacter pylori activities.

Materials and methods

The gastroprotective action of both extracts was evaluated in rodent experimental models (HCl/ethanol, ethanol or NSAID). We also evaluated anti-inflammatory (carrageenin-induced rat hind paw edema), immunomodulatory (murine peritoneal macrophages) and antibacterial action of both extracts against a standard strain of Helicobacter pylori.

Results

EDE and EDN (500 mg/kg) were able to protect gastric mucosa against HCl/ethanol solution (EDE 63%; EDN 59%), absolute ethanol (EDE 95%; EDN 88%), and also against injurious effect of NSAID (EDE 77%; EDN 67%). When EDE and EDN were challenged with sulfhydryl depleter compound, the gastroprotective action of both extracts was completely abolished. EDE had gastroprotective effect related to increase of glutathione bioavailability and stimulated higher levels of NO, H₂O₂ and TNF-α production. Otherwise EDN showed better anti-Helicobacter pylori action than EDE. Neither extracts presented anti-inflammatory activity by oral route.

Conclusion

The phytochemical investigation showed that both extracts possess phenolic acid derivatives, acylglycoflavonoids and condensed tannins with evident quantitative variations that probably influenced the pharmacological differences between extracts.