Effect of Holoptelea integrifolia (Roxb.) Planch. n-Hexane Extract and Its Bioactive Compounds on Wound Healing and Anti-Inflammatory Activity.

The stem bark of Holoptelea integrifolia (Roxb.) Planch. has been applied for the treatment of human cutaneous diseases as well as canine demodicosis in several countries. However, no detailed mechanistic studies have been reported to support their use. In this study, thin-layer chromatography and gas chromatography were used to screen phytochemicals from the fresh stem bark extract of H. integrifolia. We found the two major bioactive compounds, friedelin and lupeol, and their activity on wound healing was further investigated in keratinocytes. Both bioactive compounds significantly reduced wound area and increased keratinocyte migration by increasing matrix metalloproteinases-9 production. Subsequently, we found that the mRNA gene expressions of cadherin 1 and desmoglobin 1 significantly decreased, whereas the gene expression involved in keratinocyte proliferation and homeostasis (keratin-17) increased in compound-treated human immortalized keratinocytes cells. The expression of inflammatory genes (cyclooxygenase-2 and inducible nitric oxide synthase) and pro-inflammatory cytokine genes (tumor necrosis factor-alpha and interleukin-6) was reduced by treatment with n-hexane extract of H. integrifolia and its bioactive compounds. Our results revealed that H. integrifolia extract and its bioactive compounds, friedelin and lupeol, exhibit wound-healing activity with anti-inflammatory properties, mediated by regulating the gene expression involved in skin re-epithelialization.

Antinociceptive and anti-inflammatory effects of extract of Celtis iguanaea (Jacq.) Sargent leaves in mice.

The antinociceptive and anti-inflammatory activities of crude ethanolic extract of Celtis iguanaea leaves and their active fractions are reported. The oral treatment with crude ethanolic extract (CEE; 100, 300 or 1000 mg/Kg) inhibited the number of writhings in a dose-dependent manner. The intermediate dose also inhibited formalin-induced nociception in both phases. The oral treatment with dichloromethane fraction (DF; 9 mg/Kg) produced antinociceptive effect in both phases of formalin test; however, the treatment with ethyl acetate fraction (EAF; 16 mg/Kg) reduced pain only in the second phase of this test. The oral treatments with CEE (300 mg/Kg) or DF (9 mg/Kg) reduced the nociception induced by capsaicin and pre-treatment with naloxone did not change these effects. The oral administration of CEE (300 mg/Kg), DF (9 mg/Kg) or ethyl EAF (16 mg/Kg) reduced ear edema, leukocytes migration and myeloperoxidase activity. Furthermore, the oral treatment with CEE (300 mg/Kg) or EAF (16 mg/Kg) reduced the level of Tumor Necrosis Factor - Alpha (TNF-α) in the pleurisy test. In conclusion, the DF showed antinociceptive activity that involves the vanilloid system as well as anti-inflammatory effect and the EAF showed anti-inflammatory activity involving the reduction of TNF-α cytokine.

The extract of Celtis choseniana Nakai alleviates testosterone-induced benign prostatic hyperplasia through inhibiting 5α reductase type 2 and the Akt/NF-κB/AR pathway.

Benign prostatic hyperplasia (BPH) is a chronic male disease characterized by the enlarged prostate. Celtis chosenianaNakai (C. choseniana) is medicinally used to alleviate pain, gastric disease, and lung abscess. In this study, the effect of C. choseniana extract on BPH was investigated using testosterone-induced rats. Sprague Dawley rats were divided into five groups: control, BPH (testosterone 5 mg·kg-1), Fina (finasteride 2 mg·kg-1), and C. choseniana (50 and 100 mg·kg-1). After four weeks of TP treatment with finasteride or C. choseniana, prostate weights and DHT levels were measured. In addition, the prostates were histopathologically examined and measured for protein kinase B (Akt)/nuclear factor-κB (NF-κB)/AR signaling, proliferation, apoptosis, and autophagy. Prostate weight and epithelial thickness were reduced in the C. choseniana groups compared with that in the BPH group. The extract of C. choseniana acted as a 5α reductase inhibitor, reducing DHT levels in the prostate. Furthermore, the extract of C. choseniana blocked the activation of p-Akt, nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH. Moreover, the expression of Bax, PARP-1, and p53 increased, while the expression of bcl-2 decreased. The present study demonstrated that C. choseniana extract alleviated testosterone-induced BPH by suppressing 5α reductase and Akt/NF-κB activation, reducing AR signaling and inducing apoptosis and autophagy in the prostate. These results suggested that C. choseniana probably contain potential herbal agents to alleviate BPH.

Chemical and Physical Characterization of the Hackberry (Celtis australis) Seed Oil: Analysis of Tocopherols, Sterols, ECN and Fatty Acid Methyl Esters.

For the very first time, the nutritional and physicochemical properties of the oil extracted from hackberry Celtis australis fruit were investigated with the aim of possible applications of such wild fruit oil. The physicochemical properties such as peroxide value, acidity, saponification, iodine value and total fat content of the extracted oil were examined extensively. The obtained results showed that peroxide value, acidity, saponification, iodine value and total fat content of the extracted oil were found to be 4.9 meq O2/kg fat, 0.9 mg KOH/g fat, 193.6 mg KOH/g fat, 141.52 mg I2/g fat and ~5%, respectively. The predominant fatty acid found in this wild fruit is linoleic acid which was calculated to be 73.38%±1.24. In addition, gamma-tocopherol (87%) and ß-sitosterol (81.2%±1.08) were the major tocopherol and sterol compositions found in Celtis australis seed oil. Moreover, equivalent carbon number (ECN) analysis has indicated that the three linoleic acids are the main composition of the triacylglycerols extracted from Celtis australis. Also, the high value of omega 6 and ß-sitosterol make this oil applicable in cosmetics and pharmaceutical applications.

Hepatoprotective and neuroprotective flavanes from the fruits of Ulmus pumila L. (Ulmaceae).

Phytochemical study of the EtOAc fraction (active extract) of the fruits of Ulmus pumila L. resulted in the isolation of thirteen flavane derivatives, and they were identified by their precise spectral data and literature. All the compounds (1-13) were obtained from the fruits of U. pumila L. for the first time. Meanwhile, the compounds (1-13) were assayed for their hepatoprotective and neuroprotective activities, respectively. Compounds 1, 2, 5, 7 and 8 (10µM) exhibited remarkable hepatoprotective activities, and compounds 9, 10, and 13 showed significant neuroprotective activities with IC50 values of 4.08, 5.34, and 2.02µM, respectively.

Water-repellent plant surface structure induced by gall-forming insects for waste management.

Many animals and plants have evolved elaborate water-repellent microstructures on their surface, which often play important roles in their ecological adaptation. Here, we report a unique type of water-repellent structure on a plant surface, which develops as an insect-induced plant morphology in a social context. Some social aphids form galls on their host plant, in which they produce large amounts of hydrophobic wax. Excreted honeydew is coated by the powdery wax to form 'honeydew balls', which are actively disposed by soldier nymphs through an opening on their gall. These activities are enabled by a highly water-repellent inner gall surface, and we discovered that this surface is covered with dense trichomes that are not found on normal plant surfaces. The trichomes are coated by fine particles of the insect-produced wax, thereby realizing a high water repellency with a cooperative interaction between aphids and plants. The plant leaves on which the gall is formed often exhibit patchy areas with dense trichomes, representing an ectopic expression of the insect-induced plant morphology. In the pouch-shaped closed galls of a related social aphid species, by contrast, the inner surface was not covered with trichomes. Our findings provide a convincing example of how the extended phenotype of an animal, expressed in a plant, plays a pivotal role in maintaining sociality.

Anthelmintic effects of indigenous multipurpose fodder tree extracts against Haemonchus contortus.

Condensed tannins (CT) extracted from Balanites aegyptiaca, Tamarindus indica, and Celtis toka browses were used to evaluate their anthelmintic effect on different developmental stages of Haemonchus contortus. To achieve this objective, various serial concentrations of each CT extract of the foliages were used to test adult motility, inhibition of egg hatchability, and larval development. The fodders were selected based on their multipurpose advantage and accessibility to use as fodder for livestock in the low lands of the Gambella region. The fastest and slowest adult motility rate was observed in 2-ml (4 min) and 0.125-ml dose of C. toka, respectively, which is better than that in ivermectin. Egg hatchability inhibition was observed with dose difference within species, but there is no difference between B. aegyptiaca and T. indica. The foliage extracts of the studied browses were observed to inhibit the larvae by 100% at 2 ml, which is similar to ivermectin. There is no significant difference observed in larvae development inhibition between the species and ivermectin (p > 0.05). CT extracts of studied plants have found to own significant anthelmintic activity in a dose-dependent manner. They could serve as anthelmintic economically and eco-friendly after further and series of in vivo experiments.

Effects of an extract of Celtis aetnensis (Tornab.) Strobl twigs on human colon cancer cell cultures.

Cancers of the digestive tract, in particular colorectal cancer (CRC), are among those most responsive to dietary modification. Research has shown that approximately 75% of all sporadic cases of CRC are directly influenced by diet. Many natural compounds have been investigated for their potential usefulness as cancer chemopreventive agents as they have been thought to suppress carcinogenesis mainly during the initiation phase due to their radical scavenger activity. Since there is an increasing interest in the in vivo protective effects of natural compounds contained in plants against oxidative damage involved in several human diseases such as cancer, the aim of the present research was to test the effects of a Celtis aetnensis (Tornab.) Strobl twig extract on a human colon carcinoma cell line (Caco2). In order to elucidate the mechanisms of action of this extract, LDH release, GSH content, ROS levels, caspase-3 and γ-GCS expression were also evaluated. The results revealed that the Celtis aetnensis extract reduced the cell viability of the Caco2 cells inducing apoptosis at the lowest concentration and necrosis at higher dosages. In addition, this extract caused an increase in the levels of ROS, a decrease in RSH levels and in the expression of HO-1. The expression of γ-GCS was not modified in the Celtis aetnensis-treated Caco-2 cells. These results suggest an interference of this extract on the oxidant/antioxidant cell balance with consequent cell damage. The present study supports the growing body of data suggesting the bioactivities of Celtis aetnensis (Tornab.) Strobl and its potential impact on cancer therapy and on human health.

Antioxidant Activities and Reduced Amyloid-ß Toxicity of 7-Hydroxycalamenene Isolated from the Essential Oil of Zelkova serrata Heartwood.

The in vitro and in vivo antioxidant activities and its potential to protect against amyloid-P toxicity of essential oils from Zelkova serrata (Thunb.) Makino were investigated in the model organism Caenorhabditis elegans. The results revealed that the essential oil of Z serrata heartwood exhibited great radical scavenging activities and high total phenolic content. In vivo assays showed significant inhibition of oxidative damage in wild-type C. elegans under juglone- indueed oxidative stress and heat shock. Based on results from both in vitro and in vivo assays, the major compound in essential oil of heartwood, (-)-(S, 4S)- 7-hydroxycalamenene (IS, 4S-7HC), may contribute significantly to the observed antioxidant activity. Further evidence showed that IS, 4S-7HC significantly delayed the paralysis phenotype in amyloid beta-expressing transgenic C. elegans. These findings suggest that IS, 4S-7HC from the essential oil of Z serrata heartwood has potential as a source for antioxidant or Alzheimer's disease treatment.

Acute oral toxicity of Celtis iguanaea (Jacq. ) Sargent leaf extract (Ulmaceae) in rats and mice / Toxicidade oral aguda do extrato de folhas de Celtis iguanaea (Jacq. ) Sargent em ratos e camundongos

RESUMO Celtis iguanaea (Jacq.) Sargent is popularly used to treat urinary infections, kidneys, breast, body aches, rheumatism, asthma, cramps, poor digestion and as a diuretic medicine. This study aims to determine the acute toxicity of the aqueous leaf extract of Celtis iguanaea (Jacq.) Sargent in rodents. After the collection processes, identification, drying and grinding, the lyophilized powder of the leaves produced, by infusion, the aqueous extract and it was dissolved in saline 0.9%. The administration was made by gavage at a dose of 2000 mg kg-1to rats and mice of both genders. The oral toxicity was determined according to the OECD 423 guide. Signs of toxicity were observed for 15 days and classified from 0 to 4 respectively as missing, rare, mild, moderate and severe. The weight of the animals and the physiological parameters such as food intake and excrements production were observed. All animal tissue samples were collected for histological analysis. The extract was included in Type 5 (substance with LD50 higher than 2000 mg kg-1 and less than 5000 mg kg-1), being considered of low toxicity, but the histopathologycal findings suggested nephrotoxicity and cardiotoxicity. The absolute weight of the kidneys and the heart of the male rats and mice increased, but there was no significant raise in the relative weight of the animals’ organs.

RESUMO Celtis iguanaea (Jacq.) Sargent é uma planta usada popularmente para tratar infecções do trato urinário, rim, mama, dores no corpo, reumatismo, asma, cólicas, má digestão e também é usada como diurético. Este trabalho objetivou determinar a toxicidade aguda do extrato aquoso de folhas de Celtis iguanaea (Jacq.) Sargent em roedores. Após os processos de coleta, identificação, secagem e moagem, o pó liofilizado das folhas da planta foi utilizado para produzir o seu extrato aquoso por infusão e então dissolvido em solução salina a 0.9 %. A administração foi feita por gavagem na dose de 2000 mg kg-1 em ratos e camundongos de ambos os sexos. A toxicidade oral foi determinada de acordo com o guia 423 da OECD. Sinais de toxicidade foram observados por 15 dias e tabulados de 0 a 4, respectivamente, como ausentes, raros, leves, moderados e graves. Foi acompanhado o peso dos animais e parâmetros fisiológicos tais como alimentação e excreções. Amostras do tecido de todo o animal foram coletadas para análise histológica. A toxicidade encontrada para o extrato foi incluída na classe 5 (substâncias com DL50 superior a 2000 mg kg-1 e menor que 5000 mg kg-1) sendo considerada baixa, porém, as observações histopatológicas sugerem nefrotoxicidade e cardiotoxicidade. O peso absoluto dos rins e coração de ratos e camundongos machos aumentou, porém, não houve aumento significativo no peso relativo dos órgãos dos animais.

Responses of gas-exchange rates and water relations to annual fluctuations of weather in three species of urban street trees.

The frequency of extreme weather has been rising in recent years. A 3-year study of street trees was undertaken in Tokyo to determine whether: (i) street trees suffer from severe water stress in unusually hot summer; (ii) species respond differently to such climatic fluctuations; and (iii) street trees are also affected by nitrogen (N) deficiency, photoinhibition and aerosol pollution. During the study period (2010-12), midsummers of 2010 and 2012 were unusually hot (2.4-2.8 °C higher maximum temperature than the long-term mean) and dry (6-56% precipitation of the mean). In all species, street trees exhibited substantially decreased photosynthetic rate in the extremely hot summer in 2012 compared with the average summer in 2011. However, because of a more conservative stomatal regulation (stomatal closure at higher leaf water potential) in the hot summer, apparent symptoms of hydraulic failure were not observed in street trees even in 2012. Compared with Prunus × yedoensis and Zelkova serrata, Ginkgo biloba, a gymnosperm, was high in stomatal conductance and midday leaf water potential even under street conditions in the unusually hot summer, suggesting that the species had higher drought resistance than the other species and was less susceptible to urban street conditions. This lower susceptibility might be ascribed to the combination of higher soil-to-leaf hydraulic conductance and more conservative water use. Aside from meteorological conditions, N deficiency affected street trees significantly, whereas photoinhibition and aerosol pollution had little effect. The internal CO2 and δ(13)C suggested that both water and N limited the net photosynthetic rate of street trees simultaneously, but water was more limiting. From these results, we concluded that the potential risk of hydraulic failure caused by climatic extremes could be low in urban street trees in temperate regions. However, the size of the safety margin might be different between species.

Mechanisms involved in the gastroprotective activity of Celtis iguanaea (Jacq.) Sargent on gastric lesions in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Celtis iguanaea (Canabaceae) is popularly known as esporão-de-galo, stands out among the medicinal plants used for treatment of gastric ulcers. In Brazil, the leaves they are used traditionally in infusion forms as an analgesic, antiasthmatic, digestive and diuretic. AIM OF THE STUDY: The present study was aimed to investigate the antiulcer mechanisms of hexane extract Celtis iguanaea leaves (HE) in several induced-gastric ulcer and characterize its chemical composition. MATERIALS AND METHODS: The HE was obtained by exhaustive extraction in Soxhlet apparatus. The chemical characterization of HE was performed by Electrospray Fourier transform ion cyclotron mass spectrometry (ESI FT-ICR MS) analysis. Mice were used for the evaluation of the gastroprotective activity. HE was analyzed in the HCl/ethanol, hypothermic restraint stress ulcer and acetic acid. In the investigation of the gastroprotective mechanisms of HE, were performed the amount of adhered gastric mucus, participation of the α2-adrenoceptor, nitric oxide (NO) and prostaglandins (PGs) using the HCl/ethanol-induced gastric mucosa lesion model. RESULTS: ESI FT-ICR MS analysis of HE suggest the presence of compounds as lipids, sterol lipids, steroids glycosides and polyphenol glycosides. The oral administration of HE at doses of 100 mg/kg or 200 mg/kg was able to protect the gastric mucosa against HCl/ethanol (10 mL/kg p.o.), and HE at dose of 100mg/kg protected against hypothermic-restraint stress and acetic -induced gastric lesions. The pretreatment with Yoimbine (2mg/kg, s.c.), an antagonist α2-adrenergic, L-NAME (20mg/kg, s.c.), an inhibitor of nitric oxide synthesis or indomethacin (10mg/kg, s.c.), an inhibitor of prostaglandin production, reversed the gastroprotective activity of HE (100mg/kg, p.o.). CONCLUSIONS: Our results suggest that the Celtis iguanaea HE exhibits gastroprotective activity in different gastric ulcer models. The mechanism of gastroprotective effect of Celtis iguanaea HE suggests the participation of mucus as well as the involvement of α2-adrenergic receptors, NO and prostaglandins. The hydroxyl-linolenic acid, linoleic acids and conjugated oxo-linoleic acids are among the phytoconstituents that were identified in the Celtis iguanaea HE.

Holoptelea integrifolia (Roxb.) Planch: a review of its ethnobotany, pharmacology, and phytochemistry.

Holoptelea integrifolia (Ulmaceae) is a versatile medicinal plant used in various indigenous systems of medicine for curing routine healthcare maladies. It is traditionally used in the treatment and prevention of several ailments like leprosy, inflammation, rickets, leucoderma, scabies, rheumatism, ringworm, eczema, malaria, intestinal cancer, and chronic wounds. In vitro and in vivo pharmacological investigations on crude extracts and isolated compounds showed antibacterial, antifungal, analgesic, antioxidant, anti-inflammatory, anthelmintic, antidiabetic, antidiarrhoeal, adaptogenic, anticancer, wound healing, hepatoprotective, larvicidal, antiemetic, CNS depressant, and hypolipidemic activities. Phytochemical analysis showed the presence of terpenoids, sterols, saponins, tannins, proteins, carbohydrates, alkaloids, phenols, flavonoids, glycosides, and quinines. Numerous compounds including Holoptelin-A, Holoptelin-B, friedlin, epifriedlin, ß -amyrin, stigmasterol, ß -sitosterol, 1, 4-napthalenedione, betulin, betulinic acid, hexacosanol, and octacosanol have been identified and isolated from the plant species. The results of several studies indicated that H. integrifolia may be used as an effective therapeutic remedy in the prevention and treatment of various ailments. However, further studies on chemical constituents and their mechanisms in exhibiting certain biological activities are needed. In addition, study on the toxicity of the crude extracts and the compounds isolated from this plant should be assessed to ensure their eligibility to be used as source of modern medicines.

Desempenho de sementes e plântulas de rabanete sob ação de extrato aquoso de folhas de Trema micrantha (Ulmaceae) / Performance of radish seeds and seedlings under action of aqueous extract of leaves of Trema micrantha (Ulmaceae)

O trabalho objetivou avaliar o efeito alelopático de extrato aquoso de folhas de Trema micrantha sobre germinação de sementes e crescimento inicial de plântulas de rabanete. Para os extratos foram utilizadas folhas maduras e frescas nas concentrações 2, 4 e 8% (p/v), com aferição do pH e potencial osmótico. No bioensaio de germinação, foram empregadas cinco repetições de 25 sementes distribuídas em placas de petri forradas com papel Germitest, umedecido com 7 mL de extrato ou água e mantidos a 25 ºC em B.O.D., por cinco dias. Foram determinados a porcentagem de germinação (PG), velocidade de germinação (VG), índice de velocidade de germinação (IVG) e índice de efeito alelopático (RI). No bioensaio de crescimento inicial, foram avaliados o comprimento da radícula e do hipocótilo, a biomassa fresca e seca, o conteúdo de água e os teores de clorofila a, b e total. Todos os atributos de germinação, PG, VG, IVG e RI, foram afetados negativamente pelos extratos de T. micrantha. O crescimento inicial foi influenciado pelos extratos, ocorrendo redução do comprimento da radícula e aumento do hipocótilo. O extrato não alterou a biomassa fresca e seca e os teores de clorofila. Extratos aquosos de folhas de Trema micrantha exerceram ação alelopática sobre a germinação e crescimento inicial do rabanete, não influenciando na inibição da síntese de pigmentos fotossintéticos.

This study aimed to evaluate the allelopathic effects of aqueous extracts of Trema micrantha leaves on seed germination and early growth of seedlings of radish (Raphanus sativus L.). Leaf extracts were prepared at concentrations of 2, 4 and 8%. pH and osmotic potential were also performed from the extracts. Germination bioassay consisted of five replicates of 25 seeds of radish distributed in Petri dishes with germitest paper and 7 mL of extract or water and kept at 25°C in B.O.D. for five days. Germination percentage (PG), germination speed (VG), germination speed index (IVG) and index of allelopathic effect (RI) were determined. For bioassay initial growth, seeds were germinated until they reach 2 mm protrusion radicle and transferred to Gerbox containing germitest paper and 15 mL of extract or water, kept seven days at 25°C in B.O.D. for evaluating length of the radicle and hypocotyl, fresh and dry mass, water content and content of chlorophyll (a, b and total). Leaf extracts from T. micrantha affected negatively all parameters examined for germination (PG, VG, IVG and RI). The extracts affected the initial growth, causing reduction of the radicle length and stimulating the growth of hypocotyls, but not interfered on fresh and dry weight and content of chlorophyll. Aqueous extracts of T. micrantha leaves exerted allelopathic action on germination and early growth of radish, but not caused inhibition of synthesis of photosynthetic pigments.

Antineoplastic activity of Holoptelea integrifolia (Roxb.) Planch bark extracts (in vitro).

Cancer remains the major public health concern with a number of cancer patients relying on chemotherapy as a treatment option. Although, advances in biomedical research have led to increased anticancer agents in recent years, the treatment is not always effective due to resistance, toxicity or other factors. Phytochemicals and their active components isolated from plants have provided diversified effective drugs many of them are currently used against cancer and other diseases. Holoptelea integrifolia (Roxb) Planch (Ulmaceae) is a widely distributed plant in many parts of the world, also grown in gardens of Pakistan. It is an ornamental plant with certain medicinal characteristics due to many valuable and active phyto constituents in various parts of the plant. We looked at in vitro antineoplastic effects of four different extracts, in butanol (BMBU), hexane (BMHx), ethyl acetate (BMET) and chloroform (BMCHF), from bark of Holoptelea integrifolia on small cell lung cancer, breast, prostate, coloretal and hepatocellular cancer cell lines. Plant extracts BMHx and BMET showed significant cytotoxic effects on breast and prostate cancer cells. These preliminary studies are encouraging to proceed further this research in future, regarding the isolation of active phytoconstituents in these extracts as well as its mechanism in chemoprevention and combination anticancer therapy.

Assessment of the cytotoxic, genotoxic, and antigenotoxic activities of Celtis iguanaea (Jacq.) in mice.

Ethnobotanical surveys of Cerrado native plants show that leaves of Celtis iguanaea (Jacq.) Sargent (Cannabaceae), popularly known in Brazil as "esporão de galo", are used in folk medicine for body pain, asthma, cramps, poor digestion, urinary infection, kidney dysfunctions, as well as a stimulant and diuretic. This work aimed at evaluating possible C. iguanaea aqueous leaf extract (CALE) cytotoxicity, genotoxicity, and antigenotoxicity using the mouse bone marrow micronucleous test. To assess CALE genotoxicity, Swiss mice were orally treated with three different extract concentrations (100, 300, and 500 mgkg-1). To evaluate its antigenotoxicity, the same doses were used simultaneously with a single i.p. dose of mitomycin C (MMC, 4mg.kg-1). The frequencies of micronucleated polychromatic erythrocytes (MNPCE) were evaluated 24 h and 48 h after administration except for the negative control (24 h). Genotoxicity was evaluated using the frequency of micronucleated polychromatic erythrocytes (MNPCE), whereas cytotoxicity was assessed by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). The results showed that CALE did not exhibit a significant reduction in the PCE/NCE ratio, neither a considerable increase in the frequency of MNPCE. Nonetheless, CALE reduced bone marrow toxicity (increased PCE/NCE ratio) and decreased the micronuclei frequency induced by MMC. We can conclude that CALE presented no cytotoxic and genotoxic effects, but showed antigenotoxic and anticytotoxic actions under the experimental conditions applied in this study.

Ethyl 2,4,6-trihydroxybenzoate is an agonistic ligand for liver X receptor that induces cholesterol efflux from macrophages without affecting lipid accumulation in HepG2 cells.

The present study reports a novel liver X receptor (LXR) activator, ethyl 2,4,6-trihydroxybenzoate (ETB), isolated from Celtis biondii. Using a reporter gene assay, time-resolved fluorescence resonance energy transfer (TR-FRET), and surface plasmon resonance (SPR) analysis, we showed that ETB directly bound to and stimulated the transcriptional activity of LXR-α and LXR-ß. In macrophages, hepatocytes, and intestinal cells, ETB suppressed cellular cholesterol accumulation in a dose-dependent manner and induced the transcriptional activation of LXR-α/-ß-responsive genes. Notably, ETB did not induce lipogenic gene expression or cellular triglyceride accumulation in hepatocytes. These results suggest that ETB is a dual-LXR modulator that regulates the expression of key genes in cholesterol homeostasis in multiple cells without inducing lipid accumulation in HepG2 cells.

Selective apoptotic effect of Zelkova serrata twig extract on mouth epidermoid carcinoma through p53 activation.

Apoptosis or programmed cell death plays an essential role in chemotherapy-induced tumor cell killing, and inducers of apoptosis are commonly used in cancer therapy. Treatment with Zelkova serrata extracts was performed in human gingival fibroblast (HGF), mouth epidermoid carcinoma cell (KB), lower gingival squamous cancer cell (YD38) and tongue mucoepidermoid carcinoma cells (YD15). We observed that extract prepared from Zelkova serrata twig selectively inhibited proliferation of various oral cancer cells, but not normal gingival fibroblasts, in a dose-dependent manner. Caspase-8-mediated apoptosis was induced by treatment with the extract only in mouth epidermoid carcinoma and not in other types of cancer cells, including lower gingival squamous cell carcinoma. The selective apoptotic effect of Zelkova serrata twig extract in mouth epidermoid carcinoma was dependent on normal p53 status. Apoptosis was not remarkably induced by treatment with the extract in either lower gingival squamous or tongue mucoepidermoid carcinoma cells, both of which contain abnormalities of p53. Upon treatment with Zelkova serrata twig extract, mouth epidermoid carcinoma cells accumulated in S phase by activation of p21. These data indicate that Zelkova serrata twig extract exerted a cancer type-specific, p53-dependent apoptotic effect and disturbed the cell cycle, which suggests that herbal medicine could be a treatment for specific types of cancers.

Avaliação da atividade fitotóxica com enfoque alelopático do extrato das cascas de Celtis iguanaea (Jacq. ) Sargent Ulmaceae e purificação de dois triterpenos / Evaluation of the phytotoxic activity focused on the allelopathic effect of the extract from the bark of Celtis iguanaea (Jacq. ) Sargent Ulmaceae and purification of two terpenes

A espécie Celtis iguanaea (Jacq.) Sargent é popularmente conhecida como esporão de galo ou grão de galo. As folhas são indicadas pelo uso popular para o tratamento de dores no corpo e no peito, para reumatismo, asma, cólicas, má digestão e como diurético; as raízes são utilizadas para infecções urinárias e as cascas para a febre. O presente trabalho objetivou contribuir para o estudo fitoquímico e atividade fitotóxica com enfoque alelopático das cascas de Celtis iguanaea. O extrato etanólico foi submetido à partição com os solventes hexano, clorofórmio e acetato de etila. As substâncias friedelina e epifriedelinol (triterpenos) foram isoladas da fração hexano e identificadas por meio de métodos espectroscópicos de RMN de ¹H e 13C. O extrato bruto na concentração de 0,1 mg mL-1 causou inibição acentuada do hipocótilo em 34,97% e estimulou o crescimento da radícula em 29,64% de plântulas de Lactuca sativa. No ensaio de toxicidade frente à Artemia salina o extrato bruto e frações apresentaram uma CL50 superior a 1000 μg mL-1, indicando que o mesmo não possui efeito tóxico.

The species Celtis iguanaea (Jacq.) Sargent is popularly known as "esporão de galo" or "grão de galo". Its leaves are recommended by the popular use for the treatment of body and chest aches, as well as for rheumatism, asthma, cramps, indigestion and as diuretic; its roots are used for urinary infections and its bark for fever. This study aimed to contribute to the phytochemical investigation of the toxic activity focused on the allelopathic effect of the bark of Celtis iguanaea. The ethanol extract was subjected to solvent partition with hexane, chloroform and ethyl acetate. The substances friedelin and epifriedelinol (triterpenes) were isolated from the hexane fraction and identified by spectroscopic methods ¹H and 13C NMR. The crude extract at a concentration of 0.1 mg mL-1 caused marked inhibition of hypocotyl in 34.97% and stimulated radicle growth in 29.64% seedlings of Lactuca sativa. In the toxicity test against Artemia salina the crude extract and fractions showed an LC50 higher than 1000 μg mL-1, indicating that it has no toxic effect.

Anatomía foliar de arbustos y árboles medicinales de la región chaqueña semiárida de la Argentina / Foliar anatomy of medicinal trees and shrubs of the semi-arid Chaco region of Argentina

Se estudió la anatomía foliar de 32 arbustos y árboles medicinales de los Distritos Chaqueños Occidental y Serrano (Argentina). El objetivo de este trabajo fue proveer una clave para el reconocimiento de estos taxones a partir de hojas fragmentadas, desmenuzadas o pulverizadas. Para el estudio las muestras de herbario fueron reconstituidas y fijadas en FAA; y, en cuanto a las preparaciones, se utilizaron técnicas histológicas convencionales. Algunos de los principales caracteres de identificación fueron: los tricomas estrellados en Capparicordis tweediana y Ruprechtia triflora, cistolíticos en Celtis spp.; escamoso-peltados en Zanthoxylum coco; epidermis papilosa (e.g., Schinopsis lorentzii); los estomas ciclocíticos en Bulnesia sarmientoi, Maytenus vitis-idaea, Moya spinosa y Schinopsis spp.; idioblastos cristalíferos epidérmicos en Scutia buxifolia; la epidermis cristalífera en Maytenus vitis-idaea; la epidermis pluristrata en Jodina rhombifolia; la presencia de hipodermis en Castela coccinea, Maytenus vitis-idaea, Prosopis ruscifolia y Ziziphus mistol; los haces bicolaterales en Lycium cestroides; la presencia de arena cristalina en Calycophyllum multiflorum y Lycium cestroides; la ausencia total de cristales en la familia Capparaceae. Para la identificación de las especies estudiadas se presenta una clave dicotómica e ilustraciones originales.