Antileishmaniasis effects of monoherbal skin ointment made from bark and leaf of Holoptelea integrifolia (Roxb.) Planch. in patients of cutaneous leishmaniasis.

Prevalence of parasitic skin diseases, cutaneous leishmaniasis is very frequent in Pakistan, especially in Baluchistan where occurrence of phelbotomine sand flies (vector of protozoan parasite of genus Leishmania) is very common. This study was conducted to assess the antileishmaniasis activity of Intericutol plus ointment (2% and 3%) made with ethanolic extract of bark and leaves of Holoptelea integrifolia (Roxb.)Planch. The antileishmaniasis effect was observed by applying the ointments on the lesions of leishmaniasis patients. 150 patients were included in the study that had single and multiple painful wet and dry ulcerative lesions on the exposed area of the body. The patients were divided into two groups of 75 patients each, applying 2% and 3% ointment respectively for 28 days. Dose of 10gm/week was applied topically on wounds. Excellent antileishmaniasis effect was observed with significant quick healing properties in the patients receiving 3% Intericutol plus ointment as compare to 2% showing 89% and 81% cure (p=0.02) respectively. It can be concluded that ointment made from medicinal plant proved to be very effective in treating cutaneous Leishmaniasis.

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.

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 / 中国天然药物

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.

UHPLC-DPPH method reveals antioxidant tyramine and octopamine derivatives in Celtis occidentalis.

Celtis occidentalis L. (common Hackberry, Cannabaceae) has been applied in the traditional medicine for a long time as a remedy for sore throat, aid during menstruation and for treating jaundice. Nevertheless, the phytochemical exploration of the plant is still incomplete, literature data is limited to flavonoid derivatives isolated from the leaves. The present study reports screening approaches for bioactive compounds in C. occidentalis by fast and simple UHPLC-coupled assays. The UHPLC-DPPH method revealed six constituents in the methanolic extract of the twigs that had not been reported in C. occidentalis before. The antioxidant compounds were isolated by the means of flash chromatography and semi-preparative HPLC and identified by Orbitrap® MS and NMR spectroscopy as N-trans-p-coumaroyloctopamine (1), N-trans-feruloyloctopamine (2), N-trans-caffeoyltyramine (3), 2-trans-3-(4-hydroxyphenyl)-N-[2-(4-hydroxyphenyl)-2-oxoethyl] prop-2-enamide (4), N-trans-p-coumaroyltryramine (5) and N-trans-feruloyltyramine (6). Despite the high antioxidant activity measured in the present study and literature data suggesting potential positive effects of the compounds in the central nervous system, the PAMPA-BBB assay performed with the Celtis extract revealed that none of the aforementioned compounds are able to penetrate across the blood-brain barrier via transcellular passive diffusion.

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.

Effects of aqueous leaves extract of Holoptelea integrifolia (Roxb) Planch on liver and kidney histopathology of albino rats.

Histopathological studies are an essential element to ascertain comprehensive safety profile of a drug. Unfortunately limited data are available about the toxicity of herbal remedies. Since a popular medicinal plant Holoptelea integrifolia (Roxb) Planch. contains various bioactive molecules, the present study is aimed to assess the histopathological alterations induced by aqueous extract of Holoptelea integrifolia on liver and kidney of wistar albino rat. In this study 60 rats divided in two groups; control and treated with aqueous extract of Holoptelea integrifolia (250mg/kg body weight) for 5 days. Histopathlogical studies by hematoxylin and eosin (H&E) staining were done on the liver and kidney tissues at the end of dosing by using standard procedure. Microscopic examination was then carried out to observe any pathological changes in the animals. The result showed that there is no significant variation in the basic architecture of liver and kidney as compared to control male wistar albino rats. In conclusion, aqueous extract of leaves of H. integrifolia may be safe and nontoxic. Further work on pharmacological aspects is required to evaluate the clinical potential of this plant for different ailments.

Strategy for Screening of Antioxidant Compounds from Two Ulmaceae Species Based on Liquid Chromatography-Mass Spectrometry.

Liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics implies that annotated metabolites can serve as potential markers of the associated bioactivities of plant extracts. Firstly, we selected Aphananthe aspera and Zelkova serrata (Family: Ulmaceae) from 16 Korean plant species based on their distinct principal component analysis (PCA) patterns in LC-MS datasets and antioxidant activity assays. Further, we chose 40% solid-phase extraction (SPE) extracts of the two species displaying the highest antioxidant activities coupled with distinct PCA patterns. Examining the metabolite compositions of the 40% SPE extracts, we observed relatively higher abundances of quercetin, kaempferol, and isorhamnetin O-glucosides for A. aspera, whereas quercetin, isorhamnetin O-glucuronides, and procyanidin dimer were relatively higher in Z. serrata. These metabolites were clearly distinguished in pathway map and displayed strong positive correlations with antioxidant activity. Further, we performed preparative high-performance liquid chromatography (prep-HPLC) analysis coupled with the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assay to validate their functional correlations. As a result, quercetin O-sophoroside was determined as the main antioxidant in A. aspera, while isorhamnetin O-glucuronide and procyanidin dimer were the primary antioxidants in Z. serrata. The current study suggests that the LC-MS-based untargeted metabolomics strategy can be used to illuminate subtle metabolic disparities as well as compounds associated with bioactivities.

Chemical characterization, pharmacological effects, and toxicity of an ethanol extract of Celtis pallida Torr. (Cannabaceae) aerial parts.

ETHNOPHARMACOLOGICAL RELEVANCE: Celtis pallida Torr (Cannabaceae) is employed as a folk medicine for the treatment of inflammation, pain, skin infections, and diarrhea, among other diseases. AIM OF THE STUDY: The purpose of this work was to assess the chemical composition, the in vitro and in vivo toxicity, the antimicrobial, anti-inflammatory, antidiarrheal, antinociceptive, locomotor, and sedative effects of an ethanolic extract obtained from Celtis pallida aerial parts (CPE). MATERIALS AND METHODS: The composition of CPE was carried out by GC-MS. The in vitro and in vivo toxic activity of CPE was estimated with the comet assay (10-1000 µg/ml) for 5 h in peripheral blood mononuclear cells, and the acute toxicity test (500-5000 mg/kg p.o.), for 14 days, respectively. The antimicrobial effect of CPE was evaluated using the minimum inhibitory concentration (MIC) assay, whereas the antidiarrheal activity (10-200 mg/kg p.o.) was calculated using the castor oil test. The antinociceptive effects of CPE (50-200 mg/kg p.o.) were estimated with the acetic acid and formalin tests, as well as the hot plate test. The sedative and locomotor activities of CPE (50-200 mg/kg p.o.) were assessed with the pentobarbital-induced sleeping time test and the rotarod test, respectively. RESULTS: The main compound found in CPE was the triterpene ursolic acid (22% of the extract). CPE at concentrations of 100 µg/ml or higher induced genotoxicity in vitro and showed low in vivo toxicity (LD50 > 5000 mg/kg p.o.). Additionally, CPE lacked (MIC > 400 µg/ml) antimicrobial activity but exerts antinociceptive (ED50 = 12.5 ±â€¯1.5 mg/kg) and antidiarrheal effects (ED50 = 2.8 mg/kg), without inducing sedative effects or altering the locomotor activity. The antinociceptive activity of CPE suggests the participation of adrenoceptors, as well as the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway. CONCLUSION: C. pallida exerts its antinociceptive effects probably mediated by the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.

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.

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.

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.

Preliminary studies of gastroprotective effect of Celtis iguanaea (Jacq.) Sargent leaves (Ulmaceae).

Antiulcerogenic activity of crude ethanolic extract of Celtis iguanaea leaves (CEE) was observed with experimental models such as ethanol, indomethacin, stress and pyloric ligation-induced gastric ulcers. Results obtained from indomethacin-induced ulcer showed the hexane fraction (HF) as the active fraction of CEE. This fraction inhibits the gastric acid secretion, increasing the gastric pH, decreasing the gastric acidity and total gastric contents. Neither the CEE nor the HF alters intestinal motility, thereby excluding a cholinergic antagonist mechanism. Further studies need to be conducted with HF in order to elucidate the active principle and the pharmacological mechanism involved.