New cytotoxic compounds from the leaves of Caesalpinia benthamiana (Baill.) Herend. & Zarucchi (Fabaceae).

OBJECTIVE: The incidence of multi-drug resistant cancer and the adverse effects associated with available chemotherapy have necessitated the search for new drug candidates. This study investigates the cytotoxic activity of Caesalpinia benthamiana. MATERIALS AND METHODS: Column chromatography (CC) and preparative thin layer chromatography (PTLC) were used to isolate compounds. Structural elucidation was done by spectroscopic analysis. MTT assay was used to evaluate cytotoxicity of the compounds against three human adenocarcinoma cells, using methotrexate and dimethyl sulfoxide (DMSO) as positive and negative controls, respectively. CyQuant direct cell proliferation and caspase-3/7 green detection assays were used to investigate the dichloromethane fraction. IC50 values of isolated compounds were determined from sigmoidal dose-response curve. RESULTS: Four new cytotoxic compounds, benthamianoate (2), benthamiacone (3), benthamianin (5) and benthamianol (6), and two known compounds, methyl gallate (1) and 2-methoxyacrylic acid (4) were identified. All the compounds were active with the new monoterpenoid characterized as benthamiacone exhibiting the highest activity (IC50 13.23-21.97 µg/ml) across cancer cell lines investigated. CyQuant direct cell proliferation assay showed significant reduction in the number of live carcinoma cells, while caspase-3/7 green detection assay showed significant increase in the number of dead carcinoma cells. CONCLUSION: This study revealed potential cytotoxic compounds which are here reported for the first time from C. benthamiana.

Chemistry and Pharmacology of Alkylamides from Natural Origin.

Interest in alkylamide, as a class of compound, has grown tremendously in recent years. This interest is due to the many presumed benefits in food, cosmetics, and medicine. This review focuses on the different alkylamides naturally occurring in many plant species. Several methods have been employed for their identification as well as isolation and several in vitro and in vivo studies have revealed their therapeutic effects in various diseases. In general, alkylamides have been reported to have several biological activities and pharmacological effects which include immunomodulatory, antithrombotic, antimicrobial, antiviral, antioxidant, anti-inflammatory, analgesic, anticancer, antidiabetic, and antiprotozoal activities. Moreover, many studies have reported on their mechanisms of action, structure-activity relationship, pharmacokinetics, and toxicity. We herein present an updated report on the chemistry and pharmacology of alkylamides of natural origin.

Antioxidant and Anticholinesterase Activities of Macrosphyra Longistyla (DC) Hiern Relevant in the Management of Alzheimer's Disease.

Macrosphyra longistyla has been used in many traditional systems of medicine for its anti-hemorrhagic, antidiabetic, anti-ulcer, and anti-diarrhea properties. The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitions of the crude methanol extracts and its various partitioned fractions were determined by a modified method of Ellman. An evaluation of the antioxidant activity was carried out using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging, ferric reducing power, and nitric oxide scavenging assays. The total flavonoids were estimated based on the aluminum chloride method, while the total tannins and phenolics were estimated based on the vanillin-HCl and Folin-Ciocalteu method, respectively. The ethyl acetate fraction had the highest DPPH radical scavenging activity, and the highest ferric reducing power with a concentration providing 50% inhibition (IC50) of 0.079 mg/mL and 0.078 mg/mL, respectively, while the crude methanol extract had the highest nitric oxide scavenging activity with an IC50 of 0.008 mg/mL. The methanol extract had the highest phenolics and flavonoids contents, while the aqueous fraction had the highest tannin content. The crude methanol extract had the best AChE and BuChE inhibitory action, with an IC50 of 0.556 µg/mL and 5.541 µg/mL, respectively, suggesting that the plant had a better AChE inhibiting potential. A moderate correlation was observed between the phenolic content and DPPH radical scavenging, NO radical scavenging, and AChE inhibitory activities (r2 = 0.439, 0.430, and 0.439, respectively), while a high correlation was seen between the flavonoid content and these activities (r2 = 0.695, 0.724, and 0.730, respectively), and the ferric reducing antioxidant power correlated highly with the proautocyanidin content (r2 = 0.801). Gas chromatography mass spectrometry (GCMS) revealed decanoic acid methyl ester (24.303%), 11,14-eicosadienoic acid methyl ester (16.788%), linoelaidic acid (10.444%), pentadecanoic acid (9.300%), and 2-methyl-hexadecanal (9.285%). Therefore, we suggest that M. longistyla contain bioactive chemicals, and could be a good alternative for the management of Alzheimer's and other neurodegenerative diseases.

Hepatoprotective effects of rosmarinic acid: Insight into its mechanisms of action.

Liver diseases such as hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma are one of the major health challenges in the world and many conditions such as inadequate nutrition, viral infection, ethanol and drug abuse, xenobiotic exposure, and metabolic diseases have been implicated in the development and progression of liver diseases. Several factors including lipid peroxidation, production of reactive oxygen species (ROS), peroxynitrite formation, complement factors and proinflammatory mediators, such as cytokines and chemokines, are involved in hepatic diseases. Rosmarinic acid (RA) is a natural phenolic compound found mainly in the family Lamiaceae consisting of several medicinal plants, herbs and spices. Several biological activities have been reported for RA and these include antioxidant properties as a ROS scavenger and lipid peroxidation inhibitor, anti-inflammatory, neuroprotective and antiangiogenic among others. This review is aimed at discussing the effects of RA on the liver, highlighting its hepatoprotective potential and the underlying mechanisms.

Cytotoxicity Studies of the Extracts, Fractions, and Isolated Compound of Pseudocedrela kotschyi on Cervical Cancer (HeLa), Breast Cancer (MCF-7) and Skeletal Muscle Cancer (RD) Cells.

BACKGROUND: This study determined the cytotoxic effects of root and stem bark extracts, fractions, and isolated compounds derived from Pseudocedrela kotschyi on HeLa, MCF-7, and RD cells. MATERIALS AND METHODS: The cytotoxic activity was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay against three cell lines (RD, HeLa, and MCF 7) at concentrations ranging from 0.01 to 1000 µg/mL. Isolation of crude saponin was done from the most active ethyl acetate fraction and further purified using vacuum liquid chromatography and preparative thin layer chromatographic techniques. RESULTS: The cytotoxicity assay revealed that the methanol extract from the root bark and the ethyl acetate fraction from the stem bark exhibited marked anticancer activity with IC50 of 87.36 µg/ml and 21.53 µg/ml, respectively, on HeLa cancer cell line and 101.51 µg/mL and 38.46 µg/mL, respectively, on RD cell line. These values are comparable with that obtained from vinblastine and methotrexate used as standard drugs (IC50 values of 0.01 µg/mL and 0.05 µg/mL, respectively). The isolated crude saponins also gave IC50 values of 5.28 µg/mL and 81.52 µg/mL against the RD cell lines and IC50values of 1.05 µg/mL and 86.8 µg/mL for the MCF 7 cancer cell lines. PTLC led to the isolation of a compound from the crude saponin which was identified as 7-deacetoxy-7-oxogedunin through spectroscopic analysis and comparison with literature data. CONCLUSIONS: P. kotschyi could be considered as a potential source of chemotherapeutic agent. However, further research to determine the exact mechanism of action needs to be carried out. SUMMARY: Pseudocedrela kotschyi methanol extract from the root bark and the ethyl acetate fraction from the stem bark exhibited marked anticancer activity on HeLa, MCF-7, and RD cell lines7-deacetoxy-7-oxogedunin isolated as a white crystalline substance from the most active ethyl acetate fraction contributed to the observed activity. Abbreviations Used: MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; TLC: Thin layer chromatography; VLC: Vacuum liquid chromatography; PTLC: Preparative thin layer chromatographic; NMR: Nuclear magnetic resonance; FBS: Fetal bovine serum; DMEM: Dulbecco's modified Eagle's medium; PBS: Phosphate buffer saline; FHI: Forest Herbarium Ibadan; DMSO: Dimethylsuphoxide; SEM: Standard error of mean.

Antioxidant and acetylcholinesterase inhibitory activities of leaf extract and fractions of Albizia adianthifolia (Schumach) W.F. Wright.

BACKGROUND: This study was conducted to determine the antioxidant and acetylcholinesterase inhibitory activities of the leaf extract and different fractions of Albizia adianthifolia (Schumach.) W. Wright, and also to identify and quantify some phenolic compounds in the extract. METHODS: The antioxidant and acetylcholinesterase inhibitory activities of the methanol extract (CME), ethyl acetate (EAF), chloroform (CHF), and n-hexane (NHF) fractions of A. adianthifolia leaves were subjected to in vitro chemical analyses. RESULTS: Phytochemical screening revealed important classes of secondary metabolites. All extracts showed good antioxidant and acetylcholinesterase inhibitory activities. The EAF and CHF gave the highest total phenolic contents of 18.02±0.14 and 18.43±0.95 mg gallic acid equivalent per gram of extract, respectively. The polar extracts gave the highest activity in both assays with lower IC50 values. In the 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging activity assay, the IC50 values of CME, EAF, CHF, and NHF were 77.74±0.84, 55.76±2.30, 58.47±0.72, and 232.24±2.70 µg/mL, respectively, while in the acetylcholinesterase inhibitory assay, the IC50 values of CME, EAF, CHF, and NHF were 11.80±0.88, 10.04±1.67, 17.44±1.74, and 124.38±1.51 µg/mL, respectively. CONCLUSIONS: The results of this study suggest that the leaf of A. adianthifolia could serve as a potential candidate for future search of antioxidant and acetylcholinesterase inhibitors for the management of neurodegenerative disorders such as Alzheimer's disease.

Cholinesterase inhibitory activity and structure elucidation of a new phytol derivative and a new cinnamic acid ester from Pycnanthus angolensis

ABSTRACT The leaves of Pycnanthus angolensis (Welw.) Warb., Myristicaceae, are used as memory enhancer and anti-ageing in Nigerian ethnomedicine. This study aimed at evaluating the cholinesterase inhibitory property as well as isolates the bioactive compounds from the plant. The acetylcholinesterase and butyrylcholinesterase inhibitory potentials of extracts, fractions, and isolated compounds were evaluated by colorimetric and TLC bioautographic assay techniques. The extract inhibited both enzymes with activity increasing with purification, ethyl acetate fraction being most active fraction at 65.66 ± 1.06% and 49.38 ± 1.66% against acetylcholinesterase and butyrylcholinesterase, respectively while the supernatant had 77.44 ± 1.18 inhibition against acetylcholinesterase. Two new bioactive compounds, (2E, 18E)-3,7,11,15,18-pentamethylhenicosa-2,18-dien-1-ol (named eluptol) and [12-(4-hydroxy-3-methyl-oxo-cyclopenta-1,3-dien-1yl)-11-methyl-dodecyl](E)-3-(3,4-dimethylphenyl)prop-2-enoate (named omifoate A) were isolated from the plant with IC50 of 22.26 µg/ml (AChE), 34.61 µg/ml (BuChE) and 6.51 µg/ml (AChE), 9.07 µg/ml (BuChE) respectively. The results showed that the plant has cholinesterase inhibitory activity which might be responsible for its memory enhancing action, thus justifying its inclusion in traditional memory enhancing preparations.

Acetylcholinesterase and butyrylcholinesterase inhibitory activity of some selected Nigerian medicinal plants / Atividade inibitória da acetilcolinesterase e butirilcolinesterase de algumas plantas medicinais da Nigéria

Plants have been found to be useful as memory enhansers as well as antiaging. Twenty two of such plants from sixteen families were investigated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities using the in vitro Ellman's spectrophotometric and in situ bioautographic methods with physostigmine as standard. At least three morphological parts were examined for each of the plants investigated and the test concentration was 42.5 µg/ mL. Some plants were active on both enzymes though with some morphological parts being more active than others. The root bark of Spondias mombin showed the highest activity to the two enzymes; 64.77 percent and 83.94 percent on AChE and BuChE respectively. Other plant parts of the selected plants exhibited some remarkable selectivity in their actions. Those selectively active against AChE were Alchornia laxiflora stem bark (41.12 percent) and root bark, Callophyllum inophyllurn root bark (56.52 percent). The leaves of C. jagus (74.25 percent), Morinda lucida leaves (40.15 percent), Peltophorum pterocarpum leaves and stem bark (49.5 percent and 68.85 percent, respectively), physiostigmine gave 90.31 percent inhibition. Generally higher activities were found against BuChE. Bombax bromoposenze leaves, root bark and stem bark were particularly active. The inhibition was over 80 percent. Other selective plant parts are the leaves Antiaris africana, Cissampelos owarensis aerial parts (78.96 percent), Combretum molle leaves and stem bark (90.42 percent and 88.13 percent, respectively), Dioscorea dumentorum root bark and tuber (over 87 percent), G. kola leaves, Markhamia tomentosa root bark, Pycnanthus angolensis stem bark and Tetrapleura tetraptera leaves. Most of these plants are taken as food or are food ingredients in Nigeria and may account for the low incidence of Alzheimer's disease in the country and may play certain roles in the mediation of the disease.

As plantas podem ser úteis para estimular a memória, bem como serem usadas para combater o envelhecimento. Vinte e duas plantas, de dezesseis famílias, foram investigadas in vitro oara verificar sua atividade inibidora das enzimas acetilcolinesterase (AChE) e butirilcolinesterase (BuChE) pelo método espectrofotométrico de Ellman in situ e métodos de bioautografia utilizando fisostigmina como padrão. Pelo menos três partes morfológicas de cada planta foram analisadas e a concentração de ensaio foi de 42,5 µg/mL. Algumas plantas foram ativas em ambas as enzimas, embora com algumas partes mais ativas que outras. A casca da raiz de Spondias mombin apresentou a maior atividade as duas enzimas, 64,77 por cento para AChE e 83,94 por cento para BuChE. Outras partes das plantas selecionadas apresentaram boa seletividade em suas ações. As plantas seletivamente ativos contra AChE foram as casca do caule e casca da raiz de Alchornia laxiflora (41,12 por cento), e casca da raiz de Callophyllum inophyllurn (56,52 por cento). As folhas de C. jagus (74,25 por cento), folhas de Morinda lucida (40,15 por cento), folhas e casca do caule de Peltophorum pterocarpum (49,5 por cento e 68,85 por cento, respectivamente), physiostigmine inibiu 90,31 por cento. Em geral, atividades melhoras foram apresentadas contra BuChE. Folhas, casca da raiz e casca do caule Bombax bromoposenze foram particularmente ativos. A inibição foi acima de 80 por cento. Outras partes de algumas espécies também foram seletivas, como as partes aéreas de Antiaris africana, Cissampelos owarensis (78,96 por cento), folhas e casca do caule de Combretum molle (90,42 por cento e 88,13 por cento, respectivamente), casca da raiz e de tubérculos de Dioscorea dumentorum (mais de 87 por cento), folhas de G cola, cascas de raiz de Markhamia tomentosa, casca do caule de Pycnanthus angolensis e folhas de Tetrapleura tetraptera. A maioria destas plantas são utilizadas como alimentos ou ingredientes alimentares na Nigéria e podem ser responsáveis pela baixa incidência da doença de Alzheimer no país e desempenhar determinadas funções na mediação da doença.