An evaluation of anti-cancer activities of Hyaenanche Globosa Lamb. (Euphorbiaceae) and Maytenus Procumbens (L.F.) Loes. (Celastraceae)

Written records about medicinal plants date back at least 5,000 years to the Sumerians. The objected plants for present investigation were indigenous to South Africa and as explored, only a few biological studies were found on the previous studies on Hyaenanche globosa and Maytenus procumbens. Phytochemical studies of the ethanol extract of the fruits of H. g/obosa (F.E) resulted in isolation of two known pure sesquiterpene lactones; 'tutin 1' and 'hyenanchin 2'. The crude extract and its isolated constituents were tested on four cancerous and a normal cell lines. F.E exhibited the highest antiproliferative activity on Hela cells which followed by Caco-2 cells. None of the isolated compounds were found to be toxic to the cells tested in this experiment. F.E demonstrated potent inhibition of DPPH radical activity similar to vitamin C. 'Tutin 1' and 'hyenanchin 2' were found with marginal antioxidant activity of which 'compound 1' presented more potent activity than 'compound 2'. The amounts of ROS radicals formed by pure compounds (1 and 2) were not significantly higher than those of controls. This is the first report on phytochemical index, anticancer, antioxidant and antibacterial properties of F.E and its purified compounds. The possible biochemical activities of the acetonic/ethanolic extract of the leaves of Maytenus procumbens (L.M.P), and its isolated compounds were investigated in the present study. L.M.P showed IC50 values of 68.79, 51.22, 78.49, 76.59 and 76.64 ì/ml on Caco-2, Hela, HT29, NIH3T3 and T47D cells by use of MTT cytotoxicity assay. Bioassay guided fractionation led to the isolation and identification of two new triterpenes: '30-hydroxy-11á-hydroxy-18â-olean-12-en-3-one 3' and '30-hydroxy-11á-methoxy- 18â-olean-12-en-3-one 5'. In addition, a known terpenoid: 'asiatic acid 4' was purified. Due to the unavailability of sufficient amount of 'asiatic acid 4', this compound was not tested. Pure compounds 3 and 5 exhibited the most cytotoxicity against Hela cells and were further investigated for their abilities for induction of apoptosis (at the concentration of their IC sub>50) in Hela cells using flow cytometric method. Both compounds induced apoptosis up to 73.20%, (compound 3) and 20.40% (compound 5) in Hela cells versus control group (0.40%). Antioxidant/oxidative properties of L.M.P and its isolated compounds were investigated using extracellular (DPPH), and intracellular reactive oxygen species (ROS) assays. L.M.P and the isolated compounds exhibited marginal DPPH discoloration. Experimental samples represented a time and concentrationdependent function of ROS formation in Hela cells. ROS generation might be a part of the mechanisms by which compounds 3 and 5 induced apoptosis in Hela cells. It can therefore be concluded that the active components in L.M.P might serve as a mediator of the reactive oxygen scavenging system and have the potential to act as a prooxidant and an antioxidant, depending on the biological environment of the cells. There is no report until date on phytochemical index, anticancer, antioxidant and antibacterial properties of L.M.P and its isolated compounds.Thesis (PhD)--University of Pretoria, 2012.Plant Scienceunrestricte

Anthocyanins in the Management of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review

The term “metabolic syndrome” (MetS) refers to a combination of diabetes, high blood pressure, and obesity. The origin of MetS includes a combination of multiple factors, such as sedentary lifestyle, unhealthy diet choice, and genetic factors. MetS is highly prevalent and adversely affects the general population by elevating risk of cardiovascular complications, organ failure, and much other pathology associated with late-stage diabetes. Anthocyanins (ANTs) are health-promoting bioactive compounds belonging to the flavonoids subclass of polyphenols. Numerous studies have reported the potential therapeutic benefits on MetS syndrome and diabetes from fruits rich in ANTs. This review summarizes the role of several dietary ANTs on preventing and managing MetS as well as the pharmacological mechanisms and biopharmaceutical features of their action. We also discuss potential nanoformulation and encapsulation approaches that may enhance the bioefficacy of ANTs in MetS. Experiments have demonstrated that ANTs may attenuate the symptoms of MetS via improving insulin resistance, impaired glucose tolerance, dyslipidaemia, cholesterol levels, hypertension, blood glucose, protecting β cells, and preventing free radical production. In brief, the intake of ANT-rich supplements should be considered due to their plausible ability for prevention and management of MetS. Additionally, randomized double-blind clinical trials are obligatory for evaluating the bioefficacy and pharmacological mechanisms of ANTs and their pharmaceutical formulations in patients with MetS

Investigation of the possible biological activities of a poisonous South African plant ; Hyaenanche globosa (Euphorbiaceae)

The present study was undertaken to explore the possible biochemical activities of Hyaenanche globosa Lamb. and its compounds. Two different extracts (ethanol and dichloromethane) of four different parts (leaves, root, stem, and fruits) of H. globosa were evaluated for their possible antibacterial, antityrosinase, and anticancer (cytotoxicity) properties. Two pure compounds were isolated using column chromatographic techniques. Active extracts and pure compounds were investigated for their antioxidant effect on cultured ‘Hela cells’. Antioxidant/oxidative properties of the ethanolic extract of the fruits of H. globosa and purifi ed compounds were investigated using reactive oxygen species (ROS), ferric-reducing antioxidant power (FRAP), and lipid peroxidation thiobarbituric acid reactive substance (TBARS) assays. The ethanolic extract of the leaves and fruits of H. globosa showed the best activity, exhibiting a minimum inhibitory concentration (MIC) of 3.1 mg/ ml and a minimum bactericidal concentration (MBC) of 1.56 and 6.2 mg/ml, respectively, against M. smegmatis. The ethanolic extract of the fruits of H. globosa (F.E) showed the highest percentage of inhibitory activity of monophenolase (90.4% at 200 g/ml). In addition, F.E exhibited 50% inhibitory concentration (IC50) of 37.7 g/ml on the viability of ‘HeLa cells’ using cytotoxicity MTT assay. Subsequently, F.E was fractionated using phase-partitioning with n-hexane, ethyl acetate, and n-butanol. The cytotoxicity of these fractions were determined in vitro using different cancer cell lines. The n-hexane fraction exhibited the highest activity of toxicity. Therefore, this fraction was subjected to further separation by chromatographic methods. Two pure compounds known as: ‘Tutin’ and ‘hyenanchin’ were isolated and their structures were determined by NMR spectroscopic methods. Unpredictably, none of them showed signifi cant (P 0.01) inhibition on cell viability/proliferation at the concentrations that were used. F.E showed significant anti-tyrosinase, antibacterial, and cytotoxicity effects, therefore it can be considered as an effective inhibitor alone or in combination with other plant extracts.http://www.phcog.com

Growth inhibition and induction of apoptosis in human cancerous HeLa cells by Maytenus procumbens

The possible biochemical activities of the acetonic/ethanolic extract of the leaves of Maytenus procumbens (L.M.P), and its isolated compounds were investigated in the present study. In cytotoxicity assay, L.M.P showed IC50 of 68.79, 51.22, 78.49, 76.59, and 76.64 lg/ml on Caco-2, HeLa, HT29, NIH3T3, and T47D cells, respectively. Bioassay guided fractionation led to the isolation and identification of a new triterpene: ‘30-hydroxy-11a-methoxy-18b-olean-12-en-3-one’ (HMO) in addition to a known terpenoid: ‘asiatic acid’ (AA). HMO exhibited the most cytotoxicity against HeLa cells and was further investigated for its ability to induce apoptosis in HeLa cells. HMO induced apoptosis up to 20.41% in HeLa cells versus control group (0.40%). Antioxidant/oxidative properties of L.M.P and HMO were investigated using extracellular (DPPH), and intracellular (ROS) assays. Experimental samples represented a time and concentrationdependent formation of ROS in Hela cells. Generation of ROS seems one of the mechanisms by which HMO induces apoptosis in Hela cells. Conclusion is that the active components in L.M.P might serve as a mediator of the ROS scavenging system and have the potential to act as prooxidant or antioxidant depending on the biological environment of the cells.Pharmaceutical Sciences Research Center (PSRC) and Tehran University of Medical Sciences (TUMS), Tehran, Iran.http://www.elsevier.com/locate/foodchemtoxhb201

Endo-cannabinoids system and the toxicity of cannabinoids with a biotechnological approach

Cannabinoids have shown diverse and critical effects on the body systems, which alter the physiological functions. Synthetic cannabinoids are comparatively innovative misuse drugs with respect to their nature of synthesis. Synthetic cannabinoids therapy in healthy, chain smokers, and alcoholic individuals cause damage to the immune and nervous system, eventually leading to intoxication throughout the body. Relevant studies were retrieved using major electronic databases such as PubMed, EMBASE, Medline, Scopus, and Google Scholar. The extensive use of Cannabis Sativa L. (C. Sativa) and its derivatives/analogues such as the nonpsychoactive dimethyl heptyl homolog (CBG-DMH), and tetrahydrocannabivarin (THCV) amongst juveniles and adults have been enhanced in recent years. Cannabinoids play a crucial role in the induction of respiratory, reproductive, immune and carcinogenic effects; however, potential data about mutagenic and developmental effects are still insufficient. The possible toxicity associated with the prolong use of cannabinoids acts as a tumor promoter in animal models and humans. Particular synthetic cannabinoids and analogues have low affinity for CB1 or CB2 receptors, while some synthetic members like Δ9-THC have high affinity towards these receptors. Cannabinoids and their derivatives have a direct or indirect association with acute and long-term toxicity. To reduce/attenuate cannabinoids toxicity, pharmaceutical biotechnology and cloning methods have opened a new window to develop cannabinoids encoding the gene tetrahydrocannabinolic acid (THCA) synthase. Plant revolution and regeneration hindered genetic engineering in C. Sativa. The genetic culture suspension of C. Sativa can be transmuted by the use of Agrobacterium tumefaciens to overcome its toxicity. The main aim of the present review was to collect evidence of the endo-cannabinoid system (ECS), cannabinoids toxicity, and the potential biotechnological approach of cannabinoids synthesis

Extract from Ceratonia siliqua exhibits depigmentation properties

Skin hyper-pigmentation is a condition initiated by the overproduction of melanin existing in the melanocytes. Melanin pigment is responsible for the colour of skin in humans. It is formed through a series of oxidative reactions involving the amino acid tyrosine in the presence of the key enzyme tyrosinase. In continuation with our efforts to identify tyrosinase inhibitors from plants sources, the methanol extract from leaf, bark and fruit of Ceratonia siliqua were screened for tyrosinase inhibition and diphenolase activity. The bark extract exhibited significant inhibition on mushroom tyrosinase using L-tyrosine as a substrate and showed diphenolase activity. The extract further significantly inhibited tyrosinase mRNA levels in B16-F10 mouse melanocytes. Bioassay-guided fractionation led to the isolation of six compounds. Compounds (-)-epicatechin-3-O-gallate, 1,2,3,6-tetra-O-galloyl-ß-D-glucose and Gallocatechin-3-O-gallate showed tyrosinase inhibitions with the IC50 values of 27.52, 83.30 and 28.30 μg/mL, respectively. These compounds also exhibited L-DOPA activities with IC50 values of >200, 150 and 200 μg/mL, respectively. A clinical study was conducted using 20 volunteers in a patch testing trial for irritancy potential and skin depigmentation. The clinical results showed the sample to be non-irritant with irritancy potential of -34.21 and depigmentation trial showed an improvement in the even skin tone of UV induced pigmentation at 3% after 28 days of application.University of Pretoria and National Research Foundation (NRF).http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1099-15732016-11-30hb2016GeneticsPlant Scienc

Phytochemicals as Modulators of Paraoxonase?1 in Health and Diseases

Chronic diseases such as cardiovascular disease (CVD), atherosclerosis, chronic liver disease, and neurodegenerative diseases are major causes of mortality. These diseases have gained much attention due to their complications, and therefore novel approaches with fewer side effects are an important research topic. Free radicals and oxidative stress are involved in the molecular mechanisms of several diseases. Antioxidants can scavenge free radicals and mitigate their adverse effects. One of the most important antioxidant enzymes are paraoxonases (PONs). These enzymes perform a wide range of physiological activities ranging from drug metabolism to detoxification of neuroleptics. Paraoxonase?1 (PON1) is produced in the liver and then transferred to the bloodstream. It has been demonstrated that PON1 could have beneficial effects in numerous diseases such as atherosclerosis, CVD, diabetes mellitus, and neurodegenerative diseases by modulating relevant signalling pathways involved in inflammation and oxidative stress. These pathways include peroxisome proliferator?activated receptor gamma (PPAR??) and protein kinase B/nuclear factor kappa?light?chain?enhancer of activated B cells (AKT/NF??B)?dependent signalling pathways. Increasing PON1 could potentially have protective effects and reduce the incidence of various diseases by modulating these signalling pathways. Several studies have reported that dietary factors are able to modulate PON1 expression and activity. This review aimed at summarizing the state of the art on the effects of dietary phytochemicals on PON1 enzyme activity and the relevant signalling pathways in different diseases

Beneficial Effects of Trachyspermum ammi (L.) Sprague on Rat Irritable Bowel Syndrome

Background and objective: Trachyspermum ammi (T. ammi) has been used for the treatment of various digestive disorders with considerable therapeutic effects such as anticholinergic and anti-oxidant activities.This study aimed to evaluate the efficacy of the hydro-alcoholic extract of the fruits of T. ammi in an experimental model of irritable bowel syndrome (IBS). Methods: The rats were classified into seven groups, including sham (no stress), control (saline recipients), loperamide and fluoxetine (10 mg/kg/day) (positive controls), and the plant groups at the doses of 150, 250 and 500 mg/kg/day for 5 days under restrictive stress, 2 days before receiving the treatment. All medicines were given as gavage. The effect of the plant extract on gastric emptying and the transit of the small intestine was evaluated. The levels of the inflammatory and oxidative related biomarkers, tumor necrosis factor alpha (TNF-α) and lipid peroxidation (LPO), also the myeloperoxidase (MPO) activity were measured. Results: The gastric emptying and the transit of the small intestine were significantly reduced in all T. ammi treated groups, and no significant difference was observed at the dose of 500 mg/kg/day compared with the loperamide group. The levels of TNF-α and MPO activities decreased in the treatment groups compared with the control, and the LPO level was decreased at the concentrations of 250 and 500 mg/kg/day compared to the control. The antioxidant levels significantly increased in the rats treated with T. ammi at the doses of 250 and 500 mg/kg/day. Conclusions: The severity of stress-induced IBS was reduced in a dose-dependent manner by the hydro-alcoholic extract of the fruits of T. ammi, confirming the effectiveness of this plant in the management of IBS.  </strong

Tyrosinase inhibitors isolated from Ceratonia siliqua (L.) and Sideroxylon inerme (L.)

Please read the abstract in the section front of this document.Dissertation (MSc)--University of Pretoria, 2010.Plant Scienceunrestricte

An Update on Pharmacology of Satureja Species; From Antioxidant, Antimicrobial, Antidiabetes and Anti-hyperlipidemic to Reproductive Stimulation

Since ancient, the genus Satureja L. is well recognized for its therapeutic values. Only recently, scientists have been aware of its new medicinal aspects. In our last review, we evaluated esisting scientific data about this genus. Regarding ongoing reports and new multi-functional properties of this plant we were interested to update pharmacology of Satureja. Data was gathered using scientific books, journals, articles and websites including Pubmed, Scopus and Google Scholar up to 25th April 2010. Of initial search, 1540 records were reviewed for inclusion or exclusion in study, of which 71 publications were included. Different species of Satureja are famous for their analgesic, antiseptic, antimicrobial, antiviral, antioxidant, antiproliferative, antiprotozoal, antifungal, antidiarrheal, anti-inflammatory, anti-nociceptive, anticholinesterase and vasodilatory activities. The valuable therapeutic aspects of this genus are mostly correlated to the existence of essential oils, falvonoids and triterpenoids. The combination of two or more subspecies acting by different mechanisms to produce a synergistic effect should be considered. Based on the conducted assessments so far, antibacterial, antifungal, antiviral, antioxidant, anti-diabetic, vasodilatory and analgesic activities are characterized as the most applicable properties of Satureja subspecies. Further studies are needed to confirm novel pharmacological aspects of this genus in both animal and human