Cannabis sativa L. protects against oxidative injury in kidney (vero) cells by mitigating perturbed metabolic activities linked to chronic kidney diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Cannabis sativa L. is among numerous medicinal plants widely used in traditional medicine in treating various ailments including kidney diseases. AIMS: The protective effect of C. sativa on oxidative stress, cholinergic and purinergic dysfunctions, and dysregulated glucogenic activities were investigated in oxidative injured kidney (Vero) cell lines. METHODS: Fixed Vero cells were treated with sequential extracts (hexane, dichloromethane [DCM] and ethanol) of C. sativa leaves for 48 h before subjecting to MTT assay. Vero cells were further incubated with FeSO4 for 30 min, following pretreatment with C. sativa extracts for 25 min. Normal control consisted of Vero cells not treated with the extracts and/or FeSO4, while untreated (negative) control consisted of cells treated with only FeSO4. RESULTS: MTT assay revealed the extracts were slightly cytotoxic at the highest concentrations (250 µg/mL). There was a significant depletion in glutathione level and catalase activity on induction of oxidative stress, with significant elevation in malondialdehyde level, acetylcholinesterase, ATPase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase and glycogen phosphorylase activities. These activities and levels were significantly reversed following pretreatment with C. sativa extracts. CONCLUSION: These results portray the protective potentials of C. sativa against iron-mediated oxidative renal injury as depicted by the ability of its extracts to mitigate redox imbalance and suppress acetylcholinestererase activity, while concomitantly modulating purinergic and glucogenic enzymes activities in Vero cells.

Selective cytotoxic and anti-metastatic activity in DU-145 prostate cancer cells induced by Annona muricata L. bark extract and phytochemical, annonacin.

BACKGROUND: Annona muricata L. was identified as a popular medicinal plant in treatment regimens among cancer patients in Jamaica by a previously conducted structured questionnaire. Ethnomedically used plant parts, were examined in this study against human prostate cancer cells for the first time and mechanisms of action elucidated for the most potent of them, along with the active phytochemical, annonacin. METHODS: Nine extracts of varying polarity from the leaves and bark of A. muricata were assessed initially for cytotoxicity using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on PC-3 prostate cancer cells and the ethyl acetate bark (EAB) extract was identified as the most potent. EAB extract was then standardized for annonacin content using High-performance Liquid Chromatography - Mass Spectrometry (HPLC-MS) and shown to be effective against a second prostate cancer cell line (DU-145) also. The mode of cell death in DU-145 cells were assessed via several apoptotic assays including induction of increased reactive oxygen species (ROS) production, reduction of mitochondrial membrane potential, activation of caspases and annexin V externalization combined with morphological observations using confocal microscopy. In addition, the potential to prevent metastasis was examined via inhibition of cell migration, vascular endothelial growth factor (VEGF) and angiogenesis using the chorioallantoic membrane assay (CAM). RESULTS: Annonacin and EAB extract displayed selective and potent cytotoxicity against the DU-145 prostate carcinoma cells with IC50 values of 0.1 ± 0.07 µM and 55.501 ± 0.55 µg/mL respectively, without impacting RWPE-1 normal prostate cells, in stark contrast to chemotherapeutic docetaxel which lacked such selectivity. Docetaxel's impact on the cancerous DU-145 was improved by 50% when used in combination with EAB extract. Insignificant levels of intracellular ROS content, depolarization of mitochondrial membrane, Caspase 3/7 activation, annexin V content, along with stained morphological evaluations, pointed to a non-apoptotic mode of cell death. The extract at 50 µg/mL deterred cell migration in the wound-healing assay, while inhibition of angiogenesis was displayed in the CAM and VEGF inhibition assays for both EAB (100 µg /mL) and annonacin (0.5 µM). CONCLUSIONS: Taken together, the standardized EAB extract and annonacin appear to induce selective and potent cell death via a necrotic pathway in DU-145 cells, while also preventing cell migration and angiogenesis, which warrant further examinations for mechanistic insights and validity in-vivo.

A review on traditionally used South African medicinal plants, their secondary metabolites and their potential development into anticancer agents.

ETHNOPHARMACOLOGICAL RELEVANCE: Approximately 70% of anticancer drugs were developed or derived from natural products or plants. Southern Africa boasts an enormous floral diversity with approximately 22,755 plant species with an estimated 3000 used as traditional medicines. In South Africa more than 27 million individuals rely on traditional medicine for healthcare. The use of South African plants for the treatment of cancer is poorly documented, however there is potential to develop anticancer agents from these plants. Limited ethnobotanical studies report the use of plants for cancer treatment in traditional medicine. Plants growing in tropical or subtropical regions, such as in South Africa, produce important secondary metabolites as a protective mechanism, which could be used to target various factors that play a key role in carcinogenesis. AIMS: The aim was to collate information from primary ethnobotanical studies on South African plants traditionally used for the treatment of cancer. Evaluation of literature focused on traditionally used plants that have been tested for their in vitro activity against cancer cells. Secondary metabolites, previously identified within these plant species, were also included for discussion regarding their activity against cancer. The toxicity was evaluated to ascertain the therapeutic potential in further studies. Additionally, the aim was to highlight where a lack of reports were found regarding plant species with potential activity and to substantiate the need for further testing. MATERIALS AND METHODS: A review of ethnobotanical surveys conducted in South Africa for plants used in the treatment of cancer was performed. Databases such as Science Direct, PubMed and Google Scholar, university repositories of master's dissertations and PhD theses, patents and books were used. Plant species showing significant to moderate activity were discussed regarding their toxicity. Compounds identified within these species were discussed for their activity against cancer cells and toxicity. Traditionally used plants which have not been scientifically validated for their activity against cancer were excluded. RESULTS: Twenty plants were documented in ethnobotanical surveys as cancer treatments. Numerous scientific reports on the potential in vitro activity against cancer of these plants and the identification of secondary metabolites were found. Many of the secondary metabolites have not been tested for their activity against cancer cells or mode of action and should be considered for future studies. Lead candidates, such as the sutherlandiosides, sutherlandins, hypoxoside and pittoviridoside, were identified and should be further assessed. Toxicity studies should be included when testing plant extracts and/or secondary metabolites for their potential against cancer cells to give an indication of whether further analysis should be conducted. CONCLUSION: There is a need to document plants used traditionally in South Africa for the treatment of cancer and to assess their safety and efficacy. Traditionally used plants have shown promising activity highlighting the importance of ethnobotanical studies and traditional knowledge. There are many opportunities to further assess these plants and secondary metabolites for their activity against cancer and their toxic effects. Pharmacokinetic studies are also not well documented within these plant extracts and should be included in studies when a lead candidate is identified.

Effects of Silver Nanoparticle from Dicoma anomala Sond. Root Extract on MCF-7 Cancer Cell Line and NF54 Parasite Strain: an In Vitro Study.

Biogenic silver nanoparticles (AgNPs) continue captivating researchers in biomedicine field of research. Dicoma anomala Sond. plant, locally known as hloenya, hlonya, maagbossie, inyongwana, is widely recommended by South African traditional health practitioners (THPs) to treat against different health issues. The antiplasmodial effects of novel sesquiterpene molecules (C30H36O7; MW: 509.25) isolated from D. anomala Sond. have been reported by us (Patent US 8,586,112 B2). The aim of the study was to determine the anticancer activity of AgNPs synthesized using D. anomala plant root extract and the antiparasitic potency of AgNP-conjugated sesquiterpene. Nanoparticles have been characterized using different methods. Anticancer activity of AgNPs was evaluated against the MCF-7. This study also revealed that the AgNP-conjugated sesquiterpene has shown better antiparasitic activity against Plasmodium falciparum NF54 strain. One-pot synthesized AgNPs using Dicoma anomala Sond. root extract caused oxidative damage in breast cancer cells. These findings indicate the need for more in-depth research in the use of the AgNPs and sesquiterpene for development into potential leads as an antimalarial candidates and to improve the bioavailability of these sesquiterpenes.

Evaluation of the nutritional composition of Myrothamnus flabellifolius (Welw.) herbal tea and its protective effect against oxidative hepatic cell injury.

The nutrient composition of Myrothamnus flabellifolius leaf tea extract (MLTE) and its protective effect against oxidative hepatic cell injury were evaluated. Gallic acid, caffeic acid, ferulic acid, methyl gallate, and epicatechin were identified in MLTE by high-performance liquid chromatography (HPLC). The tea extract showed an appreciable nutritional content of proximate, sugar, vitamin E, monounsaturated fatty acids, omega 6 and 9 unsaturated fatty acids, as well as considerable amounts of various mineral elements. Nineteen amino acids were found. Moreover, MLTE exhibited potent in vitro antioxidant activities, presumably because of its richness in polyphenols (gallic acid and ferulic acid) and vitamin E. In Chang liver cells, pretreatment with MLTE suppressed oxidative lipid peroxidation (IC50  = 113.11 µg/ml) and GSH depletion (IC50  = 70.49 µg/ml) without causing cytotoxicity. These data support the local consumption of M. flabellifolius herbal tea, which may be used against oxidative stress-induced diseases while providing the body with necessary nutrients. PRACTICAL APPLICATION: Herbal teas are one of the most consumed beverages in the world today, due to their refreshing taste and additional health benefits. Myrothamnus flabellifolius herbal tea is a widely used traditional herbal tea in Southern Africa with potentials for commercialization due to its pleasant flavor. This study, for the first time, reported the nutritional composition of the leaf decoction of M. flabellifolius and its protective effect on hepatic oxidative insults. These results can inform the dietary and nutritional use of the tea for optimum benefits, as well as provide preliminary scientific validation of the use of the herbal tea as an antioxidant beverage with good nutritional value.

Comparison of structures and cytotoxicity of mupirocin and batumin against melanoma and several other cancer cell lines.

Aim: To determine the computer-predicted anticancer activity of mupirocin and to compare its activities with those determined for another polyene antibiotic, batumin. Materials & methods: Molecular docking, cytotoxicity assays, cell microscopy and cell cycle progression were studied in cancer and nontumorigenic cell lines. Results & conclusion: Cytotoxicity of mupirocin against several cancerous cell lines was detected with the highest one (IC50 = 5.4 µg/ml) against melanoma cell line. The profile of cytotoxicity of mupirocin was similar to that reported for batumin. Nevertheless, the morphology of cells treated with these antibiotics and alterations in cell cycle progression suggested possible dissimilarity in their mechanisms of action. Selective cytotoxicity of mupirocin against melanoma cells potentiates further studies to discover nontoxic drugs for melanoma prevention.

Promising anticancer activity of batumin: a natural polyene antibiotic produced by Pseudomonas batumici.

AIM: To determine the computer-predicted anticancer activity of antibiotic batumin. MATERIALS & METHODS: Cytotoxicity assays, cell morphology microscopy and cell cycle progression were studied in cancer and nontumorigenic cell lines. An in vivo experiment on Lewis lung carcinoma (3LL)-transplanted mice was conducted to evaluate potential antimetastatic. RESULTS & CONCLUSION: Cytotoxicity against melanoma and lung carcinoma cells (IC50 ≈ 5 µg/ml) was detected. Hypercondensed chromatin and apoptotic body formation in batumin-treated cells suggested the induction of apoptosis supported also by an observed increase in the quantity of cells occupying the sub-G1 cell cycle phase. Twofold reduction in the number and volume of lung metastases in Lewis lung carcinoma (3LL)-bearing batumin-treated mice was demonstrated. Highly specific cytotoxicity of batumin against cancer cell lines potentiates further studies.