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.The National Research Foundation (SARCHI)http://www.elsevier.com/locate/jethpharmhj2021Plant Production and Soil Scienc

THE ANTI-PROLIFERATIVE AND ANTIOXIDANT ACTIVITY OF FOUR INDIGENOUS SOUTH AFRICAN PLANTS.

Background: Cancer is a major cause of death worldwide. Limitations of current cancer therapies necessitate the search for new anticancer drugs. Plants represent an immeasurable source of bioactive compounds for drug discovery. The objective of this study was to assess the anti-proliferative and antioxidant potential of four indigenous South African plants commonly used in traditional medicine. Materials and Methods: The anti-proliferative activity of the plant extracts were assessed by the 2,3-Bis-(2-Methoxy-4- Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide (XTT) assay on A431; HaCat; HeLa; MCF-7 and UCT-Mel 1 cells and sulforhodamine-B (SRB) assay on HCT-116 and HCT-15 cell lines. Antioxidant activity was determined using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and superoxide scavenging assays. Results: Three of the plant extracts (Combretum mollefruit, Euclea crispa subsp. crispa leaves and stems and Sideroxylon inerme leaves and stems showed anti-proliferative activity on the A431 cells with IC50values ranging between 26.9 - 46.7 μg/ml. The Euclea crispa subsp. crispa extract also showed anti-proliferative activity on the MCF-7 cell line (45.7 μg/ml). All of the plant extracts (Combretum molle leaves and fruit, Euclea crispa subsp. crispa leaves and stems, Sideroxylon inerme leaves and stems and Terminalia prunioides leaves and stems) showed DPPH scavenging activity with IC50 values ranging from 1.8 μg/ml to 11.5 μg/ml. Conclusion: These results indicate that the active extracts of Combretum molle, Euclea crispa subsp. Crispa and Sideroxylon inerme warrants further investigation to determine the mechanism of anti-proliferative activity against cancerous cells. These plant extracts also show potential for further evaluation in the prevention and treatment of cancer

The anti-proliferative and anti-bacterial activity of argan oil and crude saponin extract from Argania spinosa (L.) skeels

INTRODUCTION: Argan oil is a well-known cosmeceutical that is commercially available. It is traditionally used for the treatment of acne and skin inflammation among others. The objective of this study was to assess the anti-proliferative and antibacterial activities of argan oil and a crude saponin extract from the argan tree (Argania spinosa (L.) Skeels) that is endemic to Morocco. MATERIALS AND METHODS: The anti-proliferative activity of argan oil and the crude saponin extract was assessed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay on A431; HaCat; HeLa; MCF-7 and UCT-Mel 1 cells. The antibacterial activity was evaluated by the broth microdilution method against two species of bacteria: Cutibacterium acnes and Prevotella intermedia. RESULTS: The results of this study indicated that the argan oil sample did not inhibit the cell growth of the specified cell lines up to 1000µg/ml, while the crude saponin extract had low anti-proliferative activity. The minimal inhibitory concentration (MIC) values for both the argan oil and the crude saponin extract were found to be 500µg/ml against Cutibacterium acnes. No antibacterial activity from the argan oil or the crude saponin extract was evident against Prevotella intermedia up to a concentration of 12.5mg/ml. CONCLUSION: The results of this study indicated that argan oil and the crude saponin extract might have direct inhibitory effects on the growth and proliferation of Cutibacterium acnes. This finding supports the use argan oil as a treatment for acne vulgaris.National Research Foundationhttp://www.phcogfirst.com/content/pharmacognosy-journalpm2020Plant Production and Soil Scienc

UPLC-MS analysis of cannabis sativa using tetrahydrocannabinol (THC), cannabidiol (CBD), and tetrahydrocannabinolic acid (THCA) as marker compounds: inhibition of breast cancer cell survival and progression

Cannabis sativa L. extracts were characterized by ultra performance liquid chromatography-mass spectrometry (UPLC-MS) using tetrahydrocannabinol (THC), cannabidiol (CBD), and tetrahydrocannabinolic acid (THCA) as marker compounds. The inhibitory effects of various extracts were determined on the survival and progression of highly metastatic breast cancer cells. A higher amount of CBD was found in the dichloromethane extract, and this was found to be effective in inhibiting breast cancer cell growth in vitro and in angiogenesis. Collectively, it may be concluded that CBD, THC, and THCA in the African variety of C. sativa can be used as marker compounds in UPLC-MS analysis. The ability of the plant to inhibit breast cancer cell survival and progression may affirm the traditional use of the drug as an anticancer agent.The National Research Foundation and DST-IKS Based Technology, South Africa.https://journals.sagepub.com/home/npxpm2020Chemistr

Potential medicinal plants for progressive macular hypomelanosis

Progressive macular hypomelanosis (PMH) is a hypopigmentation disorder caused by the bacterium identified as Propionibacterium acnes. The current treatments for PMH are antibiotics together with ultra violet radiation; however, UV radiation is not a recommended method to increase melanin production. Currently, there are no known plants used traditionally or medicinally for PMH. The objective of this study was to find plants that could stimulate tyrosinase activity induce melanin production and inhibit P. acnes' growth. Seventeen ethanol plant extracts, used traditionally in Africa for skin diseases, were screened for their antibacterial activity against P. acnes, their effect on monophenolase activity of tyrosinase and their cytotoxicity and stimulation of melanin production on mouse melanocytes (B16-F10). Hypericum revolutum Vahl subsp. revolutum (Hypericaceae) and Withania somnifera L. Dunal (Solanaceae) (twigs and leaves), combined with the known drug tetracycline, exhibited significant antibacterial activity against P. acnes, with the minimum inhibitory concentration ranging from 5.47 μg/ml to 14.06 μg/ml. The combination of a known drug with other antibacterial compounds not only decreases the concentration needed to inhibit bacterial growth, but also decreases the chances of bacterial resistance. W. somnifera was the only plant extracts that resulted in an increase in the monophenolase activity of tyrosinase. Four compounds typically present in plant extracts, namely coumarin, quercetin, withaferin and winthanone, were docked into the active site of tyrosinase enzyme to determine the interaction with active site residues. Mouse melanocytes (B16F10) treated with H. revolutum, W. somnifera (leaves) and Terminalia prunoides showed an increase in total melanin content as compared to untreated cells at 12 μg/ml, 12 μg/ml and 150 μg/ml respectively. Considering both the antibacterial activity and the stimulatory effect of the treatment on melanin production, H. revolutum and W. somnifera (leaves) could be considered as potential plants for further studies for PMH.National Research Foundationhttp://www.elsevier.com/l ocate/saj2018-07-30Plant Scienc

Evaluation of the Nutritional Composition of Myrothamnus Flabellifolius (Welw.) Herbal Tea and its Protective Effect Against Oxidative Hepatic Cell Injury

Published ArticleThe 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 AND METHODS : Molecular docking, cytotoxicity assays, cell microscopy and cell cycle progression were studied in cancer and nontumorigenic cell lines. RESULTS AND 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.AM Joubert acquired grants from the National Research Foundation (NRF; 105992, 90523 and 85818), Cancer Association of South Africa (A0V741 and A0W228), the Struwig Germeshuysen Trust (A0N074), the School of Medicine Research Committee of the University of Pretoria (AOH561) and Medical Research Council (A0W110). MH Visagie was funded from the NRF (99706), the School of Medicine Research Committee of the University of Pretoria (AOH561) and Struwig Germeshysen Trust. N Lall was funded from NRF/IKS160514165042 Grant No: 105169. ON Reva was funded from NRF grant 105996.https://www.future-science.com/journal/fmchj2019BiochemistryGeneticsMicrobiology and Plant PathologyPhysiologyPlant Production and Soil Scienc

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

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 AND 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 AND 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.https://www.future-science.com/loi/fmc2019-09-01hj2018BiochemistryGeneticsMicrobiology and Plant PathologyPhysiologyPlant Production and Soil Scienc

Antityrosinase and anti-acne potential of plants traditionally used in the Jongilanga community in Mpumalanga

In South Africa, traditional medicine remains a key source of health care, however majority of the plants used as medicines by traditional health care practitioners have not been investigated for their in vitro biological activity. The purpose of the present study was to examine the antityrosinase, anti-acne, antioxidant and cytotoxic potential of 25 ethanolic extracts from 16 different plant families which were collected in the Jongilanga community in the Mpumalanga province. The tyrosinase inhibitory activity was evaluated using the mushroom tyrosinase enzyme to determine potential plant extracts that could treat skin hyperpigmentation. Six of the plant extracts showed a fifty percent inhibitory concentration (IC50) lower than 200 μg/mL, of which Acacia nilotica (L.) Delile (12.97 ± 1.07 μg/mL) showed the highest activity, followed by Schotia brachypetala Sond. (35.07 ± 0.71 μg/mL) and Combretum collinum Fresen. (47.92 ± 1.13 μg/mL). The anti-acne potential of the extracts was evaluated by determining their antibacterial activity against Cutibacterium acnes. The highest activity was noted for Harpagophytum procumbens (Burch.) with a minimum inhibitory concentration (MIC) of 31.25 μg/mL, followed by S. brachypetala (125 μg/mL) and C. collinum, Ozoroa sphaerocarpa R. Fern & A. Fern and Pterocarpus rotundifolius DC. which all showed MIC values of 250 μg/mL. The antioxidant studies revealed that the majority of the plant extracts showed strong DPPH radical scavenging activity. The 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide salt (XTT) method was used to assess the cytotoxic effect of the plant extracts, of which only two extracts showed strong cytotoxicity against the non-cancerous human keratinocyte (HaCat) cell line namely; H. procumbens and Ipomoea oblongata Hook. The remaining extracts showed low to moderate cytotoxicity. The promising antityrosinase activity of A. nilotica, S. brachypetala and C. collinum as well as the promising antibacterial activity of O. spaerocarpa, P. rotundifolius and S. brachypetala, together with their low to moderate cytotoxicity against HaCat cells, merits further investigation of these species.Mr. Christian Courtin-Clarins, Chairman of Clarins Group for funding this study as well as the University of Pretoria for the financial contribution.http://www.elsevier.com/locate/sajb2020-11-01hj2019Plant Production and Soil Scienc