Co-Treatment of Caco-2 Cells with Doxorubicin and Gold Nanoparticles Produced from Cyclopia intermedia Extracts or Mangiferin Enhances Drug Effects.

Mangiferin (MGF) is a natural and valuable polyphenol found in significant levels in many plant species, including Cyclopia intermedia (C. intermedia). In a previous study, we synthesized gold nanoparticles (AuNPs) using MGF and a water extract of C. intermedia and reported that these AuNPs have very low cytotoxicity toward a human colon cancer (Caco-2) cell line. Although the study also showed that these biogenic AuNPs in combination with doxorubic (DOX) significantly augmented the cytotoxic effects of DOX in Caco-2 cells, the mechanism of the enhanced effect was not fully understood, and it was also not known if other cell lines would be sensitive to this co-treatment. In the present study, we examined the cytotoxicity of the co-treatment in Caski, HeLa, HT-29, KMST-6 and MDA-321 cell lines. Additionally, we investigated the mechanistic effects of this co-treatment in Caco-2 cells using several assays, including the adenosine triphosphate (ATP), the oxidative stress, the mitochondrial depolarization, the colony formation, the APOPercentage and the DNA fragmentation assays. We also assessed the intracellular uptake of the biogenic AuNPs. The study showed that the biogenic AuNPs were effectively taken up by the cancer cells, which, in turn, may have enhanced the sensitivity of Caco-2 cells to DOX. Moreover, the combination of the biogenic AuNPs and DOX caused a rapid depletion of ATP levels, increased mitochondrial depolarization, induced apoptosis, reduced the production of reactive oxygen species (ROS) and inhibited the long-term survival of Caco-2 cells. Although the study provided some insight into the mechanism of cytotoxicity induced by the co-treatment, further mechanistic and molecular studies are required to fully elucidate the enhanced anticancer effect of the co-treatment.

Green Synthesis of Metallic Nanoparticles Using Some Selected Medicinal Plants from Southern Africa and Their Biological Applications.

The application of metallic nanoparticles (MNPs), especially that of silver, gold, cobalt, and zinc as antimicrobial, anticancer, drug delivery, contrast, and bioimaging agents has transformed the field of medicine. Their functions, which are attributed to their physicochemical properties, have gained prominence in various technological fields. Although MNPs can be produced via rigorous physical and chemical techniques, in recent years, a biological approach utilizing natural materials has been developed. With the increasing enthusiasm for safe and efficient nanomaterials, the biological method incorporating microorganisms and plants is preferred over physical and chemical methods of nanoparticle synthesis. Of these bio-entities, plants have received great attention owing to their capability to reduce and stabilize MNPs in a single one-pot protocol. South Africa is home to ~10% of the world's plant species, making it a major contributor to the world's ecological scenery. Despite the documented contribution of South African plants, particularly in herbal medicine, very few of these plants have been explored for the synthesis of the noble MNPs. This paper provides a review of some important South African medicinal plants that have been utilized for the synthesis of MNPs. The enhanced biological properties of the biogenic MNPs attest to their relevance in medicine. In this endeavour, more of the African plant biodiversity must be explored for the synthesis of MNPs and be validated for their potential to be translated into future nanomedicine.

Gold Nanoparticles Synthesized Using Extracts of Cyclopia intermedia, Commonly Known as Honeybush, Amplify the Cytotoxic Effects of Doxorubicin.

Cyclopia intermedia (C. intermedia) is an indigenous South African shrub used to prepare the popular medicinal honeybush (HB) tea. This plant contains high levels of mangiferin (MGF), a xanthonoid that was reported to have numerous biological activities, including anti-tumor activity. MGF and extracts that contain high concentrations of MGF, such as extracts from Mangifera indica L. or mango have been used to synthesize gold nanoparticles (AuNPs) using green nanotechnology. It has previously been shown that when AuNPs synthesized from M. indica L. extracts are used in combination with doxorubicin (DOX) and Ayurvedic medicine, the anti-tumor effects appear to be augmented. It has also been demonstrated that MGF used in combination with DOX resulted in enhanced anti-tumor effects. In this study, C. intermedia (HB) and MGF were used to synthesize HB-AuNPs and MGF-AuNPs, respectively. The physicochemical properties of the AuNPs were characterized by the UV-Visible Spectroscopy (UV-Vis), dynamic light scattering (DLS), Fourier transform infra-red spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD) and high-resolution transmission electron microscopy (HR-TEM). The cytotoxicity of HB-AuNPs and MGF-AuNPs were assessed on human colon (Caco-2), prostate (PC-3) and glioblastoma (U87) cancer cells; as well as normal breast epithelial (MCF-12A) cells using the MTT assay. Both HB-AuNPs and MGF-AuNPs demonstrated relatively low cytotoxicity in these cells. However, when these nanoparticles were used in combination with DOX, the cytotoxicity of DOX was significantly augmented.

Attenuation of potassium dichromate and sodium arsenite toxicities by methanol extract of Rauvolfia vomitoria in mice.

OBJECTIVES: Exposure to arsenic and hexavalent chromium is a major public health concern especially in the developing part of the world and there is paucity of information on reliable treatment modalilities. It is in this regard that this study evaluates the efficacy of methanol leaf extract of Rauvolfia vomitoria (MRV) when used as pretreatment agent against potassium dichromate (K2Cr2O7) and sodium arsenite (NaAsO2) exposure. METHODS: Swiss albino mice between 7 and 10 weeks old were divided into eight cohorts of five animals each. Treatment groups consisted of a distilled water control, MRV alone (275 mg/kg po daily), K2Cr2O7 (12.0 mg/kg, single ip injection) +/- MRV pretreatment, NaAsO2 (2.5 mg/kg, single ip injection) +/- MRV pretreatment, Na2AsO2 + K2Cr2O7 +/- MRV pretreatment. MRV was given for seven consecutive days, while K2Cr2O7 and NaAsO2 were injected on day seven of the experiment. The frequency of micronucleated polychromatic erythrocytes (mPCEs) was determined in bone marrow cells, while aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were assessed in the plasma. Hepatic glutathione (GSH), malondialdehyde (MDA), catalase (CAT) and glutathione-S-transferase (GST) levels were also determined. RESULTS: The NaAsO2 and K2Cr2O7 significantly (p<0.05) increased mPCE formation, AST, ALT, and CAT when compared with the control. Simultaneous exposure to NaAsO2 and K2Cr2O7 further increased the levels of the markers. Furthermore, GSH and GST were significantly reduced by NaAsO2 or K2Cr2O7 or their combination. Pretreatment with MRV reversed the markers towards that of control. CONCLUSIONS: Methanol extract of Rauvolfia vomitoria may therefore ameliorate NaAsO2 and K2Cr2O7-induced toxicities via reduction of oxidative stress and fortification of anti-oxidant system.