Mediline Goboza

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.

Advancements in nanotechnology have provided insight into the unique opportunities for the application of nanomaterials such as gold nanoparticles (AuNPs) in medicine due to their remarkable properties, which includes low toxicity, large surface area, and the ease of synthesis and conjugation to other molecules. Therefore, AuNPs are often preferred for bio-applications. Citrate-capped AuNPs (cAuNPs) have been reported to be non-cytotoxic and are used in numerous studies as drug delivery vehicles to treat various diseases. However, the limitations of bioassays often used to assess the toxicity of AuNPs have been well documented. Herein, we investigate the cytotoxicity of 14 nm cAuNPs in the human colorectal adenocarcinoma (Caco-2) cell line. Treatment conditions (i.e. dose and exposure time) that were established to be non-toxic to Caco-2 cells were used to investigate the effect of cAuNPs on the expression of a Qiagen panel of 86 genes involved in cytotoxicity. Out of 86 studied, 23 genes were differentially expressed. Genes involved in oxidative stress and antioxidant response, endoplasmic reticulum (ER) stress and unfolded protein response, heat shock response, and lipid metabolism were more affected than others. While low concentrations of 14 nm cAuNPs was not cytotoxic and did not cause cell death, cells treated with these nanoparticles experienced ER and oxidative stress, resulting in the activation of cytoprotective cellular processes. Additionally, several genes involved in lipid metabolism were also affected. Therefore, 14 nm cAuNPs can safely be used as drug delivery vehicles at low doses.

The Catharanthus roseus plant has been used traditionally to treat diabetes mellitus. Scientific evidence supporting the antidiabetic effects of this plant’s active ingredient-vindoline has not been fully evaluated. In this study, extracts of C. roseus and vindoline were tested for antioxidant activities, alpha amylase and alpha glucosidase inhibitory activities and insulin secretory effects in pancreatic RIN-5F cell line cultured in the absence of glucose, at low and high glucose concentrations. The methanolic extract of the plant showed the highest antioxidant activities in addition to the high total polyphenolic content (p < 0.05). The HPLC results exhibited increased concentration of vindoline in the dichloromethane and the ethylacetate extracts. Vindoline showed noticeable antioxidant activity when compared to ascorbic acid at p < 0.05 and significantly improved the in vitro insulin secretion. The intracellular reactive oxygen species formation in glucotoxicity-induced cells was significantly reduced following treatment with vindoline, methanolic and the dichloromethane extracts when compared to the high glucose untreated control (p < 0.05). Plant extracts and vindoline showed weaker inhibitory effects on the activities of carbohydrate metabolizing enzymes when compared to acarbose, which inhibited the activities of the enzymes by 80%. The plant extracts also exhibited weak alpha amylase and alpha glucosidase inhibitory effects.

Cardiovascular diseases (CVDs) and kidney diseases in diabetes are linked to increased mortality and morbidity. The aim of this study was to evaluate the effect of vindoline derived from Catharanthus roseus in diabetes-induced CVDs and kidney disease through assessing inflammation, oxidative stress, hyperlipidaemia and kidney function parameters. Type 2 diabetes was induced in male Wistar rats by 10% fructose water intake for two weeks, followed by a single intraperitoneal injection of 40 mg/kg body weight of streptozotocin (STZ). Six groups (n = 8) of randomly divided rats received vindoline (20 mg/kg) or glibenclamide (5 mg/kg) daily for 6 weeks via oral gavage. Lipid profile markers and markers of atherogenic index were decreased in diabetic rats after treatment with vindoline and glibenclamide. The levels of urea were significantly increased in the diabetic control group (13.66 ± 0.9) compared to the diabetic groups treated with vindoline and glibenclamide (10.62 ± 0.6 and 10.82 ± 0.8), respectively. Vindoline did not significantly alter the levels of inflammatory cytokines; however glibenclamide lowered the levels of TNF-α in kidney and heart tissues. Vindoline improved the ferric reducing antioxidant power in diabetic hearts, while superoxide dismutase (SOD) oxygen radical absorbance capacity was increased in the kidneys. Lipid peroxidation was reduced when compared to the diabetic controls. Vindoline restored the structure of the renal parenchyma and was accompanied by significant decrease in the expression of caspase 9 in diabetic rats when compared to the diabetic controls.

Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin‐ (STZ‐) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract‐Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ‐induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ‐induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.