Cancer is the second leading cause of mortality worldwide. Skin cancer is the most common cancer in South Africa with nearly 20,000 reported cases every year and 700 deaths. If diagnosed early, the 5‐year survival rate is about 90%, however, when diagnosed late, the 5‐year survival rate decreases to about 20%. Melanoma is a type of skin cancer with an estimated 5‐year survival rate of approximately 90%. Neuroblastoma is a paediatric cancer with a low survival rate. Sixty percent of patients with metastatic disease do not survive 5 years after diagnosis. Despite recent advances in targeted therapies, there is a crucial need to identify reliable prognostic biomarkers which will be able to contribute to the development of more precision‐based chemotherapeutic strategies to prevent tumour migration and metastasis. The compound, CTCE‐9908 inhibits the binding of CXC chemokine ligand 12 (CXCL12) to the CXC chemokine receptor 4 (CXCR4) receptor leading to reduced metastasis. Kynurenine metabolites are derived tryptophan, which is an essential amino acid. Kynurenine metabolites inhibit T‐cell proliferation resulting in cell growth arrest. For this reason, chemokines receptors represent potential targets for the treatment of cancer growth and metastasis. In this review paper, the role of the CXCL12/CXCR4 signalling pathway in the development of cancer is highlighted together with the current available treatments involving the CTCE‐9908 compound in combination with microtubule inhibitors like paclitaxel and docetaxel.

Metabolic syndrome (MetS) is a prevalent, multifactorial and complex disease that is associated with an increased risk of developing diabetes and other major cardiovascular complications. The rise in the global prevalence of MetS has been attributed to genetic, epigenetic, and environmental factors. The adoption of sedentary lifestyles that are characterized by low physical activity and the consumption of high-energy diets contributes to MetS development. Current management criteria for MetS risk factors involve changes in lifestyle and the use of pharmacological agents that target specific biochemical pathways involved in the metabolism of nutrients. Pharmaceutical drugs are usually expensive and are associated with several undesirable side effects. Alternative management strategies of MetS risk factors involve the use of medicinal plants that are considered to have multiple therapeutic targets and are easily accessible. Medicinal plants contain several different biologically active compounds that provide health benefits. The impact of phytochemicals present in local medicinal plants on sustainable health and well-being of individuals has been studied for many years and found to involve a plethora of complex biochemical, metabolic, and physiological mechanisms. While some of these phytochemicals are the basis of mainstream prescribed drugs (e.g., metformin, reserpine, quinine, and salicin), there is a need to identify more medicinal plants that can be used for the management of components of MetS and to describe their possible mechanisms of action. In this review, we assess the potential health benefits of South African ethnomedicinal plants in protecting against the development of health outcomes associated with MetS. We aim to provide the state of the current knowledge on the use of medicinal plants and their therapeutically important phytochemicals by discussing the current trends, with critical examples from recent primary references of how medicinal plants are being used in South African rural and urban communities.

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AMP-activated protein kinase (AMPK) is known to regulate both glucose and lipid metabolism, which play vital roles in the development of metabolic syndrome. One way of regulating AMPK is through hormonal activation using adiponectin. Patients diagnosed with type-2 diabetes (T2D) and obesity exhibit low adiponectin concentration levels in their blood. Moreover, studies have also shown that inflammatory processes play a significant role in the etiology of these metabolic diseases. In this study, the long-term effects of neonatal intake of oleanolic acid (OA) on the AMPK gene, genes associated with glucose transport and lipid metabolism, adiponectin levels, and inflammatory biomarkers in rats fed with a high fructose diet were investigated. Seven day old pups were randomly divided into five groups and treated as follows; 0.5% dimethylsulphoxide v/v in distilled water vehicle control (CON), oleanolic acid (OA, 60 mg/kg), high fructose diet (HF, 20% w/v), high fructose diet combined with oleanolic acid (HF+OA), and high fructose diet combined with metformin (HF+MET, 500 mg/kg). The treatments were administered once daily until day 14. The rats were then weaned at day 21 and fed standard rat chow and had ad libitum access to plain drinking water until day 112. The quantitative polymerase chain reaction (qPCR) was used to analyze the gene expressions of AMPK, Glut-4, Cpt-1, AdipoR1, AdipoR2, TNF-α, and IL-6 in the skeletal muscles. Bio-Plex Pro magnetic bead-based assay was used to measure plasma levels of inflammatory markers (TNF-α, IL-6, VEGF, and MCP-1) while ELISA kits were used to measure adiponectin concentration in blood plasma. The results obtained in this study showed that neonatal supplementation with OA significantly increased AMPK gene expression approximately ~4-fold in OA fed rats compared to those that were fed with HF alone. In addition, glut-4 gene expression was also significantly higher in the OA treatment group compared to all the other experimental groups except the CON group whereas Cpt-1 gene was more expressed when OA was administered alone. Together, these results indicated that OA can play a role in glucose and lipid metabolism gene regulation. Furthermore, the results showed that the OA group had ~1.5-fold increase in adiponectin concentration when comparedto the HF group. Moreover, HF increased levels of inflammatory cytokines, which was attenuated by neonatal administration of OA. Plasma concentration and gene expression in the skeletal muscle for TNF-α and IL-6 were significantly increased in rats that were treated with HF alone when compared to all the other groups. On the contrary, the high levels of TNF-α and IL-6 were reduced when OA was administered. These findings suggest that intake of oleanolic acid during the neonatal stage of development could be a potential strategic intervention for the long-term prevention of metabolic diseases such as T2D and obesity.

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This paper reviews the properties of the most cultivated species of the Moringaceae family, Moringa oleifera Lam. The paper takes a critical look at the positive and the associated negative properties of the plant, with particular emphasis on its chemistry, selected medicinal and nutritional properties, as well as some ecological implications of the plant. The review highlights the importance of glucosinolates (GS) compounds which are relatively unique to the Moringa species family, with glucomoriginin and its acylated derivative being the most abundant. We highlight some new research findings revealing that not all M. oleifera cultivars contain an important flavonoid, rutin. The review also focuses on phenolic acids, tannin, minerals and vitamins, which are in high amounts when compared to most vegetables and fruits. Although there are numerous benefits of using M. oleifera for medicinal purposes, there are reports of contraindications. Nonetheless, we note that there are no major harmful effects of M. oleifera that have been reported by the scientific community. M. oleifera is suspected to be potentially invasive and moderately invasive in some regions of the world because of its ability to grow in a wide range of environmental conditions. However, the plant is currently classified as a low potential invasive species and thus there is a need to constantly monitor the species. Despite the numerous benefits associated with the plant, there is still a paucity of data on clinical trials proving both the positive and negative effects of the plant. We recommend further clinical trials to ascertain the properties associated with the plant, especially regarding long term use.

Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary fructose-induced NAFLD. Male and female suckling rats (n=112) were gavaged with; distilled water (DW), OA (60 mg/kg), high fructose solution (HF; 20% w/v) and OA+HF (OAHF) for 7 days. The rats were weaned onto normal rat chow on day 21 up to day 55. From day 56, half of the rats in each treatment group were continued on plain water or HF as drinking fluid for 8 weeks. Hepatic lipid accumulation and hepatic histomorphometry were then determined. Fructose consumption in adulthood following neonatal fructose intake (HF+F) caused a 47-49% increase in hepatic lipid content of both male and female rats (P<0.05). However, fructose administered in adulthood only, caused a significant increase (P<0.05) in liver lipid content in females only. NAFLD activity scores for inflammation and steatosis were higher in the fructose-fed rats compared with other groups (P<0.05). Steatosis, low-grade inflammation and fibrosis were observed in rats that received HF+F. NAFLD area fraction for fibrosis was three times higher in rats that received fructose neonatally and in adulthood compared with the rats in the negative control group (P<0.05). Treatment with OA during a critical window of developmental plasticity in rats prevented the development of fructose-induced NAFLD.

BackgroundConsumption of fructose-rich diets has been implicated in the increasing global prevalence of metabolic syndrome (MetS). Interventions during periods of early ontogenic developmental plasticity can cause epigenetic changes which program metabolism for positive or negative health benefits later in life. The phytochemical oleanolic acid (OA) possesses anti-diabetic and anti-obesity effects. We investigated the potential protective effects of neonatal administration of OA on the subsequent development of high fructose diet-induced metabolic dysfunction in rats.MethodMale and female (N = 112) suckling rats were randomly assigned to four groups and administered orally: distilled water (DW), oleanolic acid (OA; 60 mg/kg), high-fructose solution (HF; 20% w/v) or OA + HF for 7 days. The rats were weaned onto normal commercial rat chow up to day 55. From day 56, half of the rats in each treatment group were continued on plain water and the rest on a high fructose solution as drinking fluid for 8 weeks. On day 110, the rats were subjected to an oral glucose tolerance test and then euthanased on day 112. Tissue and blood samples were collected to determine the effects of the treatments on visceral fat pad mass, fasting plasma levels of cholesterol, insulin, glucose, triglycerides, insulin resistance (HOMA-IR) and glucose tolerance.ResultsRats which consumed fructose as neonates and then later as adults (HF + F) and those which consumed fructose only in adulthood (DW + F) had significant increases in terminal body mass (females only), visceral fat mass (males and females), serum triglycerides (females only), epididymal fat (males only), fasting plasma glucose (males and females), impaired glucose metabolism (females only), β-cell dysfunction and insulin resistance (males and females) compared to the other treatment groups (P < 0.05). There were no differences in fasting serum cholesterol levels across all treatment groups in both male and female rats (P > 0.05).ConclusionWe conclude that neonatal oral administration of OA during the critical window of developmental plasticity protected against the development of health outcomes associated with fructose-induced metabolic disorders in the rats.