Investigation of possible hazards and benefits of use of 'Ashkulebya' (Maerua subcordata (Gilg) DeWolf) as famine and/or potential functional food

Currently, wild edible plants are getting into the research focus of both food and pharmaceutical domains as they are considered valuable resources for improving food and nutritional security as well as for bioactive ingredients that can be used for functional foods or managing chronic diseases. Wild edible plants, in addition to their potential nutritional contribution, may provide important health benefits as the health-promoting components of plant based foods, so called nutraceuticals or functional food ingredients, are usually higher in wild plants. However, at the same time, these plants may contain toxic ingredients that may lead to adverse effects. At the current state of the art novel foods have to comply with novel food regulation while safety of the use of botanicals and botanical preparation as food is the responsibility of the provider and not subject to premarket safety evaluation. This implies that a concern requiring adequate consideration of both risks and benefits has to be addressed when introducing wild edible plants as novel components in a regular diet or as herbal medicine or food supplement. The present PhD thesis aims at investigating the possible hazards and potential health benefits of Maerua subcordata (Gilg) DeWolf, a wild plant locally called ‘ashkulebya’ by the Kunama ethnics of Northern Ethiopia, as a novel nutritional resource and/or as a health food/functional food. To meet this aim, the thesis tested the activity of different extracts of M. subcordata in a wide range of in vitro assays for both adverse and beneficial endpoints, along with, phytochemical studies to identify active constituents. Consideration of ethnobotanical data was also part of the study. The phytochemical studies identified glucosinolates and biogenic amines such as quaternary ammonium compounds and guanidine derivatives in the different M. subcordata extracts. The potential health benefits of M. subcordata extracts via their effects on the expression of electrophile-responsive element (EpRE), peroxisome proliferator-activated receptor gamma (PPARg), and  nuclear factor kappa B (NF-κB) regulated genes was  evaluated. The induction of  EpRE-mediated genes have implications of maintaining redox homeostasis. The fruit, leaf, and seed extracts induced the expression of EpRE-mediated genes while induction by the root extract was minimal. Candidate glucosinolates (or their matching isothiocyanates) exhibited strong induction while some biogenic amines exhibited either no significant induction or slight inhibition. Inhibition of NF-κB regulated genes have implications for anti-inflammatory effects while induction of PPARg regulated genes have implications for control of diseases of the metabolic syndrome. The fruit, root, and seed extracts induced PPARγ-mediated gene expression while induction by the leaf extract was minimal. Instead, all extracts inhibited bacterial lipopolysaccharide (LPS) induced nitric oxide production, with the root showing the lowest potency. Selected candidates such as isothiocyanates and some biogenic amines also inhibited the LPS induced nitric oxide production. Equally, a battery of in vitro tests was applied to identify selected endpoints that could be used to assess the potential hazards associated with the use of botanical preparations or parts of  M. subcordata. The Ames test and in silico (Derek Nexus) predictions were applied for initial genotoxicity screening whereas the aryl hydrocarbon receptor and the estrogen receptor alpha reporter gene assays as well as the embryonic stem cell test and the zebrafish embryotoxicity test were applied to investigate alerts for developmental toxicity. The overall hazard assessment results indicated that all extracts of M. subcordata do not point to a genotoxicity hazard; fruit, root, and seed extracts do not raise a concern with respect to developmental toxicity; but the data on the leaf extract may point towards a developmental toxicity hazard. In conclusion, the overall results obtained argue in favour of the use of the root, fruit, and seed parts of M. subcordata as (famine) food and/or functional food whereas the leaf part may be used as a herbal medicine. The outcomes of the study may also contribute scientific data to design further in vivo studies on safety and proper utilization of the plant while the methodology applied can be extrapolated to serve as an approach to the risk-benefit assessment of other plant based products.