Phytochemical and Safety Evaluations of Finger Lime, Mountain Pepper, and Tamarind in Zebrafish Embryos

Abstract

Plants play a pivotal role in drug discovery, constituting 50% of modern pharmacopeia. Many human diseases, including age-related degenerative diseases, converge onto common cellular oxidative stress pathways. This provides an opportunity to develop broad treatments to treat a wide range of diseases in the ageing population. Here, we characterize and assess the toxicological effects of finger lime (Citrus australasica), mountain pepper (Tasmannia lanceolata), and small-leaved tamarind (Diploglottis australis) extracts. The characterization demonstrates that these Australian native plants have antioxidant potential and, importantly, they have high concentrations of distinct combinations of different antioxidant classes. Using zebrafish larvae as a high-throughput pre-clinical in vivo toxicology screening model, our experiment effectively discriminates which of these extracts (and at what exposure levels) are suitable for development towards future therapies. The LC50-96h for finger lime and tamarind were >480 mg/L, and 1.70 mg/L for mountain pepper. Critically, this work shows that adverse effects are not correlated to the properties of these antioxidants, thus highlighting the need for combining characterization and in vivo screening to identify the most promising plant extracts for further development. Thus, we present a high-throughput pre-clinical screening that robustly tests natural plant products to utilize the diversity of antioxidant compounds for drug development.

Phytochemicals, Antioxidant Activities, and Toxicological Screening of Native Australian Fruits Using Zebrafish Embryonic Model

“…The in vivo acute toxicity tests of Australian native fruit extracts (6 different concentrations at 15, 30, 60, 120, 240, and 480 mg/L with E3 medium (0 mg/L) as a control) were analyzed by following the method of Cáceres-Vélez et al [ 2 ]. Zebrafish (AB wild type) were maintained at the Danio rerio facility at the University of Melbourne, Victoria, Australia.…”

“…Plant bioactive constituents are a vital component of traditional medicine used to treat various ailments [ 1 ]. In the past few decades, plants or plant-derived natural products have become the leading source of drug discovery [ 2 ]. Natural products from plants, marine organisms, or microorganisms have several nutritional and therapeutic properties.…”

In Vitro and Ex Vivo Evaluation of Mangifera indica L. Extract-Loaded Green Nanoparticles in Topical Emulsion against Oxidative Stress and Aging

“…GSH is found in the cytosol of cells (1–10 mM), playing a key role in regulation of oxidative stress by elimination of many ROS and these reactions are catalyzed by GSTs [ 6 ]. Catalase decomposes hydrogen peroxide to harmless products such as water and oxygen, it is used against many oxidative stress-related diseases as a therapeutic agent [ 7 ]. The extract showed significant increase in the catalase assay when compared to the negative control Figure 3 C. The M-Ext markedly increases the SODs concentration compared to the negative control ( Figure 3 E).…”

“…The extract showed significant increase in the catalase assay when compared to the negative control Figure 3 C. The M-Ext markedly increases the SODs concentration compared to the negative control ( Figure 3 E). Similarly, the positive control treated with vitamin C also significantly induced the antioxidant enzymes, catalyzing the conversion of superoxides (O 2 − ) to less reactive H 2 O 2 [ 7 ]. The loss of SOD activity is linked to membrane lipid peroxidation, protein carbonylation, and DNA breakage [ 8 ].…”

“…Mangifera indica L. is a popular fruit whose extract has been reported to have several beneficial medicinal properties other than nutritional purposes [ 4 ]. Its peels and kernel extracts comprising 40–50% of its weight contain a high amount of bioactive compounds i.e., gallic acids, quercetin, mangiferin, catechin, epicatechin, quercetin, isoquercetin, fisetin, rutin, ellagic acid, gallic acid, gallates, condensed tannins, gallotannins, anthocyanin, and astragalin [ 5 , 6 , 7 , 8 , 9 ]. These compounds have good potency to control the overproduction of FRs [ 10 ].…”