This study aimed to enhance natural gamma aminobutyric acid (GABA) production in yoghurt by the addition of simple sugars and commercial prebiotics without the need for pyridoxal 5'-phosphate (PLP) cofactor. The simple sugars induced more GABA production (42.83-58.56 mg/100 g) compared to the prebiotics (34.19-40.51 mg/100 g), with glucose promoting the most GABA production in yoghurt (58.56 mg/100 g) surpassing the control sample with added PLP (48.01 mg/100 g). The yoghurt prepared with glucose also had the highest probiotic count (9.31 log CFU/g). Simulated gastrointestinal digestion of this GABA-rich yoghurt showed a non-significant reduction in GABA content and probiotic viability, demonstrating the resistance towards a highly acidic environment (pH 1.2). Refrigerated storage up to 28 days improved GABA production (83.65 mg/100 g) compared to fresh GABA-rich yoghurt prepared on day 1. In conclusion, the addition of glucose successfully mitigates the over-use of glutamate and omits the use of PLP for increased production of GABA in yoghurt, offering an economical approach to produce a probiotic-rich dairy food with potential anti-hypertensive effects.
In view of the emergence of drug-resistant strains of Plasmodium falciparum, there is an urgent need for the development of new effective antimalarial agents to mitigate the issue of drug resistance. In this study, a series of lupeol (2) and betulin (3) derivatives were synthesised, characterised and evaluated for their antimalarial activity against the P. falciparum FCR3 strain. Eight compounds, including lupenone (1), displayed good anti-plasmodial potency with IC50 values ranging from 0.03-9.9 µM. Moreover, in vitro results showed that compound 1 and derivatives 4a and 4b were the most active compounds with potent inhibitory activity of (0.3 ± 0.3, 0.03 ± 0.05 and 0.7 ± 0.8 μM), respectively, compared to the reference drugs artemisinin and chloroquine (0.7 ± 0.3 and 10.3 ± 2.9 μM), respectively. Furthermore, molecular docking analysis of these compounds revealed good affinity to the binding site of the P. falciparum protein of the PfATP6 with a binding affinity between -9.8 and -8.4 kcal mol-1 via multiple hydrophobic interactions with the amino acid of the PfATP6 protein. The results showed hydrogen bonds and various hydrophobic interactions between the studied compounds and the amino acid of the PfATP6 protein, such as ASN1039, VAL984, ILE981 and ILE1041. Therefore, these compounds could be promising lead structures for further validation as potential candidates in developing new antimalarial drugs.