Clitoria ternatea Linn. (CT), or butterfly pea, is an Ayurvedic plant traditionally used as a brain tonic. Recently, it was reported to be of use in treating central nervous system (CNS) disorders, i.e., as an antistress treatment and antidepressant. In the present study, we report a detailed phytochemical profile of the ethyl acetate fraction of the flower of CT (CTF_EA) with significant neuroprotective and anti-neuroinflammatory properties in both LPS-activated BV-2 and SK-N-SH cells. Concurrently, the molecular network (MN) derived from the CTF_EA metabolome allows putative identification of flavonol 3-O-glycosides, hydrocinnamic acids, and primary metabolites. Molecular docking studies suggest that CTF_EA preferentially targets iNOS, resulting in a decrease in nitric oxide (NO). Furthermore, no toxic effects on normal embryonic development, blood vessel formation, and apoptosis are observed when CTF_EA is tested for in vivo toxicity in zebrafish models. The overall preliminary results suggest the anti-neuroinflammatory and neuroprotective effects of CT and provide scientific support for the efficacy of this medicinal plant at local and traditional levels. However, studies on the targeted isolation of bioactive metabolites, in-depth pharmacological efficacy, and safety in mammalian models are urgently needed to expand our understanding of this plant before it is developed into a promising therapeutic agent for brain-related diseases.

Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC₅₀ values of 1.6, 2.5 and 3.1 μM, respectively. Meanwhile, MS87 (EC₅₀ of 1.85 μM) shown the most active against the CQ-resistant Gombak A strain, and MS33A and MS33C the most effective P. knowlesi inhibitors (EC₅₀ of 3.6 and 5.1 μM, respectively). The in vitro cytotoxicity of selected diarylpentanoids (MS33A, MS33C, MS34C and MS87) was tested on Vero mammalian cells to evaluate parasite selectivity (SI), showing moderate to low cytotoxicity (CC₅₀ > 82 μM). In addition, MS87 exhibited a high SI and the lowest resistance index (RI), suggesting that MS87 may exert effective parasite inhibition with low resistance potential in the CQ-resistant P. falciparum strain. Furthermore, the in vivo toxicity of the molecules on early embryonic development, the cardiovascular system, heart rate, motor activity and apoptosis were assessed in a zebrafish animal model. The overall results indicate the preliminary potential of diarylpentanoids, which need further investigation for their development as new antimalarial agents.

Epilepsy is the third most common known brain disease worldwide. Several antiepileptic drugs (AEDs) are available to improve seizure control. However, the associated side effects limit their practical use and highlight the ongoing search for safer and effective AEDs. Eighteen newly designed fluorine-containing pyrrolylated chalcones were extensively studied in silico, synthesized, structurally analyzed by X-ray diffraction (XRD), and biologically and toxicologically tested as potential new AEDs in zebrafish epilepsy in vivo models. The results predicted that 3-(3,5-difluorophenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (compound 8) had a good drug-like profile with binding affinity to γ-aminobutyric acid receptor type-A (GABA_A, -8.0 kcal/mol). This predicted active compound 8 was effective in reducing convulsive behaviour in pentylenetetrazol (PTZ)-induced larvae and hyperactive movements in zc4h2 knockout (KO) zebrafish, experimentally. Moreover, no cardiotoxic effect of compound 8 was observed in zebrafish. Overall, pyrrolylated chalcones could serve as alternative AEDs and warrant further in-depth pharmacological studies to uncover their mechanism of action.