Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb–drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases.

The ATP-binding cassette transporter A1 (ABCA1) is a membrane-bound exporter protein involved in regulating serum HDL level by exporting cholesterol and phospholipids to load up in lipid-poor ApoA-I and ApoE, which allows the formation of nascent HDL. Mutations in the ABCA1 gene, when presents in both alleles, disrupt the canonical function of ABCA1, which associates with many disorders related to lipid transport. Although many studies have reported the phenotypic effects of a large number of ABCA1 variants, the pathological effect of non-synonymous polymorphisms (nsSNPs) in ABCA1 remains elusive. Therefore, aiming at exploring the structural and functional consequences of nsSNPs in ABCA1, in this study, we employed an integrated computational approach consisting of nine well-known in silico tools to identify damaging SNPs and molecular dynamics (MD) simulation to get insights into the magnitudes of the damaging effects. In silico tools revealed four nsSNPs as being most deleterious, where the two SNPs (G1050V and S1067C) are identified as the highly conserved and functional disrupting mutations located in the NBD1 domain. MD simulation suggested that both SNPs, G1050V and S1067C, changed the overall structural flexibility and dynamics of NBD1, and induced substantial alteration in the structural organization of ATP binding site. Taken together, these findings direct future studies to get more insights into the role of these variants in the loss of the ABCA1 function.

Cyclooxygenase-2 (COX-2) is critically implicated in various pathologies, including inflammation, cancer, disorders involving the nervous system, and multidrug resistance. In both academic and pharmaceutical research, the development of COX-2 selective drugs as anti-inflammatory and anti-tumor therapeutics is a key focus. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) have ulcerogenic, gastrointestinal adverse effects, and myocardial infarction risk, which resulted in their limited applications. In response to this challenge, we synthesized a series of glycoconjugates featuring six-membered sugar rings and acyl chains of varying lengths attached at the C-6 position. Using molecular docking techniques, we identified galactose esters with optimal acyl chain lengths that selectively and effectively bind to the active site of COX-2 over COX-1. These compounds exhibited enhanced binding affinity and superior inhibition constants (pK_i) for COX-2, thereby offering selective inhibition with potentially reduced ulcerogenic risks, as COX-1 inhibition is thought to contribute to these side effects. The molecular docking study identified two potential compounds, G6 and G8, which were validated via MD simulation for the assessment of their stability and were compared to the complex of the standard drugs, aspirin and rofecoxib. In addition, compound structures were optimized using the DFT method under the B3LYP/6-31+g(d,p) basis set to study their physio-spectral properties, frontier molecular orbitals (HOMO–LUMO), and their energy gap that correlates to their reactivity and stability. ADMET, drug-likeness, and PASS analyses were also carried out to assess their drug-ability and toxicity profiling.

Background: Active compounds from plants and herbs are increasingly incorporated into modern medical systems to address cardiovascular diseases (CVDs). Foeniculum vulgare Mill., commonly known as fennel, is an aromatic medicinal plant and culinary herb that is popular worldwide. Methods: Protective effects against cellular damage were assessed in the H9C2 cardiomyocyte hypoxia/reoxygenation (H/R) experimental model. The identities of phytochemicals in FVSE were determined by GC-MS analysis. The phytochemical’s potential for nutrients and pharmacokinetic properties was assessed by ADMET analysis. Results: GC-MS analysis of the ethanol extracts of F. vulgare identified 41 bioactive compounds, with four prominent ones: anethole, 1-(4-methoxyphenyl)-2-propanone, ethoxydimethylphenylsilane, and para-anisaldehyde diethyl acetal. Among these, anethole stands out due to its potential for nutrients and pharmacokinetic properties assessed by ADMET analysis, such as bioavailability, lipophilicity, flexibility, and compliance with Lipinski’s Rule of Five. In the H/R injury model of H9C2 heart myoblast cells, FVSE and anethole suppressed H/R-induced reactive oxygen species (ROS) generation, DNA double-strand break damage, nuclear condensation, and the dissipation of mitochondrial membrane potential (ΔΨm). Conclusions: These findings highlight the therapeutic potential of FVSE and its prominent component, anethole, in the treatment of CVDs, particularly those associated with hypoxia-induced damage.

Garlic (Allium sativum L.) is an aromatic herb known for its culinary and medicinal uses for centuries. Both unprocessed (white) and processed (black) garlic are known to protect against the pathobiology of neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), which has been attributed to their anti-inflammatory and antioxidant properties. The information on the effects of processed and unprocessed garlic on neuronal process outgrowth, maturation, and synaptic development is limited. This study aimed at investigating and comparing the effects of the ethanol extracts of unprocessed (white garlic extract, WGE) and processed (black garlic extract, BGE) garlic on the maturation of primary hippocampal neurons. Neurite outgrowth was stimulated in a dose-dependent manner by both WGE and BGE and the most effective doses were 15 μg/mL and 60 μg/mL, respectively, without showing cytotoxicity. At this optimal concentration, both extracts promoted axonal and dendritic growth and maturation. Furthermore, both extracts substantially increased the formation of functional synapses. However, the effect of WGE was more robust at every developmental stage of neurons. In addition, the gas chromatography and mass spectrometry (GC-MS) analysis revealed a chemical profile of various bioactives in both BGE and WGE. Linalool, a compound that was found in both extracts, has shown neurite outgrowth-promoting activity in neuronal cultures, suggesting that the neurotrophic activity of garlic extracts is attributed, at least in part, to this compound. By using network pharmacology, linalool’s role in neuronal development can also be observed through its modulatory effect on the signaling molecules of neurotrophic signaling pathways such as glycogen synthase kinase 3 (GSK3β), extracellular signal-regulated protein kinase (Erk1/2), which was further verified by immunocytochemistry. Overall, these findings provide information on the molecular mechanism of processed and unprocessed garlic for neuronal growth, survival, and memory function which may have the potential for the prevention of several neurological disorders.