Riham A. El‐Shiekh

Aucubin as a multifunctional iridoid glycoside: Molecular pharmacology and therapeutic mechanisms supporting its potential as a drug discovery scaffold.

Aucubin is a widely distributed iridoid glycoside that has gained increasing attention as a multifunctional scaffold in natural product-based drug discovery. Occurring predominantly in Plataginaceae and related medicinal plant families, aucubin is biosynthesized through a modified monoterpenoid pathway and stored as a stable glycoside that undergoes enzymatic activation to yield its aglycone aucubigenin. This prodrug-like behavior underlies its context-dependent biological activity. Accumulating preclinical evidence demonstrates anti-oxidant, anti-inflammatory, anti-fibrotic, metabolic-regulatory, cytoprotective, and immunomodulatory effects across models of cardiovascular disease, diabetes, chronic kidney injury, liver fibrosis, neurodegeneration, respiratory disorders, osteoporosis, wound healing, and cancer. Mechanistically, aucubin consistently modulates convergent stress-response pathways, including suppression of NF-κB signaling, activation of Nrf2/ARE anti-oxidant defense, regulation of AMPK-mediated metabolic homeostasis, preservation of mitochondrial integrity, and inhibition of TGF-β/Smad-driven fibrogenesis. In bone and metabolic disorders, aucubin restores redox balance and supports osteoblast function while limiting osteoclastogenesis. In cancer models, it suppresses proliferation and modulates tumor-associated immune signaling, including PD-L1 expression. These pathways are central to the global burden of non-communicable diseases, directly aligning aucubin research with Sustainable Development Goal 3 (Good Health and Well-being). While the breadth and internal consistency of experimental findings support its value as a multi-target cytoprotective template, translation toward clinical application remains limited by the scarcity of human studies, standardized pharmacokinetic data, and comprehensive toxicological evaluation. Collectively, this review positions aucubin as a biologically informative iridoid glycoside with substantial scaffold-level relevance for future natural-product-inspired therapeutic development, rather than as a near-term clinical drug candidate.

Neurogenesis and neuroplasticity activities of natural products: therapeutic potential in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and behavioral disturbance, largely associated with amyloid-β accumulation, tau protein pathology, synaptic dysfunction, oxidative stress and neuroinflammation. Previous research emphasizes the critical roles of impaired neurogenesis and neuroplasticity in cognitive dysfunction and neurodegenerative disorders, particularly AD. This review highlights the therapeutic potential of natural products in restoring these processes. It offers a comprehensive overview of the molecular mechanisms underlying neurogenesis and synaptic plasticity, with a focus on key regulatory pathways, such as BDNF/TrkB, ERK/CREB, PI3K/Akt and neurotransmitter signaling cascades. It also shows how the disruption of these regulatory pathways, caused by AD-associated pathological factors, results in reduced neuronal regeneration and synaptic connectivity. Furthermore, it summarizes preclinical data showing that various phytochemical compounds, such as ginsenosides, epigallocatechin gallate, curcumin, resveratrol, and flavonoids can improve neural stem cell proliferation, promote neuronal differentiation, and enhance synaptic function. Despite the promising pre-clinical studies results, clinical studies evaluating natural products remain limited due to poor bioavailability, inconsistent efficacy, and methodological constraints in human studies. To overcome these limitations, new strategies such as nanotechnology-based delivery systems and advanced brain targeting approaches are being developed. Overall, natural products represent promising candidates for managing neurogenesis and neuroplasticity in AD, although further clinical studies are required to validate their therapeutic efficacy.

Design, Synthesis, X‐Ray Crystallographic Characterization, Anticholinesterase and Antioxidant Evaluation, and Molecular Modeling of Novel Dispiroindene‐Pyrrolidine Derivatives as Multifunctional Anti‐Alzheimer Agents

LC-QTOF-MS metabolic profiling and anti-MRSA activity of Asparagus officinalis L. spear methanolic extract in a skin infection mouse model

Asparagus officinalis L. spears offer substantial potential as a functional food due to their rich nutritional profile and bioactive compounds. The emergence and spread of multidrug-resistant (MDR) pathogens, particularly in low- and medium-income countries, have necessitated extensive research and concerted efforts to combat infections. Novel One Health approaches are being sought to swiftly identify antibiotics that retain efficacy against these MDR pathogens. In this study, we evaluated the antibacterial activity of the methanolic extract of A. officinalis L. spears against Staphylococcus aureus USA300 (MARSA USA300); a MDR bacterium in vitro and in vivo. The methanolic extract demonstrated significant in vitro inhibition of the biofilm formation (IC50 value of 3.415 mg mL−1) and enhanced biofilm detachment (EC50 value of 1.573 mg mL−1) against MRSA. Additionally, topical treatment of MRSA USA300-infected BALB/C mice open lesion with the extract (50 mg mL−1 in 25% DMSO, once for three days) significantly reduced the bacterial count by 2.877 and 2.583 logs lower than that of the negative control). LC-QTOF/MS tentatively identified 99 compounds in the methanolic extract of A. officinalis spears. The findings obtained here demonstrate the potential of A. officinalis L. spears for pharmaceutical, agricultural, and food industry applications.