The present review offered an updated theoretical basis for understanding the structure-activity relationship of HKL and provided insights into its translation from bench to bedside and critically evaluated recently developed strategies to overcome its pharmacokinetic limitations.
Abstract
Honokiol (HKL), a bioactive biphenolic lignan isolated from the bark of Magnolia officinalis, possesses diverse pharmacological properties, including neuroprotective, antitumor, anti-inflammatory and metabolic regulatory effects. Despite its therapeutic promise, the clinical application of HKL is severely restricted by its hydrophobicity and low oral bioavailability. The present review systematically summarized 99 studies (90 original articles and nine reviews) on the pharmacological profile of HKL. It detailed HKL's molecular interactions with key signaling targets, such as sirtuin 3, NOD-like receptor family pyrin domain containing 3-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes, Yes-associated protein/transcriptional coactivator with PDZ-binding motif, adenosine monophosphate-activated protein kinase and signal transducer and activator of transcription 3, which underly its efficacy against cancer (ovarian, liver, breast, colorectal, and lung), neurodegeneration (Alzheimer's and Parkinson's disease), metabolic disorders (diabetes, nonalcoholic fatty liver disease and obesity) and inflammatory and infectious diseases. Furthermore, the present review critically evaluated recently developed strategies to overcome its pharmacokinetic limitations. The present review offered an updated theoretical basis for understanding the structure-activity relationship of HKL and provided insights into its translation from bench to bedside.
Pterostilbene is a bioactive phenolic compound belonging to the stilbene class; it is structurally analogous to resveratrol but possesses superior pharmacokinetic properties—such as higher oral bioavailability, metabolic stability, and a prolonged plasma half-life—that enhance its therapeutic potential. This study aimed to systematically analyze the pharmacological effects of pterostilbene, emphasizing its molecular mechanisms of action and identifying gaps in the scientific literature. A systematic review was conducted using indexed databases (PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar) and employing both controlled descriptors and free-text terms in Portuguese and English. Experimental and clinical studies published within the last fifteen years were included and analyzed using a narrative and comparative approach. The results demonstrate that pterostilbene exerts pleiotropic effects, modulating pathways related to oxidative stress, inflammation, apoptosis, and cellular energy metabolism. Key mechanisms include activation of the Nrf2/ARE pathway, reduction of pro-inflammatory cytokines (such as TNF-α, IL-1β, and IL-6), and inhibition of cyclooxygenase-2 (COX-2) expression. Its high lipophilicity facilitates cellular permeability and crossing of the blood-brain barrier, expanding its potential application in cardiovascular, neurodegenerative, metabolic, and neoplastic diseases. However, significant limitations remain, such as a scarcity of randomized clinical trials, methodological heterogeneity, and a lack of standardized dosing. Consequently, robust translational studies are required to confirm the efficacy, safety, and clinical applicability of pterostilbene, thereby consolidating its role as a promising candidate for contemporary therapeutic use.
Alessandra Nunes dos Santos, Mariane Palença Alves, Pamela Paloma da Silva Costa et al.· Revista de Estudos Interdisc...· 0 citations
The development of effective neuroprotective agents remains one of the most urgent and complex challenges in modern medical and biological research, given the increasing prevalence of neurodegenerative diseases and the limited efficacy of existing therapeutic options. In recent years, compounds belonging to the 4H-pyran chemical class have attracted significant attention due to their pronounced antioxidant, anti-inflammatory, and cytoprotective properties. These molecules exhibit structural versatility, enabling modulation of multiple molecular targets involved in neuronal survival, redox homeostasis, and mitochondrial function. This review provides a comprehensive analysis of the pharmacological activity and molecular mechanisms of action of five 4H-pyran-based compounds-maltol, kojic acid, chelidonic acid, comenic acid, and meconic acid. Special attention is paid to their effects on signaling pathways that play a central role in maintaining neuronal integrity and resistance to stress factors. In particular, the review examines how these compounds regulate key intracellular cascades such as nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response element (ARE), Nrf2/PTEN-induced putative kinase 1 (PINK1)/Parkin, nuclear factor-kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), which are critically involved in controlling oxidative stress, mitochondrial autophagy, inflammation, and neuronal plasticity. The integrated evaluation of these mechanisms demonstrates that 4H-pyran-based acids can act as multitarget neuroprotective agents capable of influencing both primary metabolic processes and secondary signaling responses to neurotoxic stimuli. Their pleiotropic action highlights the promise of these compounds as molecular scaffolds for the development of novel drugs aimed at preventing or delaying the progression of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases.
A. Kravtsov, S. Kozin, R. Kondratenko et al.· Frontiers in Bioscience· 0 citations
Wogonoside, a major flavone 7-O-glucuronide from Scutellaria baicalensis Georgi, has long been used as a quality-control marker for Scutellariae Radix and related traditional herbal formulations. Emerging evidence suggests that wogonoside is not merely an analytical marker or an inactive glucuronide, but a pharmacologically active constituent and potential precursor of bioactive metabolites. In preclinical models, it exhibits anti-inflammatory, antioxidant, anti-angiogenic, anti-fibrotic, antitumor, cardioprotective, neuroprotective, and renoprotective activities. These effects are associated with the regulation of key signaling networks involved in inflammation, oxidative stress, inflammasome activation, autophagy, angiogenesis, fibrosis, and regulated cell death. Representative mechanisms include modulation of TLR4/NF-κB/NLRP3, Nrf2/HO-1, PI3K/AKT/mTOR, AMPK/mTOR, Wnt/β-catenin, Hedgehog/SMO/Gli1, and ferroptosis-related SLC7A11/GPX4 signaling. Recent target-validation studies have identified several candidate molecular targets, including SMO, NF-κB p65, HNF4α, NEK7, GPX4, TLR4, and CD39. However, the strength of evidence varies, and direct target engagement remains to be confirmed for many of these proteins. Pharmacokinetic studies reveal complex disposition characteristics, including intestinal microbial deglycosylation to wogonin, intestinal and hepatic re-glucuronidation, transporter-mediated efflux, enterohepatic or enteric recycling, and frequent multiple-peak plasma profiles. These properties support the value of wogonoside as both a quality-control marker and a dynamic exposure-related marker in Scutellaria-containing preparations. This review summarizes current advances in the chemical analysis, pharmacokinetics, biotransformation, molecular pharmacology, and disease-specific actions of wogonoside, and discusses key challenges for future development, including variable bioavailability, metabolite contribution, target specificity, pharmacokinetic-pharmacodynamic relationships, and clinical translation.
Ming Xie, Jia Liu, Rui-feng Pu et al.· Biochemical Pharmacology· 0 citations
Background: Coumarins are benzopyrone compounds found in over 150 plant species, including cinnamon and citrus fruits, which exhibit diverse pharmacological activities. Despite extensive preclinical evidence, their clinical translation remains constrained by toxicity concerns and poor pharmacokinetic profiles.
Methods: A systematic literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar for publications from January 2000 to August 2024. Studies reporting therapeutic applications, mechanisms of action, and clinical limitations of coumarins were included, following PRISMA guidelines. Data were extracted on structural features, pharmacological outcomes, and documented toxicities, with qualitative synthesis performed.
Results: Coumarins demonstrate therapeutic potential as anticoagulants (warfarin, dicumarol), anticancer agents (daphnetin), anti-inflammatory compounds (esculetin, scopoletin), antioxidants, antimicrobials, neuroprotective agents, and anti-diabetic compounds. Their mechanisms include enzyme inhibition (MAO, PDE, vitamin K epoxide reductase, carbonic anhydrase), signaling pathway modulation (PI3K/Akt/mTOR, Keap1/Nrf2/ARE), and protein interactions (p53). Structure-activity relationship analysis reveals that hydroxyl/methoxy substitutions at positions 6 and 7 enhance antioxidant and neuroprotective properties, while 4-aryl groups improve anticancer activity. However, clinical application is limited by hepatotoxicity (psoralen-induced CYP-mediated oxidative stress), phototoxicity (furanocoumarins under UVA), drug interactions (CYP3A4 inhibition), and poor bioavailability.
Conclusion: Coumarins constitute a promising compound class with broad pharmacological actions, yet safety, bioavailability, and specificity remain major barriers to clinical translation. Future directions should focus on rational structural modification, nanotechnology-based delivery systems (liposomes, polymeric nanoparticles), multi-target hybrids, and rigorous human clinical trials to confirm therapeutic efficacy and safety profiles.
M. Mohammadi, A. Rahi, M. M. Soltan Dallal· Afghanistan Journal of Basic...· 0 citations
Orientin is a naturally occurring C-glycosyl flavonoid with a variety of pharmacological properties that is found in many medicinal plants. The isolation of orientin Physicochemical Properties, Distribution of tissues, Pharmacological Actions, Pharmacokinetics and In-Silico studies of orientin flavonoid mention in the Review. Exhibit potential Antioxidant, Anticancer, Neuroprotective, Cytoprotective, Antiviral, Anti-inflammatory, Anti-Bacterial, Radioprotective & Antiadipogenic activity has been studied. Such properties are mediated by a number of molecular Pathways, It includes NF-κB, Nrf2/HO-1, PI3K/Akt and apoptotic signalling pathways. Computational research and Molecular docking plays major role and leading point to its potential as a promising phytochemical for further therapeutic development. Also Preclinical results leads to more mechanistic research, Pharmacokinetic optimization, Toxicity assessment and clinical research studies are needed to confirm its therapeutic potential and safety in Humans.
Anupama Rai, Manoj Sharma, Sampda Jain· International Journal of Res...· 0 citations
Salvianolic acid B (Sal B), a polyphenolic constituent of Danshen. It has demonstrated therapeutic potential in cardiovascular diseases by targeting a spectrum of pathological processes. This review comprehensively summarizes the pharmacological effects, research progress and molecular mechanisms of Sal B cardiovascular protection, focusing on six aspects: antioxidant effect, anti-inflammatory activity, endothelial protective function, antifibrotic properties, inhibition of platelet aggregation and cardiomyocyte protection. This review also highlights advances over the past five years. It not only covers the discovery of new targets and new pathways (such as THBS1, Piezo1, p300); Innovative strategies to overcome its pharmacokinetic deficiencies were also discussed, including the development of advanced drug delivery systems such as responsive microspheres, dissolving microneedles, and biomimetic nanoparticles. This article aims to provide valuable reference for subsequent research by integrating these latest research results, and offers novel insights that can advancing the treatment development of Sal B for cardiovascular diseases.
Yao-Long Han, Huiyu Wang, Sujuan Ding et al.· Journal of Agricultural and...· 2 citations