Open research questions in Natural product bioactivities and synthesis
148 gap statements mined from Natural product bioactivities and synthesis papers in our 4.5M-paper local library, which holds 582 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
There is a need to understand the mechanisms of oxidative stress in carcinogenesis. The current knowledge on the dual role of reactive oxygen species and reactive nitrogen species in cancer processes is not systematized. Effective prevention and therapy strategies for cancer are needed.
Targeting Oxidative Stress in Carcinogenesis: Oleanolic Acid and Its Molecular Pathways · 2026 · DOIThe urgent need to optimize perioperative evaluation systems. The need to identify the potential binding target of Platycodin D.
Multidimensional Proteomics Reveals the Pro-apoptotic Mechanism of Platycodin D: Targeting RFC4 to Regulate the Notch Signaling Axis in Non-Small Cell Lung Cancer · 2026 · DOIThe need to reduce the environmental impact of forestry activities and transition towards a circular and sustainable economy.
Optimized ultrasound-assisted extraction of betulin from Betula pendula bark: a sustainable approach to forest residue valorization · 2026 · DOIThe poor water solubility and low bioavailability of oleanolic acid are challenges that need to be addressed. Oxidative stress is a challenge that oleanolic acid has the potential to prevent. The development of effective drug delivery systems for oleanolic acid is a challenge.
Oleanolic Acid: A Promising Antioxidant—Sources, Mechanisms of Action, Therapeutic Potential, and Enhancement of Bioactivity · 2025 · DOIMore in-depth studies are needed to fully understand the potential of phenolic chemicals from I. rotunda as pharmacological products. Further research should investigate the effects of these compounds on oxidative stress and immune response in different contexts.
Phenolics from Ilex rotunda Possess Antioxidative Effects and Block Activation of MAPK and NF-κB Signaling by Inhibiting IL-2 Production in CD3/CD28 Activated Jurkat T Cells · 2025 · DOIThe limited clinical application of Kunzea ericoides oil due to poor solubility, instability, and inadequate skin penetration. The need for a safe and effective transdermal therapy for managing inflammatory and dermatological conditions.
Development and Optimization of Kunzea ericoides Nanoemulgel Using a Quality by Design Approach for Transdermal Anti-Inflammatory Therapy · 2025 · DOIThe lack of understanding of the active ingredients, potential targets, and mechanisms of action of peppermint in treating bovine mastitis. The need for alternative treatments for bovine mastitis, as current treatments have limitations.
Network Pharmacology and Molecular Docking: Exploring the Mechanism of Peppermint in Mastitis Prevention and Treatment in Dairy Cows · 2025 · DOIThe lack of understanding of the histochemical characteristics of the submandibular gland of Bactrian camels. The need for characterization of the gland's composition and the distribution of EGF and EGFR.
However, a comprehensive review that systematically summarizes the antitumor potential of DY and its bioactive constituents is still lacking.
Therapeutic Potential of Ziyuglycosides from Sanguisorba officinalis: Anticancer and Immunomodulatory Properties · 2026 · DOIIn conclusion, schaftoside is a promising bioactive compound; however, its pharmacokinetic properties and available clinical evidence need to be further investigated.
Advances in Schaftoside Research: Pharmacological Mechanisms, Pharmacokinetics, and Therapeutic Perspectives · 2026 · DOIDespite this, UA has not been recognized as a pivotal component during Prunella vulgaris evaluation, and its specific anticancer mechanism remains elusive.
Ursolic acid, a key anticancer compound derived from Prunella vulgaris L., induces apoptosis in HepG2 cells by directly targeting the STAT3 signaling pathway · 2025 · DOIInterpretation is limited by the absence of raw chromatograms, replicate injection tables, peak purity data, exact LOD/LOQ calculation worksheets, and inferential statistical analysis.
HIGH -PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE METHOD DEVELOPMENT OF URSOLIC ACID AND MOMETASON FUROATE: DEVELOPMENT AND VALIDATION · 2026 · DOIThe lack of effective oral delivery systems for antiparasitic triterpenic compounds. The need for improved solubility and oral bioavailability of these compounds.
Antiparasitic triterpenic ester and ursolic acid lipid nanocapsule design, cytotoxicity, and permeability evaluation for oral delivery · 2026 · DOIThere is a need to understand the mechanisms by which bioactive compounds influence greenhouse gas production and carbon storage. There is a need to identify various bioactive compounds with potential to reduce emissions and enhance carbon sequestration.
Some effective components are not fully extracted, leading to significant resource waste.
Multi-Omics Unveils Inflammatory Regulation of Fermented Sini Decoction Dregs in Broilers Infected with Avian Pathogenic Escherichia coli · 2025 · DOISeveral limitations are associated with SMEDDS formulations, including in vivo drug precipitation, challenges in formulation handling, limited lymphatic uptake, absence of reliable predictive in vitro models, and the susceptibility of unsaturated fatty acids…
Targeting Oxidative Stress in Carcinogenesis: Oleanolic Acid and Its Molecular Pathways · 2026 · DOIMost studies investigating GR remain limited to in vitro assays and preclinical models not specifically related to oral diseases, - The heterogeneity of extraction methods, tested concentrations, and experimental models further limits comparison between studies, - Part of the evidence derives from studies on individual bioactive constituents identified in GR and cannot be extrapolated to the plant…
Geranium robertianum L. in Oral Health: From Phytochemical Profile to Therapeutic Potential · 2026 · DOIClinical and disease-specific experimental models are needed to strengthen the evidence, - Further research is required to confirm the potential relevance of GR in the management of oral diseases, - Investigation of plant-based remedies with antiviral potential is currently…
Geranium robertianum L. in Oral Health: From Phytochemical Profile to Therapeutic Potential · 2026 · DOIThe statistical power was limited by the scarcity of normal tissue, - The study focused on the identification of target proteins with potential binding…
Multidimensional Proteomics Reveals the Pro-apoptotic Mechanism of Platycodin D: Targeting RFC4 to Regulate the Notch Signaling Axis in Non-Small Cell Lung Cancer · 2026 · DOIFurther research could be done to optimize the extraction process for other types of tree bark, - the study could be expanded to include other variables, - the antioxidant capacity of the extracts could be further…
Optimized ultrasound-assisted extraction of betulin from Betula pendula bark: a sustainable approach to forest residue valorization · 2026 · DOIOA's poor water solubility and low bioavailability limit its pharmacological applications, - the structure of the intestinal microbiota was not significantly affected by OA, - the study on mice was conducted for a limited time…
Oleanolic Acid: A Promising Antioxidant—Sources, Mechanisms of Action, Therapeutic Potential, and Enhancement of Bioactivity · 2025 · DOIThe study identifies a gap in the understanding of the antioxidative effects of phenolic compounds from Ilex rotunda. The study identifies a gap in the understanding of the ability of these compounds to block activation of MAPK and NF-κB signaling by inhibiting IL-2 production in CD3/CD28 activated Jurkat T cells.
Phenolics from Ilex rotunda Possess Antioxidative Effects and Block Activation of MAPK and NF-κB Signaling by Inhibiting IL-2 Production in CD3/CD28 Activated Jurkat T Cells · 2025 · DOIResearch on innovative extraction methods, - Use of compatible vehicles for delivery, - Development of improved (nano)formulations for therapeutic compounds…
Mechanistic Insights into the Metabolic Pathways and Neuroprotective Potential of Pentacyclic Triterpenoids: In-Depth Analysis of Betulin, Betulinic, and Ursolic Acids · 2025 · DOIFurther studies on the mechanisms of fermented liquid of Sini decoction dregs, - Investigation of other potential applications of fermented liquid of Sini decoction dregs, - Optimization of the extraction process of active ingredients in TCM…
Multi-Omics Unveils Inflammatory Regulation of Fermented Sini Decoction Dregs in Broilers Infected with Avian Pathogenic Escherichia coli · 2025 · DOIIn vivo pharmacokinetic and efficacy studies to confirm the therapeutic potential. Further evaluation of the cytotoxicity and permeability of the formulations.
Antiparasitic triterpenic ester and ursolic acid lipid nanocapsule design, cytotoxicity, and permeability evaluation for oral delivery · 2026 · DOI
Most-cited papers in Natural product bioactivities and synthesis
- Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents · Molecules · 2022 · 545 citations
- Oleanolic Acid: Extraction, Characterization and Biological Activity · Nutrients · 2022 · 288 citations
- Therapeutic Potential of Certain Terpenoids as Anticancer Agents: A Scoping Review · Cancers · 2022 · 239 citations
- Plasminogen activator inhibitor in the blood of patients with coronary artery disease. · BMJ · 1985 · 226 citations
- Plant-Derived Saponins: A Review of Their Surfactant Properties and Applications · Sci · 2021 · 174 citations
- Tedizolid: A Novel Oxazolidinone with Potent Activity Against Multidrug-Resistant Gram-Positive Pathogens · Drugs · 2015 · 168 citations
- Biologically active pentacyclic triterpenes and their current medicine signification · Journal of Applied Biomedicine · 2003 · 167 citations
- In vivo and in vitro antiviral activity of hyperoside extracted from Abelmoschus manihot (L) medik · Acta Pharmacologica Sinica · 2007 · 101 citations
- Ethyl glucuronide · Alcohol · 2000 · 88 citations
- Progress in approved drugs from natural product resources · Chinese Journal of Natural Medicines · 2024 · 85 citations
Most recent work
- Comparative metabolomics identifies enhanced ursane-type triterpenoids and antioxidant capacity in Actinidia arguta ‘Danyang’ kiwifruit · Frontiers in Plant Science · 2026
- Targeting methicillin-susceptible and -resistant Staphylococcus aureus: Design, synthesis, and antibacterial profiling of novel beddomeilactone amides · Bioorganic Chemistry · 2026
- Targeting Oxidative Stress in Carcinogenesis: Oleanolic Acid and Its Molecular Pathways · Antioxidants · 2026
- Natural inhibitors of PTP1B: Caffeic acid, cinnamic acid, and cinnamaldehyde as promising agents against triple-negative breast cancer · Biomedicine & Pharmacotherapy · 2026
- Optimized ultrasound-assisted extraction of betulin from Betula pendula bark: a sustainable approach to forest residue valorization · Wood Science and Technology · 2026
- Antioxidant and selective cytotoxic activity of Dipterocarpus obtusifolius flower extract against gastrointestinal cancer, with bioactive component profiling · BMC Complementary Medicine and Therapies · 2026
- Recent Advances in the Development of Selected Triterpenoid-Based Hybrid Molecules and Their Antimicrobial Activities: A Review · Antibiotics · 2026
- Recent advances in dietary saponins stabilization: A review on technologies and applications · Trends in Food Science & Technology · 2026
- Ultrasound-assisted extraction of total saponins from wild bitter melon (Momordica charantia L. var. abbreviata Ser.) with response surface methodology and kinetic analysis · Applied Food Research · 2026
- Multilevel Residual Complexity Analysis Reveals Origin of Nanomolar Antiviral Bioactives of “Isoquercitrin” · Journal of Natural Products · 2026
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