Open research questions in Berberine and alkaloids research
99 unresolved questions extracted from the limitations and future-work sections of 193 Berberine and alkaloids research papers in our library. Each links back to the study that raised it.
What the literature leaves open
The study identifies methodological limitations of the included studies, including inadequate reporting of randomization methods and allocation concealment. The study notes that the available preclinical evidence has not been systematically quantified, making it difficult to draw firm conclusions. The study highlights the need for more rigorous and standardized experimental designs to strengthen the evidence base and validate the therapeutic potential of sinomenine.
Neuroprotective effects and mechanistic insights of sinomenine in ischemic stroke: a systematic review and meta-analysis of preclinical animal studies · 2026 · DOIMethodological limitations of the included studies, - Inadequate reporting of important methodological details, - Lack of standardized experimental designs, - Small sample sizes, - Limited generalizability to human populations
Neuroprotective effects and mechanistic insights of sinomenine in ischemic stroke: a systematic review and meta-analysis of preclinical animal studies · 2026 · DOIThe discovery and processing of plant-based medicinal products face numerous challenges, - Access restrictions, difficulties in material identification, and the conservation of wild species are challenges, - The precise mechanisms of action of berberine remain incompletely elucidated
Pharmacological properties and therapeutic potential of berberine: a comprehensive review · 2025 · DOIFurther systematic investigation of berberine's mechanisms of action is needed, - Clinical implementation of berberine for various diseases should be explored, - The effects of berberine on different populations and diseases should be studied
Pharmacological properties and therapeutic potential of berberine: a comprehensive review · 2025 · DOIThese findings support further investigation of plant secondary metabolites as potential adjuvants to anticancer therapy.
Antiproliferative effects of berberine, corinan and curcumo-berberine on RPMI8226 multiple myeloma cells and their interaction with vincristine · 2026 · DOIImportance: Berberine is a potential therapy for metabolic disorders, yet its effects on visceral adipose tissue (VAT) and liver fat remain uncertain.
However, the pharmacological mechanism of action of BBR in anti-chronic atrophic gastritis (CAG) remains unclear.
Elucidation of the mechanism of berberine against gastric mucosa injury in a rat model with chronic atrophic gastritis based on a combined strategy of multi-omics and molecular biology · 2025 · DOIHowever, its exact role in regulating autophagy and alleviating atherosclerotic inflammation remains unclear.
Berberine alleviates atherosclerosis by modulating autophagy and inflammation through the RAGE-NF-κB pathway · 2025 · DOIMost BIAs are derived and isolated from medicinal plants; however, these plants are predominantly wild resources that are scarce.
Numerous transcription factors have been shown to be involved in vinblastine biosynthesis, while the function of SPL members (CrSPL) has not yet been investigated in C.
Comprehensive analysis of SPL gene family and miR156a/SPLs in the regulation of terpenoid indole alkaloid biosynthesis in Catharanthus roseus L · 2025 · DOIThis combination warrants further exploration as a therapeutic strategy against resistant infections.
The in vitro evaluation of synergistic effects of ciprofloxacin and berberine hydrochloride against Pseudomonas aeruginosa · 2025 · DOITo date, no studies have examined the effects of berberine on acute hyperglycemia.
Berberine ameliorates acute hyperglycemia and hypoinsulinemia induced by ketamine/xylazine in rats: role of alpha2 adrenergic receptors, oxidative stress and inflammatory suppressing mechanisms · 2025 · DOIIn comparison with its known pathway in Coptis species, its biosynthesis in Phellodendron species remains elusive.
Previous studies have demonstrated the beneficial therapeutic effect of berberine (BBR) on SCM; however, the underlying mechanisms of action remain unclear.
Berberine ameliorates septic cardiomyopathy through protecting mitochondria and upregulating Notch1 signaling in cardiomyocytes · 2024 · DOIHowever, the evolutionary mechanisms responsible for their chemo-diversity are not well understood.
Lineage‐Specific CYP80 Expansion and Benzylisoquinoline Alkaloid Diversity in Early‐Diverging Eudicots · 2024 · DOIHowever, the mechanisms by which BBR regulates the immunological microenvironment in HCC has not been fully elucidated.
Berberine Protects against Hepatocellular Carcinoma Progression by Regulating Intrahepatic T Cell Heterogeneity · 2024 · DOIBerberine, a natural isoquinoline alkaloid, has demonstrated broad-spectrum antimicrobial activity, though its antifungal potential and underlying mechanisms against both yeast-like and filamentous fungi are not fully understood.
The Antifungal Effects of Berberine and Its Proposed Mechanism of Action Through CYP51 Inhibition, as Predicted by Molecular Docking and Binding Analysis · 2024 · DOIThe natural product, sanguinarine, displays remarkable anti-tumor properties by disturbing energy homeostasis; however, the underlying mechanism has not yet been elucidated.
Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported.
Comparative Effects of Gymnema sylvestre and Berberine on Adipokines, Body Composition, and Metabolic Parameters in Obese Patients: A Randomized Study · 2024 · DOIThe phytochemical composition and antidiabetic potential of Dactylicapnos scandens root tuber have not been fully explored. There is a need to identify novel antidiabetic therapeutics from plant sources.
Phytochemical profiling and antidiabetic potential of Dactylicapnos scandens root tuber using LC-MS, GC-MS and molecular docking · 2026 · DOIThe complexity of the gut microbiota-glycerophospholipid metabolic axis. The need for effective methods to evaluate the skeletal benefits of Berberine. The challenge of translating the findings from animal models to human applications.
Berberine Attenuates Glucocorticoid-Induced Bone Loss in Mice: Associated with the Gut Microbiota–Glycerophospholipid Metabolic Axis · 2026 · DOIinvestigate the long-term effects of BBR on bone health, - investigate the effects of BBR on human subjects, - explore the potential of BBR as a therapeutic agent for glucocorticoid-induced osteoporosis
Berberine Attenuates Glucocorticoid-Induced Bone Loss in Mice: Associated with the Gut Microbiota–Glycerophospholipid Metabolic Axis · 2026 · DOIThe lack of effective therapeutic agents for oral squamous cell carcinoma. The need for further studies on the anticancer potential of traditional Ayurvedic formulations.
Integrative in vitro and in silico assessment of the anticancer activity of Berberis aristata formulation against oral squamous cell carcinoma · 2026 · DOIPoor oral bioavailability due to berberine's permanent positive charge, limited membrane permeability, and extensive first-pass metabolism. The need for further pharmacokinetic optimization and clinical validation. The complexity of berberine's molecular mechanisms and the need for further research.
Berberine and its structural diversity: structure–activity relationships, molecular mechanisms, and drug discovery opportunities · 2026 · DOIThe need for further pharmacokinetic optimization and clinical validation of berberine. The lack of understanding of berberine's molecular mechanisms and structure-activity relationships. The need for the development of berberine derivatives with improved pharmacokinetic properties.
Berberine and its structural diversity: structure–activity relationships, molecular mechanisms, and drug discovery opportunities · 2026 · DOI
Most-cited papers in Berberine and alkaloids research
- The metabolism of berberine and its contribution to the pharmacological effects · Drug Metabolism Reviews · 2017 · 447 citations
- Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system · Acta Pharmacologica Sinica · 2016 · 288 citations
- Inhibition of inflammation by berberine: Molecular mechanism and network pharmacology analysis · Phytomedicine · 2024 · 235 citations
- Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress · Acta Pharmacologica Sinica · 2016 · 136 citations
- Berberine attenuates ischemia–reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation · Acta Pharmacologica Sinica · 2018 · 129 citations
- Understanding Diversity Blind Spots in the Performance Review. · CUPA journal · 1993 · 102 citations
- Set9, NF-κB, and microRNA-21 mediate berberine-induced apoptosis of human multiple myeloma cells · Acta Pharmacologica Sinica · 2012 · 94 citations
- Antiangiogenic activity of berberine is mediated through the downregulation of hypoxia-inducible factor-1, VEGF, and proinflammatory mediators · Drug and Chemical Toxicology · 2011 · 88 citations
- Clinical trial of berberine in acute watery diarrhoea. · BMJ · 1985 · 73 citations
- Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation · Acta Pharmacologica Sinica · 2021 · 67 citations
Most recent work
- Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD · JAMA Network Open · 2026
- Berberine as a Multifunctional Adjuvant in Cancer Therapy: Mechanistic Insights, Nanotechnological Strategies, and Translational Challenges · Pharmaceuticals · 2026
- Targeting peripheral 5-HT2AR enhances antitumor immunity in colorectal cancer · Cell · 2026
- Effects of dietary berberine hydrochloride on growth, immunity, meat quality, and fecal microbiota in broiler chickens · Frontiers in Veterinary Science · 2026
- Unique Thiazolidinedione Conjugation of Metronidazole to Largely Enhance the Antibacterial Performance of Natural Berberine against Bacterial Pathogens · Journal of Medicinal Chemistry · 2026
- The Application of Iron Nanoparticles Green‐Synthesized by Coptis chinensis Leaf Aqueous Extract in Reducing the TNF ‐α and IL1 ‐β Inflammatory Cytokines in the Rat Periodontal Model · Food Science & Nutrition · 2026
- Drug Repurposing Potential of Natural Products: Molecular Targets, Pharmacological Profiles, and Precision Therapeutic Strategies: A Narrative Review · Journal of Biomolecules, Pathogenesis and Therapeutics · 2026
- An oral berberine nanocapsule platform orchestrates microbiota for potent gastric cancer chemotherapy · Journal of Nanobiotechnology · 2026
- Berberine alleviates experimental colitis by enhancing gut-microbiota-dependent intestinal barrier function and suppressing gasdermin D activation · World Journal of Gastroenterology · 2026
- Phytochemical profiling and antidiabetic potential of Dactylicapnos scandens root tuber using LC-MS, GC-MS and molecular docking · Plant Science Today · 2026
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