ArticlePloS one2014
Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 147 citations in OpenAlex.
- Absorption Kinetics of Berberine and Dihydroberberine and Their Impact on Glycemia: A Randomized, Controlled, Crossover Pilot Trial.Nutrients · 2021Trial
- Safety evaluation of a new anxiolytic product containing botanicalsCanadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2018Trial
- The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level.International journal of molecular sciences · 2026Review
- Mitochondrial Health Through Nicotinamide Riboside and Berberine: Shared Pathways and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Nano-Encapsulated Berberine Is a Potential Therapeutic Agent for Adipose Tissue Browning in C57BL/6J Mice.Medicina (Kaunas, Lithuania) · 2025Article
- Phytochemical Profile, Vasodilatory and Biphasic Effects on Intestinal Motility, and Toxicological Evaluation of the Methanol and Dichloromethane Extracts from the Aerial Parts ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Phytochemical-based nanosystems: recent advances and emerging application in antiviral photodynamic therapy.Nanomedicine (London, England) · 2025Review
- Betulinic acid and obesity-related disorders.Frontiers in pharmacology · 2025Review
- The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential.Pharmaceutics · 2024Review
- Research progress on pharmacological effects and bioavailability of berberine.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Bioactive Compounds Formulated in Phytosomes Administered as Complementary Therapy for Metabolic Disorders.International journal of molecular sciences · 2024Review
- Advances in the pharmacological mechanisms of berberine in the treatment of fibrosis.Frontiers in pharmacology · 2024Review
- Optimization of Functional Toothpaste Formulation Containing Nano-Hydroxyapatite and Birch Extract for Daily Oral Care.Materials (Basel, Switzerland) · 2023Article
- The Impact of Berberine Loaded Selenium Nanoparticles onArchives of Razi Institute · 2023Article
- Effects of Betulinic Acid on the Proliferation, Cellular Senescence, and Type 1 Interferon-Related Signaling Pathways in Human Dermal Fibroblasts.Journal of agricultural and food chemistry · 2023Article
- Isolation, Physicochemical Characterization, and Biological Properties of Inotodiol, the Potent Pharmaceutical Oxysterol from Chaga Mushroom.Antioxidants (Basel, Switzerland) · 2023Article
- Trained immunity in monocyte/macrophage: Novel mechanism of phytochemicals in the treatment of atherosclerotic cardiovascular disease.Frontiers in pharmacology · 2023Review
- Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis.Molecules (Basel, Switzerland) · 2022Review
- The Anti-Melanoma Effect of Betulinic Acid Functionalized Gold Nanoparticles: A Mechanistic In Vitro Approach.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe poor bioavailability of Berberine (BBR) and Betulinic acid (BA) limits the development of these promising anticancer agents for clinical use. In the current study, BBR and BA in spray dried (SD) mucoadhesive microparticle formulations were prepared.
methodsA patented dual channel spray gun technology established in our laboratory was used for both formulations. Gastrointestinal (GI) permeability studies were carried out using Caco-2 cell monolayer grown in in-vitro system. The oral bioavailability and pharmacokinetic profile of SD formulations were studied in Sprague Dawley rats. A549 orthotopic and H1650 metastatic NSCLC models were utilized for the anticancer evaluations.
resultsPharmacokinetic studies demonstrated that BBR and BA SD formulations resulted in 3.46 and 3.90 fold respectively, significant increase in plasma Cmax concentrations. AUC levels were increased by 6.98 and 7.41 fold in BBR and BA SD formulations, respectively. Compared to untreated controls groups, 49.8 & 53.4% decrease in the tumor volumes was observed in SD formulation groups of BBR and BA, respectively. Molecular studies done on excised tumor (A549) tissue suggested that BBR in SD form resulted in a significant decrease in the survivin, Bcl-2, cyclin D1, MMP-9, HIF-1α, VEGF and CD31 expressions. Cleaved caspase 3, p53 and TUNEL expressions were increased in SD formulations. The RT-PCR analysis on H1650 tumor tissue suggested that p38, Phospho-JNK, Bax, BAD, cleaved caspase 3&8 mRNA expressions were significantly increased in BA SD formulations. Chronic administration of BBR and BA SD formulations did not show any toxicity.
conclusionsDue to significant increase in oral bioavailability and superior anticancer effects, our results suggest that spray drying is a superior alternative formulation approach for oral delivery of BBR and BA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.