oleandrin (PBI-05204) / Phoenix Biotech - LARVOL DELTA

RNF6 activates the AKT/mTOR signaling pathway by inhibiting PTEN via K27-linked polyubiquitination in myeloma. (PubMed, Acta Pharmacol Sin) - "Lastly, we discovered that oleandrin, a natural product, induces K48-linked polyubiquitination of RNF6 and subsequent degradation, thereby suppressing PTEN with K27-linked polyubiquitination and the AKT/mTOR signaling pathway. In conclusion, the study identifies RNF6 and USP39 as novel ubiquitin ligases or deubiquitinases responsible for K27-linked polyubiquitination of PTEN and as novel modulators of the AKT/mTOR pathway. Targeting the RNF6/PTEN/AKT/mTOR signaling axis might represent a novel therapeutic strategy for myeloma treatment."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • PTEN • RNF6

Determination of 13 prohibited alkaloids in essential oil-based cosmetics by ultra performance liquid chromatography-tandem mass spectrometry combining QuEChERS purification (PubMed, Se Pu) - "A particularly notable accomplishment of this work is the successful development of a sensitive and reliable quantification strategy for oleandrin， a potent cardiotoxic alkaloid for which standardized detection methods in complex cosmetic matrices such as essential oils have been conspicuously absent...It is comprehensively validated and clearly well-suited for the routine screening， risk monitoring， and quality control of 13 prohibited alkaloids in a wide array of essential oil-based cosmetics. The method offers reliable technical support for regulatory bodies to enforce safety standards and for manufacturers to ensure the safety and compliance of their products， thereby effectively contributing to the protection of consumer health."

Journal

Oleandrin Suppresses the PI3K/AKT Pathway to Inhibit Growth and Induce Apoptosis in T-cell Acute Lymphoblastic Leukemia Cells and Xenograft Mice. (PubMed, Planta Med) - "Integrated mechanistic studies, including network pharmacology, transcriptomics, and Western blot analysis, indicated that the anti-leukemic effects of oleandrin are associated with suppression of the PI3K/AKT signaling pathway, as evidenced by reduced levels of key proteins such as PIK3CA, phosphorylated AKT (p-AKT), phosphorylated GSK3β (p-GSK3β), c-Myc, Bcl-2, and Bcl-xL. These findings suggest oleandrin is a promising therapeutic candidate for T-ALL, likely through suppression of the PI3K/AKT pathway."

Journal • Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2 • BCL2L1 • MYC • PIK3CA

Dose-response assessment of neuroactive botanical extracts and their bioactive constituents using microelectrode array (MEA) recordings in rat primary cortical cultures. (PubMed, Pharm Biol) - "Silybin B (milk thistle), epigallocatechin gallate (green tea), yohimbine (yohimbe), dihydrokavain (kava), mitragynine (kratom), aconitine (aconite), berberine (goldenseal) and oleandrin (oleander) were tested to investigate if the distinct neuronal activity phenotypes, indicative for the presence of multiple modes of action, are due to the known bioactive constituents of the extracts. For most constituents the activity phenotype is comparable to the extract, although the extract generally has a higher potency. Botanical extracts and constituents evoke diverse activity phenotypes, highlighting the complexity of hazard characterization of botanicals."

Journal • Preclinical • Ophthalmology

Elaeodendron buchananii (Loes.) Loes. stem bark: Unveiling the phytochemical profiles and selective bioactivity to combat tongue cancer. (PubMed, Arch Oral Biol) - "The findings demonstrate that EB possesses selective cytotoxicity toward tongue carcinoma cells and exhibits significant anti-inflammatory effects. These findings support its traditional medical application and point to its potential for additional phytopharmaceutical development. This report is the first to explore the in vitro cytotoxic effects of E. buchananii on tongue cancer cells."

Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • Tongue Carcinoma

Differentially Altered Phytochemical Composition Contributes to the Pharmaco-Toxicological Conundrum of Oleander. (PubMed, Toxicon) - "Diverse metabolic pathways, such as phenylpropanoid production, differed among extracts. In conclusion, the polar extracts of red oleander present a significant risk of toxicity due to high oleandrin levels, and safer alternatives include non-polar extracts from white oleander."

Journal • Diabetes • Hepatology • Metabolic Disorders

Case Report: Oleandrin intoxication by inhalation in beef cattle. (PubMed, Front Vet Sci) - "The remaining two animals, which survived the hyperacute phase, later died due to secondary oleandrin intoxication via ingestion, which aggravated their pre-existing health conditions. To the best of the authors' knowledge, this case represents the first reported instance of inhalation intoxication by oleander in cattle."

Journal • CNS Disorders • Depression • Hematological Disorders • Myositis • Psychiatry • Pulmonary Disease • Respiratory Diseases

Oleandrin-mediated suppression of MELK induces apoptosis, autophagy, and ferroptosis in human non-small cell lung cancer cells. (PubMed, Phytomedicine) - "Oleandrin could potentially have therapeutic effects for NSCLC patients and possibly for other cancer types."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MELK

Development of CPA-Catalyzed β-Selective Reductive Amination of Cardenolides for the Synthesis and Biological Evaluation of Hydrolytically Stable Analogs. (PubMed, Chemistry) - "The subsequent in vitro evaluation of digitoxigenin and oleandrin derivatives 13a, 13g, 15a, and 15gdemonstrated that these four analogs reduced steady-state ATP1A1 levels in T98G cells in the 12-96 nM range. Interestingly, only the oleandrin analog 15g also lowered also steady-state levels of the cellular prion protein (PrPC), the main therapeutic target for the treatment of prion diseases."

Journal • CNS Disorders • Oncology • ATP1A1 • PRNP

Oleandrin Promotes Apoptosis in an Autophagy-Dependent Manner in Gastric Cancer. (PubMed, Front Biosci (Landmark Ed)) - "Ole may trigger apoptosis through the activation of autophagy in GC. It offers a secure and efficacious candidate drug for the treatment of tumors in the digestive system."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Overexpression of DWF1 Enhances Low-Nitrogen Stress Tolerance in Potato Plants. (PubMed, Int J Mol Sci) - "Hormone analyses showed that BL content of StDWF1 overexpression lines was significantly increased under LN conditions, higher Oleandrin lactone (BL) content of OE2 improved plant stress tolerance, and WT was more affected by low nitrogen stress than OE2, resulting in higher levels of stress hormones than OE2. Temporal gene expression analysis showed significant upregulation of key nitrogen metabolism-related genes (NR, NiR, AT, NRT2.1) in OE2, with StDWF1 expression reaching 79% higher than WT at 3 h. Protein-protein interaction assays, including yeast two-hybrid and BiLC assays, verified the interaction between StDWF1 and StGRP1, suggesting the existence of a functional network to enhance low-nitrogen tolerance in potato plants. In conclusion, these findings suggest that overexpression of StDWF1 significantly enhances low-nitrogen tolerance in transgenic potato lines, providing a promising strategy for improving crop performance under nitrogen-limited conditions."

Journal

Identification of Active Phytochemicals to Inhibit Signal Transducer and Activator of Transcription 5A (STAT5A) Dimerization for Prostate Cancer Therapy: An In Silico Approach. (PubMed, Anticancer Agents Med Chem) - "Pedunculagin demonstrated the strongest binding energy and stability, making it a promising candidate for further development as a novel lead compound to disrupt STAT5a/b dimerization in PCa therapy."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STAT5 • STAT5AWqe

Human Deaths Related to Oleander Poisoning: A Review of the Literature. (PubMed, Toxins (Basel)) - "Oleander contains potent cardiac glycosides, such as oleandrin and thevetin, which exert powerful effects on the cardiovascular system, leading to symptoms ranging from nausea and abdominal pain to severe arrhythmias and sudden cardiac death...While supportive care, gastric decontamination, and the administration of digoxin-specific Fab antibody fragments (Digifab) are essential therapeutic measures, limited access to Digifab, delays in intervention, and insufficient supportive care practices remain significant complicating factors...Additionally, this review highlights the socio-cultural dimensions of oleander ingestion, often linked to intentional self-poisoning, and emphasizes the need for enhanced preventive measures and public education. Future research efforts should prioritize addressing these gaps through autopsy-based studies and the development of more accessible and effective antidotes, which are essential to mitigate the global health burden of..."

Journal • Review • Cardiovascular • Pain

Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect. (PubMed, J Physiol Sci) - "Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Carcinoma

Oleandrin inhibits osteoclast differentiation by targeting the LRP4/MAPK/NF-κB signalling pathway to treat osteoporosis. (PubMed, Int Immunopharmacol) - "Further mechanistic studies showed that Oleandrin binds to low-density lipoprotein receptor-related protein 4 in osteoclast, thereby exerting inhibitory effects on osteoclast differentiation. In conclusion, this study lays the foundation for further research on the anti-inflammatory and anti-osteoporotic effects of Oleandrin on osteoporosis and its underlying mechanism and provides new possibilities for the treatment of osteoporosis."

Journal • Dyslipidemia • Inflammation • Osteoporosis • Rheumatology • LRP4

Oleander poisoning: report of three cases (EUSEM 2024) - "The symptoms of oleander poisoning are similar to those of digitalis poisoning due to the presence of cardenolide heterosides, particularly oleandrin, in all parts of the plant. The symptoms of oleander poisoning are similar to those caused by digoxin. Treatment is essentially symptomatic; specific treatment with anti-digoxin antibodies may be proposed but is not available in Tunisia."

Clinical • Cardiovascular

Digoxin and its Na+/K+-ATPase-targeted actions on cardiovascular diseases and cancer. (PubMed, Bioorg Med Chem) - "Presented herein are also the antitumor potential of monosaccharide cardiac glycoside analogues of digoxin, including (-)-cryptanoside A, (-)-oleandrin, (-)-ouabain, and (+)-strebloside. It is hoped that this contribution will provide some helpful information for the design and discovery of new cardiac glycoside-type therapeutic agents for the treatment of cardiovascular diseases and cancer."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Oncology • HIF1A

Botanical oleander extract and oleandrin have superior effects on innate immune functions pertaining to dermal allergic reactions in canine cells when compared to oclacitinib. (PubMed, Am J Vet Res) - "These results suggest that OE and oleandrin are efficacious agents to treat canine atopic dermatitis. Future studies should evaluate the efficacy of these compounds in dogs affected by atopic dermatitis."

Journal • Allergy • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Oncology • Pruritus • CCL2 • CXCL8 • IFNG • IL12A • IL6 • TGFB1 • TNFA

Update on a brain-penetrant cardiac glycoside that can lower cellular prion protein levels in human and guinea pig paradigms. (PubMed, PLoS One) - "Regrettably, when administered systemically in vivo, the levels of C4'-dehydro-oleandrin that reached the guinea pig brain remained insufficient for the PrPC lowering effect to manifest. A more suitable preclinical model is still needed to determine if C4'-dehydro-oleandrin can offer a cost-effective complementary strategy for pushing PrPC levels below a threshold required for long-term prion disease survival."

Journal • CNS Disorders • PRNP

Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19. (PubMed, Cell Biosci) - "Our findings validate GRP78 as a target of OLN anti-cancer and anti-viral activities. These proof-of-principle studies support further investigation of OLN as a readily accessible compound to dually combat cancer and COVID-19."

Journal • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor • Targeted Protein Degradation • HSPA5

Oleandrin enhances radiotherapy sensitivity in lung cancer by inhibiting the ATM/ATR-mediated DNA damage response. (PubMed, Phytother Res) - "The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants."

Journal • Lung Cancer • Oncology • Solid Tumor • Transplantation • CHEK1 • CHEK2

Evaluation of the Activity of Cardiac Glycosides on RORγ and RORγT Nuclear Receptors. (PubMed, Arch Biochem Biophys) - "Subsequently, the effects of two endogenous cardiac glycosides (marinobufagenin and ouabain) and the three most potent glycosides (bufalin, oleandrin, and telecinobufagenin) were evaluated in Th17 primary lymphocytes...Thus, we demonstrated that at nontoxic concentrations, cardiac glycosides have agonistic effects on RORγ/RORγT nuclear receptors, augmenting their activity. This potential can be harnessed to modulate the phenotype of IL17-expressing cells (e.g., Th17 or Tc17 lymphocytes) in adoptive therapy for combating various types of cancer."

Journal • Oncology • CCL20 • CXCL10 • GZMB • IFNG • IL17A

PBI-05204, a supercritical CO2 extract of Nerium oleander, suppresses glioblastoma stem cells by inhibiting GRP78 and inducing programmed necroptotic cell death. (PubMed, Neoplasia) - "Furthermore, oleandrin, a principle active cardiac glycoside component of PBI-05204, showed the ability to inhibit the self-renewal capacity in GSCs. These findings highlight the potential of PBI-05204 as a promising candidate for the development of novel therapies that target GBM stem cells."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD44 • HSPA5 • NANOG • RIPK1

Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect. (PubMed, J Physiol Sci) - "Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Carcinoma

Identification of Hub Genes and Pathways of Middle Cerebral Artery Occlusion in Aged Rats Using the Gene Expression Omnibus Database. (PubMed, Crit Rev Immunol) - "Among these 30 compounds, resveratrol, cannabidiol, honokiol, fucoxanthin, oleandrin and tyrosol were significantly enriched...Our study indicates that multiple genes and pathological processes involved in the aged people of stroke. The immune response might be the key pathway in the intervention of cerebral infarction in aged people."

Journal • Preclinical • Cardiovascular • CNS Disorders • GPNMB • IL17A • KLF4 • LGALS3 • NR4A1 • NR4A3 • SPP1