Hesperidin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Hesperidin: From Venous Disease (Licensed Use) to Myeloproliferative Neoplasm
One-Sentence Summary
Hesperidin is a citrus flavonoid marketed in Singapore as oral tablets, and the approved indication text is not recorded in the data compiled for this report. The TxGNN model predicts it may be effective for myeloproliferative neoplasm (score 99.47%), but there are 0 clinical trials and only 1 in silico publication supporting this indication. This is a model prediction only; the best-supported alternative is myeloid leukemia (preclinical evidence only).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the data compiled for this report (all 6 licenses have empty indication text) |
| Predicted New Indication | Myeloproliferative neoplasm |
| TxGNN Prediction Score | 99.47% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 6 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Hesperidin is a polyphenol flavanone glycoside (hesperetin-7-rutinoside) sold as a single-ingredient oral tablet. Its original approved indication is not available in the data compiled for this report, so a direct link between the original use and the new indication cannot be drawn.
The only publication for myeloproliferative neoplasm is an in silico repurposing screen aimed at the BCR kinase domain in chronic myeloid leukemia, a specific MPN subtype. Binding to BCR-ABL is a computational prediction without experimental or clinical validation. The very high TxGNN score reflects model output, not clinical evidence.
For context, the related indication myeloid leukemia has the most supporting data, all preclinical. Cell-line studies report that hesperidin may induce intrinsic apoptosis in leukemia cells, modulate Mcl-1 expression, and deactivate PI3K/Akt signalling (with salinomycin). It may also enhance cytarabine cytotoxicity (with silibinin) and bind CD33 in docking studies. However, a 2003 study suggests the C7 rutinoside moiety reduces pro-apoptotic activity compared with the aglycone, and hesperidin's low oral bioavailability raises doubts about achievable concentrations. These findings do not directly validate the MPN prediction.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31759365 | 2019 | In silico study | Asian Pac J Cancer Prev | Computational drug repurposing screen targeting Grb-2/BCR kinase domain in chronic myeloid leukemia; no experimental validation |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN17191P | Vessosmin Film Coated Tablet 500mg | Tablet, film coated | Not recorded |
| SIN16068P | Ruventin Film Coated Tablet 500mg | Tablet, film coated | Not recorded |
| SIN01067P | Daflon Tablet 500 mg | Tablet, sugar coated | Not recorded |
| SIN15669P | Daflon Film-Coated Tablet 1000 mg | Tablet, film coated | Not recorded |
| SIN16960P | Davmorid Film Coated Tablet | Tablet, film coated | Not recorded |
A sixth licence (SIN11942P, Diosper Film Coated Tablet, KLEVA S.A.) is also valid. All six are single-ingredient oral products.
Safety Considerations
Please refer to the package insert for safety information. No drug interaction records were found for hesperidin, and no knowledge-graph contraindications were identified.
Conclusion and Next Steps
Decision: Hold
Rationale: The MPN prediction is supported only by a single in silico study, with no clinical trials and no experimental validation (Evidence Level L5). The most plausible oncology direction is myeloid leukemia, but that evidence is entirely preclinical (L4), and hesperidin's low bioavailability is a further translational concern.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA (a blocking gap for safety screening)
- The approved indication text for the Singapore licences
- Mechanism of action data (e.g., from DrugBank)
- Experimental validation (in vitro and in vivo) in MPN models, including JAK2-mutant or BCR-ABL cell lines
- Pharmacokinetic assessment of whether effective concentrations are achievable with oral dosing
- Consideration of whether myeloid leukemia should be prioritised as the lead indication for follow-up research
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.