Disease overview

Alterations

117

Molecular (A)

Clinical (B–E)

Direct drugs

Via biomarker

165

Natural agents

Natural products

Merged ranked

167

With trial/literature evidence

Sources: Open Targets, HPO, ClinicalTrials.gov, DGIdb, ChEMBL, PubMed Literature, GreenMedInfo, Examine.com · Pipeline phase 7 · Updated 2026-07-06

Remission & chronicity

Spontaneous remission

Venous leg ulcers: spontaneous healing in 20-30% at 6 months without compression; recurrence in 70% within 1 year even after healing; CVI is progressive without intervention

Best-intervention remission

Compression therapy (graduated 40 mmHg): 70-80% healing at 24 weeks; venous ablation (EVLA, RFA) of incompetent veins + compression: 57% ulcer healing at 6 months vs 36% compression alone (VenUS IV); early intervention (within 6 months of ulcer onset) dramatically improves outcomes

Drug-free remission

—

Relapse after remission

—

Chronicity

—

Gap size

Large — venous ablation is significantly underused; compression adherence is the primary barrier in healed ulcers

Primary barrier

practice/access

Barrier detail: The Early Venous Reflux Ablation (EVRA) trial showed early ablation superior to compression-first strategy but most patients still wait 6+ months; compression stocking adherence is extremely poor without adequate education; many patients receive only wound dressings without compression or vascular assessment

Last SoC change: 2018 — EVRA trial published (early ablation as first-line for VLU with reflux); European guidelines 2015; compression as mainstay unchanged for decades; foam sclerotherapy/EVLA since early 2000s

Remission data layers: disease_db_100 · source-locked manual data · confidence: high

Identifiers: MONDO: MONDO:0000492

Alterations

Showing 80 of 117 · Types A (molecular) through E (functional)

Name	Type	Subtype	Direction	Frequency	Evidence	Sources	Links
ABO ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ACE angiotensin I converting enzyme	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ACP1 acid phosphatase 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
AGT angiotensinogen	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
AKT1 AKT serine/threonine kinase 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ALB albumin	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ALKAL2 ALK and LTK ligand 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
APOE apolipoprotein E	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ASCC3 activating signal cointegrator 1 complex subunit 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
BLOC1S2 biogenesis of lysosomal organelles complex 1 subunit 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
BMP8A bone morphogenetic protein 8a	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CAT catalase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CCDC181 coiled-coil domain containing 181	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CCL5 C-C motif chemokine ligand 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CD4 CD4 molecule	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CD40LG CD40 ligand	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CFTR CF transmembrane conductance regulator	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CLDN1 claudin 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CLDN5 claudin 5	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
COL1A2 collagen type I alpha 2 chain	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CSF2 colony stimulating factor 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CYP2A6 cytochrome P450 family 2 subfamily A member 6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Changes from baseline in the resting flux	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Clinical Etiologic Anatomic Pathophysiologic (CEAP) Classification	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
DNAJC10 DnaJ heat shock protein family (Hsp40) member C10	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Diameter of the efferent vein	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Documentation of IVC dynamics	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
EDN1 endothelin 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
EGFR epidermal growth factor receptor	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ELN elastin	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ENG endoglin	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
F10 coagulation factor X	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
F5 coagulation factor V	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FBLN1 fibulin 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FBN2 fibrillin 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FGF2 fibroblast growth factor 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FTO FTO alpha-ketoglutarate dependent dioxygenase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ICAM1 intercellular adhesion molecule 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
IL10 interleukin 10	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
IL13 interleukin 13	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
IL17A interleukin 17A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
IL4 interleukin 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
IL6 interleukin 6	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
IL7 interleukin 7	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
INS insulin	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Incapacity to work.	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Incidence of Acute Kidney Injury	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
KCNH8 potassium voltage-gated channel subfamily H member 8	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
KRT10 keratin 10	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
LOX lysyl oxidase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MACF1 microtubule actin crosslinking factor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MAPK3 mitogen-activated protein kinase 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MAPK8 mitogen-activated protein kinase 8	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MC4R melanocortin 4 receptor	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MCHR2 melanin concentrating hormone receptor 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MKI67 marker of proliferation Ki-67	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MMP1 matrix metallopeptidase 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MMP12 matrix metallopeptidase 12	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MMP13 matrix metallopeptidase 13	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MMP2 matrix metallopeptidase 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MMP9 matrix metallopeptidase 9	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MPO myeloperoxidase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MTMR11 myotubularin related protein 11	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
MTOR mechanistic target of rapamycin kinase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Mortality	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Number of Participants With PTS-induced Admission to an Emergency Room or Unplanned Visits to a Physician's Office or Hospitalization	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Number of patients with adverse events	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
PABPC4 poly(A) binding protein cytoplasmic 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDGFRA platelet derived growth factor receptor alpha	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PDGFRB platelet derived growth factor receptor beta	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PLAT plasminogen activator, tissue type	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PLG plasminogen	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PLXNA3 plexin A3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PMAIP1 phorbol-12-myristate-13-acetate-induced protein 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PPIG peptidylprolyl isomerase G	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
PROS1 protein S	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Pain.	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Patient satisfaction rate.	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Presence of Complications From GSV Intervention	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—

Therapeutics

Direct disease associations, biomarker-linked drugs, OSMF narrative-review natural agents, merged ranking, and clinical trial / literature evidence (top agents)

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
ACETAZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ACETYLCHOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ADUCANUMAB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AFATINIB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ALBUMIN HUMAN-KJDA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMLODIPINE BESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
APIXABAN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ARGIPRESSIN Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
ASPIRIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATORVASTATIN Repurposing	Small molecule	Approved	Strong	95	1 pubs View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BENAZEPRIL Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BENAZEPRIL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
BENAZEPRILAT Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BICALUTAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BISMUTH Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BUMETANIDE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BUPROPION HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CANDOXATRIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CAPIVASERTIB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CAPTOPRIL Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CARBACHOL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CEFDINIR Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CHLORTHALIDONE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CHOLESTEROL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CHORIOGONADOTROPIN ALFA Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
CILAZAPRIL Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CIPROFLOXACIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLOMIPRAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CYCLOSPORINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DABRAFENIB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DEHYDRATED ALCOHOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DESERPIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICHLORPHENAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICLOFENAC SODIUM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DIETHYLSTILBESTROL Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DONANEMAB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DONEPEZIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
DOXORUBICIN HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ENALAPRIL MALEATE Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
ENALAPRILAT Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
ENALAPRILAT ANHYDROUS Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
EPIGALLOCATECHIN GALLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
EPIRUBICIN Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ERLOTINIB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ETHOXZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
EVEROLIMUS Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
FENOFIBRATE MICRONIZED Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—

Drug	Type	Phase	Evidence	Score	Sources	Links
DIOSMIN	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
SULODEXIDE	Small molecule	Preclinical	Emerging	15	Open Targets	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
ACETAZOLAMIDE Repurposing via ABO	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ACETYLCHOLINE Repurposing via ACE	Small molecule	Approved	Strong	95	—	DGIdb	—
ADUCANUMAB Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
AFATINIB Repurposing via AKT1	Small molecule	Approved	Strong	95	—	DGIdb	—
ALBUMIN HUMAN-KJDA Repurposing via ALB	Small molecule	Approved	Strong	95	—	DGIdb	—
AMLODIPINE BESYLATE Repurposing via AGT	Small molecule	Approved	Strong	95	—	DGIdb	—
AMPHETAMINE Repurposing via ABO	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
APIXABAN Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
ARGIPRESSIN Repurposing via ACE	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
ASPIRIN Repurposing via ACE	Small molecule	Approved	Strong	95	—	DGIdb	—
ATORVASTATIN Repurposing via ACE	Small molecule	Approved	Strong	95	1 pubs View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BENAZEPRIL Repurposing via ACE	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BENAZEPRIL HYDROCHLORIDE Repurposing via ACE	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
BENAZEPRILAT Repurposing via ACE	Small molecule	Approved	Strong	95	—	DGIdb	—
BICALUTAMIDE Repurposing via ABO	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BISMUTH Repurposing via ALB	Small molecule	Approved	Strong	95	—	DGIdb	—
BUMETANIDE Repurposing via ACE	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BUPROPION HYDROCHLORIDE Repurposing via ACE	Small molecule	Approved	Strong	95	—	DGIdb	—
CANDOXATRIL Repurposing via ACE	Small molecule	Approved	Strong	95	—	DGIdb	—
CAPIVASERTIB Repurposing via AKT1	Small molecule	Approved	Strong	95	—	DGIdb	—
CAPTOPRIL Repurposing via ACE	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CARBACHOL Repurposing via ABO	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CEFDINIR Repurposing via ACP1	Small molecule	Approved	Strong	95	—	DGIdb	—
CHLORTHALIDONE Repurposing via AGT	Small molecule	Approved	Strong	95	—	DGIdb	—
CHOLESTEROL Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
CHORIOGONADOTROPIN ALFA Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
CILAZAPRIL Repurposing via ACE	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
CIPROFLOXACIN Repurposing via ABO	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CLOMIPRAMINE Repurposing via ABO	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
CYCLOSPORINE Repurposing via AGT	Small molecule	Approved	Strong	95	—	DGIdb	—
DABRAFENIB Repurposing via AKT1	Small molecule	Approved	Strong	95	—	DGIdb	—
DEHYDRATED ALCOHOL Repurposing via CAT	Small molecule	Approved	Strong	95	—	DGIdb	—
DESERPIDINE Repurposing via ACE	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing via ALB	Small molecule	Approved	Strong	95	—	DGIdb	—
DIAZEPAM Repurposing via ABO	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICHLORPHENAMIDE Repurposing via ABO	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DICLOFENAC SODIUM Repurposing via ALB	Small molecule	Approved	Strong	95	—	DGIdb	—
DIETHYLSTILBESTROL Repurposing via ABO	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
DONANEMAB Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—
DONEPEZIL Repurposing via APOE	Small molecule	Approved	Strong	95	—	DGIdb	—

Natural Products

10 natural products with the same evidence schema as repurposed drugs — registry trials, PubMed literature, and reference links (pipeline-ranked)

Reference lookups: GreenMedInfo · Examine.com

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
Horse Chestnut Natural product Cochrane review Rutosides for treatment of post-thrombotic syndrome Cochrane review Rutosides for prevention of post-thrombotic syndrome Cochrane review Rutosides for treatment of post-thrombotic syndrome	Nutraceutical	Approved	Moderate	19	3 trials 13 Cochrane 8 Meta-analysis 6 Trial pubs 6 RCT View evidence Registry trials NCT02498327 — The Efficacy of Venavine Intensive® on the Quality of Life in Females With Chronic Venous Insufficiency (COMPLETED) PHASE2 NCT06579482 — Clinical Trial of Aesculus Hippocastanum and Associations Versus Diosmina and Hesperidina in Chronic Venous Insuficiency (COMPLETED) PHASE4 NCT02483962 — Venavine Intensive® in the Treatment of Symptoms Associated With Chronic Venous Insufficiency (COMPLETED) PHASE2 Published literature Cochrane review Rutosides for treatment of post-thrombotic syndrome (The Cochrane database of systematic reviews, 2018) Cochrane review Rutosides for prevention of post-thrombotic syndrome (The Cochrane database of systematic reviews, 2018) Cochrane review Rutosides for treatment of post-thrombotic syndrome (The Cochrane database of systematic reviews, 2015) Cochrane review Rutosides for prevention of post-thrombotic syndrome (The Cochrane database of systematic reviews, 2015) Cochrane review Rutosides for prevention of post-thrombotic syndrome (The Cochrane database of systematic reviews, 2013) Meta-analysis Rutosides for treatment of post-thrombotic syndrome (The Cochrane database of systematic reviews, 2013) Meta-analysis Horse chestnut seed extract for chronic venous insufficiency (The Cochrane database of systematic reviews, 2012) Meta-analysis Treatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: a review of 5 clinical studies (Advances in therapy, 2006) Clinical trial publication Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency (Phytotherapy research : PTR, 2002) Clinical trial publication Rational therapy of chronic venous insufficiency--chances and limits of the therapeutic use of horse-chestnut seeds extract (BMC cardiovascular disorders, 2001) Clinical trial publication Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency (Arzneimittel-Forschung, 1996) Clinical trial publication Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency (Lancet (London, England), 1996) CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	Examine.com GreenMedInfo
Pycnogenol Natural product Cochrane review Pycnogenol® (extract of French maritime pine bark) for the treatment of… Cochrane review Pycnogenol(®) for the treatment of chronic disorders Clinical trial publication Effect of Pycnogenol on the Healing of Venous Ulcers	Botanical	Preclinical	Moderate	17	2 Cochrane 1 Meta-analysis 9 Trial pubs 6 RCT View evidence Published literature Cochrane review Pycnogenol® (extract of French maritime pine bark) for the treatment of chronic disorders (The Cochrane database of systematic reviews, 2012) Cochrane review Pycnogenol(®) for the treatment of chronic disorders (The Cochrane database of systematic reviews, 2012) Clinical trial publication Effect of Pycnogenol on the Healing of Venous Ulcers (Annals of vascular surgery, 2017) Clinical trial publication Improvement of signs and symptoms of chronic venous insufficiency and microangiopathy with Pycnogenol: a prospective, controlled study (Phytomedicine : international journal of phytotherapy and phytopharmacology, 2010) Clinical trial publication Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study (Angiology, 2006) Clinical trial publication Control of edema in hypertensive subjects treated with calcium antagonist (nifedipine) or angiotensin-converting enzyme inhibitors with Pycnogenol (Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 2006) Clinical trial publication Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study (Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 2006) Randomized controlled trial Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency (Phytotherapy research : PTR, 2002) Randomized controlled trial PYCNOGENOL in chronic venous insufficiency (Phytomedicine : international journal of phytotherapy and phytopharmacology, 2000) CT.gov search · Cochrane · PubMed	Examine.com	Examine.com
Gotu Kola Natural product Review Gotu kola is therapeutic in venus insufficiency, venous hypertension an…	Nutraceutical	Preclinical	Moderate	10	No indexed hits View evidence CT.gov search · Cochrane · PubMed	Examine.com, GreenMedInfo	Examine.com GreenMedInfo
Butcher's Broom Natural product Human Study Butcher's broom is a safe and effective treatment for chronic veno…	Nutraceutical	Preclinical	Moderate	10	No indexed hits View evidence CT.gov search · Cochrane · PubMed	Examine.com	Examine.com
Pycnogenol (Pine Bark) Natural product Human Study Chronic venous insufficiency and venous microangiopathy: management wit… Human Study Pycnogenol rapidly reduces clinical symptoms in patients with chronic v… Human Study Pycnogenol relieved edema, improved microcirculation in CVI patients an…	Nutraceutical	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	GreenMedInfo	GreenMedInfo
Diosmin Natural product Clinical trial publication Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After… Clinical trial publication [Non-drug methods of treatment of post-thrombophlebitic syndrome] Clinical trial publication Comparative Bioavailability of Two Diosmin Formulations after Oral Admi…	Nutraceutical	Approved	Emerging	0	8 trials 1 Meta-analysis 21 Trial pubs View evidence Registry trials NCT01321619 — Efficacy and Tolerability of the Use of Varicell Compared With Daflon (UNKNOWN) PHASE3 NCT04101201 — Clinical Trial to Assess the Efficacy of µSmin® Plus (COMPLETED) NA NCT06579482 — Clinical Trial of Aesculus Hippocastanum and Associations Versus Diosmina and Hesperidina in Chronic Venous Insuficiency (COMPLETED) PHASE4 NCT01654016 — Study of Antiinflammatory Effects of Detralex (Daflon) (COMPLETED) PHASE4 NCT01477281 — Study to Evaluate the Efficacy and Tolerability of Venaflon Use in Reducing the Symptoms Caused by Chronic Venous Insufficiency When Compared With Daflon (UNKNOWN) PHASE3 NCT01110512 — Comparative Efficacy of Two Preparations of the Association Diosmin (450 mg) + Hesperidin (50 mg) in the Treatment of Chronic Venous Insufficiency (CVI) (UNKNOWN) PHASE3 NCT03471910 — Clinical Non-inferiority Study Between Diosmin 600mg & Diosmin + Hesperidin in Symptomatic Chronic Venous Insufficiency (COMPLETED) PHASE4 NCT02927483 — Study to Assess the Efficacy and Safety of Endolex Forte VErsus Diosmin and Hesperidin in Reducing VeNous Insufficiency (UNKNOWN) PHASE3 Published literature Clinical trial publication Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial (The Journal of bone and joint surgery. American volume, 2024) Clinical trial publication [Non-drug methods of treatment of post-thrombophlebitic syndrome] (Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury, 2022) Clinical trial publication Comparative Bioavailability of Two Diosmin Formulations after Oral Administration to Healthy Volunteers (Molecules (Basel, Switzerland), 2018) Clinical trial publication Effect of Pycnogenol on the Healing of Venous Ulcers (Annals of vascular surgery, 2017) Clinical trial publication A randomized, controlled clinical pilot study comparing three types of compression therapy to treat venous leg ulcers in patients with superficial and/or segmental deep venous reflux (Ostomy/wound management, 2013) CT.gov search · Cochrane · PubMed	GreenMedInfo	GreenMedInfo
Hesperidin Natural product Human Study Daflon, a form of micronized diosmin and hesperidin, improves symptoms… Review A combination of micronized hesperidin and diosmin has therapeutic valu…	Food compound	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed	GreenMedInfo	PubChem GreenMedInfo
Buckwheat Natural product Randomized controlled trial Leg oedema protection from a buckwheat herb tea in patients with chroni…	Nutraceutical	Preclinical	Emerging	0	1 RCT View evidence Published literature Randomized controlled trial Leg oedema protection from a buckwheat herb tea in patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled clinical trial (European journal of clinical pharmacology, 1996) CT.gov search · Cochrane · PubMed	GreenMedInfo	GreenMedInfo
Rutin Natural product Human Study Buckwheat herb tea protects against leg edemia in patients with chronic…	Nutraceutical	Approved	Emerging	0	1 trials 1 Cochrane 1 RCT View evidence Registry trials NCT06579482 — Clinical Trial of Aesculus Hippocastanum and Associations Versus Diosmina and Hesperidina in Chronic Venous Insuficiency (COMPLETED) PHASE4 CT.gov search · Cochrane · PubMed	GreenMedInfo	GreenMedInfo
Butchers Broom Natural product Human Study Butcher's broom is a safe and effective treatment for chronic veno…	Nutraceutical	Phase II	Emerging	0	2 trials View evidence Registry trials NCT02498327 — The Efficacy of Venavine Intensive® on the Quality of Life in Females With Chronic Venous Insufficiency (COMPLETED) PHASE2 NCT02483962 — Venavine Intensive® in the Treatment of Symptoms Associated With Chronic Venous Insufficiency (COMPLETED) PHASE2 CT.gov search · Cochrane · PubMed	GreenMedInfo	GreenMedInfo

Alterations and therapeutics are aggregated from public databases (Open Targets, HPO, ChEMBL, DGIdb, and others). Natural agents are candidates from OSMF narrative reviews on opensourcemed.info/chronic-disease.html — not approved treatments. This page is for research orientation only — not medical advice.

Chronic Venous Insufficiency / Venous Leg Ulcers

Disease overview

Remission & chronicity

Alterations

Therapeutics

Natural Products

Part of the Open Source Medicine Foundation Network