# Catalpol: an natural multifunctional iridoid glycoside with promising therapeutic properties

**Authors:** Guannan He, Jing Song, Ruixuan Ma, Yixing Zhou, Yamin Xue, Farong Zhang

PMC · DOI: 10.3389/fmolb.2026.1768334 · Frontiers in Molecular Biosciences · 2026-02-18

## TL;DR

Catalpol is a natural compound from Rehmannia glutinosa with diverse therapeutic effects, including anti-inflammatory and anti-cancer properties, and is being studied for clinical use.

## Contribution

This review summarizes recent findings on catalpol's mechanisms and therapeutic potential, highlighting its clinical development stage in China.

## Key findings

- Catalpol shows protective effects on multiple organs and tissues through anti-inflammatory and antioxidative mechanisms.
- Recent studies focus on targeted drug delivery systems to maximize catalpol's efficacy.
- 'Catalpol tablets' have been approved for clinical trials in China.

## Abstract

Catalpol, an iridoid glycoside predominantly derived from the fresh or dried root tuber of Rehmannia glutinosa Libosch (a member of the Scrophulariaceae family), it is a representative compound with the highest content in Rehmannia glutinosa Libosch, and it is also a key index component for evaluating the quality of Rehmannia glutinosa Libosch. Since 2005, it has been continuously included in various editions of China Pharmacopoeia. In this review, we collected relevant data from the Web of Science, PubMed, China National Intellectual Property Administration and China Knowledge Resource Integrated databases in recent 5 years. Catalpol exhibits a broad range of therapeutic effects, addressing various diseases through intricate mechanisms. These include organ- and tissue-protective actions on the kidneys, bones, nervous system, heart, brain, liver, lungs, uterus, ovaries, and more, alongside notable anti-arthritis, anti-cancer, and anti-diabetic properties. The protective mechanisms of catalpol primarily involve its anti-inflammatory, antioxidative stress, anti- or pro-apoptotic, anti-fibrotic, metabolism-regulatory, anti-endoplasmic reticulum stress (ERS), and pyroptosis-modulating functions. Furthermore, catalpol influences a variety of signaling pathways, cells, and molecules, and through these multifaceted actions, it achieves its maximal therapeutic potential. In recent years, the development of different targeted drug delivery formulations and administration routes of catalpol maximise its efficacy has become a major focus of research. What’s more worth mentioning is that “catalpol tablets”, a new class I Chinese medicine developed on the basis of this monomer component, has been approved to enter the clinical trial stage in China. However, in-depth investigation is required to elucidate the mechanisms of action of catalpol, and more clinical trials are required to assess the clinical value of this compound.

## Linked entities

- **Chemicals:** catalpol (PubChem CID 91520)
- **Diseases:** arthritis (MONDO:0005578), cancer (MONDO:0004992), diabetes (MONDO:0005015)

## Full-text entities

- **Genes:** Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Rhoa (ras homolog family member A) [NCBI Gene 117273] {aka Arha, Arha2}, Notch1 (notch receptor 1) [NCBI Gene 25496] {aka NOTCH, TAN1}, Nqo1 (NAD(P)H dehydrogenase, quinone 1) [NCBI Gene 18104] {aka Dia4, Dtd, Nmo-1, Nmo1, Nmor1, Ox-1}, Icam1 (intercellular adhesion molecule 1) [NCBI Gene 25464] {aka CD54, ICAM, RICAM-I}, Nr1h4 (nuclear receptor subfamily 1, group H, member 4) [NCBI Gene 60351] {aka Fxr}, Psen1 (presenilin 1) [NCBI Gene 29192], Gpx4 (glutathione peroxidase 4) [NCBI Gene 29328] {aka Gshpx-4, Phgpx, gpx-4, snGpx}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Ephb1 (Eph receptor B1) [NCBI Gene 24338] {aka Ephb2, Erk, elk}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 116554] {aka JNK}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Bmp2 (bone morphogenetic protein 2) [NCBI Gene 29373], Lgals3 (galectin 3) [NCBI Gene 83781] {aka AGE-R3, CBP30, L-34, gal-3}, Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1}, Hmox1 (heme oxygenase 1) [NCBI Gene 24451] {aka HEOXG, Heox, Hmox, Ho-1, Ho1, hsp32}, Igf1 (insulin-like growth factor 1) [NCBI Gene 24482] {aka IGF}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, Faslg (Fas ligand) [NCBI Gene 25385] {aka Apt1Lg1, CD95-L, Fasl, Tnfsf6, Tnlg1a}, Gfap (glial fibrillary acidic protein) [NCBI Gene 24387], Sirt1 (sirtuin 1) [NCBI Gene 309757] {aka Sir2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Ptk2 (protein tyrosine kinase 2) [NCBI Gene 25614] {aka FAK, FRNK, p125FAK}, Src (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 83805], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 287362] {aka Cias1}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Cxcl12 (C-X-C motif chemokine ligand 12) [NCBI Gene 24772] {aka Sdf1}, Pik3cg (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma) [NCBI Gene 298947] {aka Pi3k}, Th (tyrosine hydroxylase) [NCBI Gene 21823], Taok2 (TAO kinase 2) [NCBI Gene 64666] {aka Tao2}, Tfam (transcription factor A, mitochondrial) [NCBI Gene 83474] {aka Mttfa}, p53-ps (Wistar clone pR53P1 p53 pseudogene) [NCBI Gene 301300], Renbp (renin binding protein) [NCBI Gene 81759], Foxo3 (forkhead box O3) [NCBI Gene 294515] {aka Fkhrl1, Foxo3a}, Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, Cxcr4 (C-X-C motif chemokine receptor 4) [NCBI Gene 60628], Hmgb1 (high mobility group box 1) [NCBI Gene 25459] {aka Ac2-008, Hmg1}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 25125], Mcam (melanoma cell adhesion molecule) [NCBI Gene 78967] {aka CD146, Muc18}, Keap1 (kelch-like ECH-associated protein 1) [NCBI Gene 50868] {aka INRF2, mKIAA0132}, Ldha (lactate dehydrogenase A) [NCBI Gene 24533] {aka CDK1, Ldh1}, Hdac4 (histone deacetylase 4) [NCBI Gene 363287], Atf4 (activating transcription factor 4) [NCBI Gene 79255], Ager (advanced glycosylation end product-specific receptor) [NCBI Gene 81722] {aka RAGE}, Casp1 (caspase 1) [NCBI Gene 25166] {aka Ice, Il1bc, p45}, Mir124-3 (microRNA 124-3) [NCBI Gene 100314155] {aka rno-mir-124-3}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56718] {aka Frap1, RAFT1}, Esr1 (estrogen receptor 1) [NCBI Gene 24890] {aka ER-alpha, Esr, RNESTROR}, Nfe2 (nuclear factor, erythroid 2) [NCBI Gene 366998], Mettl3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 361035], Ntrk2 (neurotrophic tyrosine kinase, receptor, type 2) [NCBI Gene 18212] {aka GP145-TrkB/GP95-TrkB, Tkrb, trk-B, trkB}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Casp9 (caspase 9) [NCBI Gene 58918] {aka Apaf3, Casp-9-CTD, Casp9_v1, Ice-Lap6, Mch6}, Pten (phosphatase and tensin homolog) [NCBI Gene 50557] {aka MMAC1, Mmac, TEP1}
- **Diseases:** pain (MESH:D010146), pancreatic cancer (MESH:D010190), mitochondrial dysfunction (MESH:D028361), endometriosis (MESH:D004715), skin and subcutaneous tissue abnormalities (MESH:D012871), Parkinson's (MESH:D010300), Liver disease (MESH:D008107), muscle atrophy (MESH:D009133), chronic inflammation (MESH:D007249), neuropathological damage (MESH:D004194), trauma (MESH:D014947), IR (MESH:C537629), hyperglycemia (MESH:D006943), defect (MESH:D000013), nervous system abnormalities (MESH:D009421), fibrosis (MESH:D005355), diabetic testicular lesions (MESH:D013733), aortic disease (MESH:D001018), liver fibrosis (MESH:D008103), vitiligo (MESH:D014820), traumatic brain injury (MESH:D000070642), hepatorenal toxicity (MESH:D006530), glucose metabolism disorders (MESH:D044882), neuroinflammation (MESH:D000090862), osteoporotic fractures (MESH:D058866), acute pancreatitis (MESH:D010195), anxiety (MESH:D001007), liver and lung injury (MESH:D055370), edema (MESH:D004487), chronic kidney disease (MESH:D051436), asthma (MESH:D001249), non-alcoholic fatty liver (MESH:D065626), neurotoxicity (MESH:D020258), lung cancer (MESH:D008175), secondary failure (MESH:D051437), Alzheimer's disease (MESH:D000544), Vessel diseases (MESH:C536223), Sjogren's syndrome (MESH:D012859), Cancer (MESH:D009369), Guillain-Barre syndrome (MESH:D020275), Diabetes (MESH:D003920), Lung diseases (MESH:D008171), cerebral ischemia (MESH:D002545), vascular diseases (MESH:D014652), chronic liver and kidney damage (MESH:D056487), diabetic angiopathy (MESH:D003925), myocardial (MESH:D009202), hyperthyroidism (MESH:D006980), acute kidney injury (MESH:D058186), diarrhea (MESH:D003967), stroke (MESH:D020521), fatty liver (MESH:D005234), brain edema (MESH:D001929), hypoxic (MESH:D002534), hemorrhage (MESH:D006470), Neurological diseases (MESH:D020271), autoimmune disease (MESH:D001327), organ dysfunction (MESH:D009102), cardiac arrhythmia (MESH:D001145), nausea (MESH:D009325)
- **Chemicals:** glycerophospholipid (MESH:D020404), chitosan (MESH:D048271), sugar (MESH:D000073893), azoxymethane (MESH:D001397), oxygen (MESH:D010100), fat (MESH:D005223), pyruvate (MESH:D019289), aristolochic acid (MESH:C000228), CCl4 (MESH:D002251), ADP (MESH:D000244), lactate (MESH:D019344), acetylphenylhydrazine (MESH:C006384), poly (ethylenimine) (MESH:D011094), isoflurane (MESH:D007530), glycogen (MESH:D006003), free fatty acid (MESH:D005230), sodium taurocholate (MESH:D013656), STZ (MESH:D013311), acetylcholine (MESH:D000109), S-adenosylmethionine (MESH:D012436), water (MESH:D014867), imidazole (MESH:C029899), CCK-8 (MESH:D012844), metformin (MESH:D008687), NO (MESH:D009569), ethanol (MESH:D000431), methimazole (MESH:D008713), cyclophosphamide (MESH:D003520), hyaluronate (MESH:D006820), blood glucose (MESH:D001786), pyrazole (MESH:C031280), aglycone (MESH:C458179), bleomycin (MESH:D001761), adenine (MESH:D000225), acetic acid (MESH:D019342), pyridine (MESH:C023666), adriamycin (MESH:D004317), silica (MESH:D012822), carbonyl cyanide 3-chlorophenylhydrazone (MESH:C070053), -O-catalpol (-), H2O2 (MESH:D006861), L-thyroxine (MESH:D013974), Cisplatin (MESH:D002945), iridoid glycoside (MESH:D057889), bile acid (MESH:D001647), iridoid (MESH:D039823), palmitate (MESH:D010168), amine (MESH:D000588), Fatty acid (MESH:D005227), amino acid (MESH:D000596), homocysteine (MESH:D006710), Titanium (MESH:D014025), Lipid (MESH:D008055), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MESH:D015632), dehydroepiandrosterone (MESH:D003687), LPS (MESH:D008070), polylactic acid (MESH:C033616), palmitic acid (MESH:D019308), vitamin B12 (MESH:D014805), ATP (MESH:D000255)
- **Species:** Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090], Danio rerio (leopard danio, species) [taxon 7955], Rodentia (rodent, order) [taxon 9989], Homo sapiens (human, species) [taxon 9606], Rehmannia glutinosa (Chinese foxglove, species) [taxon 99300], Rattus norvegicus (brown rat, species) [taxon 10116], Cavia porcellus (domestic guinea pig, species) [taxon 10141], Bos taurus (bovine, species) [taxon 9913], Calendula (genus) [taxon 41495]
- **Mutations:** serine/threonine, T2T
- **Cell lines:** NRK-52E — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0468), L02 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_6926), AML12 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0140), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), BxPC-3 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0186), RN-c — Homo sapiens (Human), Transformed cell line (CVCL_WT23), AC16 — Homo sapiens (Human), Transformed cell line (CVCL_HA69), HFLS-RA — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_C6JY), 293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), INS-1 — Rattus norvegicus (Rat), Rat insulinoma, Cancer cell line (CVCL_0352), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), hFOB1.19 — Homo sapiens (Human), Conditionally immortalized cell line (CVCL_3708), LOVO — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0399), HCCLM3 — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_6832), H9c2 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0286), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), ATDC5 — Mus musculus (Mouse), Mouse teratocarcinoma, Cancer cell line (CVCL_3894), KGN — Homo sapiens (Human), Ovarian granulosa cell tumor, Cancer cell line (CVCL_0375), HUH-7 — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_0336), intestinal epithelial cell-6 — Homo sapiens (Human), Finite cell line (CVCL_6C21), HUVE — Homo sapiens (Human), Finite cell line (CVCL_3722), ARPE-19 — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0145), A-427 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1055), PANC-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), LX-2 — Homo sapiens (Human), Transformed cell line (CVCL_5792), EA.hy926 — Homo sapiens (Human), Hybrid cell line (CVCL_3901), MC3T3-E1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0409), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), HGC-27 — Homo sapiens (Human), Gastric carcinoma, Cancer cell line (CVCL_1279), BV-2 — Mus musculus (Mouse), Transformed cell line (CVCL_0182), HT29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12957270/full.md

## References

243 references — full list in the complete paper: https://tomesphere.com/paper/PMC12957270/full.md

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Source: https://tomesphere.com/paper/PMC12957270