IngredientsVitexicarpin, also known by its synonym casticin, has the IUPAC name 5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-3,6,7-trimethoxychromen-4-one, carries the molecular formula C19H18O8, the CAS registry number 479-91-4, and has a molecular weight of 374.34. It is a nonisotopic tetramethoxyflavone with three phenyl rings, an orthocatechol moiety, an alkene group, two hydroxyl groups, and four methoxy groups. More specifically, casticin is a polymethylflavone with three rings, an orthocatechol moiety, a double bond, two hydroxyl groups, and four methoxyl groups. It is a solid with a melting point of 186°C–187°C and a solubility of 120.7 mg/L at 25°C.
The compound is recognized by multiple synonymous names in the scientific literature: vitexicarpin is the name most frequently used in the context of the plant Vitex rotundifolia and traditional Chinese medicine research, while casticin (also casticine) is the name most commonly used in the context of Vitex agnus-castus and Western botanical pharmacology. Casticin is also known as vitexicarpin or casticine.
Casticin has been isolated from various tissues of plants in the Vitex genus: fruits and leaves of V. trifolia, aerial parts and seeds of V. agnus-castus, and leaves of V. negundo. It has also been isolated from Artemisia annua. It is a flavonoid characteristic of Vitex spp., from which it has been isolated from leaves, fruits, and seeds; its concentration in V. agnus-castus fruits varies from 0.03% to 1.18%, while in V. trifolia leaves, it is present at a concentration of 0.01%.
Viticis Fructus (called Manjingzi in China) is the dried ripe fruits of the plant species Vitex trifolia subsp. litoralis Steenis and Vitex trifolia L. in the family Lamiaceae. These species are also distributed in Korea, Japan, Australia, and other countries. Bioassay-guided fractionation of the chloroform-soluble extract of the leaves of Vitex negundo has also led to the isolation of the known flavone vitexicarpin, which exhibited broad cytotoxicity in a human cancer cell line panel.
There are over 250 different species of Vitex shrubs, of which many have medicinal uses, though the antineoplastic effects have only been evaluated in Vitex trifolia, V. negundo, and V. agnus-castus species thus far. The compound is also present in some members of the Asteraceae family, notably Artemisia annua, the plant from which artemisinin is derived. Casticin is a methoxylated flavonol, meaning the core flavonoid structure has methyl groups attached; found in Artemisia annua, the flavonoid has been shown to enhance the antimalarial activity of artemisinin, though casticin itself has no direct antimalarial effects.
An analytical grade of casticin (98%) from V. trifolia is commercially available. In research and reference standard settings, vitexicarpin is supplied as a purified crystalline powder, typically with HPLC purity of ≥95–98%. The chemical formula is C19H18O8 and commercial reference materials are available at HPLC purity ≥98%. In traditional medicine, the compound is consumed as part of the whole dried fruit (Fructus Viticis / Manjingzi). In autumn, people gather the mature fruits of Vitex trifolia L. or Vitex trifolia L. var. simplicifolia Cham, remove impurities, dry them, and use them directly or stir-fry them to make Chinese herbal medicines.
Viticis Fructus has been used as a traditional Chinese medicine for thousands of years to treat illnesses such as colds, headache, vertigo, anesthesia, and hyperkinesias. It first appeared in the Shennong Ben Cao Jing in the late Western Han Dynasty (around 100 BCE). Viticis Fructus is known as "Manjingzi" in China, "Man Hyung Ja" in Korea, and "Man keishi" in Japan, where it is predominantly regarded as a folk remedy.
Vitex Fruit has been documented in ancient Chinese medical texts for centuries; ancient healers praised it for its ability to disperse wind-heat and clear the head and eyes, making it a go-to herb for headaches, dizziness, and eye conditions, and it was described by Li Shizhen in the Bencao Gangmu. Li Shizhen emphasized its "light and uplifting nature, excellent for dispersing wind and treating head and face disorders," while the Yaoxing Fu text concisely states that Vitex Fruit "clears wind from the head and eyes," summarizing its core function.
Vitex Fruit is characterized as pungent and bitter with a neutral nature; in TCM, it is associated with the bladder, liver, and stomach meridians, making it considered effective for head and eye issues. It is light and ascending in nature, directing its cooling and pain-relieving effects upward to the head and eyes, and is also used as a supporting herb for joint and muscle stiffness related to Wind-Dampness.
Traditional preparations in TCM used the whole dried fruit, either raw or stir-fried. The standard preparation involves removing impurities and drying; the traditional dosage is 5–15 grams. Primary conditions for which Man Jing Zi was prescribed by TCM doctors include headache, painful eyes, excessive tearing, spots in the vision, numbness of limbs, heavy limbs, and muscle cramps.
Vitex species are used for the treatment of diarrhea, rheumatic pain, inflammation, cold, headache, migraine, sore eyes, cancer, respiratory infections, and gastrointestinal disorders in traditional medicine in Asian countries. Vitex trifolia, a coastal shrub, has been traditionally used to treat inflammation, liver disorders, and tumors, and is rich in bioactive flavonoids such as vitexicarpin (casticin), persicogenin, and penduletin.
Vitex agnus-castus (VAC) grows widely on the riverbanks and shores of the Mediterranean region, central Asia, and Southern Europe, and all organs of the herb are medicinally of interest, having a long history—over 2000 years—of use since ancient Greek and Roman times; the most used part of the plant is the ripe dried fruit in the form of extracts and concentrates.
The European Medicines Agency (EMA) has registered "well-established use" and "traditional use" of VAC for premenstrual syndrome (PMS). In the European context, vitexicarpin/casticin is a key flavonoid constituent of V. agnus-castus extracts that have been approved for use by European regulatory bodies.
Vitexicarpin is itself the specific bioactive molecule of interest, rather than being a fraction of a complex extract. When isolated from Vitex fruits, it is present alongside related polymethoxyflavones. Specific methoxylated flavones isolated from V. trifolia seeds include vitexicarpin, artemetin, and chrysoplenol D. These isolated compounds have been observed to exist either as free-standing molecules or in glucosidic form, often conjugated mainly with glucose units.
In the context of phytochemical analysis, distinguishing vitexicarpin/casticin from the closely related flavonoid chrysosplenetin is a recognized analytical challenge. Distinguishing chrysosplenetin and casticin is an issue not only for NMR structure elucidation but also for chromatographic analysis of plant extracts, specifically of Artemisia species; separation of the two compounds could not be achieved on C18 reversed phases when analyzing A. annua extracts.
Casticin is a novel phosphatidylinositol 3-kinase (PI3K) inhibitor, which is considered the predominant mechanism for its anticancer activity; it can also upregulate the Bax/Bcl-2 ratio through an increase in reactive oxygen species (ROS) generation in the mitochondria.
The compound exhibits efficacy against numerous cancer cell lines through various molecular mechanisms: it hinders the processes of invasion, migration, and proliferation, and triggers programmed cell death by multiple mechanisms including the generation of reactive oxygen species and mitochondrial dependence; it also inhibits the cell cycle at different stages; these effects are achieved by modulating several signaling cascades, specifically NF-κB, PI3K/Akt, FOXO3a/FoxM1, and STAT3.
Additional upstream and downstream regulatory proteins are targeted by the casticin molecule in several oncogenic signaling pathways, such as the PI3K/Akt, nuclear factor kappa-B cell (NF-κB), STAT3, and c-Met pathways.
Specifically in prostate cancer cells, vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase; this was associated with upregulation of the proapoptotic protein Bax, downregulation of antiapoptotic protein Bcl-2, release of cytochrome c from mitochondria, and decrease in mitochondrial membrane potential.
In cervical cancer cells, casticin downregulated the expression of cyclin B1 and activated p21 to induce cell cycle arrest.
Casticin inhibits phosphorylation of Akt, PI3K, and MAPK, and blocks NF-κB subunit p65 protein translocation into the nucleus. The anti-inflammatory activity of casticin was studied in vitro in A549 human type II epithelial lung cells using an eotaxin inhibition assay, which showed that casticin can inhibit eosinophil migration and the activity of chemokines and adherence molecules participating in the process of asthma inflammation by inhibiting the NF-κB pathway.
Casticin exhibits anti-inflammatory behavior by means of its inhibitory effect on lipoxygenases and T- and B-lymphocytes. Casticin (Vitexicarpin) can significantly reduce vascular inflammation through inhibition of the ROS-NF-κB pathway in vascular endothelial cells.
Vitexicarpin (VIT) can exert anti-angiogenic effects by inhibiting VEGF-induced endothelial cell proliferation, migration, and capillary-like tube formation on matrigel in a dose-dependent manner; VIT was also shown to have an anti-angiogenic mechanism through inhibition of cell cycle progression and induction of apoptosis. Experimental validation of the target network revealed that reduced phosphorylation states of SRC and AKT are in response to the anti-angiogenesis actions of vitexicarpin.
Vitexicarpin has been found to specifically target AKT and SRC in the VEGF pathway. More recently, Anoctamin 1 (ANO1), a calcium-activated chloride channel, has been implicated in cancer progression and is an emerging therapeutic target; vitexicarpin was identified as a novel ANO1 inhibitor with anticancer potential; vitexicarpin inhibited ANO1 channel function, reduced ANO1 protein levels, decreased cancer cell viability, and induced apoptosis in CRC and NSCLC cell lines.
Casticin inhibited LX2 cell (hepatic stellate cell) proliferation and induced apoptosis in a time- and dose-dependent manner in vitro; the underlying molecular mechanisms involved inhibition of hepatic stellate cell activation and reduced expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 resulting from blocking TGF-β1/Smad signaling, as well as increased apoptosis of HSCs.
An extract of V. agnus-castus was found to bind and activate μ- and δ-, but not κ-opioid receptor subtypes. Casticin can bind to and activate μ- and δ-opioid receptor subtypes in a dose-dependent manner, reducing premenstrual syndrome effects; casticin was reported to have therapeutic effects through the upregulation of these receptors. Due to its estrogenic activity, it is being used to manage premenstrual syndrome in women.
Casticin has been shown to have anti-mitotic activity. It functions as a tubulin-binding anticancer flavonoid. Flow cytometric analyses revealed that the exposure of KB cells to casticin led to significant arrest at G2-M. P-glycoprotein (Pgp) overexpressing cells are not resistant to casticin, and its cell-killing effect is observed even in p53 mutant or null cell lines.
Evidence level: Preclinical (in vitro and animal models only). No human clinical trials of isolated vitexicarpin have been published.
Casticin possesses antineoplastic activities in various cancer cell lines conducted in vitro, including breast, bladder, cervical, colon, esophageal, gallbladder, lung, oral, ovarian, and prostate cancers, as well as hepatocellular carcinoma, leukemia, and melanoma. Casticin is one of the widely studied polymethylflavones for its antiproliferative potential against more than 25 different cancers including leukemia, liver, cervical, breast, lung, glioma, pancreatic, prostate, colon, glioblastoma, and gastric cancer.
Vitexicarpin significantly inhibited the proliferation of human cancer cells, A2780, HCT-15, HT-1080, and K562, with IC50 values of (19.1 ± 2.4) μmol/L for A2780 (48h), (0.66 ± 0.10) μmol/L for HCT-15 (48h), (0.44 ± 0.06) μmol/L for HT-1080 (48h), and (0.28 ± 0.14) μmol/L for K562 (24h). In K562, HL-60, and Kasumi-1 leukemia cell lines, casticin decreases proliferation with IC50s of 5.95, 4.82, and 15.56 µM, respectively.
In a 2025 study published in Frontiers in Pharmacology, vitexicarpin was identified as a novel ANO1 inhibitor with anticancer potential; it inhibited ANO1 channel function, reduced ANO1 protein levels, decreased cancer cell viability, and induced apoptosis in CRC and NSCLC cell lines; importantly, vitexicarpin exhibited minimal hepatotoxicity and negligible hERG channel inhibition, supporting its safety profile. This was a preclinical in vitro study; no human data were generated.
The aim of the PubMed-indexed study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells (human prostate carcinoma) and molecular mechanisms involved; MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an IC50 of ~28.8 μM; Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death.
Casticin induces apoptosis in hepatocellular carcinoma (HCC) and breast cancer cells. Casticin also prevented cadherin switching from taking place and aided cells in maintaining their normal migratory behavior in a mouse CD133+ cell line against hepatocellular carcinoma by upregulating E-cadherin and decreasing N-cadherin levels.
Casticin inhibited proliferation and induced apoptosis in a mouse xenograft model against esophageal cancer. In a leukemia WEHI-3 mouse neoplasm, casticin increased macrophage phagocytosis from peripheral blood mononuclear cells, causing cell endocytosis and eventual death.
The entirety of preclinical anticancer evidence is based on in vitro cell culture experiments and animal models. No randomized controlled trials or human clinical trials evaluating vitexicarpin as a standalone anticancer intervention in humans have been published as of the date of this article.
Evidence level: Preclinical (in vitro and animal models). No isolated vitexicarpin human trials.
The compound is effective against many cancer cell lines via different molecular mechanisms; studies have also affirmed the anti-inflammatory properties of casticin, with several molecular mechanisms identified. Casticin is a powerful immunomodulator, ameliorating pathological changes by suppressing Th2 cytokine expression in mice with asthma.
Pro-inflammatory cytokines induce injury of endothelial cells caused by increases of adhesion molecules, leading to vascular inflammation and the development of atherosclerosis; recent pharmacological studies have demonstrated that vitexicarpin, a flavonoid isolated from Vitex rotundifolia, has anti-inflammatory, antitumor, and analgesic properties; one study investigated whether vitexicarpin (5–100 nM) prevented TNF-α-induced vascular inflammation in human umbilical vein endothelial cells (HUVEC).
Evidence level: Preclinical (in vitro and murine models).
Vitexicarpin isolated from the fruits of Vitex rotundifolia has shown antitumor, anti-inflammatory, and immunoregulatory properties; work has been conducted to evaluate the anti-angiogenic effects of VIT and address the underlying action mechanism by a network pharmacology approach. VIT can exert good anti-angiogenic effects by inhibiting VEGF-induced endothelial cell proliferation, migration, and capillary-like tube formation on matrigel in a dose-dependent manner; VIT was also shown to have an anti-angiogenic mechanism through inhibition of cell cycle progression and induction of apoptosis; VIT inhibited chorioallantoic membrane angiogenesis as well as tumor angiogenesis in an allograft mouse tumor model.
It was discovered that vitexicarpin inhibits VEGF-induced endothelial cell (EC) proliferation at a half-maximal inhibitory concentration (IC50) of 3.4 μM.
Evidence level: Preclinical (in vitro and murine models).
Casticin, one of the major flavonoids in Fructus Viticis extracts, has shown hepatoprotective potential, though its effects on liver fibrosis required specific investigation; one study investigated the antifibrotic activity of casticin and its underlying mechanism in vivo and in vitro. In vivo experiments showed that treatment with casticin alone had no toxic effect while significantly attenuating CCl4- or BDL-induced liver fibrosis, as indicated by reductions in the density of fibrosis, hydroxyproline content, expression of α-SMA, and collagen α1(I) mRNA. In a mouse model of liver fibrosis, casticin at 20 mg/kg decreases TGF-β1 mRNA and phosphorylated SMAD (p-SMAD) levels.
Evidence level: Clinical evidence exists for V. agnus-castus extracts (which contain vitexicarpin), but clinical trials testing isolated vitexicarpin have not been conducted.
Other pharmacological properties attributed to casticin include antihyperprolactinemia, immunomodulatory, opioidergic, and estrogenic activities; clinical trials and commercial use of the casticin-rich fruit extract of V. agnus-castus among women with premenstrual syndrome have been discussed in the literature.
A retrospective longitudinal cohort study published in a peer-reviewed journal examined real-world clinical outcomes of Vitex agnus-castus extract products (Cyclodynon® and Mastodynon®, both casticin-containing extracts). Data from 1,700 women with a mean age of 30.2 years were analyzed; the most common menstrual cycle disorders were dysmenorrhea (43.8%) and mastodynia/mastalgia (21.1%); three-month treatment with VAC extract substantially decreased the percentage of patients with irregular cycle (from 9.1% to 0.1%) and breast tenderness (from 39.9% to 0.8%). However, this evidence pertains to the whole extract of V. agnus-castus, not isolated vitexicarpin, and the retrospective, non-randomized design limits causal interpretation.
Evidence level: Preclinical in vitro only.
Interaction between the flavones casticin and artemetin and the antimalarial activity of chloroquine and qinghaosu (artemisinin) was examined using an in vitro growth assay based on [3H]hypoxanthine incorporation in synchronized cultures of a cloned line of Plasmodium falciparum. The flavonoid has been shown to enhance the antimalarial activity of artemisinin, though casticin itself has no direct antimalarial effects.
Evidence level: Preclinical (animal model).
Casticin displays anti-inflammatory properties; in an in vivo study conducted on female BALB/c mice, casticin reduced oxidative stress in the lungs of mice with asthma alongside reduced activity by the aryl hydrocarbon receptor (AHR) and goblet cell hyperplasia; moreover, casticin downregulated the levels of proinflammatory Th2 cytokine and eotaxin, resulting in reduced lung inflammation.
Evidence level: Preclinical (in vitro).
Vitexicarpin (3′,5-dihydroxy-3,4′,6,7-tetramethoxyflavone) isolated from the fruits of Vitex rotundifolia was found to show potent inhibition against lymphocyte proliferation. It has been documented that vitexicarpin exhibits broad cytotoxicity against human cancer cell lines, exerts an inhibitory effect on T-lymphocyte proliferation, and prevents TNF-α-induced vascular inflammation.
Evidence level: Preclinical (animal model).
Using the acetic acid writhing test, the antinociceptive activity of V. agnus-castus fruit decoction was measured; results showed that it at 200 mg/kg exhibited higher analgesic activity (81.68%) than acetylsalicylic acid used as a positive control (74.35%). While this result applies to the whole fruit decoction rather than isolated vitexicarpin, the latter is identified as a key bioactive constituent.
No standardized human clinical dosage for isolated vitexicarpin has been established in the published scientific literature. The following dosages and concentrations are strictly those reported in the cited sources:
In a 2025 study, vitexicarpin exhibited minimal hepatotoxicity and negligible hERG channel inhibition, supporting its safety profile in preclinical in vitro testing. In vivo experiments in a mouse liver fibrosis model showed that treatment with casticin alone had no toxic effect. A fruit decoction of V. agnus-castus did not cause any toxicity or mortality in rats treated with doses greater than 200 mg/kg.
Vitexicarpin exerts an inhibitory effect on T-lymphocyte proliferation. This immunosuppressive activity at preclinical concentrations raises theoretical concerns about immune function in vulnerable populations, though this has not been demonstrated clinically for the isolated compound.
In vitro studies show binding of V. agnus-castus extracts to the dopamine-2 receptor, the human opioid receptor, and a selective binding affinity for the β-estrogen receptor. Due to its estrogenic activity, casticin is being used to manage premenstrual syndrome in women. The estrogenic and opioidergic binding properties of the compound imply potential interactions with hormone-sensitive conditions and medications acting on the endocrine or opioid receptor systems, though clinical interaction data for isolated vitexicarpin are not established in the peer-reviewed literature reviewed here.
In the context of TCM use of the parent plant (Manjingzi), this herb should be used with caution by those with Blood, Yin, or Stomach Qi Deficiency. People who are allergic to vitex should not take it; patients with a deficiency in the stomach should not take it; patients with blood deficiency and fire should not take it; pregnant and breastfeeding women should not take it. These contraindications apply to the traditional herbal use of the whole fruit and are not extrapolated from clinical pharmacology data on the isolated compound.
P-glycoprotein (Pgp) overexpressing cells are not resistant to casticin, and its cell-killing effect is observed even in p53 mutant or null cell lines. This in vitro observation has been noted as potentially significant in the context of chemotherapy-resistant cancer research, but no clinical data confirm this property in humans.
The research literature does not contain published human clinical trials evaluating the safety, pharmacokinetics, or tolerability of isolated vitexicarpin or casticin in human subjects. All in vivo safety data have been generated in rodent models. The compound is designated for research use only in commercial chemical supply contexts and is not approved as a pharmaceutical drug in any major jurisdiction as of the date of this article.
Vitexicarpin (casticin) is a well-characterized natural polymethoxyflavone with a substantial body of preclinical evidence spanning more than two decades. Extensive research has demonstrated that VIT possesses multiple functions, including anti-inflammatory, antioxidant, and anti-tumor activities. However, all published mechanistic and pharmacological studies have been conducted in cell lines or animal models. Clinical evidence for the isolated compound does not yet exist. Clinical evidence for PMS and menstrual disorders relates specifically to whole V. agnus-castus extract products—not isolated vitexicarpin—and regulatory recognition by the EMA applies only to those standardized extracts. The compound's broad mechanism of action across multiple oncogenic pathways, its anti-angiogenic properties, and its anti-inflammatory activities make it a subject of ongoing research interest, but translation to human therapeutic use remains to be established.
Health conditions that Vitexicarpin may help support.
Body systems that Vitexicarpin may help support.
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