Formononetin
[CAS# 485-72-3]

Identification

• Classification: Natural product >> Flavonoids
• Name: Formononetin
• Synonyms: 7-Hydroxy-3-(4-methoxyphenyl)chromone; 7-Hydroxy-4'-methoxyisoflavone; Dadein 4'-methyl ether
• Molecular Formula: C₁₆H₁₂O₄
• Molecular Weight: 268.27
• CAS Registry Number: 485-72-3
• EC Number: 207-623-9
• SMILES: COC1=CC=C(C=C1)C2=COC3=C(C2=O)C=CC(=C3)O

Properties

• Solubility: 200 mg/mL (alcohol, DMF, DMSO), 2 mg/mL (methanol), <1 mg/mL (ethanol) (Expl.)
• Density: 1.3±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.641, Calc.^*
• Boiling Point: 479.4±45.0 ºC (760 mmHg), Calc.^*
• Flash Point: 183.4±22.2 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

Formononetin is a naturally occurring isoflavonoid, widely distributed in plants, particularly in leguminous species. It is a member of the class of compounds known as phytoestrogens, which are plant-derived chemicals that can mimic the effects of estrogen in the body. Formononetin is most commonly found in the roots of red clover (Trifolium pratense), and it has gained significant attention due to its potential health benefits. The compound was first isolated in the early 20th century, and since then, it has been the subject of numerous scientific studies focusing on its pharmacological properties and therapeutic potential.

Formononetin was first identified in the 1930s during the analysis of red clover extracts. Early research showed that this compound shared structural similarities with other isoflavonoids, such as genistein and daidzein, which are known for their estrogenic activities. Over the decades, extensive studies have elucidated its wide range of biological effects, which have prompted its use in various traditional medicines as well as modern therapeutic applications.

One of the most well-known applications of formononetin is in the area of women's health, particularly in managing menopausal symptoms. As an isoflavonoid, formononetin has mild estrogenic properties, which means it can bind to estrogen receptors and exert effects similar to those of the hormone estrogen. This makes it a potential alternative treatment for symptoms of menopause, such as hot flashes, mood swings, and vaginal dryness. The compound’s ability to mimic estrogen activity is particularly significant for postmenopausal women who may be looking for natural alternatives to hormone replacement therapy (HRT).

In addition to its estrogenic effects, formononetin has been studied for its potential cardiovascular benefits. Research has suggested that formononetin may help lower cholesterol levels and reduce the risk of heart disease. This is thought to be due to its antioxidant properties, which help combat oxidative stress, a key factor in the development of cardiovascular diseases. By reducing oxidative damage to blood vessels and other tissues, formononetin may contribute to better heart health and reduced risk of stroke and atherosclerosis.

Formononetin also exhibits anti-inflammatory properties, which have led to its investigation as a potential therapeutic agent for inflammatory conditions such as arthritis. The compound has been shown to modulate inflammatory cytokines and enzymes, reducing the overall inflammatory response. This makes it a promising candidate for the treatment of conditions like rheumatoid arthritis and other autoimmune diseases where chronic inflammation plays a central role.

Another area of significant interest is the anticancer potential of formononetin. Studies have demonstrated that formononetin has anticancer effects in several types of cancer, including breast, prostate, and colon cancers. It is believed to exert these effects through mechanisms such as the inhibition of tumor growth, induction of apoptosis (programmed cell death), and suppression of angiogenesis (the formation of new blood vessels that supply tumors). The compound has been shown to modulate key signaling pathways involved in cancer cell survival, including the PI3K/Akt and MAPK pathways. As a result, formononetin is being explored for its potential use as a natural adjunct to conventional cancer therapies.

Beyond its direct biological effects, formononetin also holds promise in other areas of research. In animal studies, it has been shown to possess neuroprotective properties, which could have implications for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Its ability to reduce oxidative stress and inflammation in the brain suggests it may help protect neurons from damage and promote cognitive health.

Formononetin's applications extend beyond the medical field into agriculture and food science. In plants, formononetin acts as a secondary metabolite that helps protect against pathogens and herbivores, making it a potential natural pesticide. Additionally, as a bioactive compound, it is sometimes included in dietary supplements marketed for women's health and general well-being. Its presence in red clover has also led to the use of red clover extracts as functional foods, especially in products aimed at promoting hormonal balance in women.

Despite its promising pharmacological properties, the clinical use of formononetin has been limited by factors such as bioavailability and dosage. Like many plant-derived compounds, formononetin has low oral bioavailability, meaning it is not easily absorbed in the body when taken orally. To improve its effectiveness, researchers are exploring various delivery systems, such as encapsulating the compound in nanoparticles or combining it with other substances to enhance absorption.

In conclusion, formononetin is a versatile and biologically active isoflavonoid with a wide range of potential applications. Its estrogenic properties make it a valuable option for managing menopausal symptoms, while its antioxidant, anti-inflammatory, and anticancer effects have promising therapeutic implications. Ongoing research into its bioavailability and clinical efficacy may pave the way for its broader use in medical and wellness applications, making it a compound of growing interest in modern medicine and healthcare.

References

Li, S., & Zhang, L., 2011. The estrogenic effects of formononetin and its potential use in managing menopausal symptoms. Journal of Ethnopharmacology, 138(3), pp. 606-612.

Zhou, R., & Xie, L., 2014. Antioxidant and anti-inflammatory properties of formononetin: Implications for cardiovascular health. Phytotherapy Research, 28(11), pp. 1789-1796.

Wang, Y., & Hu, W., 2016. The anticancer effects of formononetin: Mechanisms and therapeutic potential. Journal of Cancer Research and Clinical Oncology, 142(9), pp. 1981-1988.