Ivy Leaf Extract: A Comprehensive Overview for Pharmaceutical Applications

Written by Emmanuella Ogbonna, BPharm; Reviewed by Danielle Kelvas, MD, for PTcell for Pharmaceutical Industries LL.C

Ivy leaf has long been used in Europe for its medicinal properties, especially for the treatment of acute cough and other respiratory disorders (1,2). In fact, the use of ivy leaf extract has been standardized by the German regulatory authority as far back as 1988 (3).

In addition to the use of ivy leaf extract in cough syrup, research also suggests the extract may have beneficial properties on inflammation, microbes, and fungi (4).

This article will examine ivy leaf extract, its classification, medicinal use, extraction techniques, and quality control.

Botanical Classification and Characteristics

Ivy leaf (Hedera helix) belongs to the Araliaceae family–the ginseng family of flowering plants. This plant is native to Europe and some parts of Asia, but it is now cultivated in other parts of the world, like North America (English Ivy).

Hedera helix is an evergreen climbing plant growing as high as 98ft in places with supporting surfaces like trees and walls. Ivy can also develop on the ground in areas where no vertical surfaces occur. This plant generally thrives in areas that are moist and have minimal sunlight (preferably shades).

Major bioactive compounds

The major active ingredient that has been shown to be responsible for the medicinal properties of ivy leaves is triterpene saponins (5).

Studies have found that two triterpene saponins α-hederin and hederacoside C are primarily responsible for the medicinal properties of ivy leaf extract, particularly as an antitussive agent (6,7).

As a result of the potency of the saponins in the plant, the European Pharmacopeia requires that ivy leaves used for medicinal purposes contain the compound hederacoside C (8).

In addition to saponins, ivy leaves are rich in secondary metabolites like flavonoids, coumarins, phenolic acids, and amino acids (5).

However, studies show that the geographical region of the plant predominantly determines the quality and quantity of the secondary metabolites in ivy plants (5).

Pharmaceutical uses of Ivy Leaf Extract

Studies have shown that ivy leaves contain active compounds with wide applications in the pharmaceutical industry (9).

Some potential uses of ivy leaf extract include:

Expectorant and mucolytic effects
Several clinical studies have established the use of ivy leaf plants as an antitussive agent in cough syrups or expectorants (10).

In a study that included over 228 people with acute respiratory infections (ARTIs), ivy leaf extract effectively reduced the intensity of acute cough associated with ARTIs and sped up recovery (11).

Another study revealed that ivy leaf extract might be a suitable alternative to the mucolytic agent acetylcysteine in improving respiratory function in children and adults (12).

The European medical agency has authorized the use of Hedera helix preparations as an over-the-counter non-antibiotic cough medicine in adults and children older than 2 (9).

Anti-inflammatory effects

In vitro studies have shown that the presence of ivy leaf extracts also has anti- inflammatory properties and may reduce oxidative stress (4,13).

In one study, researchers evaluated the protective effects of Hedera helix leaf extract on paracetamol-induced oxidative stress in mice (14). They found that treatment with the Hedera helix extract reduced toxic levels of creatinine, uric acid, and blood urea nitrogen, preventing kidney damage caused by paracetamol.

However, the inflammatory effects of ivy extracts as anti-inflammatory agents have not been well studied in humans.

Antimicrobial effects

In vitro, studies also suggest that ivy leaf extracts may have a significant effect on inhibiting the growth of some bacteria, particularly Klebsiella pneumonia and Streptococcus pneumonia (15, 16).

Interestingly, researchers found that the antimicrobial properties of the Hedera helix are due to the phenolic compounds, not saponins (17).

Treatment of Arthritis

Another potential use of ivy leaf extract is in rheumatoid arthritis. Studies show that the anti-inflammatory effects of ivy leaf extracts might make them effective in the treatment of arthritis (18). The researchers noted that the flavonoids in Hedera helix leaves are responsible for their effect on arthritis (18).

Quality Control and Standardization of Ivy Leaf Extract

The European Pharmacopeia has proposed that the presence of hederacoside C is the major biomarker of Hedera helix and should be used as an indicator of the quality of Ivy leaf (19).
Some techniques that have been developed to quantitatively measure hederacoside C in ivy leaf extracts and its products include (19,20):
● High-Performance Liquid Chromatography (HPLC)
● Ultra-Performance Liquid Chromatography (UPLC)
● High-Performance Thin-Layer Chromatography (HPTLC)
● Thin-Layer Chromatography—tests for the presence of α-hederin and hederacoside C
● High-performance liquid chromatography with diode array detector (latest technique). (21).
● Reversed-phase high-performance liquid chromatography RP-HPLC)

Regulatory Status and Safety Considerations

The European Medicines Agency (EMA) regulates the use of ivy leaf extracts in cough medicine in adults and children.

The recommended dose of ivy leaf extract for respiratory tract infection varies depending on the preparation. For adults, the EMA recommends a daily dose of about 45 to 105 mg (22).

Ivy leaf is generally considered safe (10, 12). Some possible side effects of ivy leaf extract include gastrointestinal effects (nausea, vomiting, or diarrhea) and allergy to the preparation.

The use of Ivy leaf extract is contraindicated in children under the age of 2. Caution is also recommended in patients with gastritis. The safety of ivy extract in pregnant and lactating mothers has not been established, so it is not recommended for this population.

Ivy leaf extract may cause drug interactions with some CYP2C19 substrates like omeprazole, citalopram, and phenytoin (23).

In addition, preparations that use alcoholic preparations should not be used in children under age 6.

Future Prospects of Ivy Extract Formulations

Researchers are making significant strides in optimizing the delivery of ivy leaf extract constituents. Usually, ivy leaf extracts often involve multiple daily doses, which can be inconvenient for patients.

One promising development is the formulation of sustained-release ivy leaf extract tablets (24). These tablets are designed to gradually release their active components over a prolonged period, reducing dosing frequency.

In addition, the tablets were engineered to be unaffected by the stomach's acidic environment, ensuring consistent and effective absorption of the ivy leaf extract (24).

This breakthrough has the potential to enhance patient compliance and improve the overall therapeutic benefits of ivy leaf extract.

Ivy leaf extract is also currently being explored as a nanocarrier in cancer therapy
(25) and even anti-aging skin treatment (26).

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