Horehound

Generic name: Marrubium Vulgare (Tourn.) L.
Brand names: Hoarhound, Horehound, Maromba, Marroio, White Horehound

Usage of Horehound

M. vulgare, a known antioxidant agent, has demonstrated some activity against cancer cells, diabetes (in rats), and liver diseases (using cell-line models). Potential anti-inflammatory, wound healing, antihypertensive, hypolipidemic, and sedative effects have also been proposed. Horehound's antimicrobial activity has also been noted, especially against gram-positive bacteria, fungi, herpes simplex virus, and parasites such as Toxoplasma gondii, Trichomonas vaginalis, and Plasmodium berghei-berghei. Additionally, M. vulgare could be used as a chicken lice repellent, herbicide, and natural insecticide against mosquito larvae and natural molluscicide.(Aćimović 2020, Salama 2012) However, clinical trials are lacking to support use for any indication.

Anti-inflammatory/Analgesic effects

Animal and in vitro data

Limited studies in rodents and in vitro experiments suggest that the chemical constituents of horehound exhibit anti-inflammatory effects. The phenylpropanoid esters acetoside, forsythoside, and arenarioside inhibited cyclooxygenase-catalyzed prostaglandin biosynthesis,(Sahpaz 2002a) while marrubiin reduced histamine-, carrageenan-, and formalin-induced edema.(Popoola 2013, Stulzer 2006)

Analgesic activity of marrubiin derivatives such as marrubiinic acid has been demonstrated by a group of researchers using animal models of pain (writhing test).(De Jesus 2000, de Souza 1998, Meyre-Silva 2005)

Antimicrobial effects

Animal and in vitro data

In screening studies, extracts of horehound and its essential oil have demonstrated activity against Helicobacter pylori(Robles-Zepeda 2011) and several other human bacterial and fungal pathogens, including methicillin-resistant Staphylococcus aureus.(Temmouri 2014, Yildirim 2013, Zarai 2011) Molluscicidal and mosquitocidal properties have also been demonstrated.(Salama 2012)

Antioxidant effects

In vitro data

Potent antioxidant activity has been demonstrated and is most likely due to the phenolic compounds in the plant leaves. However, antioxidant activity varies Depending on the type of organic solvent used for extraction and the sampling location.(Aćimović 2020, Berrougui 2006)

Antispasmodic effects

In vitro data

Antispasmodic activity has been demonstrated in isolated tissue experiments. Calcium channel antagonism and anticholinergic effects were suggested as mechanisms of action.(Popoola 2013, Schlemper 1996)

Cancer

In vitro data

In in vitro studies, horehound essential oil demonstrated activity against several cancer cell lines(Yildirim 2013, Zarai 2011); however, according to toxicity studies, marrubiin has not demonstrated cytotoxicity against 66 cell lines tested.(Popoola 2013)

Cardiovascular effects

Animal data

Limited studies in rodents suggest that marrubiin possesses anti-inflammatory and antioxidant activities, which may be beneficial in reducing the effects of myocardial infarction.(Mnonopi 2011, Yousefi 2013, Yousefi 2014) One group of researchers has demonstrated antihypertensive effects of a water extract of horehound in rodents.(El Bardai 2001, El Bardai 2004)

Diabetes

Animal data

In a study of an obese rat model, increased insulin secretion and increased low-density lipoprotein cholesterol occurred with administration of marrubiin, which was extracted from the unrelated Leonotis leonurus plant.(Mnonopi 2012, Popoola 2013) In rats with induced diabetes, an aqueous extract of M. vulgare aerial plant parts decreased blood glucose and improved lipidemic indices in a dose-dependent manner.(Boudjelal 2012)

A study using a hydroalcoholic extract dosed at 300 mg/kg via intraperitoneal injection in rats with streptozotocin-induced diabetes also noted reduced fasting blood glucose (−61%), as well as reductions in total cholesterol and triglycerides of 26% and 15%, respectively.(Azzi 2014) These activities were cOnfirmed in another study using a methanolic extract at a dose of 500 mg/kg, in which glycemic reductions were similar to those observed with the comparator glibenclamide and total cholesterol and triglycerides decreased while high-density lipoprotein increased.(Elberry 2015) Some of these effects may result from 6-octadecynoic acid obtained from the methanol leaf extract of M. vulgare, which has been identified as a potential glucose and lipid regulator that acts in a similar manner to thiazolidinediones such as pioglitazone.(Ohtera 2013)

Clinical data

A small clinical study (N=43) evaluated the effects of Cecropia obtusifolia and M. vulgare leaf extracts on blood glucose and serum lipid levels in patients with noncontrolled type 2 diabetes with poor response to conventional medical treatment. In addition to study treatments, all patients maintained their conventional medical treatment (glibenclamide at various dosages). In the patient group (n=21) receiving infusions prepared with the leaves of M. vulgare and administered in 1 g envelopes 3 times a day for 21 days, plasma glucose level was reduced by 0.64% and cholesterol and triglycerides by 4.16% and 5.78%, respectively.(Herrera-Arellano 2004)

GI effects

Animal data

In a study of rats, gastroprotective activity was demonstrated with a methanol horehound extract and with marrubiin.(Paula de Oliveira 2011)

Hepatoprotective effects

Animal data

Both a methanol extract of horehound aerial parts and an extracted terpenoid were hepatoprotective in rats, as demonstrated on histological examination and according to liver enzyme indices.(Ahmed 2010, Elberry 2010) An aqueous extract was also found to be protective against cyclophosphamide-induced hepatotoxicity.(Ettaya 2016)

Wound healing effects

In vitro data

In vitro experiments have demonstrated wound healing potential of methanolic extracts of M. vulgare L. leaves.(Amri 2017)

Horehound side effects

No serious adverse events have been reported. In a clinical trial including patients with type 2 diabetes receiving horehound infusion (1 g of dried leaves 3 times/day) coadministered with conventional glibenclamide (12 mg) treatment (n=21), 5 patients experienced adverse effects such as nausea, dry mouth, drooling, swelling, and loss of appetite. However, it is unclear whether these effects were due to the infusion.(Herrera-Arellano 2004, Rodríguez Villanueva 2016)

Older texts suggest that marrubiin has antiarrhythmic properties, which may induce cardiac irregularities in larger doses(Duke 2002); however, animal and clinical data evaluating such properties are lacking.

Before taking Horehound

Avoid use. Horehound reportedly has emmenagogue and abortifacient effects.(Duke 2002, Ernst 2002)

How to use Horehound

Clinical trials are lacking to provide dosing guidance. Horehound infusions prepared with the leaves of M. vulgare and administered in 1 g envelopes 3 times a day for 21 days were evaluated in one small clinical study of patients with type 2 diabetes receiving conventional treatment.(Herrera-Arellano 2004, Khan 2010)

Because of its high tannin content, decreased absorption of drugs coadministered with M. vulgare may occur. Drugs should be taken at least 30 minutes before or after M. vulgare. The same recommendation applies for minerals and thiamine.(Rodríguez Villanueva 2016)

Though clinical data are lacking, the EMA supports traditional use of M. vulgare as an expectorant in catarrh for a period not exceeding 7 days and in the treatment of dyspepsia symptoms such as swelling, flatulence, or temporary loss of appetite for a maximum of 2 weeks.(Rodríguez Villanueva 2016)

Warnings

The median lethal dose (LD50) of marrubiin is 370 mg/kg when administered orally to rats and 100 mg/kg when injected in mice. According to toxicity studies, marrubiin has not demonstrated cytotoxicity against 66 cell lines tested.(Popoola 2013) M. vulgare was given to rats at increasing doses of up to 1,000 mg/kg daily for 3 weeks, with no signs of toxicity.(Elberry 2015) As a flavoring agent and essential oil, horehound has been granted GRAS status by the FDA.(FDA 2019) No adequate trials on teratogenicity have been published.(Rodríguez Villanueva 2016)

What other drugs will affect Horehound

Case reports are lacking; however, in vitro studies suggest that marrubiin has anticoagulant and antiplatelet activities.(Mnonopi 2011, Popoola 2013)

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