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Ballota Nigral. – an Overview of Pharmacological Effects And International journal edited by the Institute of Natural Fibres and Medicinal Plants Vol. 66 No. 3 2020 Received: 2020-09-02 DOI: 10.2478/hepo-2020-0014 Accepted: 2020-09-22 Available online: 2020-09-30 EXPERIMENTALREVIEW PAPER PAPER Ballota nigra L. – an overview of pharmacological effects and traditional uses FILIP PRZERWA1 , ARNOLD KUKOWKA1 , IZABELA UZAR2* 1Student Science Club Department of General Pharmacology and Pharmacoeconomics Pomeranian Medical University in Szczecin Żołnierska 48 71-210 Szczecin, Poland 2Department of General Pharmacology and Pharmacoeconomics Pomeranian Medical University in Szczecin Żołnierska 48 71-210 Szczecin, Poland * corresponding author: e-mail: [email protected] Summary Ballota nigra, also known as black horehound is a common medical herb used in folk medicine around the world. First reported mentions of its medical properties and use goes as far as the 13th century. The use of black horehound depends on regions and countries. It is used mostly to treat e.g. mild sleep disorders, nervousness, upset stomach, wound healing. It can be used as an anti-inflammatory, antibacterial, antipro- tozoal, antifungal drug. Moreover, it has been reported as a potential cancer drug. This extensive usage is particularly interesting for us. The aim of this review is to present available data on B. nigra pharmacological effects and known traditional uses gathered from a wide range of scientific articles published in 1997–2020. Key words: Ballota nigra L., black horehound, pharmacology, medical herb Słowa kluczowe: Ballota nigra L., mierznica czarna, farmakologia, roślina lecznicza Herba Pol 2020; 66(3): 56-65 Ballota nigra L. – an overview of pharmacological effects and traditional uses 57 INTRODUCTION responsible for a given effect. This could be an idea for further work on this herb. Nowadays, the black horehound is an object of inter- The aim of this article is to provide an overview of est mainly in the countries of the Middle East, which information about the black horehound, with particular is reflected in the amount of articles and research con- emphasis on the possible clinical applications. The range ducted in that region. Due to the number of its poten- of its traditional uses was also taken into account. In the tial applications and common occurrence in Europe chemotaxonomy part, the chemical composition of the this article is to raise interest in this special herb. Bal- plant is included, as well as the composition of essential lota nigra is a plant from the Lamiaceae family, it is oils, depending on the part from which they were ob- a herbaceous perennial, occurring in Europe, North tained. The text also includes information on the dosage, Africa, Western Asia and North America. The whole forms of use, intake and the toxicity of B. nigra. plant is pubescent and fresh green. It has herbaceous ascending stems, wooden and branched at bottom, covered by down folded hairs. The plant has a tap- CHEMOTAXONOMY root system. The leaves are 0.5 to 1 cm long and the lower leaves are a little bit longer. It has purplish flow- B. nigra has a wide variety of phytochemical com- ers, that are organized in verticillasters, subspherical pounds. Many studies have proven that black hore- to about one-sided, with 15 to 30 flowers. The whole hound contains terpenoids, flavonoids, steroids, plant gives off an unpleasant odour [1]. carboxylic acids, phenylpropanoids. Essential oils Other names of black horehound are as follows: obtained from various parts of the plant also contain Ballota, Ballote Fétide, Ballote Noire, Ballote Puante, a wide range of chemicals. Ballote Vulgaire, Black Stinking Horehound, Mar- rube Fétide, Marrube Noir, Marrubio Negro. Phytochemicals compaunds extracted from B. nigra: The black horehound has been of interest to the medical world for many years, and to this day it is - diterpenes: 7α-acetoxymarrubiin, ballonigrin used in traditional medicine in many regions of the [9], ballotenol [10], dehydrohispanolone (his- world. Its versability translates into a large num- panone) [3], marrubiin [12], preleosibirin [13], ber of 'traditional' uses, ranging from wound care 7α-acetoxyroyleanone [14]; to psychiatric problems. Most often it is used in the - flavones: ladanein [14], apigenin, luteolin, chrys- form of leaf tea, it can also be used in the form of oeriol [15], tangeretin [16]; essential oils or tinctures [2]. It is mainly used as an ad hoc sedative agent, but it - flavonols: 5-hydroxy-3,7,4′-trimethoxyflavone, can also be used to relieve discomfort in neurotic dis- kumatakenin, retusin [17]; orders and depression. The 5-phenylpropanoids com- - flavone glycosides: apigenin-7-O-β-D- pounds from the plant are mainly responsible for these glucopyranoside [18]; properties [3]. An essential oil from aboveground parts has at least 70 chemical compounds [4]. The chemi- - acyl flavonoid glycosides: luteolin-7-lactate, cal compounds responsible for the pharmacologi- luteolin-7-O-[2-O-β-D-glucopyranosyl-lactate] [19]; cal effects of black horehound are mainly substances - C-glycosyl flavonoids: vicenin-2 [18]; from phenylpropanoid glycosides, diterpenes and carboxylic acids. One of the most important groups - triterpenoids: oleanolic acid, ursolic acid [20]; is the phenylpropanoid glycosides such as lavanduli - steroids: β-sitosterol [14]; folioside, which has a negative chronotropic effect - carboxylic acids: caffeic acid, E-caffeoyl-L-malic and it lowers the blood pressure.[5] Other important acid, chlorogenic acid, fumaric acid, quinic acid, compound in this group is forsythioside B, which has shikimic acid [21]; neuroprotective and cardioprotective properties [6, 7]. From the group of diterpenes, the substance balloni- - nitrogen-containing compounds: choline (foetida) grin is also interesting because it can potentially inhibit [22], 4-hydroxyproline betaine, stachydrine [23]; the development of cervix cancer [8]. - phenylpropanoids: alyssonoside, angoroside A, In many researches that provided evidence for arenarioside, ballotetroside, forsythoside B, lavan- the pharmacological effects of B. nigra, researchers dulifolioside [21], martynoside [14], verbascoside used an extract of black horehound, which makes it (acteoside) [24] and phytol [25]. impossible to indicate exactly which compound was Vol. 66 No. 3 2020 58 F. Przerwa, A. Kukowka, I. Uzar Main compounds: (>3% of the essential oil): caryophyllene oxide, caryophylladienol I, (E)- 2-hexenal, hexadecanoic acid, α-humulene [4]; B. nigra - fruiting aerial parts: β-caryophyllene, caryophyl- - aerial parts: caryophyllene oxide, epi-α-muurolol, lene oxide, germacrene D, (E)-2-hexenal, β-pinene, δ-cadinene, α-cadinol, γ-amorphene, β-bourbonene, limonene, 1-octen-3-ol, linalool [36]; 6,10,14-trimethyl-2-pentadecanone, (E)-caryophyl- - aerial parts flowering: β-caryophyllene, caryoph- lene, germacrene D, aromadendrene, γ-muurolene, yllene oxide, germacrene D, (E)-2-hexenal, 1-octen- germacrene D-4-ol, α-bisabolol, α-amorphene [26] 3-ol [36]; β-pinene, α-pinene, sabinene, α-phellandrene [27]; - flowers: hexenal, (E)-β-caryophyllene, ger- - corollas: palmitic acid, 2,2,6-trimethyl-4-methy- macrene D, cis-3-hexene-1-ol, pentanal, limonene, lene-3,4-dihydro-2H-pyran, hexahydrofarnesylace- (E)-2-hexenal [37]. tone, myristic acid, caryophyllene oxide, pentadeca- noic acid, palmitoleic acid, germacrene D [29]; Ballota nigra subsp. curdica - calyx: palmitic acid, dodecanal, palmitoleic acid, myristic acid, pentadecanoic acid, lauric acid, - aerial parts: caryophyllene oxide, β-caryophyllene trans-isoelemicin, hexahydrofarnesylacetone, pen- , germacrene D, 1-undecene, isoaromadendrene ep- tadecene, methyleugenol; oxide [38]. - leaves: β-caryophyllene, germacrene D, α-humulene, Ballota nigra subsp. uncinata (E)-phytol [28], palmitic acid, palmitoleic acid, myris- tic acid, pentadecanoic acid, farnesyl acetone, dihydro- - aerial parts: caryophyllene oxide, hexadecanoic actinidiolide [29]; acid, β-caryophyllene, germacrene D, hexahydro- - stems: β-caryophyllene, germacrene D, α-humulene, farnesyl acetone, spathulenol, caryophyllene II; bi- δ-cadinene, (E)-phytol [28], methyl salicylate, palmitic cyclogermacrene [31]. acid, 2,2,6-trimethyl-4-methylene-3,4-dihydro-2H- pyran, myristic acid [29]; PHARMACOLOGICAL EFFECTS - root: p-vinylguaiacol, borneol, myrtenol, trans- pinocarveol, 1-octen-3-ol, pinocarvone, 2-methyl- Various biologically active compounds that are pres- 3-phenylpropanal, p-cymen-8-ol, trans-carveol, ent in B. nigra have an impact on the human body. β-pinene, α-pinene , sabinene, α-phellandrene [28] Many of those effects can be useful in pharmacother- apy. The variety of those compounds is reflected in B. nigra subsp. anatolica numerous pharmacological effects such as: anticho- linesterase activities, antidepressant activity, antip- - aerial parts: germacrene D, nerolidol sclareol ox- roliferative and cytotoxic activities, sedative activity, ide, linalyl acetate, β-caryophyllene, spathulenol, antiprotozoal activity, hypoglycaemic activity, hypo- linalool, longipinene epoxide [30], hexadecanoic lipidemic activity and tyrosinase inhibitory activity. acid, β-bisabolene, hexahydrofarnesyl acetone, 1-isobutyl-4-isopropyl-2,2-dimethyl succinate, β-eudesmol [31], 1-hexacosanol, caryophyllene Antidepressant and sedative activity oxide, germacrene-D, α-selinene, Z-8-octadecen- 1-ol acetate, 2,5-di-tert-butyl-p-benzoquinone, Studies from 1996 showed that water extract of B. nigra, arachidic acid, tetracosane, heneicosane, heptaco- subsp. anatolica had antidepressant
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