IJPCBS 2015, 5(2), 394-402 Ekaterina Kozuharova et al. ISSN: 2249-9504

INTERNATIONAL JOURNAL OF PHARMACEUTICAL, CHEMICAL AND BIOLOGICAL SCIENCES

Available online at www.ijpcbs.com Research Article

ETHNOBOTANY AND ETHNOPHARMACOLOGY OF MACULATUM L. () IN BULGARIA WITH AN EMPHASIS ON ITS EFFECT AGAINST HAEMORRHOIDS Vladimir Kochmarov1, Ekaterina Kozuharova1*, Zheko Naychov3, Georgy Momekov2 and Irena Mincheva1 1Department of Pharmacognosy, Faculty of Pharmacy, Dunav 2, Sofia 1000, Bulgaria. 2Department of Pharmacology of Pharmacy, Dunav 2, Sofia 1000, Bulgaria. 3University Hospital Lozenetz, Sofia, Bulgaria.

ABSTRACT The objective of the present study was the contemporary folk medicine application of snakehead, Arum maculatum L. (Araceae) with an emphasis on its effect against haemorrhoids. Therefore we set ourselves the following tasks: 1) to collect the contemporary traditional knowledge about the therapeutic effects of snakehead; 2) to collect anecdotal reports from persons who are known to have used the snakehead for treating haemorrhoids; 3) to analyze the data obtained about the effectiveness of this herb against haemorrhoids and other medicinal conditions in order to determine the mechanism of its activity; 4) to investigate how popular snakehead is nowadays in Bulgaria as a medicinal . All randomly selected informants basically recognized the plant but only 16% knew about its medicinal properties. With regard to the medicinal application, its properties as a cure for haemorrhoids was most frequently cited. Less frequently mentioned was the use of A. maculatum for chronic traumatic pain, purulent infections, and for “melting of adipose formations”. Informants who had used snakeshead for haemorrhoids categorically reported improvement of the condition. The analysis of the therapeutic effect of A. maculatum tuber both directly in the treatment of various haemorrhoids and indirectly in cases of chronic traumatic pain and purulent infections allows us to hypothesise that the plant substance: 1) contracts the blood vessel walls; 2) has an anti-inflammatory effect and 3) has a painkiller effect. The knowledge about these empirically established activities will be used to design in vitro pharmacological tests to better study the therapeutic effect in the treatment of haemorrhoids. Even though the definitive treatment of haemorrhoids is basically considered surgery it has sometimes side effects that make the possible application of the herb preferable.

Keywords: folk medicine, ethnomedicine, haemorrhoids, Arum.

INTRODUCTION found in renaissance herbals, e. g. Snakehead Arum maculatum L. (Araceae, sect Zwinger, XVII century, to treat malaria. 2 Arum, with rhizomatous tuber) has been known Culpeper 3 reports that “it is a present and sure as a medicinal plant for centuries. It is remedy for poison and the plague…. and riddeth mentioned in “The pharmacopeia of Pedanius away phlegm from the stomach, chest, and Dioscorides” (20-70 AD), entitled Περί ύλης lungs”. ιατρικής (latinized as De Materia Medica, On In Bulgaria, A. maculatum is an officially Medical Matters), originally written in Greek acknowledged medicinal plant4, even though it about the year 65 AD. The plant was then is not often used.5,6 In Bulgarian traditional and believed to cure snake bites.1 It is among the folk medicine, A. maculatum tuber has been

394 IJPCBS 2015, 5(2), 394-402 Ekaterina Kozuharova et al. ISSN: 2249-9504 shown to be widely used in cases of kidney containing the flavonoid diosmin. Open stone, colitis, liver disease or hyperacidity. The haemorrhoidectomy described by Milligan and plant has been also reported as a remedy for Morgan has been one of the common haemorrhoid.5-10 Moreover, A. maculatum tuber procedures carried out for haemorrhoids up to extract has been clinically tested for its anti- the present time, but lately an easier procedure inflammatory activity in the intestinal and known as anal stretching and ligation has been respiratory tract.5 According to the herbalist suggested. 27 For more than 30 years, diosmin Georgy Nedev” A. maculatum”, known in has been used as phlebotonic (phlebotonics are Bulgarian language as “zmiiska hurka”, “zmiiski a class of drugs that are often used to treat lapad”, “zmiisko grozde”, “ustrelche”, is used in chronic venous insufficiency. 28 traditional folk medicine for haemorrhoid. 11 It is The objective of the present study was to important to note that A. orientale (sect. examine the contemporary folk medicine Dioscoridea, with discoid tuber) should not be application of snakehead, Arum maculatum L. confused with A. maculatum.6 (Araceae) with an emphasis on its effect in the In the western part of the (Peshkopia, treatment of haemorrhoids. Therefore we set eastern Albania), A. maculatum has a ritual use ourselves the following tasks: 1) to collect the in spring festivals.12 To the west of the Balkans, contemporary traditional knowledge about the e.g in south Italy, A. italicum Mill. is used in therapeutic effects of snakehead; 2) to collect traditional and folk medicine in the treatment of anecdotal reports from persons who are known warts 13,14. Leaves and tubers of A. italicum are to have used the snakehead for treating macerated in oil and applied in cases of haemorrhoids; 3) to analyze the data obtained rheumatic pains in Sicily 15,16 about the effectiveness of this herb in the To the east of the Balkans, Arum spp. is treatment of haemorrhoids and other medicinal mentioned more often in the ethnobotanical conditions in order to determine how it works;; studies. In Turkey A. maculatum is applied for 4) to assess the popularity of snakehead colitis.17 In ethnopharmacological records from nowadays in Bulgaria as a medicinal plant. western Turkey, A. maculatum is a cure for haemorrhoid.18-20 Further east (Asia Minor part MATERIAL AND METHODS of Turkey), other Arum spp. (belonging to sect. During the March – November 2013 and June – Dioscoridea, with discoid tuber) are mentioned August 2014 periods, semi-structured to have the same application as a treatment for interviews were conducted with Bulgarian haemorrhoid. According to Gürhan and Ezer21, people in order to investigate the traditional A. elongatum Steven, A. balansanum R. Mill., and ethnobotanical knowledge of the remedial A. detruncatum C.A. Meyer ex Schott together properties of Arum maculatum. with vulgaris Schott are among the plants (84 plant genera belonging to 46 families) Study sites that are used for the treatment of haemorrhoid The interviews were performed in 11 districts of in Turkey. In the Asiatic part of Turkey, A. Bulgaria (Fig. 1), in the vicinity of native maculatum is also applied in cases of populations of Arum spp. We applied this rheumatism.22 Local people of Solhan District approach, as the informants would be located in the eastern Region of Turkey potentially familiar r with snakehead plants in apply A. elongatum Steven subsp. detruncatum the vicinity of their settlements and they (C.A. Meyer ex Schott) H. Riedl as a compress or possibly might have traditional information else “drink a decoction of of the plant on an about them. These study sites were also part of empty stomach in the morning” to treat our field research on the autecology and abdominal pain, arterial hypertension, diabetes horology of Arum spp. distributed in Bulgaria. mellitus, goitre and rheumatism. 23 29,30. Haemorrhoids are vascular structures in the anal canal. They become pathological (extreme Informants in a way that is not normal or that shows an We aimed to collect as much information as illness) or piles when swollen or inflamed. possible about the medicinal properties of Haemorrhoids often break and hardly heal. They snakehead. Therefore we addressed people with can be very painful and occasionally cause different attitudes to the plant. The informants serious anemia.24,25 Haemorrhoids are a very fell into the following groups. common anorectal condition defined as the Firstly, we interviewed herb sellers (n = 3), at symptomatic enlargement and distal two markets in Sofia (two women at the market displacement of the normal anal cushions.26 Zhenski Pazar, and a man at the Market Ivan Orthodox medicine usually treats haemorrhoids Vazov), because they offered snakehead tubers through surgery combined with medication together with other herbs. This was an

395 IJPCBS 2015, 5(2), 394-402 Ekaterina Kozuharova et al. ISSN: 2249-9504 indication that they possessed traditional therapeutic effect of the plant substance Ari knowledge of the remedial properties of A. Tubera and longevity of the positive effect; side maculatum and we needed to obtain details effects, awareness of plant toxicity; attitude to about which applications they were aware of. traditional versus conventional medicine, etc. Herb sellers are seldom found in Bulgarian The following analyses and interpretations of markets and these were all we located during the data were carried out the period of investigation. 1) We calculated the ratio of people Secondly, we interviewed a random sample of (percent), who i) are familiar with local people (n = 50 of age between 18 and 88 snakeshead versus those who never heard years). We tried to interview as many local of it; ii) are ignorant versus people as possible in the vicinity of the knowledgeable about its medicinal snakehead’s populations (Fig. 1). The number of properties. Considering the data sample informants in each district corresponded to the we used descriptive statistics. size of the settlements/number of inhabitants. 2) We classified and sorted the reports about All interviews were conducted ex situ (in the the usage of this herb. settlements, without the presence of the live 3) We analyzed the feedback from the plants in their native populations) – the informants who have used the snakehead is a distinctive plant and describing snakeshead to cure haemorrhoids in the specific features of the plant (leaves, order to test the positive effect of the and infrutescence) worked very plant substance. Comparatively analyzing well. Additionally we double-checked the the medical conditions where plant recognition by using colour prints of substance Ari Tubera had positive effect, photographs. A total of 23 men and 27 women we formulated a hypothesis about the were interviewed. People often decoded the functional mechanism of the plant. question about their education and profession as an intrusion into their private space; RESULTS AND DISCUSSION therefore these data are scarce. In this random Results from our interview of random sample of group of informants we aimed to test 1) local people (n = 50, men and women; age whether the people know/recognize the between 18 and 88 years) in different regions of snakehead, A. maculatum; 2) whether they Bulgaria demonstrated that the informants possess traditional knowledge of the remedial basically knew/recognized the plant due to its properties of the snakehead; 3) their level of very specific inflorescence and fruits and only awareness of the medicinal properties of few people had never heard of it (Fig. 2). snakehead. In this group of informants (random sample of Thirdly, we interviewed a random sample of local people) only 8 persons (16%) reported local people (n = 58 of age between 40 and 80 knowledge of the medicinal properties of the years) in the Rhodopes (Fig. 1), consisting of 13 plant (Fig. 2). men and 45 womenIn this random group of We presented in Table 1 a compilation of data informants we aimed to test how the local for particular medicinal applications received people treat haemorrhoids (“majasul”) from 8 informants from the random sample of traditionally. This investigation on the folk local people and 3 herb sellers (11 informants medicine treatment of haemorrhoids was a part totally). Among all informants whose response of general ethnopharmacological research in the concerned the medicinal application of the Rhodopes. Finally we knew, based on our snakeshead, most acknowledged its application previous experience, some people who had used against haemorrhoids (72% - all of the herb A. maculatum to treat haemorrhoids. We sellers and some of the random sample of local interviewed these informants (n=4) and they people). It is less popular as a cure against provided data about persons (n=34, men and chronic traumatic pain (9%), purulent infections women) who had experienced the therapeutic (9%), and for “melting of adipose formations” effect of the plant substance Ari Tubera as a (9%). Interestingly the Bulgarian folk medicine treatment for haemorrhoids. We developed a tradition of applying rizhomes macerated in oil questionnaire to obtain feedback about the as a cure for joint pains is related with the folk effectiveness of the plant substance in this medicine tradition of local people in Sicily, medicinal condition based on their empiric where a rather similar type of application experience. The following questions were against rheumatic pains is recorded15 asked: details of the medicinal condition; plant Less than a quarter (21%) of the informants in part used; method and time of collection, the Rhodopes reported traditional treatment of method of application; conventional haemorrhoids, (12 persons – 9 of them females medications used to treat the medical condition; and 3 males). They listed for internal use Arum

396 IJPCBS 2015, 5(2), 394-402 Ekaterina Kozuharova et al. ISSN: 2249-9504 maculatum, Araceae, Juniperus communis L., Despite the fact that the plant is considered Cupressaceae (galbulae), Pulmonaria officinalis toxic no adverse reactions were reported for the L., Boraginaceae Achillea millefolium L., doses applied, except one case of irritation when Asteraceae, Viscum album L., Viscaceae trying to swallow the piece without water, but Onopordum acanthium L., Asteraceae, after drinking water, the irritation disappeared Tanacetum balsamita L., Asteraceae, Teucrium (Table 2). The toxicity is due to the presence of polium L., Lamiaceae. For external use were raphides.29 Also Arum maculatum is known to listed (sit baths) Cotinus coggygria (Scop.), storage lectins. Araceae lectins are a family of Anacardiaceae Consolida spp. Ranunculaceae, closely related proteins, the sequence of which Persicaria hydropiper (L.) Delabre, Polygonaceae contains the highly conserved domains of the Teucrium polium L., Lamiaceae Tanacetum Amaryllidaceae, Alliaceae, and Orchidaceae balsamita L., Asteraceae or unguents Calendula lectins. With respect to their specificity the officinalis L., Asteraceae. Most often reported Araceae lectins resemble the previously isolated were the snakehead Arum maculatum and Man-binding lectins from Amaryllidaceae, Cotinus coggygria (twice each). Interestingly in Alliaceae, and Orchidaceae , except that the area of the Rhodopes (East Rhodopes) it was they interact more strongly with glycoproteins. reported that the fruits of Arum maculatum 30 At the same time lectins are considered toxic. were applied, while most of the other reports 31 However we do not exclude the possibility referred to usage of the rhizome. that it is actually the lectins that are responsible Data received by the informants who have used for the therapeutic effect of the snakehead in the the snakeshead for haemorrhoids is treatment of haemorrhoids. summarized in Table 2. The results of the analysis of the therapeutic effect in cases of CONCLUSION haemorrhoids demonstrate categorically The analysis of the therapeutic effect of Arum improvement of the condition. Most informants maculatum tuber both directly in various insisted that a prolonged process of treatment haemorrhoids and indirectly in cases of festers was not necessary even though it depended on and old traumas suggests that the plant operates the level of suffering. The positive effect in the following manner: 1. it contracts the blood remained for a long time and further treatment vessel walls; 2. it has a demonstrable anti- was not necessary in many cases. Consequently, inflammatory effect; 3. it acts as a painkiller. according to the informants’ feedback, there is a Experimental tests of Arum maculatum leaf stable and positive effect of the plant substance. extract demonstrated antibacterial properties 32 It was noted that A. maculatum was more in particular against some of the tested gram efficient as a cure for haemorrhoids as negative bacteria.33 compared to medications with diosmin active There are a number of implications for further compound (Table 2). Due to the specific activity research. The knowledge about these of the flavonoids (reducing the venous stasis empirically established activities will be used to and permeability of the capillaries), medications design in vitro pharmacological tests to with diosmin active compound are used to treat undertake improved studies of the therapeutic symptoms associated with venous-lymphatic effect with regard to haemorrhoids. The fact that insufficiency characterized by weight and pain in one case the effect of Arum maculatum plant in lower limbs, the feeling of having "tired legs" substance in the treatment of haemorroids was in the morning. Medications with diosmin active compared to the effect of medication based on compound are recommended in the symptoms diosmin available in the pharmacy store and the associated with acute haemorrhoidal attacks. It result was positive for the herb (Table 2) has been applied lately for other therapeutic increases the necessity of such tests. purposes, such as cancer, PMS, colitis, and Additionally even though the definitive diabetes. Its vascular protective, anti- treatment of haemorrhoids is basically inflammatory and anti-mutagenic effects have considered to be surgery, it sometimes has been proved. 28 negative side effects. This makes the possible Notably, one of the informants warned that application of the herb preferable. during the treatment alcohol should be avoided while one of the herb sellers preserved the ACKNOWLEDGEMENTS tubers in alcohol. However in most cases the Our gratitude to Frank O'Reilly, B.A., Ph.D (Uni opinion is that the effect is stronger if the tuber London) for the correction of the English is fresh when applied even though the dried language. tuber and even the pulp of the fruits posses the above mentioned therapeutic effect.

397 IJPCBS 2015, 5(2), 394-402 Ekaterina Kozuharova et al. ISSN: 2249-9504

Table 1: Informants (N=11) who reported medicinal properties for the snakehead, Arum maculatum. Informants were divided into 2 categories – i) persons from the random excerpt who possessed knowledge about snakehead therapeutic effect (N=8) and ii) persons who are known for having experience in traditional herbal medicine (N=3). Information is organized in columns according to the medical conditions Haemorrhoids “Adipose Medical Haemorrhoids Arthralgia and chronic traumatic and other Furuncle formatio condition pain diseases ns” Number of reports for the particular 7 1 1 1 1 medical condition treatment Two women above 60 years old herb sellers at the A man above 60 A woman market A man about 50 years old, herb about 60 A man about 50 years old, mountain Informant details Five women above years old, seller at the years, guide 60 years old from biologist market teacher rural areas

Fresh tubers (or The dried if no fresh Small piece of the tubers are available) are Arum maculatum (grated) Tuber pieces The tubers are ground and mixed cut into pieces tuber is cut and are Way of aplication preserved in with salad oil. Applied as approximately the the top of the applied on spirit. formentation. size of a maize furuncle is the grain and applied touched with it. targeted per os. area. Even the hand holding the piece Precautions! Poisonous might be scalded. Use glove. Adverse reactions The only effective “They cure with no need melt after for additional The best cure for Effectiveness 2-3 The only effective remedy. treatment. furuncles applicatio

ns.”

398 IJPCBS 2015, 5(2), 394-402 Ekaterina Kozuharova et al. ISSN: 2249-9504

Table 2: Data, obtained from informants who are known to have used the snakehead for treating haemorrhoid Informants 1st Informant 2nd Informant 3rd Informant 4th Informant gender female male male male age 70 33 34 51 education university university university university profession botanist medical doctor medical doctor pharmasist Haemorrhoids – Internal Haemorrhoids – bleeding, inflamed and indications - medical Haemorrhoids and their haemorrhoids – bleeding, inflamed and painful (multiple use in condition complications. bleeding painful all of the above

mentioned conditions) The tuber: 2-3 pieces of the fresh (or fresh frozen) tuber, piece 1 piece approximately approximately the size the size of maize grain is The tubers are cut in pieces of large maize grain are swallowed (without approximately the size of maize put inside a piece of The tubers are cut chewing) 3 times a day grain. No more than 5 pieces are bread and swallowed in pieces Way of application after meals, in 3 swallowed without chewing with every day in 3 approximately the subsequent days. some water. It must be done once subsequent days. size of maize grain. The same procedure is per year. Berries: 4-5 fresh repeated after 10 days. berries are eaten every

day in 3 subsequent days without swallowing the seed. Fresh tubers have Fresh tubers are stronger effect, but Fresh tubers are stronger. stronger. dried are also usable. The tubers are poisonous and they The tubers are very pungent. The shouldn’t be taken in sensation it rather painful. This is greater dose. Optionally, The tubers are Precautions! the reason why they should be they may be put in a poisonous. taken inside a piece of bread and piece of bread. No directly swallowed. alcohol during the treatment. Not known when the correct dose is applied, but some care should be taken. Only one person Adverse reactions had irritation when trying to swallow the piece without water, but after drinking water, the irritation disappeared. * Anyway, the definitive The improvement of the treatment of the haemorrhoids is symptoms is dramatic – The effect in surgical. after the second day of unbelievable – the applications. The bleeding stops, the pain symptom free period is relieved, the nodes The only effective lasted for months. shrink. It is especially remedy, no Recently I haven had obvious in the more relapses have been Effectiveness any symptoms at all. severe cases. Even if the observed. * Generally, I prefer the problem is not entirely orthodox medicine, but cured, it is alleviated in this case, the surgery and if necessary, the often gives relapses of treatment may be the condition. repeated next year. * Note – the informer is a * Note – the informant neurologist is a surgeon I have I have recommended Do not have information from I have recommended recommended this Data from further this to 29 people, all of othеr people – personal positive this to 1 more person, to 2 people, both of recommendation them with good effect. experience who also cured. them with positive outcome. Total feedback

positive effect 29 1 2 2 neutral or negative 0 0 0 0 effect

399 IJPCBS 2015, 5(2), 394-402 Ekaterina Kozuharova et al. ISSN: 2249-9504

Fig. 1: Study sites. Legend:  random sample of local people in the vicinity of the snakehead’s populations ▲ random sample of local people (n = 58) from the Rhodopes about the traditional treatment of haemorrhoid (“majasul”). This investigation on the folk medicine treatment of haemorrhoid was a part of general ethnopharmacological research in the Rhodopes

know the plant and know other use than medicinal; 2% know the plant and know medicinal properties; 16%

never heard of this plant; 10%

know the plant but do not know medicinal properties; 72%

Fig. 2: Ratio of the informants [%] and their knowledge about the snakehead and its application

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