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Author’s Accepted Manuscript Ethnopharmacological Survey about Medicinal Plants Utilized by Herbalists and Traditional Practitioner Healers for Treatments of Diarrhea in the West Bank/ Palestine Nidal Amin Jaradat, Ola Ibrahim Ayesh, Cynthia Anderson www.elsevier.com/locate/jep

PII: DOI: Reference:

S0378-8741(16)30056-3 http://dx.doi.org/10.1016/j.jep.2016.02.013 JEP9967

To appear in: Journal of Ethnopharmacology Received date: 2 November 2015 Revised date: 9 February 2016 Accepted date: 12 February 2016 Cite this article as: Nidal Amin Jaradat, Ola Ibrahim Ayesh and Cynthia Anderson, Ethnopharmacological Survey about Medicinal Plants Utilized by Herbalists and Traditional Practitioner Healers for Treatments of Diarrhea in the West Bank/ Palestine, Journal of Ethnopharmacology, http://dx.doi.org/10.1016/j.jep.2016.02.013 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Ethnopharmacological Survey about Medicinal Plants Utilized by Herbalists and Traditional Practitioner Healers for Treatments of Diarrhea in the West Bank/ Palestine Nidal Amin Jaradat*1, Ola Ibrahim Ayesh1, Cynthia Anderson2 1

Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National

University. Nablus, Palestine. P.O. Box 7 2

English Language Center, An-Najah National University. Nablus, Palestine. P.O. Box 7

*

Corresponding author. E-mail: [email protected]

Abstract Ethnopharmacological relevance Folk herbal medicine knowledge and its utilization by aboriginal cultures are not only useful for conservation of cultural traditions and biodiversity, but also useful for community healthcare and drug discovery in the present and in the future. Aim of the study Using a semi-structured questionnaire, an ethnopharmacological survey of medicinal plants used for treatment of diarrhea in the West Bank/ Palestine was investigated. Results Information about fifty medicinal plants used for treatment of diarrhea, including the names of plants, parts used, mode and methods of preparation was obtained from 100 traditional healers and herbalists. This research is the first scientific work in the Middle East to collect data about 1

plants used by traditional healers for treatments of diarrhea and their evidence based effects against this disease. The fidelity levels were 97% for Salvia fruticosa, Teucrium polium and Musa paradisiaca, 95% for Camellia sinensis and Aegle marmelos, 79% for Oryza sativa and Solanum tuberosum, 77% for Quercus boissieri, 66% for Psidium guajava, 56% for Anthemis palestina, 54% for Solanum nigrum and 52% for Juglans regia while the highest use and choice values were for Salvia fruticosa, Teucrium polium and Musa paradisiaca as well as the factor of informant’s consensus for medicinal plants used for treatment of diarrhea was 0.505.The leaves were the most commonly used parts, followed by fruits, roots and rhizomes, while decoctions and infusions are the preferred methods of preparation. Conclusions The Palestinian traditional medicine is rich with herbal remedies for treatment of diarrhea in comparison with other countries, but most of these herbal remedies lack standard in-vitro and invivo evaluations to establish their antidiarrheal effects. Therefore, the information obtained can serve as a basis for further phytochemical and pharmacological studies to determine their efficacy and safety which might contribute to a better integration of Palestinian traditional medicine into the national health system in the future. Keywords: Medicinal plants; Diarrhea; Herbalists; Traditional Practitioner Healers; West Bank/ Palestine 1. Introduction

2

Herbal medicine has a long history of usage and has become an important source of information for health care systems in both developed and developing countries (Pan et al., 2014). This kind of medicine needs extensive knowledge of practical skills and theory and most of it is based on cultural beliefs and experiences, which aim for the maintenance of health and prevention of diseases (Kamsu-Foguem et al., 2013). Folk uses of medicinal natural products in healthcare practices can provide clues to new areas of research and are considered as invaluable sources of pharmaceutical products (Ji et al., 2009). In all types of folk medicine, natural plant products are considered the most available and cheapest sources for the treatment and prevention of various diseases (Cowan, 1999; Eisenberg et al., 1993; Hostettmann et al., 2000). They have been a unique source of pharmaceuticals and constituted the most common human use of biodiversity (Hamilton, 2004; Hiremath and Taranath, 2010). All over the world about 4,200,000 flowering plants have been reported and more than 50,000 plants species are used for medicinal purposes (Govaerts, 2001). Diarrhea is one of the most common diseases worldwide, especially in the developing countries and is still the second leading cause of death among children under five years globally; about 1.5 million children die each year due to diarrhea. It kills more young children than AIDS, malaria and measles combined (Croft and Weiss, 1999; WHO, 2009). Palestine is considered a small country when compared with other Middle Eastern and other countries worldwide (Cohen, 1995). Despite its small geographic area, Palestine has extraordinary plant diversity. In fact, about 2700 plant species are available in this country and

3

about 300 plant species are currently used in the Palestinian traditional medicine (Fulder and Said, 2009). Traditional medicine is the most widely used medical system in the rural setting of the all regions in the West Bank area (Ali-Shtayeh et al., 2008). Conventional medicine is often costly and frequently inaccessible in these regions due to the political conflicts. Not only is traditional medicine popular and acceptable due to its important role in primary health-care delivery systems, but in many areas it has been the only health care system available (Ben-Arye et al., 2009). The percentage of children who had diarrhea in the West Bank- Palestine was 14.8% in 2012 while 11.7% in 2006 (PCBS, 2012), indicating an increase of distribution of this gastrointestinal disease. Regarding this, our research focuses on medicinal plants used in the West Bank (Palestine) in all its regions used by traditional herbal practitioners and herbalists to treat this. 2. Materials and methods 2.1. Study Areas West bank is an important territory of Palestine. The climate in the West Bank is mostly Mediterranean, slightly colder in mountains and hills compared with the shorelines in the west lands. In the east, it includes the desert and the shoreline of the Dead Sea, both with dry and hot climate. The shores of the Dead Sea are about 430 meters below sea level and it is considered the Earth's lowest elevation on land. Accordingly, all these factors reflected the huge diversity of the West bank flora. This diversity is directly reflected on the distribution and diversification of

4

agricultural patterns, from the rain-fed farming in the mountains (Jerusalem, Ramallah, Hebron, Nablus, Bethlehem, Salfeit) to an irrigated agriculture as in Jenin, Tobas, Toulkarem , Qalqilya and Jericho lands (Ali-Shtayeh and Jamous, 2002; Ali-Shtayeh et al., 2008). Palestine is classified as a low income country according to the World Bank. West Bank relatively is a small area of Palestine with total area of 5,655 km2, is still under the Israeli occupation which further affect its economy. The socio-demographic, political and socioeconomic situation of the population are very similar (Akhlaq et al., 2015). Accordingly, it seems that these factors did not play an essential role in the selection of the plants by herbalists and traditional healers to treat diarrhea. An ethnopharmacological survey (questioner-based cross sectional study) on medicinal plant remedies employed in the treatment of diarrhea was conducted by researchers. Areas visited included all regions of the West Bank/ Palestine, including Nablus, Jenin, Tubas, Toulkarem, Salfeit, Qalqilya, Ramallah, Jericho, Jerusalem, Bethlehem and Hebron (Figure 1) between February and June, 2015. The study protocol and the informed consent forms were approved by the Institutional Review Board (IRB) at An-Najah National University. The study was conducted in accordance with the requirements of the declarations of Helsinki (World Medical Association 2008), the current Good Clinical Practice (GPC) Guidelines (EME 1997) and the International Conference Harmonization (ICH1996) Guidelines, and written informed consent for participation in the study was obtained from participants.

5

To protect the interest of traditional healers and herbalists, they were informed by the researchers in details about the current study and its purposes, also they were not offered any incentives and they were able to withdraw from this study at anytime. The investigation was carried out using interviews among 100 traditional healers and herbalists (N = 100) that utilized medicinal plants to treat common illnesses in the West Bank/ Palestine. The herbal practitioners consulted were trained healers of repute within the various Palestinian communities. (Social demographic factors are presented in Table 1). Table 1: Social demographic factors related to the respondent Variable

Number of herbalists and traditional healers (N = 100)

Gender Male

69

Female

31

Education level Uneducated

17

Elementary

9

Secondary school

28

High secondary school

33

Undergraduate

12

Graduate (higher

1

education)

6

Residency (region names) Bethlehem

9

Hebron

12

Jenin

8

Jericho

7

Jerusalem

10

Nablus

13

Qalqilya

6

Ramallah

9

Salfeit

8

Tubas

8

Toulkarem

10

Age (mean ± SD) years

55.1 (20.4)

Experience (mean ± SD) years

29.7 (12.4)

Questionnaires were administered through personal contact discussions. The personal discussion between the researcher and informants was important in order to agree on the exact name when there was a difference in the Arabic names among the different districts. This method has proven to be a very effective and doable option of data collection. The questionnaire was anonymous, pretested by a pilot study using 10% of the sample for reliability and to check the validity and clarity of the questionnaire.

7

The herbal practitioners provided information on plants used to treat or relieve diarrhea, describing names, plant parts used, and modes and methods of preparation. About twenty five visits were conducted involving one hundred traditional healers, herbalists and hawkers in traditional medicines during with interviews ranging from 30 to 90 min, with more than one visit per interviewee in most cases. Interviews were conducted in Arabic, the local language of the informants; the plant names were given in Arabic later translated into English and Latin using reference books (Evans, 2009; Ghazanfar, 1994; Gledhill, 2008; Zohary, 1966; Zohary, 1972). In most cases, the interviews often started in the form of informal discussions to gain the confidence of the interviewees. The collected plant samples from these informants were stored in the pharmacognosy and herbal products laboratory at An-Najah National University in special glassware and special frames. They were identified later by a team of teaching assistants and technicians under the supervision of the pharmacognosist Dr. Nidal Jaradat, and the voucher specimens were stored and deposited for all collected plants in the pharmacognosy and herbal products laboratory, at the Pharmacy Department, Faculty of Medicine and Health Sciences, An-Najah National University. All the fifty plants species which were mentioned by the informants were identified and confirmed by using photographs from reference books (Feinbrun Dothan, 1978; Zohary, 1966; Zohary, 1972) and live herbarium specimens. 2.2. Data analysis 8

The Fidelity level (Fl) quantified the importance of a species for a given purpose and defined as the ratio between the number of informants who independently suggested the use of a species for treatment of diarrhea and the total number of informants (Hoffman and Gallaher, 2007). Fl can be calculated according to the following equation:

Where: Np: is the number of informants that reported a use of a plant species to treat diarrhea. N: is the number of all informants. The use-value (UV) is a quantitative method that can be used in order to prove the relative importance of species known locally. It is can be calculated according to the following equation:

Where UV is the use value of a species; U is the number of citations per species; n is the number of informants (Friedman et al., 1986; Jaradat et al., 2016) Factor of informant’s consensus (Fic) was calculated according to the following equation:

9

Where Nur is the number of use citations in antidiarrhea category and Nt is the number of taxa used for treatment of diarrhea.

This factor is employed to indicate how homogenous the information is. Fic value is close to 0 if plants are chosen randomly, or if informants do not exchange information about their use. High values of Fic (close to 1) occur when there is a well-defined selection criterion in the community and/or if information is frequently exchanged between informants (Gazzaneo et al., 2005). The Choice Value (CV) method considered important assessment tool to measure relative plant species for treatment of diarrhea (Kremen et al., 1998). The CV is calculated as in the following equation:

Pcs: percent of informants that cited Species 1 for treatment of certain disease. Sc: is the total number of species mentioned for treatment of disease by all informants. Choice values are ranked from 0-100 with 100 indicating complete preference and/or fewer alternatives

3. Results and discussion As shown in Table 1, most of the respondents who worked in this field were males. Most of them had higher educational level. In fact about 33% of the interviewed were high secondary school graduates. The table also showed that the majority of respondents were from areas of the West 10

Bank that mostly depended on agriculture or grazing as a mean of income (Nablus, Hebron, Jerusalem and Toulkarem). Regarding the issue of training and knowledge acquisition, 67% of the respondent herbalists and traditional healers acquired their skills through observing their parents or other family members in a family business, 29% acquired their skills through course works and apprenticeship and about 4% claimed they had a divine gift for the healing of certain diseases. The leaves were the most commonly used parts of plants for the treatment of diarrhea followed by fruits and roots. The modes and methods of preparation varied considerably from one healer to another; however, all of these methods were administered orally as described by the interviewees and shown in Table 2. Table 2: The medicinal plants used for treatment of diarrhea, the plants parts used, fidelity level, modes and methods of preparation.

Plant #

Scientific names/ Common names/ Arabic names/ Voucher specimen code

Family

1. Salvia fruticosa Mill./ Lamiaceae Sage / Maramiya/ Pharm-PCT-2117

Part used and mode of preparation

Method of preparatio n, reference to evidence based uses

Aerial parts/ Boil about 10 grams of the plant in 100 ml water. 50 ml of this decoction is to be given orally before each meal.

Decoction 97 / Antispasm odic effect (Khan et al., 2011).

11

Fl ,%

UV

CVspecies

0.97

1.94

2. Teucrium polium L./ Teucrium/ Ja’da/ Pharm-PCT-2418

3. Musa paradisiaca L./ Banana / Moz/ Pharm-PCT-2715

4. Camellia sinensis (L.) Kuntze/ Black Tea/ Shae/ PharmPCT-2706

Lamiaceae

Leaves / Steep about 15 grams of the leaves in 100 ml water for two hours. This infusion is to be given after each meal.

Infusion/ 97 Antispasm odic and antidiarrhe al effects (Allahtava koli et al., 2013; Sadraeisad raei et al., 2001)

0.97

1.94

Musaceae

Fruit/ Crushed fresh green fruit. To be given instead of food.

Crushed raw fruit/ Antidiarrh eal activity; also its fruits are rich in carbohydr ates, vitamins and some minerals which are very useful in case of diarrhea (Adeyemi and Oladiji, 2009; Hossain et al., 2011)

97

0.97

1.94

Decoction / Astringent effect was

95

0.95

1.9

Theaceae

Leaves/ Boil about 20 grams of Tea leaves with 100 ml 12

water. This is to be orally given when required.

approved for use against diarrhea (Ratnasoo riya and Fernando, 2009).

Fruit/ Extract 80 ml of juice to be given orally five times a day.

Unripe 95 fruit juice/ Rich with tannins (astringent effect) This plant was approved for use against diarrhea (Sekar et al., 2011).

0.95

1.9

6. Oryza sativa L. / Rice Poaceae / Roz/ Pharm-PCT2718

Seed/ Boil 50 gram rice in 150ml water for 15 minutes. Give 50ml rice water orally every 30 minutes until the diarrhea stops.

Decoction / Rich in carbohydr ates which can be useful in case of diarrhea (Jing et al., 2012).

79

0.79

1.58

7. Solanum tuberosum L. / Potato / Batata/ Pharm-PCT-2723

Tubers/ Boil 250 grams potatoes in 500ml water for 25 minutes. The cooked potato is to

Decoction / Rich in carbohydr ates therefore it is useful in case of diarrhea

79

0.79

1.58

5. Aegle marmelos (L.) Correa / Quince / Safarjal/ Pharm-PCT2702

Rutaceae

Solanaceae

13

8. Quercus boissieri Reut. / Oak /

be eaten three times a day instead of food.

(Garcia et al., 2003).

Fagaceae

Bark/ Boil 100 grams from the ground bark in 200 ml water for 20 minutes. 20 ml of this decoction is to be given twice daily.

Decoction / Rich in tannins (Mikaili et al., 2012).

Myrtaceae

Balloot/ Pharm-PCT1977

9. Psidium guajava L./ Guavas / Jauafa/ Pharm-PCT-2720

10. Anthemis palestina Compositae (Reut. ex Kotschy) Reut. ex Boiss./ Chamomile/ Babonaj/ Pharm-PCT-188

11. Solanum nigrum L./ African night-

Solanaceae

77

0.77

1.54

Leaves/

Decoction 66 / Boil about 30 Antimicro grams of bial and leaves in 100 antidiarrhe ml water for al 5 minutes. activities This (Jaiarj et decoction is al., 1999). to be given three times a day after meals.

0.66

1.32

Flowers/

Decoction 56 / Boil about 10 Antispasm grams of the odic and flowers in antimicrob 100 ml ial effects water. This (Bardawee decoction is l et al., to be given 2014). before meals three times daily.

0.56

1.12

Leaves/ Boil about 25

0.54

1.08

14

Decoction /

54

shade/ Bandoret alhya/ Pharm-PCT2301

grams from the leaves in 100 ml water. 10 ml of this decoction is to be orally given when required.

Antinocic eptive, antiinflammat ory and antipyretic effects (Zakaria et al., 2006).

12. Juglans regia L. Juglans / Walnut / Joz/ Pharm-PCT2714

Juglandacea e

Fruits (hull)/ Boil about 20 grams from the green hull in 50 ml water. This decoction is to be orally given five times a day.

Decoction / Antiviral activity (Mouhajir et al., 2001).

52

0.52

1.04

13. Inula viscosa (L.) Aiton/ Inula/ Altayon/ PharmPCT-2713

Compositae

Leaves/ Boil about 20 grams from the ground leaves in 100 ml water, 50ml from the decoction is to be given 5-6 times daily.

Decoction 45 / Antimicro bial activity (AliShtayeh et al., 1998) .

0.45

0.9

14. Sesamum indicum L./ Sesame / Semsem/ Pharm-PCT-2722

Pedaliaceae

Leaves/ Boil about 20 grams from the leaves in 100ml water, 50ml of this is to be given orally three times daily after meals.

Decoction / Antimicro bial activity (Bankole et al., 2008).

0.43

0.86

15

43

15. Achillea falcata L. / Achillea / Alalfya/ Pharm-PCT-18

Compositae

Flowers/ Steep 2 grams of the flowers with 100ml water for 5 hour. About 20ml of this infusion is to be given orally three times a day.

Infusion/ Antibacter ial effect (Karaalp et al., 2009).

42

0.42

0.84

Compositae

Leaves/ Steep 15grams of the leaves in 100ml water for 12 hours, About 10ml from this infusion is to be given twice a day.

Infusion / Contains vitamins and minerals which can be useful in case of diarrhea (Leheda et al., 2006).

41

0.41

0.82

17. Hibiscus micranthus L.f./ Roselle / Karkade balade/ Pharm-PCT-1195

Malvaceae

Flowers/ Steep 40 grams of the flower petals with 100ml boiled water for two hours. About 20ml of the infusion is to be given three times a day.

Infusion / 39 Contains high content of tannins and has antimicrob ial effects (Okoli et al., 2010).

0.39

0.78

18. Curcuma longa L. / Turmeric / Curcum/ Pharm-PCT-2709

Zingiberace ae

Rhizomes/ Steep 50 grams of ground rhizomes in

Infusion/ Antiviral and antibacteri al effects

0.38

0.76

16. Lactuca undulata Ledeb. / Bitter lettuce / Khas barey/ PharmPCT-1321

16

38

100ml water (Chengaia for one night. h et al., 10ml of the 2010). infusion is to be given three times daily. 19. Foeniculum vulgare Mill./ Fennel / Showmer/ PharmPCT-1041

20. Arctostaphylos uvaursi (L.) Spreng./Bearberry / Enab aldob/ PharmPCT-2705

21. Ziziphus lotus (L.) Lam./ Lotus jujube/ Zyzafun/ PharmPCT-2691

Apiaceae

Fruits/ Boil about 20 grams of the grounded Fennel fruits in 100 ml water, 30 ml of this decoct is to be given three times daily before meals.

Decoction 37 / Antidiarrh eal, antimicrob ial and antispasm odic effects (Brandelli et al., 2009; Ruberto et al., 2000; Savino et al., 2005)

0.37

0.74

Ericaceae

Leaves/ Boil about 10 grams dried leaves with 100 ml water. 20 ml of this decoction is to be given before meals 3-4 times a day.

Decoction / Rich in tannins and have antibacteri al effect (Dykes et al., 2003; Pegg et al., 2008).

34

0.34

0.68

Rhamnacea e

Leaves/ Boil 20 grams ground leaves in 100 ml water. About 40ml of the

Decoction / Antimicro bial activity (Naili et al., 2010).

33

0.33

0.66

17

decoction is given 4-6 times daily 22. Ceratonia siliqua L. /Carob / Kharob/ Pharm-PCT-584

23. Crataegus aronia (L.) Bosc ex DC./ Hawthorn/ Za’ror/ Pharm-PCT-711

24. Artemisia judaica L/ wormwood / Sheeh/ Pharm-PCT-238

Leguminosa e

Leaves/ Boil about 100 grams from the leaves in 100 ml water. About 50ml of this decoction is to be given three times daily

Decoction /

27

0.27

0.54

Rosaceae

Fruits/ Boil 100 grams of white sugar with 50 grams of these fruits in 100 ml water for 30 minutes, 15ml from the produced jam are to be given twice daily.

Fruit juice 27 jam/ Contain tannins and flavonoids which have antiviral and antimicrob ial effects (Orhan et al., 2007).

0.27

0.54

Compositae

Flowers/ Steep 50 grams of the dried flowers in 100ml boiled water for one night. About 50ml from the infusion is to be given three times daily.

Infusion/ 26 Essential oil has antimicrob ial, antispasm odic and antidiarrhe al effects (Al-Gaby and Allam, 2000; Al Harbi and

0.26

0.52

18

Antimicro bial effect (Aissani et al., 2012).

ElAshmawy, 2015; Charchari and Hamadi, 2007) 25. Trigonella arabica D elile/ Fenugreek/ Helba Mora/ PharmPCT-2511

Leguminosa e

Seeds/ Boil over 100 grams from the ground seeds in 500 ml water. About 100 ml of this decoction is to be given with meals twice daily.

Decoction / Antidiarrh eal activity due the presence of flavonoids . (Boyina and Kosanam, 2014).

22

0.22

0.44

26. Hordeum bulbosum L Poaceae ./ Wild Barley / Sha’er bsele/ PharmPCT-1206

Seeds/ Boil about 100 grams from the leaves in 100 ml water. About 50ml barley water is to be given three times daily

Decoction / Rich in carbohydr ates (Lev et al., 2005).

22

0.22

0.44

27. Rhus coriaria L. / Sumac/ Somak/ Pharm-PCT-2037

Fruits/ Boil about 20 grams from the ground fruits in 100ml water, 50ml from this decoction are to be given 5-6 times daily.

Infusion/ 21 Contains tannins and minerals (Özcan and Hacisefero gullari, 2004).

0.21

0.42

Anacardiace ae

19

28. Punica granatum L. Pomegranate/ Roman/ Pharm-PCT2721

29. Pistacia lentiscus L. Lentisk / Botom/ Pharm-PCT-1869

30. Cinnamomum verum J.Presl/ Cinnamon/ Kerfa/ Pharm-PCT2707

31. Fragaria vesca L. / Wild Strawberry/ Farawla/ PharmPCT-2711

Lythraceae

Fruits (peels)/ About 10 grams of dried and ground fruit peels is to be given orally twice daily with a cup of water.

Fruit peel dry powder/ Rich in tannins with antibacteri al activity (Rani and Khullar, 2004).

20

0.20

0.4

Anacardiace ae

Leaves/ Steep 40 grams of ground leaves in 100ml water for 12-15 hours. About 5ml from the infusion is to be given three times daily.

Infusion/ Antimicro bial activity (Magiatis et al., 1999).

19

0.19

0.38

Lauraceae

Bark/ Boil about 25 grams of ground bark in 100ml water for about 10 minutes. 50ml of this decoction is to be given 5-6 times daily.

Decoction 19 / Contains phlobatan nin which has antimicrob ial activity (Puangpro npitag and Sittiwet, 2009).

0.19

0.38

Rosaceae

Leaves/ Boil about 100 grams from the leaves in

Decoction / Antibacter ial effect

0.18

0.36

20

18

100 ml water. 50ml from this decoction is to be given 5-6 times daily.

(Mukunda m Borah and Das, 2012).

32. Citrus limon L. Osbeck / Lemon/ laemon/ Pharm-PCT2741

Rutaceae

Fruits/ Boil about 20 grams from the ground fruits in 100ml water for 10 minutes. 50ml from this decoction is to be given three times daily

Decoction / Contains vitamins and minerals (Paul and Shaha, 2004).

18

0.18

0.36

33. Rubus sanctus Schreb./ Raspberry / Olek/ Pharm-PCT2065

Rosaceae

Leaves/ About 100 grams from fresh Raspberry leaves boiled in 330 ml water. 100ml of this decoction is to be given orally three times daily after meals.

Decoction / Antibacter ial effect (Orhan et al., 2012).

17

0.17

0.34

34. Datura stramonium L./ Datura / Aldatura/ Pharm-PCT-2710

Solanaceae

Leaves/ Boil about 5 grams of the leaves in 100ml water. About 10 drops of this

Decoction 16 / Antispasm odic and antidiarrhe al effects (Abbas,

0.16

0.32

21

decoction is to be given three times daily.

2013; Stella et al., 2010).

Amaryllidac eae

Bulb/ One fresh bulb eaten raw with yogurt three times per day.

Eaten fresh / Antiviral and antibacteri al activities (Daka, 2013; Romeilah et al., 2010).

15

0.15

0.3

Apiaceae

Roots/ Fresh carrot juice is given four times daily (about 300ml each time).

Carrot fresh juice/ Contains vitamins and minerals (Kaack et al., 2001; Sant’Ana et al., 1998).

15

0.15

0.3

37. Origanum jordanicu m Danin & Kunne/ Thyme/ Za’atar/ Pharm-PCT-1729

Lamiaceae

Leaves/ About 25grams of fresh leaves are eaten raw three times a day.

Fresh leaves/ Antibacter ial effect (Bartol and Bari cevic, 2002).

15

0.15

0.3

38. Althaea officinalis L. / Marshmallow / Khotme/ PharmPCT-122

Malvaceae

Root/ Steep 40grams of the ground roots in 100ml boiled

Infusion/ Antibacter ial and demulcent effects

12

0.12

0.24

35. Allium sativum L./ Garlic/ Thom/ Pharm-PCT-2704

36. Daucus carota L./ Carrot/ Jazar/ PharmPCT-829

22

39. Urtica pilulifera L. / Stinging Nettle/ Korees/ Pharm-PCT2561

40. Ocimum basilicum L./ Basil / Rehan/ Pharm-PCT-2717

41. Plantago ovata Forss k./Plantain/ lesan alhmal/ Pharm-PCT1891

water for 6 hours. About 20ml from the infusion is to be given three times a day.

(Al-Snafi, 2013; Ozturk and Ercisli, 2007).

Urticaceae

Roots/ Boil about 40 grams from the dried powdered roots in 100ml water. About 10ml from this decoct is to given three times daily after meals.

Decoction / Antimicro bial effect (Kukric et al., 2012)

12

0.12

0.24

Lamiaceae

Leaves/ Boil about 50grams from the fresh leaves with 100 ml water. About 20 drops from this decoction is to be given three times a day.

Decoction / Antiviral and antibacteri al effects (Chiang et al., 2005; Shirazi et al., 2014).

11

0.11

0.22

Plantaginac eae

Leaves/ Steep 40 grams of the leaves in 100ml boiled water for 12hours. 15ml from this infusion

Infusion/ Demulcen t effect due to their high contents of mucilages (Samuelse

11

0.11

0.22

23

is to be given two times a day..

n et al., 1998).

42. Hyoscyamus niger L./ Solanaceae Hebane/ Alskran/ Pharm-PCT-2712

Leaves/ Boil about 10grams from the leaves in 100 ml water. About 10 drops from this decoction is to be given three times daily.

Decoction 11 / Contains hyoscyami ne which has antispasm odic effects (Ghorbanp our et al., 2013).

0.11

0.22

43. Allium cepa L./ Onion/ Basal/ PharmPCT-2703

Amaryllidac eae

Bulb/ About 20-30 ml of the bulb juice are to be given five times a day.

Eaten fresh / Antimicro bial and antiviral properties (Kyung, 2012; Romeilah et al., 2010).

10

0.10

0.2

Myristicace ae

Seeds/ Boil about 10 grams from the ground nutmeg in 100 ml water. Give 10ml three times a day after meals.

Decoction / Antimicro bial and antiviral properties (Vinothku mar et al., 2013).

8

0.08

0.16

Passiflorace ae

Leaves/ 10 drops of the fresh leaf juice are to

Fresh leaves juice/ Analgesic,

8

0.08

0.16

44. Myristica fragrans Houtt./ Nutmeg/ Jozet alteeb/ PharmPCT-2716

45. Passiflora subpeltata Ortega /Passion / Baseflora/ PharmPCT-2719

24

46. Apium graveolens L. /Celery / Krafs/ Pharm-PCT-204

47. Citrus aurantium L. / Sweet Orange / Bortokal/ PharmPCT-2708

48. Centaurea procurren s DC. / Procumbent Centaury-thist /Kantarion momtad/ Pharm-PCT-552

be given twice daily.

antiinflammat ory and antipyretic effects (Saravana n et al., 2014).

Apiaceae

Stalks/ 15 drops of fresh celery stalk juice are to be given orally every two hours.

Fresh juice/ Contains minerals and vitamins which can be useful in case of diarrhea (Sowbhag ya, 2014).

7

0.07

0.14

Rutaceae

Fruits (peels)/ Boil about 40 grams of the peels in 40ml water. 20ml of this decoction is to be given three times a day with meals.

Decoction 7 / Antiviral activity also rich in pectin adsorbent antidiarrhe al agent (Kim et al., 2012; Wang et al., 2008).

0.07

0.14

Compositae

Leaves/ Steep 4 grams of the powdered leaves in 100ml boiled water for 2-3 hours. About 10ml from this infusion

Infusion / Antibacter ial effect (Saroglou et al., 2005).

0.06

0.12

25

6

is to be given three times daily. 49. Amaranthus blitum L. Amaranthac / Purple Amaranth eae /Kateefa/ PharmPCT-134

Aerial parts/ Boil about 60 grams from the dried powdered plant in 100 ml water. About 50 ml from this decoction is to be given 3-5 times daily.

Decoction 5 / Antibacter ial activity (Wiart et al., 2004)

0.05

0.1

50. Zingiber officinale Roscoe / Ginger / Zingabil/ PharmPCT-2724

Rhizomes/ Boil about 30 grams of the powder in 100 ml water. About 50ml of this decoction is to be given three times a day after meals.

Decoction 3 / Antimicro bial activity as well as ginger rhizomes inhibit the production of cholera toxin (Dubreuil, 2013; Sivasothy et al., 2011; Valera et al., 2015).

0.03

0.06

Zingiberace ae

The fidelity level were 97% for Salvia fruticosa, Teucrium polium and Musa paradisiaca, 95% for Camellia sinensis and Aegle marmelos, 79% for Oryza sativa and Solanum tuberosum, 77%

26

for Quercus boissieri, 66% for Psidium guajava, 56% for Anthemis palestina, 54% for Solanum nigrum and 52% for Juglans regia peels. Other plants species which were recommended by traditional herbal practitioners and herbalists, had fidelity levels less than 50%. As calculated by the use-value (UV) and choice value (CV) in Table 2, Salvia fruticosa, Teucrium polium, Musa paradisiaca, Camellia sinensis and Aegle marmelos (UV more than 0.9 and CV more than 1.9 ) were reported to be of the highest use and choice values. In addition to that the factor of informant’s consensus (Fic) was calculated for medicinal plants used for treatment of diarrhea and was 0.505, which means that the Fic value obtained for the reported disease indicated the degree of shared knowledge among informants for the treatment of diarrhea by certain medicinal plants. Ethnopharmacological information obtained from the study area on medicinal plants used in the treatment of diarrhea revealed 50 plants species belonging to 27 families. All of the Latin scientific names have been checked with www.theplantlist.org on August 10, 2015. In many cases the usage of specific plants for the treatment of diarrhea may be due to the presence of tannins which have astringent properties by which they are able to draw together or constrict body tissues and are effective in stopping the flow of fluids or other diarrheal secretions. Tannins strengthen veins by repairing the connective tissues surrounding veins and decrease capillary fragility, they are also known as antimicrobial and antiviral agents (Akiyama et al., 2001; Zhang et al., 1995).

27

In addition to their tannin contents, most of these plants are rich in electrolytes, carbohydrates and vitamins which are considered very useful and necessary in case of diarrhea (Indrayan et al., 2005). According to our results, most of the published studies on the plants used for treatment of diarrhea in the West Bank/ Palestine have focused on their astringent, antibacterial and antiviral effects. However, in most cases they have not been evaluated for their potential antidiarrheal activity. Furthermore, there is lack of standardization and quality control for these oral administration forms (Bekalo et al., 2009; Nanyingi et al., 2008). In a study conducted by Olajuyigbe and Afolayan in 2012, 36 plant species representing 24 families have been found to be commonly used in the treatment of a variety of gastrointestinal disorders in the ethnomedicine in South Africa, but only 46.15% of these plants were used to treat diarrhea (Olajuyigbe and Afolayan, 2012). Another study was done by Johnsy et al, 2013; in the forest areas of Kanyakumari district (India). They found 50 plant species which were distributed among 37 botanical families being used in treatment of diarrhea and dysentery; from them only 34 species were used for treatment of diarrhea (Johnsy et al., 2013). The survey conducted by Rout and Panda, from Mayurbhanj district, India, in 2011, found 17 species used for treatment of diarrhea from 77 plant species represented by 41 families used by the local people in traditional healthcare for treatment of various diseases (Rout and Panda, 2010).

28

In the Middle East areas, to date there have been no previous reports of ethnopharmacological surveys investigating plant products used to treat diarrhea. In this study, the in-vivo and in-vitro antidiarrheal activities as well as the side effects and toxicity for the most cited medicinal plants with fidelity levels more than 50%, have been investigated and compared with similar studies available in the literature using databases such as: Pubmed, Sciencedirect, Google scholar, and Scopus, using; ethnopharmacological uses; ethnomedicinal uses; Ethnobotanical uses; Folk uses; Traditional uses; in-vivo; in-vitro; side effects; toxicological properties as keywords with each plant, the results are summarized in Table 3. Table 3: Literature review on identified plants with fidelity levels more than 50%. Plant species

Antidiarrheal ethnopharmacological usage and country with reference source

Salvia fruticosa

No reference found for No reference found treatment of diarrhea but used for treatment of in the traditional medicine for diarrhea. stomach disturbances in Palestine (Yaniv et al., 1987), for treatment of digestive system disorders in Libya (Carmona et al., 2005) and for treatment of intestine gases Turkey (Fakir et al., 2009).

Teucrium polium

No reference found for treatment of diarrhea but used in treatment of stomach and intestinal spasms in Iran (Parsaee and Shafiee-Nick, 2006), Turkey (Cakilcioglu 29

In-vitro and in-vivo Side effects and antidiarrheal effects toxicity with with reference reference source source

In vitro study proved that T. polium volatile oil has a similar effect to diphenoxylate on the reduction of

The antifertility and antiimplantation reproductive toxicity potentials after ingestion of aqueous and ethanolic extracts of S. fruticosa leaves have been investigated in male and female rats (Elbetieha et al., 1998). Jaundice hepatotoxicity associated consumption of quantities of polium in a tea

and after large T. form

and Turkoglu, 2010) Palestine (Jaradat, 2015).

and osmotic diarrhea (Starakis et al., 2006; symptoms and also Zal et al., 2001). reduces the volume of excreted water (Allahtavakoli et al., 2013).

Musa paradisiaca

Its unripe fruits are traditionally used in Indian (Khare, 2007) and Bangladeshi (Ghani, 1998) ethnomedicines for treatment of diarrhea.

It has a beneficial M. paradisiaca may role in the causes food allergy management of (Grob et al., 2002). persistent diarrhea (Alvarez-Acosta et al., 2009; Arias et al., 1997).

Camellia sinensis

In Iran (Nabati et al., 2012), India (Natarajan et al., 2000), Jordan (Wazaify et al., 2013) and Palestine (Jaradat et al., 2014), C. sinensis is used in the folk medicine for treatment of diarrhea.

In-vitro study C. sinensis possesses marked antidiarrheal activity (Besra et al., 2003).

C. sinensis consumption resulted in iron deficiency for healthy individuals (Disler et al., 1975).

Aegle marmelos

In the Mexican (Gutiérrez et al., 2007), Indian (Acharya and Rai, 2011; Baliga et al., 2011) and Palestinian (Jaradat, 2005) ethnomedicines it is used as an antidiarrheal agent

In-vitro study of antidiarrheal activity of A. marmelos was approved (Shoba and Thomas, 2001).

The leaves have antispermatogenic activity (Sur et al., 1999), while the ripe fruits are contraindicated in patients suffering from irritable bowel disease (Neha et al., 2014).

Oryza sativa

Rice based oral rehydration solution used in the ethnomedicines for treatment of diarrhea in Yemen (Tomson and Sterky, 1986), India (Deepak and Gopal, 2014), Bangladesh (Fontaine et al., 2002) and Mexico (Martínez et

In-vivo study, O. No reference sativa based oral rehydration solution used to stop diarrhea in Peru (Zavaleta et al., 2007).

30

al., 1997). Solanum tuberosum

Used in the Italian (Maxia et al., 2008), Kosovo (Mustafa et al., 2012), Albanian (Quave and Pieroni, 2009), Indian (Manikandan, 2008), United States (Cavender, 2006) and Iranian (Bahmani et al., 2014) folk medicine for treatment of diarrhea.

In-vivo study, No reference Potato oral rehydration solution was made for treatment of diarrhea (Mehta, 2004).

Quercus boissieri

No reference

No reference

Psidium guajava

Used in the traditional medicine for treatment of diarrhea in China (Teixeira et al., 2003), Philippines (Smith et al., 1992), Congo (Tona et al., 1998), Brazil (Holetz et al., 2002), South Africa (Semenya and Maroyi, 2012) and India (Namsa et al., 2011; Panda et al., 2012).

A group of 50 adult No reference patients with acute diarrheic disease was treated with Psidium guajava leaves (Lozoya et al., 2002). In-vitro study proved that the Guava leaves extract inhibited diarrhea caused by bacteria (Kamath et al., 2008).

Anthemis palestina

No reference

No reference

31

No reference

Anthemis palestina flowers volatile oil showed general cytotoxicity effect (Tawaha et al., 2015).

Solanum nigrum No reference

Juglans regia

No reference

S. nigrum is considered to be an edible plant; its toxicity is mainly due to the presence of solanine, a glycoalkaloid causing varying degrees of toxicity (Lee et al., 2004).

Used in the folk medicine for No reference treatment of diarrhea in India (Sharma et al., 2014), Iraq (Ahmad and Askari, 2015) and Morocco (Mouhajir et al., 2001).

Juglone compound when isolated from all plant parts has multiple effects on cells such as the reduction of p53 protein levels, induction of DNA damage, inhibition of transcription and induction of cell death (Paulsen and Ljungman, 2005).

Of the 12 highly rated plants only 4 species had evidence, in- vitro or in -vivo, to support the antidiarrheal activity. In fact, these 4 plants showed potential antibacterial, antiviral and astringents effects which may explain their antidiarrheal usage. In addition, they showed additional nutritional benefits that can be very useful in cases of diarrhea. From the information available, the other 8 plants lack in-vivo and in-vitro studies to support their antidiarrheal effects. These plants need to be investigated further in order to establish their potential therapeutic antidiarrheal activity as well as their side effects or toxicity. In addition, herbalists and herbal practitioners should be aware that a number of these plants may cause side effects or toxic 32

reactions. Furthermore, adulteration, inappropriate formulation, or lack of understanding of these plants and herb-drug interactions can lead to adverse reactions that sometimes can be potentially life threatening. This study will be very useful for the Palestinian community healthcare system which can provide them the required data about these plants’ uses for treatment of diarrhea and their side effects, and also may help in contribution to better integration of Palestinian ethnomedicine into the national health system in the future. Additionally, this study may be useful in new drug discoveries. 4. Conclusion Traditional herbal medicine knowledge is important for discovering new drugs, drug development and for improving community healthcare awareness. In this study, fifty plant species were reported to be used as ethnopharmacological remedies for the treatment of diarrhea in the West Bank. Reasons for the choice of these plants, the parts used and their modes and preparation methods were documented based on the experiences of herbal healers. There is a need to educate the traditional practitioner about the need to consider issues of conservation and sustainability of the plant species to avoid over exploitation. Further investigation into ethnopharmacology is needed to confirm the antidiarrheal effects in-vitro and in-vivo, isolate the phytochemical active compounds, and understand their modes of action. This could improve the usage of traditional antidiarrheal treatments and help contribute to better integration of Palestinian ethnomedicine into the national health system in the future. Conflict of interests

33

Authors declare no conflicts of interests

Authors' contributions Nidal Jaradat conceived and designed the study, analyzed the data obtained. This paper was drafted by Nidal Jaradat, Cynthia Anderson and Ola Ayesh. Nidal Jaradat and Ola Ibrahim Ayesh interviewed local healers and herbal practitioners. All authors read and approved the final manuscript. Funding None. References Abbas, D.A., 2013. Analgesiac, anti-inflammatory and antidiarrhoeal effects of Datura stramonium hydroalcoholic leaves extract in mice. Int. J. Res. Rev. Appl. Sci. 14, 193-199. Acharya, D., Rai, M., 2011. Traditional Knowledge about Indian Antimicrobial Herbs: Retrospects and Prospects. CRC Press. Adeyemi, O., Oladiji, A., 2009. Compositional changes in banana (Musa ssp.) fruits during ripening. Afr. J. Biotechnol. 8, 858-859. Ahmad, S.A., Askari, A.A., 2015. Ethnobotany of the Hawraman Region of Kurdistan Iraq. Harv. Pap. Bot. 20, 85-89.

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