Ethnopharmacological survey of herbal remedies used for treatment of various types of cancer and their methods of preparations in the West Bank-Palestine

Background Plants have been the primary source of medicines since life on earth; more than 50 % of existing cancer treatments are derived from plants. Methods An ethnopharmacological survey of herbal remedies used in cancer treatment was carried out in the West Bank/ Palestine. A questionnaire was distributed to one hundred and fifty herbalists, traditional healers and rural dwellers. Collected information included the names of plants, the used parts, types of cancers for which these plants were used and also their methods of preparation. To identify the most important species used, Factor of informant’s consensus (Fic), Fidelity level (Fl) and the Use-value (UV) were calculated. Results Collected data has shown that 72 plants are utilized for treatment of cancer, belonging to 44 families; from them Compositae and Lamiaceae were the most common. Leaves and fruits were the most commonly used parts, while decoctions, infusions and syrups were the main methods of preparation. Lung cancer was the most common type of cancer treated with these plants and Ephedra alata was the most commonly used plant for treatment of cancer in Palestine. The Fic was high for all the plants; Fl was 100 % for many plants, the highest UV (0.72) was for Ephedra alata. Conclusions This study showed that many herbal remedies are still used by herbalists in Palestine for treatment of cancer; some of them have been approved scientifically while others are not. A combined effort between informants and scientific institutions working in this field can help in the discovery of new anticancer agents. Moreover, scientists must explore the most suitable method of extraction, formulation and dose determination in order to achieve the best benefits from these herbals.


Background
The Holy Land/ Palestine has miscellaneous ethnic groups (Muslims, Christians, Druze, Jews from East and West and Samaritans), so its characteristic cultures are numerous and varied, including folkloric herbal medicine. However, these traditions in herbal remedies have waned over hundreds of years. Palestine is a unique land, in its ecological diversity due to its geographical location between Africa, Asia and Europe. Different zoogeographic, climatic, and phytogeographic zones covered Palestine, creating great biological multi-diversity [1,2]. In addition to that it was as an important international trade crossroad from ancient times, between North Africa, East Asia and West Europe; this added to its culture in herbal medicines [3][4][5].
Plants provide a continual source of medicines for animals and humans; they have been used since ancient times in crude forms as decoctions, syrups, liniments, powders, infusions and ointments [6,7]. Evidence of medicinal plant use around 60 000 years ago was found in a cave discovered in 1960 in the Middle East [8,9]. In recent time, people in both developed and developing countries utilize herbal medicines for improving their health [10][11][12]. According to the World Health Organization (WHO) evaluations, about 80 % of populations in developing countries have utilized ethnomedicines for their health care requirements and more than 60 % of cancer patients have used natural plant products with vitamins in fighting this disease [13][14][15]. While 50 % of modern pharmaceutical medications in clinical practice are derived from plants, many of them have strong anticancer effects [16,17].
According to the WHO and the American Cancer Society about eight million died from cancer and about fourteen million new cancer cases occurred in 2012. The highest percentages of patients were with lung, breast and colorectal cancers respectively. WHO also estimates a substantive increase up to nineteen million new cases of cancer per year by 2025, due to the growth of global population. More than half of all cancers and cancer deaths occurred in less developed countries, and these proportions may be further increased [18][19][20].
Nowadays, chemotherapeutic anticancer agents are the most common method of treatment, but they may cause serious side effects and toxicity [21][22][23].
Due to the high death rate among patients with cancer and the hazardous side effects and adverse reactions of the radiotherapy and chemotherapy, cancer patients often start seeking alternative methods of treatments, like herbal medicine with or instead of conventional medicine [24][25][26].

Methods
An ethnopharmacological survey on herbal remedies used for treatment of various types of cancer was conducted from March 2015 to June 2015. Areas visited included all regions of the West Bank/Palestine; Nablus, Jenin, Tubas, Toulkarm, Salfeit, Qalqilya, Ramallah, Jericho, Jerusalem, Bethlehem and Hebron (Fig. 1).
The study aims, protocols and the informed consent forms were approved by the Institutional Review Board (IRB) at An-Najah National University (IRB archived number 25/Jan/ 2015). The study was conducted in accordance with the requirements of the declarations of Helsinki.
The study was carried out by interviews with herbalists, traditional healers and rural dwellers that used herbal remedies in the treatment of different types of cancer. The number of registered herbalists in the West Bank is 222. According to the Raosoft calculator the minimum sample should be 141 participants, so we included 150 [27]. These informants represented most of the practitioners in this field in the West Bank (Sociodemographic characteristics are presented in Table 1).
A convenience sample of herbalists and practitioners from various regions were met by researchers and asked to answer a face to face questionnaire. They were interviewed in Arabic after getting their verbal consent only once.
Statistical analyses were performed by using Statistical Package for Social Sciences (SPSSversion17.0). Mean ± Fig. 1 Map of the West Bank/ Palestine showing all surveyed regions standard deviation were computed for continuous data. Frequencies and percentages were calculated for categorical variables. Means were compared using Student's ttest. Categorical variables were compared using Chisquared and Fisher's exact tests, as applicable. A p-value of less than 0.05 was considered to be statistically significant for all analyses.
Questionnaires were administered through personal contact discussions. This method is an effective and easy option of data collection. This survey aimed to obtain information on the names of plants commonly used in the treatment of cancer, the type of cancer treated by herbs, the methods of preparing and the parts used for administration. Interviews were conducted in the Arabic language of the informants. Names of plants were translated later to English and Latin. In most cases, the interviews often started in the form of informal discussions to gain the confidence of the interviewees.
All of the 72 plant materials were collected from the interviewees (herbalists, traditional healers and rural dwellers) and kept in special glass frames and later identified by the pharmacognosist Dr. Nidal Jaradat. The identity of each plant species mentioned by the interviewees was confirmed and verified by using photographs and live specimens. A medicinal use was accepted as valid only if it was mentioned by at least three independent herbal practitioners. Samples of these collected herbs were given a herbarium specimen number as shown in Table 2 and voucher samples were kept at the Pharmacognosy Laboratory of the Department of Pharmacy at An-Najah National University, Faculty of Medicine and Health Sciences (Table 2).

Data analysis
All citations were placed into ailment categories for each type of cancer. Factor of informant's consensus (F ic ) was employed to indicate how homogenous the information is. In fact, its main use is to select disease categories where there is consensus on the use of plants among the informants. F ic value is close to 0 if plants are chosen randomly, or if informants do not exchange information about their use. High values of F ic (close to 1) occur when there is a well-defined selection criterion in the community and/or if information is frequently exchanged between informants [28].
The F ic is calculated as in the following equation: Where Nur is the number of use citations in each category and Nt is the number of taxa used.
Fidelity level (Fl) was defined as the ratio between the number of informants who independently suggested the use of a species for the same major purpose and the total number of informants who mentioned the plant for any use. Fl is of equal importance to F ic and it 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 a particular disease and N is the number of informants that used the plants as a medicine to treat any given disease [29].
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 the number of citations per species; n the number of informants [30].
Results of calculated F IC , Fl and UV are shown in Tables 2, 3 and 4.  Apiaceae Fruits/About 500-600 grams from the ground dry fruits boiled with one liter water for 30 minutes; 300 ml of this decoction is to be given orally three times daily. Apocynaceae Aerial parts (latex)/ Ten grams from air dried latex from the fruits is boiled with 40 ml water; 20 ml of this decoct is to be given twice daily. Araceae Leaves/Boil about 10 grams of the dried leaves with 100 ml water, fifty ml of this decoction is to be given orally before meal. Araceae Leaves/Boil about 10 grams of the dried leaves with 150 ml water, fifty ml of this decoction is to be given orally three times daily before meals. Compositae Aerial parts/Steep 15grams from the plant with 100 ml water for 2 hours, 10 ml from this infusion is to be given internally twice daily.
Liver Infusion (oral) 0.11 19. Cichorium endivia L./Common chicory/ Shokar/ Pharm-PCT-617 Compositae Flowers/Steep 100 grams from the plant with 100 ml water for 2 hours; 30 ml from this infusion is to be given once daily.

Results and discussion
Traditional herbal medicine knowledge and their utilization by indigenous cultures are not only useful for conservation of biodiversity and cultural traditions but also useful for the population's healthcare and drug discovery in the present and in the future [31,32].
Several studies have shown that around 80 % of rural populations in the developing countries consider herbal remedies as integral parts of treatments available. Recently, the use of natural herbal products is increasing in both developed and developing countries due to many reasons [33,34]. Zingiberaceae Rhizomes/ About 100 grams of the ground dry rhizomes are boiled in 300 ml water for 10 minutes and given twice daily after meals.

Stomach and liver
Infusion (oral) 0.51 As shown in (Table 1), most of the respondents who work in this field were males. Most of them had educational level equal or higher than high school. In fact about 19.3 % of the total interviewed were university graduates. The table also showed that the majority of respondents were from areas of the West Bank that mostly depend on agriculture or grazing as a mean of income (Jenin, Nablus, Salfeit and Toulkarem). In fact these areas are geographically close to each other (Fig. 1).
Notably the results of this research have revealed that 72 plant species belonging to 44 families were frequently used for treatment of cancer by the 150 herbalists, traditional practitioner healers, rural dwellers and people of the West Bank, Palestine (Table 2).
Echoing our findings in this research, members of the family Compositae and Lamiaceae were the most commonly used as presented in Table 2. The methods of preparation were decoctions (boiling the plants parts in water), infusions (steeping the plants in water for limited time), syrup (boiling the plants with water and sugar (1:1), creams (mixing the plant powders with goat fat or lanolin), paste, fresh juice, ingested entire plant, powder and vapor inhalations. Decoctions and infusions were the most frequently used methods of preparation as presented in Fig. 2.
Leaves, fruits and seeds were reported to be the most frequently used parts of plants for the treatment of cancer, constituting about 56.9 % of the preparations. This was followed by flowers, aerial parts, entire plants, roots, rhizomes, barks, bulb and stalks as presented in Fig. 3.
The most common cancer type treated with herbal remedies was lung cancer followed by liver, skin, colon and breast cancers as reported in (Fig. 4).
This research shows that the medicinal plants still play a role in the care of cancer patients in Palestine. Ephedra alata, Arum dioscoridis, Arum palaestinum were the most commonly used medicinal plants for treatment of cancer and all of these three plants were prepared as decoctions.
However, Ephedra alata were reported to treat three different types of cancer (brain, liver and colon). Accordingly, three Fl values were calculated. The highest one (40.74 %) was for liver cancer. The same consideration can be raised for Arum palaestinum which was reported to treat four different cancers (Liver, colon, kidney and breast). Breast cancer showed the highest Fl value (45.74 %). According to table 4, only Fl values higher than 50 % were included.
In the Mediterranean region and especially in the Holy land (Palestine), the traditional medicine has been highly appreciated and trusted. Many patients go to herbalists or informants to get benefit from this field. Most practitioners are males and this was confirmed in this study; some of them have university degrees. Complementary and alternative medicines are widely used among cancer patients throughout the world. In a previous study from Palestine, 60.9 % of cancer patients reported using medicinal herbs [35]. Medicinal plants utilized in indigenous health traditional system are gradually becoming wiped out due to over utilization, human overpopulation and from other human impact on the environment. The main problem is destructive harvesting of the subterranean parts of the medicinal plants, or even the entire plant.
Medicinal plants maintain the health and vitality of individuals, and may help in treatment of various diseases, including cancer. In this study, some anticancer medicinal plants of foreign origin have been presented. Many of these medicinal plants possess good immunomodulatory and antioxidant properties, which may lead to anticancer activities. The antioxidant phytochemicals protect the cells from oxidative damage. Thus, consuming a diet rich in antioxidant plant foods (e.g. fruits and vegetables) will provide health-protective effects. In 2013, a traditional practitioner living in Jenin claimed that he could cure a cancer patient completely using Ephedra alata. The local media here were interested in this story and many researchers have started working on this plant.
A multidisciplinary approach combining traditional herbal knowledge with pharmaceutical research is a  valuable method for identifying potential herbs with possible clinical significance in cancer care [36].
To achieve a positive response to herbal preparations, the proper part of the plant that contains the active constituents should be chosen. It is well known that not all the plant parts contain the same concentration of the active constituents. The other factors to be considered are the harvesting time of the herb (collection time), the soil, the climate conditions, and the method of drying, processing, and extraction [37,38]. Methods of preparation were mainly decoction and infusion. This is similar to previous studies in our country conducted by Ali-Shtayeh et al., 2011 and Jaradat, 2005 [35,39]. In an ethnopharmacological survey of medicinal herbs in Golan Heights and the West Bank region performed by Said et al., 2002, only seven plant species were found to treat cancer among 81 species used for treating 115 different ailments and diseases [40]. In another study conducted in the West Bank, Ali-Shtayeh and Rana, 2011, found only 25 plant species used for treatment in cancer without mentioning which type of cancer they can treat [41].
In another study conducted by Ali-Shtayeh et al., 2011, in Palestine, 58 plant species were collected for cancer treatments [35], while in the survey which was conducted by Hudaib et al., 2008 in Jordan, Mujib Nature Reserve and surrounding area, only six plant species were found for treatment of cancer also without mentioning the type of cancer [42].
The methods of preparation mentioned by the informants are not supported by scientific evidence; this could be suitable for some plants but not for the others. In fact, the boiling process can cause severe degradation of the medicinal components in some plants.
The dosage is another concern. To have the expected benefits, the patients should receive a fixed well defined dosage, but in traditional medicine the suitable doses are not clear [37], so studies are needed to determine the concentration of active ingredients depending on their method of preparation to give the suitable recommended doses.   Table 3 shows the F ic values calculated for the categorized cancers. F ic values obtained for the reported cancers indicate the degree of shared knowledge among informants for the treatment of a cancer by certain medicinal plants. Most cancers had high F ic values; however the highest F ic =1 was scored for spinal cord and gallbladder cancers. Fl was 100 % for many plants; the highest UV (0.72) was for Ephedra alata.
Most of the mentioned plants in Table 2 are edible plants and the most of the non-edible plants were used externally. Therefore minor restrictions could be included as they have minor risk compared to the obtained therapeutic benefits from their use for cancer.
Resulting from this information, scientific practical work is in progress on the phytochemical and pharmacological analysis of the plants. This study is important to preserve the knowledge of medicinal plants used by the people of the West Bank regions. Also, it is of significance to utilize new therapeutic natural plant products in various treatments of diseases. Moreover, clinical studies approved according to international guidelines should be considered in order to prove the safety and efficacy of treatment, especially for the most frequently reported medicinal plants.

Conclusion
Many plant species are still used by herbalists and traditional practitioner healers in Palestine for treating various types of cancer. This article provides the knowledge about anticancer medicinal plants of local and foreign origin, which are used by the people all over the Palestinian area in addition to their method of preparation. Many of the used plants have been approved scientifically to have some anticancer activity. A combined scientific effort between informants and the scientific community working in this field may help in the discovery of new anticancer agents. Moreover, scientists may explore the most convenient method of extraction, formulation and dose determination in order to achieve the best benefit from these plants.
Further scientific laboratory studies are required to explore and to investigate the safety and efficacy of these plants, their potential therapeutic effects as well as probable interactions of these medicinal products with conventional anticancer medicines.