Ethnopharmacological survey of medicinal plants used by patients with psoriasis in the West Bank of Palestine

Background Psoriasis is a frequent skin inflammatory disorder that inflicts millions of patients around the globe. To meet their healthcare needs, patients with psoriasis often seek treatment outside the allopathic paradigm. Use of medicinal plants has emerged as one of the most common and preferred modalities of complementary and alternative medicine (CAM). The aim of this study was to investigate the use of medicinal plants by patients with psoriasis in the West Bank of Palestine. Methods The current study was a questionnaire based cross-sectional descriptive study on the use of medicinal plants by psoriasis patients in the West Bank of Palestine. A sample of 149 patients with psoriasis who were visiting outpatient clinics responded to the questionnaire in face to face interviews. Results Medicinal plants were used by 81 (54.4%) patients with psoriasis. Patients used 33 medicinal plants belonging to 26 families. Plants belonging to Lamiaceae and Leguminosae were the most commonly used by the study patients. Aloe vera, Trigonella arabica, Catharanthus roseus and Anthemis cotula were the most frequently used medicinal plants to treat psoriasis. Leaves and fruits were the most commonly used parts by the study patients. Paste was the most commonly used form of preparation. The use of medicinal plants was significantly associated with age and monthly household income of the patients. Enhancement of immunity, improving conventional therapy and reduction of side effects were the most commonly self-reported reasons for using medicinal plants. Conclusions Patients with psoriasis in Palestine seem to use medicinal plants as a CAM modality to manage their psoriasis. Many medicinal plants were commonly used by patients with psoriasis. More randomized clinical trials are needed to demonstrate safety and efficacy for the majority of these medicinal plants reported to be used by patients with psoriasis in Palestine. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1503-4) contains supplementary material, which is available to authorized users.


Background
Psoriasis is a frequent skin inflammatory disorder that inflicts approximately 2-3% of the populations around the globe [1,2]. However, prevalence of psoriasis varies across geographical locations and races. Research conducted in the Middle East showed that the incidence of psoriasis in Algeria, Tunisia and Morocco was estimated at 10.36, 13.26 and 15.04 per 1000, respectively [3]. The severity of psoriasis varies from scattered papules to generalized scaly plaques [4]. Depending on location and severity of lesions, psoriasis might have negative consequences on the quality of life of the patients in terms of physical and emotional well-being [4].
Management of psoriasis largely depends on the severity and location of lesions. Systemic therapy, phototherapy and agents applied topically have emerged as therapeutic options in the management of psoriasis [5]. Retinoids, cyclosporine, methotrexate and biologics are approved by the US Food and Drug Administration (FDA) for systemic therapy of psoriasis [6]. The American Academy of Dermatology recommends the use of systemic therapy and phototherapy for sever lesions. Agents applied topically are recommended for mild and localized lesions that do not affect the daily activities of the patient [5]. However, previous studies have shown that systemic therapy and phototherapy are underused because patients prefer topical preparations [7,8]. Recent statistics showed that only 43% of patients diagnosed with severe psoriasis received systemic therapy [8].
Poor patient adherence and physician reluctance to prescribe systemic treatments were associated with many factors including adverse effects, intolerance, affordability and development of resistance to therapies [1,[9][10][11].
Published therapeutic guidelines for the management of psoriasis do not fully satisfy the expectations of patients. Moreover, patients with psoriasis experience inevitable avoidance behavior and psychological disturbances that deteriorate their quality of life [1,12]. Not surprisingly, patients with psoriasis often seek treatments outside the allopathic paradigm to meet their healthcare needs considering the chronic and frustrating nature of the disease [13][14][15]. Patients with psoriasis were shown to use different modalities of complementary and alternative medicine (CAM) [14,16]. The use of medicinal plants has evolved as one of the most preferred CAM modalities across different cultures around the globe [13]. Some medicinal plants are used topically while others are ingested for systemic effects. We believe that healthcare professionals should be aware that patients might be using such medicinal plants as an alternative to or in combination with allopathic treatments.
The use of medicinal plants has long been regarded as non-evidence based practice [17]. Today, leading academic and regulatory institutions are setting standards to encourage conducting randomized clinical trials using different CAM modalities including the use of medicinal plants in a scientifically rigorous fashion [18,19]. A considerable number of randomized controlled clinical trials have been conducted using different medicinal plants to treat signs/symptoms of psoriasis [15]. Some medicinal plants were shown to improve signs and symptoms of psoriasis while other did not shown any significant improvements [14,15,17].
As using medicinal plants is based on centuries old traditions, their patterns of use differ from culture to another. Globally, little is known on the association of different sociodemographic factors like age, gender, educational and economic status with the pattern of use of medicinal plants to treat psoriasis. In Palestine, little is known on the use of medicinal plants by patients with psoriasis. The present study was conducted to investigate the pattern of use of medicinal plants among psoriasis patients in Palestine, to assess clinical and sociodemographic predictors of using medicinal plants and to identify perceived benefits from using medicinal plants by patients with psoriasis. The study also aims to identify the sources of information and the underlying reasons for using medicinal plants to treat psoriasis. This study was conducted with special emphasis on the use of medicinal plants as a CAM modality.

Methods
The present study was undertaken in a cross-sectional observational design at outpatient clinics all over the West Bank of Palestine. A convenient sample was recruited from outpatient clinics in the period of August 2015 to December 2015.

Structured interview and validation of the questionnaire
The method used in this study was based on our previously published study [13]. Briefly, ten psoriasis patients were interviewed in the first stage of the study to explore their views on the use of medicinal plants to treat their psoriasis and the methods they use in the preparation of these medicinal plants.
A questionnaire containing two sections was developed as in our previous study [13]. In the first section, patients were requested to provide their sociodemographic details such as age, educational status, marital status, place of residence, monthly household income, disease stage, period relapsed since the patient was diagnosed with the disease, type of treatments used, whether the patient used medicinal plants or not (Additional file 1). Inclusion of these sociodemographic variables was based on a literature review of previous studies. In the second section, patients were requested to answer open-ended questions to provide the names of medicinal plants used, reasons why the patient used these medicinal plants, who informed the patient about these medicinal plants, methods of preparing medicinal plants and the sources of these medicinal plants.
The questionnaire was piloted and revised to help understanding. Two trained researchers conducted the interviews and collected the questionnaires from the study participants.

Statistical analysis
For statistical analysis, patients recruited for this study were categorized as either users of medicinal plants or nonusers based on whether they used medicinal plants or not in the last 6 months. Some data pertaining to period relapsed since the patient was diagnosed with the disease, disease stage and previous treatments were obtained from the medical records of the patients. Pearson's Chi-Square (χ 2 ) or Fisher's Exact Tests were used to compare categorical groups, as appropriate. Spearman's rank correlation was used to correlate categorical data. Statistical significance was considered when the p value was less than 0.05. Data were processed using IBM SPSS for Windows v.21.0 (IBM-SPSS, Chicago, Illinois, USA). In this analysis, users of medicinal plants were considered equally without regard to the number of medicinal plants they used.

Ethical approval
The protocol and ethics of the present study were approved by the Institutional Review Board (IRB) of An-Najah National University (protocol No. 62/Aug/ 2015). Participants signed an informed consent before they took part in the present study. No financial incentives were offered to participants during this study. Participants were assured of their anonymity and all data obtained were kept confidential.

Characteristics of participants
In the present study, a total of 149 patients diagnosed with psoriasis were approached and completed the questionnaire. The sociodemographic details of the study patients are shown in Table 1. More than half (53%) of the participants were below 40 years old. About 81 (54.4%) used medicinal plants instead of chemotherapy while the rest of 68 (45.6%) did not used medicinal plants instead of chemotherapy.
When the sociodemographic variables of users and nonusers of medicinal plants were compared, characteristics like age and household income were significantly associated as shown by the χ 2 or Fisher's exact tests and Spearman's correlation coefficients (Table 2). There was a significant low correlation between the marital status and use of medicinal plants as shown in Table 2.

Medicinal plants used
In this study, 81 patient with psoriasis declared that they used at least one medicinal plant in the last 6 months to treat signs/symptoms of their psoriasis. The majority of these patients used more than one medicinal plant concurrently.
All patients with psoriasis who participated in this study declared that they used Aloe vera. The second most commonly used medicinal herb was Trigonella arabica which was reported by 65 (80.2%) patients followed by Catharanthus roseus which was reported by 60 (74.1%) and Anthemis cotula which was reported by 28 (71.6%). A detailed list of the medicinal plants reported in this study are shown in Table 3.
Leaves and fruits were the most commonly used parts of the medicinal plants. The rest of parts used by the study patients are shown in Table 3. Medicinal plants were most frequently prepared in the form of pastes (Table 3). Medicinal plants were obtained from different sources. The majority of the patients obtained their medicinal plants from wild life (Table 4). When asked about their source of knowledge on medicinal plants, the majority of the study participants stated that medicinal plants were recommended by other patients with psoriasis (Table 4).

Reasons for using or not using medicinal plants
When asked why they use medicinal plants to manage their psoriasis, patients using medicinal plants gave various reasons. The most commonly reported reason was safety. Other reasons reported in this study are shown in Table 4.
When nonusers were asked why they were not using medicinal plants to manage their psoriasis, again they mentioned many reasons of which concerns over safety was the most frequently reported reason. Other reasons are shown in Table 4.

Discussion
This is the first investigation on the use of medicinal plants in patients with psoriasis in Palestine. The findings from this study showed that 54.4% of the patients included in this study used medicinal plants to treat signs/symptoms of their psoriasis. Our results were consistent with prior studies in which the prevalence of  [15,[20][21][22]. Comparisons using χ 2 or Fisher's exact analyses showed that users of medicinal plants differed with regard to age and monthly household income. However, educational level, place of residence, stage of the disease and time relapsed since diagnosis were not significantly associated with the use of medicinal plants. Nonparametric correlation showed that age and marital status were significantly and positively correlated with the use of medicinal plants. However, monthly household income was significantly and negatively correlated with the use of medicinal plants. In this study, the most commonly reason for using medicinal plants was the belief that these CAM modalities were safe (27.5%). Patients also reported enhancing immunity and reducing side effects of conventional therapies (16.7%). These results were in line with those reported in the UK in which dissatisfaction with the results of conventional therapies was the most commonly reported reason for using CAM modalities (including the use of medicinal plants) by patients with psoriasis [23]. This study showed that 33 different plants were used with various methods of preparation by patients to treat their psoriasis. The most commonly used plants were Aloe vera, Trigonella arabica, Catharanthus roseus and Anthemis cotula. Some results were not surprising as Aloe vera was reported to be commonly used by patients with psoriasis in prior studies [15,17,24,25]. Randomized clinical trials were conducted using a cream containing Aloe vera in patients with psoriasis which showed statistically significant improvements [24]. Progressive reduction of lesions, desquamation, decreased erythema, infiltration, lower psoriasis area and severity index score (PASI) were considered as improvements [24]. PASI scores in the treatment group decreased from 9.7 to 2.2 compared to 8.9 to 8.2 in the placebocontrolled group [24]. Untoward effects were not reported in this study. Paulsen et al. used a gel containing Aloe vera in a randomized placebo-controlled trails [25]. Modified PASI scores decreased in 75.2% of patients in the treatment group compared to placebo group [25]. Probably, patients in our study witness   improvements from using Aloe vera based preparations and spread the word to family, friends and other patients. Interestingly in this study, a significant number of patients with psoriasis learned about medicinal plants from family friends and other patients with psoriasis. Many of the plants reported by the patients in this study were used for their promised activity against psoriasis [26]. The rhizomes of Curcuma longa has been in use in traditional medicine since thousands of years to treat various inflammatory disorders including psoriasis [26]. The main constituent in Curcuma longa is curcumin to which anti-psoriatic activities are attributed. It is thought that curcumin targets various transcription factors such as NF-KB, AP-1 and PPARγ, enzymes such as COX2, 5-LOX, iNOS and hemeoxygenase-1, cell cycle proteins such as cyclin D1 and p21, cytokines like TNF, IL-1, IL-6 and some cell surface adhesion molecules [26][27][28]. Zingiber officinale is also thought to exhibit anti-psoriatic activity though 6-Gingerol which is a natural analogue of curcumin [29]. Glycyrrhiza glabra was shown to possess anti-proliferative and anti-inflammatory activities in psoriasis [30]. The use of Glycyrrhiza glabra was reported to be safe, effective and inexpensive [26,30].
Some of the medicinal plants used by the patients who participated in this study were not previously reported to be used to treat psoriasis. These plants include Trigonella arabica. However, other members of the same leguminosae family like Psoralea corylifolia L. were shown to contain phenolic glycosides which might inhibit keratinocytes replication in psoriasis [31]. Crotalaria emarginella Vatke is another member of the same family was shown to contain crotalic acid which exhibited anti-inflammatory action in psoriasis [26].
Interestingly, many of the medicinal plants reported to be used in this study are edible and widely used in folk diet. This might suggest that these plants could be nontoxic or possess low toxic activities. However, it is important not to overestimate the safety and efficacy of the medicinal plants reported to be used in ethnopharmacological surveys. Prior studies showed that some of the medicinal plants used were associated with unwanted side effects. For example, some Trigonella arabica species were reported to have hypoglycemic effect when used systemically [32]. However, it is noteworthy to mention that topical application on the skin is often associated with less severe side effects than systemic exposure.
It is also important to note that the efficacy of some treatments were questionable as randomized clinical trials failed to demonstrate significant improvements in psoriasis patients [15,17]. For example, Stucker et al. treated 13 patients with psoriasis topically with a combination of vitamin B12 and avocado oil, after 12 weeks no statistically significant reduction in PASI scores was observed [33].
As Aloe vera, Trigonella arabica, Catharanthus roseus and Anthemis cotula were the most frequently used medicinal plants by patients with psoriasis who participated in this study, a brief review of their uses, side effects, in vivo and in vitro activity in psoriasis are briefly reviewed and summarized in Table 5.
In the present study, the majority of the medicinal plants were prepared in the form of pastes. Pastes were most commonly prepared from leaves and fruits. This was consistent with the nature of the disease and the intended action as agents were meant to be applied  Side effects and toxicity with reference source
Hydrophilic cream and gel of Aloe vera were tried and showed significant improvement against psoriasis in a randomized clinical trial [24,25]. In another study, topical Aloe vera with 0.1% triamcinolone acetonide was used in mild to moderate plaque psoriasis. Aloe showed its ability to reduce the clinical symptoms of psoriasis [41]. Aloe extract showed anti-psoriatic activity of 81.95%, compared with 87.94 for tazarotene in the mouse tail model of psoriasis [42].

Trigonella arabica
The plant was used in ethnomedicine for treatment of psoriasis in Palestine [45] and Pakistan [46].

No reference No reference
Catharanthus roseus No reference C. roseus reduced the expression of psoriatic marker, keratin 17 (K17) in human keratinocytes [47].