Analysis of herbal medicine among Bedouin of the Saint Catherine Protectorate (southern Sinai Peninsula) and its comparison to modern drug design

ABSTRACT The Saint Catherine region of southern Sinai Peninsula’s drylands encompasses a unique combination of geophysical conditions. These features have formed highly diverse habitats, which support extremely complex plant communities. Throughout history, the local Bedouin population has used many of these plants for therapeutic purposes. The objectives of this study were to document the medicinal knowledge for as many as possible plant species, evaluate this ethnobotanic knowledge against a modern biomedical database, and identify links between the two disciplines. On-site gathering of information, through structured interviews with two local key informants, revealed the traditional use of 90 native vegetation species for a range of therapeutic purposes. Surveying the modern biomedical uses of these plant species in the PubMed database revealed medicinal use for 41 of them, as well as other plant species without known traditional therapeutic uses. Of the 41 plant species, in-depth integration of traditional and modern knowledge was implemented for 20 species, for which sufficient information was found in the PubMed. The results highlight the common ground between the two disciplines, and propose bridges between traditional and modern medicines. The study stresses the need for additional research in ethnobotany, which may assist in developing new plant-based medications.


Introduction
The Upper Sinai Massif-located in the drylands of southern Sinai Peninsula-encompasses unique geophysical features, and is characterized by various geological beds, topographical landforms, geomorphic settings, and pedogenic conditions.These features form multiple habitats, micro-habitats, and ecological refugia, enabling the establishment, growth, and survival of extremely complex vegetation communities, and resulting in high species richness and diversity (Moustafa & Klopatek, 1995;Moustafa et al., 2019;Zalat et al., 2008).This is consistent with recent knowledge gained in the field of dryland geodiversity, providing new insights on the impact of geodiversity on soil-water dynamics and surface hydrology (Stavi et al., 2018), as well as on soil quality and functions (Stavi et al., 2019), with the consequent regulation of the structure and composition of plant communities (Lausch et al., 2020).
Many species of Sinai Peninsula's flora have been traditionally utilized by the local Bedouin communities as medicinal plants.Numerous studies that investigated the traditional therapeutic plant-use among Sinai's Bedouin tribes have either focused on northern Sinai or surveyed the entire peninsula.For example, the studies by Bailey and Danin (1981), Abd El-Wahab (2008), Saleem (2012), El-Seedi et al. (2013), Eissa et al. (2014), Elbadry et al. (2015), and Abd El-Wahab et al. (2018) all listed numerous plant species, and the corresponding traditional knowledge on diseases, illnesses, and health disorders that can potentially be cured by them.At the same time, only scant studies have focused on the medicinal plant-use among the Bedouin of the Saint Catherine Protectorate region.A rare exception is the study by Ramadan et al. (2018), who identified five medicinal chamaephyte species across the region, including Cleome droserifolia (Forssk.)Delile, Achillea fragrantissima (Forssk.)Sch.Bip., Chiliadenus montanus (Vahl) Brullo, Origanum syriacum L., and Thymus decussatus Benth.Further, relatively few studies (e.g.El-Seedi et al., 2013;Elbadry et al., 2015;Saleem, 2012) have assessed the traditional folkloristic information against contemporary medicinal knowledge.Such an assessment is important both for an academic validation of ethnobotanic knowledge and for proposing leads for new, modern medications.
Therefore, the main objective of this study was to cross information between traditional knowledge on medicinal plant-use among the Bedouin inhabiting the drylands of the Upper Sinai Massif, and modern clinical information.The study's specific objectives were to (1) list the native plant species traditionally utilized by local Bedouin, detailing specific medicinal purposes; (2) search for relevant bibliography of both in vitro and in vivo studies about potential therapeutic properties of these plant species; (3) identify metabolites (and metabolite combinations) that are active against human disease models, obtained by in vitro and/or in vivo studies; and (4) establish an integrative approach to identify information gaps between traditional knowledge of plant-based medicine and scientific-based drug design, while proposing directions for future research.The study hypothesis was that traditional/Bedouin knowledge and modern/clinical information on plants' medicinal properties and uses are substantially compatible.This hypothesis was based on the centuries-old wisdom that has been obtained by Saint Catherine's Bedouin community, which has demonstrated high skills in medicinal use of a wide range of vegetation lifeforms, including phanerophytes (trees and shrubs), chamaephytes (dwarf shrubs), hemicryptophytes (perennial herbaceous plants), therophytes (annual herbaceous plants), and geophytes (bulb and tuber plants).This hypothesis also relied on modern knowledge, according to which metabolites of desert plants contain a wide range of active materials with a substantial therapeutic potential (Ofir, 2020).
In phytogeographical terms, the Irano-Turanian chorotype is predominant in the Upper Sinai Massif region, but Saharo-Arabian, Sudanese, and Mediterranean chorotypes are also found (Moustafa & Klopatek, 1995).Of the approximately 1,000 plant species found across the peninsula, about a half grow in the Massif region, with relatively high representativeness of rare, very rare, and endemic species.Also, the region hosts an abundance of relict plant species that characterize currently colder/moister biomes (Ayyad et al., 2000;Danin, 1983;Kamel et al., 2001).The plant species occurring across the region represent over 140 genera and more than 40 families, with Gramineae (Poaceae), Compositae (Asteraceae), Labiatae (Lamiaceae), Leguminosae (Fabaceae), and Boraginaceae being the most widespread (Kamel et al., 2001).
The Saint Catherine Monastery, established by the Eastern Orthodox Church approximately during the mid-6 th century CE at the foot of Mount Sinai, has generated wide Christian interest in the region.Following the establishment of the monastery, the Byzantine Emperor Justinian I sent servants from the Balkans to reside in the vicinity of the monastery.Over time, the servants intermarried with Bedouin of the local Jabaliya tribe, and eventually converted to Islam (von Sarnowski, 2010).Over the years, as a source of subsistence farming, the Jabaliya Bedouin have developed a dense system of agricultural gardens along the region's wadis, which are irrigated by water obtained from numerous springs and wells (Danin, 1983).The rare combination of biophysical properties across the southern Sinai mountainous region, alongside its unique archaeological, historic, social, anthropological, and theological features, led the Egyptian government to declare the region as a natural protectorate in 1988.In 2002, the United Nations Educational, Scientific and Cultural Organization (UNESCO) nominated the region as a World Heritage site (UNESCO, 2002).

Structured interviews
Structured interviews were separately conducted with two local key informants (their names are kept with the authors), who have served as herbal therapists among the Jabaliya community over several decades.The interviewer (the third co-author of this manuscript) is an expert botanist, who has gained rich experience in ethnobotanic studies, and holds profound knowledge of plant communities native to the Saint Catherine Protectorate.The interviews were implemented using a structured trilingual (Arabaic, Hebrew, and Latin) spreadsheet encompassing a list of over 200 native plant species, which was prepared in advance based on previous vegetation surveys across the region.Also, three designated fieldtrips across the Protectorate were conducted by the authors of this manuscript with one of the key informants, aimed at obtaining information for selected plant species.Whether mentioned in the spreadsheet or identified in the field, the key informant was questioned about each plant species' therapeutic/medicinal potential and its specific uses, whenever relevant.The two key informants gave us their consent for academically publishing of the information provided by them.

Bibliographic survey
For the bibliographic survey, we used the PubMed database (https://pubmed.ncbi.nlm.nih.gov/), which covers more than 34 million citations for biomedical literature from MEDLINE, life science journals, and online books.Accompanying information was obtained from the Flora of Israel and Adjunct Areas website (https:// flora.org.il/en/plants/ACHFAL/).Information was searched using keywords, including names of specific plant families; names of specific plant species; disease indications (e.g.heart failure, stomach diseases, Crohn's disease, ache, sore, wound, bacterial/fungi infection, organ inflammation, cancer, degenerative diseases, depression, impotence, sterility, etc.); in vitro disease models (e.g.mouse/rat/human cancer cells, primary brain cells, etc.), and in vivo disease models (e.g.genetic modified, Caenorhabditis elegans, mice, drosophila, animal injected with cancer cells, animal infected with virus, animal infected with bacteria, etc.).Further, combinations of keywords and disease models were also searched.

In-depth survey and integration of traditional and academic knowledge for selected species
Among the native plant species for which both traditional and modern knowledge was recorded, 20 species were selected for an in-depth survey.These 20 plants have been traditionally used to treat disease and disorders such as skin wounds, stomach ache/irritation, sore throat and infections, digestive disorders, colitis, eye inflammation, kidney stones, pain relief, toothache, arthritis, hemorrhage/blood clot, colon problems/constipation, etc.The rationale for selecting these specific 20 species was the discovery of sufficient clinical and/or preclinical information in the PubMed database, which allowed the thorough integration of modern knowledge with the ethnic experience.

Results and discussion
Traditional use of plants for medicinal/therapeutic purposes involves actual trials on patients.This method of treatment is usually suitable for remote and isolated human populations without other available healthcare options.It relies on profound beliefs in the therapeutic potency of local plants.A list of 90 plant species traditionally utilized for therapeutic purposes by the Bedouin population of Saint Catherine is detailed in Table 1.
Plant-based pharmaceuticals are developed according to a procedure starting with the screening of plant materials (extracts and metabolites) against in vitro and in vivo disease models, followed by pre-clinical studies for toxicity/safety, and assessments for efficacy.In this study, we identified correlations between human diseases that are treated by traditional medicine, and plantbased activities identified using disease models that have been established by the academic community.The match is defined here as a 'bridge' between these two disciplines.It seems that plant metabolites hold the promise of the 'wisdom of the desert' for discovering new leads for drugs.Thorough research of this promise may become a novel track for drug developments in the future.
The therapeutic uniqueness of desert plants is attributed to the fact that under abiotic stress conditions, such as those that define drylands, plants stimulate oxidative stress reactive oxygen species (ROS), regulating the amounts of effective disease-controlling secondary metabolites (Alshehri et al., 2022).The ROS plays a key role in plants' acclimation to abiotic stress by acting as signal transduction molecules that regulate different pathways during plant adaptation to stress but is also a toxic byproduct of stress metabolism (Choudhury et al., 2017).
In this study, we demonstrate and discuss the bridge between traditional knowledge and academic information for 20 plant species, with information for additional 21 species (totaling 41 species) detailed in Table 2: (1) Achillea fragrantissima (Forssk.)Sch.Bip. is used by local Bedouin to treat skin wounds.
is used in traditional Bedouin medicine for treating kidney stones.In modern medicine, an accepted treatment for kidney stones is antibiotics.Indeed, academic studies suggested that H. salicornicum contains anti-bacterial properties (Yousif et al., 2021).Compounds identified in this species belong to various classes like fatty acids, triglycerides, steroids, coumarins, monocyclic naphthene derivatives, and peptides that depend on salinity (Panda et al., 2020).The specific anti-bacterial activity of these compounds is still unknown.The anti-bacterial activity of H. salicornicum against kidney stones is a suggested bridge between traditional treatments and academic studies.(11) Launaea spinosa (Forssk.)Sch.Bip.ex Kuntze is traditionally used by local Bedouin for pain relief.According to in vivo studies, methanolic extracts of L. spinosa contain anti-inflammatory and anti-angiogenic activities (Asif et al., 2020).In addition, the major phenolic compounds isolated from L. spinosa displayed a substantial cytoprotective effect against oxidative stress, sustaining the normal redox status of cells (Abdallah et al., 2016).A new phenolic compound-identified as 2,3-diferulyl R,R-(+) methyl tartrate-alongside five known metabolites including esculetin, esculetin-7-O-d-glucoside (cichoriin), fertaric acid, acacetin-7-O-d-glucoside, and acacetin-7-O-d-glucuronic acid, were isolated and demonstrated protective effects against oxidantinduced damage in HepG2 cells (Abdallah et al., 2016).A specific combination of the metabolites identified in L. spinosa can be considered as the active moiety against pain.Pain is the bridge between the two disciplines, as in many instances, it is a result of redox stress and inflammation that lead to cytokine secretion.(12) Majorana syriaca L. is traditionally used by local Bedouin in treating toothache.In vitro academic studies reported antioxidant and anti-carcinogenic activities of the species (Husein et al., 2014).The major volatile and semi-volatile metabolites of M. syriaca include alpha-pinene, beta-myrecene, o-cymene, p-cymene, gamma-terpinene, thymol, and carvacrol, in amounts depending on harvesting time and location (Abu-Lafi et al., 2008;Cala et al., 2021).Xanthine oxidase inhibitory activity was found as an effective treatment for gout and other Xanthine oxidase-related disorders (Hudaib et al., 2011).

Bridging between plant's traditional use and academic knowledge: Insights and conclusions
This study surveys traditional knowledge and modern information regarding the therapeutic or biomedical uses of plants native to the Saint Catherine Protectorate, and evaluates the potential for bridging between the two disciplines.The assessed uses were wound healing, pain relief, inflammation control, digestive disorder treatment, chronic colitis prevention, bowel damage care, Candida control, constipation treatment, blood clot prevention, cardioprotective therapy, etc.Overall, more than 200 native plant species were surveyed in this study.Vegetation species with identified traditional and/or modern uses were sorted according to categories of organ-related disorders and their related medical fields.For many of the plant species, we identified uses that fitted two or more categories.11) blood/hematology (Figure 1).Due to a certain similarity and substantial overlap between the categories of internal medicine and intestine/gastroenterology, and for the purpose of simplicity, we hereby combine them into one inclusive category, entitled as internal medicine.Within this combined field, a total of 59 species were located, of which 21 (36%) for traditional use only, 16 (27%) for modern use only, and 22 (37%) for both of the disciplines.For the ear, nose, throat/otorhinolaryngology category, a total of 19 species were located, of which 18 (95%) for traditional use only, and 1 (5%) for modern use only.For the head/neurology category, a total of eight species were located, of which five (62%) for traditional use only, two (25%) for modern use only, and one (13%) for both of the disciplines.For the teeth/dentistry category, a total of 12 species were located, all of which for traditional use only.For the ear, eyes/ophthalmology category, a total of nine species were located, all of which for traditional use only.For the heart/cardiology category, a total of three species were located, of which two (67%) for traditional use only, and one (33%) for modern use only.For the fertility/venereology category, a total of 14 species were located, all of which for traditional use only.For the joint, nerves, muscles/orthopedics category, a total of 19 species were located, of which 18 (95%) for traditional use only, and 1 (5%) for modern use only.For the skin, wounds/dermatology category, a total of 29 species were located, of which 18 (62%) for traditional use only, 3 (10%) for modern use only, and 8 (28%) for both of the disciplines.For the blood/hematology category, a total of six species were located, of which five (83%) for traditional use only, and one (17%) for modern use only.
We acknowledge the fact that receiving information only from two key informants may have introduced bias to the data.One way or another, bibliographic information on ethnic use of plants not mentioned by the key informants was found only for few more species, demonstrating the high reliability of the data gathered on site.Specifically, in addition to the 90 species identified by the local key informants as medicinal plants, the bibliographic survey in the PubMed database revealed traditional therapeutic uses for additional eight species native to the Saint Catherine protectorate, which are under medicinal utilizations elsewhere across the rest of the Sinai Peninsula, the remainder of Egypt's territory, the Jordanian Kingdom, or the Arabian Peninsula.These species are (in alphabetic order) Arnebia hispidissima (Lehm.)DC. for treating infections (SPNI, 2017); Lavandula coronopifolia Poir.and Lavandula pubescens Decne.that are used for treating a range of internal disorders (Abdoul-Latif et al., 2022;Al-Badani et al., 2017); Leptadenia pyrotechnica (Forssk.)Decne.for treating several diseases including cancer (Abu-Darwish & Efferth, 2018); Moringa peregrine Fiori that is used for treating a wide range of internal disorders, infections, skin irritations, etc (Senthilkumar et al., 2018);.Senna alexandria Mill., which is used for treating internal disorders (SPNI, 2017); Thymelaea hirsute (L.) Endl., which is used for treating skin irritations and wounds (Alkaraki et al., 2021); and Urginea maritima (L.) Stearn that is used for treating sore throat (El-Seedi et al., 2013).
Overall, results of this study suggest that vegetation species native to Saint Catherine Protectorate, which have been traditionally utilized by the local Bedouin community as medicinal plants, hold the promise of the 'wisdom of the desert' for discovering new leads for drugs.Thorough research of this promise may become a novel track for drug developments in the future.Specifically, knowledge of the unique compounds of plant metabolites may assist in identifying the constituents that determine the specific plant activities against a wide range of human diseases.Progressing this track may provide an added value of co-fostering nature conservation and related economic activities (e.g.eco-tourism) across the region.As such, this track should be promoted by both conservationists and policymakers, simultaneously sustaining environmental quality and empowering the local Bedouin community.

Figure 1 .
Figure 1.Medicinal/Therapeutic plant species' use, according to categories of organ-related disorders and their related medical fields (in black script), where spp. in blue script indicates traditional/ethnic knowledge; spp. in red script indicates modern/academic knowledge; and spp. in green script indicates both of the disciplines.

Table 2 .
Coupled traditional use and academic knowledge on Saint Catherine's medicinal plants

)
Solenostemma arghel (Delile) Hayne is used by local Bedouin populations in treating colon