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This review article underlines individual Traditional Islamic and Arabic plant (TAI) and their role in treating cancer. The aim of the study is to specifically evaluate the progress of herbs, Arabic and Islamic traditional herbs in particular, applied in cancer treatment, so far.
Islamic and Arabic plants were selected and identified through different literature survey using “Google scholar”, “Web of science”, “Scopus” and “PubMed”. Each plant, from identified Arabic and Islamic plants list, was search individually for the most cited articles in the aforementioned databases using the keywords, “Anticancer”, “Uses in cancer treatment”, “Ethno pharmacological importance in cancer” etc.
The current review about Islamic and Arabic plants illuminates the importance of Islamic and Arabic plants and their impact in treating cancer. There is a long list of Islamic and Arabic plants used in cancer as mentioned in review with enormous amount of literature. Each plant has been investigated for its anticancer potential. The literature survey as mentioned in table shows; these plants are widely utilized in cancer as a whole, a part thereof or in the form of isolated chemical constituent.
This review strongly supports the fact; Arabic and Islamic traditional plants have emerged as a good source of complementary and alternative medicine in treating cancer. Traditional Arab-Islamic herbal-based medicines might be promising for new cancer therapeutics with low toxicity and minimal side effects. The plants used are mostly in crude form and still needs advance research for the isolation of phytochemicals and establishing its cellular and molecular role in treating cancer.
The use of herbal medicine is leading modality, followed in Middle east, Europe, Israel and certain other advance countries, in order to treat cancer patients. According to latest WHO reports, even advanced countries have adapted traditional system of herbal treatment including; Belgium (31%), Australia (48%), France (49%), Canada (70%) and Germany (77%).1 The 25% of the crude drugs used in last two decades are derived from plants, out of which only 5–15% have been investigated for bioactive compounds. Recent surveys reveal the use of such phytochemical for cancer treatment due to the fact; relatively low/nontoxic, antitumor property with minimal side effects, failure of the standard cancer therapy. A research finding on complementary and alternative medicines identified 143 articles from different Middle-Eastern countries. The report findings performed in Turkey, Israel and other advance countries showed, half of the patient diagnosed with cancer used CAM therapy even during chemotherapy.2
The history of cancer treatment reveals, the interest in cancer treatment goes back to the times of Islamic renaissance scholar.3 As suggested by the famous scholar “Avicenna”, “if it is the start of a cancer, it is possible to make it static and prevent it from growth and hence ulceration”. Sometime it happens, that the starting cancer may be cured, but once it reaches to advance stages, verily it will not.4 In order to reduce resistance to the existing mechanisms, modern medical research shifted its focus towards finding of new anticancer agents as an alternate. The most promising alternate which took place are herbs and other natural plant products. The easy availability, low in cost along with possessing minimal side effects, makes the herbs as mainstream for treating and playing a vital role in the prevention and treatment of cancer.5 The wisdom of the past in the shape of folkloric and traditional uses served the better source for treatment of various human diseases including cancer. The most emerging role as observed for treatment or prevention in case of cancer was disclosed by Traditional Arab-Islamic (TAI) herbal-based medicines. The literature from ancient time as well as the use of Arabic and Islamic plants for cancer treatment by various Muslim and religious scholars, in contrast with standard use of these herbs in cancer now-a-days by different physicians and practitioners, is a self-comprehensible prove revealing the role of TAI herbs in cancer. The TAI herbs are promising for new cancer therapeutics due to low toxicity and minimal side effects also.6, 7, 8
Despite of advancement in treating diseases, the hallmark to cure cancer completely is not accomplished till to date. Although, endless efforts of researcher to eradicate cancer led to different molecular and cellular understanding i.e. signal transduction involved in angiogenesis, protein expression and apoptosis, the morbidity of this disease is so far rising. Research statistics showed that 20% of death in the world results from cancer, affecting more than one third of the world population.9 Several treatment are available i.e. drugs from synthetic or semisynthetic origin, radiation therapy, chemotherapy etc. but these approaches are least effective and accompanied by severe side effects in most of the cases. The major effective alternate is herbal treatment, with less side effects and potentially safer in cancer. The CAM study conducted (2007) in the U.S. population reports; almost 4 out of 10 adults had used some form of CAM within the past year.10 The American spent 33.0 billion U.S dollar (USD), accounting for 11.2% of total out-of-pocket health care expenditure, on Traditional products.2 Even in the more developed countries the use of CAM and traditional medicine is comparably extensive.11 According to WHO latest fact sheet; in India 70% of the population, in Ethiopia more than 90% of the population depends on traditional medicine for primary health care.12 Proportionally, more than 70% population in Chile and 40% population in Colombia adopted the traditional medicine for their healthcare system.13 The China (40%), too is in the list of countries using traditional medicine.14 The advanced countries i.e. Belgium (31%), Australia (48%), France (49%), Canada (70%) and Germany (77%) showed a comparable data for the use of different CAM and traditional treatment modalities.
The importance of the traditional herbal medicine can be assumed from the fact that, the number of member state regulating the herbal medicine increased from 65 (1999) to 119 (2012) along with the upgradation of the research institute for herbal medicine from 19 (1999) to 73 (2012), respectively.1
The demand of traditional medicines and practitioners is raising on regular basis. The fact can be supported by the enormous data available i.e. an increase of 30% (1995–2005), when 750,000 visits were recorded in a two week period in Australia15; 907 million visits (2009) for the Traditional Chinese medicines, accounting for 18% of all medical visits16; a total of 18226 traditional health care services for 80% of population in Lao People's Democratic Republic17 and the 560 U.S dollar/annum out-of-pocket expenditure for traditional medicines in Saudi Arabia.18 Likewise, hundreds of literature data is available, which just shows the importance and utilization of herbal and traditional medicine for the treatment of diseases including cancer.
The study plans; to evaluate the claims i.e. TAI plants have folkloric uses in treatment of cancer. The main focus is on TAI alternative medicinal plants for establishing their role in prevention, treatment or procurement of cancer. This review is an eye-bird view on the ancient TAI plants used in cancer treatment along with herbal treatment research.
Cancer, more appropriately described as, an uncontrolled growth or cell proliferation which invades other tissues as well. The mechanism behind tissue invading is through direct cell migration or blood and lymphatic system. The risk factors for cancer consist of chemicals, radiations, unhealthy diet, environmental factors, infection and tobacco smoke.19
There are hundred different types of cancer usually named by the tissue or organ or type of cell in which they begins. There severity can be benign (usually earlier stage) or malignant (end stage, mostly called cancer).20 Cancer identified in earlier stages are cured most likely, as mentioned in their first time treatments of cancer, by Avicenna, Abulcasis and Rhazes in the earlier Islamic and Arabic era.3, 21
The advancement in drug discovery technology, diversification of the health sector and reduced funding for natural product-based drug discovery, couldn't kneel the herbs and herbal treatment systems. The natural products from plants and biological sources still remain an unlimited and uncondensed source of new phytochemicals and nutraceuticals. The World Health Organization22 estimates; about 80% of the world population presently uses herbal-based medicines for some aspect of primary health care. The fact sheet also mentions the fact; herbal medicines are the most lucrative form of traditional medicine, generating billions of dollars in revenue.22 The era of 1984–2003, witnessed numerous natural product-derived small molecules patent, despite of decrease in the industrial funding for natural product-based drug discovery, at the same time. A comprehensive review of human drugs introduced since 1981 suggests that, out of 847 small molecule-based drugs, 43 were natural products, 232 were derived from natural products (usually semi synthetically), and 572 were synthetic molecules. However, 262 of the 572 synthetic molecules had a natural product inspired pharmacophore or could be considered natural product analogs. Natural products continue to make the most dramatic impact in the area of cancer. From 155 anticancer drugs developed since the 1940s, only 27% could not be traced to natural products, with 47% being either a natural product or a direct derivation thereof. According to recent surveys, there are about 450 medicinal plants in the Eastern region of the Mediterranean and about 230 medicinal plants in the coastal Mediterranean region in Egypt. These plants are used by healers for the treatment and prevention of almost all types of human disease, such as cancer; skin, respiratory, digestive, and liver diseases; diabetes and others.23
Advanced tumors are treated usually by chemotherapy and although these drugs are effective, they are associated with severe adverse events and drug resistance.24, 25 Traditional Arab-Islamic herbal-based medicines might be promising candidates for new cancer therapeutics with low toxicity and minimal side effects.5, 6, 8
The origins of Arab-Islamic medicine can be traced back to the time of the Prophet Mohammad, Peace Be upon Him (PBUH) as a significant number of Hadiths concerning medicine are attributed to him. Several Sahaba were successfully treated of certain diseases by following the medical advice of the Prophet Mohammad (PBUH). Despite great progress in allopathic medicine, Arab-Islamic medicine has continued to be practiced within the Mediterranean as well as most Arab and Islamic countries. In addition, Arab-Islamic therapies are most often utilized by people who have faith in spiritual healers and herbalists. These people are the first to be consulted for problems such as infertility, impotence, diabetes, obesity, epilepsy, psychosomatic troubles, and many other diseases.23
The spreading of cancer is increasing over the world and the percentage of deaths caused by this fatal disease is rising, especially in the developing countries. Scientists and researchers are now giving more of their attention to the herbal medicine to provide treatment for more difficult diseases like cancer due to the fact that, the treatments of cancer patients with chemical therapy have serious side effects. Recently herbal medicines are coming to play a more vital role in the reduction and prevention of cancer. The rapid interest in traditional Arabic herbal medicine (TAHM) worldwide is stimulated by many factors; that herbal products are safe and economical, they exhibit an extensive spectrum of biological activities such as, stimulation of the immune system, antibacterial, antiviral, anti-hepatotoxic, antiulcer, anti-inflammatory, antioxidant, anti-mutagenic, and anti-cancer effects.5, 7, 26, 27, 28
A variety of grains, cereals, nuts, soy products, olives, beverages such as tea and coffee, and spices including turmeric, garlic, ginger, black pepper, cumin and caraway confer a protective effect against cancer.26, 27, 29, 30, 31 Several studies have also documented the relationship between decreased cancer risk and high consumption of vegetables, including cabbage, cauliflower, broccoli, Brussels sprout, tomatoes, and fruits such as, apples and grapes.5, 28, 30, 32 In addition, a number of medicinal plants and herbs have also been reported to reduce the risk of cancer in multiple sites.33, 34
Traditional herbal medicines provide a remarkable source for new drug development. Indeed, about 50% of the modern drugs are herbal based.35 Since natural based products are inherently better tolerated in the body compared to synthetic chemicals and have higher chance to be approved as new drugs, searching for and purification of natural drug candidates is imperative. In the case of anticancer drugs, various drugs are derived from plant sources including but not limited to paclitaxel (Taxol), vinblastine, capsaicin, vincristine, the camptothecin derivatives, topotecan, irinotecan and etoposide.28, 36, 37, 38 Many commonly used anti-cancer herbs possess chemo preventive effects within their diverse pharmacological properties. Since cancer evolves over a long period of time, agents that inhibit or retard one or more of its stages could affect the overall course of the disease. Certain micronutrients (Oleuropein and Diallyl sulfide compounds found in olives and garlic respectively) possess potent cancer-preventive abilities.
The databases used for literature search are; “PubMed”, “web of Science”, “Google scholar” and “Science direct”. The relevant research/review article, illuminating the use of Arabic and Islamic plants in cancer, was downloaded using the free access portal of University of Dammam, for specific libraries.
The keywords used mostly during the literature search were as follows;
The Islamic and Arabic plants used in the review were confirmed and referenced from the literature sources i.e.4, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 The search for appropriate synonym of each plant, successively followed the step after confirmation.
The searching, confirmation and literature download step was repeated for each individual plant. This sequentially was followed by, a detail and extensive literature study for extracting out the material as mentioned in Table 1. The literature study showed an enormous contribution of these plants in cancer treatment. Table 1 shows the plants, synonym and their respective use in cancer as preventive or for treatment purposes.
In recent years, traditional Arab-Islamic herbal medicine has been gaining interest in the scientific community, and more specifically, regarding cancer treatment. Herbal medicine is the leading modality used by patients with cancer in the Middle East (e.g., 35% of cancer patients using CAM in Jordan)49 along with spiritual practices that are also prevalent (e.g., 75% of CAM users in Iranian study).50 CAM use is also popular among patients with pediatric,51 gynecological52 and hematological53 malignancies and among patients with an advanced disease.54
Several studies have been carried out for Arabic and Islamic plants. The Table 1 shows in-vivo and in-vitro studies for individual plants being applied in cancer and cancer related complications. Most of the research studies involve the application of these traditional plants against various human and animal cell lines. The same way, most of the plants, have been subjected to active isolation for the chemical entities responsible for cancer treatment.
The Table 1, mentions all the research work and literature available in order to cover or evaluate the progress of plants in cancer treatment. This study sum up the research activities specifically in the area of cancer and will help the researchers in order to utilize the available knowledge under one heading, for the applied research.
The modalities applied for treatment consists of plants in different forms i.e. crude extract (aqueous, alcoholic, hydroalcoholic, methanolic, ethanolic etc.), fractions, sub-fractions as well as isolated active compounds. Table 1 reveals the fact i.e. traditional plants in any form are efficacious in reducing the progression or treatment of cancer. Allium cepa & Allium sativum considered as common food herbs have shown considerable results in treatment of cancer. Anethum graveolens, Apium graveolens, Artemisia absinthium, Acorus calamus, Beta vulgaris, Cucumis melo, Zingiber officinal, Triticum aestivum, Thymus vulgaris, Nigella sativa and Crocus sativus as well as many other such plants have been utilized since long as plants for food, nutritious or common ailments treatments purposes. These plants have folkloric and traditional uses and their applications in cancer showed considerable results in treating or reducing the cancer progression. Most of the aforementioned (Table 1) plants have been studied in-depth for immunomodulatory and cancer treatment purposes i.e. N. sativa, Acacia seyal, A. sativum, Olea europaea, Vitis vinifera, resulting in isolation of lead compound with promising results in treating cancer. Resveratrol is a leading example isolated from V. vinifera applied effectively in treating cancer. Likewise Thymoquinone from N. sativa is proved an immunomodulatory for treatment in cancer therapy along with alliin and alliicin from A. sativum and Oleuropein/omega-3 fatty acids from Oleae europeae showed antioxidant and anticancer effects.
The aforementioned examples are an indication for the folkloric TAI plants implicated in the form of crude extract, fractions or sub-fraction in treating cancer, to be studied further in order to isolate active drug for cancer treatment. This review article provides data regarding TAI plants having folkloric uses and utilized in TAI system for treating cancer. The purpose of this study is to highlight these plants in order to be studied more for their biological, therapeutic and toxicological properties. Advancement in science and analytical techniques provides opportunities to study these plants for reducing any toxicological effects related to the use of these plants in cancer. These plants, as showed considerable results in treating cancer, even in the form of crude extract can be converted to nanoparticles or nanoemulsions in order to enhance its bioavailability and targeted therapy in the affected areas of cancer. These plants have a wide scope to be utilized for covering the deficient areas and hurdles of treating cancer as they having reports for folkloric uses with well-established research literature mentioned in Table 1 for individual plants.
The Table 1, helps to provide a list of plants used in cancer as well as available literature in order to accomplish the purpose of study i.e. TAI plants needs more research exploration. Despite the fact; some plants have been studied in the form of crude extract as well as isolation of therapeutic ingredient, via bioassay guided isolation, still most of the plants having lack of studies with respect to toxicity and mechanism involved during cancer treatment and hence needs further research profiling. Similarly most of the isolated active drugs showed greater toxicity as compared to crude extract. Table 1 gathers all these plants and the literature study regarding use in cancer providing sufficient information to use these plants in crude form as well as combination of these plants in raw or crude extract form for the treatment of cancer.
As mentioned in table, different types of cancer and tumors have been treated with these TAI plants which includes; hepatocellular carcinoma, breast adeno carcinoma, lung carcinoma, colorectal carcinoma, colorectal, breast, and lung cancers, esophageal and stomach cancer, prostate cancer, solid melanoma in the skin and benign prostate hyperplasia. The TAI plants showed cytotoxicity against different cell lines i.e.; larynx HEp-2 cells, BJAB cells, PC-3, A-549 and MCF-7 cancer cells, PC12 and HepG2 cells, HCT116 human colon cancer cells, human bladder carcinoma RT112, human laryngeal carcinoma Hep2 and human myelogenous leukemia K562, HL60 and K562 cell lines, 6C3HED solid lymphosarcoma cells, A549 (human lung cancer cell), and DU-145 and LNCaP (human prostate cancer cell lines), (ER)-positive (ER+; MCF-7 and BT474) and ER-negative (ER−; MDA-MB-231 and BT20) human breast cancer cell lines and HO-8910 & 7721 cell lines showing effective cancer treatment by these plants.
Different mechanism i.e.; chemo preventive, antioxidants, Topoisomerase-I and II enzymes inhibitory, suppresses tumor necrosis factor alpha, G1-phase cell cycle arrest with an induction of p21 and a reduction of cyclin D1, inhibitory effect on nuclear factor κB (NF-κB) activity, mitogen-activated protein (MAP) kinase activation, protected DNA against oxidative damage to its deoxyribose moiety and inhibition of adenosine deaminase activity in prostate cancer were evaluated for these TAI showing promising result.
The literature cited in current review article highlights the lead compounds isolated which may be a target and source of new drug development for researchers in order to modify, carry out SAR and study new pathways in order to find a complete cure for cancer. The lead compounds isolated and discussed are; Hirsutanone, Flavonoid glycosides, Lignans, isoflavones, and phenolic acids, Anthocyanins, Harmane and Harmine alkaloids, Oleuropein and hydroxytyrosol, Hydroxytyrosol, Thymoquinone, Pseudolycorine alkaloid, Cucurbitane-type triterpenoids, Crocin and carotenoid ingredients of saffron, Cucurbitacins-type triterpene glucoside, Subamone a novel Cinnamomum monoterpenoid and Camphorin, Sesquiterpene lactones and Dihydrochrysanolide derivatives, Acetyl-11-keto-β-boswellic acid, 3-n-butyl phthalide and sedanolide and Senkyunolide-N, Senkyunolide-J & 3-hydroxymethyl-6-methoxy-2, 3-dihydro-1H-indol-2-ol and Anethofuran. The nature and structures as well as classes of aforementioned compounds are source of knowledge for finding effective class of drugs to be utilized in cancer treatment.
The table also includes herbs which are used as food or nutraceuticals. These Arabic and Islamic plants, used in any of the modality as aforementioned, showed the better alternative source for the treatment of cancer and malignancies. The extracted material from literature survey of these Arabic and Islamic traditional medicinal plants as mentioned in Table 1 justifies the fact; Arabic and Islamic traditional plant as medicine, are well documented in literature. The next major outcome of the study proved significant is; the active use of these folkloric used traditional plants by most of the practitioners, even today. These plants are the major source for research too and numerous pharmacological, toxicological, biological and cytotoxicity studies have been carried out for these herbs as shown by the unlimited literature available for each plant.
The wisdom of the past led to the discovery of chemo-preventive drugs. The Arabic and Islamic plants studied in this review article are more important as alternate for cancer research and treatment. These traditional plants and their folkloric/traditional pharmacological profile need to be preserved. The main area of emphasis; isolation of the active chemical having potency to treat cancer with minimal side effects and ensuring the safe use of these medicinal plants, should be strived more. These plants need effective utilization in order to make a hallmark through complete cancer cure and cheap regimen to be available for ordinary population.
Peer review under responsibility of The Center for Food and Biomolecules, National Taiwan University.