Bioactive Phytochemicals from Himalayas: A Phytotherapeutic Approach E-Book
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- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
- Veröffentlichungsjahr: 2008
Bioactive Phytochemicals from Himalayas: A Phytotherapeutic Approach covers herbal medicines from the Himalayan mountains. Chapters in this book detail molecular mechanisms and experimental tools and techniques for research on plants in this region. Phytochemical experts guide the readers through the role of Himalayan plants in therapy for metabolic diseases like cancer and diabetes, hepatic diseases, inflammatory diseases, and neurodegenerative diseases. Some chapters focus on diseases and how various plants from Himalayan origin are beneficial in these diseases.
This compilation,with professional contributors, aims to inform a wide scientific community from various research fields about basic research on medicinal plants with a focus on Himalayan herbs. The book also serves as a handbook for pharmacologists working on the broad therapeutic aspects of these plants.
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FOREWORD
Dr. Satwinderjeet KaurNatural products are continually attracting researchers, and gaining popularity all over the globe as other alternative drug discovery methods are failing to provide a satisfactory number of novel lead compounds which can qualify as drugs against various diseases. The Himalayas are noted for their vast plant richness, as well as their abundance of bioactive phytoconstituents due to their extreme ecological circumstances. In folklore and traditional medicine, a variety of Himalayan-based plants are employed for their medicinal use. There are growing experimental studies that substantiate the pharmacological potential of various phytochemicals of Himalayan-origin. This book will serve as an important literature discovery tool for researchers engaged in drug discovery using plant medicines. This book compiled the experimental evidence that implicates the role and effectiveness of bioactive phytochemicals derived from these valuable plants for the treatment and management of various diseases. The book has been divided into 11 chapters that explore the pharmacological properties of Himalayan plants in the management of cancer, hepatic diseases, diabetes, neurodegenerative, inflammatory diseases, etc. A special account of bioactive properties of various Himalayan plants such as Grewia sp., Atropa belladonna, Tinospora cordifolia, Swertia and chirayita, against various diseases has also been given in the book. This book also covers two methodological chapters. One of the chapters gives an account of phytochemical databases and the other chapter guides through some of the tools and procedures for isolating phytochemicals from Himalayan plants. This unique compilation will serve as a reference guide for academicians, researchers, and students interested in exploring various therapeutic aspects of Himalayan plants.
PREFACE
Drug discovery remains a challenge currently despite the advancements such as high throughput screening (HTS) of the synthetic libraries of candidate compounds. Even in the modern era of medicine, getting a drug to the market is extremely difficult and we still continue to rely on our traditional knowledge of medicinal plants in the hope to get new drugs for better therapies. Plants have traditionally been used for the treatment of various illnesses and despite the discovery of drugs derived other than plants such as antibiotics and HTS of synthetic drugs, plant-based products remain significant in numbers as drug molecules. Various plant-based medicines such as paclitaxel, artemisinin, quinine, digoxin, etc. are in clinical use. These drugs have revolutionized the medical world as they are highly potent against various diseases.
The Himalayan region is considered one of the richest biodiversity regions of the world exhibiting a wide variety of plant wealth, generally regarded as the Gold mine of medicinal and aromatic plants. In addition to the description of Himalayan plants in traditional medicine systems such as Ayurveda or Chinese medicines, plants of the Himalayas are utilized by the local people of the region in the preparation of a variety of herbal formulations for the treatment of a number of aliments including cancer, gut diseases, diabetes, etc. Several plant-based drugs viz. Artemisinin, Berberine, Quinine, Emetine, Ephedrine, Digoxin, Taxol, Podophyllotoxin, etc. are obtained from plants in the Himalayan region. This book compiles recent studies on the developments in the role of bioactive phytochemicals derived from Himalayan plants in protection against various disorders and associated research tools.
The first chapter authored by Bhatia and coworkers discussed the anticancer potential of some of the Himalayan botanicals and their underlying pathways. The second chapter of the book by Pandit et al. summarized the hepatoprotective activities of several high-altitude Himalayan plants and tabulated heptoprotective molecules from these plants. Singh and Singh demonstrated the potential role of Himalayan botanicals in neuroprotection in the third chapter. Chapter four by Pandey et al. collated the antidiabetic potential of Swertia chirayita, which is an important herb of Himalayan origin. Several pathways modulated by Grewia berries in metabolic diseases such as cancer, diabetes, and hepatic disorders are described in chapter five by Rajput et al. Sharma et al. discussed the therapeutic role of Atropa belladona obtained from the Himalayas in chapter six. Rajak et al. focussed on the immunomodulatory aspects of Tinospora cordifolia in chapter seven, and Kavita et al. described the immunomodulatory potential of Withania somnifera in chapter 8. In chapter 9, Mishra et al. discussed Himalayan plants, which confer immunomodulation and antioxidant protection. Chapter Ten by Shagun and Masakapalli comprehensively describes the tools and techniques to isolate phytochemicals from Himalayan plants. Shagun and Masakapalli in the last chapter discussed various phytochemical databases and demonstrated how to use them to look for the botanicals derived from Himalayan plants to facilitate phytotherapy research. The last two chapters hold great significance as tools for researchers working in this area.
It is to be noted that the authors of various chapters are responsible and answerable for any scientific queries and questions. We are highly grateful to the scientists, who have contributed their research and made this book a unique compilation of studies in the field. The book can serve as a handbook for researchers working on various aspects of Himalayan plants focusing on therapy.
List of Contributors
Anticancer Phytochemicals from the Himalayas: Underlying Mechanisms and Chemopreventive Significance in Cancer
Anjana Bhatia1,Saroj Arora2,Bikram Singh3,Avinash Nagpal2,*Abstract
High-altitude plants have traditionally been a rich source of preventive and curative medicinal compounds. The rich repository of herbs found in the Himalayan region has not only been a source of health and general well-being for local communities but also for the modern pharmaceutical industry. In the current scenario, medicinal plants from the Himalayas are a promising resource for numerous metabolites which can serve as lead molecules against various deadly diseases. Plants growing at high altitudes suffer from an onslaught of stressful conditions, including mutagenic radiations, high-velocity winds, dehydration, etc. Plants of this region usually cope with these by altering their biochemical profile and producing chemicals that are called secondary metabolites. These secondary metabolites belong to chemical classes like phenols, terpenes, and alkaloids in general. The primary objective of this chapter is to study the anticancer potential of phytochemicals from some high-altitude plants. The underlying mechanism of their anticancer and chemopreventive action will also be discussed.
INTRODUCTION
Despite the huge progress made by humankind, preventive and therapeutic measures for diseases like cancer remain a challenge. Cancer, being a major cause of human fatality, is a matter of great concern. Globally, cancer incidence is on the rise. It is expected that by 2035, the number of cancer cases will double worldwide [1]. Furthermore, the treatment of cancer is very expensive. Phytochemicals must be screened for their cancer chemopreventive and thera-
peutic abilities so that the side effects of synthetic drugs may be minimized [2]. Many research studies have been dedicated to investigating the anticarcinogenic, antimutagenic, and antioxidant properties of phytochemicals. Plants used in the traditional medicinal system have been a subject of interest for such studies [3, 4]. India is especially advantaged as it has a rich biodiversity of plants that have been used by locals for several ailments. The plants growing at high altitudes, especially, in the alpine zone (3000-4500m) of Indian Himalayan Region (IHR) have been a time-tested remedy for some ailments. Such plants need to be explored to find cancer combating phytochemicals.
THE INDIAN HIMALAYAS: A TREASURY OF MEDICINAL PLANTS
The Indian Himalayas are one of the youngest mountain ranges in the world. They are the crowning glory of India, not only geographically, and aesthetically but also in terms of rich floral biodiversity. They encompass approximately two and a half thousand kilometers in length and about two and fifty kilometers in width. The area accounts for fifty percent forest area of the entire nation. Amongst a range of dry deciduous, subtropical, rainforests, temperate vegetation, and alpine meadows are found an astonishing diversity of plants with enormous medicinal value. Almost two thousand medicinal plants have been identified from the Indian Himalayan region [5]. In the present chapter, Himalayan plants used in the traditional medicinal system by the local inhabitants are discussed for their anticancer and cancer-preventive effects.
Hypericum Perforatum Linn.
“St. John's wort doth charm all the witches away.
If gathered at midnight on the saint's holy day”
(An old English poem depicting the favor St. John's wort enjoyed during the pre-Christian era).
St Johns wort (SJW) is a plant that is considered a weed in most of the countries of the world. Scientifically, this plant is known as Hypericum perforatum. The plant derives its name from its supposed ability to drive off evil spirits. It is called St. Johns wort because of its anthesis time matching with St. John's day [6].
Phytochemicals from Hypericum Perforatum and their Cancer Chemopreventive Activities
Many different types of secondary metabolites are found in different species of Hypericum. Out of all the species, scientists have majorly been interested in H. perforatum due to its varied biochemistry. Several different types of chemicals have been reported from the species [7]. Hypericum perforatum is a very useful plant in pharmacognosy, because of the presence of various chemical classes like phenolic acids, naphthoquinones, phloroglucinol, flavonoids, etc [8].
Many investigations have been carried out to assess the cancer chemopreventive and anticarcinogenic activities of Hypericum. In fact, due to its antidepressant properties, Hypericum is often used and well endured by cancer patients and throughout usage, it showed no genotoxicity [9]. Hypericin, a bioactive molecule from H. perforatum showed tamoxifen-like activity in inhibiting the growth of glioma cell lines [10]. It was also deduced that the inhibitory activity of hypericin was due to its action on Protein Kinase C (PKC). In another report [11], it was seen that hypericin and peudohypericin isolated from H. perforatum exerted antiproliferative activity by inhibiting the PKC. It is noteworthy to mention here that PKC [Protein Kinase C] is responsible for causing several tumors. It has also been seen that hypericin possesses marked phototoxicity towards cancer cells [12]. The antineoplastic activity of hypericin against many cell lines has been reported [13]. Furthermore, the extracts prepared from SJW showed anti-carcinoma activity. Detailed investigations demonstrated that the plant exerted its anticancer activity through diverse mechanisms including synergism, apoptosis, and activation of caspases [14, 15]. Hyperforin, another bioactive molecule from H. perforatum inhibited the growth of mononuclear cells as well as breast carcinoma cells [16].
Juniperus sp.
Junipers thrive at an elevation of 1500-4500 meters above sea level. They lend unparalleled beauty to the mountains. They are evergreen shrubs with rigid, oval leaves. The plants are much used in folk medicine by local communities of Ladakh, Jammu and Kashmir, Kishtwar, Himachal Pradesh, Uttarakhand, Nepal and other areas of the Indian Himalayan Region. These aromatic plants belonging to the family Cupressaceae produce bluish berries which are reported to have potent medicinal value [17]. People from Indian Himalayas have been using various parts of the plant in traditional medicine to treat diseases like rheumatism, skin ailments, fever, headaches, stomach problems, gynecological disorders, etc. A major use of various species of the genus Juniper is as incense or agarbatti [17].
Phytochemicals from Juniperus sp. and their Cancer Chemopreventive Activities
The plants of the genus Juniper are a rich source of medicinal and aromatic secondary metabolites including various tannins, phenolics, alkaloids, glycosides, flavonoids, etc. Many studies have proven the potential of Junipers to act as cancer chemopreventive agents. In a recent study [18], oil from the berries of Juniperus sp. was tested for its efficacy in cancer prevention. It was concluded that the oil possessed a significant ability to reduce adenoma and adenocarcinoma. Researchers also evaluated cancer opposing effect of J. communis on hepatocarcinoma cells and reported that the extract showed potent ability to inhibit the growth of cancer cells by employing mechanisms like apoptosis, suppressing the metastatic protein expression, and by arresting cell division [19]. They recommended further investigation of Juniperus extract for its development into a useful anticancer agent. Another team investigated the anticancer potential of Juniper extract and reported that the extract suppressed the division of cancer cells by stimulating G0/G1 arrest via regulation of cycle regulatory proteins [20]. Water extract from Juniperus sp was investigated for its efficacy against cancer [21]. The extract was examined for its activity against various cancer cell lines and it was seen that Juniperus berry extract was quite efficacious in decreasing lung, prostate and liver cancer. The researchers further deduced that the mechanism of Juniper extract to decrease cancer cells involved cell death using p53 and Akt mechanisms. Earlier, in a study [22], it was seen that deoxypodophyllotoxin which was obtained by bioassay-guided fractionation of extracts from Juniperus sp. acted as a potent anticancer agent and induced apoptosis in breast cancer cells.
Lavandula sp.
Lavender belongs to the family Lamiaceae. Most of the plants belonging to this family like rosemary, thyme, and mint are highly aromatic. Lavender is also an aromatic plant that grows extensively in cold climates. The Latin word for lavender is ‘lavare’ which means 'to wash'; the flowers of lavender used to be put in baths for relaxation. Lavender used to be an important constituent of smelling salt used for fainting spells.
In India, the plant is grown in the high-altitude states of Uttarakhand, Himachal Pradesh, Jammu and Kashmir. With light purple flowers, the plant extends great beauty to the landscape. The genus Lavandula contains several herbs with fragrant pale purple flowers which are a rich source of aromatic essential oils. In a review, it was reported that Lavendula Angustifolia and L. latifolia are the most widespread species of lavender. L. angustifolia is considered to be the true lavender whereas L. latifolia is called the spike lavender [23]. Lavender flowers have been investigated extensively for many therapeutic uses. Lavender is considered to be one of the best sleep disturbance remedies. The plant is considered a valuable source of anti-depressants [24].
Phytochemicals from Lavender and Cancer Chemoprevention
The phytochemistry of lavender has been investigated in a number of studies using standard protocols. Various researchers confirmed the presence of tannins, flavonoids, saponins, terpenoids, carbohydrates, anthraquinones, cardiac glycosides, alkaloids, coumarins, proteins, sterols, cyanogenic compounds, essential oils, O-heterosides and C-heterosides [25]. Other chemicals identified in lavender include p-vinyl guaiacol, methane carboxylic acid, pentadecanoic acid, dimethylamine, and N, N-dimethyl methanesulfonamide [26]. It has been recently reported that linalool, camphor, and borneol are present in lavender species [27]. Other studies revealed the anticancer potential of Lavandula sp. against a number of cancer cell lines. Extracts from lavender were able to decrease Hodgkin lymphoma cells. Researchers also studied the efficacy of lavender oil on the human hepatocyte cancer cell line. They used various concentrations of lavender oil and found that lavender oil killed cancer cells by destroying the plasma membrane [28-30]. Anticancer, antioxidant, and anti-inflammatory activities of lavender were also reported [31]. Studies on the anti-tumor effect of lavender on prostate cancer cell lines were carried out and it was reported that the essential oil of lavender and its components exert a potent antiproliferative effect [31, 32]. Significant anticancer effects of lavender essential oil on MCF human breast cancer cells were also demonstrated [33]. Antiproliferative and antitumor activity of lavender essential oil was investigated [34]. It showed a significant cytotoxic effect on C6 glioma cells. A team of scientists [35] investigated the efficacy of the inhalation of lavender oil for pain relief after colorectal cancer surgery. They concluded that inhalation of linalyl acetate is an efficient intrusion to relieve pain in patients who went through CRC surgery. It was also pointed out that lavender essential oils possess therapeutic action on cancer, and it was further suggested that lavender can be used on cancer patients for a calming effect and as an anxiolytic agent [36]. Strong antimutagenic activity of lavender oil in the TA98 strain of Salmonella typhimurium has also been reported in a number of studies [37, 38]. Perillyl alcohol (POH), a component of lavender essential oil inhibits tumor cells and exerts cancer preventive and therapeutic effects [39]. Linalool is an active component of lavender essential oil. Linalool is reported to possess chemopreventive potential against lung cancer by interacting or modulating selected biomarkers associated with a lung cancer diagnosis, progression, and proliferation [40]. Researchers investigated various members of the Lamiaceae family including Lavandula and concluded that chemical compounds present in them are potent in alleviating the side effects of radiotherapy and should be considered as a complementary therapy for cancer [41].
NO suppressing effect of lavender characterized by high terpenoid content and enhanced antioxidant enzymes and protein synthesis in wounds was also confirmed [42]. The chemical composition and biological activities of L. stoechas were also studied [43]. They reported remarkable antiradical and antileishmanial activities of lavender essential oil. Lavender extracts also demonstrated strong antioxidant activities in the DPPH assay. Also, essential oil from lavender was found to possess antioxidant, anti-inflammatory and analgesic activities. Essential oils from L. angustifolia were found to exhibit protective effects against oxidant-induced DNA damage. Essential oil of lavender is also proposed to be a modulator of oxidative stress [44]. Antioxidant and broad anticancer properties of limonene (a component of Lavandula essential oil) were reported to be connected with stress enzymes [45].
Pinus sp.
“Between every two pines is a doorway to a new world”. Munir
Pines are beautiful, pyramidal trees found in the lower, middle, and upper reaches of the Himalayas at a range of altitudes varying from 16090-6300 feet. Pinus is the largest genus of the family Pinaceae. Pines are attributed many medicinal properties, specifically, the essential oils found in pines are considered have potent biological efficacy against many diseases including antimicrobial, antioxidant, promoting blood circulation, etc. Many formulations containing Pinus essential oils are reported to have a myriad of various activities like larvicidal, antiviral, antifungal, mosquito repellant and free radical scavenging effects [46].
Phytochemicals from Pinus and their Cancer Chemopreventive Activities
Essential oils from Pinus plant are found to possess several potent phytochemicals. Scientists have isolated approximately 50 phytochemicals from the essential oil of Pinus radiata [47]. The oil possessed potent phytotoxic activity. Recently, the phytochemical composition of seed oil of Pinus nigra was evaluated and it was concluded that unripe seeds can be used as functional foods because of their chemical composition [48]. Researchers have extracted essential oils from various morphological parts of P. roxburghii. They identified a number of chemical compounds in the essential oils of P. roxburghii species and reported their antibacterial as well as antioxidative activities [49]. In yet another study, more than a hundred and thirty compounds were isolated from P. cembra [50].
Procyanidins isolated from the bark of P. koraiensis were studied for antitumor potential [51]. The procyanidins exhibited antitumor activities on U14 cervical carcinoma mice. The researchers suggested that their antitumor activity may be associated with the inhibition of free radical production. Cancer chemopreventive activity of rosin constituents of Pinus sp. including isopimaric acid, mercusic acid, neoabietic acid, dehydroabietic acid, and podocarpic acid, as well as resin acid derivatives 8β,9α,13α-H-tetrahydroabietic acid, 8α,9α,13α-H-tetrahydroabietic acid, 13α-H-Δ [8]-dihydroabietic acid, maleopimaric acid, and fumaropimaric acid, were studied for their possible inhibitory effects on Epstein-Barr virus early antigen [EBV-EA] activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The results revealed that rosin possesses a pronounced anticarcinogenic effect, and its high activity is due to the synergism of the diterpenes contained in it. Researchers also [52] reported that the extracts of wood from P. resinosa showed selective cytotoxicity against human lung carcinoma cells, and human colorectal adenocarcinoma cells. Antitumor activity of Pinus bark extract was studied [53]. Extracts obtained from Pinus massoniana bark demonstrated a potent potential to induce programmed cell death. Further, in the same study, it was seen that the extracts reduced the tumor cell growth by inducing cell apoptosis and improving lymphoproliferation. Essential oils of P. wallichiana showed significant anticancer efficacy in a study [54]. Seventeen compounds were detected in the study and pinene was found to be the most potent. Scientists [55] also carried out a study to assess the antitumor activity of extract from the bark of P. sylvestris. Pine bark extract reduced viability and induced apoptosis in HeLa cell. The cones of P. koraiensis were subjected to in vivo antitumor studies [56]. It was discovered that the main compounds responsible for antitumor activity of pinecones were polyphenols which activated apoptotic pathways of cancer cells. Antitumor activity of essential oils from pinecones of P. korainesis was also studied [57]. It was concluded that the antiproliferative activity of the essential oils was due to their apoptosis-inducing ability. The anticancer potential of P. roxburghii essential oils was also assessed in yet another study employing a battery of tests [MTT assay, FACS analysis, cell viability test] against various cancer cells. The study revealed the potent efficacy of the essential oils in inhibiting cancer cell growth [58].
Scientists [59] investigated the anticancer effect of essential oils obtained from pine needles and reported their anticancer activity in various test systems including apoptosis assay, cell counting assay, focus formation assay, wound healing assay, cell invasion assay, etc. They reported that the essential oils regulated apoptosis and the cell cycle of MCF-7 cells and the mechanism of anti-proliferative activity involved AMPK (AMP-activated protein kinase) activation. The polysaccharides isolated from pollens of P. massoniana repressed the replication of tumor cells [60].
Bark extract from P. nigra was examined for antioxidative and antiproliferative activities. The bark extracts demonstrated a high cytotoxic activity [61]. Antimutagenic, anticarcinogenic, and antioxidant potential of P. densiflora was assessed and confirmed in a number of in vivo as well as in vitro tests [62].
CONCLUSION
Phytochemicals from high-altitude plants have been traditionally used against several ailments. These plants contain a plethora of secondary metabolites that can be used as cancer chemopreventive as well as therapeutic agents. Many of these plants act as potent sources of nutraceuticals and antioxidants. They can exert anticancer and cancer-preventive effects through various mechanisms. Hypericum perforatum grows in high altitude zone and has shown considerable anticancer effects in various studies. The active molecules present in H. perforatum, hypericin and hyperforin, exert cancer opposing effects mainly by inhibiting the protein kinases along with various other mechanisms like synergism, apoptosis, activation of caspases, phototoxicity, free radical scavenging, etc. Similarly, Juniperus
