Final Nature Cures Book pdf format with updated photos Dec 5th 2022

Chapter 6 Bioprospecting Marine Plant:Window to the Blue World Dr. Suphala Gupta & Dr. Niha Dhar Introduction Oceans cover most of the earth's surface, inhabiting approx- imately five million species, most being distinctive and un- classified. The diverse marine environment and its associated chemical diversity amount to indefinite resource of novel compounds. Marine resources are classified as the principal reservoir of natural molecules with unique chemical scaf- folds. The distinctiveness in the chemistry of metabolites produced is imparted due to adaptation in very difficult, competitive, dynamic and aggressive surroundings, which is diverse in several aspects from the terrestrial environment (Bowen et al. 2013). Oceanic plants range from single-celled organisms to large, complicated organization inhabiting near water surfaces, deep black Ocean to ice. They grow and evolve under high pressure, predominantly surrounded by sa- line water and aquatic animals adjusting to specific condi- tions, such as limited light making them phosphorescent and high flow remodelling body shape etc. Seagrasses, algae and seaweeds correspond to the majority of marine plants (Bianchi and Morri 2000). Algae and seaweeds represent simpler forms and are often microscopic, while Seagrasses have complex organization. It is hard to imagine the evolution of marine animals or their survival if marine plants had not existed. Through ages, these marine plants have provided elementary nourishment to the food chain. Phytoplanktons, the smallest single-celled marine along with algae develop the base of the unique marine food chain which is vital for the balanced ecosystem. Marine plants constitute an imperative position in the formation and upholding of the coral reefs, providing nourishment and shel- 156

ter for animals wherein algae living inside marine animals consume nitrogen from coral waste and provide nutrients in a symbiotic relationship. Despite having crucial functions in the ecological network, they are increasingly becoming vulnerable to pollution. Dredging and harvesting coral has drastically injured their wholesome assortment. The excess use of fertilizers and pes- ticides in the fields, oils exploration and spillage in the oceans, radioactive material, sewage and hazardous wastes drainage from cities into oceans have damaged seagrass beds and reefs extensively. Explosives used by tropical commer- cial fishers to stun fishes have destroyed marine plant habi- tats hampering a range of symbiotic associations as in Ches- apeake Bay in Maryland where seagrasses have witnessed enormous wreckage (Rick et al. 2017). Some scientists speculate growing ozone hole, along with other alarming consequences, might cause irreparable dam- age to Antarctica‘s marine plants. Further, marine plants transported by shipping vessels can occasionally dominate the native plant species growing in distant areas resulting in newer challenges. Several man-made changes in ocean com- position also alter marine biodiversity at large. The presence of high nitrogenous waste allows the algae population to de- velop fungi quite frequently depleting carbon supplies. This can lead to algal blooms or toxic red tide which in due course can smother coral reefs due to nitrogen imbalance and starve marine plants and organisms of oxygen. As was seen in 1996 when a red algal tide killed many Florida manatees. Global warming has its share in contributing to this mess. Increased water temperature in the oceans may result in corals expel- ling out algae thereby appearing bleached white because the algae is the reason behind coral's energy and colour. 157

Uses Marine plants are the largest oxygen resource on earth con- tributing to approximately 70% of oxygen generation and regulation in the atmosphere. The oceans encompass about three-fourth of the surface of our planet representing over 99% of the biosphere inhabiting in the extremes of salinity, temperature, light, and pressure conditions. Adaptation to harsh environments has led to a rich, diverse and unexplored marine bioresource with potential biotechnological applica- tions for developing new resources and industrial processes. The marine organisms are the biomarkers of the environment and the organisms including the residents of land and under water health indicates environmental problems that humans and land organisms might encounter in the longer run. Hu- mans have been using marine plants for medicinal uses since ages. The marine plant based biotoxins are a valuable source for developing pharmaceuticals. Oceanographers and ocean research scientists have joined hands in exploring seas using latest deep-diving techniques to gather samples in the quest to identify and understand the unexplored resource hidden in the blue seas. The promising research outcomes are advanta- geous for the pharmaceutical manufactures as well to seek putative new chemical compounds for drug development. The diversity, novelty and uniqueness of marine plants have raised hopes of proposing new treatments for diseases re- sistant to existing non marine-plant-derived drugs as in mi- crofibrous collagen sheets which are a promising drug carrier for cancer treatment (Sato, Kitazawa, Adachi, & Horikoshi, 1996) due to its two desirable qualities of maintenance of drug concentration for long-term and controlled release at target site, besides, playing a critical role in the formation of cells, tissues and organs. Clinical investigations have demonstrated collagen/gelatin hydrolysates intake as pain-reliever in osteoarthritis and car- 158

tilage matrix synthesis, and as a gene delivery agent promot- ing bone and cartilage formation (Nakagawa and Tagawa 2000). The pharmaceutical companies are marketing colla- gen/gelatin as a supplement for maintaining bone integrity and nourishing scalp hair. Various classes of compounds in- cluding polyphenols, polysaccharides, alkaloids, and peptides are the potent bio actives predominantly having anticancer properties. United States Food and Drug Administration (USFDA) has approved marine resourced anticancer drugs including cytarabine, trabectedin for myelogenous leukemia and advanced soft tissue sarcoma, respectively. Several other drugs like Eribulin mesylate, brentuximab ve- dotin for breast cancer and liposarcoma, and anaplastic large cell lymphoma respectively extracted from marine source have been marketed. The examples of marine-derived drugs include an antibiotic from fungi, two closely related com- pounds from a sponge that treat cancer and the herpes virus, and a neurotoxin from a snail that has painkiller properties making it 10,000 times more potent than morphine without the side effects. There are several more marine-resourced compounds currently in clinical trials and it is likely that many more will advance to the clinic as more scientists look to the sea for these biotechnological uses. Chitosan Chitosan is a chemical substance present in the exoskeleton of marine shell fishes like snails and crabs. Research has shown it to be an excellent nano-delivery system for anti- cancer targets due to its hydrophilic nature and biocompati- bile, and biodegradable properties making it a desirable anti- cancer drug delivery system. Stable, porous, and bioactive chitosan nanocarriers have been successfully designed which has enabled extensive use of chitosan in the distribution of anticancer medicines. In addition to new medicines, other us 159

Exclusive Species From Ladakh Dracocephalum heterophylum, Khardungla (Ladakh); Science Citation: Surinder Kitchlu© 160

for marine-derived compounds includes cosmetics (algae, crustacean and sea fan compounds), nutritional supplements (algae and fish compounds), artificial bone (corals), and in- dustrial applications (fluorescent compounds from jellyfish, novel glues from mussels, and heat resistant enzymes from deep-sea bacteria). Generation of the immense quantity of underutilized marine processing by-products has long been recognized as waste, and efforts are on to use these materials in various applications. Researches on marine based by- products have resulted in the identification of biologically ac- tive compounds with application for human utilization. Po- tential applications of proteins, lipids, chitin and minerals in marine bio-processing leftovers as bioactive materials have increased the value of processing by-products in recent years. Marine plants like algae, Seacucumber, Seagrasses and Red Alga have also been used as a source of nutrients, cosmeceu- tical and pharmaceutical properties. The two most important long-chain poly unsaturated fatty acids omega-3 (ω-3), namely Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the involved in human physiology, and vital to infants' brain development are almost exclusively based on microalgae. Approximately 40% of baby formula is made from these algae‘s. The plant has an advantage of easily grown under controlled conditions with a constant biochemi- cal composition and ensuring sustainable supply making it an obvious choice for the biotechnology industry. Dunaliella bardawil biosynthesizes the orange pigment beta- carotene, which the human body converts into vitamin A. Commercial production of this alga manufactures carotene. Similarly, the red algae are the used in seaweed drinks and cooking. Other commercialization of marine plants includes post harvest value addition of seaweed for various products, including foods and fertilizer as in Chlorella and Spirulina. Researchers aspire to transfer gene responsible to tolerate ex- 161

treme saltiness and sun exposure identified from D. bardawil on to land plants cultivated in places with high salinity and sunlight. Hopes are high in achieving results from studies on the physiological relationship of algae and water for opti- mum cell growth and photosynthesis to reduce crop losses, and to understand how terrestrial plants as corn can tolerate droughts. Researchers are also investigating molecular exam- inations of marine and land plants to comprehend relation- ship between water supply, growth rate and metabolism in underwater plants. The cells of the alga Chara corallina are large enough to observe how dehydration affects them over a short period of time. Evolutionary adaptations of marine species resulting in unique modifications both physiologically and morphologi- cally to thrive in these environments have resulted in a living library of biological and genetic diversity with limitless bio- technological potential. Biodiversity is essentially adaptation to constant changes in the environment. Diverse forms have evolved in response to various environmental factors; distinct species arose and diversified to occupy and exploited new niches including the Oceans. The simple unicellular forms to the complex multi-cellular organization are more diverse and uniquely adapted than the terrestrial forms. Also, the limita- tions of the desired exploration vehicles (manned or un- manned) to the deepest parts of the ocean is hampering the exploration of the diversity. The oceans truly are among the last frontiers of exploration on the planet. Yeasts have received enormous consideration for over one hundred years as these can produce numerous kinds of bioac- tive substances. In this regard, terrestrial yeasts have been mined more than their marine counterparts. However, various studies have reported bioactive substances from wide marine yeast varieties, which escalate their remedial significance. Using marine yeast as a potential bioactive resource would 162

help save freshwater resources as seawater, the most abun- dant water resource in the world could be used in its process of fermentation. Therefore, the investment in the expansion of marine yeasts as a reserve of bioactive substances and a gene resource is desirable. Enzymes Resource from marine yeast Numerous studies encompassing useful enzyme study has re- vealed marine yeasts to be a rich source of enzymes like am- ylase, protease and phytase. Amid the amylase-producing yeasts, Saccharomycopsis fibuligera can synthesize the prime amount of amylase. It has also been found that it might also convert starch into trehalose efficiently. Aureobasidium pul- lulans in the Pacific Ocean could produce very high units of amylase per mg protein within a short (56 h) span of fermen- tation. Similarly, the Alkaline phosphatase in the gut of ma- rine animals has received much attention in recent years (Lin et al. 2013; Chung et al. 2003). The protein isolated from more than four hundred marine yeast was shown to produce protease(Gong et al. 2007). Similarly, some marine yeast can produce a large amount of phytase, which stands a chance for incorporation into the diets of marine animals. Recently, marine yeast isolates were studied to produce a large amount of phytase, some of which are cell-bound while others are extracellular. Therefore, the phytase-producing marine yeasts will have many applications in mariculture. β- carotenoid have extensive use in medicine, cosmetics, chem- istry and food industries. The Rhodotorula spp. has been found to produce large amount of β-carotenoid, widely re- sourced in mariculture in China (Misawa and Shimada, 1998). In recent years, many studies on enhanced production of carotenoid by mutants of Rhodotorula spp. and optimiza- tion of the fermentation processes for cultivation were under- taken. Mutant derived from R. glutinis NCIM 3253 produced 163

76-fold more carotene than the original. The marine yeasts were capable of adhering to the intestinal muscosa, thus providing potential applications as a probiotic supplement for human and animal health(Gong et al. 2007). Marine yeasts have been regarded as safe with a beneficial impact on bio- technological processes. Single Cell Protein (SCP) and Amino Acids Compared to algal cultivation, the large-scale yeast cell pro- duction in the fermenter is easy to manage. Because most yeast are characterized by flocculation and the cell size of yeast cells is much bigger than that of bacterial cells, it is easier to collect and concentrate the yeast cells from the liq- uid culture. Additionally, several yeasts can grow well on cheap products, such as molasses and corn starch which are widely available from the sugar industry and agriculture. However, many relevant parameters indicate that nucleic ac- id safety in algae is better than that in fungi and bacteria (Anupama and Ravindra 2000). Fungal sources can be exploited as nutritive SCP if the nucle- ic acid content is considerably reduced to levels comparable to the nucleic acid content of algae (Anupama and Ravindra 2000). The isolated 33 strains of marine yeasts from the coastal and offshore waters and found that the isolates had the ability to use starch, gelatin, lipid, cellulose, urea, pectin, lignin, chitin and prawn-shell wastes. The isolates when in- oculated into the prawn-shell wastes showed increased pro- tein content in the final products. It was found that the high carbohydrate content and good amino acid composition in marine yeasts and saturated fats in some marine yeast. This finding promises wide application in aquaculture, particularly as a feed supplement. 164

Exclusive Species From Leh Tanacetum Gracile Science Citation: Surinder Kitchlu© 165

Marine by-products The marine processing by-products have long been recog- nized as waste. The waste from the world fisheries is esti- mated to be as huge as 25% annually. Research in this area is encouraging as these by-products are now finding various applications. Potential applications of proteins, lipids, chitin and minerals in marine bio processing left over as bioactive materials have increased the value of processing by-products in recent years fishmeal, silage, animal feed and the bioactiv- ities of fish muscle-derived peptides are few examples. The bioactive peptides hydrolysates have shown numerous bioac- tivities such as antihypertensive, antithrombotic, immuno- modulatory and anti-oxidative activities. Research has shown that the antihypertensive activity inhibit- ing the activity of angiotensin I converting enzyme (ACE) is higher than many other natural peptides. The unique fish peptides possess hormone-like growth factors that enhance calcium absorption. Also they can bind to cell surface recep- tors present on osteoclasts and regulate calcium metabolism. The calcium deficiency due to the formation of insoluble compounds inside the digestive tract, or deficient dietary cal- cium is associated with several life-style diseases worldwide including osteoporosis, osteoarthritis, cardiovascular disease (hypertension and stroke), diabetes, obesity and cancer in humans. Further, research applying new technologies could identify biologically active compounds with the application for human utilization. Therefore the development in search of novel bioactive compounds from marine processing by- products will bring more value out of what is today consid- ered waste and represents unique challenges. Health-promoting roles of omega-3 fatty acids Fish oil is a marine source of omega-3 fatty acids (ω3), eicosapentaenoic acid (EPA) and docosahexanaenoic acid 166

(DHA) and has been linked to the promotion of human health to fight against numerous diseases including cardiac func- tioning. They are beneficial in regulating blood pressure and heart function, and maintaining blood vessel and lipid there- by imparting antithrombotic, anti-inflammatory and anti- oxidative actions. Supplementation of ω3 fatty acid is ad- vised by doctors to prevent cardiac related diseases to general public who prefer vegetarian diet(Mori 2017). Research has found a strong correlation between omega-3 fatty acid levels and coronary heart disease. Further, the anti-inflammatory property of fish oil is also beneficial in the treatment of other inflammatory diseases such as Crohn‘s disease, kidney relat- ed diseases and against various human carcinomas including breast, colon, skin, pancreatic, prostate, lung and larynx can- cer. Moreover, omega -3 fatty acids of fish oil are reported to be associated with brain development and are important for vision and the reproductive system probably due to DHA be- ing a component of brain nerve synapses, in the retina of the eye and in the testes and sperms. Bioactivities of chitin, chitosan and their oligomers The polysaccharide chitin and and its deacetylated form, chi- tosan are produced from the shells of crabs and shrimps, and bone plate of squid. These marine polysaccharides have at- tracted lot of research because of their distinctive biological and physicochemical characteristics. The characteristics of these polysacchrides depend on the production processes and conditions (Nwe et al. 2014). The positively charged chitosan and its oligomers have been shown to be involved in several crucial biological activities as in in reducing LDL-cholesterol levels in the liver and blood. These properties are quite ad- vantageous to open a way to new biotechnological applica- tions. These marine-derived unique type of polymeric mate- rials are environmental friendly, non-toxic with film- and fi- 167

ber-forming properties (Kurita 2006). The metal ions adsorp- tion, coagulation of suspensions or solutes, and distinctive biological activities of the biofunctional polymers have greater potential than cellulose in many fields as in biomedi- cal applications in drug delivery systems to obtain controlled release. Chitin and its derivatives also act as inhibitors of an- giotensin-converting enzyme, an enzyme which is associated with hypertension. They act as antioxidants in a molecular weight and deactivation-dependent manner. Low-molecular weight of chitosan oligomers is preferred over higher molec- ular weights for the activity. These oligomers also possess antitumor activities tested both under in vitro and in vivo conditions. Partially deacetylated chitin, as well as chitin with a carboxymethyl group shown to effectively demote tumour progression. Involvement of chitin and chitosan in wound-healing was found to be associated with their immune stimulating property, which involves higher production of macrophages that release cytokines nec- essary for the healing process. Also, it is suggested that the wound-healing property of chitosan oligomers is due to their ability to stimulate fibroblast production by affecting the fi- broblast growth factor and further facilitates the formation of connective tissues (Schmitz et al. 2019; Shahidi 2007). Bioactive peptides from sponges Oceans are the richest sources of bioactive compounds wait- ing to be explored, one such potential lies in marine bioactive peptides extracted from sponges, ascidians, seaweeds, and mollusks. The marine peptides have shown potential health benefits as nutraceuticals due to their antihypertensive, anti- oxidant, and antimicrobial properties. Sponges are the di- verse group of colonial organisms belonging to phylum Po- rifera with different species distributed from superficial wa- ters near the sea shores up to deep waters of the ocean. These 168

species are exposed to extreme conditions starkly different from the terrestrial plants leading to significantly altered amino acid compositions and sequences from them. The marine bioactive peptides extracted from diverse life forms ranging from marine animals, plants to lower organ- isms are unique possessing special characteristics and bioac- tivity sometimes better than land bioactive peptides. The flo- ra and fauna is largely unexplored for drug discovery, but their highly metabolically plastic and potentially amenable to culturing characteristic are invitation for research (Wang et al. 2017) offering the possibility of obtaining a sustainable source of unique bioactive compounds to meet the challeng- ing demands of pharmaceutical industries. (Jo et al. 2017; Giordano et al. 2018). Sponges have been traditionally known as a source of novel bioactive metabolites like terpenoids, alkaloids, macrolides, polyethers, nucleoside derivatives and many other organic compounds (Rosellini et al. 2020; Ngo et al. 2012). They are the reservoir of active peptides with majority having unique unprecedented structures. These compounds are often cyclic or linear peptides containing unusual amino acids which are either rare in terrestrial and microbial systems or novel pre- dominantly having uncommon condensation between amino acids. The cell growth inhibitory tetradecapeptide from Discoder- mins was one of the first novel peptides isolated from spong- es (Aneiros and Garateix 2004). Discodermins A–H and the structural related Polydiscamide A, obtained from sponges of the genus Discodermia are a group of cytotoxic peptides con- taining 13 to14 known and rare amino acids as a chain, with a macrocyclic ring constituted by lactonization of a threonine unit with the carboxy-terminal (Gogineni and Hamann 2018). 169

It is suggested that the unique origin of some of these pep- tides could be attributed to the symbiont relationship between microbial source and the sponges, due to the similarity of some of the molecules to marine microbial metabolites. Conus toxins The venoms of the marine genus Conus is the reservoir of a valuable neuro pharmacologically active peptides named conotoxins. Conotoxins are highly diverse both in term of structure and function (Robinson and Norton 2014). The ge- nus Conus (Mollusca) has about 500 species of predatory cone snails with venom. Each Conus species has unique pep- tide composition with relatively short strings of amino acids (50 and 200 amino acids) which are rich in disulfide bonds. These specific and high potency peptides are important in the defence, prey capture and other biotic interactions of the Molluscs (Robinson and Norton 2014). The beta conopeptides represent the best structurally studied class. The conopeptides are active on a wide variety of volt- age/ ligand-gated ion channels ion channels such as sodium, potassium, and calcium channels and nicotinic acetylcholine receptors (nAChRs) (Robinson and Norton 2014). Mode of action of conotoxins are still in the early stages of investiga- tion; however, they act as antagonists of the nicotinic acetyl- choline receptors (AchRs). These neurotoxins are unique as they can discriminate between muscle and neuronal type AchRs. It has been postulated that these peptides could be of interest in the treatment of anxiety, Parkinson's disease, pain, hypertension, cancer and also as muscle relaxants, pain and epilepsy (Lebbe et al. 2014; Ekberg et al. 2008). The best studied of these compounds are µ-conotoxins which act as selectively blockers on vertebrate skeletal muscle sub- types of the voltage-dependent sodium channel (Ekberg et al. 2008). A Conotoxin-GmVIA, purified from C. gloriamaris, 170

when injected into land snails induces convulsive-like con- tractions specifically on molluskan sodium channels but no detectable effects in mammals opening up avenues for fur- ther research. The C. purpurascens toxin is the first cone snail toxin that operates by blocking potassium channels. These conotoxins although operates by blocking channel but differs in target sites. The serotonin receptors are molecular target for conotoxins, specifically sigma-conotoxin GVIIIA which selectively inhibits the 5-HT3 receptor (Li et al. 2021; Ekberg et al. 2008). The oceans are centres of biodiversity, and very likely the point of origin for life on earth. All but two of the 36 living animal phyla are found in the sea. Less than half that number occurs on land. Marine species diversity can be extraordi- nary. On some tropical coral reefs, for example, there can be 1,000 species per square meter. Yet, for all the promise they contain, there are vast ocean regions that remain almost en- tirely unexplored. Future marine sanctuaries are envisioned to protect such po- tentially potent natural resources. There is a growing concern that we are losing many of the oceans' untold resources be- fore we could even fully see and understand them. But, there is also excitement in the marine biotechnology community that we are on the cusp of a new age of discovery. Hopefully, the knowledge that many of these discoveries will impart will directly benefit humanity and awaken the sense of steward- ship and preservation of the oceans that have long been dormant in many of us. Appendix VI – page 235 Contact: Dr. Suphala Gupta - [email protected] Dr. Neha Dhar - [email protected] 171

Exclusive Species From Ladakh Plantago Major, Ladakh, Science Citation: Surinder Kitchlu© 172

Chapter 7 Medicinal plants from Himalayan Region Dr. Swati & Dr. Jyotsna Gairola Introduction: There is no fairer country in the world than the slopes of the Himalayas ~ Sir Joseph Dalton, Darjeeling. In India the knowledge of medicinal plants is very old whose properties are described in the scriptures of Rigveda and in Athar- vaveda (3500-1500 B.C.) from which Ayurveda was developed. In Ayur- veda, the ancient well- known scripture is the ―Charak Samhita deal- ing mostly with plants and while the Sushrut Samhita scripture addresses medicine as well as surgery. Besides India people of China, Egypt and Mesopotamia use medicinal plants for their daily use. An- cient Egyptians are known for use of plants for medicinal purposes. The Nile Valley is known as the ―Cradle of Med- icine. The Himalayan ranges, the Gangetic plains, the Eastern and Western ghats, arid and semi-arid zone, cold deserts are known to be rich source of medicine for more than 5000 years. They continue to occupy an important place both in traditional, as well as modern systems of medicine. Out of about 18,000 species of flowering plants, known to grow in India, at least 2,500 species are supposed to possess 173

medicinal properties1. Himalayas are known as the ―Cradle of Medicinal Plants with more than 1500-2000 plants identi- fied to be of rare medicinal significance. The flora of Kashmir Himalayas comprises about 3,000 species. About 880 species are found in Ladakh. The flora of the Jammu district comprises 500 species. This chapter has made an effort of introducing rare en- dangered ethno-medicinal plants found in the Himalayan re- gions2 that can be used by common man as well as invested for research by the corporations. It has also provided a basic understanding of the taxonomy, genetic diversity, geographic distribution, ecological adaptation and ethnobotany of these plants. This is an effort to ensure effective acceptance of Ayurvedic as well as Integrative forms of medicine around the world. Particularly, when there is a clear shift in the glob- al scientific communities, towards the use of medicine of herbal or natural origin over modern or allopathy medicines. Majority of Ayurvedic formulation are prepared from herbs. This book will also make an effort towards providing sci- ence of all herbs and medicinal plants featured here to make it acceptable in modern system of medicine. This will help towards quality control of crude drugs and herbal formula- tions that is of paramount importance in justifying their ac- ceptability in modern system of medicine. The current world market for nutraceuticals & their sup- plements is approximately USD 142.1 billion in 2011 and is expected to reach USD 204.8 billion by 2017. Asia Pacific is expected to have the second largest market share after North America by 2017. Many marketed drugs are extracts of flow- 174

ers, fruits, leaves, seeds, twigs and roots mixed with pedicels and thinner twigs of the plant ( Dutt, 1922, Nadkarni, 1954, Chopra et al., 1956 and Ahuja, 1965). The flowers are being used in the preparation of Ayurvedic fermented drugs called Aristha's and Asava's (Atal et al., 1982), and very popular in the Indian subcontinent as also in other South Asian coun- tries (Jayaweera, 1981 and Kroes et al., 1993). Within this context and the current state of affairs of me- dicinal plants in Himalayan region, this chapter will make an attempt to introduce 31 rare & indigenous ethnomedicinal plants of medicinal values from 31 plant families & their 25 corresponding genera that has the potential of playing a piv- otal role in the Indian economy, if invested & conserved ap- propriately. In pharmacognsy, detailed classification of plant is ex- tremely vital for both pratical application and in selecting the right plant for study. In modern pharmacognosy the im- portance of this classification is decreasing. In morphological classification drugs are arranged accord- ing to their morphological or external characters.  Drug Groups  Leaves: Tulsi, senna and vasaka  Barks: cinchona, cinnamon and kurchi  Similarly seeds, fruits, subterranean parts are ar- ranged A variety of organic compounds are synthesized by plants that are chiefly classified as primary and secondary metabo- lites. Primary metabolites are required for basic processes 175

like photosynthesis, respiration, growth and development. Secondary metabolites are other phytochemicals which are accumulated in unusually high amount – not as mere inter- mediates of chemical processes. These compounds are very diverse and their distribution is often limited to related spe- cies. Plant Secondary metabolites are the major source of novel compounds, and about 60% all FDA approved drugs are either natural products or their derivatives. Taxol and Ar- timisin are examples of a few blockbuster drugs that are nat- ural products. Following are few blockbuster medicinal plants that have potential medicinal values: 1.) Aconitum heterophyllum Wall. ex Royale, genus known for its ethnomedicinal uses such as Chronic fever, diabetes, & leucorrhoea.It belongs to family Ra- nunculaceae and is local- ly called as Atish in Kashmir region. Roots are generally used for treatment. Aconitum heterophyllum, is showing 17 known com- pounds in the Directory of Natural Product. Atidine found in the roots of this plant are known to be used to treat the symp- toms of allergies, such as sneezing, watery eyes, and runny nose. It is also used to treat skin hives and itching in people with chronic skin reactions. The details4 of Atidine are as fol- lows, Molecular Formula: C22H33NO 3; Molecular Weight: 359.508; Accurate Mass: 359.246044; Percentage Composi- tion: C 73.50%; H 9.25%; N 3.90%; O 13.35%; Biological Source: Alkaloid from the roots of Aconitum heterophyllum (Ranunculaceae); Physical Description: Prisms (C6H6 or Et2O); & Melting Point: Mp 182.5 - 183.5°. 176

2.) Berberis aristata DC an important herb in Ayurveda, is known for its anti-inflammatory activity that alleviates joint aches and pains associated with rheumatism, arthritis and os- teoporosis. It is from family Berberidaceae and is primarily cultivated in Assam and Sikkim region, where locals call it Kirmod or Daru Haldi or Chitra. Dictionary of Natural Plant (DNP) is showing presence of 2 prominent constituents; Karachine found as a minor & Tax- ilamine as major compound in the root of the plant which is traditionally used5 in inflammation, urinary complaints, wound healing, curing skin disease, menohrrhagia, diarrhea, jaundice and infection of eyes. A pharmacological study on the plant has revealed its proven ac- tivity as a hypogly- caemic, antibacterial, antifungal, antipyretic, anti-inflammatory, hepatoprotective, antioxidant, & anticancer agent. Taxilamine has the molecu- lar formula: C20H19NO6, molecular weight: 369.373, per- centage composition: C 65.03%; H 5.18%; N 3.79%; O 25.99%, biological source: Alkaloid from the root bark of Berberis aristata (Berberidaceae). 3.) Podophyllum hexandrum Royale plant is from the family Podophyllaceae that is commonly known as the Himala- yan mayapple or In- dian May apple while the locals callit ―Shon Kakdi and is primarily found in Himachal Pradesh. 177

Root is the important biological resource of this plant. DNP shows presence of 6 compounds. One of the com- pound Podophyllotoxin is extracted from the roots and rhi- zomes of Podophyllum hexandrum and is sold in the market as Condylox, a topical gel, that it is used on the skin to treat external genital warts, caused by some types of the human papillomavirus (HPV). This plant is also used in curing of diabetes, leucorrhoea, and chronic fever. 4.) Bergenia ciliata (Haw.) Sternb genus belongs to family Saxifragaceae that has Anti-lithiatic and lithotriptic activi- ty primarily used for cur- ing & dissolving of kid- ney stones respectively, curing abdominal ail- ments, combating urinary tract infections and as a hair tonic. Locals from Assam call it ―Silpari. Its roots are of primary biological importance. DNP is showing presence of five constituents. One of the compounds Bergenin is known for its antioxidant activity whose scientific details are the following: Molecular Formu- la: C14H16O9; Molecular Weight: 328.275; Accurate Mass: 328.079435; Percentage Composition: C 51.22%; H 4.91%; O 43.86%. Its other key ingredients such as Small Caltrops (Gokshura) & Pashanabheda (Saxifraga Ligulata) play pivi- tol role in managing uro-genital diseases and urinary tract in- fections. 178

Exclusive Species From Zanskar Swertia petiolata, Zanskar; Science Citation: Surinder Kitchlu© 179

5.) Woodfordia fruticosa (L.) Kurz is from family Lythe- raceae; the locals of Jammu call it as Dholu, Dhai phul (Bh), Dhadki (Mu), whose flowers are of extremely valueable with regards to its astringent, stimulant, depurative, sedative, anti- helmentic, constipating, antibacterial, vulnerary, alexeteric and febrifuge bioactivity (Fi- nose, AJPSR, 2011). Locals use leaf infusion with black pepper (3:1) that is given twice daily for a week for indi- gestion; flower paste with honey (2:1) is administered to prevent nausea and cough (Chakraborty MK, IJTK, 2006). Dictionary of Natural Products shows 14 constituents, of which Woodfordin A is an important compound known to been used as an astringent to treat dysentery and sprue, and also for the treatment of bowel complaint, and rheumatism. Molecular Formula: C75H56O48; Molecular Weight: 1725.239; Accurate Mass: 1724.19412; Percentage Composition: C 52.21%; H 3.27%; O 44.51% A dimer ―ellagitannin has been extracted from the flow- ers of Woodfordia fruticosa that are chewed thrice a day for a month to improve semen quality. Dried flowers are used as tonic to cure hemorrhoids, and as a febrifuge (Dangwal, New York Science Journal, 2010). 6.) Trichosanthes tricuspidata Lour genus is from the family Cu- curbitaceae. Roots and seeds of this plant are important as they are used for curing Pnuemonia and Bronchitis. In DNP 23 compounds 180

have been isolated of which Cucurbit-5-ene-3, 11, 24, 25- tetrol has shown promising results as it is used for skin irrita- tions and sunburns. A slice of cucumber over puffy eyes acts as an anti-inflammatory agent to help reduce puffiness. The silicon and sulfur helps to stimulate hair growth. Molecular Formula: C30H52O4; Molecular Weight: 476.738; Accurate Mass: 476.38656; Percentage Composition: C 75.58%; H 10.99%; O 13.42% 7.) Angelica glauca Edgew genus research indicates 6 com- pounds in DNP of which Angelicolide & 3-Butylidene- 1(3H)-isobenzofuranone; (Z)-form is known for antihypogylemic ac- tivity. Molecular Formula: C24H28O4; Molecular Weight: 380.483; Accurate Mass: 380.19876; Percentage Composition: C 75.76%; H 7.42%; O 16.82%; Biological Source: Constitution of roots of Angelica glauca. 8.) Rubia Cordifolia genus has been extensively researched for its biological significance & is showing 95 constituents as per DNP database. The constituent ―Mollugin is known for its Antiproliferative and cancer chemo preventive agent. Molecular Formula: C17H16O4; Molecular Weight: 284.311; Accurate Mass: 284.10486 Percentage Composition: C 71.82%; H 5.67%; O 22.51%; Physical Description: Yellow cryst. (EtOAc); Melt- ing Point: Mp 132 - 134° 181

9.) Valeriana jatamansii Jones genus is showing one com- pound Acacetin in DNP which is known for its anti- inflammatory activity, as well as being a capillary protection and spasmolytic agent. Molecular Formula: C16H12O5; Mo- lecular Weight: 284.268; Accurate Mass: 284.068475; Percentage Composition: C 67.60%; H 4.25%; O 28.14% Root of the plant is dried in shade, powdered and given approximately ½ teaspoonful twice a day, in morning and at night for 2-3 months in the treatment of hysteria and urinary disorders. The plant is used as substitute of Nardostachys jatamansi by the inhabitants of Tehri. Plant used in rituals and various religious ceremonies. 10.) Cirsium wallichii DC. genus is showing only one com- pound Jacoline whose synonyms is O - Acetyl Jacoline. Molecular Formula: C18H27NO7; Molecular Weight: 369.414; Accurate Mass: 369.178754 Biological Source: Alkaloid from Senecio jacobaea (Compositae) 11.) Tanacetum gracile: The essential oil of Tanacetum gracile, a cold desert alpine highly aromatic herb, has 40 constituents including lavendulol. 182

12.) Saussurea lappa (Dcne.) Sch. genus is showing 63 compounds in DNP, of which the compound Alantolactone, whose synonyms are Helenine‡, Alantic anhydride, Alantcamphor is known for its Antibacterial, antineoplastic, antihypertensive agent and anthelmintic ac- tivity. Molecular Formula: C15H20O2; Molecular Weight: 232.322; Accurate Mass: 232.14633; Percentage Composi- tion: C 77.55%; H 8.68%; O 13.77% Use / Importance: Reference substance in chromatography and chemotaxonomy 13.) Lyonia ovalifolia (Wall.) Drude genus is showing 18 compounds in DNP. Of these compounds, 3-O-trans- Coumaroylmaslinic acid is having biological significance as a DNA polymerase B\" inhibitor; & a bleo- mycin cytotoxicity potentiator. Mo- lecular Formula: C39H54O6; Molecu- lar Weight: 618.852; Percentage Composition: C 75.69%; H 8.79%; O 15.51% 14.) Rhododendron arboreum Smith, genus has only one om- pound Artocarpetin 4′-glucoside extracted till date. It has not shows tyrosinase inhibitory activity. Mo- lecular Formula: C22H22O11; Molecular Weight: 462.409; Percentage Composition: C 57.14%; H 4.80%; O38.06% Bi- ological Source: Isolation from the leaves of Rhododendron arboreum. It is known as “Kuth” in local language. 183

Exclusive Species From Kashmir Humulus lupulus, Kashmir; Science Citation: Surinder Kitchlu© 184

The sweet- scented root of this Kuth is a valuable medicine for colds, asthma and skin diseases, and even leprosy. 15.) Swertia chiraita (Roxb. ex Flem.) Karsten, genus show- ing one compound in DNP called Chiratol which is known for being an anti-hepatotoxic, anti-inflammatory & anti ul- cerogenic agent. Molecular Formula: C15H12O6; Molecu- lar Weight: 288.256; Per- centage Composition: C 62.50%; H 4.20%; O 33.30% 16.) Hyoscyamus niger L., genus shows 25 compounds in DNP. Calystegine shows glycosidase inhibitory activity, an alkaloid from Hyoscyamus ni- ger. Molecular Formula: C7H 14N2O3; Molecular Weight: 174.199; Percentage Compo- sition: C 48.26%; H 8.10%; N 16.08%; O 27.55% 17.) Ajuga parviflora Benth. genus shows 24 compounds in DNP. One of the compounds Jacaranone is known to be a cy- totoxic agent & Metamorphosis inducer for Pecten larvae. Molec- ular Formula: C9H10O4; Molecu- lar Weight: 182.176; Percentage Composition: C 59.34%; H 5.53%; O 35.13% 185

18.) Plantago depressa Willd. Genus shows only one com- pound in the DNP database, which is β-Oxoacteoside or To- mentoside A known for its antiox- idant activity. Molecular Formula: C8H8O4; Molecular Weight: 638.578; Percentage Composition: C 54.55%; H 5.37%; O 40.09% 19.) Rheum spiciforme: common name: Spiked Rhubarb, found in Ladakh; locals call it Lachhu; Family: Polygona- ceae (Knotweed family). The root is used as a purgative10. 20.) Dactylorhiza hatagirea (D. Don) genus shows 9 com- pounds in DNP data- base. Dactylose A is the major constituent present in the root that is widely used as a cure for dysentery, diarrhoea, chronic fe- ver, and cough. Molecular Formula: C12H16O6; Molecular Weight: 256.255; Percentage Composition: C 56.25%; H 6.29%; O 37.46% 186

21.) Hedychium spicatum Buch.-Ham. ex J.E. Smith genus shows 10 researched compounds in DNP database. 1, 3- Elemadien-11-ol compound found in the roots shows anti- ulcer activity. Molecular Formula: C15H26O; Molecular Weight: 222.370; Percentage Composition: C 81.02%; H11.78%; O 7.19% 22.) Acorus calamus L. genus is widely investigated show- ing 52 compounds in the DNP database. Of thèse 52 com- pounds, Acorenone inhibits chloramphenicol acyltransferase & shows multidrug resistance (MDR) inhibitory active ty on bacteria. Molecular Formula: C15H24O; Molecular Weight: 220.354; Percentage Composition: C 81.76%; H 10.98%; O 7.26% 23.) Carissa Opaca genus shows only 1 compound in the DNP database. 4-Eudesmene-3, 11-diol is present in the plant. Molecular Formula: C15H26O2; Molecular Weight: 238.369; Percent- age Composition: C 75.58%; H 10.99%; O 13.42% 187

24.) Peganum harmala: One of the component 7-Methoxy- 1-methyl-β-carboline, also known as Telepathine, Yageine, Banisterine, Harmine; is an alkaloid from Peganum harmala. This plant is found in Ladakh. Molecular Formula: C13H12N2O; Molecular Weight: 212.251; Percentage Composition: C 73.57%; H 5.70%; N 13.20%; O 7.54% Use / Importance: Acid-base fluorescence indicator (pH 7.2-8.9, colour change blue → yellow) Biological Use / Importance of this plant: It is an anti- parkinsonian agent, a CNS stimulant, a Component of a South American hallucinogenic drink and active against gram-positive bacteria and fungi. 25.) Ephedra Gerardiana, also known as Soma or Somlata or plant of the moon, according to Vedic scriptures is tradi- tional used for making a tea with the dried stems for treating the flu, coughs, colds, arthritis, asthma, and other lung infec- tions. Mostly found in the high altitudes of Ladakh and Kash- mir. 188

26.) Rosa webbiana, is identified as a rich source of vitamins A, C and E, flavanoids and other bio-active compounds. It is being investigated as a food that is capable of reduc- ing the incidence of can- cer and also as a means of halting or reversing the growth of cancers. It exclusively grows in the Ladakh re- gion. Appendix VII – page 239 Contact: Dr. Swati - [email protected] Dr. Jyotsana Gairola - [email protected] 189

Exclusive Species From Leh Salvia sclavia, Leh; Science Citation: Surinder Kitchlu© 190

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