Table of Contents
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FOREWORD
PREFACE
List of Contributors
Bioactive Molecules from Marine Macroalgae for the Management of Diabetes Mellitus with Reference to their Inhibitory Activity: An Overview
Abstract
INTRODUCTION
Diabetes Mellitus
Mechanisms of Carbohydrates Hydrolyzing Enzymes
Mechanisms of Commercially Available Antidiabetic Drugs
Natural Antidiabetic Drugs from Marine Resources
Marine Macroalgae as a Potential Source of Bioactive Compounds
Bioactive Compounds from Different Marine Macroalgae and their Properties
CONCLUSION
ACKNOWLEDGEMENTS
REFERENCES
Disease Treatment Using Health Supplements from Herbs
Abstract
INTRODUCTION
Vitamins
Fat-soluble Vitamins
Vitamin A
Vitamin D
Vitamin E
Vitamin K
Water Soluble Vitamins
Vitamin B1 (Thiamine)
Vitamin B2 (Riboflavin)
Vitamin B3 (Niacin)
Vitamin B5 (Pantothenic Acid)
Vitamin B6 (Pyridoxine)
Vitamin B7 (Biotin)
Vitamin B9 (Folate)
Vitamin B12 (Cobalamin)
Vitamin C (Ascorbic acid)
Minerals and their Complexes
Major Minerals
Trace Elements
CONCLUSION
REFERENCES
Herbal Nutraceuticals for Disease Prevention and Management
Abstract
INTRODUCTION
Infectious Diseases
Antimicrobial Activity
Antifungal Activity
Antiviral Activity
Non-infectious Diseases
Activity Against Tumors and Cancers
Activity Against Neurodegenerative Diseases
Activity Against Cardiovascular Diseases
Activity Against Diabetes
Activity Against Cholesterol
CONCLUSION
REFERENCES
Herbs as Dietary Medicine
Abstract
INTRODUCTION
PRIMARY METABOLITES
Vitamins
Carbohydrates
Proteins
Secondary Metabolites
Flavonoids
Antioxidant Activity
Anticancer Activity
Activity Against Neurodegenerative Disorders
Activity Against Cardiovascular Disorders
Antiviral Activity
Antibacterial Activity
Antifungal Activity
Terpenes and Terpenoids
Anticancer Activity
Anti-inflammatory Activity
Hepatoprotective Activity
Alkaloids
Carotenoids
Antioxidant/Pro-oxidant Activity
Anticancer Activity
Saponins
Applications of Herbal Dietary Supplements
CONCLUSION
REFERENCES
Evaluation of Anti-aflatoxicosis Potential of Solanum americanum Mill. – An Important Traditional Medicinal Plant
Abstract
INTRODUCTION
Materials and methods
Sample Collection
Experimental Procedure
Molecular Docking Studies (Induced Fit Docking)
Statistical Analysis
RESULTS
The Changes in Haematological Parameters in Antiaflatoxicosis Activity
Discussion
Biochemical Analysis
Molecular Docking Studies (Induced-Fit Docking - IFD)
CONCLUSION
REFERENCES
Herbal Medicine: History, Contemporary Use and the Future
Abstract
INTRODUCTION
Sacred Knowledge of Babylonian Medicine and Treatments
Egyptian Medical Papyri, Herbs and Complementary Medicine
Medical Science in Ancient China
India, the Land of Diversity in Herbs
Emergence and Impact of Ayurveda in the World of Herbalism
Other Important Lineages of Herbalism in India
GEOGRAPHICAL DISTRIBUTION OF RARE MEDICINAL PLANTS IN ASIA-HIMALAYAN INDIA
Spread of Medicinal Plants in Asia
Hotspot of Herbal Plants in the Himalayan Region
Rare Plants of India
Techniques Involved in Herbal Studies
Collection and Methods of Sample Preparation
Extraction
Conventional Methods
Non-Conventional Method
Clinical Trials and Toxicity of Herbal Medicine
CONCLUSION
ACKNOWLEDGEMENTS
REFERENCES
Identification of Phytochemicals Using GC-MS / LC-MS-MS Techniques and Modeling Studies against COVID-19 Targets
Abstract
INTRODUCTION
Pathophysiology of COVID-19
Treatment of COVID-19
Role of Phytocompounds in the Control of COVID-19
Drug Repurposing for COVID-19
Role of Bioinformatics Tools in COVID-19 Drug Design
Literature Survey
GCMS and LCMS Studies of Certain Herbs and Important Phytochemicals Identified as Inhibitors of SARS-CoV Targets
Authors’ Work on Four Formulations and Comparison of the Phytochemicals
Docking and Simulation Study of Some Phytocompounds
Docking Studies of Some Anti-virals
CONCLUSION
REFERENCES
Herbs in the Traditional Healthcare System of North East India
Abstract
INTRODUCTION
Polygonum hydropiper
Coptis Teeta Wall
Lasia Spinosa
CONCLUSION
References
Plant Edible Oils - Detection of Disease-Causing Compounds due to Repeated Heating of Oils
Abstract
INTRODUCTION
Materials and Methods
Sample Collection
Experimental Procedure
Sample Preparation and Derivatization of Fatty Acid Methyl Esters
GC-MS Analysis of Fatty Acid Methyl Esters
Extraction of Amino Acid from the Oil Samples
RESULTS AND DISCUSSION
Fatty Acid Methyl Ester Profiling from the Subjected Oil Samples by GC-MS
Amino Acids Profiling from the Subjected Oil Samples by HPLC
CONCLUSION
FUNDING
ACKNOWLEDGEMENTS
REFERENCES
A Way to Treat Kidney Diseases with Plants in Humans
Abstract
GENERAL INTRODUCTION
ACUTE KIDNEY FAILURE
General Introduction
Stages of Kidney Failure
Aerva sp. and other medicinal plants
Introduction
Role of Aerva plants in Humans
Aerva lanata (Sirupoolai)
A. lanata In Various Treatments
Aerva javanica (Perumpoolai)
A. javanica in Various Treatments
Other Medicinal Plants
Senna auriculata (Aavaram poo)
Azadirachta indica (Vembu)
METHODS
Information Retrieval of Medicinal Plant – Entrez
Computational Identification of Genes Responsible for Kidney Failure
Network Analysis
Drug-Gene Interaction
CONCLUSION
References
Herbs for Disease Prevention and Treatment
Edited by
Velmurugan Devadasan
Department of Biotechnology, School of Bioengineering
Faculty of Engineering and Technology, SRM Institute
of Science and Technology, Kattankulathur-603203
Chengalpet Dt., Tamil Nadu, India
Atanu Bhattacharjee
Department of Biotechnology and Bioinformatics
North Eastern Hill University
Shillong-793022, India
Raman Pachaiappan
Department of Biotechnology, School of Bioengineering
Faculty of Engineering and Technology, SRM Institute
of Science and Technology, Kattankulathur-603203
Chengalpet Dt., Tamil Nadu, India
&
Gayathri Dasararaju
Department of Biophysics and Crystallography
University of Madras, Guindy Campus
Chennai-600025, Tamil Nadu, India
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FOREWORD
The author of this book has more than 40 years of research experience in the field of crystallography of small molecules, particularly the structure and functional studies of phytochemicals. He has published more than 600 research articles. His contributions to drug discovery using plant products are significant. This book provides valuable information on the potential therapeutic applications of plant products and gives evidence of the nutritional values of phytochemicals. It gives details on the function of herbalism in the context of its history and significance. The diversified geographical terrains sustaining several indigenous species of plants of medicinal importance are also described. The usage of herbal practices and several techniques are highlighted. The role of nutraceuticals in improving wellness, reducing the rate of aging, averting chronic diseases, and prolonging life, as well as keeping the body in good shape, has been discussed in detail. The importance of dietary supplements to boost health has been discussed in detail. Although better diet quality is imperative to fix various problems, people who are at risk for deficiencies may benefit from dietary supplements and/or food fortification to assist them in fulfilling their nutritional needs. The need for the key minerals as well as fat-soluble and water-soluble vitamins that are vital for human health and well-being has been established. The contamination of aflatoxin in animal diet manifests harmful effects on animal health and productivity. The use of phytochemicals against diseases such as cancer and inflammation has been shown. The importance of plant products that are widely used to treat women's reproductive health, such as polycystic ovary, dysmenorrhea, endometriosis, anovulation, early menopause, painful menstruation, abnormal menstrual cycles, and recurring abortions and also cholera, tuberculosis, leprosy, dysentery, and vector-borne illnesses like malaria and hookworm infection has been described. The utility of phytocompounds for controlling the spread of SARS-CoV2 has also been presented in this book. Overall, this book provides highly useful information for the health benefits of all.
Prof. T.P. Singh
SERB Distinguished Fellow
Department of Biophysics
All India Institute of Medical Sciences
PREFACE
Herbals/natural products have been used by humankind for more than 5,000 years. At present, about 60% of people prefer herbals at the global level for treating common ailments as they believe that even if any side effects arise, they would not be as severe as in allopathy medicine. Traditional medicine, folk medicine, naturopathy, Tibetan medicine, traditional Chinese medicine, Indian traditional medicine, etc. use herbs or certain plants for preventing or curing human ailments.
This book deals with the control of various diseases using plants. Most of the herbs considered have proven to be not harmful to health, and they either control or cure the diseases. In silico methods have been used in many chapters in docking calculations to confirm the binding of the phytoconstituents at the binding site of the disease-related macromolecular targets. This work was carried out to understand the principle behind the cure. In practice, mostly the whole parts of the herb or certain parts are used for the treatment, and synergism plays a major role in the activity of these herbs.
Chapter 1 deals with the bioactive compounds from marine macroalgae for the management of diabetes mellitus. Chapter 2 deals with the treatment of diseases using herbs as supplements. Herbal nutraceuticals for disease prevention and management are dealt with in Chapter 3. The use of herbs as dietary medicine is described in Chapter 4. In Chapter 5, the evaluation of the anti-aflatoxicosis potential of Solanum americanum Mill, an important traditional medicinal plant, is discussed. The use of herbs in the traditional healthcare system of North East India is discussed in Chapter 6 - with regard to its history, contemporary use, and future aspects. Chapter 7 deals with the identification of phytochemicals using GC-MS/LC-MSMS techniques and also docking techniques against COVID-19 targets. Chapter 8 deals with three herbs used in traditional health care system of North-Eastern India to treat conditions like arthritis and rheumatism. Detection of fatty acid modifications from plant edible oils after repetitive use and deep frying of plant and animal-based food items is discussed in Chapter 9. The last chapter, namely, Chapter 10 deals with plants intertwined with humans in treating kidney diseases.
This book thus covers, in general, many common diseases and deals with the ways of overcoming these ailments with natural products/herbs. I hope that this book will serve as a sourcebook for scientists and students of pharmacy, pharmacology, Siddha, and Ayurveda courses.
Velmurugan Devadasan
Department of Biotechnology, School of Bioengineering
Faculty of Engineering and Technology, SRM Institute
of Science and Technology, Kattankulathur-603203
Chengalpet Dt., Tamil Nadu, IndiaAtanu Bhattacharjee
Department of Biotechnology and Bioinformatics
North Eastern Hill University
Shillong-793022, IndiaRaman Pachaiappan
Department of Biotechnology, School of Bioengineering
Faculty of Engineering and Technology, SRM Institute
of Science and Technology, Kattankulathur-603203
Chengalpet Dt., Tamil Nadu, India
&Gayathri Dasararaju
Department of Biophysics and Crystallography
University of Madras, Guindy Campus
List of Contributors
Anantha Krishnan DhanabalanDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur–603 203, Chengalpet Dt., Tamil Nadu, IndiaAngneh NgoruhDepartment of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong-793022, IndiaAtanu BhattacharjeeDepartment of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong-793022, IndiaArchana SaikiaMolecular Endocrinology and Reproductive Biology Research Laboratory, Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar-791112, Arunachal Pradesh, IndiaHarykrishnan SureshDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur–603 203, Chengalpet Dt., Tamil Nadu, IndiaHirendra Nath SarmaMolecular Endocrinology and Reproductive Biology Research Laboratory, Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar-791112, Arunachal Pradesh, IndiaJanani PrabaharanDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur–603 203, Chengalpet Dt., Tamil Nadu, IndiaJayaprakash ChinnappanAnthropology and Health Informatics Lab, Department of Bioinformatics, Bharathiar University, Coimbatore-641046, IndiaKareem AltaffDepartment of Marine Biotechnology, AMET University, Chennai-603112, IndiaK. AbinayaDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur-603203, Chengalpet Dt., Tamil Nadu, IndiaM. Syed AliPG and Research Department of Biotechnology, Mohamed Sathak College of Arts and Science, Sholinganallur, Chennai-600119, Tamil Nadu, IndiaN. YogananthPG and Research Department of Biotechnology, Mohamed Sathak College of Arts and Science, Sholinganallur, Chennai-600119, Tamil Nadu, IndiaNagasathiya KrishnanDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur-603203, Chengalpet Dt., Tamil Nadu, IndiaRaman PachaiappanDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur–603 203, Chengalpet Dt., Tamil Nadu, IndiaProsperwell IngtyDepartment of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong-793022, IndiaPinki Kumari SinghDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur-603203, Chengalpet Dt., Tamil Nadu, IndiaR. SelviResearch and Evaluation, Bharathiar University, Coimbatore, Tamil Nadu, IndiaR. MuthezhilanDepartment of Marine Biotechnology, AMET University, Chennai-603112, IndiaRik GangulyDepartment of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong-793022, IndiaShashi Kumar YadavDepartment of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong-793022, IndiaSonam DoimaMolecular Endocrinology and Reproductive Biology Research Laboratory, Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar-791112, Arunachal Pradesh, IndiaS. NagarjunDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur – 603 203, Chengalpet Dt., Tamil Nadu, IndiaS. ThulasiramDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur – 603 203, Chengalpet Dt., Tamil Nadu, IndiaSubash C.B. GopinathInstitute of Nano Electronic Engineering, Universiti Malaysia Perlis (UniMAP), Kangar 01000, Perlis, Malaysia
Faculty of Chemical Engineering & Technology, Universiti Malaysia Perlis (UniMAP), Arau 02600, Pauh Campus, Perlis, Malaysia
Micro System Technology, Centre of Excellence, Universiti Malaysia Perlis (UniMAP), Arau 02600, Pauh Campus, Perlis, MalaysiaShankari GopalakrishnanAnthropology and Health Informatics Lab, Department of Bioinformatics, Bharathiar University, Coimbatore-641046, IndiaTrinankur MitraDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur – 603 203, Chengalpet Dt., Tamil Nadu, IndiaVijayaraj RadhaDepartment of Marine Biotechnology, AMET University, Chennai-603112, IndiaVinduja VasudevanDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur–603 203, Chengalpet Dt., Tamil Nadu, IndiaVelmurugan DevadasanDepartment of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur–603 203, Chengalpet Dt., Tamil Nadu, India
Bioactive Molecules from Marine Macroalgae for the Management of Diabetes Mellitus with Reference to their Inhibitory Activity: An Overview
Vijayaraj Radha1,Kareem Altaff1,*
1 Department of Marine Biotechnology, AMET University, Chennai-603112, India
Abstract
Diabetes mellitus is a global health issue related to insulin that is associated with a high rate of morbidity and mortality. Synthetic hypoglycemic medications can be used to treat diabetes; however, long-term use of these medications has several negative effects. As a result, there is a paradigm change in favor of using natural agents that may be antidiabetic. The marine environment is a rich source of both biological and chemical diversity, which is being investigated to identify novel compounds with potential for use in the pharmaceutical, cosmetic, and nutritional supplement industries. Marine organisms, especially marine macroalgae, comprise numerous significant novel secondary metabolites possessing strong pharmacological characteristics that have been identified. Sources of marine macroalgae include various bioactive compounds exhibiting various health-promoting properties. Hence, the present chapter aimed to discuss the different antidiabetic mechanisms of bioactive compounds from marine macroalgae and also talked about the variety of marine macroalgal bioactive substances that could help avoid or manage type 2 diabetes by focusing on several pharmacologically significant pathways, such as preventing the activity of enzymes like lipase, α-glucosidase, α-amylase, aldose reductase, protein tyrosine phosphatase 1B, and dipeptidyl-peptidase-4.
Keywords: Bioactive compounds, Diabetes mellitus, Marine macroalgae, Marine drugs, Pathways.
*Corresponding author Kareem Altaff: Department of Marine Biotechnology, AMET University, Chennai-603112, India; Tel: +91- 9444108110, Fax: 91-44-27472804 / 2747 2904; E-mail:
[email protected]INTRODUCTION
Diabetes Mellitus
Diabetes is one of the major global metabolic disorders characterized by chronic hyperglycemia and insulin resistance [1]. The impact of diabetes mellitus is deter-
mined by the degree of fat accumulation, enlarged visceral adiposity, and abdominal waist-to-hip ratio. Besides body fat distribution, abnormal glucose homeostasis occurs, leading to an irregular transportation and storage of glucose in the peripheral tissues, such as skeletal muscle, adipocytes, and hepatocytes [2-4]. The identification of molecular target drugs involved in the regulation of glucose and lipid metabolism can be crucial in the management of the metabolic syndrome.
Diabetes mellitus is the fastest-growing pandemic associated with metabolic syndrome [5]. The International Diabetes Federation estimates that 415 million people worldwide presently have diabetes, which is projected to increase to 642 million by 2040. In India, around 69.2 million adults are assessed as afflicted with diabetes, and by 2040, over 100 million people are projected to be affected by diabetes. Type 2 Diabetes mellitus (T2DM) is a polygenic disorder of carbohydrate and lipid metabolism, accounting for 90-95% of the diabetic population [6]. Type 1 Diabetes mellitus (T1DM) typically affects children and about 5% – 10% of the overall diabetic population [7].
T2DM is characterized by an improper secretion and action of insulin leading to modulations in the insulin signaling cascade causing an elevated blood glucose level and an impaired insulin resistance with disturbed carbohydrate and fat metabolism [8]. The etiologies of T2DM are complex and include genetic predisposition, consumption of a high-fat diet, sedentary lifestyle, and aging. This leads to other associated metabolic complications such as obesity, cardiovascular disease (CVD), stroke, liver steatosis, and microvascular complications such as renal failure (nephropathy), foot ulcer, and blindness [9].
Mechanisms of Carbohydrates Hydrolyzing Enzymes
Reducing the conversion of dietary complex carbohydrates into glucose and reducing the passage of glucose across the intestinal wall into the bloodstream are the two key components of treating Type 2 diabetes. Postprandial blood glucose levels can be decreased by inhibiting enzymes that hydrolyze carbohydrates. Amylase and glucosidase are the two main carbohydrate hydrolyzing enzymes in charge of breaking down dietary polysaccharides. Pancreatic amylase catalyzes the initial stage of dietary starch digestion by breaking down the starch into a combination of tiny oligosaccharides. Following this process, glucosidase continues to break down oligosaccharides into glucose. After that, the gut wall allows this glucose to pass into the blood, raising postprandial blood glucose levels (Fig. 1).
Fig. (1))
Mechanisms of carbohydrates hydrolyzing enzymes.
Mechanisms of Commercially Available Antidiabetic Drugs
Although an effective treatment is focused on the reduction of blood glucose levels, the therapeutic approach is mostly targeted toward improvement in insulin secretion and action [10]. Currently, there are several agents for therapeutic use that mostly target the transportation and metabolism of glucose (biguanidine and thiazolidinediones), insulin secretion and insulin action (sulfonylureas, meglitinides, GLP1 Mimetics and DPP4 inhibitors) and inhibitors (α- glucosidases) of glucose absorption [11].
Metformin, a biguanidine class of drug, is used as a first-line treatment for increasing insulin sensitivity and its glucose-lowering potential [12]. It has also been claimed to reduce fatty acid-mediated insulin resistance by activating the enzyme 5' AMP-activated protein kinase (AMPK) in the liver and inhibiting the enzyme acetyl CoA carboxylase as a result [13]. The usage of this drug exhibits adverse effects such as intestinal discomfort, renal failure and lactic acidosis [14].
Thiazolidinediones (TZDs) are a glitazone class of drugs targeting insulin action chiefly in skeletal muscle and adipocytes [15]. TZDs, including rosiglitazone and pioglitazone, reduce insulin resistance through the activation of peroxisome proliferator-activated receptor Ȗ (PPARȖ) and AMPK. The long-term usage of TZDs leads to an increased accumulation of lipids in the adipose and ectopic tissues, resulting in adverse effects, including weight gain, cardiovascular diseases, and hepatic steatosis [16].
Another class of antihyperglycemic agents used to decrease glucose absorption from the gut is α-glucosidase inhibitors. They function independently of insulin secretion and action, decrease the postprandial increase in blood glucose level by gastric emptying, and suppress glucose absorption via inhibition of gut enzyme Į-glucosidase [17].
In recent times, a few antihyperglycemic agents have been developed and approved by the Food and Drug Administration (FDA), including incretin mimetics, which are GLP1 (glucagon-like peptide 1) agonists that increase the circulating levels of GLP1 and DPP4 (dipeptidyl peptidase-4 inhibitors) [18]. GLP1 mimetics enhance insulin secretion, slow the rate of gastric emptying, suppress the release of glucagon, and protect against ß-cell damage, increased blood pressure, and weight gain [19]. Despite their beneficial use, they cause various adverse effects, including diarrhea, nausea, hypoglycemia, and some local skin reactions [20].
Although there are various hypoglycemic agents available, including metformin, thiazolidinediones, and insulin secretagogues, the usage of these drugs is limited owing to their single targeted action and sometimes their unfavorable side effects [21]. Alternate therapeutic strategies include bioactive compounds from natural resources with their multi-targeted action, which could be useful for the treatment of complex metabolic disorders [22].
Drugs that generally act as either inhibitors or activators on a specific target sometimes fail to exhibit favorable effects on the overall biological system. There is no single drug available as an effective monotherapy for treating complex diseases, including diabetes, obesity, cancer, and neurodegenerative and cardiovascular ailments. This is because the biological system coordinately affects the effectiveness of the target drug through a self-compensatory mechanism [23, 24].
Currently, considerable attention is being focused on the development of multi-targeted drugs and network pharmacology as effective therapeutic interventions for complex diseases [25]. Complex diseases can possibly be treated or cured by synchronized regulation of multiple targets [26]. Several multi-targeted combination therapies are being used for the management of complex diseases, including metabolic syndrome, AIDS, and neurological disorders, and for anticancer therapy [27]. For instance, herceptin (an inhibitor of estrogen receptors) is combined with the antivascular endothelial growth factor, avastin, for the treatment of breast cancer [28]. Oral antihyperglycemic drug metformin (suppressor of hepatic gluconeogenesis and AMPK-mediated glucose transporter) is combined with both insulin secretagogue (glyburide) and (pioglitazone) to improve insulin secretion and sensitivity [29].
Natural Antidiabetic Drugs from Marine Resources
Natural products are a huge reservoir for the development of novel drugs owing to their complex and diversified structure. Many of the natural bioactive compounds and their derivatives have been well explored as multi-targeted drugs and are being used for the treatment of various complex disorders [30, 31]. The previous report on the high throughput screening of new molecules derived from natural products would be a potential strategy for the identification of compounds exhibiting multi-targeted action [32].
The traditional uses of various plants, animals, and marine resources are considered while developing and discovering new medicine compounds today [33]. Marine resources have been used as an exemplary source for centuries as an alternative remedy for treating human diseases because they contain numerous active chemical constituents of immense therapeutic value [34, 35].
Since the oceans make up more than 70% of the earth's surface and are among the most valuable natural resources on the planet, they continue to provide remarkable scaffolding that enhances the quality of human existence [36]. The last few years have seen an increase in interest in marine-related disciplines as researchers look into potential sources of biochemical diversity and other assets like marine-derived bioactive chemicals [37-39]. The acquired results were encouraging and motivated the conduct of additional research to find novel medicines derived from natural sources and meet the needs of the global market [40, 41]. Combined with their chemical and genetic diversity, marine species account for around half of all biodiversity on Earth. As such, they hold great potential as a source of a wide range of diverse and economically valuable compounds, including polysaccharides, enzymes, peptides, lipids, steroids and terpenoids [42]. In the past few decades, 12,000 unique compounds have been found from more than 300,000 identified organisms, generating a lot of curiosity [43]. The majority of these substances are created as secondary metabolites as a defense strategy against invading organisms. Nutraceuticals, among other therapeutic applications, include antiviral and anticancer properties of materials derived from marine sources as dietary supplements and food additives, agrochemicals with insecticidal, herbicidal, and fungicidal activities and cosmetics as photoprotective and antiaging compounds [44]. These substances are thought to be innovative chemically and have the capacity to elicit more prospective behaviors than those found in terrestrial nature [45]. The primary sources of these are various marine taxonomic categories, such as Mediterranean sponges, marine macroalgae, Antarctic fungi, bacteria, and epiphytic bacteria and fungi [46].
Marine Macroalgae as a Potential Source of Bioactive Compounds
In many regions of the world, marine macroalgae are often consumed by people [47]. Depending on their chemical and nutritional makeup, marine macroalgae are categorized as red algae (Rhodophyta), brown algae (Phaeophyta), or green algae (Chlorophyta). Minerals, vitamins, free amino acids, and polyunsaturated fatty acids can all be found in marine algae [48]. Marine macroalgae constitute one of the commercially important renewable marine living resources [49]. They are the exclusive source for the manufacture of phytochemicals like agar, carrageenan, and sodium alginate, which are widely utilized in the food, confectionery, pharmaceutical, dairy, textile, paper, paint, and varnish industries as gelling, stabilizing, and thickening agents [50]. Soups, salads, curries, and other foods for human consumption often contain a variety of protein-rich macroalgae, such as Ulva, Enteromorpha, Caulerpa, Codium, and Monostroma (green algae), Sargassum, Hydroclarthrus, Laminaria, Undariua, and Macrocystis (brown algae), and Porphyra, Gracilaria Eucheuma, Laurencia, and Acanthapora (red algae). One can use certain macroalgae for making wafers, relish, chocolate, jam, and jelly [51]. Because they contain more than 60 trace elements, carbohydrates, iodine, bromine, vitamins, and some bioactive substances, marine macroalgae are also used in various parts of the world as animal feed and fertilizer for land crops. Consuming macroalgae can increase dietary fiber intake and reduce the risk of developing certain chronic diseases, such as inflammation, obesity, heart disease, and cancers, which are linked to low-fiber diets. Additionally, the global market for marine biotechnology, often known as blue biotechnology, has the potential to grow to US $6.4 billion by 2025 from US $4.8 billion in 2020.
Marine macroalgae are available in abundance as free-floating and submerged plants along most of the sea coasts [52]. Tuticorin, being a coastal town, has a large amount of unlimited supply of macroalgae, which have been used as medicine and food for a long time by people of other countries [53]. In India, particularly in Tamil Nadu, the importance of marine macroalgae is not well known whereas the pharmaceutical importance of marine macroalgae is well known all over the world, and there are several reports regarding their medicinal importance [49, 54]. Numerous reports indicated that the macroalgae showed a broad range of biological activities such as antibacterial, anti-inflammatory, antioxidant, anticancer, analgesic, antidiuretic, hepatoprotective, antipyretic, antiulcer, and so on (Table 1).
Table 1Pharmacological properties of bioactive compounds from marine macroalgae.Phytochemicals and Pharmacological Properties of Marine MacroalgaeReferencesAntioxidant compounds like caffeic acid, phytol and mannoheptulose have been reported from the methanolic extract of the marine macroalga, Gelidiella acerosa, which protects human peripheral blood mononuclear cells against TCDD-induced toxicity.[55]Studies on marine macroalgae as nutritional supplements were reported. Analysis of the nutritional profile, physicochemical properties, and proximate composition of G. acerosa revealed the presence of fatty acids like linoleic acid, amino acids like valine, methionine, lysine and phenyl alanine and vitamin C, which can be used as a nutritional supplement.[56]Evaluation of anticholinesterase activity of G. acerosa benzene extract showed the inhibition of butyryl cholinesterase (BuChE) and acetylcholinesterase (AChE) competitively, which may have therapeutic potential against Alzheimer's disease.[57]In vitro screening of secondary metabolites and antimicrobial activities of ethanol and acetone extracts from red marine macroalgae G. acerosa reported that ethanolic extract had maximum number of secondary metabolites and had high antimicrobial activity than acetone extract.[58]In vitro evaluation of antioxidant activity and antimicrobial activity against food-borne bacteria Staphylococcus aureus in relation to polyphenolic content of methanolic extract of G. acerosa was reported.[59]Biochemical composition of G. acerosa from sunderban mangrove was reported to have high quantities of C16 and C18 polyunsaturated fatty acids, which are responsible for anticancer, obesity and antidiabetic activity.[60]Activity of a sulfono glycolipid derived from maritime red algae G. acerosa in Sri Lanka to stimulate human sperm motility was found to have dose-dependent sperm-stimulating activity, but the highest dose impaired sperm motility.[61]A sphingosine derivative was discovered by NMR studies after being isolated from the hexane fraction of the marine red alga G. acerosa from Sri Lanka.[62]Studies on the post-coital contraceptive mechanisms of crude extract of Sri Lankan marine red algae, G. acerosa, revealed that foetal death occured because of high post implantation loss, which also had an antiprogestational effect.[62]Significant post-coital contraceptive effects were obtained without any noticeable side effects when female rats were given oral (500 mg/kg/day) preparations of red algae G. acerosa in a 1:1 ratio. This was done from day 1 to day 7 of pregnancy.[63]In vitro antioxidant and antiinflammatory activity of ethanolic (70%) extract of Sargassum ilicifolium revealed dose-dependent DPPH scavenging and HRBC membrane stabilization.[64]Pharmacognostical and phytochemical evaluation of S. ilicifolium reported the macroscopy of marine macroalgae and the evaluation of mineral and inorganic constituents as well as powder microscopy.[65]Acute and subacute oral toxicity studies on rodents revealed that marine macroalgae tolerated up to 2000 mg/kg b.wt. in the acute toxicity study, and the subacute toxicity, slight alterations were seen in the liver histopathology at 800 mg/kg b.wt.[66]A fatty compound steroid was isolated from the marine macroalgae S. ilicifolium, and 50 µg of the steroid was able to inhibit 16.8% of ACE activity and proved to have antihypertensive activity.[67]Bioactive potentials and antioxidant activity of S. ilicifolium revealed the presence of high carbohydrate and low lipid content. It also showed high phenolic content, which was responsible for its antioxidant effect. FT-IR analysis also revealed the characteristic peaks of alginic acid.[68]Analgesic and anti-inflammatory activity of bioactive compound from methanolic extract of S. ilicifolium reported dose-dependent reduction of acetic acid and carrageenan-induced paw edema.[69]Antibacterial activity against five clinical pathogens showed impediment of growth at nanomolar concentrations, and in-vitro cytotoxicity assay against brine shrimp using silver nanoparticles synthesized from S. ilicifolium showed an LD50 value of 10 nm/mL. Antibacterial activity against five clinical pathogens showed impediment of growth at nanomolar concentrations, and in-vitro cytotoxicity assay against brine shrimp using S. ilicifolium showed an LD50 value of 10 mg/mL.[70]Immunomodulatory activity of ethyl acetate extracts of brown algae S. ilicifolium with reference to phagocytosis was reported.[71]There have been reports of the antitumor and immunomodulatory properties of Sargassum fusiforme polysaccharides. The sulfated polysaccharide from the marine macroalgae significantly inhibited the growth of A549 lung adenocarcinoma.[72]Inhibition of lipopolysaccharide (LPS) – induced inflammatory response by Sargassum hemiphyllum sulfated polysaccharide extract in RAW 264.7 macrophage cells was reported. The anti-inflammatory activity was attributed to the down-regulation of NF-κB.[73]Structural features, chemical modification and antiviral activity of polysaccharides from Sargassum tenerrimum were studied. The results suggested inhibition of HSV infection by blocking viral entry with specific structures of polysaccharides.[74]In vitro cancer chemopreventive properties through antiinflammatory and protective modulation of carcinogen metabolism of a polysaccharide extract from the brown alga, S. latifolium, reported it as an antileukemic agent.[75]Purification of three main fractions of polysaccharides from the brown marine macroalga Sargassum pallidum and its antitumor activity by MTT assay and antioxidant activity by DPPH radical scavenging activity in vitro were reported.[76]The role of sulfated polysaccharides as hepatoprotective from Sargassum wightii in Cyclosporine A-induced oxidative liver injury in rats was reported.[77]It has been noted that heparin is a weaker anticoagulant than the acid-sulfated polysaccharide isolated from fermented brown marine macroalgae Sargassum fulvellum. Both the intrinsic and extrinsic blood coagulation pathways were suppressed.[78]Dose-dependent antioxidant activity of sulfated polysaccharides isolated from S. fulvellum was reported, which was compared with that of commercially available fucoidan and BHA. Sulfated polysaccharide from the brown alga Sargassum patens against herpes simplex virus type 1 was reported. It was found that it significantly inhibited in vitro replication of both acyclovir-sensitive and herpes simplex virus type 1 resistance strains.[79]Sarga A, a polysaccharide isolated from the marine macroalgae Sargassum stenophyllum, showed a dose-dependent antiangiogenic activity as well as antitumoral properties.[80]Antiviral properties and mechanisms of a sulfated polysaccharide from the brown alga Sargassum patens against herpes simplex virus type 2 were reported. Sulfated polysaccharides showed dose-dependent inhibition of replication and had virucidal activity at high concentrations.[81]Aqueous extract of Turbinaria conoides was evaluated for its anti-inflammatory effect using ethyl phenylpropiolate (EPP)-induced ear edema and carrageenin-induced hind paw edema tests. Results revealed the anti-inflammatory activity of T. conoides comparable to the phenylebutazol and acetylsalicylic acid used as standard control.[82]
Bioactive Compounds from Different Marine Macroalgae and their Properties
However, there are examples of marine-derived bioactive compounds/molecules from marine macroalgae that show excellent clinical potential. In general, a lot of research has been conducted on the pharmacological activity of macroalgae. However, research on using marine microalgae as a source for novel bioactive substances is still in its infancy, even though numerous novel bioactive compounds have been isolated over the last few years (Table 2).
Table 2Bioactive compounds from different marine macroalgae.Name of theMarine MacroalgaeBioactive CompoundsBiological ActivityReferencesGracilaria asiaticaProstaglandin (PG) EAnti-inflammatory[85]Saccharina japonicaFucoidansAnti-inflammatory[86]Eisenia bicyclisPhloroglucinolAntiHIV, Anticancer, Antioxidant[87]Taonamaria atomariaStypoldioneAntiinflammatory and Anticancer activity[88]Laurencia mariannensis10-Hydroxy kahukueneAntimicrobial[89]Undaria pinnatifidaFucoxanthinAnticancer[90]Ecklonia cavaPolysaccharideAntiinflammatory[91]Ulva reticulatePheophytinAntiinflammatory[92]Enteromorpha proliferaFucoidansAntiinflammatory[93]Peyssonnelia sp.Peyssonoic acidAntimicrobial[94]Laurencia sp.Tiomanene AcetylmajapoleneAntimicrobial[95]Polysiphonia lanora3-DibromobenzaldehydeAntimicrobial[96]Dictyopteris zonarioidesZonarol and isozonarol sesquiterpenesAntimicrobial[96]Sargassum macrocarpumDiterpene sargafuranAntimicrobial[97]Myagropsis myagroidesFucoxanthinAntiinflammatory[98]Laurencia microcladiaSesquiterpene elatolAnticancer and Larvicidal activity[99]Schizymenia dubyiSulfated glucuronogalactanAnticoagulant[100]PhaeophyceaeSulfated fucoidansImmune modulatory effect[101]RhodophyceaeSulfated galactansAnticoagulant activity[102]Codium fragileXyloarabinogalactansAnticoagulant activity[103]Codium cylindricumSulfated galactanAnticoagulant activity[102]Sargassum thunbergiiPhlorotanninsAntibacterial activity[104]Bossiella orbignianaEicosapentaenoic acid.Antiinflammatory[105]Turbinaria conoidesFucoidansAntiinflammatory[106]Gracilaria lichenoidesProstaglandinsAntiinflammatory[107]Cottoniella filamentosaHepoxlin B3Antiinflammatory[108]Porphyra sp.PhycoerythrobilinAnticancer[109]Ecklonia cavaPhlorotannin 6,6′-bieckolAntiHIV[110]Porphyria dentateCatechol, rutin and hesperidinAntiinflammatory[111]
Recently, several findings have reported that marine macroalgae are rich in fatty acids (unsaturated, monounsaturated, and polyunsaturated), along with their use as nutraceuticals for the management of T2DM (Table 3). Among the various fatty acids, monounsaturated fatty acids have been reported to improve insulin sensitivity in healthy and glucose-intolerant individuals without any gain in fat intake. They also enhance the absorption of glucose by activating the cell membrane's GLUT1 and GLUT4 glucose transporter systems, in particular, and cytoprotective effect on pancreatic-β cells. The monounsaturated fatty acids isolated from Ulva lactuca have induced various antioxidant-responsive element-driven genes in various mouse tissues. Compared to monounsaturated fatty acids, polyunsaturated fatty acids play a crucial role in regulating diabetes, and they are found in marine macroalgae as the necessary fatty acids omega-3 and omega-6 found in the diet of humans. Consumption of omega-3 fatty acids through diet reduces triglyceride concentration and blood pressure. They can be used as inflammatory markers in T2DM patients [39, 83, 84].
Table 3Antidiabetic properties of marine macroalgae.Name of the Marine MacroalgaeExperimental ModelMechanisms ofAntidiabetic ActivityReferencesE. bicyclisIn vitroInhibition of advanced glycation end product[112]C. racemosaIn vitroα-amylase inhibition[113]S. schroederiIn vitroα-amylase inhibition[113]A. nodosumIn vitroα-amylase and α- glycosidase inhibition[114]A. nodosumIn vitroGlucose uptake by cells[114]E. stoloniferaIn vitroα-glucosidase inhibition[115]E. stoloniferaIn vitroα-glucosidase inhibition[116]Petalonia binghamiaeIn vivoInsulin sensitizing action in adipocytes[117]Hypnea musciformisIn vivoAntihyperglycemic, stimulated plasma insulin effects[118]U. rigidaIn vivoReduction of postprandial blood glucose level, Antioxidant activity[118]A. nodosumIn vitroα-amylase and α- glycosidase inhibition[114]E. cavaIn vitroReduction of postprandial blood glucose level[119]A. nodosumIn vitroα-amylase and α-glucosidase inhibition[120]L. japonicaIn vitroInhibition of AGE formation and aldose reductase[121]F. vesiculosusIn vitroα-glucosidase inhibition[120]S. binderiIn vitroDipeptidyl peptidase-4 inhibition[122]P. sulcataIn vitroDipeptidyl peptidase - 4 inhibition[122]T. conoidesIn vitroDipeptidyl peptidase - 4 inhibition[122]S. binderiIn vitroStimulation of gastric inhibitory polypeptide[122]P. sulcataIn vitroStimulation of gastric inhibitory polypeptide[122]T. conoidesIn vitroStimulation of agstric inhibitory polypeptide[122]S. binderiIn vitroStimulation of gastric inhibitory polypeptide[122]P. sulcataIn vitroStimulation of gastric inhibitory polypeptide[122]S. polycystum,S. wightii andT. ornataIn vitroα-Amylase, α-Glucosidase and DPP-IV inhibition[118]
The enzyme inhibitors are a new class of oral medication for the management of diabetes [114]. The list of marine macroalgae metabolites and their inhibitory activity against enzymes linked to diabetes are tabulated in Table 4. Among these, α-amylase and α-glucosidase inhibitors are known to reduce postprandial hyperglycemia by delaying starch digestion and intestinal absorption. Dipeptidyl peptidase-IV (DPP-IV) inhibitors help in maintaining glucose homeostasis by promoting α and β cell functions. The extracts of Ecklonia cava, brown marine macroalgae, were reported for both α-amylase and α-glucosidase inhibitory activity. Further studies on bioactivity-guided isolation resulted in the compound dieckol [107]. This compound was also reported for hepato-protective activity [119]. Similarly, two compounds (dibenzo [1, 4] dioxine-2, 4, 7, 9-tetraol and eckol) were isolated from Ecklonia maxima, having effective α-glucosidase inhibition and DPPH radical scavenging activity compared to the commercial drug acarbose and synthetic antioxidant BHT. Phlorotannins are a group of tannins that are oligomers of phloroglucinol, which are found abundant in brown marine macroalgae. Phlorotannins isolated from Ecklonia stolinifera also showed significant α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) inhibitory activity [116]. Dioxinodehydroeckol, fucofuroeckol, and a new phloroglucinol derivative (1-(3′,5′-dihydroxyphenoxy)-7-(2″,4″,6″-trihydroxyphenoxy)-2,4,9- trihydroxydibenzo-1,4-dioxin) isolated from Eisenia bicyclis showed a notable α-glucosidase and amylase inhibitory activity [123] (Table 4).
Table 4Antidiabetic compounds from marine macroalgae and their inhibitory mechanisms.Name of the Marine MacroalgaeBioactive Compounds Isolated from Marine MacroalgaeInhibitory Mechanisms of Bioactive CompoundsReferencesSymphylocladia latiuscula2,3,6-tribromo-4,5-dihydroxybenzyl alcoholInhibition of α - Glucosidase activity[124]Odonthalia corymbifera4- bromo-2,3-dihydroxy-6-methoxymethylphenyl 2,5-dibromo-6-hydroxy-3Inhibition of carbohydralyzing enzymes[125]Polysiphonia morrowii3-bromo-4,5-dihydroxybenzyl alcoholα-glucosidase inhibitory activity[125]Eisenia bicyclisFucoxanthin and DieckolInhibition of α - amylase and glucosidase[118]Pelvetia siliquosaFucosterolReduction Of serum glucose concentration in STZ-induced diabetic rats[126]Eisenia bicyclisPhloroglucinol derivative:
1-(3′,5′- dihydroxyphenoxy)-7-(2″,4″,6″trihydroxyphenoxy)- 2,4,9-trihydroxydibenzo-1,4-dioxinα-amylase inhibition, reduction of lipid accumulation by inhibiting adipocyte cells (3T3-L1 fibroblast)[127]Grateloupia Elliptica2,4,6-tribromophenol; 2,4-dibromophenolα-amylase inhibition, inhibiting glucose uptake[128]Ishige okamuraePhloroglucinol derivative:
Diphloetho hydroxycarmalolInhibition of α amylase and α glucosidase[129]Eisenia bicyclis1-(3′,5′- dihydroxyphenoxy)-7-(2″,4″,6″trihydroxyphenoxy)- 2,4,9-trihydroxydibenzo-1,4 dioxinInhibition of carbohydrates hydrolyzing enzymes and enhancement of glucose uptake[127]Laminaria sp.butyl-isobutylphthalateInhibition of α amylase and α glucosidase[130]Laurencia similis3′,5′,6′,6-tetrabromo-2,4-dimethyldiphenyl etherPTP1B inhibitory[131]Polyopes lancifoliabis(2,3-dibromo-4,5-dihydroxybenzyl) etherInhibiting α-glucosidase enzyme[132]SargassumYezoenseMeroterphenols A-DInhibition of α amylase and α glucosidase[133]Gracilaria edulis11-methoxy-2-methyltridecane-4-olInhibition of α amylase enzyme[134-136]
CONCLUSION
The exploration of marine natural products has led to the discovery of various bioactive compounds having potential pharmacological importance. Here, we have highlighted the importance of marine macroalgae and their potential role in the management of diabetes. Currently, there are no marine macroalgae-derived enzyme inhibitors available as antidiabetic drugs in the market. Although several studies have been reported on the bioactivity of marine macroalgae and their therapeutic applications, consumption of edible macroalgae and their therapeutic implications are lacking.
ACKNOWLEDGEMENTS
The authors are thankful to the management of AMET University for providing the facility to carry out this research work. R.V. acknowledges with gratitude the fellowship granted by AMET University to carry out this research work. The authors acknowledge the immense help received from the scholars whose articles are cited and included in the references of this manuscript. The authors are also grateful to the authors/editors/publishers of all those articles, journals, and books from where the literature for this article has been reviewed and discussed.
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