John Wiley & Sons Phytopharmaceuticals Cover Medicinal plants contain a variety of bioactive compounds, (also referred to as phytochemicals). in .. Product #: 978-1-119-68191-5 Regular price: $195.33 $195.33 In Stock

Phytopharmaceuticals

Potential Therapeutic Applications

Chauhan, Durgesh Nandini / Shah, Kamal (Editor)

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1. Edition August 2021
496 Pages, Hardcover
Wiley & Sons Ltd

ISBN: 978-1-119-68191-5
John Wiley & Sons

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Medicinal plants contain a variety of bioactive compounds, (also referred to as phytochemicals). in the leaves, stems, flowers and fruits. This book covers these bioactive compounds, their available sources, how the bioactive molecules are isolated from the plants, the biochemistry, structural composition and potential biological activities. Also discussed are the pharmacological aspects of medicinal plants, phytochemistry and biological activities of different natural products, ethnobotany and medicinal properties, as well as a novel dietary approach for various disease management and therapeutic potential. The importance of phytopharmaceutical of plants and potential applications in the food and pharma industries is highlighted.

Preface xvii

1 A Great Challenge on the Reproducibility of Therapeutic Results of Phytopharmaceuticals 1
Idha Kusumawati

1.1 Introduction 1

1.2 Common Challenges in Phytopharmaceuticals 2

1.2.1 Authentication of Raw Material 3

1.2.2 Variability of Chemical Content in Raw Material 4

1.2.2.1 Intrinsic Factor 5

1.2.2.2 Extrinsic Factor 5

1.2.2.3 Harvesting 6

1.2.2.4 Post-Harvesting Process 7

1.2.2.5 Storage 8

1.2.2.6 Complex Mixture of the Pharmacologically Active Constituent 8

1.3 Strategy to Guarantee the Quality of Phytopharmaceutical 10

1.3.1 Marker Compound Concept 11

1.3.2 Phytoequivalence Concept 13

1.4 Conclusion 15

Acknowledgment 15

References 15

2 Ibero-American Network as a Collaborative Strategy to Provide Tools or the Development of Phytopharmaceuticals and Nutraceuticals 19
Pilar Buera, Cecilia Abirached, Liliana Alamilla-Beltrán, Verónica María Busch, Cristina Isabel dos Santos, Abel Farroni, Leonardo Cristian Favre, Aldo Fernández-Varela, Fabiano Freire-Costa, Julieta Gabilondo, Micaela Galante, María Eugenia Hidalgo, Romina Ingrassia, Milagros López Hiriart, Alejandra Medrano, Oscar Micheloni, Miguel Navarro Alarcón, Luis Panizzolo, Silvia del Carmen Pereyra-Castro, Viridiana Pérez-Pérez, Carla Patricia Plazola-Jacinto, Patricia Risso, Paz Robert-Canales, Analía Rodriguez, Silvio David Rodríguez, Erick Rojas-Balcazar, José Angel Rufián Henares and Franco Emanuel Vasile

2.1 Introduction 20

2.2 Some Unexplored Botanicals From Ibero-America as Potential Sources of Bioactive Compounds 21

2.2.1 South America Regions: Tropical Savanna and Atlantic Forest 21

2.2.2 Central South America Semiarid Regions 22

2.2.3 Northern South America, Central America and Caribbean 23

2.2.4 Exploitation of Undervalued Resources From Fabaceae Family to Obtain Hydrocolloids 24

2.2.4.1 Gums From Native Fabaceae Family Seeds 24

2.2.4.2 Gums From Fabaceae Family Exudates 26

2.2.5 Healthy Fatty Acid Sources From Ibero America 27

2.2.6 Bioactives From Agroindustrial Wastes 27

2.2.6.1 Commercial Edible Flowers 27

2.2.6.2 Coffee Grounds as Source of Prebiotics 29

2.2.6.3 Healthy Compounds From Olive Oil Wastes 30

2.3 Technologies for Obtaining Stable Natural Bioactive Extracts 31

2.3.1 Extraction Techniques 31

2.3.2 In Vitro Tests for Assessing Antioxidant and Antiglycant Activities 32

2.3.2.1 Antioxidant Activity 33

2.3.2.2 Antiglycant Agents Detection 36

2.3.3 Biocompounds Conservation and Controlled Delivery Systems 37

2.3.3.1 Spray Drying 38

2.3.3.2 Coacervation 39

2.3.3.3 Management of Protein-Hydrocolloid Interactions for Designing Bioactive Delivery Systems 41

2.4 Multivariate Analysis for Phytopharmaceuticals Development 42

2.5 Conclusions 45

Acknowledgements 46

Abbreviations 46

References 47

3 Use of Hydrodistillation as a Green Technology to Obtain Essential Oils From Several Medicinal Plants Belonging to Lamiaceae (Mint) Family 59
Karamatollah Rezaei, Nahal Bashiri Hashemi and Samar Sahraee

3.1 Introduction 59

3.2 Essential Oils and Applied Extraction Techniques 61

3.3 Use of Hydrodistillation to Bridge the Nature With Novel Green Applications 62

3.4 Specific Gravities of Essential Oils as Related to Their Chemical Compositions 67

3.5 Use of Microwave-Assisted Hydrodistillation in the Extraction of Essential Oils From Ziziphora (A Case Study) 68

3.5.1 Extraction Yield 68

3.5.2 Microstructure of Ziziphora Leaves 68

3.5.3 Physical Properties of Essential Oil 68

3.5.4 Differences in the Chemical Compositions 68

3.6 Conclusion and Future Perspectives 69

Acknowledgements 72

References 72

4 The Hidden Danger in Phytopharmaceuticals: Adulteration 77
Miray Ege

4.1 Introduction 77

4.2 What is Adulteration in Plants and Phytopharmaceuticals? 78

4.3 Standardization and Quality in Medicinal Plants and Phytopharmaceuticals 79

4.3.1 Standardization Problems in Identified Plants 81

4.3.1.1 Inter-Species or Species Variation 81

4.3.1.2 Environmental Factors 82

4.3.1.3 Harvesting Time 82

4.3.1.4 Plant Part Used 82

4.3.1.5 Post-Harvest Factors 83

4.3.2 Quality and Standardization Problems 83

4.3.3 Standardization Parameters and Content Analysis on Medicinal Plants and Phytopharmaceuticals 84

4.3.3.1 Phytochemical Analyses for Phytopharmaceuticals and Medicinal Plants 85

4.3.3.2 Analysis of Extracts and Isolated Compounds 85

4.3.3.3 Standardization Parameters (Monograph Parameters) 86

4.4 Adulteration in Phytopharmaceuticals With Synthetic Drugs 87

4.4.1 Adulteration in Phytopharmaceuticals Used for Slimming 88

4.4.2 Adulteration in Phytopharmaceuticals With Aphrodisiac Effect 89

4.4.3 Adulteration in Phytopharmaceuticals Used in Rheumatic Diseases and as Antiinflammatory Drugs 90

4.4.4 Adulteration in Phytopharmaceuticals Used for Regulate Blood Sugar 90

4.4.5 Adulteration in Phytopharmaceuticals Used for Blood Pressure Regulating 90

4.5 How to Analyze Adulteration in Phytopharmaceuticals? 90

4.5.1 TLC and HPTLC 92

4.5.2 HPLC and GC 92

4.5.3 H NMR 93

4.6 Future Perspective for Phytopharmaceuticals 94

4.7 Conclusion 94

References 95

5 Medicinal Plants from the Balkan Peninsula--From Traditional To Modern Pharmacy/Medicine 99
Aleksandra Cvetanovic, Alena Stupar, Mirjana Petronijevic and Zoran Zekovic

5.1 Introduction 99

5.2 Calendula officinalis L. 101

5.2.1 Chemical Composition of C. officinalis 105

5.2.2 Traditional Use vs. Modern Application of C. officinalis 105

5.3 Taraxacum officinale 108

5.3.1 Chemical Composition of T. officinale 108

5.3.2 Traditional Use vs. Modern Application of T. officinale 110

5.4 Hypericum perforatum L. 112

5.4.1 Chemical Composition of Hypericum perforatum 113

5.4.2 Traditional Use vs. Modern Application of H. perforatum 114

5.5 Conclusion 116

Acknowledgement 116

List of Abbreviations 116

References 117

6 Plant-Based Peptides With Biological Properties 123
Jessika Gonçalves dos Santos Aguilar

6.1 Introduction 123

6.2 Production of Plant-Based Peptides 124

6.3 Bioactive Plant-Based Peptides 126

6.3.1 Antimicrobial 126

6.3.2 Antioxidant 127

6.3.3 Antihypertensive 128

6.3.4 Antithrombotic 128

6.3.5 Other Activities 129

6.4 Conclusion 129

List of Abbreviations 130

References 130

7 Potential of Flavonoids as Anticancer Drugs 135
Pradeep Kumar, Jyoti Dixit, Rajesh Saini, Pooja Verma, Awadhesh Kumar Mishra and Kavindra NathTiwari

7.1 Introduction 135

7.2 Causes of Cancer 144

7.3 Synthetic and Natural Chemotherapeutic Drugs 145

7.4 Biosynthesis of Flavonoids 148

7.5 Flavonoid Chemistry 149

7.5.1 Flavonols 150

7.5.1.1 Quercetin 150

7.5.1.2 Kaemferol 150

7.5.2 Flavones 151

7.5.2.1 Apigenin 152

7.5.3 Flavanones 152

7.5.4 Isoflavonoids 153

7.5.5 Anthocyanins 154

7.6 Mode of Action of Plant-Based Anticancer Compounds 155

7.7 Conclusions 155

References 156

8 Phytomedicine Against Infectious Diseases 161
Biswajyoti Sarkar, Sondipon Chakraborty and Chiranjib Pal

8.1 Introduction 161

8.1.1 What are the Phytomedicines? 162

8.1.2 A Brief Synopsis of the History of Phytomedicine Uses,

in Relation With Geographical Regions and Sources 162

8.1.3 The Relevance of Application of Phytomedicine in Today's World 163

8.2 Names, Sources, and Types of Phytomedicines in Use in the Modern World 164

8.3 Chemical Moieties Responsible for the Inhibitory Activity of Different Phytomedicines on Different Organisms 166

8.4 Phytomedicines in Use Against Bacterial, Viral and Protozoan Diseases 167

8.4.1 In Clinical Use 167

8.4.2 In Experimental Therapeutics 168

8.5 Conclusion 169

References 170

9 Herbal Traditional Remedies for Male Infertility 173
Shalaka Sudhir Ramgir, Abilash Valsala Gopalakrishnan and Selvaraj Mohana Roopan

9.1 Introduction 173

9.2 Application of Indian Traditional Medicine (Ayurveda) for Male Infertility 174

9.3 The Significant Role of Traditional Chinese Medicine in Male Infertility Management 178

9.4 Iranian/Persian Traditional Medicine (ITM) Restores Male Fertility 181

9.5 Traditional Korean Medicine and Male Infertility 182

9.6 Traditional African Medicine in the Treatment of Male Infertility 183

9.7 Conclusion 184

References 184

10 The Therapeutic Applications of Phytopharmaceuticals in Dentistry 191
Bilal Ege and Miray Ege

10.1 Introduction 191

10.2 Historical Development of Phytopharmaceuticals in Dentistry 193

10.3 Phytochemical Contents of Plants 194

10.3.1 Alkaloids 194

10.3.2 Phenolic Compounds 195

10.3.3 Polyphenols 195

10.3.4 Terpenoids 195

10.4 Dental Materials of Plant Origin 195

10.5 Phytotherapeutics in Dentistry 196

10.5.1 Usage in Tooth Decays 196

10.5.1.1 Effective Factors in Caries Formation 197

10.5.1.2 Anticariogenic Plants Effective in Preventing Dental Caries 198

10.5.2 Usage in Oral Mucosal Lesions 202

10.5.3 Usage in Endodontic Treatment 204

10.5.3.1 Phytopharmaceutical Irrigants 205

10.5.3.2 Phytopharmaceutical Intracanal Drugs 206

10.5.4 Usage in Dental Traumatology 207

10.5.5 Usage in Oral Surgery 208

10.5.6 Usage in Periodontal Diseases 209

10.5.7 Usage in Treatment of Halitosis 213

10.6 Conclusion 215

References 215

11 Prevention of Vascular Endothelial Dysfunction by Polyphenols: Role in Cardiovascular Disease Prevention 223
Kazuo Yamagata

11.1 Introduction 223

11.2 Endothelial Dysfunction and Cardiovascular Disease 225

11.2.1 Production and Elimination of Reactive Oxygen Species in Endothelial Cells 225

11.2.2 Regulation of Nitric Oxide Bioavailability by Oxidative Stress 227

11.3 Inflammation and Endothelial Cell Dysfunction Associated With Arteriosclerosis in Endothelial Cells 228

11.4 Preventive Effects of Resveratrol on Endothelial Dysfunction 230

11.5 Preventive Effects of EGCG on Endothelial Dysfunction 233

11.6 Preventive Effects of Quercetin on Endothelial Dysfunction 235

11.7 Preventive Effects of Chlorogenic Acid on Endothelial Dysfunction 237

11.8 Conclusion 238

References 238

12 Quercetin-Rebuttal Behavior in Male Reproductive Potential 247
Kaviyarasi Renu, AbilashValsala Gopalakrishnan and Selvaraj Mohana Roopan

12.1 Introduction 247

12.2 Quercetin as Antioxidants 248

12.3 Quercetin, In Vitro Antioxidant Activity 248

12.3.1 Quercetin, Direct Scavenging of ROS and Activates Antioxidant Enzymes 248

12.3.2 Metal Chelating Activity of Quercetin 249

12.3.3 Inhibition of Oxides by Quercetin 249

12.3.4 Reduction of alpha-Tocopheryl Radicals by Quercetin 250

12.3.5 Elevated Pro-Oxidant Properties of Low Molecular Antioxidants 250

12.4 Quercetin Metabolism With In Vitro and In Vivo Antioxidant Activity of its Metabolites 250

12.5 Quercetin as Pro-Oxidant 250

12.5.1 Quercetin Pro-Oxidant Function 250

12.6 Quercetin, Phenoxyl Radicals Oxidation 251

12.7 Impairment of Respiration of Mitochondria by Quercetin 251

12.8 Quercetin, Low Molecular Weight Antioxidant Oxidation 251

12.9 Quercetin Damage Directly DNA 252

12.10 Spermatogenesis and Oxidative Stress 252

12.11 Quercetin and Male Reproduction 252

12.12 Amelioration of Male Reproductive Dysfunction by Quercetin 253

12.13 Contradictory Reports of Quercetin With Respect to Male Reproductive Potential 254

12.14 Conclusion 254

References 254

13 Traditional Uses and Bioactivities of Common Rubus Species With Reference to Cancer: A Mini-Review 259
Blassan P. George and Heidi Abrahamse

13.1 Introduction 259

13.2 Traditional Uses of Common Rubus Species 260

13.2.1 Rubus fruticosus 260

13.2.2 Rubus ellipticus 260

13.2.3 Rubus idaeus and Related Rubus Species 261

13.3 Biological Activity Studies of Rubus Extracts 261

13.4 Bioactive Compounds From Rubus Species 262

13.5 Rubus as an Antitumor Agent 262

13.6 Conclusion 265

Acknowledgements 265

References 265

14 Therapeutic Compounds From Brown Seaweeds: Antitumor Properties on Various Cancers and Their Mechanisms of Action 271
Dilek Unal and Inci Tüney Kizilkaya

14.1 Introduction 271

14.2 Type of Bioactive Compounds From Brown Algae 273

14.2.1 Terpenoids (Terpens) 273

14.2.2 Polysaccharides 274

14.2.2.1 Alginic Acid 274

14.2.2.2 Fucoidans 274

14.2.2.3 Laminarin 275

14.2.3 Polyphenols 275

14.2.4 Pigments 276

14.3 Type of Cancer and Molecular Action Mechanisms 276

14.3.1 Breast Cancer 278

14.3.2 Colon Cancer 279

14.3.3 Prostate Cancer 280

14.4 Conclusion 280

References 280

15 Medicinal Plants and Polycystic Ovary Syndrome 287
Yogamaya D Prabhu, Abilash Valsala Gopalakrishnan and Selvaraj Mohana Roopan

15.1 Introduction 287

15.2 Clinical Manifestations of PCOS 288

15.3 Importance of Phenotypes in PCOS 289

15.4 Conventional Therapies for PCOS Treatment 290

15.5 Herbal Medicine and PCOS 290

15.6 Conclusion 295

List of Abbreviations & Symbols 296

References 296

16 The Potential Role of Phytochemical in Establishing Prophylactic Measurements Against Neurological Diseases 301
Srivastava P. and Tiwari A.

16.1 Introduction 301

16.2 Focused Neurological Disorder for Herbal Promises 302

16.2.1 Cases of Attention 303

16.2.2 Target Identification 303

16.2.3 Physicochemical Characterization and Secondary Structure Prediction 303

16.2.4 Molecular Modeling Studies 304

16.2.5 Virtual Screening for Potential Phytochemicals 305

16.2.6 Molecular Interaction Studies 307

16.3 Conclusion 311

References 311

17 Immunomodulatory Activity of Cannabinoids: From Abuse to Therapy 315
Farid A. Badria and Abdullah A. Elgazar

17.1 Introduction 315

17.2 Immunity System, Related Diseases and Current Therapeutic Options 318

17.3 Historical and Traditional Uses of Cannabis Herb 320

17.4 Chemistry of Cannabinoids 321

17.5 Pharmacology of Phytocannabinoids 323

17.5.1 Pharmacological Effect of THC 323

17.5.2 Pharmacological Effect of CBD 324

17.6 Conclusion 326

References 326

18 Botany, Geographical Distribution, Phytochemistry and Phytopharmaceutical Potential of Rheum emodi Wall. ex Meisn.: An Overview 331
Mohd. Shahnawaz, Refaz Ahmad Dar, Syed Mudassir Jeelani, Tahoora Batool Zargar, Malik Mohd. Azhar, Sajad Ahmed, Sabeena Ali, Rekha Chouhan, Gulfam Sheikh, Puja Gupta, Abhishek Kumar Nautiyal, Manisha K. Sangale and Avinash B. Ade

18.1 Introduction 332

18.2 Botany and Taxonomic Status of R. emodi 332

18.3 Origin and Geographical Distribution of R. emodi 333

18.4 Phyto Constituents of R. emodi 334

18.5 Traditional Uses of R. emodi 341

18.6 Pharmaceutically Active Biomolecules of R. emodi 341

18.7 Conclusion 342

18.8 Future Prospective 342

Acknowledgements 342

References 343

19 Taxonomic Status, Phytochemical Constituents and Pharmaceutical Active Components of Genus Alseodaphne: A Literature Update 347
Puja Gupta, Mohd. Shahnawaz, Sajad Ahmad, Rekha Chouhan, Sundeep Jaglan, Yash pal Sharma, Madangchanok Imchen and Ranjith Kumavath

19.1 Introduction 347

19.2 Botany and Taxonomic Status of Some Important Members of Alseodaphne 348

19.2.1 Alseodaphne archboldiana Kosterm 348

19.2.2 Alseodaphne andersonii Kosterm 348

19.2.3 Alseodaphne corneri Kosterm 349

19.2.4 Alseodaphne hainanensis Merr 349

19.2.5 Alseodaphne pendulifolia Gamble 349

19.2.6 Alseodpahne peduncularis (Wall. ex Nees) 349

19.2.7 Alseodaphne perakensis (Gamble) Kosterm 349

19.2.8 Alseodaphne semecarpifolia Nees 350

19.3 Origin and Geographical Distribution of Some Important Members of Genus Alseodaphne 350

19.3.1 A. archboldiana 350

19.3.2 A. andersonii 350

19.3.3 A. corneri 350

19.3.4 A. hainensis 350

19.3.5 A. pendulifolia 350

19.3.6 A. peduncularis 350

19.3.7 A. perakensis 351

19.3.8 A. semecarpifolia 351

19.4 Phytochemical Studies of a Few Important Members of Alseodaphne 351

19.4.1 A. archboldiana 351

19.4.2 A. andersonii 351

19.4.3 A. corneri 351

19.4.4 A. hainensis 352

19.4.5 A. pendulifolia 352

19.4.6 A. peduncularis 352

19.4.7 A. perakensis 352

19.4.8 A. semicarpifolia 352

19.5 Traditional and Pharmaceutical Importance of Some Important Members of Alseodaphne 353

19.5.1 A. archboldiana 353

19.5.2 A. andersonii 353

19.5.2.1 Effect on Inflammation and Central Nervous System 353

19.5.2.2 Antimicrobial Activity 353

19.5.2.3 Immunomodulatory Activity of A. andersonii 354

19.5.2.4 Major Fatty Acids and Oil Content of A. andersonii 354

19.5.3 A. corneri 354

19.5.4 A. hainensis 354

19.5.5 A. pendulifolia 355

19.5.6 A. peduncularis 355

19.5.7 A. perakensis 355

19.5.8 A. semicarpifolia 356

19.6 Future Prospective 356

19.7 Conclusions 356

Acknowledgments 356

References 357

20 Bioactive Compounds From Schinus terebinthifolius Raddi and Their Potential Health Benefits 363
Nayara Bispo Macedo, Daylín Díaz Gutierrez, Andreza Santana Santos, Raquel Oliveira Pereira, Gopalsamy Rajiv Gandhi, Maria das Graças de Oliveira e Silva, Alexis Vidal, Lucindo José Quintans Júnior, Jullyana de Souza Siqueira Quintans and Ana Mara de Oliveira e Silva

20.1 Introduction 363

20.2 Search Strategies 364

20.3 Bioactive Compounds 365

20.3.1 Phenolic Compounds 372

20.3.2 Terpenes 373

20.4 Biological Activities 373

20.4.1 Antimicrobial Activity 373

20.4.2 Healing Activity 383

20.4.3 Anti-Inflammatory Activity 385

20.4.4 Antioxidant Activity 389

20.5 Toxicity 395

20.6 Conclusion and Future Considerations 395

Acknowledgements 396

References 396

21 Composition and Biological Properties of Rambutan (Nephelium lappaceum) 403
Andreza de Santana Santos, Anne Karoline de Souza Oliveira, Raquel Oliveira Pereira, Erivan Vieira Barbosa Junior, Adalgisa de Lima Sayao and Ana Mara de Oliveira e Silva

21.1 Introduction 403

21.2 Chemical Characterization 404

21.2.1 Centesimal Composition 404

21.2.1.1 Peel 404

21.2.1.2 Pericarp or Pulp 404

21.2.1.3 Seed 411

21.2.2 Bioactive Compounds 411

21.2.2.1 Peel 411

21.2.2.2 Pericarp or Pulp 411

21.2.2.3 Seed 412

21.3 Biological Properties 412

21.3.1 Antioxidant Activity 412

21.3.2 Antimicrobial Activity 418

21.3.3 Antidiabetic Activity 421

21.3.4 Antiobesogenic Activity 421

21.3.5 Other Health Benefits 425

21.4 Toxicity Aspects 430

21.5 Conclusion 430

References 433

22 Phytochemicals and Health: An Update 437
Semih Otles and Gozde Turkoz Bakirci

22.1 Introduction 437

22.1.1 Types of Phytochemicals 438

22.1.2 Reported Phytochemicals 438

22.1.2.1 Steroids 439

22.1.2.2 Flavonoid C-Glycoside 439

22.1.2.3 Flavones 439

22.1.2.4 Essential Oil Component 439

22.1.2.5 Tannins 439

22.1.2.6 Miscellaneous 442

22.2 Health Effect of Phytochemicals 442

22.2.1 Wheat 448

22.2.2 Barley 449

22.2.3 Fruit and Vegetables 449

22.2.4 Legumes 451

22.2.5 Tea 451

22.2.6 Spices and Herbs 451

22.3 Advanced Analysis of Phytochemicals 451

22.4 Conclusion 452

References 452

Index 455
Durgesh Nandini Chauhan completed her M.Pharma in pharmaceutics from Uttar Pradesh at the Dr. A.P.J. Abdul Kalam Technical University, Lucknow in 2006. She is currently working as assistant professor in Columbia Institute of Pharmacy, Raipur, Chhattisgarh, India. She has written more than 10 articles in national and international journals, 15 book chapters, and edited 4 books including Natural Oral Care in Dental Therapy (Wiley-Scrivener 2020).

Kamal Shah has more than 14 years of research and teaching experience and currently is an associate professor at the Institute of Pharmaceutical Research, GLA University, Mathura, India. He has completed B.Pharma from Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal (M.P.) in 2003. He was gold medalist in B.Pharm., M.Pharm. from the Department of Pharmaceutical Sciences, Sagar University, Sagar, India and PhD from APJ Kalam University Lucknow, India. He has written more than 30 articles published in national and international journals and 6 book chapters and co-edited Natural Oral Care in Dental Therapy (Wiley-Scrivener 2020).