Studies on Biomarkers and New Targets in Aging Research in Iran: Focus on Turmeric and Curcumin (Advances in Experimental Medicine and Biology, 1291)

The Middle East is known as the cradle of civilization. It was the crossroads of ancient empires and the birthplace of major world religions. Today it is the center of many world issues due to its economic, religious and political importance. Although it has lagged behind many other regions of the world in medicinal research, this has increased dramatically in recent years with increasing numbers of relevant publications and the country of Iran has spearheaded this progress. Much of the research has focused on increasing our understanding of the aging process and attempting to identify biomarkers and natural products to improve the human healthspan. This book provides a comprehensive overview of the research conducted in the Middle East on the health benefits of curcumin, a phytochemical derived from the famous spice turmeric. Hundreds of studies have now been published describing the health benefits of this spice. The importance of this research is exemplified by poor data regarding health and longevity as only 0.08% of the population in Iran consists of individuals over 90 years of age. This is approximately 10 times lower than the percentage of this same age group in the United Kingdom and the United States of America and almost 20 times lower than that in Japan. This book presents a series of reviews and meta-studies describing research which has resulted in identification potential new biomarkers and drug targets for age-related disorders. All of the studies have focussed on the testing of curcumin and related products, which have already shown some promising leads in age-related conditions such as heart-disease, diabetes, cognitive impairment and cancer. The authors in this series come from different centers and cities of Iran, including Mashhad, Tehran, Isfahan, Ahvaz, Birjand, Quchan and Yazd, and many of the chapters feature collaborations with other countries of the Middle East and throughout the world, including Brazil, Italy, Mexico, Oman, Poland, Switzerland, the United Kingdom and the United States of America. This underscores the emergence of the Middle East into this arena of research. The book will be of high interest to scientific and clinical researchers in the subject of aging and age-related disease, and to physicians and pharmaceutical company scientists since it gives insights into the latest strategies, biomarkers and targets involved in the mechanism of action of curcumin to promote healthy aging. It will also provide important information on disease mechanisms related to age-related disorders, as each chapter will be presented in the context of specific chronic diseases. Preface Contents 1: Research in the Middle East into the Health Benefits of Curcumin 1.1 Introduction 1.2 Current Uses 1.3 The Growth in Curcumin Research in the Middle East 1.4 The Health Situation in the Middle East 1.4.1 Bahrain 1.4.2 Cyprus 1.4.3 Egypt 1.4.4 Iran 1.4.5 Iraq 1.4.6 Israel 1.4.7 Jordan 1.4.8 Kuwait 1.4.9 Lebanon 1.4.10 Oman 1.4.11 Qatar 1.4.12 Saudi Arabia 1.4.13 Syria 1.4.14 Turkey 1.4.15 UAE 1.4.16 Yemen 1.5 Conclusions and Future Prospects References 2: Turmeric and Curcumin: From Traditional to Modern Medicine 2.1 Introduction 2.2 Traditional View 2.2.1 Turmeric in Islamic Traditional Medicine (ITM) 2.2.2 Indian Traditional Medicine (Ayurveda) 2.2.3 Traditional Chinese Medicine (TCM) 2.2.4 Traditional Thai Medicine (TTM) 2.3 Clinical View 2.3.1 Anti-Inflammatory and Antioxidant Activities 2.3.2 Metabolic Disorders 2.3.2.1 Cardio- and Vaso-Protective 2.3.2.2 Hepato-Protective 2.3.3 Neuroprotective and Antidepressant 2.3.4 Indications Supported by Both Traditional Medicine and Clinical Trials References 3: Targeting Nuclear Factor-Kappa B Signaling Pathway by Curcumin: Implications for the Treatment of Multiple Sclerosis 3.1 Introduction 3.2 NF-κB 3.2.1 NF-κB in the Nervous System 3.3 Curcumin 3.3.1 Immunoregulatory Effects of Curcumin 3.4 TLR 4 3.5 PPARγ 3.6 COX-2 3.7 Pro-inflammatory Cytokines 3.8 Conclusions References 4: Carbon-based Nanomaterials and Curcumin: A Review of Biosensing Applications 4.1 Introduction 4.2 Biosensing Applications of Carbon-based Nanomaterials 4.3 Carbon Nanotube-Based Biosensors 4.4 Graphene-based Biosensors 4.5 Carbon Dot-based Biosensors 4.6 Conclusions References 5: Effects of Curcumin and Its Analogues on Infectious Diseases 5.1 Introduction 5.2 Bacterial-Associating IDs 5.3 Mechanisms Underlying Native Curcumin in Bacterial-Associating IDs 5.4 Mechanisms Underlying Curcumin Analogues in Bacterial-Associating IDs 5.5 Parasitic-Associating IDs 5.6 Mechanisms Underlying Native Curcumin in Parasitic-Associating IDs 5.7 Mechanisms Underlying Curcumin Analogues in Parasitic-Associating IDs 5.8 Promises and Controversies of Curcumin on Bacterial- and Parasitic-Associating IDs 5.9 Conclusions and Future Perspectives References 6: Protective Effects of Curcumin on Endothelium: An Updated Review 6.1 Introduction 6.2 In Vitro Studies and Ex Vivo Experiments with Curcumin Addiction 6.3 Animal Studies 6.4 Clinical Trials 6.5 Mechanisms of Action 6.6 Conclusions References 7: The Effect of Curcumin Supplemsentation on Anthropometric Indices in Overweight and Obese Individuals: A Systematic Review of Randomized Controlled Trials 7.1 Introduction 7.2 Methods 7.2.1 Search Strategy 7.2.2 Study Selection 7.2.3 Inclusion and Exclusion Criteria 7.2.4 Data Extraction 7.2.5 Quality Assessment 7.3 Results 7.3.1 Search Results and Study Selection 7.3.2 Characteristics of the Included Studies 7.3.3 Quality Assessment 7.3.4 Effect of Curcumin on Body Weight 7.3.5 Effect of Curcumin on BMI 7.3.6 Effect of Curcumin on Waist Circumference 7.3.7 Effect of Curcumin on Hip Circumference 7.3.8 Effect of Curcumin on Total Body Fat 7.3.9 Effect of Curcumin on Visceral Fat 7.3.10 Effect of Curcumin on Waist-Hip Ratio 7.3.11 Effect of Curcumin on Arm Circumference 7.4 Discussion 7.5 Conclusion References 8: Effect of Curcumin on Glycemic Control in Patients with Type 2 Diabetes: A Systematic Review of Randomized Clinical Trials 8.1 Introduction 8.2 Methods 8.2.1 Search Strategy 8.2.2 Study Selection 8.2.3 Inclusion and Exclusion Criteria 8.2.4 Data Extraction 8.2.5 Quality Assessment of Studies 8.3 Results 8.3.1 Study Characteristics 8.3.2 Quality Assessment 8.3.3 Effect of Curcumin on FBS, HbA1c, and HOMA-IR 8.4 Discussion 8.5 Conclusions References 9: Antidiabetic Properties of Curcumin: Insights on New Mechanisms 9.1 Introduction 9.2 Diabetes 9.3 Curcumin and Type 2 Diabetes 9.3.1 The Incretin Pathway 9.3.2 Alpha-Glucosidase and Alpha-Amylase Inhibition 9.3.3 Regulation of Glucose Transporters 9.3.4 Increased Expression of Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) 9.4 Conclusions and Future Perspectives References 10: The Effect of Curcumin in Improving Lipid Profile in Patients with Cardiovascular Risk Factors: A Systematic Review of Clinical Trials 10.1 Introduction 10.2 Material and Methods 10.2.1 Search Strategy 10.2.2 Inclusion Criteria 10.2.3 Exclusion Criteria 10.2.4 Data Extraction 10.2.5 Quality Assessment 10.3 Results 10.3.1 Search Results and Study Selection 10.3.2 Quality Assessment 10.3.3 Effect of Curcumin Supplementation on Triglycerides 10.3.4 Effect of Curcumin Supplementation on Total Cholesterol 10.3.5 Effect of Curcumin Supplementation on LDL-C 10.3.6 The Effect of Curcumin Supplementation on HDL-C 10.4 Discussion 10.5 Conclusions References 11: The Effects of Curcumin in the Treatment of Gingivitis: A Systematic Review of Clinical Trials 11.1 Introduction 11.2 Materials and Methods 11.2.1 Search Strategy 11.2.2 Eligibility Criteria 11.2.3 Study Selection 11.2.4 Data Extraction 11.2.5 Quality Assessment in Included Studies 11.3 Results 11.3.1 Search and Selection Results 11.3.2 Assessment of the Study Quality 11.3.3 Baseline Prophylaxis, Polishing, and Process of Scaling and Root Planing 11.3.4 Intervention and Regimens 11.3.5 Clinical Parameter 11.3.5.1 Plaque Index 11.3.5.2 Gingival Index 11.3.5.3 GBI 11.3.5.4 Other Clinical Parameters 11.3.6 Study Outcome 11.3.6.1 Intragroup Comparison 11.3.6.2 Intergroup Comparison 11.3.7 Adverse Effects 11.4 Discussion 11.4.1 Summary of Evidence 11.4.2 Strengths and Limitations 11.5 Conclusions References 12: Does Curcumin Have an Anticaries Effect? A Systematic Review of In Vitro Studies 12.1 Introduction 12.2 Methods and Materials 12.2.1 Protocol 12.2.2 Focus Question 12.2.3 Search Strategy 12.2.4 Eligibility Criteria 12.2.5 Study Selection 12.2.6 Data Extraction 12.3 Results 12.3.1 Search and Selection Results 12.3.2 Target Tissue/Cell 12.3.3 Type of Intervention 12.3.4 Mode of CUR Administration 12.3.5 Methods of Evaluation 12.3.6 Study Outcomes 12.4 Discussion 12.5 Conclusion References 13: The Clinical Use of Curcumin for the Treatment of Recurrent Aphthous Stomatitis: A Systematic Review of Clinical Trials 13.1 Introduction 13.2 Methods 13.2.1 Search Strategy 13.2.2 Study Selection 13.2.3 Inclusion and Exclusion Criteria 13.2.4 Data Extraction 13.2.5 Quality Assessment 13.3 Results 13.3.1 Search Results and Study Selection 13.3.2 Characteristics of the Included Studies 13.3.3 Quality Assessment 13.3.4 Effects of Curcumin/Turmeric on RAS: Intragroup Comparison 13.3.5 Effects of Curcumin/Turmeric on RAS: Intergroup Comparison 13.4 Discussion 13.5 Conclusions References 14: Antibacterial Activity of Curcumin Against Periodontal Pathogens: A Systematic Review 14.1 Introduction 14.2 Methods 14.2.1 Focused Question 14.2.2 Search Strategy 14.2.3 Screening and Identification of Eligible Studies 14.2.4 Data Extraction 14.2.5 Quality Assessment of Studies 14.3 Results 14.3.1 Search 14.3.2 Study Characteristics 14.3.3 Antibacterial Effects 14.4 Discussion 14.5 Conclusion References 15: The Clinical Use of Curcumin for the Treatment of Rheumatoid Arthritis: A Systematic Review of Clinical Trials 15.1 Introduction 15.2 Methods 15.2.1 Search Strategy 15.2.2 Study Selection 15.2.3 Inclusion and Exclusion Criteria 15.2.4 Data Extraction 15.2.5 Quality Assessment of Studies 15.3 Results 15.3.1 Search Results and Study Selection 15.3.2 Characteristics of the Included Studies 15.3.3 Quality Assessment 15.3.4 Effects of Curcumin on RA Disease Activity 15.3.4.1 Disease Activity Score of 28 Joints (DAS-28) Scale 15.3.4.2 Visual Analog Scale (VAS) 15.3.4.3 American College of Rheumatology (ACR-20) Scale 15.3.4.4 ESR, CRP, and Rheumatoid Factor (RF) 15.3.5 Side Effects 15.4 Discussion 15.5 Conclusion References 16: A Systematic Review of the Clinical Use of Curcumin for the Treatment of Osteoarthritis 16.1 Introduction 16.2 Materials and Methods 16.2.1 Eligibility Criteria 16.2.2 Search Strategy 16.2.3 Selection of Studies 16.2.4 Data Extraction 16.2.5 Quality Assessment of Studies 16.3 Results 16.3.1 Search Results 16.3.2 Study Characteristics 16.3.3 WOMAC and VAS Outcomes 16.3.4 Other Outcomes and Quality Assessment 16.4 Discussion 16.4.1 Summary of Evidence 16.4.2 Limitations 16.5 Conclusion References 17: Effects of Curcumin on Depression and Anxiety: A Narrative Review of the Recent Clinical Data 17.1 Introduction 17.2 Curcumin and MDD 17.3 Curcumin and Other Disorder Apart from MDD 17.4 Mechanism 17.4.1 Depression 17.4.2 Anxiety Disorder 17.5 Conclusion References 18: A Systematic Review of the Clinical Use of Curcumin for the Management of Gastrointestinal Diseases 18.1 Introduction 18.2 Material and Methods 18.2.1 Search Strategy 18.2.2 Study Selection 18.2.3 Inclusion and Exclusion Criteria 18.2.4 Data Extraction 18.3 Results 18.3.1 Search Results and Study Selection 18.3.2 Characteristics of the Included Studies 18.3.3 Studies on the Effect of Curcumin Consumption on IBS 18.3.4 Studies on the Effect of Curcumin Consumption in Ulcerative Colitis 18.3.5 Studies on the Effect of Curcumin Supplementation on H. pylori 18.3.6 Studies on the Effect of Curcumin on Peptic Ulcer Disease 18.3.7 Studies on the Effect of Curcumin on Crohn’s Disease 18.3.8 Studies of the Effect of Curcumin on Familial Adenomatous Polyposis 18.3.9 Studies of the Effect of Curcumin on Proctosigmoiditis 18.3.10 Quality Assessment 18.4 Discussion 18.4.1 The Effect of Curcumin on IBS 18.4.2 The Effect of Curcumin on Ulcerative Colitis 18.4.3 The Effect of Curcumin Supplementation on H. pylori Infection 18.4.4 The Effect of Curcumin on Peptic Ulcer Disease 18.4.5 The Effect of Curcumin on Crohn’s Disease 18.4.6 The Effect of Curcumin on Familial Adenomatous Polyposis 18.5 Conclusions References 19: The Use of Curcumin for the Treatment of Renal Disorders: A Systematic Review of Randomized Controlled Trials 19.1 Introduction 19.2 Methods 19.2.1 Search Strategy 19.2.2 Study Selection 19.2.3 Inclusion and Exclusion Criteria 19.2.4 Data Extraction 19.2.5 Quality Assessment 19.3 Results 19.3.1 Quality Assessment 19.3.2 Effects of Curcumin on the Inflammatory and Stress Oxidative Status of Patients 19.3.3 Effects of Curcumin on the Clinical and Biochemical Parameters of the Kidney 19.3.4 Effects of Curcumin on Lipid Profile, Glycemic Indices, and Liver Functional Tests 19.3.5 Effects of Curcumin/Turmeric on Other Outcomes and Adverse Effects 19.4 Discussion 19.5 Conclusions References 20: Curcumin for the Treatment of Prostate Diseases: A Systematic Review of Controlled Clinical Trials 20.1 Introduction 20.2 Methods 20.2.1 Search Strategy 20.2.2 Study Selection 20.2.3 Inclusion and Exclusion Criteria 20.2.4 Data Extraction 20.2.5 Quality Assessment 20.3 Results 20.3.1 Search Results and Study Selection 20.3.2 Characteristics of the Included Studies 20.3.3 Quality Assessment 20.3.4 Outcome Assessments 20.3.5 Adverse Effects 20.4 Discussion 20.5 Conclusion References 21: Curcumin: A Review of Its Effects on Epilepsy 21.1 Introduction 21.2 Herbal Medicine for Epilepsy 21.3 Curcumin in Animal Models of Epilepsy 21.3.1 Pentylenetetrazol (PTZ) Kindling Model 21.3.2 Pilocarpine Model 21.3.3 Kainic Acid Model 21.3.4 Iron Model 21.3.5 Other Studies 21.4 Conclusions References Index Prostate cancer is one of the significant causes of morbidity and mortality worldwide. Benign prostatic hyperplasia is another condition of the prostate which, like prostate cancer, is more common among ageing men and is linked to inflammation. In this study, a systematic review was undertaken to estimate the effect of turmeric or curcumin supplementation on prostate diseases. A comprehensive search was conducted in PubMed, Scopus, ISI Web of Science and Google Scholar up to 15 April 2020 to identify clinical trials assessing the effects of curcumin/turmeric alone or in combination with other herbs on prostate diseases. This led to the identification of 11 records comprising 745 patients who met the eligibility criteria. Eight studies were conducted on patients with prostate cancer, and three were on other diseases of the prostate. Although outcomes across the studies were heterogeneous, in some studies curcumin/turmeric supplementation had some favourable effects. This included beneficial effects on the levels of prostate-specific antigen (PSA) (2/6 studies), quality of life (1/2 studies), as well as on oxidative stress markers, feelings of incomplete bladder emptying, urination frequency, intermittency, urgency, weak stream, straining and nocturia. Curcumin/turmeric supplementation had no significant adverse effects among patients. This study demonstrated that turmeric or curcumin supplementation might have beneficial effects on some parameters related to prostate diseases, but it should be noted that some studies showed no effect. Therefore, further studies using curcumin-related compounds, particularly in highly bioavailable forms, are needed to assess the impact of curcumin on prostate conditions.