Influence of Nutrients, Bioactive Compounds, and Plant Extracts in Liver Diseases

By Seyed Mohammad Nabavi

Influence of Nutrients, Bioactive Compounds, and Plant Extracts in Liver Diseases provides evidence-based knowledge of the mechanism of action of natural compounds, as well as the relation of structure and function of phytochemicals in hepatitis B and C, fatty liver disease, nonalcoholic fatty liver disease, liver cancer, biliary cirrhosis, and primary sclerosing cholangitis. The effect of phytochemicals in the hepatotoxicity of drugs is also addressed. Written for health professionals seeking reliable and up-to-date information on the beneficial or toxic effects of natural compounds on liver disease, this book is sure to be a welcomed resource for nutritionists, food chemists, natural product researchers, pharmacists, medical doctors, and pharmacognosists alike.

• Explores the benefits of phytonutrients, especially those with a wide spectrum of biological activities
• Addresses various liver diseases, including hepatitis B, hepatitis C, alcoholic fatty liver disease, nonalcoholic fatty liver disease, liver cancer, biliary cirrhosis, and primary sclerosing cholangitis
• Provides reliable, up-to-date information on the natural compounds that have protective or toxic effects on liver diseases

• Language: English
• Publisher: Academic Press
• Release date: Nov 20, 2020
• ISBN: 9780128175231

Book preview

Pakistan

Preface

Seyed Mohammad Nabavia; Seyed Fazel Nabavia; Seyed Moayed Alavianb; Ana Sanches Silvac,d, a Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran,

b Middle East Liver Disease Center (MELD), Tehran, Iran,

c National Institute of Agrarian and Veterinary Research, Vila do Conde, Portugal,

d Center for Study in Animal Science (CECA), University of Oporto, Oporto, Portugal

Impressive advances have emerged in therapeutics related to liver diseases, including new chirurgic and pharmacology approaches. Hepatitis, cancer, and cirrhosis are among the most prevalent liver diseases. These diseases can often remain undiagnosed and untreated for years. Nowadays, interest in the use of natural compounds in the prevention and treatment of diseases is increasing, mainly due to their wide spectrum of biological activities including antioxidant, antimicrobial, anticancer, and antiinflammatory activities as well as modulation of the intracellular signal cascade and immunological response and a good safety profile. However, there is still a lack of scientific-based knowledge to assure the biological effects claimed by these substances, namely regarding liver diseases.

The aim of this book is to provide reliable, up-to-date information on nutrients, bioactive compounds, and plant extracts that have protective or toxic effects in liver diseases. Extensive coverage is given to the mechanism of action of these compounds and on the structure-function relationship of nutrients, bioactive compounds, and plant extracts in hepatitis B, hepatitis C, alcoholic fatty liver disease, nonalcoholic fatty liver disease, liver cancer, biliary cirrhosis, and primary sclerosing cholangitis. Moreover, their effect in the hepatotoxicity of drugs is also addressed.

The book Influence of Nutrients, Bioactive Compounds, and Plant Extracts in Liver Diseases is divided into two parts. The first part is dedicated to the hepatoprotective activity of natural compounds and plant extracts in liver diseases and each of the chapters addresses different liver diseases, including hepatitis B and C, alcoholic and nonalcoholic fatty liver disease, liver cancer, and chronic liver diseases (e.g., steatosis, fibrosis, primary sclerosing cholangitis, biliary cirrhosis). The final chapter of the first part of the book is dedicated to drug-induced hepatotoxicity. The second part of the book is dedicated to the influence of nutrients, plant extracts, and natural compounds in liver diseases. In this part of the book, special emphasis is given to the influence of omega-3 fatty acids and monounsaturated fats, vitamins (C, B3, D, and E), and other nutrients (e.g., l-arginine, taurine, and choline) in the liver. Finally, this part of the book also focuses on the antioxidants with hepatoprotective activity and on the plant extracts with hepatoprotective and hepatotoxic effects.

Health professionals have to face new challenges daily in a field that is in rapid growth, with a continuous increase in the number of compounds discovered and in the update of the health-promoting properties of a wide range of compounds, namely natural compounds.

This book will provide the most valuable and consistent information currently available on nutrients, bioactive compounds, and plant extracts that have protective or toxic effects in liver diseases. Therefore, we hope it will be a welcome resource for medical doctors, pharmacists, nutritionists, food chemists, natural product researchers, and pharmacognosists, helping health professionals to offer better therapeutic and nutritional advice.

Chapter 1: Introduction

Fatma Tugce Guragac Derelia; Ali Guragacb; Tarun Belwalc    a Department of Pharmacognosy, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Turkey

b Urology Department, Private Denizli Tekden Hospital, Denizli, Turkey

c College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China

Abstract

The liver plays an important functional role in the body and maintains homeostasis. The main function of the liver is to detoxify and thus reduce the chances of damage that can result in chronic liver diseases and death. Many allopathy medicines are available in the market that claim a protective effect on the liver and associated disease conditions; however, the chances of side effects and low effectiveness are greater. Plants contain various bioactive compounds that are shown to have protective effects against liver damage and also maintain liver health. These bioactive compounds and plant extracts exert protective effects through various cellular and molecular mechanisms. A more detailed examination of these bioactive compounds along with more preclinical and clinical trials are requested to fully utilize these naturally effective nutrients, bioactive compounds, and plant extracts in maintaining liver health and mitigating associated disease conditions.

Keywords

Liver function; Liver diseases; Bioactive compounds; Plant extract; Nutrients; Mechanism

The liver, the largest organ as well as the largest parenchymatous gland in the human body, is critically important for several vital physiological processes (Fig. 1.1), especially the regulation of immunity and the metabolism (Carotti et al., 2020; Nemeth et al., 2009).

Fig. 1.1 Main functions of the liver.

The anatomy of the liver seems to be specifically designed to maximize its functional properties. It comprises nonparenchymal and parenchymal cells (hepatocytes, HCs). The nonparenchymal cells include sinusoidal endothelial cells (SECs), hepatic stellate cells (myofibroblast-like cells, HSCs), Kupffer cells (hepatic macrophages, KCs), smooth muscle cells (SMCs), dendritic cells (DCs), pit cells (PCs), and oval cells (OCs). All these cells have different structural characteristics and cytokines are responsible for their communication among each other. The activation of signaling cascades, the metabolism of nutrients, and the clearance of toxins and infectious agents are modulated in this way (Carotti et al., 2020; Jenne and Kubes, 2013; Juza and Pauli, 2014).

HCs are predominant cell types in the liver (80% by volume) that provide the main contribution to liver functions, including synthesis, distribution, detoxification and, storage (Si-Tayeb et al., 2010). HSCs are known for their characteristic star-like morphology and they serve as a storehouse for vitamin A. The activation of HSCs results in myofibroblastic differentiation to produce collagens and extracellular matrix proteins (ECM) This production process triggers the formation of liver fibrosis (Friedman, 2008; Geerts, 2001; Gressner and Weiskirchen, 2006). KCs are mononuclear phagocytes involved in the pathogenesis of injury. Activated KCs are responsible for the release of chemokines and proinflammatory cytokines. This event promotes inflammatory cascades. The major role of KCs is the clearance of foreign materials from portal circulation (Bilzer et al., 2006; Naito et al., 2004). PCs are liver-specific natural killer cells (NKs) that contribute to immunity in the liver with potent cytolytic activity. Upon activation, PCs produce interferon-gamma (IFN-γ) and promote changes in the liver. The modulation of T cell responses and cell lysis or hepatocyte death is induced by PCs (Dong et al., 2007; Luo et al., 2000).

The liver, a well-vascularized organ, has a dual blood supply that comes from systemic circulation via the hepatic arterial flow and the gastrointestinal tract via the hepatic portal venous flow (Carotti et al., 2020). Due to its anatomic location, the liver is the first organ to be faced with nutrients, pathogens, drugs, and toxins absorbed from the intestine (Guicciardi et al., 2013). It takes the front line in host defence, and this situation makes the liver susceptible to a whole range of pathological conditions. It is able to clear blood flowing from the pancreas and intestine to the rest of the body. Therefore, one of the most important functions of the liver is detoxification (Duncan, 2000). As a multifunctional organ, the liver takes important roles in the regulation of blood clotting, immune responses, and blood glucose-lipid-ammonia levels (Juza and Pauli, 2014). It is responsible for the production and secretion of enzymes, cholesterol, hormones, cofactors, cytokines, bile, plasma proteins, and apolipoproteins (Si-Tayeb et al., 2010). The other multifold function of the liver is storing iron and vitamins such as A, B12, and D (Ramadori et al., 2008). This crucial organ is also important for the maintenance of the metabolic homeostasis of urea, lipids, triglycerides, vitamins, carbohydrates, and several ingested nutrients (Si-Tayeb et al., 2010). All these life-saving functions of the liver may be compromised by various diseases and by overexposure to viruses, toxins, and drugs. Liver dysfunction can impair the quality of life by causing several pathological symptoms in the digestive, cardiovascular, respiratory, hematopoietic, endocrine, and central nervous systems (De Wolf, 2006; Soleimanpour et al., 2015).

Liver diseases may be classified as focal liver diseases (FLDs) and diffuse liver diseases (DLDs) (Bansal et al., 2019). In the case of FLDs, the anomaly is concentrated in a little part of the liver tissue. Some of the most prevalent FLDs are hemangioma, liver cysts, and hepatocellular cancer (HCC). Hemangioma is known as the most frequently seen tumor in infancy. Liver cysts are benign malformations in the liver. The underlying pathogenic event of this disease is isolated aberrant intrahepatic bile ducts (Diez et al., 1998). Among cancers of the liver, HCC is one of the most frequently occurring in individuals. The most common cause of HCC is chronic infections caused by hepatitis B (HBV) and C viruses (HCV) (Kew, 2002). DLDs are characterized by an abnormality distributed throughout the liver tissue. Steatosis (fatty liver disease), hemochromatosis, hepatitis, cirrhosis, and fibrosis are among the most common DLDs (Luersen et al., 2015). Steatosis, namely fatty liver disease, is an abnormal condition of lipid accumulation within the hepatocyte. It is a common histopathological finding of the infection caused by HCV (Adinolfi et al., 2001). Hepatitis is a liver infection that causes inflammation and cell damage. Several viruses such as HBV and HCV are considered the main reasons for this occurrence (Tahir et al., 2015). Hemochromatosis is an iron-overload disease characterized by the overabsorption of iron from the gastrointestinal tract that reaches toxic levels in some endocrine organs, including the liver (Wallace et al., 2002). The formation of liver fibrosis begins in response to damage (infections, toxic chemicals, etc.) and causes the accumulation of ECM, particularly interstitial collagens. The scarring process leads to alterations in liver morphology and functions (Hernandez-Gea and Friedman, 2011). Cirrhosis, a late-stage version of fibrosis, involves irreversible liver degeneration. It is a consequence of long-term injury by viruses or the use of alcohol (Zhou et al., 2014).

The aforementioned liver diseases are among the most frequently encountered in clinical practices. According to epidemiological surveys, the progression of chronic liver diseases (Fig. 1.2) leads to high rates of morbidity and mortality (Asrani et al., 2019). Unfortunately, currently available allopathic therapeutics are far from ideal due to their low therapeutic efficacy, high cost, and common adverse effects. Consequently, the investigation of alternative therapeutic options with more efficacy and lower or no toxicity is vital. In this context, nutrients, bioactive compounds, and plant extracts, mainly from medicinal plants, seem like an option worth exploring (De Smet, 2002; Stickel and Schuppan, 2007). In recent decades, medicinal plants have received increasing interest among researchers for their safety profile and therapeutic value in the management of diverse diseases related to the liver. Increasing evidence from experimental investigations has indicated that various medicinal plants could be useful in this regard by virtue of their antioxidant, antilipid peroxidative, antiinflammatory, antiviral, anticancer, antifibrotic, phagocytic, free radical scavenging, and immunomodulatory properties (Ezhilarasan, 2020; Li et al., 2020; Yao et al., 2016). Several nutrients, bioactive components, and plant extracts have been reported as being healthy for the liver and mitigate the liver and associated disease conditions (Table 1.1) with a wide range of mechanisms. This book addresses in the following chapters both the hepatoprotective and hepatotoxic effects of natural compounds (nutrients, bioactives, and plant extracts).

Fig. 1.2 Stages of chronic liver diseases related to damage.

Table 1.1

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