Plant-derived Hepatoprotective Drugs

The largest organ in the human body is the liver which captures 2 to 3% of the human body weight, located on the right side of the anterior quadrant in the abdomen and below the anterior hemidiaphragm ribcage. It performs various important functions such as digestion of food, protein production, fluid production, detoxification of waste, etc. Liver injury known as liver trauma can be categorized into four types: hepatocellular, autoimmune, cholestatic and infiltrative. Drug-induced liver injury can match with any form of acute or chronic liver injury. Acute injury to the liver is mainly due to the action of cytochrome P450, which disintegrates drugs into electrophiles or free radicals; these reactive metabolites can covalently act on protein and unsaturated fatty acids for induction of lipid peroxidation which leads to calcium homeostasis or death. Toxicology of the liver is a complex concept that entails either concurrent as well as sequential events. These events determine the pathways, severity and effects of liver injury. Pharmacogenetics has made great progress in current years which indicates the creation of refined algorithms that take drug, host and environmental risk variables into account, allowing for the selection of better medicine based on accurate risk-benefit ratio calculations. In this chapter, we will discuss the anatomy, functions of the liver, types of liver injury, risk factors, and various treatment strategies for the treatment of liver diseases.

With its ability to self-regenerate, the liver is considered an important gland in the human body, performing essential functions such as the production of vital proteins, lipids, lipoproteins, glucose homeostasis as well as the production and secretion of vitamin stores and bile acids. Therefore, any impairment of the organ can lead to serious problems in our bodies. There are various forms of disorders associated with an unhealthy liver, which affect the liver in different ways and can be detected by observing various general symptoms and some specific diagnostic tests. To treat and control these hazardous effects on our bodies, various medicines are available in the market that are mainly derived from plants and plant products. As they have fewer side effects, herbal medicines have attracted much attention for alleviating various liver diseases while maintaining a healthy lifestyle. Moreover, nanobased delivery of natural products shows higher hepatoprotective activity than crude extracts. In this chapter, various hepatoprotective functions of medicinal plants and their nano-based drug delivery have been highlighted.

The liver plays an essential role in metabolic management, and detoxification associating the metabolisms of toxins, lipids, alcohols, carbohydrates and various drugs. It also plays a role in the immune response. However, some conditions, such as viral infections (hepatitis), inflammation, continuous liquor consumption, periodic use of antibiotic-related drugs, and non-alcoholic fatty liver illness, can produce free radicals and cytokines, enhance lipid peroxidation, and induce damage to hepatocytes. Hepatoprotective agents are often the treatment of choice to improve liver function and protect the liver from exposure to harmful compounds. Based on scientific reports, Silybum marianum, Moringa oleifera, Garcinia mangostana, Glycyrrhiza glabra, Mangifera indica, Amaranthus spinosus, Andrographis paniculata, Phyllanthus species (amarus, niruri, emblica), Curcuma species (longa, xanthorrhiza, manga), and Citrus species (aurantium, sinensis, unshiu, grandis) have been broadly administered for the liver ailments therapy through antioxidant-associated abilities. Impressive studies have exposed that the health-promoting outcomes of bioactive constituents derived from plants have often been applied to their antioxidant characteristics and raise the cellular antioxidant protection system, scavenge free radicals, suppress lipid peroxidation, stimulate anti-inflammatory capacity, and assure the liver from destruction. These compounds are chlorogenic acid, curcumin, quercetin, hesperidin, rutin, betalains, apigenin, silymarin, phyllanthin, mangiferin, α-mangostin, bellidifolin, ginsenosides, glycyrrhizin, lycopene, and andrographolide.

The liver is an important organ in the body's metabolism and excretory system. The prevalence of many forms of hepatic illnesses is on the rise, resulting in a major increase in morbidity and mortality worldwide. Viral hepatitis, alcoholic/non-alcoholic fatty liver disease, liver fibrosis, cirrhosis, hepatocellular cancer, and drug-induced liver injury are all important health concerns that take millions of lives each year throughout the world. Pharmaceutical medications are frequently linked to liver injury, and so have limited efficacy in the treatment of liver diseases. As a result, herbal drugs have grown in popularity and are widely used. For a long time, herbal remedies have been utilized to treat liver problems. There are a variety of herbal preparations on the market. Herbal medicine has been used to treat liver disorders for thousands of years. A large range of medicinal plants have been examined as hepatoprotective agents in preclinical and clinical investigations. However, more thorough research is needed to screen and evaluate the usage of herbal medicines in the treatment of diverse liver illnesses. The goal of this review is to compile information on promising medicinal plants that have been tested in hepatotoxicity models using cutting-edge scientific methods. The damage to liver cells caused by various toxic chemicals (antibiotics, chemotherapeutic agents, carbon tetrachloride (CCl4 ), thioacetamide (TAA), and microbes have been well studied. In this scenario, the current synthetic medications to treat liver problems promote more liver damage. The purpose of this chapter is to examine various hepatoprotective plants and herbal formulations. 

Various parameters/guidelines regulating the safety and efficacy of herbal pharmaceuticals, as well as their manufacturing and distribution, have been strongly implemented by regulatory bodies. To understand the pre-marketing requirements, the legislative status of herbal drugs/products was analyzed in this chapter for various countries in Southeast Asia, Africa, America, Europe, and Austria. Apart from the challenges of herb availability and conservation, it has been shown that there is a lack of harmony in the regulatory requirements for herbal products across the world. A critical evaluation was performed in order to detect the obstacles in the harmonization of herbal products. The worldwide trade and development of herbal products are being hampered by these issues. The herbal drug industry is inadequately regulated in most countries, and herbal medicines are often neither registered nor controlled. Quality compliance and assurance of the safety and efficacy of the marketed herbal drugs are major issues faced by developing as well as developed countries across the globe. The problem arises when herbal medication is utilized without legitimate permission, or in huge dosages, or in combination with other drugs for a longer period, or without discussion with a doctor, and produced properly. Taking these factors into account, the World Health Organization's International Drug Monitoring Program (WHO) has published standards for herbal assessment and quality control testing in order to improve the safety and efficacy of herbal-based therapeutics. This chapter covers the importance of regulatory affairs to be used in the processing of herbs and herbal products, and a comparative study of regulatory situations in different countries

Liver diseases are considered a major global public health problem that is always underestimated. Damage to hepatocytes caused by drugs, toxins, viruses, etc. is a major cause of hepatic disorders, including liver cancer. Oxidative stress is considered a primary underlying mechanism of liver disorders. Cytokine produced in response to ROS plays an important role in damaging the liver. Plants are also considered an important source of phytoconstituents with hepatoprotective activity. As part of the diet, edible plants could play an important role in protecting the liver from injury caused by oxidative stress, microorganisms, or other exogenous substances. Many vegetables, fruits, and spices have been investigated for their hepatoprotective activity in pre-clinical studies. Phytoconstituents like curcumin, catechin, rutin, myristicin, fumaric acid, silybin, picroside, kutkoside, glycyrrhizin, silymarin, and apigenin were found to exhibit hepatoprotective and antioxidant activity through diverse mechanisms including antioxidant activity, and anti-inflammatory activity. This chapter highlighted edible plants with hepatoprotective activity.

The liver is the body's primary organ responsible for metabolism and excretion. Oxidation, reduction, hydration, condensation, hydrolysis, conjugation, and isomerization are some of the metabolic routes used by the human liver to metabolise chemicals. Any of the aforementioned processes can be disrupted, resulting in liver cell damage or hepatotoxicity, which can lead to a variety of disorders. These disorders are linked to increased death rates over the world. Medicines, chemicals, dietary changes, and herb-induced liver injury via hepatotoxins can all cause hepatotoxicity. A number of herbal and herbomineral preparations are available in Ayurveda, the traditional Indian Medicine, which has been investigated for their hepatoprotective potential to treat different types of liver disorders. The present review is focused on different herbal plants that have the potential to cure hepatotoxicity.