1. INTRODUCTION:The most serious disease in the world is hepatitis. Liver is the biggest organ in human body. It has area in the upper right of midriff and about size of football. We can’t live without the working of liver. It is the warehouse and body’s filter. It can have serious impact on human working when something turns out badly as practically all tissues and cells rely upon liver. The liver regulate the levels of certain substances in the body like cholesterol, hormones and sugars, which are necessary for survival and are potentially harmful when out of balance.
Essential role of liver is digesting food since it produces bile. The liver controls blood-clotting factors, which counteract excessive bleeding. Inflammation (Swelling) of the liver is alluded as hepatitis. The Ancient Greek word hepa alludes to the liver, and it implies inflammation (as in joint pain, dermatitis and pancreatitis)1.Exposure to poisons and chemicals, for example, excessive amount of liquor, autoimmune diseases that prompt the immune system to assault healthy tissues in the body, fat which may lead to fatty liver disease, microorganisms, including viruses is significant reason for hepatitis.
Liver cells called as hepatocytes give the best conditions to these viruses like HAV, HBV, HCV to replicate. As a reaction to these infection, the body’s immune system target the liver, which causes Swelling (hepatitis). On the off chance that where the inflammation is extreme (which can occur with HAV and HBV) or continues for a significant period of time (which can occur with HBV and HCV), hardened fibers can develop in the liver, a condition called fibrosis.Normal liver tissue get replaced by hardened scar tissue, which can block the normal flow of blood through the liver and truly influence its structure and capacity to function legitimately after the long time infection because of these virus. This procedure is called cirrhosis. Blood gets accumulated into the spleen and the digestive organs, if liver is seriously harmed, which may result in high pressure in these organs2. This condition is called as portal hypertension include bleeding and fluid in the abdomen (as cites). Significant liver harm diminishes the production of bile required for proper digestion, and it can diminish the liver’s ability to store and process nutrients required for survival. The inability to remove toxins from the bloodstream, which can eventually lead to mental confusion and even coma (hepatic enthelopathy) are other effect of liver damage. There are five viruses known to affect the liver and cause hepatitis: HAV, HBV, HCV, the delta hepatitis infection (HDV, which only causes problems for people infected with HBV) and hepatitis E infection (HEV). Most of the death occurs due to cirrhosis or liver cancer in men and women aquired with HBV and HCV infection3, 4.Although vaccines exist and its coverage globally averages 84% , infants whose mothers have very high viral loads, for them vaccines are not always protective. Even though several drugs treatment are available as antiviral drugs for hepatitis B and C but it is not available in developing country and not even cost effective. Till date there is no vaccine reported for HCV as the genotype of virus observed in different areas is different. HCV virus exists at least in 6 distinct genetic forms (genotypes) with multiple subtypes. Almost 50 subtypes have been identified. A global vaccine be developed so as to protect against all these variants of the virus. Even if several anti-viral drugs, including interferon-± and nucleoside analogues, have been approved for the treatment of hepatitis B. Still huge issues remain as including moderate efficacy, dose-dependent side- effects, and drug resistance. Along these lines significant medical need for safe and efficacious anti- HCV drugs exists and finding new anti- HCV agents remains a challenge5, 6.Symptoms: Infection for longer period of time with the hepatitis C virus (HCV) is known as chronic hepatitis C. Signs and symptoms of these infection are easy bleeding, Bruising, Fatigue, Poor appetite, Yellow discoloration of the skin and eyes (jaundice), Dark-colored urine, Itchy skin, Fluid development in your stomach area, Swelling in legs, Weight loss, Confusion, drowsiness and slurred speech (hepatic encephalopathy), Spider-like blood vessels on your skin (spider angiomas).2. RATIONALE AND SIGNIFICANCE OF STUDY Majority of men and women die of cirrhosis or liver cancer acquired with HBV and HCV infection. Even though vaccines exist it is not always protective in infants whose mothers have very high viral loads. Vaccines coverage globally averages 84%. Even though several drugs treatment are available as antiviral drugs for hepatitis B and C but it is not available in developing country. Till date there is no vaccine reported for HCV as the genotype of virus observed in different areas is different. HCV virus exists at least in 6 distinct genetic forms (genotypes) with multiple subtypes. There are alomost 50 subtypes of HCV and the worldwide immunization would need to secure against all of these variants of the virus.several antiviral drugs, including interferon-± and nucleoside analogs, have been approved for the treatment of hepatitis B. Still huge issues remain, including moderate viability, portion subordinate reactions, and drug resistance. Subsequently there is significant medicinal requirement for safe and efficacious anti-HCV drugs exists and finding new anti-HCV agents remains a challenge.. The Indian ancient literature mentions various medicinal herbs that may be useful for hepatitis; however they are not approved for anti-viral treatment. Thus there is a growing need to focus on medicinal plants as anti-hepatitis agents and establish their safety as well as efficacy in the treatment of hepatitis7, 8,9,10.Nanotechnology is a field of applied science and technology which include application of nanoparticles and are currently under development and intends to develop devices and dosage forms in the range of 1 to 100 nm. The drug is dissolved, entrapped encapsulated or attached to nanoparticle matrix. Nano-sized drug delivery systems of herbal drugs have a potential future for enhancing the activity and overcoming problems associated with plant medicines 11. Nature is a storage facility of various restorative herbs containing dynamic bio-atoms which are potential source of medication against wellbeing and ailments. Fossil record of use of plants as medication dated back in any event to middle Paleolithic age just about 60,000 years ago.The nanoparticles have approached as the methodology in novel medication for well-organized delivery of drugs used in the treatment of different various diseases by crossing the reticulo endothelial system, improved penetrability and retention effect and tumor-specific targeting. Nanotechnology is the field of medicine with promising hopes for assistance in diagnostic and treatment innovations just as improving quality of life. Humans can possibly live more beneficial lives sooner rather than later because of the developments of nanotechnology.12-15.Novel drug delivery systems not just lessen the repeated administration to defeat non-compliance, yet additionally help to increase the therapeutic value by reducing the toxicity and increasing the bioavailability, etc. As of late, pharmaceutical researchers have moved their concentration to designing the drug delivery system for herbal medicines using a scientific aprroach. For quite a while herbal medicines were not considered for advancement as novel formulations due to lack of scientific justifcation and processing difficulties, for example, standardization, extraction and identification of individual drug components in complex polyhedral systems. Neverthless, modern phytopharmaceutical research solves the scientific needs for herbal medicines as in modern medicine, which gives way for developing novel formulations such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles, and so on17-19.The project work is thus aimed to study various medicinal plants that may be useful in the treatment of hepatitis and possibly identify the active ingredients responsible their activity.These herbal plants can further be evaluated for their synergy in the treatment of hepatitisThe study can put forth potential herbal treatment of hepatitis.3. LITERATURE SURVEY:Chung Y, et al.,16 reported that despite the fact that recently developed direct-acting antiviral (DAAs) have revolutionized hepatitis C treatment, most of them are unsuitable for immunotherapy because of risks of resistance, consequently requiring combination with interferon (IFN)-alpha, ribavirin, or additional DAAs. The high cost DAAs restricts their accessibility to most parts of the world. These article through light upon activity-based and fraction-guided analysis of extracts from the medicinal plant Phyllanthus urinaria (P. urinaria), which yields fraction 13 (F13) as possessing the most potent inhibitory activity against early viral entry of cell-culture HCV infection. Mukherjee K. P, Wahile A, Kumar V et al.,7 detailed that plant-based therapeutic agents like silybin, silymarin from Silybum marianum (milk thistle), are accepted and uutilized worldwide as hepatoprotective. Many plants mentioned in the ISM, like Andrographis paniculata and Phyllanthus amarus are used either alone or in combination as hepatoprotectives. Further more instability in highly acidic pH, liver metabolism, short half-life, solubility etc. are some limitations of these herbal extracts/ plant actives.Quanfang Huang et al., 20 detailed the isolation and identification of an anti-HBV compound from herb Hydrocotyle sibthorpioides (Apiaceae). Results reported that asiaticoside could efficiently inhibit HBV replication both in vitro and in vivo, and asiaticoside may be a major bioactive ingredient in Hydrocotyle sibthorpioides. Ethnopharmacological relevance: Hydrocotyle sibthorpioides (Apiaceae) have been utilized as a traditional medicine for the treatment of fever, edema, detoxication, throat pain, psoriasis and hepatitis B virus infections in China. EASL 20121 reported that the absence of reverse transcriptase proof reading activity leads to frequent transformation of the viral genome. This results in the outcome of coexistence of genetically distinct viral species in infected individuals, also called viral quasi species, which evolve depending on the pressure from the host environment.Shelley N. Facente et. al.,22 detailed that the only a fraction of HCV-infected individuals are offered treatment within specialty settings although direct-acting antiviral regimens have driven up demand for hepatitis C virus (HCV) treatment. In 2016 to 2017, the San Francisco Health Network (SFHN) worked to improve treatment access and better understand barriers still inhibiting SFHN primary care providers from prescribing HCV treatment.Jordan Mayberry et. al., 23 reported that HCV infections typically goes unrecognized at onset and develops into a chronic infection that can prompt to cirrhosis, liver failure and liver cancer. In the last 5 years safe novel treatments without significant side effects and nearly 100% effective became available. Sustained viral response (SVR”no virus detectable 12 weeks after end of treatment) is synonymous with life-long cure. Ongoing surveillance for liver cancer is required for SVR pateints with cirrhosis. Other challenges like identifying those who are not aware but have infection and providing treatment for those lacking funding.Paul G. Barnett, Vilija R. Joyce et. al., 24 elaborated that previous treatment gaps for HIV-positive patients were closed by uses of interferon-free direct-acting antiviral regimens . Unobstrusive treatment gaps stay for African American and Hispanic patients and for those with substance use disorder. Health plans, same negotiated discounts and lack of special appropriation are limiting treatment to patients with demonstrated liver disease who are abstinent from drugs.Missaka Priyadarsana Bandara Wijayagunawardane and co-authors25 reported about the indegenious herbal receipes for treatment of hepatitis C. The major causes of morbidity and mortality throughout the world are hepatic fibrosis and its end satge sequelae of cirrhosis and liver cancer. Their predominance is rising, largely due to the increasing impact of chronic viral hepatitis and nonalcoholic steatohepatitis (NASH). Therapies currently available are only to manage patients suffering from or progressing to liver cirrhosis. In Western medicine the lack of treatments to target the arrest or reverse the progression of disease hampered the clinicians to successfully treat these patients with established cirrhosis. This review focused on the prevention and treatment of chronic liver diseases using study of hepatic fibrosis and important herbal medicines .Pradyumna R. Raval and Ramchandra M. Rava26 reported the Treatment of infective hepatitis: Where biomedicine has no answers, Ayurveda has. Ayurvedic medicine definitely has a lot to offer to the society by way of improving liver health and this is quite evident from the various studies reported in literature. G. Brusotti, I. Cesari et. Al., 27 elaborated the isolation and characterizations of bioactive compounds form the plant resources. It includes different methods which includes the combination of extraction and sample preparation tools and analytical techniques for isolation and characterization of bioactive secondary metabolite from the plant resources.4. AIMS AND OBJECTIVES:Medicinal Plants are integral part of human health system. India is one of the leading bio-diversity centers with the presence of over 50000 different plant species. From this flora 20000 to 30000 of them have good medicinal value. Among those only 6000 are used in different sources.The present centuries have more health problems than earlier centuries. Drugs for disease like AIDS, cancer, Alzheimer’s, Parkinsonism, hepatitis, dengue, are yet to be discovered. Multidisciplinary research on plants has lead to many drugs as well as prototype active molecules and biological tools. There is need for development of complementary and alternative drugs for HCV infection from clinical and economic point of view. Hepatitis C virus belongs to family Flaviridae which has infected several populations worldwide.However, there is neither vaccine nor effective antiviral drugs treatment. The advent of herbal treatment / folk medicine in the management of hepatitis, has paved way to research in this area. The study is designed to find the phytoconstiutents and investigate the anitviral activity of the selected herbs. Thus the aim of the present work is to screen various medicinal plants based on literature survey followed by their extraction, characterization and evaluation as antihepatitis drugs. So work will be done to achieve following objectives:- Selection /Screening of medicinal plants with potential antihepatitis acitvity Extraction of selected medicinal plants Phytochemical screening and Characterization of extracts Evaluation of antihepatitis C activity5. METHODOLOGIES AND TECHNIQUESThe selected plants will be procured and authenticated. Different extracts of selected medicinal plants will be prepared. The prepared extracts will be characterized by chromatographic and non-chromatographic techniques followed by evaluation of anti-dengue activity. 6. POSSIBLE OUTCOMES: The study may lead to development of herbal intervention for the treatment of dengue, which may be efficacious and safe as compared to the current line of treatment.7. PLAN OF RESEARCH:1. Literature survey2. Selection of medicinal plant- The selection of medicinal plants will be based on their potential anti-hepatitis activity and availability.3. Procurement of selected medicinal plants & authentication4. Extraction- The extraction of selected plants will be carried out by different solvents using suitable technique. Optimization of solvent and extraction technique to be used will be carried out. The extracts will further be evaluated by various chromatographic and non-chromatographic techniques.30-33 (Table 1)5. Characterization of extract- Various extracts of selected plants will be subjected to phytochemical evaluation29.6. Evaluation of anti-hepatitis activity- In vitro/ In vivo cytotoxicity screening to determine maximum nontoxic dose followed by evaluation of anti-hepatitis activity