Phyllanthus niruri in liver dysfunction
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Phyllanthus niruri is a small herb used in indigenous medicine systems to treat liver dysfunction. It contains several active constituents like lignans, flavonoids, and tannins that have been shown to protect the liver from damage caused by toxins, drugs, and viruses. Studies demonstrate that extracts of P. niruri can reduce elevated liver enzymes and protect liver cells induced by chemicals like carbon tetrachloride, galactosamine, and paracetamol overdose. The primary active constituents, phyllanthin and hypophyllanthin, have hepatoprotective and antioxidant properties. P. niruri is considered effective for treating liver diseases and injuries based on its long traditional use and
Phyllanthus niruri in liver dysfunction
- 1. ACTIVE CONSTITUENT OF CERTAIN CRUDE DRUGS USED IN INDIGENOUS SYSTEM –LIVER DYSFUNCTION – Phyllanthus niruri NAME-PRIYA BARDHAN RAY ROLL NO-05 STREAM:- MASTER OF PHARMACY IN PHARMACEUTICAL CHEMISTRY SEMESTER-1ST SUBJECT:- CHGEMISTRY OF NATURAL PRODUCTS
- 2. INTRODUCTION • WHAT IS INDIGENOUS SYSTEM? • An indigenous system is a natural form of medicine outside the stream of Western or allopathic medicine practiced by majority of doctors all over the world today. Indigenous systems have existed since time immemorial, but few of them have been developed into fully-fledged working systems. Among the most prominent of them are ayurveda, homeopathy, yoga & naturopathy, siddha, unani. Some of these, such as yoga & ayurveda, are ancient medical system in India, some like homeopathy are highly symptomatic, some like yoga depend on exercise and meditation as methods of treatment, and some, like naturopathy. avoid any artificial aid. Thus, these systems have served as inspiration for drug discovery. • WHAT IS LIVER? • Liver is the heaviest gland & second largest organ of the human body. • Primary functions of liver include Detoxification, Energy conversion, Immunity, Hormonal balance, Digestion, Fat regulation, Synthesis of Albumin, α and β globulins,coagulation factors, Storage of fluids, vitamins, minerals etc. • Liver, the key organ of metabolism and excretion has an immense task of detoxification of xenobiotics, environmental pollutants and chemotherapeutic agents. Hence, this organ is subjected to variety of diseases and disorders. • WHAT IS LIVER DYSFUNCTION? • Liver dysfunction is a condition in which liver is not working efficiently or overloaded with toxins. • Other diseases of liver include, Hepatocellular diseases (viral hepatitis, ALD), Cholestatic disease (intra and extra hepatic obstruction) Cirrhosis, Cancer (secondary or primary) , Fatty Liver, Genetic Disorders :-Hemochromatosis (iron storage) & Wilsons disease
- 3. PHYLLANTHUS • INTRODUCTION • Phyllanthus is a large genus of shrubs, trees and rare herbs of the family Euphorbiaceae, comprising more than 600 species, of which, • P. accuminatus, P. amarus, P. pulcher, P. niruroides, P. anisolobus, P. orbiculatus, P. emblica, P. oxyphyllus, P. flexuosus, P. raticulatus, P. fraternes, P. simplex, P. mullernus, P. urinaria, P. mytrifolis, P. virgatus, P. niruri and P. watsonii were investigated for their phytochemical and pharmacological properties. • The genus is found in almost over all warmer parts of the world • In this topic P. niruri will be discussed.
- 4. Phyllanthus niruri • INTRODUCTION:- It is a small erect annual herb growing up to 30–40 cm in height and is indigenous to the Amazon rainforest and other tropical areas, including South East Asia, Southern India and China.It is known since the time of “Charaka”, because it is known to be useful for various liver disorder. • SYNONYMS:- Phyllanthus, Bhui-Amla, Bhūmī āmalakī, Dukong anak, Chanca Piedra, Gale of the wind, Stonebreaker, Seed-under-leaf. • BIOLOGICAL SOURCE:- It consists of all aerial parts of the plant, Phyllanthus niruri belonging to family Euphorbiaceae. Indian variety available is Phyllanthus fraternus and Phyllanthus armarus. It contains not less than 0.25 per cent of total phyllanthin and hypophyllanthin on dried basis. • GEOGRAPHICAL SOURCE:- The plant is found growing abundantly throughout India, mainly in the states of Maharashtra, Uttar Pradesh, Punjab, Bihar, Orissa, Andhra Pradesh and some parts of Madhya Pradesh, Karnataka and Bengal. Also found in Sri Lanka. • CULTIVATION & COLLECTION:- It grows well under tropical climatic conditions. However, very dry temperature or very low temperature conditions are not preferred. It can grow up to 700 - 800 metres above the sea level. Suitable temperature ranging from 25 - 40°C with average humidity is desired. Well distributed rainfall in the range of 40 - 50 cm is suitable. Bhuiamla grows in variety of soils, preferably well drained rich organic and light textured soils. It also grows well on sandy loam to calcareous soil. Soil pH should be alkaline to acidic. Even water logging soil does not show adverse effects on its growth. Propagated well through seeds or by raising seedlings and transplanting. The plants mature within 3 to 4 months. They are usually harvested after rainy season is over, when the amount of green leaves is in abundance. Since, the active constituent is present in leaves, higher leaf mass is expected during harvesting. For harvesting, the whole plants are uprooted. The collected whole plants are cleared of external matter and are allowed to dry in shade. The fresh juice of plant is also used in medicine. Total yield of fresh herb per hectare is about 2 - 3 tones.
- 5. Phyllanthus niruri • MACROSCOPIC CHARACTER:- o COLOUR- Green to yellowish green in colour o TASTE- Bitter o ODOUR- None o STEMS- 1 - 1.5 cm in length and 1.4 mm in diameter stems are stout. o LEAVES- Short-stalked, oblong in shape and about 5 × 3 mm in size. • PHOTOGRAPH OF PLANT
- 6. EXTRACTION METHOD OF Phyllanthus niruri Fresh plants The plant was dried and grinded into fine powder Hundred gram of the powder was soaked in 1000 mL of 95% ethanol for 3 days Then, the mixture was filtered using filter paper (Whatman No. 1) Distilled under reduced pressure in a rotating evaporator (Buchi, Switzerland). The ethanol extract was then dissolved in 10% Tween 20.
- 7. ACTIVE CHEMICAL CONSTITUENTS & TYPES OF PHYTOCHEMICALS • Many of the active constituents to which the biological activity of P. niruri has been attributed include lignans, tannins, coumarins, terpenes, flavonoids, alkaloids, saponins & phenylpropanoids. • These are found in the leaves, stems & roots of this plants. • Common lipids, sterols & flavonols also occur in the plant. • It contains, leucodelphimidin alkaloids, flavonoids as quercetin, astralgin, nerurin quercitrin, isoquercitrin and rutin. It also contains |< 0.25 percent of total phyllanthine and hypophyllanthine. Mainly these two lignans are responsible for hepatoprotective & anti- hepatitis activity • Niruriside, a carbohydrate from methanolic extract of phyllunthus niruri has shown anti-HIV activity. It is specific inhibitor of REV protein, with an IC50 value of 3.3 µm.
- 8. Types of chemicals found in the plant CHEMICAL CLASS PHYTOCHEMICALS PRESENT PHARMACOLOGICAL EFFECT FLAVONOIDS Rutin, Quercetin, Quircitin, Astragalin, Catachin Blood vessel strengthener, Anti-oxidant, Anti- Cancer, Anti-inflammatory, Antiseptic, Anti- leishmanial, Antidiarrhoeal, Diuretics. TERPENES LIMONENE, P-cymene, LUPEOL Anticarcinogenic, Antioxidant, COUMARINS Ellagic Acid, Methyl Brevifolincarboxylate Chemopreventive effect in cancer, Vasorelaxent TANNINS Repandusinic Acid, Geraniin, Corilagin Reverse transcriptase inhibitor, Anti-hypertensive, Anti-fungal, Thrombolytics. SAPONINS Diosgenin Anti-fungal, Cardiovascular active LIGNANS Phyllanthin, Hypophyllanthin, Niranthin, Nirtetralin, Phyltetralin, Linletralin, Isolintetralin, Cubebin, Urinatetralin Hepatoprotective, Antigenotoxic, Anti-HIV, Anti- inflammatory, Anti-viral, Anti-tumour FLAVANONE GLYCOSIDE Nirurin, Niruriflavone Radical scavenging properties. ALKALOIDS Norsecuririne, Nirurine, Phyllanthine, Phyllochrysine, Securirine Anti-spasmodic, Anti-malarial, Anti-microbial, Anti- bacterial, Selective GABA antagonist CARBOHYDRATE Niruriside Anti-HIV, specific inhibitor of REV protein
- 9. Structure of Lignans PHYLLANTHIN HYPOPHYLLANTHIN SAR of Phyllanthin
- 10. Phyllanthus niruri IN LIVER DYSFUNCTION • Phyllanthus primarily contains lignans (e.g., phyllanthine and hypophyllanthine) & have been shown to possess hepatoprotective activity. • Phyllanthus niruri has a very long tradition of use as cure for liver diseases as it was mentioned as one of herbs for treatment of jaundice in ancient texts of Ayurveda. Many laboratory and clinical tests has proved niruri's effectiveness of protecting liver from damage (by alcohol, chemical toxines, drugs such as Paracetamol, Nimesulide, CCl4 induced liver toxicity, galactosamine induced cytotoxicity), in tonifying and strenghtening liver, balancing liver enzymes, and killing pathogens that infect liver (including hepatitis B virus, Staphylococcus aureus). • Drug-induced liver injury is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. • The Carbon tetrachloride and Galactosamine induced cytotoxicity can be decreased by the P. niruri hexane extract. Phyllanthin and hypophyllanthin protects against the CCL4- & Galactosamine induced cell lesions and GalN induced Hepatotoxicity in liver transferase enzymes levels & significantly increased protein levels. Also, the protein isolated from this plant protects the liver from Carbon tetrachloride induced hepatotoxicity and this can be measured by the liver enzymes and reduced levels of antioxidant enzymes.
- 11. Phyllanthus niruri IN LIVER DYSFUNCTION • Phyllanthus niruri can reduce Nimesulide induced hepatic damage. By measuring the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) in serum it was concluded that the levels of three enzymes are decreased in the extract treated group. By these observations intra peritoneal treatment was found to be more effective than oral administration. • The over dose of Paracetamol leads to hepatotoxicity same as viral infection. The glutamic pyryvic transaminase (GPT) levels of serum were decreased in the P. niruri extract administration. The serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) was decreased in the invivo studies. The ethanol extract and hexane extract were administered and the serum parameters (serum bilirubin, serum alkaline phosphatase, serum aspartate (AST), serum alanine transferase (ALT), hepatic reduced glutathione (GSH) were analysed and these parameters were controlled after the treatment with hexane extract and .hence, it was stated that P.niruri can control the paracetamol induced hepatotoxicity. • Protein isolated from this plant was found to enhance cell viability against Tertiary butyl hydroperoxide induced cytotoxicity and cell death; and it protects hepatocytes against Thioacetamide induced cytotoxicity. The extract prevents the alterations in GSH levels and it also reduces the lipid peroxidation induced by TAA. • Alcohol is a toxin in higher doses and when it is associated with poly unsaturated fatty acids (PUFA) induces oxidative stress & hepatotoxicity. This can be efficiently reduced by P.niruri extract analyzed by the antioxidant potentials of liver enzymes and histopathological studies. • In alcoholic extracts treated groups there was statistical significant decrease in the levels of serum bilirubin, SGOT, SGPT and ALP as compared to the hepatotoxic group. In significant reduction in the activity levels of superoxide dismutase, catalase, glutathione peroxidase, gluthaione-s-transferase, and also glutathione reductase content were observed in the liver of S. aureus intoxicated rats over controls. Thus, the results suggest the beneficial role of Phyllanthus niruri might be due to its antioxidative properties against S. aureus infection induced oxidative stress in liver.
- 12. Phyllanthus.niruri has been used to inhibit the hepadnaviridae extensively for hepatitis B virus. • MECHANISM OF ACTION:- • Phyllanthus niruri has been used to inhibit the hepadna virus and it is extensively used to treat jaundice and hepatitis B virus. It inhibits hepatitis B virus by inhibiting 50 % of DNA polymerase. Hepatitis B is the most prominent disease in emerging era. Phyllanthus niruri extract can prevent Hepatitis B by binding to the endogenous DNA polymerase and even it can bind to the hepatitis B surface antigen in in vitro. • DNA polymerase is the one of the enzyme which is responsible for the synthesis of DNA molecule and after the inhibition of these enzyme there is no formation of the DNA molecule of the virus. So the net result is multiplication of these virus totally affected. • When the phyllanthin binds on the hepatitis B surface antigen damage, of cell wall of the virus is prominently occur by this mechanism phyllanthin act as anti- Hepatitis agent.
- 13. Marketed formulations • It has been used as a cure since ancient times in Ayurveda, Siddha, Unani and other traditional systems of medicine. • This herb is available on the market in form of whole dried herb, tea sachettes, powder, capsules, tablets, and liquid alcoholic and non-alcoholic extracts. And is still commonly gathered from wild, but more and more plantations is now established. Whole fresh plants are used in the same way as dried ones. • The active compounds phyllanthin and hypophyllanthin isolated from P. niruri are major components of many popular liver tonics in India including Liv.-52.
- 14. REFERENCES 1. Kokate C.K., Purohit A.P., Gokhale S. B. ‘PHARMACOGNOSY’, Edition 43rd, 2009, Nirali Prakashan, Page No:-13.89-13.91 2. G. Bagalkotkar, S. R. Sagineedu, M. S. Saad and J. Stanslas, ‘Phytochemicals from Phyllanthus niruri Linn. and their pharmacological properties: a review’, Journal of Pharmacy and Pharmacology, 2006, 58: 1559–1570, https://www.researchgate.net/publication/6475974 3. K. Narendra, J. Swathi, K. M. Sowjanya, A. Krishna Satya, ‘Phyllanthus niruri: A Review on its Ethno Botanical, Phytochemical and Pharmacological Profile’, Journal of Pharmacy Research, 2012, 5(9), 4681-4691, https://www.researchgate.net/publication/259758390 4. V. Ramamurthy & T. Abarna, ‘Hepatoprotective Activity Of Phyllanthus Niruri Whole Plant Extract Against Staphylococcus Aureus Intoxicated Albino Rats’ , Global Journal of Biology, Agriculture & Health Sciences, 2014, Vol. 3(3), 256-260. https://www.longdom.org/archive/gjbahs-volume-3-issue-3- year-2014.html 5. Zahra A. Amin, Mehmet Bilgen, Mohammed A. Alshawsh, Hapipah M. Ali, A. Hamid A. Hadi,3 and Mahmood A. Abdulla, ‘Protective Role of Phyllanthus niruri Extract against Thioacetamide-Induced Liver Cirrhosis in Rat Model’, Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 241583, 9 pages, 2012. doi:10.1155/2012/241583