Jacobs Journal of Gastroenterology and Hepatology

Herbal Drugs-An approach for the Treatment of Liver Disorders

*Swapnil Pandey
Department Of Pharmacognosy, Varanasi College Of Pharmacy, Varanasi, India

*Corresponding Author:
Swapnil Pandey
Department Of Pharmacognosy, Varanasi College Of Pharmacy, Varanasi, India
Email:pankajmeen@rediffmail.com

Published on: 2019-05-16

Abstract

The liver is an amazingly complex organ which virtually affects every physiological process of the body. The liver is the largest glandular organ in body, and has more function than any other organs. Hepatic disorders which stem from a stressful life style, inappropriate eating habits and lack of exercise have become one of the major causes of morbidity and mortality in human being. The acute hepatic symptoms may be cured by some general prevention such as avoidance of constipation and balance between intake quantity of protein and disaccharides in normal food. An alternative and a progressively increasing adaptation is the use of herbal extracts. Many of the plant-based drugs show effective response to managing the hepatotoxicity and secondary symptoms of liver damage. While, the models used for conventional hepatotoxicity evaluation are still outdated, in the present review we have attempted to provide an updated information of the molecular pathogenesis and aspects for the role of herbal pharmacotherapy in alleviation of hepatic ailments. Furthermore, we have attempted to summarize the critical findings on hepatoprotective herbs over a period of last 20 years.

Keywords

Hepatotoxicity; Hepatoprotective herbs; Hepatic injury; Hepatic function test; Silybum marianum; Allium sativum

Introduction

Medicinal plants may serve as a vital source of potentially useful new compounds for the development of effective therapy to combat a variety of disease. Herbal medicine is used by about 80% of the world population primarily in the developing countries for primary health care. Ancient literatures also mention herbal therapy for age related diseases namely memory loss, osteoporosis, diabetic wounds, immune and liver disorder, etc. 1998. The Indian traditional medicine like Ayurveda, siddha and unani are predominantly based on the use of plant materials. Herbal drugs have gained importance and popularity in recent year because of their safety, efficacy and cost effectiveness [1].Recently, World Health Organization defined traditional medicine including herbal drugs as therapeutic practice that have been in existence, often for hundreds of years, before the development and spread of modern medicine and are still in use today [2]. The association of medical plants with other plants in their habitat also influences their medicinal value in some cases. One of the most important and well documented uses of plant product is their use as medication. Hence, there is an even increasing need for the safe medication[3].

Role of Liver in Human Physiology

Liver is absolutely crucial to life. Because it is responsible for so many vital functions, when the liver is damaged, our health is affected. The liver can do 500 functions - that’s some multitasking! This is one powerful organ, the one organ in the body that is capable of regenerating itself. There is no organ that is more important to healthy metabolism than the liver- in many ways, it is as central to metabolisms the heart is to the circulation of blood. The liver plays a critical role in four key areas of metabolism: fuel management, nitrogen excretion, the regulation water distribution between the blood & tissues, and the detoxification of foreign substances. It also produces prothrombin and fibrinogen which helps in blood clotting and heparin, a mucopolysaccharide, sulphuric acid and ester that helps keeps blood from clotting within the circulatory system. The liver converts sugar in to glycogen. Liver play a vital role for disease free life. Because of

1.Storage of vitamins, minerals, and sugars.

2. Filter your blood and remove harmful substances.

3. Store extra blood for emergencies. Being prepared can be a lifesaver.

4. It keeps the electrolyte balance maintained. Electrolytes like calcium and potassium help the heart to keep beating.

5. It helps to utilize fat-soluble vitamins like A (for eyesight), D (helps calcium to absorb), E (good for wound healing), F (essential fatty acids for normal growth and behavior), and K (helps blood to clot).

6. It helps use or eliminates excess hormones.

7. It creates bile, which helps break down fats.

8. It helps to manage blood sugar - helping to keep blood sugar stable. Without the liver functioning correctly, it can lead to diabetes or hypoglycemia, or reactive hypoglycemia (highs and lows).

9. Processing digested food from the intestines.

10. Whatever wastes that the kidney does not remove from circulation, the liver removes from circulation.

11. Clearing bacterial infection and combating infections in general. An impaired liver means an impaired ability to fight infections.

12. Neutralizing toxins and drugs.

A few signs that the liver needs to be cleansed could be (if other things are not causing the symptoms)

If you experience any of the following symptoms, you may be experiencing autointoxication (a process whereby you are poisoned by substances produced by your own body as a result of inadequate digestion and elimination),

1. Breaking out in acne - which, of course is hard on the self-esteem

2. Hair breakage

3. Nightmares - bad dreams

4. Insomnia

5. Exhaustion

6. Flu-like feelings

7. Difficulty thinking or focusing

8. Pain under right rib

9. Blood sugar imbalance

Cause of Liver Disorders

Liver diseases have become of the major cause of morbidity and mortality in human being. Among the many diseases that can affect the liver the most common is viral hepatitis (figure1). Hepatitis can be caused by drugs, viruses, bacteria and parasites like amoebiasis and giardiasis. The use of natural remedies for the treatment of liver diseases has a long history and medicinal plants and their derivatives are still used all over the world in the form or the older for this purpose [4]. The liver protective plants contain wide variety of chemical constituent phenols, coumarins, monoterpenes, carotenoids, glycoside and polyphones. The main cause of hepatotoxicity is yet unknown. It appears to involve two pathways- direct hepatotoxicity and adverse immune reaction [5]. The most common hepatotoxicity induced by the bio activation of drugs to the active metabolites, which have ability to react interact with cellular macromolecules such as proteins, lipids and nucleic acid leading to protein dysfunction, lipid peroxidation, DNA damage and oxidative stress (figure 2).

The reactive metabolites may induce disruption of ionic gradients and intracellular calcium stores, resulting in mitochondrial dysfunction and loss of energy production. Its dysfunction releases excessive number of oxidants which in turn causes injury to hepatic cells. Activation of some enzymes in the cytochrome P-450 system such as CYP2E1 also leads to oxidative stress (figure3). Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside the liver. This promotes further liver damage. This impairment of cellular function can culminate in cell death and possible liver failure. Thus, it is the delicate balance of inflammatory and hepatoprotective mediators produce after the activation of the innate system that determines an individual’s susceptibility and adaptation to hepatic injury [6].

Figure 1: Difference between normal liver cells and infected liver cells.

Figure 2: Route of hepatic injury

Figure 3: Mechanism of liver injury

Management of Hepatic Encephalopathy

Some most common factors which helps to manage the hepatic injury.

• Avoid constipation.

• Avoid other precipitating factors.

• Maintain adequate protein and energy intakes.

• Non absorbable disaccharides- lactulose 20-40 ml daily.

• Pharmacological evaluation of hepatoprotective plants.

• To investigate hepatotoxic substances, it is customary to subject animals to a range of toxic substances. These include carbon tetrachloride, alpha amanitin and phalloidin, Paracetamol, liquid paraffin, thioacetamide etc., which induce animals’ liver damage, and changes in serum ALT and AST and further histological observation are evaluated.

•  In vivo models: The various in vivo models are studied for the evaluation of hepatic protective drugs. The models are listed below.

• Paracetamol induced hepatotoxicity: The method of acetaminophen induced acute hepatotoxicity can be used most widely. Albino Rats are used for the pharmacological evaluation of the test drug. The standard and test drug of various concentrations is given to the rats and different parameters like evaluation of serum bilirubin, SGPT, SGOT are tested.

Carbon tetra chloride induced hepatotoxicity: The carbon tetra chloride is used for the induced hepatotoxicity in to the animal. The animal shows fatty changes, gross necrosis, broad inflammation of the lymphocytes and Kupffer cells around the central vein. SGPT, SGOT, ALP serum bilirubin is most sensitive test which are consider as an index to estimate the liver disease.

Thioacetamide induced hepatotoxicity: Adult female wistar rats weighting 180-200 g are kept in wiere bottomed cages at control temperature with 12 h. The thioacetamide and test group received the saline from the rats and evaluated different parameters like SGPT, SGOT, ALP and AST.

Alcohol and carbon tetra chloride induced hepatotoxicity

Carbon tetra chloride and liquid paraffin induced hepatotoxicity [7]

In vitro models: Developed in the past years. Next to their use in drug development, they can also be applied to study environmental toxins and their hepatotoxicity. The 3 main approaches are ex vivo isolated and perfused organ models, precision-cut liver slice and cell culture models. Although the advantage of whole organ perfusions is based on the assessment of physiologic parameters such as bile production and morphologic parameters such as tissue histology, cell culture models can be efficiently used to assess cellular metabolism, cytotoxicity and genotoxicity. The advantage of precision-cut liver slices is based on the juxtaposition of cellular assays and tissue morphology.

Hepatoprotective Herbs

Silybum marianum: Milk thistle (Silybum marianum) has a long and important history in herbal medicine dating back over 2,000 years in European herbal traditions. The root, leaf and steam have medicinal use. But flavonolignans most widely used now a days. The extracts were injected to the rats, at a dose of 25 mg kg-1 body weight together with thioacetamide at a dose of 50 mg kg body weight. Significant decrease in the activity of aminotransferases, alkaline phosphatase and bilirubin was observed in the groups treated with extracts and compared with the group that was treated only with thioacetamide [8]. Other plants dugs which are reported as hepatoprotective is given below:

Table 1: List of various hepatoprotective herbs with proper biological screening method.

Table 2: List of various Hepatic functions tests with their interpretations [50].

Discussion

Hepatoprotective disorder is the most common disorder and affects normal physiology of liver. This review discusses the plant drugs which have shown significant result as the hepatoprotective agent even in some cases with good potency. There is an increasing demand by patient to use the natural product with hepatoprotective activity. Large number of herbal species has been used traditionally as a medicine against hepatotoxicity ailments. Many of them have been studied scientifically and proved to be beneficial for liver as a hepatoprotective. The success has been attained to isolate various single chemical entities responsible for hepatoprotective activity [51]. Most of the plant extract is water soluble so the achievement of successful bioavailability is tough task. To overcome these problems different kinds of targeted formulation have been developed. In this aspect phytosomes and liposomes have emerged as prospective tools for delivery of bioactive to hepatic tissues. The different kind of marketed formulation such as silyphos phytosomes, ginkgo liposomes, quercetin phytosomes are available in the market which achieve maximum bioavailability [52].

Conclusion

Plants have played a remarkable role in health care since the ancient time. traditionally plant-based medicine exerts a great deal of importance to people living in developing countries and also lead to discovery of new drugs. Herbal medicines make an enormous contribution to primary health development. In the recent day’s hepatotoxicity is a major cause for the human being so this review includes all the study of plants drug which gives significant response for the treatment of hepatotoxicity. The research of botanical medicines shows different result for the treatment of liver dysfunction. The different herbal remedies such as green tree, ginger, and curcumin are the well-known drugs for the treatment of acute liver toxicity. In other way many hepatic trails are done by the scientist today and much research yet to be done, but list of these plants has an appreciable response for the treatment of viral hepatitis, cirrhosis of liver and liver toxicity. The single drug cannot be show significant response; the combination of two or more plant extract may prove very effective treatment of liver disorders caused by over drinking of alcohol, toxic elements and different viral infections. Acknowledgement: I have taken efforts in this review paper. However, it would not have been possible without the kind support and help of Library Personals of organizations, thus I would like to extend my sincere thanks to all of them.

References

1. Agarwal SS. Development of hepatoprotective formulations from plant sources: In Pharmacology and Therapeutics in the New Millennium. New Delhi 2001; 357- 358.

2. Handa SS. Plants as drugs: The Eastern Pharmacist1999; 79 -85.

3. Thyagarajan S.P, Jayaram S, Gopalakrishnan V, et al. Herbal medicines for liver diseases in India. J Gastroenterol Hepatol 2002; 17(3): 370-376.

4. Nadeem MPC, Dandiya P.C, Pasha M, et al. Fitoterapia 1997; 68: 245-251.

5. Lewis H.W, Elvin-Lewis M.P.H. Medical Botany: Plants Affecting Man’s Health. American Anthropological Association 1978; 10(1): 15-16.

6. Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 2007; 76(3): 391-396.

7. Mukharjee k Pulok. Evaluation of herbal drugs an approach to evaluation of botanicals. Published by Horizons pharmaceutical 2012; 519-521.

8. Madani H, Talebolhosseini M, Asgary S, et al. Hepatoprotective activity of Silybum marianum and Cichorium intybus against thioacetamide in Rat. Pak J. Nutrition 2008; 7(1): 172-176.

9. Rajalakshmi GK, Jothi Arul, Venkatesa RS, et al. Hepatoprotective Activity of Andrographis paniculata on Paracetamol Induced Liver Damage in Rats. Journal of Pharmacy Research 2012; 5(6): 2983-2986.

10. Chattopadhyay RR, Bandyopadhyay M. Possible mechanism of Hepatoprotective activity of Azadirachta indica leaf extract against Paracetamol induced hepatic damage in rats 2005;37(3): 184-185.

11. Nasim ilyas, M. Sadiq, Adnan Jahangir. Hepatoprotective effect of garlic (allium sativum) and milk thistle (silymarin) in isoniazid induced hepatotoxicity in rats. Biomedica 2011; 27: 166-170.

12. Jeong HG, You HJ, Park SJ, et al. Hepatoprotective effects of 18-glycyrrhetinic acid on carbon tetrachloride induced liver injury inhibition of cytochrome P450 2E1expression. Pharmacol Res 2002; 46(3): 221-227.

13. Chattopadhyay RR, Bandyopadhyay M. Possible mechanism of Hepatoprotective activity of Azadirachtaindica leaf extract against Paracetamol induced hepatic damage in rats. Journal of Ethnopharmacology 2003;89(2- 3):217-219.

14. Aghela N, Rashidib I, Mombeinia A. Hepatoprotective Activity of Capparis spinosa Root Bark against CCl4 Induced Hepatic Damage in Mice. Iran. J 2007; 6 (4): 285- 290.

15. Rawat A.K.S, Tripathi S.K, Showme U. Hepatoprotective activity of Boerhaavia diffusa L. roots: A popular Indian ethnomedicine. J Ethnopharmacology 1997; 56(1): 61- 66.

16. Somchit MN, Sulaiman MR, Noratunlina R. Hepatoprotective effects of Curcuma longa rhizomes in paracetamol induced liver damage in rats. International journal of Pharmacology 2005; 1(3): 252-256.

17. Kumar Mukesh, Ahuja Munish, Sharma Surendra. Hepatoprotective Study of Curcumin- Soya Lecithin Complex. Scientia Pharmaceutica 2008; 76: 761-774.

18. Haldar Kanti Pallab, Gupta Malaya, MazumderKantiUpal, et al. Hepatoprotective Effect of WedeliaCalendulaceae against Thioacetamide Induced Liver damage in Rats. Pharmacology online 2007; 3: 414-421.

19. Singaravel S, Srinivasan D, JothivelN,Rsilingam D, et al. Hepatoprotective Activity of Camellia Sinensis and its Possible Mechanism of Action. PharmaThera 2008; 7(1): 9-14.

20. Aghela N, Rashidib I, Mombeinia A. Hepatoprotective Activity of Capparis spinosa Root Bark against CCl4 Induced Hepatic Damage in Mice. Iranian Journal of Pharmaceutical research 2007; 6: 285-290.

21. Vetrivel R, Shanmugavalli N, Greety S, et al. Hepatoprotective effects of Cassia tora on CCl4 induced liver damage in albino rats. J. Sci Tech 2009; 2(3): 41-44.

22. Sadeghi H, Nikbakht M, Ghaitasi I. Hepatoprotective effect of Cichorium intybus on CCl4- induced liver damage in rats. J.Biochem 2008; 2 (6): 141-144.

23. Jeong H.G, You H.J, Park S.J, et al Hepatoprotective effects of 18-glycyrrhetinic acid on carbon tetrachloride induced liver injury inhibition of cytochrome P450 2E1 expression. Pharmcol Res 2002; 46(3):221-227.

24. Shenoy K.A, Somayaji S.N, Bairy K.L. Hepatoprotective effects of Ginkgo biloba against carbon tetra chloride induced hepatic injury in rats. J. Pharmacol 2001; 33: 260-266.

25. He S.X, Luo J.Y, Wang Y.P. Effects of polyprenols from Ginkgo biloba on carbon tetrachloride-induced liver injury in rats. Fitoterapia 2011; 82(6): 384-340.

26. Kingshuk Lahon, Swarnamoni Das. Hepatoprotective activity of Ocimum sanctum alcoholic leaf extract against paracetamol-induced liver damage in Albino rats. Pharmacognosy Res 2011; 3(1): 13-18.

27. Bhattacharjee Rajesh, Parames C. Sil. Protein isolate from the herb Phylanthus niruri L(Euphorbiaceae). plays hepatoprotective role against carbon tetrachloride induced liver damage via its antioxidant properties. Food Chem Toxicol 2007; 45(5): 817–826.

28. Akhtar M. S, Amin M, Alamgeer Maqsood Ahmadand. Hepatoprotective Effect of Rheum emodi Roots Against Paracetamol-induced Hepatotoxicity in Rats. J.Ethnobotanical Leaflets 2009; 2: 310-315.

29. Singh.A, Malhotra S, Subban R. Dandelion (Taraxacum officinale)-Hepatoprotective Herb with Therapeutic Potential J.Pharmacog 2008; 2(3):163-167.

30. Park J.Y, Park C.M, Song Y.S. Hepatoprotective Activity of Dandelion Taraxacum officinale Water Extract against D Galactosamine-Induced Hepatitis in Rats. Nutrition (American society for Nutrition) 2008; 21(6): 177-183.

31. Orhan DD, Orhan N, Ergun E , et al. Hepatoprotective effect of Vitis vinifera L. leaves on carbon tetrachloride induced acute liver damage in rats. J. Ethnopharmacol 2007; 112(1): 145-151.

32. Bishayi B, Roychowdhury S, Ghosh S. Hepatoprotective activity and immunomodulatory properties of Tinosporia cordifolia in CCl4 intoxicated mature albino Rats. J Toxicol Sci 2002; 27(3):139-146.

33. Murthy Sree Rama, Srinivasn M. Hepatoprotective effects of Tephrosia Purpurea experimental animals. J Pharmaco 1993; 25(1): 34-36.

34. Elkoy T. A, Mouneir S. M, Kamel Gehan, et al. Hepatoprotective Effect of Methanol Extracts of Zingiber officinale and Cichorium intybus. Indian J. Pharm Sci 2010; 72(5): 564–570.

35. Singh B, Saxena AK, Chandan BK. In vivo hepatoprotective activity of active fraction from ethanolic extract of Eclipta alba leaves Indian J Physiol Pharmacol 2001;45(4): 435-441.

36. Hanefiozbek, SerdarUgras, IrfanBayram, et al. Hepatoprotective effect of Foeniculum vulgare essential oil ,A carbon-tetrachloride induced liver fibrosis model in rats . J. Lab Anim Sci 2004; 31(1): 9-17.

37. Kaviarasan S, Viswanathan P, Anuradha C.V. Fenugreek seed (Trigonella foenum graecum) polyphenols inhibit ethanol-induced collagen and lipid accumulation in rat liver. Cell Biol Toxicol 2007; 23(6): 373-383.

38. Mohan G.K, Pallvi E, Ravi Kumar B. Hepatoprotective activity of Ficuscarica Linn leaf extract against carbon tetrachloride-induced hepatotoxicity in rats. DARU Journal of Pharmaceutical Sciences 2007; 15(13):162-166.

39. Mohamed T S Saleem , Christina AJ M , Chidambaranthan N, et al. Hepatoprotective activity of Annona squamosa Linn on Experimental animal model. J Applied Research in Natural Products 2008; 1(3): 1-7.

40. Afaf I. Abuelgasim, H.S Nuha, A.H.Mohammed. Hepatoprotective Effect of Lepidium sativum Against Carbon Tetrachloride Induced Damage in Rats. J.Animal and Veterinary Sciences 2008; 3: 20-23.

41. Meena B, Anbin R Ezhilan, R. Rajesh, et al. Antihepatotoxic potential of Sargassum polycystum on antioxidant defense status in D-galactosamine induced hepatitis in rats. J. Biochemistry Research 2008; 2(2): 51-55.

42. Rosa MP, Gutiérrez, Rosario V.S. Hepatoprotective and inhibition of oxidative stress of Prostechea michuacana 2009; 3(1): 46-51.

43. Pornpen Pramyothin, Chanon Ngamtin, Somlak Poungshompoo, et al. Hepatoprotective activity of Phyllanthusamarus extract in ethanol treated rats. J Ethnopharmacol 2007; 142(2): 169–173.

44. Rao K.S, Mishra SH. Indian journal of pharmaceutical science 1997; 59(4): 165-70.

45. Madani H, Talebolhosseini M, Asgary S, et al. Hepatoprotective activity of Silybum marianum and Ci-chorium intybus against thioacetamide in rat. J.Nutrition 172-176.

46. Arul kumaran KS, Rajasekaran A, Ramasamy A, et al. Cassia rox-burghiiseeds protect liver against toxic effects of ethanol and carbontetrachloride in rats. J. Pharm-Tech Res 2009; 1(2): 273-246.

47. Vadivu R, Krithika A, Biplab C, et al. Evaluation of hepatoprotective activity of the fruits of Coccinia grandis Linn. J. Health Res 2008; 1(3): 163-168.

48. Sultana S, Perwaiz S, Iqbal M, Athar M. Crude extracts of hepatoprotective plants, Solanum nigrum and Ci-chorium intybus inhibit free radical-mediated DNA damage, J. Ethnopharmacol 1995;45(3): 189-192.

49. Maheswari C, Maryammal R, Venkatanarayanan R. Hepatoprotective activity of ortho siphonstamineus on liver damage caused by paracetamol in rats, J.Jordan Biological Sciences 2008; 1(3): 105-108.

50. Kashaw Varsha, NemalkumarAmit, Agarwal Abhinav. Hepatoprotective Prospective of Herbal Drugs and Their Vesicular Carriers. International Journal of Research in Pharmaceutical and Biomedical Sciences 2011.

51. Stickel F, Schuppan D. Herbal medicine in the treatment of liver diseases. Journal of gastroenterology and hepatology 2007; 39(4): 293-304.

52. Murray. Phytosomes- Increase the absorption of herbal extract Available.