|Year : 2021 | Volume
| Issue : 4 | Page : 226-234
Review of clinical and preclinical studies on Ayurveda drugs used in management of liver diseases: A search for proof of concept
Bhavana Sharma1, 1, Meenakshi Sharma1, Shalini Rai1, Anand B More2
1 Department of Rog Nidan Evum Vikriti Vigyan, All India Institute of Ayurveda, Sarita Vihar, Delhi, India
|Date of Submission||27-Jun-2021|
|Date of Decision||20-Aug-2021|
|Date of Acceptance||30-Sep-2021|
|Date of Web Publication||29-Dec-2021|
Dr. Shalini Rai
Department of Rog Nidan Evum Vikriti Vigyan, All India Institute of Ayurveda, Sarita Vihar, Delhi 110076.
Source of Support: None, Conflict of Interest: None
Introduction: Liver disease has become a matter of public health concern. The worldwide prevalence of liver disease is rapidly increasing due to changes in our cultural and lifestyle norms. Western medicine is known to have serious adverse effects in patients with liver disease. Ayurveda is enriched with various herbo-mineral formulations and their efficacy and safety in treating liver disease has been evidenced in various forms of research. This potential of Ayurveda formulation can be utilized to treat liver disease. The present review is aiming at summarizing a well-organized and comprehensive analysis of various clinical and cell line studies using Ayurveda hepato-protective drugs. Materials and Methods: A thorough search was conducted in online databases of Google Scholar and PubMed on Ayurveda and modern drugs acting in liver disorders. Studies meeting our selection criteria were included and evaluated. Observations and Results: Eighty-six relevant articles were found, of which 55 were used in this review. Conclusions: Ayurveda drugs have been used for centuries in liver diseases of varied etiology. In this systematic analysis, a detailed description of reviewed studies on hepato-protective plants clearly indicates the efficacy and safety of widely used medicinal drugs used in alleviating chronic liver disease and that have an enormous potential to protect the liver from oxidative injury. It is inferred from the study that Ayurveda formulations can be used to combat various liver diseases both safely and efficiently.
Keywords: Antioxidant, yurveda, hepato-protective, liver diseases
|How to cite this article:|
Sharma, B, Sharma M, Rai S, More AB. Review of clinical and preclinical studies on Ayurveda drugs used in management of liver diseases: A search for proof of concept. J Indian Sys Medicine 2021;9:226-34
|How to cite this URL:|
Sharma, B, Sharma M, Rai S, More AB. Review of clinical and preclinical studies on Ayurveda drugs used in management of liver diseases: A search for proof of concept. J Indian Sys Medicine [serial online] 2021 [cited 2022 Jan 28];9:226-34. Available from: https://www.joinsysmed.com/text.asp?2021/9/4/226/334260
| Introduction|| |
The liver is one of the vital organs that regulates the physiological process of the body to maintain homeostasis. It is involved in protein synthesis, detoxification of toxic metabolites, metabolism and distribution of nutrients, and in regulating homeostasis of the body. Liver diseases pose a grim hazard to human health. It has become a serious public health problem in this modern era, affecting more than 10% of the world population, and also the fifth most common cause of death worldwide. Due to increasing prevalence, liver diseases are categorized in the top priority areas of health maintenance. Approximately 1.5 billion cases of chronic liver disease (CLD) are reported worldwide. CLD is a slow progressive process of inflammation, destruction, and degeneration of liver parenchyma leading to fibrosis and cirrhosis. It is one of the major causes of ascites in most patients. It involves varied liver pathology such as fatty liver, hepatocellular carcinoma, cirrhosis, fibrosis, chronic hepatitis, etc. Approximately 50% of patients with CLD progress toward ascites within 10 years. The causes of CLD include viral infections such as Hepatitis B, Hepatitis C, metabolic cause (nonalcoholic fatty liver disease [NAFLD]), the use of toxic substances and drugs, that is, excessive alcohol consumption (alcoholic liver disease), and autoimmune factor (causing primary sclerosing cholangitis and primary biliary cholangitis). Symptoms of CLD include poor appetite, jaundice, ascites, peripheral edema, itchy skin, decreased weight, small spider angioma, anemia, and splenomegaly. The underlying pathophysiology is due to increased capillary permeability, resulting in increases in hydrostatic pressure and decreased osmotic pressure. In Ayurveda, several disease conditions are described that enumerate on the earlier mentioned stages of CLDs and their treatment.
The therapeutic choices for liver diseases in contemporary medicine are very limited. Safety and efficacy of various herbal drugs in the treatment of liver diseases have been reported in clinical trials. This review is a comprehensive, well-organized analysis of experimental trials, clinical and in vitro studies on widely used Ayurveda herbo-mineral compounds in the management of liver diseases; it also focuses on their composition, potential role, pharmacology, underlying molecular mechanisms, and outcomes. The results of preclinical as well as clinical trials on herbal medicines have been utilized in the present review. The article further aims at summarizing in vivo and in vitro studies conducted on Ayurveda hepato-protective drugs.
| Materials and Methods|| |
Sources and article selection criteria—Ayurveda compendium was searched for the drugs classically described and used in clinical practice for the management of liver diseases and documented with Ayurveda perspectives and principles. Electronic databases of Dhara, PubMed, and Google Scholar were thoroughly explored by using phrases and keywords such as “Ayurveda drugs,” “Hepatoprotective activity,” “Liver diseases,” “Medicinal plants,” “Herbal drugs,” “Treatment,” and “Management of CLD.” After the combination of the keywords and subsequent analysis, about 86 relevant articles were extracted. Among them, 18 were case reports, 7 review articles, 13 clinical articles, and 48 experimental studies. After a narrow search as per inclusion criteria, 55 full-text articles that studied in vivo and in vitro hepato-protective potential and clinical trials on Ayurveda drugs were finally selected. The observations and results of the study were then systematically presented, mainly focusing on the active principle of compounds, hepato-protective activities, and the probable mechanism of action.
| Observations and Results|| |
The selected 55 articles revealing the hepato-protective potential of Ayurveda drugs were thoroughly searched to explore active principles and their probable mode of action. The studies scrutinized the following findings.
In an open-labeled single-group observational clinical study, Patel et al. orally administered single and compound herbal preparations combined with dietary and lifestyle measures in 56 patients with hepatic cirrhosis who were complicated by ascites (HCcA) for a period of 18 weeks. The outcomes were assessed by evaluating the ChildPugh prognostic grade score, measuring the liver and statistically significant improvements were found. Another clinical trial reported the combined effect of two herbo-mineral formulations Triphala Guggulu and Arogyavardhini Vaṭi, along with wholesome diet and lifestyle in a randomized, retrospective, open-ended study in 32 subjects of NAFLD, and they demonstrated significant improvement in outcomes. In a randomized, double-blind placebo-controlled trial by Vaidya et al. on 32 patients of acute viral hepatitis, the treatment group was administered with Kutki (Picrorhiza kurroa Royle ex Benth) root powder 375 mg thrice a day, for 15 days; a significant change was reported in serum bilirubin and liver enzymes (AST and alanine aminotransferase [ALT]) in the treatment group as compared with the placebo group. In the treatment group, total serum bilirubin also declined to 2.5 mg % in 27.4 days as compared with 75.9 days in the placebo group, proving the efficacy of P. kurroa as a hepato-protective candidate in acute viral hepatitis. In another double-blind, placebo-controlled trial on Ayurveda herbo-mineral preparation,Arogyavardhini Vati (consisting 50% P. kurroa) was also found to be effective in acute viral hepatitis, resulting in symptomatic relief and a significant reduction in the total serum bilirubin in just four days and a remarkable decline in alanine amino-transferase at the end of the first week in the treatment group.
In a systematic analysis including 22 randomized trials (n = 1,947) on Phyllanthus niruri L (Bhumiamalaki) in chronic Hepatitis B, Liu et al. reported its effectiveness in the clearance of serum HBeAg HBV DNA and HBsAg without any serious adverse effects.
Another study proved 72.2% survival rate in the patients with subacute hepatic failure due to viral hepatitis received. Stronger Neo Minophagen-C, that is, SNMC containing mainly Glycyrrhiza (solution of 0.2% Glycyrrhizin, 0.1% cysteine, and 2% glycine in water) given for 12 weeks as compared with 31.1% survival in the control group received standard supportive therapy. Glycyrrhiza alone has antioxidant, detoxifying effects and it stimulates endogenous interferon production in subacute hepatic failure when given in a physiologic saline solution along with cysteine and glycine.
Glycyrrhiza extract is also found to be beneficial in acute and chronic hepatitis administered through the oral route. Eighty patients having hepatitis (40 acute and 40 chronic) received oral glycyrrhizin (approximately 750 mg, like 7.5 g of crude herb) or Poly I:C (polyinosinic-polycytidylic acid, an antiviral) and inosine intramuscularly. It was found that in the glycyrrhizin group, 85% of subjects with acute hepatitis showed all predictors of liver function to be normal within one month of treatment as compared with 35% in the control group. Overall, 75% of subjects with chronic hepatitis experienced normalization of liver function, in contrast to 10% in the control group. Therapeutic potential of glycyrrhizin in hepatitis was also confirmed in another placebo-controlled clinical trial in Europe. It was found that 47% of ALT decreased within the six-time glycyrrhizin treatment/week group and 26% for the three-time treatment/week group (P < 0.001). In the six-time/week treatment group, 20% of the patients got normal serum ALT levels and the result was about 10% in the three-time/week treatment group. However, no evident changes in ALT level were found in the placebo group. The antifibrosis efficacy and safety of glycyrrhizin were confirmed in a Phase 3 clinical trial by Manns et al. in 379 patients with chronic Hepatitis C, where earlier interferon-based treatment got no response. The clinical study indicated that glycyrrhizin can decrease serum ALT level after 12 weeks of administration and suppress inflammation and fibrosis after 52 weeks of treatment against the placebo group. Trials did not report any obvious side effect due to glycyrrhizin. The efficacy of Liv-52, an Ayurveda herbal formulation frequently used in CLDs, is well established. The active ingredient of Liv-52 is Capparis spinosa L. (Himsra). In another double-blind, placebo-controlled trial for six months on 36 patients with cirrhosis, the group treated with Liv.52 (combination of C. spinosa, Terminalia arjuna, Cassia occidentalis, Achillea millefolium, Cichorium intybus, Mandura bhasma, Solanum nigrum, and Tamarix gallica) reported significantly better Child-Pugh score, decreased serum ALT and AST levels, and ascites compared with the placebo group. The anti-inflammatory, antioxidative, diuretic, and immune-modulating effects of the component herbs of Liv-52 are well documented.
Hepato-protective effects of the methanol extract of Carissa opaca (Karmardika) leaves (MCL) on carbon tetrachloride (CCl4)-induced damage in rat were proven in a clinical study. Group I (control) was given olive oil and DMSO. Groups II, III, and IV were administered with CCl4 (0.5 mL/kg) as a 20% (v/v) solution in olive oil through the intraperitoneal route twice a week. Group II was given only CCl4. Group III rats were given MCL through the intragastric route (200 mg/kg body weight), and Group IV received silymarin (50 mg/kg body weight twice a week). Group V was treated with MCL (200 mg/kg bw twice a week). All the interventions were given for eight weeks. The altered biochemical profiles due to CCl4 exposure were reversed toward normalization in the MCL-treated group due to its antioxidant and membrane-stabilizing properties. The regenerative and reparative capacity of the liver was enhanced due to its contents. The hepato-protective activity of alcoholic and aqueous extracts of the leaves of Paarijata (Nyctanthes arbor-tristis) against CCl4-induced liver damage in rats was evaluated by Hukkeri et al. A significant decrease in the elevated serum enzymes levels (serum glutamate pyruvate transaminase [SGPT/ALT], serum glutamate oxaloacetate transaminase [SGOT/AST], and serum bilirubin) and regeneration of hepatocytes were revealed in the study. In vivo and in vitro hepato-protective effects of ethanolic Andrographis paniculata (Bhunimba) leaf extract (ELAP) on thioacetamide (TAA)-induced hepatotoxicity in rats were investigated by Bardi et al. Due to TAA-induced hepatotoxicity, the serum liver biomarkers alkaline phosphatase (ALP), ALT, AST, and gamma-glutamyl transferase (GGT) were significantly elevated. The treatment group (ELAp) reported marked lower liver/body weight ratios, normal liver surfaces, which were reduced in elevated liver biomarkers compared with the cirrhosis group. Histopathological changes after ELAP treatment revealed a low degree of lymphocyte infiltration, minor fibrotic septa, minimal distraction of hepatic cellular structure, and minimal collagen deposition. Hence, both in vivo and in vitro studies documented ELAP that was significantly protected against TAA-induced liver damage. In addition, no sign of liver damage was noticed in ELAP treated at 2500 mg/kg dose.
Significant protection against acute paracetamol-induced hepatotoxicity (150 mg/kg) in Swiss albino mice through oral administration of ethanolic extract of A. paniculata or S. chirayita (100–200 mg/kg) was reported. It not only reduced hepatotoxicity markers but also restored the antioxidant levels and decreased the lipid peroxidation levels in the liver. Clinical studies also revealed that the aqueous extract of A. paniculate repressed BHC-induced hepatotoxicity in Swiss male mice,, and ethanol-induced liver toxicity in albino Wistar rats.
Several in vivo and cell line studies evaluated the antiviral effects and safety of P. niruri L. Suppression of HBsAg secretion and downregulation of the expression of HBsAg mRNA by ethanolic extract of P. niruri was reported in a study by Lam et al. Another study revealed that the aqueous extract of P. niruri has a significant and potent hepato-protective and oxidative effect against Staphylococcus aureus induced oxidative stress and damage in the liver in rats evidenced by an increase in antioxidant enzyme activity, a decrease in glutathione levels, and a reduction in the lipid peroxidation products. In another study, Zarzour et al. proved that a 50% methanolic extract of P. niruri standardized extract exhibits maximum inhibitory effects against the development of NAFLD and reduces atherosclerotic risk in rats induced by the administration of a high-fat diet. The NAFLD score was found to be decreased along with a reduction in visceral fat weight (22%), hepatomegaly (16%), ALT (45%), ALP (38%), serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), LDL/HDL (66%), and hepatic content of cholesterol (43%) as compared with a non-treated group. Fifty percent of ME of P. niruri decreased hepatic lipid peroxidation and fat accumulation, visceral adiposity, and improved liver enzymes’ irregularity.
The hepato-protective activity of the methanolic extract of Achyranthes aspera (Apamarga) arial parts on rifampicin-induced hepatotoxicity was studied in albino rats by Bafna and Mishra. A remarkable decline in elevated liver enzymes and total bilirubin levels was observed. The NAFLD induced by a high-fat diet animal model demonstrated reversal of liver enzyme and lipid profile changes and hepatic lipid lesions. In a study on male Wistar rats challenged with a 30% butter diet for two weeks administered orally with hydroalcoholic extract of Kutki (P. kurroa Royle ex Benth) in 200 mg/kg and 400 mg/kg doses for four weeks, Shetty et al. revealed that P. kurroa decreased lipid content (mg/g) and reversed the fatty infiltration of the liver considerably at 400 mg/kg dose, demonstrating its hepato-protective potential. In a study on rats in whom liver damage was induced by CCl4 when treated with Kasani (C. intybus L.) root extracts, a significant reduction in elevated serum enzymes and bilirubin levels and an increase in albumin and proteins value were reported. However, C. intybus cell culture was found to be more effective and anti-hepatotoxic as compared with natural root extract. In an Indonesian study, hepato-protective properties of ethyl acetate fraction of root bark (EAFCR) of Bharangi (Clerodendrum serratum L.) on rats in whom liver damage was induced by CCl4 were evidenced. After pretreatment with EAFCR at the dose of 100 mg/kg.bw, SGPT/ALT, ALP, SGOT/AST, and bilirubin were significantly decreased whereas the total protein level was increased. The antioxidant action of the active compounds contained in this plant was responsible for the hepato-protective changes. In another study on CCl4-induced hepatotoxicity in male Wistar rats, the root extract C. serratum reported highly significant hepato-protective activity of ursolic acid isolated from C. serratum root (10 mg/kg.bw dosage) as compared with its ethanolic extract (20 mg/kg.bw dosage). In another study on rifampicin-induced hepatotoxicity in Swiss albino mice, alcoholic and aqueous extracts of C. serratum leaves (200 mg/kg.bw dosage) were found to have significant hepato-protective activity. In bioassay-based fractionation of the extract, Manvar et al. evaluated anti-viral (anti-HCV) activity in Bhringraja (Eclipta alba) extract, and they identified anti-HCV compounds present in the active fractions (Wedelolactone, luteolin, and apigenin). Dose-dependent inhibition of HCV replicase and anti-HCV replication activity in the cell culture system of these compounds indicated potent antiviral activity against HCV. In vitro inhibition of RNA-dependent RNA polymerase activity by E. alba extract was reported. Infective hepatitis cases are successfully treated by E. alba in India. E. alba ethanolic extract has been proven to have hepato-protective effects in the damaged liver of rat and mice., The advantageous effects of 3,5-dihydroxy-40,7-dimethoxyflavone isolated from Jhavuka (T. aphylla L.) against CCl4-induced liver injury in mice were its antiangiogenic, antioxidant, and antiapoptotic properties. It was suggested that the flavone inhibited liver injury in mice due to apoptotic oxidation and angiogenesis mechanisms.
Bardhan et al. reported that oral feeding of a multiherbal drug preparation Liv- 52 to mice, rats, and rabbits reduced mortality and resulted in significant hepato-protection against liver damage due to CCl4 toxicity.
In chronic liver damage induced by repeatedly injecting the horse serum in rats, the hepato-protective effect of Guduchi (Tinospora cordifolia) was evaluated on Kupffer cell function, using the carbon clearance test as a parameter.T. cordifolia decreased fibrosis in animal models of liver injuries (reversible and irreversible) induced by CCl4. In chronic liver damage, depressed Kupffer cell activity has been reported by Noda et al. Gora et al. investigated that oral supplementation of Sharapunkha (Tephrosia purpurea) extract in 500 mg/kg dosage daily for 28 days in arsenic-induced toxicity in Wistar rats remarkably decreased elevated LDH and glucose levels along with an increase in hematological levels toward normal, indicated its cell protective effect. Jamuna (Eugenia jambolana) fruit extract [JFE] was reported with partial protective effects against fibrosis, cholestatic liver injury, and inflammation in mice. Its active compound in extracts decreased oxidative stress, hepatic inflammation, and protected against hepatocellular injury. It also decreased bile-duct ligation (BDL)-induced liver injury, pro-inflammatory cytokine; reduced BDL-induced fibrosis markers and macrophage infiltration in liver after BDL. In two nonalcoholic steatohepatitis (NASH)-induced models in mice Ashwagandha (Withania somnifera) extract, Withaferin A (WA) was reported to possess both preventive and therapeutic action in improving liver injury, which was documented by a decrease of liver inflammation, elevated liver enzyme levels, hepatic steatosis, and fibrosis. WA also lowered ceramides and restored oxidative stress, probably possible due to the earlier mentioned action. Numerous other studies evaluated hepato-protective activity of WA., WA is evidenced to have hepato-protective action against acetaminophen-induced acute liver injury, and Vedi and Sabina, in another study, proved that it alleviates bromobenzene-induced liver injury.
Glycyrrhiza has flavonoids that provide protection to hepatocytes exposed to carbon tetrachloride and they aid in its hepato-protective action. Another study reported that the galactosamine content in Glycrrhiza is responsible for the liver-protecting mechanism. It was observed in various in vitro studies that Glycyrrhiza has antiviral activity against a wide range of viruses, including hepatitis A, varicella zoster, and HIV. The component glycyrrhizin was also reported to reduce MCD diet-induced NASH without affecting the weight loss, again showing its hepato-protective action. Curcumin present in turmeric (Curcuma longa) was reported to reverse the liver damage induced by aflatoxin in ducklings. It reduced biliary hyperplasia, fatty changes in liver, and necrosis.Dhataki (Woodfordia fruticosa L.) has been associated with reversing fibrotic changes in the liver. Lin et al. proved that the aqueous extract of S. nigrum (Kakmachi) effectively lowered the CCl4-induced elevated levels of liver enzymes, total bilirubin, hydroxyl, and superoxide radicals in rats. It also reversed the decreased levels of detoxification enzymes and glutathione-S-transferase. Histopathological changes revealed that the extract reduced the hepatic cells’ cloudy swelling, liver lesions, lymphocyte infiltration, CCl4-induced hepatic necrosis, and fibrous connective tissue proliferation.
In the animal study, the extract of Dugdha pheni (Taraxacum officinale) was found to be effective in chemical and drug-induced hepatic fibrosis. Al Malki et al. observed that on administration of T. officinale leave extract to CCl4-induced hepatic steatosis, steatosis grade was significantly reduced in rats. Another study reported that the root water-ethanolic extract (DWE) of T. officinale (600 mg/kg dosage) for 10 days in mice shows significant replacement of AST and ALT enzymes, alpha-smooth muscle actin protein expression, superoxide dismutase, and hydroxyproline in CCl4-induced hepatic fibrotic mice, revealing its antifibrotic and hepatic regenerative properties. The study by Patel et al. revealed the significant hepato-protective effect of ethanolic extract of Rohitak bark (Tecomella undulata Sm.) on paracetamol-induced hepatotoxicity in rats. It was found that T. undulata reversed the physiological integrity of hepatocytes by decreasing elevated levels of liver enzymes, total bilirubin, increased the level of total protein and liver weight and volume, and induced sleeping time. Rana et al. also reported the hepato-protective nature of the bark of T. undulata against liver injury in experimental rat models. In an experimental study on rats, T. undulata was observed to possess hepato-protective nature against thioacetamide-induced hepatotoxicity. Rats treated with aqueous and ethanolic aerial parts extract of T. purpurea (500 mg/kg) and ethanolic extract of stem bark of T. undulata (1,000 mg/kg) demonstrated a reduction in necrosis, total bilirubin, liver malondialdehyde (MDA), and liver enzyme levels along with remarkable improvement in liver glutathione.
| Discussion|| |
Numerous drugs are described in Ayurveda, with the hepato-stimulant properties prescribed in treating liver ailments. Charak Samhita, the oldest documented text of Ayurveda, documents several drugs in context for the treatment of medical conditions similar to jaundice (clinical presentation similar to Kamala), hepatomegaly (clinical presentation similar to Yakriddalyodara), cirrhosis (clinical presentation similar to Kumbhkamala), and ascites (clinical presentation similar to Jalodara meaning fluid in abdomen). Classics have described liver as the anatomical seat of Rakta (blood) and Pitta (bile). Hence, the pathology of liver diseases arises mainly due to hampered digestive fire (Mandagni), vitiation of Rakta or Pitta, obstruction and hampered movement of bile (Pitta), or the combination of these factors. Some poisons and toxins are also described to vitiate the liver and produce liver diseases.
Ayurveda classics have described various formulations for the management of liver disorders, among which the most abundant and prescribed ones are Kutaki (P. kurroa Royle ex Benth), Bhunimba (A. paniculata Nees.), Bhumiamalaki (P. niruri Linn.), Kakmachi (S. nigrum Linn.), Mulethi (Glycyrrhiza glabra Linn.), Giloy (T. cordifolia [Willd.] Hook. F. and Thoms.), Bhringraj (E. alba [L.] Hassk.), Pippali (Piper longum L.), Rohitaka (Tecoma undulate G.Don.), Nimba (Azadirachta indica A. Juss.), Sharapunkha (T. purpurea Pers. Linn. Pers.), Ashwagandha (W. somnifera Linn.), Vasa (Adhatoda vasica Nees.), Paarijata (N. arbor-tristis Linn.), Bharangi (C. serratum Linn. Moon.), Haridra (C. longa), etc.
Drugs such as Jhavuka (T. aphylla Linn.), Dhaatki (W. fruticosa Kurz.), Jambu (Syzygium cumini Linn.), Kasani (C. intybus Linn.), Dugdhapheni(T. officinale Weber ex Wiggers), Nimba (A. indica A. Juss.), Apamarga (A. aspera Linn.), Himsra (C. spinosa), and Kasamarda (C. occidentalis) are relatively less used clinically for the management of liver diseases but they are more employed in other diseases.
The Mode of Action and Properties of Hepato-protective Drugs—Ayurveda Perspective
The mode of action of these drugs are described in terms of functions such as Rechana (cause increased bowel movement and cleanse the body of deposited wastes, toxins, and bile juices), Pittasaraka (excrete the bile and other inflammatory markers), Yakrituttejaka (stimulates the liver), Pleehahara or Pleehaghna (reduce the size of spleen [liver also]), Anulomana (carminative or correcting the movement), and Shothahara (reduces swelling, edema inflammation, and clears the body channels), which are described for these drugs [Table 1].
|Table 1: The mode of action of herbs as described in Ayurveda classics|
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In classical texts, C. opaca (Karmardika and Karaunda) are more employed as hridya, trishna-nashaka, and ruchi-janaka but are used for hepato-protective effects in experimental studies.
Most of these drugs have bitter (Tikta), pungent (Katu), and astringent (Kashaya) tastes, with drugs such as G. glabra (L.) and W. somnifera (L.) having sweet (Madhura) tastes. They are light to digest (Laghu, with the exception of Glycerriza and Tinospora which are heavy to digest) and produce properties similar to pungent taste in the body after digestion (Katu Vipaka with the exception of P. longum, G. glabra, T. cordifolia, P. niruri, and W. somnifera, which develop sweet properties after digestion, and hence are used as nourishing [Rasayan] drugs).
Being Tikta and Kashaya, these drugs provide blood-purifying properties along with digestive stimulant action and Pitta pacification, which is aided by their Laghu property, Katu Rasa, and Katu Vipaka. The improved digestion process consumes the vitiated Kapha and Ama, thus clearing the obstruction of channels, restoring the natural flow of Pitta. Being Pitta-Saraka, once the passages are clear, they facilitate bile flow and clear inflammation and swelling. Yakridottejaka action stimulates the liver cells to function properly. Further, due to their Deepana-Pachana, Yakridottejaka, and Rasayan properties, they cause the regeneration of liver cells and protect them from damage caused due to toxins and chemicals.
The peculiar administration method of P. longum in customized ascending and tapering doses as its vardhamana pippali formulation coupled with an exclusive milk diet imposes a rejuvenation effect (rasayana) and is used widely and successfully for treatment for ascites due to liver diseases., Compound formulations such as Triphala (combination of three fruits—Amalaki [Emblica officinalis L.], Haritaki [T. chebula L.], and Vibhitaki [T. bellerica L.]). Arogyavardhini Vati,Triphala Guggulu, and Phaltrikadi kwath are also described and used predominantly for the management of liver diseases in Ayurveda. Arogyavardhini Vaṭi contains Katuka (P. kurroa) as the major ingredient (50%). Katuka is bitter in taste and thus helps in the digestion of toxins (Ama-Pachana). Triphala Guggulu is a mixture of (i) Triphala (ii) Pippali (P. longum), and (iii) Guggulu (Commiphora mukul) combined by using trituration with infusion of Triphala decoction. Triphala as per Ayurveda improves the digestion and metabolism process, clears phlegm (kapha), clears the channels of circulation, destroys swelling, and urinary disorders, besides being rejuvenative and restorative to all tissues.Pippali reduces body fat and acts as a drug potentiator, and Guggulu is a purifier of the channels and reduces obesity. Thus, Triphala Guggulu is lekhaniya (obesity scraper) by action and is thereby useful in reducing the triglyceride levels along with body fat in patients with NAFLD.Phaltrikadi kwath is also a very widely used herbal drug that has Guduchi, Vasa (A. vasica Nees.), Kalmegh, Nimba (A. indica A. Juss.), and Katuki as the main ingredients along with Triphala. Clinical studies have evidenced its effectiveness in the management of hepatitis.,Triphala possesses hepato-protective, appetite stimulation, chemopreventive, and hyperacidity reduction potential.S. chirayita is widely used in the treatment of hepatitis, digestive disease, and chronic liver ailments. Hepato-protective and antioxidant effects of P. kurroa are well established.,
A combination of these drugs is used in routine Ayurveda practice; these are documented for their beneficial effects in case reports and in case series in conditions of NAFLD FLD, ALD,, acute viral hepatitis, hepatitis B, hepatitis C, hepatic encephalopathy, ascites,,, liver cirrhosis, etc. with very significant results clinically as well as in biochemical and ultrasonography reports.
The Ayurveda drugs described in the management of liver ailments stimulate the digestive and metabolic processes, purify the blood, remove obstruction (caused due to undigested metabolic waste), clear the flow of bile, stimulate bile flow, and thus reduce or mitigate the swelling or edema and inflammation, resulting in the clinical relief associated with significant changes in biochemical and radiological parameters. The drugs are reported to have hepato-protective potential on the basis of choleratic and cholegogue action, antioxidant effect, antiviral effect, antiedemic, anti-inflammatory, diuretic, antioxidative, rejuvenative, and hepato-splenoprotective, metabolism-promoting actions, and immune-modulating effects.
| Conclusion|| |
Ayurveda drugs have been used for centuries in liver diseases of a varied etiology. In this systematic analysis, a detailed description of medicinal drugs used in alleviating CLD due to various causes is provided. The studies reviewed earlier on hepato-protective plants clearly indicate that medicinal plants and phytochemicals have enough power to combat liver injuries. The major mechanism as seen in most of the trials is combating the oxidative stress that damages the liver by the virtue of their hepato-protective effect. Other mechanisms involved are inhibiting suppression of fibrogenesis, inhibition of oxidative damage, tumor growth, and antiviral effect of formulations. Although the safety and efficacy of Ayurveda drugs in treating liver disorders have been established by research works, limited data are available on randomized clinical trials. There is a need of more randomized, multicentric clinical trials to develop evidence-based therapeutics for CLD treatment. Further research is also needed for some medicinal plants to identify, isolate, confirm, and standardize the active components or molecules and then test them in suitable culture or animal experiments to promote the rational use of chosen drug candidates.
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| References|| |
Wood NJ. Liver: Nonobese individuals in the developing world are at risk of nonalcoholic fatty liver and liver disease. Nat Rev Gastroenterol Hepatol 2010;7:357.
Moon AM, Singal AG, Tapper EB. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin Gastroenterol Hepatol 2020;18:2650-66.
Lee G. CECIL Text Book of Medicine. New Delhi: Elsevier; 2003. p. 941.
Patel MV, Patel KB, Gupta S, Michalsen A, Stapelfeldt E, Kessler CS. A complex multiherbal regimen based on ayurveda medicine for the management of hepatic cirrhosis complicated by ascites: Nonrandomized, uncontrolled, single group, open-label observational clinical study. Evid Based Complement Alternat Med 2015;2015:613182.
Singhal P, Nesari T, Gupta GS. Efficacy of herbomineral compounds and pathya (Ayurvedic dietary regime and physical exercise) in the management of Yakrit Roga (non-alcoholic fatty liver disease). Ancient Sci Life 2015;34:216-22.
] [Full text]
Vaidya AB, Antarkar DS, Doshi JC, Bhatt AD, Ramesh V, Vora PV, et al
. Picrorhiza kurroa
) royle ex benth as a hepatoprotective agent: Experimental & clinical studies. J Postgrad Med 1996;42:105-8.
] [Full text]
Antarkar DS, Vaidya AB, Doshi JC, Athavale AV, Vinchoo KS, Natekar MR, et al
. A double-blind clinical trial of arogya-wardhani–an ayurvedic drug–in acute viral hepatitis. Indian J Med Res 1980;72:588-93.
Liu J, Lin H, McIntosh H. Genus Phyllanthus
for chronic hepatitis B virus infection: A systematic review. J Viral Hepat 2001;8:358-66.
Acharya SK, Dasarathy S, Tandon A, Joshi YK, Tandon BN. A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra
in the treatment of subacute hepatic failure. Indian J Med Res 1993;98:69-74.
Su XS, Chen HM, Wang LH, Jiang CF, Liu JH, Zhao MQ, et al
. Clinical and laboratory observation on the effect of glycyrrhizin in acute and chronic viral hepatitis. J Tradit Chin Med1984;4:127-32.
Van Rossum TG, Vulto AG, Hop WC, Schalm SW. Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C. Am J Gastroenterol 2001;96:2432-7.
Manns MP, Wedemeyer H, Singer A, Khomutjanskaja N, Dienes HP, Roskams T, et al
; European SNMC Study Group. Glycyrrhizin in patients who failed previous interferon alpha-based therapies: Biochemical and histological effects after 52 weeks. J Viral Hepat 2012;19:537-46.
Fleig WW, Morgan MY, Hölzer MA. The ayurvedic drug LIV 52 in patients with alcoholic cirrhosis: Results of a prospective, randomized, double-blind, placebo-controlled clinical trial. J Hepatol 1997;26(suppl 1):S127.
Huseini HF, Alavian SM, Heshmat R, Heydari MR, Abolmaali K. The efficacy of Liv-52 on liver cirrhotic patients: A randomized, double-blind, placebo-controlled first approach. Phytomedicine 2005;12:619-24.
Sahreen S, Khan MR, Khan RA. Hepatoprotective effects of methanol extract of Carissa opaca
leaves on ccl4-induced damage in rat. BMC Complement Altern Med 2011;11:48.
Hukkeri VI, Kusum SA, Sureban RR, Gopalakrishna B, Byahatti VV, Rajendra SV. Hepatoprotective activity of the leaves of Nyctanthes arbor-tristis
Linn. Indian J Pharm Sci 2006;68:542-3. [Full text]
Abdulaziz Bardi D, Halabi MF, Hassandarvish P, Rouhollahi E, Paydar M, Moghadamtousi SZ, et al
. Andrographis paniculata
leaf extract prevents thioacetamide-induced liver cirrhosis in rats. Plos One 2014;9:e109424.
Nagalekshmi R, Menon A, Chandrasekharan DK, Nair CK. Hepatoprotective activity of Andrographis paniculata
and Swertia chirayita
. Food Chem Toxicol 2011;49:3367-73.
Sutha D, Jegathambigai KP, Sivaramakrishnan S. A study on the hepatoprotective effect of Andrographis paniculata
(Burm.F) Nees on mice. J Phytol 2010;2:25-30.
Trivedi NP, Rawal UM. Hepatoprotective and toxicological evaluation of Andrographis paniculata
on severe liver damage. Ind J Pharmacol 2000;32:288-93.
Trivedi NP, Rawal UM, Patel BP. Hepatoprotective effect of andrographolide against hexachlorocyclohexane-induced oxidative injury. Integr Cancer Ther 2007;6:271-80.
Sivaraj A, Vinothkumar P, Sathiyaraj K, Sundaresan S,Devi K, Senthilkumar B. Hepatoprotective potential of Andrographis paniculata
aqueous leaf extract on ethanol induced liver toxicity in albino rats. J Appl Pharm Sci2011;1:204-8.
Lam WY, Leung KT, Law PT, Lee SM, Chan HL, Fung KP, et al
. Antiviral effect of Phyllanthus nanus
ethanolic extract against hepatitis B virus (HBV) by expression microarray analysis. J Cell Biochem 2006;97:795-812.
Ramamurthy V, Abarna T. Hepatoprotective activity of Phyllanthus niruri
whole plant extract against Staphylococcus aureus
intoxicated albino rats. Glob J Biol Agric Health Sci 2014;3:256-60.
Al Zarzour RH, Ahmad M, Asmawi MZ, Kaur G, Saeed MAA, Al-Mansoub MA, et al
. Phyllanthus niruri
standardized extract alleviates the progression of non-alcoholic fatty liver disease and decreases atherosclerotic risk in Sprague-Dawley rats. Nutrients 2017;9:766.
Bafna AR, Mishra SH. Effect of methanol extract of Achyranthes aspera
Linn. on rifampicin-induced hepatotoxicity in rats. ARS Pharma 2004;45:343-51.
Shetty SN,Mengi S, Vaidya R, Vaidya AD. A study of standardized extracts of Picrorhiza kurroa
Royle ex Benth in experimental nonalcoholic fatty liver disease. J Ayurveda Integr Med2010;1:203-10.
] [Full text]
Elgengaihi S, Mossa AT, Refaie AA, Aboubaker D. Hepatoprotective efficacy of Cichorium intybus
L. extract against carbon tetrachloride-induced liver damage in rats. J Diet Suppl 2016;13:570-84.
Nasrudin N,Wahyono W, Mustofa M, Asmah R. Hepatoprotective activity of ethyl acetate fraction of Senggugu’s root bark (Clerodendrum serratum
L. Moon) on rats induced by carbon tetrachloride. Indonesian J Pharm 2017;28:2338-9427.
Vaidya SM, Krishna V, Manjunatha BK, Mankani KL, Ahmed M, Singh SD. Evaluation of hepatoprotective activity of Clerodendrum serratum
L. Indian J ExpBiol 2007;45:538-42.
Agrawal SK, Jat RK, Chippa RC. Pharmacological evaluation of hepatoprotective activity of Clerodendrum serratum
. Int J Pharmacol Toxicol. 2013;3:67-70.
Manvar D, Mishra M, Kumar S, Pandey VN. Identification and evaluation of antihepatitis C virus phytochemicals from Eclipta alba
. J Ethnopharmacol 2012;144:545-54.
Singh B, Saxena AK, Chandan BK, Agarwal SG, Anand KK. In vivo hepatoprotective activity of active fraction from ethanolic extract of Eclipta alba
leaves. Indian J Physiol Pharmacol 2001;45:435-41.
Singh B, Saxena AK, Chandan BK, Agarwal SG, Bhatia MS, Anand KK. Hepatoprotective effect of ethanolic extract of Eclipta alba
on experimental liver damage in rats and mice. Phytother Res 1993;7:154-8.
El-Aarag B, Khairy A, Khalifa SAM, El-Seedi HR . Protective effects of flavone from Tamarix aphylla
against CCl4-induced liver injury in mice mediated by suppression of oxidative stress, apoptosis and angiogenesis. Int J Mol Sci2019;20:5215.
Bardhan P, Sharma SK, Garg NK. In vitro effect of an Ayurvedic liver remedy on hepatic enzymes in carbon tetrachloride treated rats. Indian J Med Res 1985;82:359-64.
Nagarkatti DS, Rege NN, Desai NK, Dahanukar SA. Modulation of Kupffer cell activity by Tinospora cordifolia
in liver damage. J Postgrad Med 1994;40:65-7.
] [Full text]
Rege NN, Dahanukar SA, Karandikar SM. Hepatoprotective effect of Tinospora cordifolia
against carbon tetrachloride induced liver damage. Indian Drugs 1984;21:544-55.
Noda T, Mimura H, Orita K. Assessment of Kupffer cell function in rats with chronic liver injury caused by CCL4. Hepatogastroenterology 1990;37:319-23.
Gora RH, Baxla SL, Kerketta P, Toppo R, Kumar N, Roy BK. Ameliorative potential of Tephrosia purpurea
against arsenic induced toxicity in Wistar rats. Vet World 2013;6:493-6.
Donepudi AC, Aleksunes LM, Driscoll MV, Seeram NP, Slitt AL. The traditional Ayurvedic medicine, Eugenia jambolana
(jamun fruit), decreases liver inflammation, injury and fibrosis during cholestasis. Liver Int 2012;32:560-73.
Patel DP, Yan T, Kim D, Dias HB, Krausz KW, Kimura S, et al
. Withaferin A improves nonalcoholic steatohepatitis in mice. J Pharmacol Exp Ther 2019;371:360-74.
Jadeja RN, Urrunaga NH, Dash S, Khurana S, Saxena NK. Withaferin-A reduces acetaminophen-induced liver injury in mice. Biochem Pharmacol 2015;97:122-32.
Palliyaguru DL, Chartoumpekis DV, Wakabayashi N, Skoko JJ, Yagishita Y, Singh SV, et al
. Withaferin A induces Nrf2-dependent protection against liver injury: Role of Keap1-independent mechanisms. Free Radic Biol Med 2016;101:116-28.
Vedi M, Sabina EP. Assessment of hepatoprotective and nephroprotective potential of WithaferinA on bromobenzene-induced injury in Swiss albino mice: Possible involvement of mitochondrial dysfunction and inflammation. Cell Biol Toxicol 2016;32:373-90.
Wang GS, Han ZW. The protective action of Glycyrrhiza
flavonoids against carbon tetrachloride hepatotoxicity in mice. Yao Xue Xue Bao 1993;28:572-6. Chinese.
Kiso Y, Tohkin M, Hikino H, et al
. Mechanism of antihepatotoxic activity of glycyrrhizin, I: Effect on free radical generation and lipid peroxidation. PlantaMedica 1984;50:298-302.
Crance JM, Biziagos E, Passagot J, van Cuyck-Gandré H, Deloince R. Inhibition of hepatitis A virus replication in vitro by antiviral compounds. J Med Virol 1990;31:155-60.
Baba M, Shigeta S. Antiviral activity of glycyrrhizin against varicella-zoster virus in vitro. Antiviral Res 1987;7:99-107.
Ito M, Nakashima H, Baba M, Pauwels R, De Clercq E, Shigeta S, et al
. Inhibitory effect of glycyrrhizin on the in vitro infectivity and cytopathic activity of the human immunodeficiency virus [HIV (HTLV-III/LAV)]. Antiviral Res 1987;7:127-37.
Yan T, Wang H, Cao L, Wang Q, Takahashi S, Yagai T, et al
. Glycyrrhizin alleviates nonalcoholic steatohepatitis via modulating bile acids and meta-inflammation. Drug Metab Dispos 2018;46:1310-9.
Soni KB, Rajan A, Kuttan R. Reversal of aflatoxin induced liver damage by turmeric and curcumin. Cancer Lett 1992;66:115-21.
Nitha A, Prabha SP, Ansil PN, Latha MS. Methanolic extract of Woodfordia fruticosa
Kurz flowers ameliorates carbon tetrachloride-induced chronic hepatic fibrosis in rats. Toxicol Ind Health 2016;32:1224-36.
Lin HM, Tseng HC, Wang CJ, Lin JJ, Lo CW, Chou FP. Hepatoprotective effects of Solanum nigrum
Linn extract against CCl(4)-induced oxidative damage in rats. Chem Biol Interact 2008;171:283-93.
Al-Malki AL, Abo-Golayel MK, Abo-Elnaga G, Al-Beshri H. Hepatoprotective effect of dandelion (Taraxacum officinale
) against induced chronic liver cirrhosis. J Med Plants Res 2013; 7:1494-505.
Domitrović R, Jakovac H, Romić Z, Rahelić D, Tadić Z. Antifibrotic activity of Taraxacum officinale
root in carbon tetrachloride-induced liver damage in mice. J Ethnopharmacol 2010;130:569-77.
Patel KN, Gupta G, Goyal M, Nagori BP. Assessment of hepatoprotective effect of Tecomella undulata
(Sm.) Seem., Bignoniaceae, on paracetamol induced hepatotoxicity in rats. Rev Bras Farmacogn 2010;21:133-8.
Rana MG, Katbamna RV, Dudhrejiya AV, Sheth NR. Hepatoprotection of Tecomella undulata
against experimentally induced liver injury in rats. Pharmacol Online 2008;3:674-82.
Khatri A, Garg A, Agrawal SS. Evaluation of hepatoprotective activity of aerial parts of Tephrosia purpurea
L. and stem bark of Tecomella undulata
. J Ethnopharmacol 2009;122:1-5.
Bhavana KR, Shreevathsa . Medical geography in Charaka Samhita. Ayu
(ascites). Ayu 2014;35:371-7.
] [Full text]
Bhagiya SG, Shukla RB, Joshi NP, Thakar AB. A single-case study of management of Jalodara
(ascites). Ayu 2017;38:144-7.
] [Full text]
Shastri K, Chaturvedi GN editors. Agnivesha, Charaka, Dridhbala, Rasayana Adhyaya Pada-3, Shloka no. 436–40. In: Charaka Samhita, Vidyotini Hindi Commentary. 14th ed. Varanasi: Chaukhamba Bharti Academy;1987. p. 39.
Antiwal M, Singh JP. Clinical study of Pippali vardhman rasayan
in the management of Jalodar
with special reference to refractory cirrhotic ascites. J Res Educ Indian Med 2011;17:101-6.
Girhepunje KS, Gupta V, Jain R, Nakanekar A, Singh OP. Effect of integrated paracentesis and oral Vardhaman Pippali Rasayan
(vpr) therapy in ascites due to alcoholic liver cirrhosis: A case report. World J Pharm Sci2017;6:1402-17.
Mishra SN, editor. Udararogadhikara, Chapter no. 40, Verse no. 59. In: Bhaisajya Ratnavali of Kaviraj Govinda Das Sen edited with Siddhipada Hindi Commentary. 1st ed. Varanasi: Chaukhamba Surbharati Prakashana; 2012. p. 736.
Mishra SN, editor. Kustharogadhikara, Chapter no. 54, Verse no. 117. In: Bhaisajya Ratnavali of Kaviraj Govinda Das Sen edited with Siddhipada Hindi Commentary. 1st ed. Varanasi: Chaukhamba Surbharati Prakashana; 2012. p. 871.
Mishra SN, editor. Pandurogadhikara, Chapter no. 12, Verse no. 22. In: Bhaisajya Ratnavali of Kaviraj Govinda Das Sen edited with Siddhipada Hindi Commentary. 1st ed. Varanasi: Chaukhamba Surbharati Prakashana; 2012. p. 377.
Srivastava S. Madhyamakhanda 6. Ver. 9–11. In: Sharangdhara’s Sharangdhara Samhita with Commentary. Varanasi: Chaukhamba Orientalia; 2009. p. 185.
Chunekar KC, Pandey GS, editors. Bhavamishra, Bhavaprakasha Nighantu. Varanasi: Chaukhamba Surbharti Academy; 2006.
Srivastava S. Madhyamakhanda 7. Ver. 82–83. In: Sharangdhara’s Sharangdhara Samhita with Commentary. Varanasi: Chaukhamba Orientalia; 2009. p. 205.
Kumar N, Singh AK, Ghildiyal S. Potent hepatoprotective Phaltrikadi Kwath
: A clinical study. SM J Pharmac Ther 2015;1:1005.
Panda AK, Das D, Dixit AK, Giri R, Hazra J. The effect of Arogyavardhini Vati
and Phalatrikadi Kvatha
in non-alcoholic fatty liver disease: Case studies. Int J Adv Case Rep 2016;3:59-62.
Baliga MS, Meera S, Mathai B, Rai MP, Pawar V, Palatty PL. Scientific validation of the ethnomedicinal properties of the Ayurvedic drug Triphala
: A review. Chin J Integr Med 2012;18:946-54.
Bhatt A, Rawal RS, Dhar U. Ecological features of a critically rare medicinal plant, Swertia chirayita
, in Himalaya. Plant Species Biol 2006;21:49-52.
Mutnali KKV, Patil R. Management of alcoholic liver disease through Ayurveda. J AyuCaRe 2017;1:30-5.
Huddar VG, Mangane MP, Mumbaraddi SS. Clinical profile of a case of alcoholic liver disease: An Ayurvedic management. Indian J Health Sci 2015;8:142-6.
Ratha KK, Meher SK. Ayurvedic management of acute viral hepatitis: A case report. Indian J Case Reports 2018;4:511-4.
Anupam , et al
. Ayurvedic management of hepatitis b: A case report. World J Pharm Pharm Sci 2016;5:862-71.
Rastogi S, Srivastav PS. Ayurveda in critical care: Illustrating ayurvedic intervention in a case of hepatic encephalopathy. Ayu 2011;32:345-8.
] [Full text]
Singh MP, Kuchewar V. Management of Jalodara
(ascites) through treatment principles of Ayurveda: A case report. J Indian Sys Med 2019;7:185-8.
Aswathy G, Dharmarajan P, Sharma AR, Sasikumar VK, Vasudevan Nampoothiri MR. Ayurvedic management of cirrhotic ascites. Anc Sci Life 2016;35:236-9.
Sharma PV. Dravya Guna Vijnana-II. Reprint 2009. Varanasi: Chaukhambha Bharti Academy; 2006.