Table 3 Clinical trial with different promising hepatoprotective leads in patients with different liver diseases
From: Promising hepatoprotective agents from the natural sources: a study of scientific evidence
S. no | Name of hepatoprotective lead | Condition | Study design (n) | Treatment (n) | Duration | Outcome with hepatoprotective leads | References |
|---|---|---|---|---|---|---|---|
1 | Silymarin | Epileptic children having antiepileptic treatment and experienced drug-induced liver injury (DILI) | Randomized clinical trial (55) | Randomized children were administered either silymarin (5 mg/kg per day) or folic acid (1 mg per day) for 1 month | Three months | Folic acid group had significantly decreased ALT, AST, and GGT levels compared to the patients in the silymarin groups. Both treatments were safe and effective in the management of DILI, but folic acid seems to be superior | [10] |
Patients with severe preeclampsia whose pregnancy was terminated | Randomized clinical trial (30) | Case group received 70 mg of silymarin, and control group received the placebo at 3 and 24 h after the termination of pregnancy | Three days | Hepatic enzymes ALT and AST level decreased significantly during 36 and 60 h after the termination of pregnancy in the study group compared to control group. This indicates that silymarin improves liver disorder in severe preeclampsia | [12] | ||
Non-cirrhotic patients with non-alcoholic steatohepatitis (NASH) | Randomized double-blind placebo control phase II clinical trial (78) | Silymarin treatment group 400 mg (26 patients) and 700 mg (27 patients) and placebo group (25 patients) in dosing frequency thrice a day | 48 weeks | Significant variation was not observed in side effect among the treatment group and patient treated with silymarin in patients. Whether NASH is treated with silymarin is inconclusive due to the lack of substantial number of patients who meet the histological criteria and therefore required additional clinical trial | [115] | ||
New cases of pulmonary tuberculosis patients | Randomized double-blind clinical trial (70) | Test group received silymarin 140 mg three times a day + standard antituberculosis treatment, and control group received standard antituberculosis treatment only | Two weeks | Silymarin was proved to be safe without adverse event, but measurable hepatoprotective effect was not observed among patients receiving tuberculosis treatment | [99] | ||
Liver disease (78% with daily alcohol use) | Double-blind control study (97) | Test group (47) received silymarin 420 mg/day, and control group (50) received placebo | 4 weeks | Liver function parameters, liver histology, ALT, and AST were observed to be improved | [145] | ||
Alcoholic liver disease (ALD) (50% with cirrhosis) | Double-blind comparative study (116) | Test group (57) received silymarin 420 mg/day, and control group (59) received placebo | 3 months | No significant effects | [166] | ||
ALD or non-alcoholic fatty liver disease (NAFLD) (70% with cirrhosis) | Randomized control trial (170) | Test group (87) received silymarin 420 mg/day, and control group (59) received placebo | Median 41 months | Ameliorate the survival rate, and difference in survival was observed mostly in patients with ALD and liver cirrhosis and those with less serious aliments (Child class A) | [46] | ||
ALD | 36 | Test group (17) received silymarin, and control group (19) received placebo | 6 months | Decrease in ALT, bilirubin and procollagen synthesis | [45] | ||
ALD | Double-blind protocol NA (not available) | Test group received silymarin 420 mg/day, and control group received placebo | 6 months | Improvement in antioxidative system by decreasing MDA and increasing GSH in liver cell | [113] | ||
ALD (72% with cirrhosis) | Double-blind randomized control trial (59) | Test group (25) received silymarin 280 mg/day, and control group (34) received placebo | 15 months | Blood glucose level was observed to get improved (including fasting); HbAlC and MDA daily dose of insulin administration get decreased in ALT and AST | [18] | ||
Insulin-treated type 2 diabetic mellitus with alcoholic cirrhosis | Randomized clinical trial (60) | Test group (30) received silymarin 680 mg/day + standard treatment, and control group (30) received standard treatment only | 12 months | No measurable effect was observed on progression, and survival of cells involved in liver disease | [171] | ||
ALD with cirrhosis | Double-blind randomized control multicenter trial (200) | Test group (103) received silymarin 450 mg/day, and control group (97) received placebo | 2 years | Decrease MDA and aminoterminal propeptide of procollagen type 3 | [127] | ||
ALD with cirrhosis | Randomized double-blind placebo control clinical trial (49) | Test group (24) received silymarin 450 mg/day, and control group (25) received placebo | 6 months | Slight upsurge in the level of glutathione and down surge of lipid peroxidation were observed in the patient with ALD was silymarin administration | [88] | ||
2 | Picroside | Liver disease patients | Double-blinded placebo randomized clinical trial | Test group received the herbal formulation contains picroside, and control group received placebo | NA | Reduction in bilirubin value by 2.5 mg was achieved by 27.4 days for the picroside herbal formulation treatment group, whereas 75.9 days are required for the placebo group | [6] |
Hypolipidemic patients with liver disease | Double-blind placebo study | Test group receive 2 gm kutaki formulation along with atorvastatin 20 mg two times a day, and control group received 500-mg starch powder with atorvastatin 20 mg in same duration | NA | Test group showed significant increase in the liver function enzyme parameters as compared to the placebo group | [105] | ||
3 | Phyllanthin | Oxidative stress, liver damage, and patients with hangover symptoms | Randomized placebo-controlled trial | Test group received 750 mg/day; Phyllanthus amarus ethanol extract and control group received placebo (15) | Ten days | Phyllanthus amarus treatment group showed significant control over hangover, inflammation, and liver function following intoxication by reducing blood alcohol and upregulating cytokine IL-8 and IL-10 as compared to control group | [49] |
Patients suffering from liver disease | Clinical study (107) | Test group received 3 g of Phyllanthus amarus powder for three times for a day orally with water (98) | 45 days | Significant decrease in SGPT and bilirubin and increase in hemoglobin with patient treated with test drug | [128] | ||
4 | Glycyrrhizin | A healthy individual consume alcohol (vodka) nightly for 12 days | Randomized, double-blind, placebo, cross over study (12; six males and six females) | Test group received the glycyrrhizin product with daily alcohol, and control group received alcohol alone daily | 12 days | Plasma glutathione level and ALP significantly decreased in alcohol control group suggested that consumption of glycyrrhizin product during the alcohol consumption may improve the liver health compared with the consumption of alcohol alone | [29] |
Digestive tract cancer patients | Clinical trial (84) | Test group treated with the saponin (160 mg i.v once a day) with standard cancer chemotherapy, and control group received only standard cancer chemotherapy alone | NA | Test group showed significantly lower liver transaminase level and higher level of neutrophile, granulocyte, and white blood cells when compared with the standard chemotherapy control group | [55] | ||
Patients with hepatitis E and severe jaundice | Clinical trial (78) | Test group received magnesium isoglycyrrhizinate, and control group received an intravenous injection of 150 mg of magnesium once a day | 6 weeks | Use of magnesium isoglycyrrhizinate in test group showed improved effective against the hepatitis E virus infection with severe jaundice as compared to the control group | [182] | ||
Patients with chronic hepatitis B | Clinical trial (64) | Test group received magnesium isoglycyrrhizinate, and control group received an intravenous injection of saponin once a day | 4 weeks | Liver function was improved in both patients group, but no statistically significant difference observed in test group and control group | [19] | ||
5 | Curcumin | Patients with liver cirrhosis | Randomized double-blind placebo control trial (70) | Test group (35) received 1000 mg/day curcumin, and control group received the placebo | 3 months | Curcumin supplement showed beneficial effect in decreasing disease activity score and severity of cirrhosis in patients with liver cirrhosis as compared to placebo group | [120] |
Chronic alcoholic patients | Randomized double-blind placebo control trial (48) | One group received curcumin-galactomannoside complex 500 mg/day, and another group received placebo drug per day | 8 weeks | Curcumin-galactomannoside complex group showed significant decrease in liver function markers such as transaminase and GGT increase in endogenous antioxidant (GSH, SOD, GPx) and decrease in inflammatory markers (IL-6 and CRP) level as compared to placebo group | [159] | ||
Type 2 diabetic mellitus (T2DM) patients and measure glycemic, hepatic, and inflammatory biomarker measure | Randomized double-blind placebo control trial (100) | Test group received standard treatment, dietary advice plus curcuminoids 500 mg/day coadministered with piperine 5 mg/day, and control group received the standard treatment, dietary advice plus placebo drug | 3 months | Intervention group showed significant reduction in serum level of glucose, HbA1c, and low serum level of ALT and AST as compared to the placebo group. The study concluded that curcuminoid mixed with piperine when coadministered with diabetic medicine shows improved hepatoprotective and glycemic control in T2DM patients | [124] | ||
Patients with non-alcoholic fatty liver disease (NAFLD) | Double-blind randomized clinical trial (46; 21 males and 25 females) | Intervention group received six turmeric capsules containing 500 mg in each, and control group received placebo drug daily | 12 weeks | Turmeric consumption decreased the serum level of glucose, insulin, HOMA-IR, and leptin as compared to the placebo group. This may be useful in control of NAFLD complications | [116] | ||
Patients diagnosed with non-alcoholic fatty liver disease (NAFLD) | Randomized double-blind placebo control trial (102) | Intervention group received 1000 mg/day curcumin in 2 divided dose (n = 50), and control group received the placebo drug (n = 52). Both groups received the dietary and lifestyle advice before the start of clinical trial | 8 weeks | Curcumin supplement group showed reduction of body mass index, waist circumference, decrease level of AST and ALT as compared to the placebo drug treatment group. This indicated that intervention improve the liver fat and normalize liver biomarker level in patients with NAFLD | [125] | ||
Non-alcoholic fatty liver disease (NAFLD) | Randomized double-blind placebo control trial (80) | Intervention group received amorphous curcumin powder 500 mg/day (equivalent to 70 mg/day curcumin), and control group received the placebo drug | 8 weeks | Curcumin-treated group showed reduction of liver fat, body mass index, total cholesterol, low-density lipoprotein, triglyceride, AST, ALT, glucose, glycated hemoglobin as compared to the placebo drug-treated group. This indicated that curcumin amorphous powder improves liver of patients with NAFLD | [137] | ||
6 | Berberine | Non-alcoholic fatty liver disease (NAFLD) | Randomized parallel controlled open-label clinical trial (184) | Lifestyle intervention group or placebo group (n = 62) (60) is lifestyle intervention plus pioglitazone 15 mg qd (n = 60), lifestyle intervention plus 0.5 g berberine t.i.d. (n = 62) | 16 weeks | As compared to the placebo and pioglitazone treatment group, intervention group showed significant reduction in serum lipid profile, body weight, HOMA-IR which help to ameliorate NAFLD and related metabolic disorder by directly regulating the hepatic lipid metabolism | [185] |