Table 2 Summary of therapeutic activities of different phytochemicals of Bergenia ciliata
From: Bergenia ciliata as a future candidate for liver diseases: a concise review
S. no | Phytochemical | Class | Protective action | Model | References |
|---|---|---|---|---|---|
1 | Gallic acid | Phenol | Decreases liver steatosis, body weight and plasma insulin levels. Hepatic steatosis related genes expression show that acetyl-CoA carboxylase and fatty acid synthase mRNA are significantly reduced | HFD-induced steatosis in mice | Sousa et al. (2020) |
2 | Gallic acid | – | Elevation of liver SOD and CAT activities and reduction of the liver TNF-α expression, MDA and serum protein carbonyl | Fluoxetine-induced liver damage in rats | Karimi-Khouzani et al. (2017) |
3 | Gallic acid | – | Reduces body weight, liver, adipose tissue, serum parameters (TAG, phospholipid, total cholesterol, LDL, cholesterol, insulin and leptin) and hepatic steatosis. Also decreases oxidative stress (declining GSSG and enhancing GSH, GPx, GRd and GST) | HFD-induced obesity in rats | Hsu and Yen (2007) |
4 | Gallic acid | – | Diminishes HA, collagen IV, MDA as well as the serum levels of ALT, AST, and γ-GT. Also decrease in MMP-2, TIMP-1 mRNA, and MMP-2 protein levels | CCl4-induced hepatic fibrosis in mice | Wang et al. (2014) |
5 | Gallic acid | – | Reduces cellular oxidative stress by decreasing ROS production, which in turn is unfavorable for HCV | Hepatocarcinoma cell lines (Huh7) | Govea-Salas et al. (2016) |
6 | Gallic acid | – | Reverses HFD-induced disturbances to a wide range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism | NAFLD-induced in mice | Chao et al. (2014) |
7 | Gallic acid | – | Lessens inflammation, activated HSCs, deposition of collagen. Also decline in COX-2 positive cells in liver | NDEA-induced liver injury | Latief et al. (2016) |
8 | Gallic acid | – | Limits hepatocyte necroptosis, which was characterized by reduced expression of distinct necroptotic signals RIP1 and RIP3 and release of high mobility group box protein 1. Also induces NRF2 expression in ethanol-incubated hepatocytes | Ethanol-induced hepatocyte necroptosis | Zhou et al. (2019) |
9 | Gallic acid | – | Inhibitory effect on lipid accumulation through the activation of AMPK in hepatocytes. Also suppresses hepatocyte apoptosis and inflammation | Human hepatoma cell lines (HepG2) | Tanaka et al. (2020) |
10 | Gallic acid | – | Decreases AST, ALT, LDH activity. Increases paraoxonase and arylesterase activity | Ethanol-induced liver injury in rats | Kartkaya et al. (2013) |
11 | Gallic acid | – | Decline in AST, ALT, MDA, and elevation of GSH, CAT, SOD and GST | Cyclophosphamid-induced hepatotoxicity in rats | Oyagbemi et al. (2016) |
12 | Gallic acid | – | Triglyceride and blood glucose concentrations are significantly improved. PPAR-γ expression and the Akt signaling pathway are activated | Diet-induced obesity mice | Bak et al. (2013) |
13 | Gallic acid | _ | Decreases AST, ALT, ALP acid phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, bilirubin, alpha-fetoprotein, carcinoembryonic antigen, argyophillic nucleolar organizing regions and PCNA | NDEA-induced hepatocellular carcinoma in rats | Jagan et al., (2008 |
14 | Gallic acid | – | Diminishes levels of lipid peroxidation, serum marker enzyme activity with a concomitant increase in GSH, CAT, SOD, GPx and GST | Lindane-induced hepatic and renal toxicity | Padma et al. (2011) |
15 | Gallic acid | – | Downregulation in the gene expression levels of hepatic gamma-glutamyl transferase and heat shock protein gp96. Regulation of STAT3 signaling pathway via the outstanding bioactivities of gallic acid including antioxidant potential, anti-inflammatory effect, apoptotic action, and antitumor impact | NDEA-induced hepatocellular carcinoma in rats | Aglan et al. (2017) |
16 | Bergenin | Phenol | Liver injury alters the pharmacokinetic behavior of bergenin and enhances its absorption after an oral dosing, which may promote the therapeutic efficacies of bergenin | CCl4-induced liver injury in rats | Rong-Hua et al. (2016) |
17 | Bergenin | – | Reduces the release of ROS, downregulates inflammatory factors, and inhibited apoptosis and autophagy. Additionally, expression of PPAR-γ-related genes is increased and phosphorylation of P38 MAPK, NF-κB p65 and JAK2/STAT1-related proteins is decreased | Hepatic ischemia reperfusion in mice | Xiang et al. (2020) |
18 | Bergenin | – | Diminishes HA, FN, laminin, type I collagen, α-SMA, matrix metalloproteinases and tissue inhibitors of metalloproteinases. Activates PPAR-γ and inhibits TGF-β and autophagy | CCl4 and bile duct ligated mice | Xia et al. (2020) |
19 | Bergenin + metformin | – | Lower body weight gain, plasma glucose and insulin. Whereas the level of Hb and liver glycogen is significantly increased. Gluconeogenic enzymes (glucose-6-phosphatase and fructose-1, 6-bisphosphatase) are significantly decreased and glycolytic enzymes (Hexokinase and glucose-6- phosphate dehydrogenase) are increased | HFD-induced type 2 diabetes in mice | Ambika and Saravanan (2016) |
20 | Bergenin + Gallic acid | – | Improve cell morphology, elevate cell viability, lower LDH, AST, ALT and MDA levels. Also promote SOD and CAT activities and total GSH content | Ethanol and tert-butyl hydroperoxide-induced oxidative stress in human hepatoma cells (HepG2) | Sriset et al. (2020) |
21 | β-Sitosterol | Sterol | Inhibits oxidative stress by causing diminution of intracellular enyzmic antioxidants such as SOD and CAT. Significantly reduces expression of HSCs activation markers (hydroxyproline, collagen, α-SMA, desmin, vimentin, and MMP 9) | CCl4-induced liver injury in rats | Devaraj et al. (2020) |
22 | β-Sitosterol | – | Expression of PPAR-γ ligand and PON-1/ARE enzymes activities increases. Also, the activities of SOD, CAT enzymes and HDL-c levels display elevation. Whereas, significant decrease in MDA content, cholesterol, TG and LDL-c levels are revealed | Gamma Irradiated rats | Moustafa and Thabet (2017) |
23 | β-Sitosterol and its derivatives | – | Decrease the serum activity of AST ALT, TNF-α, IL-1β, IL-6) levels. Improve the activities of antioxidant enzymes such as SOD, GSH and CAT. Meanwhile, the expressions of Nrf2 and HO-1 are enhanced | Lipopolysaccharide/ D-galactosamine-induced acute hepatic injury in mice | Yin et al. (2018) |
24 | β-Sitosterol + Stigmasterol | – | Decrease in hepatic cholesterol, TGs with polyunsaturated fatty acids and alterations of free hepatic FFA | NAFLD-induced in mice | Feng et al. (2018) |
25 | Arbutin | Glycoside | TB test and MTT assays reveal the improvement in cell viability | Tert-Butyl hydroperoxide-induced toxicity in Hep-G2 Cell Line | Seyfizadeh et al., (2012 |
26 | Arbutin | – | Raises the levels of serum albumin and lowers the bilirubin and lipid peroxidation | CCl4-induced hepatotoxicity in rats | Mirshahvalad et al. (2016) |
27 | Arbutin | – | Decrease in ALP, ALT and AST enzyme | X-irradiated mice | Nadi et al. (2019) |
28 | Tannic acid | Phenol | Increases activities of SOD, CAT, GSH-Px, eNOS and serum level of NO. Moreover, reduces expression of angiotensin II receptor-1, IL-1β, TNF-α, TGF-β, caspase-3, c-fos, c-jun, the ratio of Bax/bcl-2, TIMP-1. Increases MMP-9 and MMP-1 | CCl4-induced liver injury in mice | Chu et al. (2016) |
29 | Tannic acid | – | Suppresses overexpression of IL-1β, TNF-α, c-fos, c-jun, NF-κB (p65) and caspase-3, downregulates bax and upregulates bcl-2, Nrf2 and HO-1 | Acetaminophen-induced hepatotoxicity in mice | Zhang et al. (2017) |
30 | d-Limonene | Terpene | Preserves glutathione, SOD, catalase. Decreases hydroxyproline, malondialdehyde content, TNF-α, TGF β, and α-SMA expressions | CCl4-induced liver toxicity in Wistar rats | Ahmad et al. (2018) |
31 | d-Limonene | – | Diminishes the levels of plasma glucose and elevates insulin. It also restores the declines the lipid peroxide and restores antioxidant enzyme levels in liver and kidney | Streptozotocin-induced diabetic rats | Murali et al. (2012) |
32 | d-Limonene | – | Reduces systolic blood pressure, heart rate, fasting blood glucose, plasma insulin, hepatic marker enzymes, hepatic lipids, circulatory lipid peroxidation by-products and hepatic phase I enzyme activities. Increases circulatory nonenzymic antioxidant concentrations and hepatic phase II enzyme activities | HFD and L-NAME-induced NAFLD in Wistar rats | Santiago et al. (2012) |
33 | d-Limonene | – | Decreases cellular alteration foci, neoplastic nodules and hepatocellular carcinomas and increases apoptotic indices of cellular alteration foci | Hepatocarcinogenesis in Sprague–Dawley rats | Kaji et al. (2001) |
34 | β-Caryophyllene | Sesquiterpene | Reduces the gene expressions of Collagen-1α1, TGF-β1 and TIMP1 | CCl4-induced liver fibrosis in Wistar rats | Calleja et al. (2013) |
35 | β-Caryophyllene | – | Attenuates the pro-inflammatory phenotypic `M1` switch of Kupffer cells and decreases the expression of vascular adhesion molecules intercellular adhesion molecule 1, E-Selectin and P-Selectin as well as the neutrophil infiltration | Alcoholic steatohepatitis-induced in mice | Varga et al. (2018) |
36 | β-Caryophyllene | – | Lowers hepatic lipid accumulation, TC, LDL and elevates HDL | Hypercholesterolemia-induced in Wistar rats | Harb et al. (2018) |