Co-Treatments of Gardeniae Fructus and Silymarin Ameliorates Excessive Oxidative Stress-Driven Liver Fibrosis by Regulation of Hepatic Sirtuin1 Activities Using Thioacetamide-Induced Mice Model

Abstract

Gardeniae Fructus (GF, the dried ripe fruits of Gardenia jasminoides Ellis) has traditionally been used to treat various diseases in East Asian countries, such as liver disease. Silymarin is a well-known medicine used to treat numerous liver diseases globally. The present study was purposed to evaluate the synergistic effects of GF and silymarin on the thioacetamide (TAA)-induced liver fibrosis of a mouse model. Mice were orally administered with distilled water, GF (100 mg/kg, GF 100), silymarin (100 mg/kg, Sily 100), and GF and silymarin mixtures (50 and 100 mg/kg, GS 50 and 100). The GS group showed remarkable amelioration of liver injury in the serum levels and histopathology by observing the inflamed cell infiltrations and decreases in necrotic bodies through the liver tissue. TAA caused liver tissue oxidation, which was evidenced by the abnormal statuses of lipid peroxidation and deteriorations in the total glutathione in the hepatic protein levels; moreover, the immunohistochemistry supported the increases in the positive signals against 4-hydroxyneal and 8-OHdG through the liver tissue. These alterations corresponded well to hepatic inflammation by an increase in F4/80 positive cells and increases in pro-inflammatory cytokines in the hepatic protein levels; however, administration with GS, especially the high dose group, not only remarkably reduced oxidative stress and DNA damage in the liver cells but also considerably diminished pro-inflammatory cytokines, which were driven by Kupffer cell activations, as compared with each of the single treatment groups. The pharmacological properties of GS prolonged liver fibrosis by the amelioration of hepatic stellate cells’ (HSCs’) activation that is dominantly expressed by huge extracellular matrix (ECM) molecules including α-smooth muscle actin, and collagen type1 and 3, respectively. We further figured out that GS ameliorated HSCs activated by the regulation of Sirtuin 1 (Sirt1) activities in the hepatic protein levels, and this finding excellently reenacted the transforming growth factor-β-treated LX-2-cells-induced cell death signals depending on the Sirt1 activities. Future studies need to reveal the pharmacological roles of GS on the specific cell types during the liver fibrosis condition.

6-Shogaol Ameliorates Liver Inflammation and Fibrosis in Mice on a Methionine- and Choline-Deficient Diet by Inhibiting Oxidative Stress, Cell Death, and Endoplasmic Reticulum Stress

“…Moreover, hepatic levels of malondialdehyde (MDA), another biomarker for lipid oxidation [ 23 ], were also significantly reduced by 6-shogaol ( p < 0.05; Figure 5 C). Immunofluorescence (IF) staining for 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker for oxidative DNA damage [ 24 ], showed that the increased number of 8-OHdG-stained cells in mice exposed to the MCD diet was largely mitigated by 6-shogaol ( p < 0.001; Figure 5 D,E). Additionally, 6-shogaol effectively restored the reduced hepatic glutathione (GSH) levels in mice exposed to the MCD diet ( p < 0.05; Figure 5 F).…”

“…Molecules 2024, 29, x FOR PEER REVIEW 7 of 19 malondialdehyde (MDA), another biomarker for lipid oxidation [23], were also significantly reduced by 6-shogaol (p < 0.05; Figure 5C). Immunofluorescence (IF) staining for 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker for oxidative DNA damage [24],…”

Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment

“…Silymarin has also demonstrated antifibrotic effects, inhibiting the conversion of hepatic stellate cells into myofibroblasts, downregulating the expression of genes involved in fibrosis, such as procollagen III, alpha-SMA , and TGF-beta [ 187 ]. Silymarin also has a high antioxidant capacity, having the ability to neutralize free radicals, maintain the correct mitochondrial function, and activate the synthesis of protective molecules against oxidation and with reparative capacity, such as several heat shock proteins (HSPs), thioredoxin and sirtuins [ 194 ].…”

Circular RNA circ_0003609 ameliorates hypertrophied ligamentum flavum by regulating the miR-155/SIRT1 axis

“…The miR-155/SIRT1 axis regulates HLF fibrosis Next, we examined miR-155's target and its connection to HLF fibrosis. SIRT1, a recognized regulator of fibrosis [21], was identified by bioinformatics analysis as a potential miR-155 target (Fig. 4A).…”