Abstract
Endotoxin-induced acute liver injury is mediated by an excessive inflammatory response, hepatocellular oxidative stress, and apoptosis. Traditional medicinal plants have been used to treat various disorders. Platycodon grandifloras (PG) has been shown to be beneficial in relieving cough and asthma and to have anti-tumor, anti-inflammatory, anti-diabetic activities. The pharmacological action of PG is mainly due to saponins, flavonoids, phenolic, and other compounds. However, raw PG exhibits some side effects at high doses. Here, we extracted raw PG with varying fermentation methods and examined its anti-inflammatory effect and associated signaling kinases in Raw264.7 cells. Then, we investigated the effect of fermented black PG (FBPG) on endotoxin-induced liver injury. Mice were administered FBPG orally at 1 h before the lipopolysaccharide and D-galactosamine (LPS/GalN) injection and sacrificed after 5 h. Black PG (BPG) and FBPG showed a significant reduction in pro-inflammatory cytokines and extracellular nitric oxide (NO); p-38 and ERK signaling was involved in reducing inducible NO synthase in Raw264.7 cells. Consistently, FBPG attenuates LPS/GalN-induced liver injury; plasma ALT and AST, hepatic necrosis, pro-inflammatory cytokines, apoptosis, and lipid peroxidation were all reduced. In conclusion, PG extracts, particularly FBPG, play anti-inflammatory, antioxidant, and anti-apoptotic roles, alleviating endotoxin-induced acute liver injury. Processing raw PG into FBPG extract may be clinically useful by improving the pharmacologically active ingredients and reducing the required dosage.
Highlights
The liver is an essential organ involved in energy metabolism, protein synthesis, fat metabolism, glycemic control, and detoxification; many patients with acute and chronic liver diseases suffer from multiple layers of serious complications
Among the eleven flavonoids, the contents of epigallocatechin, catechin, epicatechin, and quercetin were significantly increased in Black PG (BPG) and fermented black PG (FBPG), and the total flavonoid content was almost three times higher than dried PG (DPG) (Table 2)
Raw Platycodon grandifloras (PG) was processed by an optimized extraction and fermentation method to become BPG and FBPG
Summary
The liver is an essential organ involved in energy metabolism, protein synthesis, fat metabolism, glycemic control, and detoxification; many patients with acute and chronic liver diseases suffer from multiple layers of serious complications. Animal models of liver injury include carbon tetrachloride-, galactosamine-, or alcohol-induced hepatotoxicity and choline deficiency; the addition of lipopolysaccharide (LPS), serving as cofactor, augments the hepatitis with severe hepatic congestion resulting in rapid death [6,7,8]. In these liver injury models, Kupffer cells are major sources of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and IL-18. Galactosamine (GalN) is a potent hepatotoxin that depletes uridine nucleotides (UTPs), which decreases RNA and protein synthesis, primarily in the liver; GalN enhances sensitivity to elevated TNF-α levels [10]
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