Platycodon grandiflorus Fermented Extracts Attenuate Endotoxin-Induced Acute Liver Injury in Mice

Nutrients. 2020 Sep 13;12(9):2802. doi: 10.3390/nu12092802.

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.

Keywords: Acute liver injury; Platycodon grandiflorus; anti-inflammation; antioxidant; fermentation; nitric oxide.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Apoptosis
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Cytokines / metabolism
  • Endotoxins
  • Fermentation
  • Galactosamine
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Lipid Peroxidation / drug effects
  • Lipopolysaccharides
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Necrosis
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Platycodon*
  • RAW 264.7 Cells
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Endotoxins
  • Lipopolysaccharides
  • Plant Extracts
  • Nitric Oxide
  • Galactosamine
  • Nitric Oxide Synthase Type II