Antihyperlipidemic effect of iridoid glycoside deacetylasperulosidic acid isolated from the seeds of Spermacoce hispida L. - A traditional antiobesity herb

J Ethnopharmacol. 2019 Dec 5;245:112170. doi: 10.1016/j.jep.2019.112170. Epub 2019 Aug 18.

Abstract

Ethnobotanical relevance: The interest on herbal health supplements for obesity is increasing globally. Our previous ethnobotanical survey in Tiruvallur district, Tamil Nadu, India indicated the use of Spermacoce hispida L. seeds for the treatment of obesity.

Aim of the study: This study was aimed to validate the traditional claim and to identify the antihyperlipidemic principle in the seeds of Spermacoce hispida using bioassay guided fractionation method.

Methods: Bioassay monitored fractionation of the aqueous extract from Spermacoce hispida seeds was carried out using triton WR 1339 induced hyperlipidemic animals. It yielded deacetylasperulosidic acid (DAA) as the active ingredient. Pharmacokinetic properties of DAA were predicted using DataWarrior and SwissADME tools. In vitro antiobesity and antihyperlipidemic effects of DAA were evaluated in 3T3L1 preadipocytes and HepG2 cells, respectively. The chronic antihyperlipidemic efficacy of DAA was evaluated in high fat diet fed rats.

Results: DAA did not show any mutagenic and tumorigenic properties. It bound with PPARα with comparable ligand efficiency as fenofibrate. The treatment with DAA significantly lowered the proliferation of matured adipocytes, but not preadipocytes. The treatment of steatotic HepG2 cells with DAA significantly decreased the LDH leakage by 43.03% (P < 0.05) at 50 μM concentration. In triton WR 1339 induced hyperlipidemic animals, the treatment with 50 mg/kg dose significantly lowered the TC, TG and LDL-c levels by 40.27, 46.00 and 63.65% respectively. In HFD fed animals, the treatment at 10 mg/kg decreased BMI and AC/TC ratio without altering SRBG. It also improved serum lipid, transaminases and phosphatases levels of HFD fed animals. The treatment lowered adipocyte hypertrophy and steatosis of hepatocytes.

Conclusion: This preliminary report supported the traditional use of Spermacoce hispida for the treatment of obesity. Further detailed investigations on the long term safety, efficacy and molecular mode of action of Spermacoce hispida and DAA will throw more light on their usefulness for the management of obesity.

Keywords: Bioassay guided fractionation; Healthcare supplements; Obesity; Siddha.

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Anti-Obesity Agents / pharmacokinetics
  • Anti-Obesity Agents / pharmacology
  • Anti-Obesity Agents / therapeutic use*
  • Cell Survival / drug effects
  • Hep G2 Cells
  • Humans
  • Hyperlipidemias / drug therapy*
  • Hypolipidemic Agents / pharmacokinetics
  • Hypolipidemic Agents / pharmacology
  • Hypolipidemic Agents / therapeutic use*
  • India
  • Iridoid Glycosides / pharmacokinetics
  • Iridoid Glycosides / pharmacology
  • Iridoid Glycosides / therapeutic use*
  • Lipid Metabolism / drug effects
  • Male
  • Medicine, Traditional
  • Mice
  • Rats, Wistar
  • Rubiaceae*
  • Seeds

Substances

  • Anti-Obesity Agents
  • Hypolipidemic Agents
  • Iridoid Glycosides