Anti-inflammatory, antioxidant, anti-fibrotic and schistosomicidal properties of plumbagin in murine schistosomiasis

Parasite Immunol. 2022 Nov;44(11):e12945. doi: 10.1111/pim.12945. Epub 2022 Sep 6.

Abstract

Schistosomiasis is still a major health problem affecting nearly 250 million people worldwide and causes approximately 280,000 deaths per year. The disease causes a serious granulomatous inflammatory response that produces significant mortality. Plumbagin reportedly displays anti-inflammatory, anti-fibrotic, antioxidant and anthelmintic properties. This study further elucidates these properties. Mice were infected with schistosomes and divided into five groups: non-infected untreated (C); infected untreated (IU); non-infected treated with plumbagin (P); infected treated with plumbagin (PI) and infected treated with praziquantel (PZ). Mice treated with 20 mg plumbagin/kg body weight showed reduction of 64.28% and 59.88% in male and female animals, respectively. Also, the number of eggs/g tissue was reduced 69.39%, 68.79% and 69.11% in liver, intestine and liver/intestine combined, respectively. Plumbagin alleviated schistosome-induced hepatosplenomegaly and reduced hepatic granuloma and liver collagen content by 62.5% and 35.26%, respectively while PZQ reduced hepatic granuloma and liver collagen content by 41.11% and 11.21%, respectively. Further, plumbagin treatment significantly (p < .001) reduced IL-4, IL-13, IL-17, IL-37, IFN-γ, TGF-β and TNF-α levels and significantly (p < .001) upregulated IL-10. Plumbagin treatment restored hepatic enzymes activity to nearly normal levels and induced an increase in catalase, SOD, GSH, total thiol and GST in liver tissue homogenate. NO and LPO content was, however, decreased. Moreover, serum IgG levels significantly increased. The present study is the first to report immunomodulatory and schistosomicidal activities of plumbagin in schistosomiasis.

Keywords: Schistosoma mansoni; antioxidants; cytokines; liver enzymes; liver fibrosis; plumbagin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthelmintics* / pharmacology
  • Anthelmintics* / therapeutic use
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Catalase / therapeutic use
  • Female
  • Granuloma / drug therapy
  • Immunoglobulin G
  • Interleukin-10
  • Interleukin-13
  • Interleukin-17
  • Interleukin-4
  • Liver
  • Male
  • Mice
  • Naphthoquinones
  • Praziquantel / pharmacology
  • Praziquantel / therapeutic use
  • Schistosoma mansoni
  • Schistosomiasis mansoni* / drug therapy
  • Schistosomiasis* / drug therapy
  • Schistosomicides* / therapeutic use
  • Sulfhydryl Compounds / therapeutic use
  • Superoxide Dismutase / therapeutic use
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha

Substances

  • Anthelmintics
  • Anti-Inflammatory Agents
  • Antioxidants
  • Immunoglobulin G
  • Interleukin-13
  • Interleukin-17
  • Naphthoquinones
  • Schistosomicides
  • Sulfhydryl Compounds
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Praziquantel
  • Catalase
  • Superoxide Dismutase
  • plumbagin