Extracts of Sida cordifolia contain polysaccharides possessing immunomodulatory activity and rosmarinic acid compounds with antibacterial activity

BMC Complement Med Ther. 2022 Jan 27;22(1):27. doi: 10.1186/s12906-022-03502-7.

Abstract

Background: The overuse of antibiotics has led to increased antimicrobial resistance, but plant-derived biological response modifiers represent a potential alternative to these drugs. This investigation examined the immunomodulatory and antibacterial activities of Sida cordifolia (used in ethnomedicinal systems to treat infectious disease).

Methods: Successive extractions were performed from the roots of these plants in hexane, chloroform, methanol and water. Immunomodulatory activity was determined in a series of experiments measuring the responses of splenocytes, macrophages and an in vivo model of innate immunity (Galleria mellonella). Antibacterial activity was assessed by determining minimum inhibitory/bactericidal concentrations (MIC/MBCs) for various Gram-positive and Gram-negative bacterial strains.

Results: Immunomodulatory activity was confined to the aqueous extract, and further fractionation and biochemical analysis yielded a highly potent polysaccharide-enriched fraction (SCAF5). SCAF5 is a complex mixture of different polysaccharides with multiple immunomodulatory effects including immune cell proliferation, antibody secretion, phagocytosis, nitric oxide production, and increased expression of pro-inflammatory cytokines. Furthermore, Galleria mellonella pre-treated with SCAF5 produced more haemocytes and were more resistant (P < 0.001) to infection with methicillin-resistant Staphylococcus aureus (MRSA) with a 98% reduction in bacterial load in pre-treated larvae compared to the negative control. The antibacterial activity of Sida cordifolia was confined to the methanolic fraction. Extensive fractionation identified two compounds, rosmarinic acid and its 4-O-β-d-glucoside derivative, which had potent activity against Gram-positive antibiotic-resistant bacteria, including MRSA.

Conclusions: Sida cordifolia counters bacterial infections through a dual mechanism, and immunomodulatory polysaccharides from this plant should be isolated and characterised to realise their potential as anti-infective agents. Such properties could be developed as an antibiotic alternative (1) in the clinic and (2) alternative growth promoter for the agri-food industry.

Keywords: Antibiotic alternative; Antibiotic resistance; Antimicrobial; Feed supplement; Galleria mellonella; Immunomodulation; Immunostimulant; Plant-derived biological response modifiers; Polysaccharides; Rosmarinic acid; Sida cordifolia.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Cinnamates / pharmacology*
  • Depsides / pharmacology*
  • Drug Resistance, Bacterial / drug effects*
  • Female
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects*
  • Immunologic Factors / pharmacology*
  • Larva / microbiology
  • Malvaceae / chemistry*
  • Medicine, Traditional
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Moths / microbiology
  • Plant Extracts / pharmacology
  • Plant Roots / chemistry
  • Polysaccharides / pharmacology*
  • Rosmarinic Acid

Substances

  • Anti-Bacterial Agents
  • Cinnamates
  • Depsides
  • Immunologic Factors
  • Plant Extracts
  • Polysaccharides