Mulberry leaf reduces inflammation and insulin resistance in type 2 diabetic mice by TLRs and insulin Signalling pathway

BMC Complement Altern Med. 2019 Nov 21;19(1):326. doi: 10.1186/s12906-019-2742-y.


Background: It has been testified that Diabetes mellitus (DM) has a close association with chronic inflammation and Toll-like Receptors (TLRs), and DM could be prevented by mulberry leaf. Therefore, a hypothesis came into being that mulberry leaf could ameliorate proinflammation and insulin resistance (IR) through TLRs and insulin signalling pathways.

Methods: Water extracts of mulberry leaf (WEM) was given to diabetic mice by gavage for 10 weeks, and the diabetic mice was injected with low-dose streptozocin, fed with high-fat and high-sugar diet. Oral glucose tolerance tests (OGTTs) were conducted. At the same time, homeostasis model assessment of insulin (HOMA-IR) and the level of the inflammatory factor, tumour necrosis factor-α (TNF-α) was measured. The expressions of critical nodes of TLRs and insulin signalling pathway were also examined.

Results: WEM contributed to a significant decrease in fasting blood glucose, AUC from the investigation of OGTTs and HOMA-IR. The levels of the inflammatory factor, tumour necrosis factor-α (TNF-α) also declined. Moreover, WEM suppressed the expression of TLR2, myeloid differentiation primary-response protein 88 (MyD88), tumour-necrosis-factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B (NF-κB) in the skeletal muscle. WEM could up-regulate the expression of insulin receptor (InsR) and insulin receptor substrate 1 (IRS1), and down-regulate the phosphorylation of IRS1 in adipose tissue.

Conclusion: Through this study, a conclusion could be made that WEM mitigates hyperglycemia, IR, and inflammation through the interactions among TLR2 signalling pathway, insulin signalling pathway and TNF-α.

Keywords: Diabetic mice; Inflammation; Insulin resistance; Mulberry leaf.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism
  • Inflammation / metabolism*
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance / physiology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Morus*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Signal Transduction / drug effects
  • Toll-Like Receptor 2 / blood
  • Toll-Like Receptor 2 / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism


  • Blood Glucose
  • Insulin
  • Plant Extracts
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha