Amelioration of dry eye syndrome in db/db mice with diabetes mellitus by treatment with Tibetan Medicine Formula Jikan Mingmu Drops

J Ethnopharmacol. 2019 Sep 15:241:111992. doi: 10.1016/j.jep.2019.111992. Epub 2019 May 29.

Abstract

Ethnopharmacological relevance: Jikan Mingmu Drops (JMD), a traditional Tibetan medicine containing six herbs, has been used to treat dry eye syndrome (DES) in individuals with diabetes mellitus.

Aim of study: However, the activity of JMD ameliorates DES with diabetes mellitus has not been previously examined. The aim of the study is to investigate the molecular mechanism of JMD on db/db mice.

Materials and methods: The main chemical constituents of JMD were analyzed by high-performance liquid chromatography and gas chromatography-mass spectrometry. DES was then induced in db/db mice by applying 0.2% benzalkonium chloride to the ocular surface for 7 days. Eye drops containing JMD (0.25, 0.5, or 1 g/mL) or vehicle subsequently were administered three times daily for another 7 days, and the therapeutic effects were evaluated by phenol red thread tear and sodium fluorescein tests. Conjunctival specimens were subjected to hematoxylin and eosin staining and periodic acid-Schiff staining to examine pathological changes and number of goblet cells. ELISA was performed to assess the levels of various inflammatory cytokines.

Results: JMD contains hydroxysafflor yellow A, magnoflorine, jatrorrhizine hydrochloride, palmatine hydrochloride, berberine hydrochloride, gallic acid, ellagic acid, tauroursodeoxycholic acid, camphor, isoborneol, borneol, trans-cinnamic acid, and muscone. JMD treatment significantly increased the tear volume, decreased the corneal fluorescein staining score, restored the morphology and structure of conjunctival epithelial cells, and markedly downregulated the levels of interleukin (IL)-6, IL-17α, IL-1β, tumor necrosis factor-α, and vascular endothelial growth factor in the conjunctiva. Further data showed that these protective effects were accompanied by inhibition of inflammation in a dose-dependent manner.

Conclusions: Amelioration of DES in db/db mice with diabetes mellitus by treatment with Tibetan medicine formula JMD maybe related to its anti-inflammatory effects.

Keywords: Db/db mice; Diabetes mellitus; Dry eye syndrome; Inflammation; Jikan mingmu drops.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cytokines / immunology
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / immunology
  • Disease Models, Animal
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / immunology
  • Male
  • Medicine, Tibetan Traditional
  • Mice

Substances

  • Anti-Inflammatory Agents
  • Cytokines