Microbial bionic nano-aromatic drugs for prevention of depression induced by chronic stress

Abstract

Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Keywords: Aromatherapy; Chronic stress; Microbial bionic nano-aromatic drugs; Prevention of depression; Sustain release of essential oils.

Fig. 1

The schematic diagram. (A) The schematic diagram of biomimetic nano-aromatic drugs. (B) The schematic diagram of adhesion of bionic nano-aromatic drugs on wallpaper and preventing depression of bionic nano-aromatic drugs

Fig. 2

Preparation and characterization of bionic nano-aromatic drugs. (A) SEM and TEM images of MSNRs, (B) morphology-bionic nano-aromatic drugs, (C) functional bionic nano-aromatic drugs, and (D) bionic plus nano-aromatic drugs. (I) SEM, (II) TEM (E) Nitrogen adsorption-desorption isotherms. (F) Pore diameter distributions. (G) TGA of morphology-bionic nano-aromatic drugs. (H) TGA of function-bionic nano-aromatic drugs. (I) TGA of bionic plus nano-aromatic drugs. (J) The release of mixed essential oils from nano-aromatic drugs

Fig. 3

Adhesion and de-adhesion of nano-aromatic drugs with wallpaper. (A) Adhesion of nano-aromatic drugs on wallpaper. (B) De-adhesion of nano-aromatic drugs from wallpaper. Samples: (I) Non-bionic nano-aromatic drugs. (II) Morphology-bionic nano-aromatic drugs. (III) Function-bionic nano-aromatic drugs. (IV) Bionic plus nano-aromatic drugs

Fig. 4

Molecular dynamics simulation between bionic nano-aromatic drugs and wallpaper. (A) Variation of system potential energy with molecular dynamics simulation time of non-bionic nano-aromatic drugs, (B) morphology-bionic nano-aromatic drugs and (C) function-bionic nano-aromatic drugs. (D) Variation of RMSD of cellulose in the system with molecular dynamics simulation time. (E) Variation of the mass center distance and (F) variation of hydrogen bond number between cellulose and nano-aromatic drugs were investigated. (G) Variation of the binding energy of cellulose and nano-aromatic drugs with time

Fig. 5

Modes of cellulose-binding on the surface of nano-aromatic drugs. (A-B) The combination mode of cellulose and non-bionic nano-aromatic drugs. (C-D) The combination mode of cellulose and morphology-bionic nano-aromatic drugs. (E-F) The combination mode of cellulose and functional bionic nano-aromatic drugs. Si, O, C, N, and H atoms were represented by yellow, red, cyan, blue, and white, respectively

Fig. 6

Evaluation of despair and exploratory behavior in mice. (A) The movement routes of mice in containers of FST. (B) Immobility time of mice in FST. (C) Struggling time of mice in FST. (D) Immobility time of mice in TST. (E) The movement routes of mice in open field tests. (F) Movement distances of mice in the central zone. (G) Time in the central zone of mice. (H) Number to enter the central zone of mice. (I) The movement routes of mice in NSF tests. The mean ± SD was shown (n = 3). *P < 0.05, **P < 0.01, ***P < 0.005

Fig. 7

The mechanism exploration of nano-aromatic drugs preventing depression. (A) The content of 5-HT in the brain. (B) The content of NE in the brain. (C) Nissl staining of the hippocampal dentate gyrus in mice. The mean ± SD was shown (n = 3). *P < 0.05