Bazi Bushen capsule attenuates cognitive deficits by inhibiting microglia activation and cellular senescence

Pharm Biol. 2022 Dec;60(1):2025-2039. doi: 10.1080/13880209.2022.2131839.


Context: Bazi Bushen capsule (BZBS) has anti-ageing properties and is effective in enhancing memory.

Objective: To find evidence supporting the mechanisms and biomarkers by which BZBS functions.

Materials and methods: Male C57BL/6J mice were randomly divided into five groups: normal, ageing, β-nicotinamide mononucleotide capsule (NMN), BZBS low-dose (LD-BZ) and BZBS high-dose (HD-BZ). The last four groups were subcutaneously injected with d-galactose (d-gal, 100 mg/kg/d) to induce the ageing process. At the same time, the LD-BZ, HD-BZ and NMN groups were intragastrically injected with BZBS (1 and 2 g/kg/d) and NMN (100 mg/kg/d) for treatment, respectively. After 60 days, the changes in overall ageing status, brain neuron morphology, expression of p16INK4a, proliferating cell nuclear antigen (PCNA), ionized calcium-binding adapter molecule 1 (Iba1), postsynaptic density protein 95 (PSD95), CD11b, Arg1, CD206, Trem2, Ym1 and Fizz1, and the senescence-associated secretory phenotype (SASP) factors were observed.

Results: Compared with the mice in the ageing group, the HD-BZ mice exhibited obvious improvements in strength, endurance, motor coordination, cognitive function and neuron injury. The results showed a decrease in p16INK4a, Iba1 and the upregulation of PCNA, PSD95 among brain proteins. The brain mRNA exhibited downregulation of Iba1 (p < 0.001), CD11b (p < 0.001), and upregulation of Arg1 (p < 0.01), CD206 (p < 0.05), Trem2 (p < 0.001), Ym1 (p < 0.01), Fizz1 (p < 0.05) and PSD95 (p < 0.01), as well as improvement of SASP factors.

Conclusions: BZBS improves cognitive deficits via inhibition of cellular senescence and microglia activation. This study provides experimental evidence for the wide application of BZBS in clinical practice for cognitive deficits.

Keywords: Synaptic plasticity; ageing; microglia polarization; senescence-associated secretory phenotype; traditional Chinese medicine.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Animals
  • Calcium
  • Cellular Senescence
  • Cognition
  • Cyclin-Dependent Kinase Inhibitor p16* / genetics
  • Cyclin-Dependent Kinase Inhibitor p16* / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16* / pharmacology
  • Disks Large Homolog 4 Protein
  • Galactose*
  • Male
  • Membrane Glycoproteins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Microglia / metabolism
  • Nicotinamide Mononucleotide / pharmacology
  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • Receptors, Immunologic


  • Calcium
  • Cyclin-Dependent Kinase Inhibitor p16
  • Disks Large Homolog 4 Protein
  • Galactose
  • Membrane Glycoproteins
  • Nicotinamide Mononucleotide
  • Proliferating Cell Nuclear Antigen
  • Receptors, Immunologic
  • RNA, Messenger
  • Trem2 protein, mouse

Grants and funding

This work was supported by funding from the National Key Research and Development Program of China (2017YFC1700500); and the Strategic Consulting Project of Chinese Academy of Engineering-Strategic Research on Anti-Aging Effect of Traditional Chinese Medicine (2022-XY-45); and the Natural Science Foundation of Hebei Province (H201906059); and the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine (2021273).