The total alkaloids of Aconitum tanguticum protect against lipopolysaccharide-induced acute lung injury in rats

Abstract

Ethnopharmacological relevance: Aconitum tanguticum has been widely used as a remedy for infectious diseases in traditional Tibetan medicine in China. The total alkaloids of Aconitum tanguticum (TAA) are the main active components of Aconitum tanguticum and have been demonstrated to be effective in suppressing inflammation. Our aim was to investigate the protective effects of TAA on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats.

Materials and methods: TAA was extracted in 95% ethanol and purified in chloroform. After vacuum drying, the TAA powder was dissolved in dimethyl sulfoxide. Adult male Sprague-Dawley rats were randomly divided into six groups. Rats were given dexamethasone (DXM, 4 mg/kg) or TAA (60 mg/kg, 30 mg/kg) before LPS injection. The PaO2and PaO2/FiO2 values, lung wet/dry (W/D) weight ratio and histological changes in lung tissue were measured. The cell counts, protein concentration, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF), and myeloperoxidase (MPO) activity in lung tissue were determined at 6, 12 or 24 h after LPS treatment. In addition, the NF-κ B activation in lung tissue was analyzed by western blot.

Results: In ALI rats, TAA significantly reduced the lung W/D ratio and increased the value of PaO2 or PaO2/FiO2 at 6, 12 or 24 h after LPS challenge. TAA also reduced the total protein concentration and the number of total cells, neutrophils or lymphocytes in BALF. In addition, TAA decreased MPO activity in the lung and attenuated histological changes in the lung. Furthermore, TAA inhibited the concentration of TNF-α, IL-6 and IL-1β in BALF at 6, 12 or 24 h after LPS treatment. Further study demonstrated that TAA significantly inhibited NF-κ B activation in lung tissue.

Conclusions: The current study proved that TAA exhibited a potent protective effect on LPS-induced ALI in rats through its anti-inflammatory activity.

Keywords: 6-benzoylheteratisine (PubChem CID: 5487064); Aconitine (PubChem CID: 245005); Acute lung injury; Atisine (PubChem CID: 6426913); Benzoylaconitine (PubChem CID: 49868330); Benzoylhypacoitine (PubChem CID: 3047329); Benzoylmesaconine (PubChem CID: 3036967); Heteratisine (PubChem CID: 441735); Heterophylline (PubChem CID: 251575); Hordenine (PubChem CID: 68313); Hypaconitine (PubChem CID: 23337); IL-1β; IL-6; NF-κ B; TNF-α; Total alkaloids of Aconitum tanguticum.