Effect of Tetrandrine on Calcium‐Dependent Tumour Necrosis Factor‐α Production in Glia‐Neurone Mixed Cultures

Abstract

Tumour necrosis factor-a is believed to have a deleterious role in the pathophysiology of brain injury. Tetrandrine has protective effect on neuronal cells, however, the mechanisms involved in its action have not been clearly established. The aim of this study was to investigate the role of tetrandrine on calcium-dependent tumour necrosis factor-a production in glia-neurone mixed cultures. Glia-neurone mixed cultures were treated by addition of Ca 2π regulating agents for a period of 6 hr. Tetrandrine or/and TMB-8 were added 30 min. before the stimulation. The supernatant tumour necrosis factor-a levels were quantified by enzyme-linked immunosorbent assay. Exposure of lipopolysaccharide 10 and 100 ng/ml caused significant increase in tumour necrosis factor-a production respectively, with no alteration in cultures treated with 1 ng/ml lipopolysaccharide. Glia-neurone mixed cultures exhibited a marked elevation in tumour necrosis factor-a production after exposure to CaCl 2 , KCl, thapsigargin, BHQ and norepinephrine in the presence of lipopolysaccharide at 1 ng/ ml respectively. Tetrandrine 0.3, 1, and 3 mM concentration-dependently reduced tumour necrosis factor-a production evoked by CaCl 2 or KCl. Tetrandrine preincubation had no significant effect on the response to Ca 2π -ATPase inhibitor thapsigargin or BHQ. Norepinephrine-induced tumour necrosis factor-a production was significantly reduced by tetrandrine and almost abolished by combination of tetrandrine and intracellular Ca 2π release inhibitor TMB-8. These results suggested that tetrandrine at a concentration of 0.3, 1, or 3 mM inhibited tumour necrosis factor-a production induced by Ca 2π entry in glia-neurone mixed cultures.

Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-κB pathway

“…TET also inhibited IκBα kinases and protein kinase C activity [6,7] , and prevented tumor necrosis factor-α (TNF-α) production in activated monocytes [8] . In addition, TET was found to have an inhibitory effect on calcium-dependent TNF-α production in glia-neuron mixed cultures [9] .…”

Alkaloids

“…409 Furthermore, cepharanthine at a dose of 10 μM inhibited the enzymatic activity of acid sphingomyelinase (ASM), which converts sphingomyelin into ceramide 410 in the presence of Ca 2+ . 414 Additionally, tetrandrine at a dose of 40 mg/kg protected rodents against β-amyloid (Aβ 1-42 ) peptide-induced dementia in the Morris water maze test with a reduction in cerebral IL-1β and TNF-α. 412 It is therefore plausible to suggest that cepharanthine, by blocking Ca 2+ channels and consequently ceramide production, may sustain the viability of neurons challenged with pro-apoptic stimuli.…”

Study on the mechanism of oral administration of tetrandrine during neoadjuvant chemotherapy for colon cancer

“…Furthermore, tetrandrine can also be used in the treatment of patients with simple silicosis and coal sputum lung, early mild hypertension, rheumatic pain, joint pain and neuralgia (26)(27)(28). Studies have demonstrated that as a calcium antagonist, tetrandrine can directly and effectively inhibit intracellular calcium-dependent TNF-α production and can also indirectly inhibit the expression and production of TNF-α by cells (such as glial cells-neurons and monocytes) (29,30). However, whether the application of tetrandrine in the adjuvant chemotherapy of colon cancer is effective and efficient has not been fully elucidated.…”