Tinospora cordifolia chloroform extract inhibits LPS-induced inflammation via NF-κB inactivation in THP-1cells and improves survival in sepsis

Tinospora cordifolia 氯仿提取物通过 NF-κB 失活抑制 THP-1 细胞中 LPS 诱导的炎症并提高脓毒症患者的存活率

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作者:Sheena Philip, Greeshma Tom, Padmaja Balakrishnan Nair, Sankar Sundaram, Asha Velikkakathu Vasumathy

Background

Tinospora cordifolia (Willd).Miers is a perennial climbing medicinal shrub that has been traditionally used for the treatment of chronic inflammatory ailments. Our previous pre- clinical studies on anti-inflammatory effects, proved that the chloroform extract of T. cordifolia (CETC) suppressed the LPS induced up-regulation of pro-inflammatory biomarkers, hence, further follow up study was carried out to evaluate whether CETC can exhibit a protective effect against LPS induced lethal endotoxemia in vivo and also to analyze the impact of CETC pre-treatment on the secretion of pro-inflammatory cytokines in vitro by THP-1 cells.

Conclusion

These findings concomitantly reveal the anti-inflammatory mechanism of CETC and support us to move forward for the development of drugs against disorders resulting from deregulated immune reactions.

Methods

To corroborate our previous preclinical studies on inflammation, we investigated the mechanism of the anti-inflammatory effect of T. cordifolia on THP-cells which were pre-incubated with CETC (30 min) and stimulated subsequently with LPS (1 μg/ml) for 20 h. Levels as well as gene expressions of various cytokines were compared with that of LPS alone incubated cells. Alongside, in vivo oral anti-inflammatory efficacy against LPS induced endotoxemia study was effectuated, wherein rats were administered with CETC 48, 24, 12 and 1 h prior to the injection of LPS and the survival of rats were monitored upto 10 days. Cytokine levels were quantified by ELISA. Nitrite levels were measured using Griess reagent. Expression of pro-inflammatory proteins was inspected in rat tissues by histochemical and immuno -histochemical examinations.

Results

CETC was able to down-regulate the up-regulation of pro-inflammatory biomarkers in THP-1 macrophages though blockade of NF-κB nuclear translocation and could improve the survival rate during endotoxemic episodes with a marked suppression of the tissue expression of pro-inflammatory proteins.

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