Non‑cytotoxic doses of shikonin inhibit lipopolysaccharide‑induced TNF‑α expression via activation of the AMP‑activated protein kinase signaling pathway

Abstract

Shikonin has been reported to exhibit a wide variety of medical functions. However, the strong non-selective cytotoxicity of shikonin can restrict its clinical application. The aim of the present study was to investigate the effects of shikonin at non-cytotoxic doses on the pro-inflammation functions of monocytes and macrophages. The present results suggested that the non-cytotoxic doses of shikonin effectively inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production, NF-κB activation and TNF-α expression in RAW 264.7 mouse macrophages via AMP-activated protein kinase (AMPK) signaling pathway. In addition, the non-cytotoxic doses of shikonin downregulated LPS-induced TNF-α expression via AMPK signaling activation in primary murine bone marrow-derived macrophages, and also in monocytes cultured ex vivo from patients with chronic obstructive pulmonary disease (COPD). The present in vivo results indicated that the low-toxic dose of shikonin suppressed LPS-induced endotoxin shock and TNF-α expression in mice. Collectively, the present results may provide clinical and translational relevance for treating COPD and other TNF-α-related inflammatory disorders.

Natural Shikonin Potentially Alters Intestinal Flora to Alleviate Acute Inflammation

“…Importantly, the interactions between gut microbiota and natural products can help us better understand the mechanism of different diseases. However, several adverse features in vivo have been reported with shikonin, including its low water solubility, non-selective toxicity, and poor bioavailability, all of which could limit its pharmacological use [ 43 , 44 , 45 ]. Future investigations should pay considerable attention to improve its water solubility and bioavailability, which will broaden its applications without question.…”