Tanshinone IIA Has a Potential Therapeutic Effect on Kawasaki Disease and Suppresses Megakaryocytes in Rabbits With Immune Vasculitis

Abstract

Background and ObjectiveIt is urgent to find out an alternative therapy for Kawasaki disease (KD) since around 20% patients are resistant to intravenous immunoglobulin (IVIG) or aspirin. Tanshinone IIA is the active component of the traditional Chinese medicine Danshen (Salvia miltiorrhiza), which has anti-inflammatory and anti-platelet properties; however, whether or not tanshinone IIA has a therapeutic effect on KD remains unclear. Therefore, the present study aimed to examine the effect of tanshinone IIA on KD patients and rabbits with immune vasculitis, and to identify the potential mechanisms with special emphasis on megakaryopoiesis and megakaryocytic apoptosis.MethodsKawasaki disease patients were recruited and prescribed with tanshinone IIA in the absence or presence of aspirin and IVIG, and the inflammatory responses and platelet functions were determined. Megakaryocytes (MKs) isolated from rabbits with immune vasculitis and human megakaryocytic CHRF-288-11 cells were treated with tanshinone IIA to examine the colony forming unit (CFU) and apoptosis, respectively. Microarray assay was conducted to identify potential targets of tanshinone IIA-induced apoptosis.ResultsTanshinone IIA reduced the serum levels of C-reactive protein (CRP), interleukin (IL)-1β, IL-6, and P-selectin in KD patients; such inhibitory effect was more significant compared to aspirin and IVIG. It also dose-dependently lowered the levels of tumor necrosis factor (TNF)-α and IL-8 in peripheral blood mononuclear cells isolated from KD patients. In rabbits with immune vasculitis, tanshinone IIA significantly reduced the serum levels of proinflammatory cytokines and platelet functions. In addition, tanshinone IIA significantly decreased the number of bone marrow MKs and inhibited the Colony Forming Unit-Megakaryocyte (CFU-MK) formation. In human megakaryocytic CHRF-288-11 cells, tanshinone IIA induced caspase-dependent apoptosis, probably through up-regulating TNF receptor superfamily member 9 (TNFRSF9) and the receptor (TNFRSF)-interacting serine/threonine-protein kinase 1 (RIPK1), which may contribute to its anti-platelet and anti-inflammatory properties.ConclusionTanshinone IIA exerts better anti-inflammatory and anti-platelet effects in treating KD patients than aspirin and IVIG. It attenuates immune vasculitis likely by inhibiting IL-mediated megakaryopoiesis and inducing TNFRSF9/RIPK1/caspase-dependent megakaryocytic apoptosis. The findings therefore suggest that tanshinone IIA may be a promising alternative therapy for the treatment of KD.

Renoprotective Effects of Tanshinone IIA: A Literature Review

“…However, studies on the renoprotective effects of Tan IIA still leave room for improvement as follows: (1) The exact mechanism of Tan IIA in the treatment of kidney diseases remains to be further elucidated. Many studies have reported that Tan IIA has regulatory effects on non-coding RNAs [ 84 ], RNA methylation [ 85 ], immune-related factors [ 86 ] and ferroptosis [ 87 ], and the above mechanisms have also been reported to be crucial in the occurrence and development of kidney diseases. In the future, more attention may be paid to the regulatory mechanism of Tan IIA in kidney diseases.…”

The mechanisms of tanshinone in the treatment of tumors

“…While, the components that dissolve in water are salvianolic acid A, salvianolic acid B, purple oxalic acid, and rosmarinic acid. Among these two categories, the fat-soluble component, tanshinone, is highly valued due to its minimal toxicity, high effectiveness, safety, and ability to produce various pharmacological actions that are against tumors ( Jin et al, 2021 ), inflammation ( Ye et al, 2020 ), myocardial ischemia ( Zhu et al, 2023 ), oxidative stress ( Wu et al, 2021 ) and thrombosis ( Feng et al, 2021 ), inhibit left ventricular hypertrophy ( Pang et al, 2014 ), dilate blood vessels ( Lu et al, 2021 ), resist atherosclerosis ( Wen et al, 2020 ), protect brain tissue ( Wang et al, 2022 ), improve microcirculation ( Qin et al, 2023 ), significantly inhibit pulmonary fibrosis ( Feng et al, 2020 ), and activate immunity ( Chen et al, 2022 ).…”

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy

“…Tanshinone IIA (Tan), one of the effective components of Salvia miltiorrhiza Bge., has been reported to play an important role in anti-inflammation, anti-oxidative stress, dilation of vascular endothelium, inhibition of cell differentiation by regulating PI3K/AKT/mTOR, JNK, NF-κB, and other signal pathways (Zhang et al 2022a ; Peng et al 2022 ; Chen et al 2022 ). In recent years, cardiovascular disease is the main cause of death of patients with DN.…”