Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway

Cervical cancer is the fourth most common cancer in women globally. Lack of effective pharmacotherapies for cervical cancer mainly attributed to an elusive understanding of the mechanism underlying its pathogenesis. Pyroptosis plays a key role in inflammation and cancer. Our study identified microRNA (miR) 145 (miR-145)/gasdermin D (GSDMD) signaling pathway as critical mediators in the effect of tanshinone II A on HeLa cells. In the present study, we found that treatment of tanshinone II A led to an obvious repression of cell proliferation and an increase in apoptosis on HeLa cells, especially in high concentration. Compared with the controlled group, tanshinone II A enhanced the activity of caspase3 and caspase9. Notably, the results demonstrated that tanshinone II A regulated cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway. Treatment of tanshinone II A significantly up-regulated the expression of GSDMD and miR-145. After transfection of si-miR-145 plasmids, the effects of tanshinone II A on HeLa cells were converted, including cell proliferation, apoptosis and pyroptosis. In addition, the results showed that tanshinone II A treatment altered the expression level of PI3K, p-Akt, NF-kB p65 and Lc3-I. Collectively, our findings demonstrate that tanshinone II A exerts anticancer activity on HeLa cells by regulating miR-145/GSDMD signaling. The present study is the first time to identify miR-145 as a candidate target in cervical cancer and show an association between miR-145 and pyroptosis, which provides a novel therapy for the treatment of cervical cancer.

Preliminary Studies on Liquiritin, Deoxyschizandrin, and Tanshinone II A as Potential Anti-Neurodegenerative Disease Agent: Determination by Reverse-Phase Liquid Chromatography in Tianwang Buxin Pills

Tianwang Buxin pill (TWBXP) is an ancient Chinese classic prescription. Liquiritin, deoxyschizandrin, and tanshinone II A are three bioactive components in TWBXP, which have been proven to be closely related to the therapy effect of neurodegenerative disease. Their contents are very low in TWBXP. In this study, we used a diode array detector (DAD) to perform a full wavelength scanning in order to choose a most suitable detection wavelength to establish an HPLC method for the simultaneous determination of these three components in TWBXP. Various chromatographic conditions were investigated to verify its applicability. Finally, a Kromasil C18 column (250 × 4.6 mm, 5 μm) thermostated at 30°C, mobile phase as 0.2% phosphoric acid solution (eluent A), and 0.1% phosphoric acid-acetonitrile solution (eluent B) were used. Both external standard method and internal standard method were used for quantification. The results showed that both methods were simple and convenient in operation without special pretreatment and exhibits excellent precision, repeatability (RSD < 3.0%), good linearity (R2 > 0.9990), and good recoveries (recovery value between 95% and 105%). Because of the low contents in samples, the internal standard method provided a better accurate result than the external standard method. The stability results showed the sample became stable within 24 hours at room temperature. The method provides a convenient and effective way for the quality control of TWBXP, and it can help the research about AD in the future.

Tanshinone II A Affects Diabetic Peripheral Neuropathic Pain via Spinal Dorsal Horn Neuronal Circuitry by Modulating Endoplasmic Reticulum Stress Pathways

Diabetic peripheral neuropathic pain (DPNP) is a common manifestation of diabetic peripheral neuropathy (DPN). Although the pathogenesis of DPNP remains unclear, the disinhibition of spinal dorsal horn neuronal circuitry mediated by endoplasmic reticulum stress (ERS) is an important mechanism underlying neuropathic pain (NP). Tanshinone II A is mainly used to treat cardiovascular diseases but has also been shown to relieve various types of neuralgia, including DPNP. This study investigated the effects of tanshinone II A in DPNP model rats. We divided animals into two groups: 1) the model (diabetic) group and 2) the tanshinone II A-treatment group. Our results demonstrated that diabetic rats exhibited a decrease in the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), and that NMT is increased and TWL is prolonged in rats treated with tanshinone II A. Additionally, the levels of ERS-signaling pathway factors in the spinal dorsal horns of rats were lower in the tanshinone II A-treated group than in the diabetic group. Overall, our study demonstrated that the disinhibition of spinal dorsal horn neuronal circuitry mediated by endoplasmic reticulum stress underlies DPNP and is modulated by tanshinone II A treatment.