Mechanism Of Tanshinone IIA Research Articles

Tanshinone IIA Alleviates Pulmonary Fibrosis by Inhibiting Pyroptosis of Alveolar Epithelial Cells Through the MAPK Signaling Pathway.

The current dearth of safe and efficacious pharmaceutical interventions for pulmonary fibrosis (PF) has prompted investigations into alternative treatments. This study aim to investigate the underlying mechanisms of Tanshinone IIA in the treatment of PF. PF was induced in a mouse model by intratracheal infusion of bleomycin (BLM), followed by gavage administration of varying concentrations of Tanshinone IIA. Lung tissue was obtained for pathological slides, proteomic and transcriptomic analyses. The target was predicted and analyzed using network pharmacology. Initially, an invitro model in A549 cells was established by adding BLM, followed by treatment with varying concentrations of Tanshinone IIA. Subsequently, NAC and the ERK inhibitor, U0126, were individually introduced. Treatment with Tanshinone IIA invivo decreased lung tissue lesions. Proteomic, transcriptomic, and network pharmacology analyses suggested that Tanshinone IIA may offer therapeutic benefits for PF by mitigating oxidative stress damage via the MAPK signaling pathway. Invitro studies demonstrated that BLM treatment in A549 cells induced exposure of the N-terminal end of the pyroptosis core protein GSDMD, and elevated oxidative stress levels in A549 cells, concomitant with the upregulation of P-ERK protein expression. Subsequent administration of Tanshinone IIA, NAC, and U0126 reduced the number of A549 cells undergoing pyroptosis, decreased oxidative stress levels, and decreased P-ERK protein expression. These findings suggested that Tanshinone IIA potentially delays the progression of PF. The mechanism of action involves the inhibition of oxidative stress and reduced epithelial cell pyroptosis via the MAPK-related pathway. The findings may provide a new reference for treatment of PF.

Tanshinone IIA Inhibits the Endoplasmic Reticulum Stress-Induced Unfolded Protein Response by Activating the PPARα/FGF21 Axis to Ameliorate Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a critical stage in the progression of nonalcoholic fatty liver disease (NAFLD). Tanshinone IIA (TIIA) is a tanshinone extracted from Salvia miltiorrhiza; due to its powerful anti-inflammatory and antioxidant biological activities, it is commonly used for treating cardiovascular and hepatic diseases. A NASH model was established by feeding mice a methionine and choline-deficient (MCD) diet. Liver surface microblood flow scanning, biochemical examination, histopathological examination, cytokine analysis through ELISA, lipidomic analysis, transcriptomic analysis, and Western blot analysis were used to evaluate the therapeutic effect and mechanism of TIIA on NASH. The results showed that TIIA effectively reduced lipid accumulation, fibrosis, and inflammation and alleviated endoplasmic reticulum (ER) stress. Lipidomic analysis revealed that TIIA normalized liver phospholipid metabolism in NASH mice. A KEGG analysis of the transcriptome revealed that TIIA exerted its effect by regulating the PPAR signalling pathway, protein processing in the ER, and the NOD-like receptor signalling pathway. These results suggest that TIIA alleviates NASH by activating the PPARα/FGF21 axis to negatively regulate the ER stress-induced unfolded protein response (UPR).

Possible Mechanisms of Tanshinone IIA in the Treatment of Spinal Cord Injury Repair

Possible Mechanisms of Tanshinone IIA in the Treatment of Spinal Cord Injury Repair

Effects and mechanisms of tanshinone IIA on PTSD-like symptoms

BackgroundIn recent years, Salvia miltiorrhiza and its active substances have remarkably progressed in treating central neurological disorders. Tanshinone IIA (TSA) is an active ingredient derived from the rhizome of Salvia miltiorrhiza that has been found to alleviate the symptoms of several psychiatric illnesses. Post-traumatic stress disorder (PTSD) is a mental disorder that results after experiencing a serious physical or psychological injury. The currently used drugs are not satisfactory for the treatment of PTSD. However, it has been reported that TSA can improve PTSD-like symptoms like learning and memory, cognitive disorder, and depression through multi-target regulation. PurposeThis paper discusses the ameliorative effects of TSA on PTSD-like symptoms and the possible mechanisms of action in terms of inhibition of neuronal apoptosis, anti-neuroinflammation, and anti-oxidative stress. Based on the pathological changes and clinical observations of PTSD, we hope to provide some reference for the clinical transformation of Chinese medicine in treating PTSD. MethodsA large number of literatures on tanshinone in the treatment of neurological diseases and PTSD were retrieved from online electronic PubMed and Web of Science databases. ConclusionTSA is a widely studied natural active ingredient against mental illness. This review will contribute to the future development of TSA as a new clinical candidate drug for improving PTSD-like symptoms.

The mechanism of Tanshinone ⅡA on regulating EMT in cutaneous melanoma A375 cells through TAMs autophagy

The mechanism of Tanshinone ⅡA on regulating EMT in cutaneous melanoma A375 cells through TAMs autophagy

Tanshinone IIA ameliorates myocardial ischemia/reperfusion injury in rats by regulation of NLRP3 inflammasome activation and Th17 cells differentiation.

Tanshinone IIA is a well-known lipophilic active constituent refined from traditional Chinese medicines, danshen. It has been previously demonstrated to possess various biological properties, including anti-inflammatory, antioxidant, promoting angiogenesis effect and so on. However, the mechanism of tanshinone IIA on myocardial ischemia-reperfusion injury (MI/RI) remains unclear. In this study, we investigated the effect of tanshinone IIA on MI/RI. MI/RI rat models were set up. Echocardiographic evaluation and hematoxylin and eosin staining were performed to analyze the cardiac function and morphology of MI/RI. Western blot was conducted for the detection of protein expression of pyrin domain containing 3 (NLRP3) and caspase-1 in heart tissues. Flow cytometry and real-time polymerase chain reaction were used for the detection of proinflammatory cytokines and Th17 cells differentiation. We found that tanshinone IIA alleviated the myocardial damage of MI/RI, ameliorated the overall and local inflammatory reaction, and produced a cardioprotective effect by inhibiting of NLRP3 inflammasome activation and Th17/Treg cells differentiation. Our results highlighted the cardio-protective effect of tanshinone IIA on MI/RI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition and the modulation of Th17/Treg cells differentiation.

Recent Research Progress (2015-2021) and Perspectives on the Pharmacological Effects and Mechanisms of Tanshinone IIA.

Tanshinone IIA (Tan IIA) is an important characteristic component and active ingredient in Salvia miltiorrhiza, and its various aspects of research are constantly being updated to explore its potential application. In this paper, we review the recent progress on pharmacological activities and the therapeutic mechanisms of Tan IIA according to literature during the years 2015–2021. Tan IIA shows multiple pharmacological effects, including anticarcinogenic, cardiovascular, nervous, respiratory, urinary, digestive, and motor systems activities. Tan IIA modulates multi-targets referring to Nrf2, AMPK, GSK-3β, EGFR, CD36, HO-1, NOX4, Beclin-1, TLR4, TNF-α, STAT3, Caspase-3, and bcl-2 proteins and multi-pathways including NF-κB, SIRT1/PGC1α, MAPK, SREBP-2/Pcsk9, Wnt, PI3K/Akt/mTOR pathways, TGF-β/Smad and Hippo/YAP pathways, etc., which directly or indirectly influence disease course. Further, with the reported targets, the potential effects and possible mechanisms of Tan IIA against diseases were predicted by bioinformatic analysis. This paper provides new insights into the therapeutic effects and mechanisms of Tan IIA against diseases.

Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway

In the present study, we aimed to find the target of Tanshinone IIA (Tan-IIA) in Cholangiocarcinoma by network pharmacology-based prediction and investigate the possible mechanism through experimental verification. In this study, we combined Tan-IIA-specific and Cholangiocarcinoma-specific targets with protein–protein interactions (PPI) to construct a Tan-IIA targets-Cholangiocarcinoma network, and network pharmacology approach was applied to identify potential targets and mechanisms of Tan-IIA in the treatment of Cholangiocarcinoma. The anti-cancer effects of Tan-IIA were investigated by using subcutaneous tumorigenic model in nude mice and in the human Cholangiocarcinoma cell lines in vitro. Our results showed that Tan-IIA treatment considerably suppressed the proliferation and migration of Cholangiocarcinoma cells while inducing apoptosis of Cholangiocarcinoma cells. Western blot results demonstrated that the expression of PI3K, p-Akt, p-mTOR, and mTOR were inhibited by Tan-IIA. Meanwhile, After treatment with Tan-IIA, the level of Bcl2 was downregulated and cleaved caspase-3 expression increased. Further studies revealed that the anticancer effects of Tan-IIA were severely mitigated by pretreatment with a PI3K agonist. Our research provides a new anticancer strategy and strengthens support for the use of Tan-IIA as an anticancer drug for the treatment of CCA.

Tanshinone IIA Regulates Osteoblast Differentiation and Promotes Fracture Healing via Mammalian Target of Rapamycin Complex 1 Signaling Pathway

This study assessed the effect and potential molecular mechanism of tanshinone IIA on fracture healing. Mice model with fracture were established. Digital radiographic photographic system was used to detect callus formation after treatment with tanshinone II A (Tan IIA) and alkaline phosphatase (ALP) staining analyzed ALP activity. Osteoblast proliferation was also measured. Western blot and Quantitative real-time PCR (qRT-PCR) measured osteogenic markers expression. Compared with control group, Tan IIA treatment could increase callus formation, stimulate osteoblast proliferation, osteogenic proteins and genes expression, and activate mTORC1 signaling pathway. However, Tan IIA’s effects were significantly inhibited after rapamycin treatment. Tan IIA regulates osteoblast differentiation by mTORC1 signaling and promotes intramembranous ossification in the process of callus formation, which accelerates bone healing.

Pharmacological Activity and Mechanism of Tanshinone IIA in Related Diseases.

Salvia miltiorrhiza: (Danshen) is a significant (traditional Chinese medication) natural remedy, enhancing blood circulation and clear blood stasis. In this view, it is widely used against several heart diseases, eg, cardiomyopathy, arrhythmia, and congenital heart defects. Tanshinone IIA (tan-IIA) is the main fat-soluble component of Salvia miltiorrhiza. Modern pharmacological study shows that tan-IIA has anti-inflammatory and anti-oxidant activities. Tan-IIA induces remarkable cardioprotective effects via enhancing angiogenesis which may serve as an effective treatment against cardiovascular diseases (CVD). There is also evidence that tan-IIA has extensive immunomodulatory effects and plays a significant role in the development and function of immune cells. Tan-IIA reduces the production of inflammatory mediators and restores abnormal signaling pathways via regulating the function and activation of immune cells. It can also regulate signal transduction pathways, ie, TLR/NF-κB pathway and MAPKs/NF-κB pathway, thereby tan-IIA has an anti-inflammatory, anticoagulant, antithrombotic and neuroprotective role. It plays a protective role in the pathogenesis of cardiovascular disorders (ie, atherosclerosis, hypertension) and Alzheimer’s disease. It has also been revealed that tan-IIA has an anti-tumor role by killing various tumor cells, inducing differentiation and apoptosis, and has potential activity against carcinoma progression. In the review of this fact, the tan-IIA role in different diseases and its mechanism have been summarized while its clinical applications are also explored to provide a new perspective of Salvia miltiorrhiza. An extensive study on the mechanism of action of tan-IIA is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.

Tanshinone IIA Alleviates Pirarubicin-Induced Cytotoxicity in H9c2 Cardiomyocytes via Regulation of Hippo Signaling Pathway

Malignant tumor is considered as one of the fatal diseases worldwide with high incidence and mortality. Pirarubicin (THP) is an anti-cancer drug commonly used in the treatment of patients with malignancies. In view of that THP exists the cardiotoxic effects, its clinical application is restricted. Tanshinone IIA (TSA) is a core active monomer drawn from Salvia miltiorrhiza that possesses the cardioprotective properties. In the present study, we proposed to unveil the potential and latent mechanism of TSA in the cardiotoxicity caused by THP. Our results validated that THP treatment gave rise to the injury of cardiomyocytes. Moreover, administration of TSA abrogated the impacts of THP on H9c2 cells. A myriad of literatures demonstrate that Hippo pathway plays a critical role in the development of multiple cardiovascular disorders. Hence, we further explored the relationship between TSA and Hippo pathway. It was proven that THP contributed to the activation of Hippo pathway and TSA treatment inhibited Hippo pathway. More importantly, we revealed that TSA attenuated THP-mediated cytotoxicity in cardiomyocytes through modulating Hippo pathway, which provide insights into the improvement of THP-induced toxic and side effects.

Tanshinone IIA Alleviates CCL2-Induced Leaning memory and Cognition Impairment in Rats: A Potential Therapeutic Approach for HIV-Associated Neurocognitive Disorder.

Chemokine CC motif ligand 2 (CCL2) is one of the most recognized proinflammatory chemokines, and the expression of CCL2 in the cerebrospinal fluid of patients infected with HIV-1 is significantly higher than that of healthy people. As such, it is seen as an important cause of HIV-associated neurocognitive disorder (HAND). Our previous investigation has confirmed the pathological role of CCL2 in mediating brain damage leading to cognitive dysfunction. Currently, however, research on therapeutic drugs for the central nervous system targeting CCL2 is very limited. Our present study used brain stereotactic technology to induce cognitive impairment in rats by injecting CCL2 (5 ng) into the bilateral hippocampus. To investigate the protective effect and mechanism of Tanshinone IIA (25, 50, 75 mg/kg/d) on CCL2-induced learning memory and cognitive impairment in rats, we performed the Morris water maze (MWM) and novel object recognition tests (NORT) on the rats. The results showed that Tanshinone IIA significantly alleviated CCL2-induced learning memory and cognitive dysfunction. Further studies on the hippocampal tissue of the rats revealed that Tanshinone IIA treatment significantly increased the activity of SOD and GSH-Px while the level of MDA decreased compared to the model group. Additionally, the relative expression of apoptosis-associated genes caspase-3, caspase-8, and caspase-9 and inflammation-associated genes IL-1β and IL-6 in Tanshinone IIA-treated rats was lower than that in model rats. Finally, we confirmed hippocampal neuron loss and apoptosis by Nissl staining and TdT-mediated dUTP Nick end labeling (TUNEL). Taken together, these data imply that Tanshinone IIA can ameliorate CCL2-induced learning memory and cognitive impairment by impacting oxidative stress, inflammation, and apoptosis. Tanshinone IIA may be a potential therapeutic agent for the treatment of HAND.

Tanshinone IIA contributes to the pathogenesis of endometriosis via renin angiotensin system by regulating the dorsal root ganglion axon sprouting

AimsOur study was designed to explore the function and mechanism of Tanshinone IIA in alleviating pain syndrome caused by endometriosis (EMs). Main methodsFemale Sprague-Dawley rats went through autotransplantation operation to establish EMs model. The rats were randomly divided into five groups: sham, model, positive, Tanshinone IIA (L) (3 mg/kg/d) and Tanshinone IIA (H) (12 mg/kg/d) group. Volume of ectopic endometrium was measured after 21 days of continuous administration. Serum estradiol (E2) was detected by enzyme linked immunosorbent assay (Elisa). The protein expression of angiotensinogen (AGT), renin (REN), angiotensin converting enzyme (ACE), angiotensin II (ANGII) and angiotensin II type 2 receptor (AT2) in the dorsal root ganglion (DRG) neurons were measured by immunohistochemistry and Western Blotting. The mRNA expression levels of AGT and ANGII were measured by Real-time polymerase chain reaction (PCR). Key findingsTissue measurements showed that tanshinone IIA significantly inhibited the growth of ectopic endometrium. Tanshinone IIA could improve the paw withdrawal threshold thus reducing the mechanical hyperalgesia of EMs rats. Moreover, Tanshinone IIA regulated the DRG renin angiotensin system (RAS) by reducing the protein expression of AGT, REN, ACE, ANGII and AT2 in DRG neurons. Furthermore, Real-time PCR results also showed that the mRNA expression levels of AGT and ANGII in the DRG neurons were decreased. SignificanceThe Tanshinone IIA inhibitory effect on the EMs associated pain in EMs rats might occur through decreasing the expression of E2, ANGII and AT2, thus halting DRG sprouting and promoting hyperalgesia threshold.

Tanshinone IIA protects against lipopolysaccharide-induced lung injury through targeting Sirt1.

This study was designed to investigate the effects and the mechanism of Tanshinone IIA (TIIA) on endotoxic shock-induced lung injury in a mouse model. Mice were administered intraperitoneally with TIIA (10mg/kg) 0.5h before lipopolysaccharide (LPS) challenge and then received additional injections every 24h during the 3-day experimental period. The physiological indexes, thesurvival rate and the parameters for lung injury were examined. The protein levels of Sirt1, and the acetylation and activation of NF-κB p65 were determined.The expression and secretion of pro-inflammatory factors were evaluated, respectively. Treatment with TIIA significantly improved physiological indexes and increased the survival rate of mice in response to LPS challenge. TIIA treatment displayed an obvious up-regulation of Sirt1 protein, in accompany with reduced acetylation and activation of NF-κB p65 following LPS stimulation. In addition, TIIA attenuated LPS-induced lung injury and prevented the expression and secretion of pro-inflammatory factors. However, the protective effects of TIIA were abolished by Sirt1 inhibitor. Tanshinone IIA prevents LPS-induced secretion of pro-inflammatory cytokines thus exerts protective effects against acute lung injury, probably via modulation of Sirt1/NF-κB signalling pathway.

Abstract 3624: Tanshinone IIA could decrease programmed death ligand 1 expression in human breast cancer BT-20 cells

Abstract Breast cancer is the leading cause of cancer-related death in women. Many prescriptions for chemotherapy have been derived from plants. Danshen (Salviae miltiorrhizae radix) has been used in traditional Chinese medicine and appeared in the Chinese book, Shennong Bencao Jing (ca. 100 A.D.). Tanshinone IIA (Tan-IIA) is extracted from danshen and first described by researchers in 1968. Tan-IIA is well known to have antioxidant and anti-inflammatory properties. Tan-IIA could inhibit many human breast cancer cell lines through different molecular mechanisms in vitro and in vivo have been well documented. Our previous study showed Tan-IIA could inhibit human breast cancer cells through increased Bax to Bcl-xL ratios. Tan-IIA inhibits BT-20 (estrogen-, progesterone-, and HER2-negative subtype (TNBC)) human breast cancer cell proliferation through increasing caspase 12, GADD153 and phospho-p38 protein expression. Tan-IIA also inhibits human breast cancer MDA-MB-231 cells (estrogen-, progesterone-, and HER2-negative subtype (TNBC)) by decreasing LC3-II, Erb-B2 and NF-κBp65 in vivo. However, the effects and molecular mechanisms of Tan-IIA in human breast cancer have not been elucidated clearly. Programmed cell death-ligand 1 (PD-L1) is expressed on many cancer cells, which played a protective role against the cytotoxicity. PD-L1 interacts with programmed cell death-1 receptor (PD-1) to inhibit the T cells and block the antitumor immune response. PD-L1 antibodies, has demonstrated the possibility of dismiss immune suppression in many cancer cells. PD-L1 expression is a favorable biomarker for the prognosis of breast cancer; therefore, immune checkpoint blockade agents may be offering the opportunity to be the future treatment for breast cancer. The present study focused to evaluate the efficacy of Tan-IIA to be one of the immune checkpoint blockade agents for human breast cancer cells. Material and Method: In the present study, the human breast cancer BT-20 cells were treated with SJKJT in vitro. The effects of Tan-IIA on the protein expressions of PD-1, PD-L1, Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), B7-1 (CD80) and B7-2 (CD86) were measured by Western blotting. Results: The results showed that Tan-IIA can inhibit the protein expressions of PD-L1, in breast cancer BT-20 cells significantly. Conclusion: Breast cancer BT-20 cells were treated with Tan-IIA could inhibit the activity of PD-L1, CTLA-4, B7-1 (CD80) and B7-2 (CD86) significantly. These results suggest that one of the molecular mechanisms for Tan-IIA to inhibit breast cancer BT-20 cells maybe through inhibiting the protein expression of PD-L1. The use of Tan-IIA may become a feasible novel therapy option. Further studies are warranted to fully elucidate its mechanisms of action. Citation Format: Chin Cheng Su. Tanshinone IIA could decrease programmed death ligand 1 expression in human breast cancer BT-20 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3624.

GW26-e4374 Tanshinone IIA Protects H9c2 Cells From Oxidative Stress-Induced Cell Death Via Up-Regulation of MicroRNA-133 and Akt Activation

In this study the cardioprotective effect and molecular mechanisms of tanshinone IIA were investigated. Cardiac H9c2 cells were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. For transfection experiments, cells were transfected with 50 nM miR-133 mimic or

Mechanism of tanshinone ⅡA in inhibiting transformation of aortic valvular myofibroblast to osteoblast-like phenotype

Mechanism of tanshinone ⅡA in inhibiting transformation of aortic valvular myofibroblast to osteoblast-like phenotype

Inhibition of Tanshinone IIA, salvianolic acid A and salvianolic acid B on Areca nut extract-induced oral submucous fibrosis in vitro.

Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA1 (Tan-IIA1), salvianolic acid A (Sal-A) and salvianolic acid B (Sal-B), the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE)-induced oral submucous fibrosis (OSF) in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion and the activation of PI3K/AKT, ERK/JNK/p38 MAPK and TGF-β/Smads pathways were detected. The results showed that Tan-IIA1, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs), inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2/-9 activity, decrease TIMP-1/-2 expression and inhibit the transcription and release of CTGF, TGF-β1, IL-6 and TNF-α; Tan-IIA1, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-β/Smads pathway in HaCaT cells. In conclusion, Tan-IIA1, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.

The molecular mechanisms of Tanshinone IIA on the apoptosis and arrest of human esophageal carcinoma cells.

Objective. To explore the possible mechanisms of Tanshinone IIA (TanIIA) on esophageal carcinoma cell lines. Methods. Two human esophageal carcinoma cell lines (EC-1 cells and ECa-109 cells) were treated with different concentrations of TanIIA. Cell proliferation was measured by CCK-8, colony-forming efficiency was calculated, cell cycle and apoptosis were measured, and changes in cell cycle- and apoptosis-related gene expression were measured by Western blotting. Results. The CCK-8 and colony formation assay indicated that TanIIA inhibited the cell proliferation of human esophageal cancer cells (IC50 below 1 μg/mL) at 48 h. Hoechst 33258 and flow cytometry showed that TanIIA induced apoptosis in both esophageal cancer cell lines. Flow cytometry showed that TanIIA arrested cell cycle in S phase and G2/M phase. Western blotting analysis showed that Akt1 and its phosphorylation were inhibited, the Bax/Bcl-2 ratio increased, and both caspase-9 and caspase-3 were activated after treatment with 1.3 μg/mL TanIIA at 48 h. Meanwhile, p53 and p21 protein levels increased, whereas cyclin B1, CDC2, and CDC2 phosphorylation were inhibited. Conclusion. TanIIA inhibits the growth of esophageal cancer cells and induces apoptosis in a time-dependent and concentration-dependent manner, possibly by affecting cell cycle- and apoptosis-related signaling pathways.

Tanshinone IIA inhibits the dihydrotestosterone-induced secretion of lipids and activation of sterol regulatory element binding protein-1 in HaCaT cells.

To study the effects and mechanisms of Tanshinone IIA (Tan IIA) on the dihydrotestosterone (DHT)-induced expression of sterol regulatory element binding protein-1 (SREBP-1), the synthesis and secretion of lipids in HaCaT cells were examined. HaCaT cells were treated with DHT and Tan IIA at different concentrations. Real-time PCR was used to detect the expression of SREBP-1c, fatty acid synthase (FAS), acyl-CoA synthetase (ACS), stearoyl-CoA desaturase (SCD) and HMG-CoA reductase (HMGCR) mRNA in HaCaT cells. Western blotting was used to analyze the protein expression of SREBP-1 and phosphorylation of Akt. Flow cytometry and Nile red staining were used to detect the synthesis and secretion of lipids in HaCaT cells. We observed that Tan IIA inhibited the DHT-induced expression of SREBP-1 and p-AKT in HaCaT cells, which produced an effect similar to that of LY294002. Tan IIA significantly inhibited the transcription of lipid synthesis-related genes and decreased lipid secretion in HaCaT cells. In conclusion, Tan IIA downregulates the expression of lipid synthesis-related genes and decreases lipid secretion in HaCaT cells, which is correlated with the inhibitory effect on the DHT-induced mRNA and protein expression of SREBP-1 in HaCaT cells.