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• Here, we investigate the role of SmERF73, a group VII ETHYLENE RESPONSE FACTOR stress response transcription factor, in the regulation of post-modification of the skeleton precursors of diterpene tanshinones in Salvia miltiorrhiza. • Most genes found to be involved in tanshinone biosynthesis are located on chromosome 6, and five of these genes comprise a large gene cluster in S. miltiorrhiza. We found that SmERF73 overexpression in S. miltiorrhiza coordinately up-regulated the transcription of seven tanshinone biosynthetic genes, four of which were located in the tanshinone gene cluster, consequently increasing tanshinone accumulation, while SmERF73 silencing reduced corresponding gene transcription and tanshinone accumulation. • SmERF73 recognizes GCC-box promoter elements of four tanshinone-associated genes (DXR1, CPS1, KSL1 and CYP76AH3) and activates their expression. Moreover, SmERF73 and its targets were up-regulated by stress elicitors; SmERF73 appears to be at least partly mediated by the jasmonic acid (JA) signaling pathway via interaction with SmJAZ3. • SmERF73 coordinately regulates tanshinone biosynthetic gene expression, suggesting a potential link between tanshinone production and plant stress responses.

Tanshinone IIA (Tan IIA) is a pharmacologically lipophilic active constituent isolated from the roots and rhizomes of the Chinese medicinal herb Salvia miltiorrhiza Bunge (Danshen). Tan IIA is currently used in China and other neighboring countries to treat patients with cardiovascular system, diabetes, apoplexy, arthritis, sepsis, and other diseases. Recently, it was reported that tan IIA could have a wide range of antitumor effects on several human tumor cell lines, but the research of the mechanism of tan IIA is relatively scattered in cancer. This review aimed to summarize the recent advances in the anticancer effects of tan IIA and to provide a novel perspective on clinical use of tan IIA.

Cardiovascular diseases (CVDs) remain the leading cause of mortality among non-communicable diseases worldwide. Vascular smooth muscle cells (VSMCs), as the predominant cellular component of the tunica media, are essential for maintaining vascular homeostasis through phenotype-dependent regulation of vascular tone, blood pressure, and hemodynamics. Under pathological conditions such as hypoxia or inflammation, VSMCs undergo phenotypic switching from a contractile to a synthetic state. This transition is characterized by excessive proliferation, migration, and pro-inflammatory secretion, all of which contribute to the progression of atherosclerosis and restenosis. Tanshinones, bioactive diterpenoid compounds isolated from Salvia miltiorrhiza , exert cardioprotective effects through their anti-inflammatory, antioxidant, and VSMC-modulating activities. Increasing evidence suggests that tanshinones attenuate maladaptive VSMC behaviors by regulating calcium signaling, modulating programmed cell death pathways, and suppressing pro-inflammatory signaling cascades. These actions collectively inhibit phenotypic switching and mitigate vascular remodeling and plaque formation. Despite these advances, a comprehensive understanding of the precise molecular targets and signaling networks of tanshinones in VSMCs is still lacking. This review aims to integrate current evidence to delineate tanshinone-mediated VSMC regulatory mechanisms, provide mechanistic insights, and identify potential therapeutic targets for phenotype-directed interventions in CVDs.

The progression of neurological diseases is mainly attributed to oxidative stress, apoptosis, inflammation, and trauma, making them a primary public concern. Since no drugs can stop these neurological disorders from happening, active phytochemical intervention has been suggested as a possible treatment. Among the several phytochemicals being studied for their potential health advantages, tanshinone-IIA (Tan-IIA ) stands out due to its wide range of therapeutic effects. Tan-IIA, derived from the Salvia miltiorrhiza plant, is a phenanthrenequinone. The pharmacological characteristics of Tan-IIAagainst various neurodegenerative and neuropsychiatric illnesses have led researchers to believe that the compound possesses neuroprotective potential. Tan-IIA has therapeutic potential in treating neurological diseases due to its capacity to cross the blood-brain barrier and its broad range of activities. In treating neurological disorders, Tan-IIA has been shown to have neuroprotective effects such as anti-apoptotic, anti-inflammatory, BBB protectant, and antioxidant properties. This article concisely summarises the latest scientific findings about the cellular and molecular aspects of Tan-IIA neuroprotection in relation to various neurological diseases. The results of preclinical studies on Tan-IIA provide insight into its potential application in future therapeutic development. This molecule rapidly establishes as a prominent bioactive compound for clinical research.

Tanshinone IIA (Tan IIA) is a fat-soluble compound extracted from Salvia miltiorrhiza , which has a protective effect against atherosclerosis (AS). Tan IIA can inhibit oxidative stress and inflammatory damage of vascular endothelial cells (VECs) and improve endothelial cell dysfunction. Tan IIA also has a good protective effect on vascular smooth muscle cells (VSMCs). It can reduce vascular stenosis by inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs), and improve the stability of the fibrous cap of atherosclerotic plaque by inhibiting apoptosis and inflammation of VSMCs. In addition, Tan IIA inhibits the inflammatory response of macrophages and the formation of foam cells in atherosclerotic plaques. In summary, Tan IIA improves AS through a complex pathway. We propose to further study the specific molecular targets of Tan IIA using systems biology methods, so as to fundamentally elucidate the mechanism of Tan IIA. It is worth mentioning that there is a lack of high-quality evidence-based medical data on Tan IIA treatment of AS. We recommend that a randomized controlled clinical trial be conducted to evaluate the exact efficacy of Tan IIA in improving AS. Finally, sodium tanshinone IIA sulfonate (STS) can cause adverse drug reactions in some patients, which needs our attention.

Tanshinones are the bioactive nor -diterpenoid constituents of the Chinese medicinal herb Danshen ( Salvia miltiorrhiza ). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae. Salvia miltiorrhiza is a medicinal plant that can produce the bioactive tanshinones. Here, the authors report the improved genome assembly and reveal the possible roles of three CYP71Ds in catalyzing the reactions leading to the formation of the characteristic furan D-ring of transhinones.

Aims/Introduction Tanshinone IIA (TIIA) is one of the main components of the root of the red‐rooted Salvia miltiorrhiza Bunge. However, the molecular mechanisms underlying TIIA‐mediated protective effects in diabetic nephropathy (DN) are still unclear. Materials and Methods High glucose (HG)‐induced mouse podocyte cell line (MPC5) cells were used as the in vitro model of DN and treated with TIIA. Cell viability, proliferation and apoptosis were detected using 3‐(4, 5‐dimethylthiazolyl‐2)‐2, 5‐diphenyltetrazolium bromide, 5‐ethynyl‐2′‐deoxyuridine and flow cytometry assays. The protein levels were assessed using western blot assay. The levels of inflammatory factors were deleted by enzyme‐linked immunoassay. Fe+ level, reactive oxygen species, malondialdehyde and glutathione products were detected using special assay kits. After ENCORI prediction, the interaction between embryonic lethal abnormal visual‐like protein 1 (ELAVL1) and acyl‐coenzyme A synthetase long‐chain family member 4 (ACSL4) was verified using co‐immunoprecipitation assay and dual‐luciferase reporter assays. ACSL4 messenger ribonucleic acid expression was measured using real‐time quantitative polymerase chain reaction. Results TIIA repressed HG‐induced MPC5 cell apoptosis, inflammatory response and ferroptosis. ACSL4 upregulation relieved the repression of TIIA on HG‐mediated MPC5 cell injury and ferroptosis. ELAVL1 is bound with ACSL4 to positively regulate the stability of ACSL4 messenger ribonucleic acid. TIIA hindered HG‐triggered MPC5 cell injury and ferroptosis by regulating the ELAVL1–ACSL4 pathway. TIIA blocked DN progression in in vivo research. Conclusion TIIA treatment restrained HG‐caused MPC5 cell injury and ferroptosis partly through targeting the ELAVL1–ACSL4 axis, providing a promising therapeutic target for DN treatment. Tanshinone IIA might repress high glucose‐induced mouse podocyte cell line cell apoptosis, inflammatory response and ferroptosis by regulating acyl‐coenzyme A synthetase long‐chain family member 4 protein stability through embryonic lethal abnormal visual‐like protein 1.

Bioactive chemical constitutes from the root of classified in two major groups, viz., liposoluble tanshinones and water-soluble phenolics. Tanshinone IIA is a major lipid-soluble compound having promising health benefits. The and studies showed that the tanshinone IIA and salvianolate have a wide range of cardiovascular and other pharmacological effects, including antioxidative, anti-inflammatory, endothelial protective, myocardial protective, anticoagulation, vasodilation, and anti-atherosclerosis, as well as significantly help to reduce proliferation and migration of vascular smooth muscle cells. In addition, some of the clinical studies reported that the preparations in combination with Western medicine were more effective for treatment of various cardiovascular diseases including angina pectoris, myocardial infarction, hypertension, hyperlipidemia, and pulmonary heart diseases. In this review, we demonstrated the potential applications of , including pharmacological effects of salvianolate, tanshinone IIA, and its water-soluble derivative, like sodium tanshinone IIA sulfonate. Moreover, we also provided details about the clinical applications of preparations in controlling the cardiovascular diseases.

Cardiovascular disease, a disease caused by many pathogenic factors, is one of the most common causes of death worldwide, and oxidative stress plays a major role in its pathophysiology. Tanshinone I (Tan I), a natural compound with cardiovascular protective effects, is one of the main active compounds extracted from Salvia miltiorrhiza . Here, we investigated whether Tan I could attenuate oxidative stress and oxidative stress–induced cardiomyocyte apoptosis through Nrf2/MAPK signaling in vivo and in vitro . We found that Tan I treatment protected cardiomyocytes against oxidative stress and oxidative stress–induced apoptosis, based on the detection of relevant oxidation indexes such as reactive oxygen species, superoxide dismutase, malondialdehyde, and apoptosis, including cell viability and apoptosis-related protein expression. We further examined the mechanisms underlying these effects, determining that Tan I activated nuclear factor erythroid 2 (NFE2)–related factor 2 (Nrf2) transcription into the nucleus and dose-dependently promoted the expression of Nrf2, while inhibiting MAPK signaling activation, including P38 MAPK, SAPK/JNK, and ERK1/2. Nrf2 inhibitors in H9C2 cells and Nrf2 knockout mice demonstrated aggravated oxidative stress and oxidative stress–induced cardiomyocyte injury; Tan I treatment suppressed these effects in H9C2 cells; however, its protective effect was inhibited in Nrf2 knockout mice. Additionally, the analysis of surface plasmon resonance demonstrated that Tan I could directly target Nrf2 and act as a potential Nrf2 agonist. Collectively, these data strongly indicated that Tan I might inhibit oxidative stress and oxidative stress–induced cardiomyocyte injury through modulation of Nrf2 signaling, thus supporting the potential therapeutic application of Tan I for oxidative stress–induced CVDs.

Background: Tanshinone IIA, derived from Radix Salviae Miltiorrhizae ( Salvia miltiorrhiza Bunge ), constitutes a significant component of this traditional Chinese medicine. Numerous studies have reported positive outcomes regarding its influence on cardiac function. However, a comprehensive comprehension of the intricate mechanisms responsible for its cardioprotective effects is still lacking. Methods: A rat model of heart failure (HF) induced by acute myocardial infarction (AMI) was established via ligation of the left anterior descending coronary artery. Rats received oral administration of tanshinone IIA (1.5 mg/kg) and captopril (10 mg/kg) for 8 weeks. Cardiac function was assessed through various evaluations. Histological changes in myocardial tissue were observed using staining techniques, including Hematoxylin and Eosin (HE), Masson, and transmission electron microscopy. Tunel staining was used to detect cell apoptosis. Serum levels of NT-pro-BNP, IL-1β, and IL-18 were quantified using enzyme-linked immunosorbent assay (ELISA). Expression levels of TLR4, NF-κB p65, and pyroptosis-related proteins were determined via western blotting (WB). H9C2 cardiomyocytes underwent hypoxia-reoxygenation (H/R) to simulate ischemia-reperfusion (I/R) injury, and cell viability and apoptosis were assessed post treatment with different tanshinone IIA concentrations (0.05 μg/ml, 0.1 μg/ml). ELISA measured IL-1β, IL-18, and LDH expression in the cell supernatant, while WB analysis evaluated TLR4, NF-κB p65, and pyroptosis-related protein levels. NF-κB p65 protein nuclear translocation was observed using laser confocal microscopy. Results: Tanshinone IIA treatment exhibited enhanced cardiac function, mitigated histological cardiac tissue damage, lowered serum levels of NT-pro-BNP, IL-1β, and IL-18, and suppressed myocardial cell apoptosis. Moreover, tanshinone IIA downregulated the expression of TLR4, NF-κB p65, IL-1β, pro-IL-1β, NLRP3, Caspase-1, and GSDMD-N pyroptosis-related proteins in myocardial tissue. Additionally, it bolstered H/R H9C2 cardiomyocyte viability, curbed cardiomyocyte apoptosis, and reduced the levels of TLR4, NF-κB p65, IL-1β, pro-IL-1β, NLRP3, Caspase-1, and GSDMD-N pyroptosis-related proteins in H/R H9C2 cells. Furthermore, it hindered NF-κB p65 protein nuclear translocation. Conclusion: These findings indicate that tanshinone IIA enhances cardiac function and alleviates myocardial injury in HF rats following AMI. Moreover, tanshinone IIA demonstrates potential suppression of cardiomyocyte pyroptosis. These effects likely arise from the inhibition of the TLR4/NF-κB p65 signaling pathway, presenting a promising therapeutic target.