Functional Redox Proteomics Reveal That Salvia miltiorrhiza Aqueous Extract Alleviates Adriamycin-Induced Cardiomyopathy via Inhibiting ROS-Dependent Apoptosis

Abstract

The anticancer agent adriamycin (ADR) has long been recognized to induce a dose-limiting cardiotoxicity, while Salvia miltiorrhiza (SM) is a Chinese herb widely used for the treatment of cardiovascular disorders and its aqueous extract (SMAE) has shown anticancer as well as antioxidant effects. In the current study, we aimed at investigating the synergistic effect and potent molecular mechanisms of SMAE with a focus on the cardioprotective benefit observed under ADR adoption. Histopathological analysis indicated that SMAE could substantially alleviate cardiomyopathy and cell apoptosis caused by ADR. Meanwhile, the two-dimensional electrophoresis (2-DE) oxyblots demonstrated that SMAE treatment could effectively reduce carbonylation of specific proteins associated with oxidative stress response and various metabolic pathways in the presence of ADR. SMAE application also showed protective efficacy against ADR-mediated H9c2 cell death in a dose-dependent manner without causing any cytotoxicity and significantly attenuated the reactive oxygen species production. Particularly, the simultaneous administration of ADR and SMAE could remarkably suppress the growth of breast cancer cells. We also noticed that there was a marked upregulation of detoxifying enzyme system in the presence of SMAE, and its exposure also contributed to an increase in Nrf2 and HO-1 content as well. SMAE also amended the ERK/p53/Bcl-xL/caspase-3 signaling pathways and the mitochondrial dysfunction, which eventually attribute to apoptotic cathepsin B/AIF cascades. Correspondingly, both the ERK1/2 inhibitor (U0126) and pan-caspase inhibitor (Z-VAD-FMK) could at least partially abolish the ADR-associated cytotoxicity in H9c2 cells. Collectively, these results support that ROS apoptosis-inducing molecule release is closely involved in ADR-induced cardiotoxicity while SMAE could prevent or mitigate the causative cardiomyopathy through controlling multiple targets without compromising the efficacy of chemotherapy.

Resveratrol Derivative, Trans‐3, 5, 4 ′‐Trimethoxystilbene Sensitizes Osteosarcoma Cells to Apoptosis via ROS‐Induced Caspases Activation

“…Intracellular cues, such as cellular DNA damage, can induce apoptosis primarily via the intrinsic pathway. The intrinsic apoptosis pathway, which involves activation of conserved signaling proteins, such as that of p53, is physically associated with [28]. The 11 Oxidative Medicine and Cellular Longevity extrinsic apoptosis pathway is activated by extracellular ligands binding to cell-surface death receptors, which results in the formation of a death-inducing signaling complex (DISC).…”

Asiatic Acid Prevents Cognitive Deficits by Inhibiting Calpain Activation and Preserving Synaptic and Mitochondrial Function in Rats with Kainic Acid-Induced Seizure

“…We used two algorithms for the network analysis: (i) the analysis network algorithm, to deduce the scoring processes regulated by the differentially expressed proteins; and (ii) the shortest path algorithm, to build a network consisting of the smallest possible number of direct interactions between the differentially expressed proteins. The statistical relevance of the ontological matches was calculated as the p value [ 35 ].…”

Polyphenols of Salvia miltiorrhiza in Aging-Associated Cardiovascular Diseases and Cancer

“…As we know either chemotherapy or radiotherapy was usually associate with uncomfortable side-effects which are burdens to clinical physicians. Our previous researches find the aqueous extract of Danshen has shown anticancer as well as antioxidant effects, besides, it could prevent or mitigate the causative cardiomyopathy through controlling multiple targets without compromising the efficacy of chemotherapy (Table 2) [107,108].…”