Abstract
Oxidative stress plays a central role in the pathogenesis of many human diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating the intracellular antioxidant response and is an emerging target for the prevention and therapy of oxidative stress-related diseases. Salviae Miltiorrhizae Radix et Rhizoma (SMRR) is a traditional Chinese medicine (TCM) and is commonly used for the therapy of cardiac cerebral diseases. Cumulative evidences indicated that the extract of SMRR and its constituents, represented by lipophilic diterpenoid quinones and hydrophilic phenolic acids, were capable of activating Nrf2 and inhibiting oxidative stress. These bioactive constituents demonstrated a therapeutic potential against human diseases, exemplified by cardiovascular diseases, neurodegenerative diseases, diabetes, nephropathy, and inflammation, based on the induction of Nrf2-mediated antioxidant response and the inhibition of oxidative stress. In the present review, we introduced the SMRR and Nrf2 signaling pathway, summarized the constituents with an Nrf2-inducing effect isolated from SMRR, and discussed the molecular mechanism and pharmacological functions of the SMRR extract and its constituents.
Highlights
Oxidative stress is defined as an imbalance of the oxidants/antioxidants tilting toward an oxidative status and characterized by the overproductions of reactive oxygen species (ROS) and reactive nitrogen species (RNS) compared with the basal state [1]
Cumulative evidences have verified that oxidative stress impairs cellular components and plays a central role in the pathogenesis of many human diseases, such as cardiovascular diseases, neurodegenerative diseases, chronic obstructive pulmonary disease (COPD), atherosclerosis, chronic kidney diseases, diabetes, and cancer [2,3,4,5,6,7,8]
In our systematic investigation of nuclear factor erythroid 2-related factor 2 (Nrf2) activators from traditional Chinese medicines (TCM) [1, 20,21,22], we found that the extract of Salviae Miltiorrhizae Radix et Rhizoma (SMRR) promoted the activity of Nrf2mediated phase II detoxifying enzyme, NAD(P)H: quinone reductase, and displayed potency on the activation of the Nrf2 signaling pathway [21]
Summary
Oxidative stress is defined as an imbalance of the oxidants/antioxidants tilting toward an oxidative status and characterized by the overproductions of reactive oxygen species (ROS) and reactive nitrogen species (RNS) compared with the basal state [1]. Cumulative evidences have verified that oxidative stress impairs cellular components (e.g., lipids, proteins, and nucleic acids) and plays a central role in the pathogenesis of many human diseases, such as cardiovascular diseases, neurodegenerative diseases, chronic obstructive pulmonary disease (COPD), atherosclerosis, chronic kidney diseases, diabetes, and cancer [2,3,4,5,6,7,8]. Activation of the Nrf2-mediated cellular defense system definitely intervenes the pathogenesis of oxidative stress-induced diseases, such as cancer [10], diabetes [11], respiratory diseases [12], chronic inflammation [13], cardiovascular diseases [14], and neurodegenerative diseases. The protective roles of Nrf against oxidative insults and xenobiotic have been verified by bioassays using Nrf2-null mice. We introduced the SMRR and Nrf pathway, summarized the Nrf activators from SMRR, and discussed their molecular mechanisms and pharmacological functions against human diseases
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