Stroke is the second most common cause of death worldwide, and effective treatment methods have not yet been developed [
1].
Dracocephalum moldavica L., the dry aerial parts of which are widely used as a traditional Chinese medicine in Xinjiang, is a member of the family Lamiaceae [
2]. The active components of
D. moldavica L. (TFDM) have heart- and brain-tonifying functions, activate blood circulation and improve blood stasis [
3‐
6]; therefore, it is mainly used for the treatment of cerebrovascular diseases. TFDM contains the main active components of
D. moldavica L., accounting for 53.06% of the total activity. The main active ingredients of TFDM are tilianin (13.0 to 17.0%), acacetin-7-O-β-D-glucuronide (10.0 to 13.5%), luteolin-7-O-β-D-glucuronide (8.0 to 9.0%), diosmetin − 7-O- β-D-glucuronide (7.0 to 8.6%) and apigenin-7-O-β-D-glucuronide (2.0 to 3.0%). It has been reported that these flavonoids have anti-inflammatory and antioxidant stress effects [
7‐
12]. In general, flavonoids are the most powerful and widely used bioactive compounds in plants and have cardioprotective and neuroprotective effects and have cardioprotective and neuroprotective effects [
13‐
16]. Single-drug preparations of
D. moldavica L., called Yixin Badiran Jibuya granules, have been used in the treatment of angina pectoris. Our previous studies found that TFDM can inhibit myocardial ischemia and stroke through the inhibition of oxygen free radical production [
17‐
20], and recent evidence confirms that TFDM functions as an effective and stable free radical scavenger [
21]. The purpose of this study was to investigate the role of TFDM in astrocytes, which are the most abundant cells in the central system and comprise approximately 20% of the total brain cells in mammals.
In the brain, neuronal cells are sensitive to oxidative and stress injury, and their survival depends on the protection of neighboring astrocytes against oxidation [
22]. It has been reported that neuronal degeneration and astroglial scar destruction caused by astrocyte failure are associated with poststroke inflammatory diffusion and infarct volume in mice [
23,
24]. Mitochondria are the main target of oxidative stress injury, and ROS result in an increased free Ca
2+ concentration in mitochondria, which ultimately leads to apoptosis in astrocytes. Therefore, the survival of astrocytes under oxidative stress may be critical for reducing neuronal death [
25]. Human glioma U87 cells have been used as model astrocytes in vitro [
26].
Calmodulin kinase II (CaMKII) is an important target for cerebral ischemic nerve injury; phosphorylated CaMKII migrates from the cytoplasm to the cell membrane [
27]. The effect is enhanced neuronal discharge and calcium inflow, aggravation of mitochondrial dysfunction and upregulation of the expression of downstream proteins related to apoptosis. The current study explored whether TFDM protects astrocytes against oxidative stress-induced apoptosis by attenuating a CaMKII-dependent mitochondria pathway.