Table 2.
Summarized in vivo mechanism of action of tanshinone IIA and STS.
| Biological activity | Animal | Disease model | Drug used | Drug dose | Timing | Key regulated factors | Physiological effect | Ref. |
|---|---|---|---|---|---|---|---|---|
| Antioxidative | Male Sprague–Dawley rats | High cholesterol diet-driven atherosclerotic calcification | TanIIA | 35-70 mg/kg, oral | 12 weeks | Cu/Zn SOD (↑) LDL (↓) Superoxide anion (↓) |
Reduces atherosclerotic calcification | [148] |
| Male–Sprague Dawley rats | Two-kidney, two-clip (2K2C) hypertensive rats | TanIIA | 35-70 mg/(kg·d), oral | 6 weeks (starting from 4 weeks after surgery) |
Superoxide (↓) NOX2, NOX4, p47phox (↓) |
Reduces myocardial fibrosis, cardiac hypertrophy and dysfunction | [149] | |
| Male C57BL/6 mice | LPS-induced cardiac fibrosis | TanIIA | 10 mg/(kg·d), i.p. | 2 weeks | gp91phox (↓), p67phox (↓) Collagens (↓), MMP2/9 (↓) TIMP1/2 (↓) |
Suppresses cardiac fibrosis | [150] | |
| Male Sprague–Dawley rats | Isoproterenol-induced myocardial infarction | STS | 4-16 mg/kg, i.v. | 7 d (prior to ISO injection) |
p-ERK1/2 (↓) SOD, GSH, GPx (↑) Nrf2, HO-1 (↑) AMPK/CPT-1 (↓) |
Maintains the levels of circulating lipids and stabilizes cardiac functions | [64] | |
| Male ICR mice | Acute pancreatitis (caerulein, taurocholate injection) | STS | 25 mg/kg, i.p. | 2 h prior to surgery | Nrf2 (↑) | Ameliorates acute pancreatitis | [66] | |
| Male C57BL/6 mice | Lewis lung carcinoma + intermittent hypoxia | STS | 10 mg/(kg·d), i.p. | 5 weeks (starting from 5-7 d After tumor implantation) |
Nrf2 (↑) MDA, SOD (↓) NF-κB (↓) |
Reduces tumor size driven by intermittent hypoxia | [65] | |
|
| ||||||||
| Anti-inflammatory | Male C57BL/6 mice | Adjuvant-induced arthritis (AIA) | TanIIA | 30 mg/(kg·d), intragastric | 2-31 d After arthritis induction |
IL-6, IL-17, TNF-α (↓) | Ameliorates arthritis severity in AIA models | [71] |
| Male ApoE−/− mice | High-fat diet | TanIIA | 10-90 mg/(kg·d), gavage | 13-26 weeks | TLR4, MyD88, NF-κB (↓) MCP-1, TNF-α (↓) |
Reduces atherosclerosis severity, stabilizes plaque, and decreases the blood lipid levels | [73] | |
| Male beagle dogs | Occlusion of left anterior descending | STS | 1.3-5.2 mg/kg, i.v. | 15 min After occlusion |
TXNIP (↓), NLRP3 inflammasome, IL-18 (↓), p-JAK2, p-STAT3 (↓) SOSC3 (↑), p-insulin receptor, p-AkT, p-ERK1/2 (↑), PPARα (↑) | Reduces myocardial infarct size and attenuates inflammatory cells infiltration | [76] | |
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| ||||||||
| Anti-fibrotic | Spontaneously hypertensive rats | None | TanIIA | 1-10 mg/(kg·week), i.p. | From 21 weeks | cTn-I, ADMA, Col1a1, Col3a1 (↓), NOX4 (↓), eNOS, NO (↑), Cys-C/Wnt signaling (↓) | Reduces systolic blood pressure and cardiac fibrosis in spontaneously hypertensive rats | [120] |