Table 5.
Effects on cardiovascular diseases.
| Disease model | Type | Solvent composition of extract | Animal/cell | Signal pathway | Major findings | References |
|---|---|---|---|---|---|---|
| Pulmonary hypertension | In vivo+in vitro | Asiaticoside | Male SD rats, rats’ PASMCs | TGF-β1/Smad | Mean pulmonary artery pressure ↓, right ventricular hypertrophy↓, vessel thickness ↓, media wall thickness ↓, TGF-β1 ↓, TGF-βRII ↓, p-Smad2/3 ↓ | (Wang et al., 2015) |
| Renovascular hypertension | In vivo | Asiatic acid | Male SD rats | Ang II/AT 1R/NADPH oxidase/NF-κB | SP↓, DP↓, MAP↓, HBF↑, HVR↑, Ang II↓, AT1R↓, AT2R↑, O2−↓, MDA↓, TNF-α↓ | (Maneesai et al., 2017) |
| Transverse aortic constriction | In vivo | Asiatic acid | Male C57BL/6 mice | TGF-β1/Smad2/3 | Ventricular wall thickness ↓, left ventricular posterior wall diastolic Dimensions ↓, LVEDD ↓, FS ↑, cardiac output ↑, Bax/Bcl-2↓,caspase-9 ↓, caspase-3 ↓, cytochrome c ↓, TGF-β1 ↓, α-SMA ↓, collagen I ↓, TNF-a ↓, IL-6 ↓, NF-kB ↓, JNK ↓, p-mad2/3/Smad2/3 ↓, Smad7 ↑ | (Si et al., 2015) |
| Myocardial ischemia/reperfusion (MI/R) injury | In vivo | Asiatic acid | Male SD rats | Akt/GSK-3β | LVEDV ↓, LVESV ↓, HR ↑, LV dp/dtmax ↑, LV dp/dtmin ↑, myocardial infarction size ↓, LDH ↓, CK ↓, p-Akt ↑, p-GSK-3β ↑, plasma glucose ↓, plasma lactate ↓ | (Dai et al., 2018) |
| – | In vitro | Asiaticoside | Human umbilical vein endothelial cells (HUVECs/7th passage) | – | Endothelial permeability ↓, ATP ↓, NO ↓, H2O2 ↓, IL-18 ↓, sICAM-1 ↓, sVCAM-1 ↓, E-selectin ↓ | (Jing et al., 2018) |
| Pulmonary hypertension | In vivo + In vitro | Asiaticoside | Male SD rats; HPAECs | PI3K/Akt/eNOS | Mean pulmonary artery pressure ↓, medial wall thickness ↓, Right ventricular hypertrophy ↓, pulmonary arteriole wall thickening ↓, inflammatory cell infiltration ↓, NO ↑, cGMP ↑, p−Akt ↑, p−eNOS ↑, caspase−3 ↓ | (Wang X. et al., 2018) |
| Atherosclerosis | In vitro | Asiatic acid | Human aortic endothelial cells (HAECs). | – | F-actin rearrangement ↓, stabilize the F-actin filaments, MLC dephosphorylation ↓, stabilize peripheral diphospho-MLC, VE-cadherin ↑, inhibit redistribution of occludin and ZO-1 | (Fong et al., 2019) |
| Atherogenic | In vitro | Asiaticoside | Human aortic endothelial cells | Vascular permeability ↓ | (Fong et al., 2015) | |
| Myocardial ischemic/reperfusion injury | In vitro | Asiatic Acid | Rat H9c2 Cardiomyocytes | Akt/GSK-3β/HIF-1α | Apoptotic cells ↓, caspase-9 ↓, caspase-3 ↓, Bax/Bcl-2 ↓, MMP ↑, Ca2+ ↓, ROS ↓, p-AKT ↑, p-GSK-3β↑, HIF-1α↑ | (Huang et al., 2016) |
| Atherogenesis | In vitro | Asiatic acid | Human aortic endothelial cells(HAECs). | NF-κB | sE-selectin ↓, sICAM-1 ↓, p-IκBα ↓, VCAM-1 ↓ | (Fong et al., 2016) |
TGF-β, transforming growth factor beta; SP, systolic blood pressure; DP, diastolic blood pressure; MAP, mean arterial blood pressure; HBF, hindlimb blood flow; HVR, hindlimb vascular resistance; Ang II, angiotensin II; FS, fractional shortening; LVEDD, left ventricular end-diastolic diameter; a-SMA, a-smooth muscle actin; LVESV, left ventricular end systolic volume; HR, heart rate; LDH, lactate dehydrogenase; CK, creatine kinase; eNOS, endothelial nitric oxide synthase; cGMP, cyclic guanosinc monophosphate; MLC, myosin light chain; ZO-1, zona occludens -1; HIF-1a, hypoxia-inducible factor 1a.