Asiatic acid, a pentacyclic triterpene from Centella asiatica, exhibits anticancer activities, induces apoptosis in melanoma cells, and provides barrier protective effects in human aortic endothelial cells (HAEC). It also demonstrates anti-inflammatory properties by inhibiting TNF-α-induced endothelial barrier dysfunction and the NLRP3 inflammasome activation along with the NF-κB pathway. These actions result in significant inflammation reduction in rats and offer neuroprotection in rat spinal cord injury models[1][2][3][4][5].
体内研究
Asiatic acid, administered via intragastric gavage at dosages ranging from 5 to 75 mg/kg once daily, has been found to effectively inhibit pelvic inflammatory disease (PID) in rats within a pathogen-induced disease model, demonstrating antioxidant and anti-inflammatory effects[3].
Asiatic acid, administered through intragastric injection at dosages of 30 mg/kg and 75 mg/kg once daily, exhibits neuroprotective effects on spinal cord injury (SCI) in rats by mitigating inflammation and oxidative stress[4].
体外研究
Asiatic acid stabilizes the barrier against TNF-α by preserving the structure of adherens junctions (AJs) and preventing the redistribution of tight junctions (TJs)[2].
Asiatic acid at a concentration of 40 μM maintains the stability of F-actin and diphosphate-MLC at the cellular periphery, thereby inhibiting their reorganization triggered by TNF-α (10 ng/mL for 1 hour). Conversely, Asiatic acid, within the range of 10-30 μM over 6 hours, does not diminish F-actin aggregation[2].
Asiatic acid, at a concentration of 40 μM administered for 6 hours, maintains the network structure of cell-cell contact regions and counteracts the TNF-α-induced structural rearrangement of vascular endothelial (VE)-cadherin and β-catenin[2].
Nonetheless, Asiatic acid, when applied in doses ranging from 10 to 40 μM for a duration of 6 hours, does not exhibit any inhibitory effect on the increased endothelial cell permeability caused by cytochalasin D (5 μM for 15 minutes). It has been observed that Asiatic acid enhances the diphosphorylation of myosin light chain (MLC)[2].
Asiatic acid/积雪草酸 细胞实验
Cell Line
Concentration
Treated Time
Description
References
LLC cells
20, 40, 80 μM
24 h
Asiatic acid inhibited LLC cell proliferation and induced apoptosis.
Acta Pharm Sin B. 2017 Jan;7(1):65-72.
H1299 cells
20, 40, 80 μM
24 h
Asiatic acid inhibited H1299 cell proliferation and induced apoptosis.
Acta Pharm Sin B. 2017 Jan;7(1):65-72.
A549 cells
20, 40, 80 μM
24 h
Asiatic acid induced apoptosis in A549 cells in a dose- and time-dependent manner, accompanied by mitochondrial membrane potential collapse and increased ROS generation.
Acta Pharm Sin B. 2017 Jan;7(1):65-72.
mouse mesangial cells (mMES)
20 µM
24 h
The combination of AA and NG showed insignificant cytotoxicity on mMES cells at 24h in vitro.
Int J Biol Sci. 2022 Aug 29;18(14):5489-5502.
mouse tubular epithelial cells (mTEC)
20 µM
24 h
AANG pre-treatment markedly upregulated Smad7 while significantly inhibiting AGE-induced Smad3 and NF-κB activation, thereby inhibiting collagen I and α-SMA expression in the mTEC in vitro.
Int J Biol Sci. 2022 Aug 29;18(14):5489-5502.
splenic NK cells
10 μM
24 h
Combined treatment with AA and NG increased IFN-γ and granzyme B production
Mol Ther. 2018 Sep 5;26(9):2255-2266.
bone marrow-derived NK cells
10 μM
24 h
AA restored TGF-β1-suppressed Smad7 expression and inhibited Smad3 phosphorylation
Mol Ther. 2018 Sep 5;26(9):2255-2266.
primary culture of rat embryo mesencephalic neurons
20 μM
24 h
AA reversed METH-induced TH expression reduction, inhibited ERK phosphorylation and NF-κB/STAT3 translocation, and reduced TNF-α and IL-6 secretion.
J Neuroinflammation. 2017 Dec 11;14(1):240.
murine microglial BV2 cell line
20 μM
24 h
AA inhibited METH-induced NF-κB/STAT3 translocation and JAK2/ERK phosphorylation, reducing TNF-α and IL-6 secretion.
J Neuroinflammation. 2017 Dec 11;14(1):240.
human dopaminergic neuroblastoma SH-SY5Y cell line
1, 10, 20 μM
24 h
AA significantly suppressed METH-induced TNFR expression and inhibited TNF-α and IL-6 secretion and mRNA expression.
J Neuroinflammation. 2017 Dec 11;14(1):240.
cardiac fibroblasts
20μM
24 h
AA attenuated Ang II-induced accumulation of collagen I and collagen III by activating AMPKα and suppressing mTOR and ERK signaling pathways.
Int J Biol Sci. 2016 May 25;12(7):861-71.
neonatal rat cardiac myocytes
20μM
24 h
AA inhibited Ang II-induced cardiomyocyte hypertrophy by activating AMPKα and suppressing mTOR/P70S6K/S6 and ERK signaling pathways.
Int J Biol Sci. 2016 May 25;12(7):861-71.
neonatal mouse cardiomyocytes
2–50μM
12 h
To evaluate the protective effects of AA on OGD cardiomyocytes, results showed that AA significantly increased cell viability and improved energy metabolism (increased ATP level and phosphocreatine/ATP ratio).
Acta Pharmacol Sin. 2022 Jun;43(6):1395-1407.
Asiatic acid/积雪草酸 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
Lewis lung cancer xenograft model
Oral
50 and 100 mg/kg
Once daily for 13 days
Asiatic acid significantly inhibited tumor volume and weight, accompanied by significant apoptosis of lung cancer cells.
Acta Pharm Sin B. 2017 Jan;7(1):65-72.
Dbb mice
Type-2 diabetic nephropathy model
Oral
300 mg/kg
Once daily for 20 weeks
Preventive treatment significantly reduced the urinary albumin-to-creatinine ratio (UACR) and HbA1c levels in dbb mice, improved insulin sensitivity and glucose metabolism, and restored islet β-cell development.
Int J Biol Sci. 2022 Aug 29;18(14):5489-5502.
C57BL/6 mice
B16F10 melanoma and LLC lung carcinoma models
Intraperitoneal injection
10 mg/kg
Daily for 27 days
Combined treatment with AA and NG significantly inhibited melanoma and lung carcinoma growth and enhanced NK cell-mediated anti-tumor immunity
Mol Ther. 2018 Sep 5;26(9):2255-2266.
C57/B6 mice
Aortic banding model
Oral
10 or 30mg/kg
Daily for 7 weeks
AA attenuated pressure overload-induced cardiac hypertrophy and fibrosis by activating AMPKα and suppressing mTOR/P70S6K/S6 and ERK signaling pathways.
Int J Biol Sci. 2016 May 25;12(7):861-71.
Mice
Spinal cord injury model
Intraperitoneal injection
550 μg/kg
Once daily for 3 days
To test whether SS-31 regulated cPLA2 partially through the MAPK-P38 signalling pathway
J Neuroinflammation. 2023 Jan 7;20(1):6
Sprague-Dawley rats
Permanent and transient middle cerebral artery occlusion models
Intravenous injection
75 mg/kg
Single dose, observed for 24 hours or 14 days
To evaluate the neuroprotective effects of Asiatic acid in multiple stroke models, results showed AA significantly reduced infarct volume, improved neurological outcomes, and protected mitochondrial function and inhibited MMP-9 induction and activity.
Stroke. 2012 Jun;43(6):1632-8
C57BL/6 mice
Myocardial infarction model
Oral
5–125 mg/kg
Once daily for 7 consecutive days
To evaluate the protective effects of AA on the myocardial infarction mouse model, results showed that AA significantly reduced infarct size, improved cardiac function, and promoted mitophagy and glycophagy.
Acta Pharmacol Sin. 2022 Jun;43(6):1395-1407.
Sprague-Dawley rats and ICR mice
Unilateral ureteral occlusion (UUO) model
Oral
Rats: 10 mg/kg; Mice: 15 mg/kg
Rats: once a day for 7 days; Mice: once a day for 3 days
Asiatic acid attenuates renal injury and fibrosis in the UUO model by promoting the production of the endogenous ligand 15d-PGJ2, which activates PPAR-γ
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