Research Progress on the Pharmacological Effects and Mechanisms of Asiaticoside

Asiaticoside is one of the main components of triterpenoid saponins extracted from Centella asiatica, with a molecular formula of C48H78O19. Modern pharmacological studies have confirmed that Asiaticoside possesses anti-inflammatory, anti-scar formation, wound healing promotion, neuroprotective, anti-anxiety, and immune regulatory effects.

1. Anti-inflammatory Mechanism

Asiaticoside can ameliorate various inflammatory responses, and its mechanism is related to downregulating the expression of IL-6, IL-1β, and TNF-α in the NF-κB pathway and inhibiting oxidative stress. Research has found that on one hand, Asiaticoside can exert anti-inflammatory effects by inhibiting the NF-κB signaling pathway and downregulating the expression of nitric oxide (NO), TNF-α, and IL-6. On the other hand, Asiaticoside can also inhibit the production of proinflammatory factors and the activity of peroxidase by regulating the heme oxygenase 1 (HO-1) signaling pathway, thus exerting anti-inflammatory effects. Asiaticoside can alleviate inflammatory responses caused by hypoxic conditions by inhibiting the NF-κB/p38 signaling pathway, and can reduce inflammatory responses caused by hyperoxic conditions by downregulating the expression of microRNA-155 (miR-155) and upregulating the expression of suppressor of cytokine signaling 1 (SOCS1).

2.Improvement Mechanisms for Liver, Lung, and Kidney Injury

Asiaticoside can improve liver, lung, and kidney injuries, and its mechanism is related to inhibiting oxidative stress inflammatory responses and enhancing antioxidant capabilities. Research has shown that Asiaticoside has an ameliorating effect on sepsis-induced lung injury and sepsis-induced acute kidney injury. On one hand, Asiaticoside can improve lung injury by upregulating the expression of PPAR-γ and inhibiting the activity of MAPK and NF-κB signaling pathways. On the other hand, Asiaticoside can improve kidney injury by downregulating the expression of IL-6 in serum and iNOS protein in kidney tissue. Asiaticoside can improve renal injury in rats with a kidney disease model, and its mechanism is related to upregulating the mRNA expression of synaptophysin, endorphin, and podocalyxin and downregulating the mRNA expression of desmin. Through in vivo and in vitro experiments studying the improvement effects of Asiaticoside on hyperoxia-induced lung injury, it was found that Asiaticoside can alleviate lung injury in rats by reducing the levels of myeloperoxidase (MPO), malondialdehyde (MDA), TNF-α, IL-1β, and IL-6 in serum of lung injury models, and increasing total antioxidant capacity (TAOC). Additionally, Asiaticoside can improve liver injury by inhibiting the expression of TNF-α and MAPK.

3.Mechanism of Inhibiting Scar Formation and Repairing Skin Injury

Asiaticoside can inhibit scar formation and repair skin injury. Its mechanism is related to inhibiting the expression of collagen types I and III, TNF-α, IL-6, IL-1β, and the activity of the Wnt/β-catenin signaling pathway, as well as upregulating the expression of TGF-β1, VEGF, iNOS, and MCP-1.

Asiaticoside can inhibit the proliferation of scar fibroblasts. When the drug concentration is between 0.1 and 1.0 mg/ml, the proliferation of fibroblasts is significantly inhibited, indicating that Asiaticoside reduces the synthesis of extracellular matrix such as granulation tissue and collagen by inhibiting fibroblasts, thereby reducing scar formation. At the same time, when Asiaticoside is at 1.0 mg/ml, it can inhibit the expression of type I and III collagen mRNA in scar fibroblasts, suggesting that Asiaticoside can inhibit scar formation by reducing collagen production and extracellular matrix synthesis. This demonstrates that Asiaticoside can inhibit overly active fibroblasts, suppressing their collagen secretion function, thereby inhibiting collagen proliferation and intervening in scar formation.

In vitro experiments have shown that the mechanism of Asiaticoside inhibiting the proliferation of scar fibroblasts is related to inhibiting the expression of proteins associated with the RhoA/Rho kinase I (RhoA/ROCK I) signaling pathway, as well as downregulating the autocrine expression of collagen types I and III and TGF-β1 mRNA. Related research found that in a rabbit ear scar model, with increasing drug administration time, the scar area gradually decreased, and its mechanism was related to reducing the expression level of TGF-β1. Asiaticoside can inhibit the formation of hyperplastic scars in rabbits by downregulating the expression of collagen types I and III, IL-1β, IL-6, and IL-8 mRNA, and upregulating the expression of Smad7 and PPARγ mRNA, showing a dose-dependent relationship. Studies have found that coaxial nanofibers loaded with Asiaticoside can promote the healing of deep second-degree burn wounds in rats by upregulating the expression of VEGF, PCNA, and endothelial cell adhesion molecule (CD31), and downregulating the expression of TNF-α and IL-6. Additionally, other research has found that Asiaticoside can also promote the production of monocyte chemoattractant protein-1 (MCP-1), further contributing to the healing of burn wounds.

Asiaticoside complexes can alleviate inflammatory responses in diabetic cutaneous ulcer (DCU) model rats, inhibit bacterial growth at the wound site, and promote wound healing. They also upregulate the expression of VEGF, iNOS, endothelial nitric oxide synthase (eNOS), and CD34. Its mechanism of action is related to downregulating the Wnt/β-catenin signaling pathway. Arbitrary skin flaps are a commonly used technique in skin burns and surgical repairs. They involve selecting an area similar to the damaged skin site based on the skin defect, and then transferring the skin flap to the defect area for repair, achieving the purpose of skin defect repair. Research has found that Asiaticoside can increase the survival area of skin flaps in rats, and its mechanism is related to upregulating the expression of superoxide dismutase (SOD) and VEGF, while downregulating the expression of inflammatory factors. Other studies have also found that Asiaticoside-based sodium alginate repair patches and Asiaticoside nanoemulsions have good repairing effects on skin injuries.

4.Mechanism of Anti-Alzheimer's Disease Action

Asiaticoside can improve Alzheimer's disease (AD), and its mechanism of action is related to inhibiting the apoptosis of HUVECs, the activity of the TLR4/NF-κB signaling pathway, and the expression of inflammatory factors IL-1, IL-6, and TNF-α. According to literature reports, Asiaticoside can alleviate neuroinflammation by reducing the level of NO in astrocytes and the expression of iNOS mRNA. Asiaticoside can improve the damage caused by Aβ to vascular endothelial cells (HUVECs), and its mechanism of action is related to inhibiting cell apoptosis and the expression of IL-1, IL-6, and TNF-α. Studies on the intervention of Asiaticoside in apoptosis induced by Aβ1-42 in human brain microvascular endothelial cells (hBMECs) have found that Asiaticoside can inhibit hBMECs apoptosis, and its mechanism is related to inhibiting the expression of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), p-NF-κB p65 protein, and the nuclear translocation of NF-κB, as well as the expression of TNF-α and IL-6 in the TLR4/NF-κB signaling pathway. Asiaticoside can regulate the production of Aβ before neurodegeneration, thus preventing the occurrence of AD. Asiaticoside has a protective effect on HUVEC damage caused by Aβ1-42, and its mechanism is related to upregulating the expression of Bcl-2 and downregulating the expression of Bax. Research has found that Asiaticoside has a significant reversing effect on AD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and its mechanism is related to increasing the Bcl-2/Bax ratio. Moreover, Asiaticoside has strong blood-brain barrier penetration ability, showing potential in the treatment of neurodegenerative diseases.

5.Anti-Fibrosis Mechanism of Action

Asiaticoside can reduce the degree of fibrosis in various tissues and organs such as the lungs, liver, kidneys, and heart. Its mechanism of action is related to downregulating the expression of TGF-β1, CTGF, ALT, Asiaticoside T, and Hyp. Relevant studies have found that when the concentration of Asiaticoside reaches 400 μg/mL, it exhibits inhibitory effects on both human embryonic skin fibroblasts and human lung fibroblasts. Asiaticoside exerts an anti-fibrotic effect by inhibiting the production of inflammatory cytokines and reducing the expression level of TGF-β1mRNA. Asiaticoside can significantly improve renal fibrosis in rats with unilateral ureteral obstruction, and its mechanism is related to downregulating the expression of renal interstitial connective tissue growth factor (CTGF) and type III collagen (Col III). Additionally, Asiaticoside can also improve myocardial fibrosis after myocardial infarction in rats. Asiaticoside can reduce the degree of fibrosis in rat liver tissue and significantly decrease ALT, Asiaticoside T levels in rat serum, as well as Hyp levels in liver tissue, indicating that Asiaticoside has an improving effect on immune liver fibrosis. Asiaticoside can improve bleomycin (BLM)-induced pulmonary fibrosis in rats, and its mechanism is related to regulating the TGF-β1/Smad pathway. Other studies have found that Asiaticoside can also significantly reduce the degree of fibrosis in lung tissues of pulmonary fibrosis model mice, and its mechanism is through activating the A2AR-assisted cyclic adenosine monophosphate (cAMP)/R Asiaticoside-related protein 1 (RAP1) signaling pathway to improve pulmonary fibrosis.

6.Mechanism of Action for Improving Learning and Memory Abilities

Asiaticoside can enhance the learning and memory abilities of mice, and its mechanism of action is related to reducing the deposition of Aβ in the hippocampus and upregulating the expression of synaptophysin (SYN) protein. It is also associated with upregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) protein and downregulating the expression of inflammatory factors IL-6, TNF-α, and IL-1. Related studies have found that Asiaticoside also has a good preventive and therapeutic effect on diabetic cognitive dysfunction, and its mechanism is related to regulating oxidative stress and the PI3K/Akt/NF-κB pathway.

Currently, most research on the mechanisms of Asiaticoside still remains in the initial stages. However, with the widespread application of various cellular and molecular biological techniques in the field of drug mechanism research, we believe that our understanding of the mechanisms of action of Asiaticoside will become increasingly clear, which will provide a foundation for the clinical development of new formulations and new therapeutic areas.

References

[1] Qin Huizhen, Lin Si, Deng Lingyu, Zhu Hua. Research Progress on the Pharmacological Effects and Mechanisms of Asiaticoside [J]. China Pharmacy, 2021, 32(21): 2683-2688.

[2] Guo Yujie, Xu Jun. Research Progress on the Pharmacological Effects of Asiaticoside [J]. Shanxi Medical Journal, 2017, 46(15): 1829-1832.

[3] Ding Yuan, Zhang Zhu, Wang Suogang. Research Progress on Asiaticoside [J]. Li Shizhen Medicine and Materia Medica Research and Development Company, engaged in drug inspection analysis and verification of analytical methods.

About the Author

Xiaomichong, a researcher in pharmaceutical quality, has been dedicated to pharmaceutical quality research and verification of drug analysis methods for a long time. Currently, she works in a large domestic pharmaceutical research and development company, engaged in drug inspection analysis and verification of analytical methods.