The anti-inflammatory effects of asiatic acid in lipopolysaccharide-stimulated human corneal epithelial cells

Chen, Hao; Hua, Xiaomin; Ze, Bai-Chen; Wang, Bin; Li, Wei

doi:10.18240/ijo.2017.02.01

Cited by 10 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatments that reduce oxidative stress in RGCs may be a novel therapeutic strategy for glaucoma; however, no effective neuroprotectants are available to be applied as a treatment for glaucoma. AA was reported to possess antioxidant, anti-inflammatory, and antiexcitotoxic properties and to improve mitochondrial function ( Huang et al, 2016 ; Chen et al, 2017 ; Nataraj et al, 2017 ) and is thus believed to target multiple mechanisms underlying glaucoma development. In humans, elevated IOP is the major risk factor for glaucoma.…”

Section: Discussionmentioning

confidence: 99%

Asiatic Acid Prevents Retinal Ganglion Cell Apoptosis in a Rat Model of Glaucoma

Huang

Gao

et al. 2018

Front. Neurosci.

View full text Add to dashboard Cite

Asiatic acid (AA), a pentacyclic triterpene derived from the tropical medicinal plant Centella asiatica, has been widely used as an antioxidant and anti-inflammatory agent. Evidence regarding the neuroprotective properties of AA is emerging. However, the protective effects of AA and its mechanism in glaucoma are poorly understood. In the current study, we investigate the neuroprotective effect and mechanism of AA on retinal ganglion cells (RGCs) in a rat model of glaucoma. Elevated intraocular pressure (IOP) was induced in adult rats by injecting microspheres into the anterior chamber. AA was intravitreally injected into glaucomatous rats. RGC densities were analyzed by evaluating surviving RGC number of the retinal flatmounts and retinal sections, and the apoptotic cell number were evaluated by analyzing retinal sections. RGC function was assessed by measuring the photopic negative response (PhNR). Retinal Bcl-2, Bax, and cleaved caspase-3 expression were determined using a Simple Western System, real-time PCR and immunofluorescence staining. AA reduced the loss of RGCs and decreased the apoptotic RGC number. AA exerted neuroprotective effects and ameliorated retinal dysfunction in impaired RGCs in a rat model of glaucoma. AA protected RGCs by upregulating the expression of the antiapoptotic protein Bcl-2 and downregulating the expression of the pro-apoptotic proteins Bax and caspase-3. This study has provided important evidence indicating that AA may be a potential therapeutic agent for glaucoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Asiatic Acid Prevents Retinal Ganglion Cell Apoptosis in a Rat Model of Glaucoma

Huang

Gao

et al. 2018

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Extreme environments including hyperglycaemic and hyperosmolar environments may cause excess ROS accumulation, which is considered an upstream suppressor of the EGFR-mediated PI3K/AKT signalling pathway, and delays healing of the CE [ 60 ]. In vitro and in vivo studies have shown that inhibition of ROS production reactivates PI3K/AKT signalling, which decreases apoptosis and inflammation in CECs [ 22 , 23 ]. Furthermore, the expression of the cellular tumour antigen P53, a PI3K/AKT substrate, is upregulated by ROS in hCECs [ 61 , 62 ].…”

Section: Interactions Between Ros and Akt In Cecsmentioning

confidence: 99%

“…Importantly, dysregulation of CE homeostasis caused by impaired CEC responses is associated with many corneal diseases, such as DK, DED, and keratitis [ 18 , 20 , 21 ]. Therefore, an in-depth understanding of the pathophysiology of CE with a focus on the PI3K/AKT signalling pathway is important for maintaining the integrity of patients’ corneas and seeking reliable treatments and new drugs [ 22 , 23 ]. In this review, we provide evidence for the regulatory role of the PI3K/AKT signalling pathway in CECs to support its clinical application.…”

Section: Introductionmentioning

confidence: 99%

The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

Chen

Zhang

et al. 2022

Cell Death Dis

View full text Add to dashboard Cite

Phosphatidylinositol 3 kinase (PI3K)/AKT (also called protein kinase B, PKB) signalling regulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism, and telomere activity. Corneal epithelial cells (CECs) are the outermost cells of the cornea; they maintain good optical performance and act as a physical and immune barrier. Various growth factors, including epidermal growth factor receptor (EGFR) ligands, insulin-like growth factor 1 (IGF1), neurokinin 1 (NK-1), and insulin activate the PI3K/AKT signalling pathway by binding their receptors and promote antiapoptotic, anti-inflammatory, proliferative, and migratory functions and wound healing in the corneal epithelium (CE). Reactive oxygen species (ROS) regulate apoptosis and inflammation in CECs in a concentration-dependent manner. Extreme environments induce excess ROS accumulation, inhibit PI3K/AKT, and cause apoptosis and inflammation in CECs. However, at low or moderate levels, ROS activate PI3K/AKT signalling, inhibiting apoptosis and stimulating proliferation of healthy CECs. Diabetes-associated hyperglycaemia directly inhibit PI3K/AKT signalling by increasing ROS and endoplasmic reticulum (ER) stress levels or suppressing the expression of growth factors receptors and cause diabetic keratopathy (DK) in CECs. Similarly, hyperosmolarity and ROS accumulation suppress PI3K/AKT signalling in dry eye disease (DED). However, significant overactivation of the PI3K/AKT signalling pathway, which mediates inflammation in CECs, is observed in both infectious and noninfectious keratitis. Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.

show abstract

“…AA in HaCaT cells reduced glycative stress by blocking AGE-RAGE interaction, inhibiting MAPK pathway and MMP expression along with amelioration of oxidative and inflammatory stress. AA also exhibited potent free radical scavenging property and inhibited pro-inflammatory cytokines against LPS-induced inflammatory response in human corneal epithelial cells (Chen et al, 2017 ). It also inhibited LPS-induced p-Akt and TGF-β and retained glutathione levels.…”

Section: Asiatic Acid In Photoagingmentioning

confidence: 99%

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

et al. 2018

View full text Add to dashboard Cite

Asiatic acid (AA) is a naturally occurring aglycone of ursane type pentacyclic triterpenoids. It is abundantly present in many edible and medicinal plants including Centella asiatica that is a reputed herb in many traditional medicine formulations for wound healing and neuropsychiatric diseases. AA possesses numerous pharmacological activities such as antioxidant and anti-inflammatory and regulates apoptosis that attributes its therapeutic effects in numerous diseases. AA showed potent antihypertensive, nootropic, neuroprotective, cardioprotective, antimicrobial, and antitumor activities in preclinical studies. In various in vitro and in vivo studies, AA found to affect many enzymes, receptors, growth factors, transcription factors, apoptotic proteins, and cell signaling cascades. This review aims to represent the available reports on therapeutic potential and the underlying pharmacological and molecular mechanisms of AA. The review also also discusses the challenges and prospects on the pharmaceutical development of AA such as pharmacokinetics, physicochemical properties, analysis and structural modifications, and drug delivery. AA showed favorable pharmacokinetics and found bioavailable following oral or interaperitoneal administration. The studies demonstrate the polypharmacological properties, therapeutic potential and molecular mechanisms of AA in numerous diseases. Taken together the evidences from available studies, AA appears one of the important multitargeted polypharmacological agents of natural origin for further pharmaceutical development and clinical application. Provided the favorable pharmacokinetics, safety, and efficacy, AA can be a promising agent or adjuvant along with currently used modern medicines with a pharmacological basis of its use in therapeutics.

show abstract

The anti-inflammatory effects of asiatic acid in lipopolysaccharide-stimulated human corneal epithelial cells

Cited by 10 publications

References 30 publications

Asiatic Acid Prevents Retinal Ganglion Cell Apoptosis in a Rat Model of Glaucoma

Asiatic Acid Prevents Retinal Ganglion Cell Apoptosis in a Rat Model of Glaucoma

The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

Contact Info

Product

Resources

About