Glabridin inhibits osteoarthritis development by protecting chondrocytes against oxidative stress, apoptosis and promoting mTOR mediated autophagy

Dai, Jihang; Zhang, Yaxin; Chen, Deng; Chen, Duoyun; Li, Xiaolei; Wang, Jingcheng; Sun, Yu

doi:10.1016/j.lfs.2020.118992

Cited by 26 publications

(25 citation statements)

References 35 publications

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“…We conducted a systems computational approach to predict the pharmacological actions of active compounds from licorice. In our results, among the 21 active compounds, four compounds (quercetin, glabridin, isoliquiritigenin, and kaempferol) were experimentally validated with surgically induced OA animal models in previous studies [30][31][32][33]. Quercetin is a flavonoid compound that exhibits anti-proliferative, anti-oxidative, and anti-arthritic effects [62][63][64][65].…”

Section: Discussionmentioning

confidence: 74%

“…Glabridin is a flavonoid compound that has been reported for its pharmacological activity such as antioxidant, anti-cancer, anti-osteoporotic, anti-inflammatory, and antimicrobial effects [66]. In an ACLT-induced OA model in rats, glabridin inhibited MMP-13 and Adamts5 expression whereas it increased Collagen II and SOX9 expression from the OA cartilage [31]. Glabridin prevented the apoptosis of human chondrocytes from oxidative stress by inducing autophagy in an mTOR-dependent manner [31].…”

Section: Discussionmentioning

confidence: 99%

“…In an ACLT-induced OA model in rats, glabridin inhibited MMP-13 and Adamts5 expression whereas it increased Collagen II and SOX9 expression from the OA cartilage [31]. Glabridin prevented the apoptosis of human chondrocytes from oxidative stress by inducing autophagy in an mTOR-dependent manner [31]. Isoliquiritigenin is a flavonoid compound that exerts anti-cancer, anti-inflammatory, anti-diabetic, hepatoprotective, and cardioprotective effects [67].…”

Section: Discussionmentioning

confidence: 99%

“…Among the 21 active compounds, licoricidin showed the lowest docking energy with PTH1R, RUNX2, PRKACA, VEGFA, and COL2A (Figure 8A). Recent studies in vivo have suggested that quercetin, kaempferol, glabridin, and isoliquiritigenin possess therapeutic effectiveness for OA [30][31][32][33]. Quercetin, kaempferol, and glabridin deeply interacted with the S1'-specificity pocket of MMP-13 (Figure 8B).…”

Section: Validation Of Major Active Compounds In Licorice Based On the Experimental Oa Modelmentioning

confidence: 95%

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In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis

Ali¹,

Park²,

Lee

et al. 2021

Pharmaceuticals

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Osteoarthritis (OA) is a common degenerative joint disorder that affects joint function, mobility, and pain. The release of proinflammatory cytokines stimulates matrix metalloproteinases (MMPs) and aggrecanase production which further induces articular cartilage degradation. Hypertrophy-like changes in chondrocytes are considered to be an important feature of OA pathogenesis. A Glycyrrhiza new variety, Wongam (WG), was developed by the Korea Rural Development Administration to enhance the cultivation and quality of Glycyrrhizae Radix et Rhizoma (licorice). This study examined the regulatory effect of WG against hypertrophy-like changes such as RUNX2, Collagen X, VEGFA, MMP-13 induction, and Collagen II reduction induced by IL-1β in SW1353 human chondrocytes. Additionally, in silico methods were performed to identify active compounds in licorice to target chondrocyte hypertrophy-related proteins. WG showed inhibitory effects against IL-1β-induced chondrocyte hypertrophy by regulating both HDAC4 activation via the PTH1R/PKA/PP2A pathway and the SOX9/β-catenin signaling pathway. In silico analysis demonstrated that 21 active compounds from licorice have binding potential with 11 targets related to chondrocyte hypertrophy. Further molecular docking analysis and in vivo studies elicited four compounds. Based on HPLC, isoliquiritigenin and its precursors were identified and quantified. Taken together, WG is a potential therapeutic agent for chondrocyte hypertrophy-like changes in OA.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Validation Of Major Active Compounds In Licorice Based On the Experimental Oa Modelmentioning

confidence: 95%

See 2 more Smart Citations

In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis

Ali¹,

Park²,

Lee

et al. 2021

Pharmaceuticals

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“…Dai et al found a significant increase in LC3-II levels in human chondrocytes after the administration of glabridin, suggesting that it could protect them from oxidative stress, apoptosis by enhancing autophagy. In vivo experiments revealed that glabridin could activate autophagy, which is to reduce mTOR expression, and increase LC3-II levels attenuated ACLT-induced apoptosis in OA rats, thereby delaying their cartilage degeneration ( Dai et al, 2021b ). The clinical application of glabridin is limited due to its poor water solubility and therefore low bioavailability, but studies have shown that this situation can be improved by combining it with β -Lactoglobulin.…”

Section: Phytochemicals For the Treatment Of Oa By Promoting Autophagymentioning

confidence: 99%

Phytochemicals Mediate Autophagy Against Osteoarthritis by Maintaining Cartilage Homeostasis

2021

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Osteoarthritis (OA) is a common degenerative joint disease and is a leading cause of disability and reduced quality of life worldwide. There are currently no clinical treatments that can stop or slow down OA. Drugs have pain-relieving effects, but they do not slow down the course of OA and their long-term use can lead to serious side effects. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Autophagy is an intracellular protective mechanism, and targeting autophagy-related pathways has been found to prevent and treat various diseases. Attenuation of the autophagic pathway has now been found to disrupt cartilage homeostasis and plays an important role in the development of OA. Therefore, modulation of autophagic signaling pathways mediating cartilage homeostasis has been considered as a potential therapeutic option for OA. Phytochemicals are active ingredients from plants that have recently been found to reduce inflammatory factor levels in cartilage as well as attenuate chondrocyte apoptosis by modulating autophagy-related signaling pathways, which are not only widely available but also have the potential to alleviate the symptoms of OA. We reviewed preclinical studies and clinical studies of phytochemicals mediating autophagy to regulate cartilage homeostasis for the treatment of OA. The results suggest that phytochemicals derived from plant extracts can target relevant autophagic pathways as complementary and alternative agents for the treatment of OA if subjected to rigorous clinical trials and pharmacological tests.

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Natural products: A potential immunomodulators against inflammatory-related diseases

Sai Priya,

Ramalingam,

Suresh Babu

2024

Inflammopharmacol

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Glabridin inhibits osteoarthritis development by protecting chondrocytes against oxidative stress, apoptosis and promoting mTOR mediated autophagy

Cited by 26 publications

References 35 publications

In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis

In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis

Phytochemicals Mediate Autophagy Against Osteoarthritis by Maintaining Cartilage Homeostasis

Natural products: A potential immunomodulators against inflammatory-related diseases

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