Polysaccharide from Angelica sinensis attenuates SNP-induced apoptosis in osteoarthritis chondrocytes by inducing autophagy via the ERK1/2 pathway

Abstract

Objective Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism. Method Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP. Results The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway. Conclusion ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.

Angelica sinensis polysaccharide (ASP) attenuates diosbulbin-B (DB)-induced hepatotoxicity through activating the MEK/ERK pathway

“…According to the preliminary data from our previous publications [ 4 , 5 ] and other teams [ 16 , 26 ] that high-dose DB exerted its cytotoxic effects on hepatocytes and ASP is effective to attenuate liver injury, we explored whether ASP attenuated high-dose DB-induced cell death in the hepatocytes. The primary rat hepatocytes were sequentially exposed to high-dose DB (100 μM) and ASP (12 μg/ml) according to our preliminary experiments (data not shown) and published data [ 4 , 5 , 16 , 26 ].…”

“…According to the preliminary data from our previous publications [ 4 , 5 ] and other teams [ 16 , 26 ] that high-dose DB exerted its cytotoxic effects on hepatocytes and ASP is effective to attenuate liver injury, we explored whether ASP attenuated high-dose DB-induced cell death in the hepatocytes. The primary rat hepatocytes were sequentially exposed to high-dose DB (100 μM) and ASP (12 μg/ml) according to our preliminary experiments (data not shown) and published data [ 4 , 5 , 16 , 26 ]. The MTT assay was used to determine cell proliferation abilities, and data in the Figure 1a showed that DB significantly suppressed cell proliferation in a time-dependent manner, while ASP alone had little effects on hepatocytes proliferation.…”

“…In addition, interplay of autophagy and apoptosis plays important role in regulating the development of liver injury [ 19–21 ], and to our knowledge, induction of protective autophagy suppressed cell apoptosis [ 22–24 ], and DB promotes liver injury by inducing apoptotic cell death [ 4 ,2 5 , 5] and inactivation of autophagy flux [ 25 ]. Of note, ASP is capable of regulating both cell autophagy [ 26 ] and apoptosis [ 15 , 16 ], but it is still largely unknown whether ASP can attenuate DB-induced hepatotoxicity via modulating cell autophagy and apoptosis.…”

“…For example, Fu et al find that activation of the MEK/ERK pathway ameliorates hypoxic/ischemic-induced bone mesenchymal stem cell apoptosis [ 29 ], and Wang et al evidence that MEK/ERK-induced autophagy contributes to cell survival in IPEC-J2 cells with Ochratoxin A exposure [ 31 ]. Notably, according to the data from Xu et al, ASP regulates the MEK/ERK pathway to induce protective autophagy and suppress sodium nitroprusside (SNP)-induced cell apoptosis in osteoarthritis chondrocytes [ 26 ], which convinces us to speculate that ASP may regulate the MEK/ERK pathway mediated autophagy to attenuate DB-induced cell apoptosis in hepatocytes.…”

Multi-Pharmaceutical Activities of Chinese Herbal Polysaccharides in the Treatment of Pulmonary Fibrosis: Concept and Future Prospects

“…Its main chain is composed of (1→3)-connected Galp, (1→6)-connected Galp and 2-OMe-(1→6)-connected Galp, with three branches connected to 2-OMe-(- 1→6) link Galp and terminate with GlcpA and Araf ( Zhang et al, 2016a ). ASP has immune regulation, anti-tumor, anti-oxidation and anti-proliferatsion functions ( Li M. M. et al, 2020 ; Xu et al, 2021 ). There is also the ability of the compound Danggui Buxue Decoction total glycosides (containing astragalus and angelica) to inhibit abnormal lung tissue ECM and reverse the expression of MMP/TIMP ( Gao et al, 2012 ).…”