Integrated analysis identifies microRNA-188-5p as a suppressor of AKT/mTOR pathway in renal cancer.

Many current microRNA (miRNA) expression datasets for renal cell carcinoma (RCC) often show inconsistent analysis results, so a shift to comprehensive analysis of multiple datasets can effectively accelerate molecular screening for precision medicine and translational medicine research. MicroRNA (miR)-188-5p is a clinically noteworthy miRNA whose aberrant expression was previously observed in a variety of cancers, but its role in RCC is unclear. In this study, we undertook a comprehensive analysis of four RCC miRNA expression datasets and validated the results using The Cancer Genome Atlas (TCGA) dataset and a cohort of collected clinical samples. Fifteen miRNAs were identified as potential diagnostic markers by the analysis of four RCC miRNAs datasets. Analysis of the TCGA kidney renal clear cell carcinoma dataset showed significantly shorter survival in RCC patients with reduced miR-188-5p expression levels, and our collection of RCC clinical samples showed low miR-188-5p expression in the tumors. Overexpression of miR-188-5p in Caki-1 and 786-O cells inhibited cell growth, colony formation, invasion, and migration. In contrast, miR-188-5p inhibitors reversed these cell phenotypes. We identified a binding site for miR-188-5p in the 3'-UTR region of myristoylated alanine-rich C-kinase substrate (MARCKS) mRNA and demonstrated an interaction between these two molecules. Quantitative RT-PCR and western blot analysis revealed that miR-188-5p could regulate the AKT/mTOR signaling pathway through MARCKS. Mouse transplantation tumor assay indicated that miR-188-5p reduced the tumorigenicity of RCC in vivo. MicroRNA-188-5p could be a valuable new molecule for RCC diagnosis and prognosis.

Long non-coding RNA PANDAR promoted radiation and cisplatin-induced DNA damage repair through ATR/CHK1 in NSCLC.

BACKGROUND: DNA-damaging agents, including radiation and platinum-based chemotherapy, are indispensable treatments for non-small cell lung cancer (NSCLC) patients. However, cancer cells tend to be resistant to both radiation and chemotherapy, thus resulting in treatment failure or recurrence. The purpose of this study was to explore the effect and mechanism of long non-coding RNA (lncRNA) PANDAR (promoter of CDKN1A antisense DNA damage-activated RNA) on NSCLC sensitivity to radiation and chemotherapy. METHODS: Cell counting kit (CCK-8), colony formation and flow cytometry were respectively performed to determine the cell cycle and apoptosis of NSCLC cells treated with γ-ray radiation and cisplatin. The extent of DNA damage was evaluated using a comet assay and immunofluorescence staining against γH2AX. In addition, we explored the role of PANDAR in DNA damage response pathways through western blot analysis. Finally, a nude mouse subcutaneous xenograft model was established to assess the sensitivity to radiation and chemotherapy in vivo. RESULTS: In cell experiments, PANDAR knockdown can increase the sensitivity of NSCLC cells to radiation and cisplatin. The CCK-8 results showed that cell viability was significantly increased in the overexpression group after radiation and cisplatin treatments. The overexpression group also showed more colonies, less apoptosis and DNA damage, and G2/M phase arrest was aggravated to provide the time necessary for DNA repair. Contrary to PANDAR overexpression, the trends were reversed in the PANDAR knockdown group. Furthermore, PANDAR knockdown inhibited radiation and cisplatin-activated phosphorylation levels of ATR and CHK1 in NSCLC cells. Finally, our in vivo model showed that targeting PANDAR significantly sensitized NSCLC to radiation and cisplatin. CONCLUSION: Our study showed that PANDAR knockdown promoted sensitivity to radiation and cisplatin in NSCLC by regulating the ATR/CHK1 pathway, thus providing a novel understanding as well as a therapeutic target for NSCLC treatment. In NSCLC cells, lncRNA PANDAR negatively regulates sensitivity to radiation and cisplatin. PANDAR can promote the repair of radiation and cisplatin-induced DNA damage and activation of the G2/M checkpoint through the ATR/CHK1 pathway. PANDAR knockdown results in defects in DNA damage repair accompanied by more cell apoptosis.

LncRNA ANRIL promotes HR repair through regulating PARP1 expression by sponging miR-7-5p in lung cancer.

BACKGROUND: Radiotherapy is an important treatment for lung cancer, mainly by triggering DNA double-strand breaks to induce cell death. Blocking DNA damage repair can increase the radiosensitivity of tumor cells. Recent studies have identified long noncoding RNAs as key regulators in DNA damage repair. The lncRNA ANRIL was previously shown to be involved in homologous recombination (HR) repair, but its specific mechanism has not been fully elucidated. METHODS: The downstream interacting miRNAs of ANRIL were predicted according to miRanda software. Fluorescence quantitative PCR was used to detect the expression levels of ANRIL and candidate miRNAs. Clone formation experiment and cell viability assays detect cell viability after ionizing radiation. Apoptosis assay was used to detect the apoptosis of cells after 8 h of ionizing radiation. Western blot analysis and immunofluorescence assays verified the protein expression levels of the downstream target molecule PARP1 of miR-7-5p and key molecules in the HR pathway. Fluorescent reporter gene experiments were used to verify the interaction between ANRIL and miR-7-5p and between miR-7-5p and PARP1. RESULTS: Bioinformatics analysis and qPCR validation suggested that miR-7-5p might be a downstream molecule of ANRIL. The expression of miR-7-5p was up-regulated after knockdown of ANRIL, and the expression of miR-7-5p was down-regulated after overexpression of ANRIL. Meanwhile, there was a negative correlation between ANRIL and miR-7-5p expression changes before and after ionizing radiation. The luciferase reporter gene assay confirmed the existence of ANRIL binding site with miR-7-5p, and found that transfection of miR-7-5p inhibitor can reduce the radiation sensitivity of ANRIL-KD cells. A downstream target molecule of miR-7-5p related to HR repair, PARP1, was screened through website prediction. Subsequently, it was confirmed by Western blot and luciferase reporter assays that miR-7-5p could down-regulate the expression of PARP1, and there was a miR-7-5p binding site on the 3'UTR of PARP1 mRNA. This suggests that ANRIL may act as a competitive endogenous RNA to bind miR-7-5p and upregulate the expression of PARP1. Western blot and immunofluorescence staining were used to detect the expression changes of HR repair factors in ANRIL-KD cells after ionizing radiation, and it was found that knockdown of ANRIL can inhibit the expression of PARP1, BRCA1 and Rad51, hinder radiation-induced HR repair, and eventually result in resensitizing ANRIL-KD cells to ionizing radiation. CONCLUSIONS: Our findings provide evidence that ANRIL targets the miR-7-5p/PARP1 axis to exert its regulatory effect on HR repair, suggesting that altering ANRIL expression may be a promising strategy to overcome radiation resistance.

Bufotalin attenuates pulmonary fibrosis via inhibiting Akt/GSK-3ß/ß-catenin signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with no cure. Bufotalin (BT), an active component extracted from Venenum Bufonis, has been prescribed as a treatment for chronic inflammatory diseases. However, whether BT has antifibrotic properties has never been investigated. In this study, we report on the potential therapeutic effect and mechanism of BT on IPF. BT was shown to attenuate lung injury, inflammation, and fibrosis as well as preserve pulmonary function in bleomycin (BLM)-induced pulmonary fibrosis model. We next confirmed BT's ability to inhibit TGF-ß1-induced epithelial-mesenchymal transition (EMT) and myofibroblast activation (including differentiation, proliferation, migration, and extracellular matrix production) in vitro. Furthermore, transcriptional profile analysis indicated the Wnt signaling pathway as a potential target of BT. Mechanistically, BT effectively prevented ß-catenin from translocating into the nucleus to activate transcription of profibrotic genes. This was achieved by blunting TGF-ß1-induced increases in phosphorylated Akt Ser437 (p-Akt S437) and phosphorylated glycogen synthase kinase (GSK)-3ß Ser9 (p-GSK-3ß S9), thereby reactivating GSK-3ß. Additionally, the antifibrotic effects of BT were further validated in another in vivo model of radiation-induced pulmonary fibrosis. Collectively, these data demonstrated the potent antifibrotic actions of BT through inhibition of Akt/GSK-3ß/ß-catenin axis downstream of TGF-ß1. Thus, BT could be a potential option to be further explored in IPF treatment.

TLR4 Agonist MPLA Ameliorates Heavy-Ion Radiation Damage via Regulating DNA Damage Repair and Apoptosis.

Heavy-ion radiation received during radiotherapy as well as the heavy-ion radiation received during space flight are equally considered harmful. Our previous study showed that TLR4 low toxic agonist, monophosphoryl lipid A (MPLA), alleviated radiation injury resulting from exposure to low-LET radiation. However, the role and mechanism of MPLA in heavy-ion-radiation injury are unclear. This study aimed to investigate the role of MPLA on radiation damage. Our data showed that MPLA treatment alleviated the heavy-ion-induced damage to microstructure and the spleen and testis indexes. The number of karyocytes in the bone marrow from the MPLA-treated group was higher than that in the irradiated group. Meanwhile, western blotting analysis of intestine proteins showed that pro-apoptotic proteins (cleaved-caspase3 and Bax) were downregulated while anti-apoptotic proteins (Bcl-2) were upregulated in the MPLA-treated group. Our in vitro study demonstrated that MPLA significantly improved cell proliferation and inhibited cell apoptosis after irradiation. Moreover, immunofluorescence staining and quantification of nucleic γ-H2AX and 53BP1 foci also suggested that MPLA significantly attenuated cellular DNA damage repair. Collectively, the above evidence supports the potential ability of MPLA to protect against heavy-ion-radiation injury by inhibiting apoptosis and alleviating DNA damage in vivo and vitro, which could be a promising medical countermeasure for the prevention of heavy-ion-radiation injury.

SENP5 promotes homologous recombination-mediated DNA damage repair in colorectal cancer cells through H2AZ deSUMOylation.

BACKGROUND: Neoadjuvant radiotherapy has been used as the standard treatment of colorectal cancer (CRC). However, radiotherapy resistance often results in treatment failure. To identify radioresistant genes will provide novel targets for combined treatments and prognostic markers. METHODS: Through high content screening and tissue array from CRC patients who are resistant or sensitive to radiotherapy, we identified a potent resistant gene SUMO specific peptidase 5 (SENP5). Then, the effect of SENP5 on radiosensitivity was investigated by CCK8, clone formation, comet assay, immunofluorescence and flow cytometric analysis of apoptosis and cell cycle to investigate the effect of SENP5 on radiosensitivity. SUMO-proteomic mass spectrometry combined with co-immunoprecipitation assay were used to identify the targets of SENP5. Patient-derived organoids (PDO) and xenograft (PDX) models were used to explore the possibility of clinical application. RESULTS: We identified SENP5 as a potent radioresistant gene through high content screening and CRC patients tissue array analysis. Patients with high SENP5 expression showed increased resistance to radiotherapy. In vitro and in vivo experiments demonstrated that SENP5 knockdown significantly increased radiosensitivity in CRC cells. SENP5 was further demonstrated essential for efficient DNA damage repair in homologous recombination (HR) dependent manner. Through SUMO mass spectrometry analysis, we characterized H2AZ as a deSUMOylation substrate of SENP5, and depicted the SUMOylation balance of H2AZ in HR repair and cancer resistance. By using PDO and PDX models, we found targeting SENP5 significantly increased the therapeutic efficacy of radiotherapy. CONCLUSION: Our findings revealed novel role of SENP5 in HR mediated DNA damage repair and cancer resistance, which could be applied as potent prognostic marker and intervention target for cancer radiotherapy.

ATR-binding lncRNA ScaRNA2 promotes cancer resistance through facilitating efficient DNA end resection during homologous recombination repair.

BACKGROUND: Our previous study first showed that ATR-binding long noncoding RNA (lncRNA) is necessary for ATR function and promotes cancer resistance. However, the specific lncRNAs instrumental in ATR activation remain largely unclear, which limits our comprehensive understanding of this critical biological process. METHODS: RNA immunoprecipitation (RIP) followed by RNA sequencing was employed to identify ATR-binding lncRNAs, which were further validated using RIP-qPCR assays. Immunofluorescence staining and Western blotting were applied to detect the activation of DNA damage repair factors. After the effect of scaRNA2 on cellular sensitivity to DNA-damaging reagents was determined, the effects of scaRNA2 on radiotherapy were investigated in patient-derived organoids and xenograft preclinical models. The clinical relevance of scaRNA2 was also validated in tissues isolated from rectal cancer patients. RESULTS: ScaRNA2 was identified as the most enriched ATR-binding lncRNA and was found to be essential for homologous recombination (HR) mediated DNA damage repair. Furthermore, scaRNA2 knockdown abrogated the recruitment of ATR and its substrates in response to DNA damage. Mechanistically, scaRNA2 was observed to be necessary for Exo1-mediated DNA end resection and bridged the MRN complex to ATR activation. Knockdown of scaRNA2 effectively increased the sensitivity of cancer cells to multiple kinds of DNA damage-related chemoradiotherapy. Preclinically, knockdown of scaRNA2 improved the effects of radiotherapy on patient-derived organoids and xenograft models. Finally, an increase in scaRNA2 colocalized with ATR was also found in clinical patients who were resistant to radiotherapy. CONCLUSIONS: ScaRNA2 was identified as the most abundant lncRNA bound to ATR and was demonstrated to bridge DNA end resection to ATR activation; thus, it could be applied as a potent target for combined cancer treatments with chemoradiotherapy.

PRDM15 interacts with DNA-PK-Ku complex to promote radioresistance in rectal cancer by facilitating DNA damage repair.

Neoadjuvant radiotherapy is a standard treatment for locally advanced rectal cancer, however, resistance to chemoradiotherapy is one of the main obstacles to improving treatment outcomes. The goal of this study was to explore the role of PRDM15 involved in the radioresistance of colorectal cancer and to clarify the underlying mechanism. In present study, we demonstrated that, after DNA damage, PRDM15 was upregulated and localized to DNA damage sites, co-localizing with γ-H2AX. Knockdown of PRDM15 inhibited DNA damage repair and increased radiosensitivity in colorectal cancer cells. Mechanistically, PRDM15 promoted DNA repair by interacting with DNA-PKcs and Ku70/Ku80 complex. In preclinical models of rectal cancer, knockdown of PRDM15 sensitized cell derived xenograft and patient derived xenograft to radiotherapy. In 80 rectal cancer patients treated with neoadjuvant chemoradiotherapy, higher PRDM15 expression was observed associated with weaker tumor regression and poorer prognosis. Our findings revealed that inhibiting PRDM15 was potent to overcome radioresistance through abrogating DNA repair in colorectal cancer cells. Additionally, the expression level of PRDM15 could be applied to predict radiotherapy responsiveness and the outcome of neoadjuvant radiotherapy in rectal cancer patients.

Intermediate role of gut microbiota in vitamin B nutrition and its influences on human health.

Vitamin B consists of a group of water-soluble micronutrients that are mainly derived from the daily diet. They serve as cofactors, mediating multiple metabolic pathways in humans. As an integrated part of human health, gut microbiota could produce, consume, and even compete for vitamin B with the host. The interplay between gut microbiota and the host might be a crucial factor affecting the absorbing processes of vitamin B. On the other hand, vitamin B supplementation or deficiency might impact the growth of specific bacteria, resulting in changes in the composition and function of gut microbiota. Together, the interplay between vitamin B and gut microbiota might systemically contribute to human health. In this review, we summarized the interactions between vitamin B and gut microbiota and tried to reveal the underlying mechanism so that we can have a better understanding of its role in human health.

Hepatoprotective effect of gentiopicroside in combination with leflunomide and/or methotrexate in arthritic rats.

AIMS: This study aimed to examine whether gentiopicroside (GPS) could exert hepatoprotective effects on leflunomide (LEF)- and/or methotrexate (MTX)-treated arthritic rats through anti-inflammatory and antioxidant pathways. MAIN METHODS: We observed the external symptoms of joints, analysed serum indicators, measured haematological parameters and mRNA levels, and performed HE staining. KEY FINDINGS: LEF and/or MTX combined with GPS ameliorated oxidative stress by increasing the mRNA levels of the antioxidant gene Nrf2, GCLC, HO-1, and NQO1, increasing the antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), reducing the oxidant substance malondialdehyde (MDA), reducing the inflammatory response by decreasing the mRNA levels of NF-κB, tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), and inhibiting the secretion of the pro-inflammatory cytokines TNFα, IL-6, IL-1ß and reducing C-reactive protein (CRP), as well as alleviating the external symptoms of arthritis. SIGNIFICANCE: These results show that GPS plays an antioxidant and anti-inflammatory role in LEF- and/or MTX-treated arthritic rats by affecting the Nrf2 and NF-κB signalling pathways, thus exerting hepatoprotective effects.

Grape Seed Proanthocyanidins play the roles of radioprotection on Normal Lung and radiosensitization on Lung Cancer via differential regulation of the MAPK Signaling Pathway.

Radiation-induced lung injury (RILI) is a common serious complication and dose-limiting factor caused by radiotherapy for lung cancer. This study was to investigate radioprotective effects of grape seed proanthocyanidins (GSP) on normal lung as well as radiosensitizing effects on lung cancer. In vitro, we demonstrated radioprotective effects of GSP on normal alveolar epithelial cells (MLE-12 and BEAS/2B) and radiosensitizing effects on lung cancer cells (LLC and A549). In vivo, we confirmed these two-way effects in tumor-bearing mice. The results showed that GSP inhibited tumor growth, and played a synergistic killing effect with radiotherapy on lung cancer. Meanwhile, GSP reduced radiation damage to normal lung tissues. The two-way effects related to the differential regulation of the MAPK signaling pathway by GSP on normal lung and lung cancer. Moreover, GSP regulated secretion of cytokines IL-6 and IFN-γ and expression of p53 and Ki67 on normal lung and lung cancer. Our findings suggest that GSP is expected to be an ideal radioprotective drug for lung cancer patients who are treated with radiotherapy.

The combination of ursolic acid and empagliflozin relieves diabetic nephropathy by reducing inflammation, oxidative stress and renal fibrosis.

Studies have shown that ursolic acid (UA) and empagliflozin (EM) exert therapeutic effects in the treatment of diabetic nephropathy (DN), but both drugs have disadvantages. This study explores the effect of combining these drugs compared to that of either monotherapy. A diabetic rat model was established by feeding a high-fat diet (HFD) with high-sugar content and administering a low dose of streptozotocin (STZ) via intraperitoneal injection. UA (50 mg/kg/day, po), EM (10 mg/kg/day, po) or both were administered for 8 weeks. The development of DN was determined by observing increases in urine protein, serum creatinine, urea nitrogen, and uric acid and abnormal changes in kidney morphology. UA and EM either alone or in combination can alleviate the increases in blood glucose, glycosylated haemoglobin, blood lipid levels, inflammatory factors (TNF-α, IL-1ß, IL-6), oxidation factors (SOD, MDA, GSH, CAT, NO), renal fibrosis and pro-fibrosis factors (FN, E-cad, MMP-9, TIMP-1, SMA-α, TGF-ß1, SMAD, MAPK). The treatments could also ameliorate DN by preventing the abnormal proliferation of glomerular mesangial cells under high-glucose conditions, aberrant apoptosis and excessive production of reactive oxygen species (ROS). In addition, UA reduces the increase in LDL-L, reverses abnormal bladder morphology and mitigates the increase in colony count caused by EM, and the combination treatment can overcome the disadvantages of the slow hypoglycaemic effect of UA. In short, UA combined with empagliflozin is more effective than either monotherapy in the treatment of DN and can cancel the adverse effects of each other. The protective effect of this regimen on the kidney may be related to reducing inflammation, oxidative stress and renal fibrosis.

Andrographolide ameliorates oxidative stress, inflammation and histological outcome in complete Freund's adjuvant-induced arthritis.

OBJECTIVES: As one of the main active ingredients of Chinese herbal medicine Andrographis paniculate, andrographolide is used in domestic clinical treatment for respiratory infections and inflammation. This study was designed to investigate the effects of andrographolide as an antioxidant on the level of oxidative stress, neutrophil accumulation and infiltration in joints and synovial tissue of arthritis rats induced by complete freund's adjuvant. METHODS: A rat model of rheumatoid arthritis was induced by subcutaneous injection of complete Freund's adjuvant in the footpad. The model was established 14 days after induction. The treatment was performed from 14th day to 35th day with different doses of andrographolide (25, 50, 100 mg/kg) and positive control methotrexate (3 mg/kg). The effects of andrographolide on oxidative stress, neutrophil accumulation and infiltration were measured by the paw swelling, arthritis score, the hot plate test, biochemical analysis, and histology. RESULTS: The medium and high-dose andrographolide (50, 100 mg/kg) group declined the levels of tumor necrosis factor-α, interleukin-6 and CXC chemokine ligand2, articular elastase and myeloperoxidase, and increased the levels of antioxidant enzymes superoxide dismutase, catalase, and glutathione. The activity of malondialdehyde and nitrite/nitrate in andrographolide (50, 100 mg/kg) group was weakened than the model group. The degree of swelling and arthritis score of andrographolide group was lower than the model group. The results of hot plate test showed that high dose of andrographolide significantly improved the anti-injury ability of rats; Radiological and histological results showed that the joint osteoporosis, inflammatory cell infiltration, synovial hyperplasia and other phenomena in the andrographolide group were significantly improved. CONCLUSIONS: Andrographolide acts as a protective agent for the treatment of complete freund's adjuvant induced rheumatoid arthritis by inhibiting lipid peroxidation and nitrite/nitrate levels in a dose-dependent manner, enhancing antioxidant enzyme activity, reducing levels of chemokines and inflammatory factors, preventing neutrophil accumulation and infiltration.

In vitro and in vivo assessment of the antibacterial activity of colistin alone and in combination with other antibiotics against Acinetobacter baumannii and Escherichia coli.

OBJECTIVES: Limited therapeutic options exist for treating severe infections caused by multidrug-resistant (MDR) and extensively drug-resistant Gram-negative bacteria (GNB). In this study, the activity of colistin (COL) as monotherapy and in combination with other antibiotics against Acinetobacter baumannii in vitro was investigated. In addition, the efficacy of intravenous colistimethate sodium (CMS) was evaluated in a murine model of urinary tract infection (UTI) induced by MDR Escherichia coli. METHODS: Minimum inhibitory concentration (MIC), Monte Carlo simulation, fractional inhibitory concentration index (FICI), time-kill study and erythrocyte lysis assay were applied to evaluate the effect and cytotoxicity of COL, meropenem, imipenem, doripenem (DOR) and sulbactam alone and in combination. For the in vivo experiment, determination of the bacterial burden and histopathological examination were performed to evaluate the efficacy of CMS against UTI. RESULTS: Of 106 A. baumannii isolates, 104 (98.1%) were susceptible to COL. In the chequerboard assay, COL + DOR showed the highest rate of synergism (60%). No antagonism or cytotoxicity was observed. All COL-based combinations were able to inhibit or slow bacterial re-growth in a time-kill assay. In an in vivo activity study, intravenous CMS reduced not only the bacterial load but also inflammation and maintained structural integrity of infected bladders and kidneys. CONCLUSION: The effectiveness of COL alone in vitro and in vivo suggested that intravenous CMS will be an effective and available therapeutic strategy for UTI due to MDR-GNB. In-depth in vitro tests demonstrated that COL + DOR could be an attractive option, especially when the COL MIC is ≥1 µg/mL.

Therapeutic effects of gentiopicroside on adjuvant-induced arthritis by inhibiting inflammation and oxidative stress in rats.

The purpose of this research was to evaluate the therapeutic effects of gentiopicroside (GPS) on adjuvant-induced arthritis (AA) rats. Rats were injected with complete Freund's adjuvant (CFA) for 0.1 mL in the right hind paw to induce AA. Thirty rats from three groups were treated with GPS (30, 60, 90 mg/kg) from day 15 to day 26. Arthritis was evaluated by arthritis index, paw volume, paw thickness, and X-ray. The effect of GPS on inflammation was assessed by measuring the levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6 and IL-17, as well as related mRNA. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH) protein carbonyl (PCO) and malondialdehyde (MDA) were measured to assess the effect of GPS on oxidative stress. These results indicate that GPS increases the levels of GSH-Px, SOD and GSH, and reduces the levels of MDA and PCO. GPS can significantly down-regulate the levels of IL-1ß, TNF-α, IL-6 and IL-17, as well as related mRNA. In addition, X-ray and histopathological results show that GPS has a therapeutic effect on joints in AA rats. In summary, the therapeutic effects of GPS on AA rats are associated with anti-inflammation and antioxidation.