Physalin A alleviates intervertebral disc degeneration via anti-inflammatory and anti-fibrotic effects

Lu, Rui; Xu, Haoran; Deng, Xiaofeng; Wang, Yingguang; He, Zhiyi; Xu, Shimeng; Liang, Shuang; Huang, Xiaojian; You, Hongbo; Guo, Fengjing; Peng, Cheng; Chen, Anmin

doi:10.1016/j.jot.2023.01.001

Cited by 13 publications

(4 citation statements)

References 62 publications

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“…The mechanism may be linked to modification of IκB kinase-β and inhibition of NF-κB activity [13]. In arthritis, PA alleviates chondrocyte inflammation, promotes anabolic metabolism and reduces cartilage destruction by inhibiting MAPK and NF-κB pathways [7,14]. Similarly, we here also revealed that PA suppressed inflammation of PC12 cells treated by OGD/R via targeting MAPK pathway.…”

Section: Discussionsupporting

confidence: 58%

Physalin A exerts neuroprotective effects: inhibition of OGD/R-induced cellular pyroptosis and inflammatory responses in nerve cells

2023

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A prevalent cerebrovascular disease like the acute cerebral infarction is caused by cerebral thrombosis or arteriosclerosis that can result in ischemic necrosis of brain tissues. Treatment drugs of higher efficiency are required to be developed for acute cerebral infarction. Physalin A (PA) is a major compound from Physalis alkekengi L. and has pharmacological properties. However, the neuroprotective effects of PA are less reported and the mechanism remains unclear. The acute cerebral infarction cell model was constructed by treating PC12 cells with oxygen-glucose deprivation/reoxygenation (OGD/R). The impacts of PA on cell viability were determined by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) releasing assays. Immunoblot and Enzyme-linked Immunosorbent assay (ELISA) were conducted to examine PA effects on inflammation. PA effects on pyroptosis were detected by performing immunoblot and immunostaining. Moreover, immunoblot was further conducted to confirm the mechanism. In this study, the survival and inhibition of the pyroptosis of OGD/R-induced PC12 cells were regulated by PA. Furthermore, PA suppressed the inflammation. PA inhibited mitogen-activated protein kinase (MAPK) pathway activation, and the activation of MAPK pathway reversed the neuroprotective effect of PA. Therefore, PA exerts neuroprotective effects by suppressing OGD/R-induced cellular pyroptosis and inflammatory responses in nerve cells.

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Section: Discussionsupporting

confidence: 58%

Physalin A exerts neuroprotective effects: inhibition of OGD/R-induced cellular pyroptosis and inflammatory responses in nerve cells

2023

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“…MMPs, the major matrix‐degrading enzymes in the progression of IVDD, are abnormally highly expressed with the stimulation of IL‐1β. 28 , 36 Therefore, we detected the protein expression of MMP2, MMP13, MMP9, and MMP3 to analyze the effects of API on catabolism. Western blotting revealed that the increase in MMPs protein levels stimulated by IL‐1β could be decreased by API (Figure 3A,B ).…”

Section: Resultsmentioning

confidence: 99%

“…MMPs, the major matrix‐degrading enzymes in the progression of IVDD, are abnormally highly expressed with the stimulation of IL‐1β 28,36 . Therefore, we detected the protein expression of MMP2, MMP13, MMP9, and MMP3 to analyze the effects of API on catabolism.…”

Section: Resultsmentioning

confidence: 99%

“…According to a previous study, 5 ng/mL IL-1β was used to create the IVDD cell model. 28 Following the protocol, the same number of NPCs were seeded into 96-well plates and treated with IL-1β (5 ng/mL) and/or various concentrations of API (5,10,25,50, and 100 μM) and 3-MA (5 mM) for 24 h. After that, each well was incubated with the CCK-8 reagent for 1 h. Then, a microplate reader (BioTek, USA) was used to measure the absorbance at a wavelength of 450 nm.…”

Section: Cell Viability Assessmentmentioning

confidence: 99%

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Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy

Xu,

Zhao,

et al. 2024

JOR Spine

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BackgroundIntervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti‐inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro.MethodsIn vitro, western blotting, real‐time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin‐1 beta (IL‐1β)‐induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture‐induced IVDD rat models.ResultsIn vitro, API played a crucial role in anti‐inflammation and autophagy enhancement in IL‐1β‐induced NPCs. API improved inflammation by inhibiting the nuclear factor‐kappaB and mitogen‐activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3‐kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture‐induced IVDD model.ConclusionsAPI inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.

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Preserving the Immune‐Privileged Niche of the Nucleus Pulposus: Safeguarding Intervertebral Discs from Degeneration after Discectomy with Synthetic Mucin Hydrogel Injection

Wang,

Chen,

Liu

et al. 2024

Advanced Science

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Intervertebral disc (IVD) herniation is a prevalent spinal disorder, often necessitating surgical intervention such as microdiscectomy for symptomatic relief and nerve decompression. IVDs comprise a gel‐like nucleus pulposus (NP) encased by an annulus fibrosus (AF), and their avascular nature renders them immune‐privileged. Microdiscectomy exposes the residual NP to the immune system, precipitating an immune cell infiltration and attack that exacerbates IVD degeneration. While many efforts in the tissue engineering field are directed toward IVD regeneration, the inherently limited regenerative capacity due to the avascular and low‐cellularity nature of the disc and the challenging mechanical environment of the spine often impedes success. This study, aiming to prevent IVD degeneration post‐microdiscectomy, utilizes mucin‐derived gels (Muc‐gels) that form a gel at the surgical site, inspired by the natural mucin coating on living organisms to evade immune reorganization. It is shown that type I macrophages are present in severely degenerated human discs. Encapsulating IVDs within Muc‐gels prevents fibrous encapsulation and macrophage infiltration in a mouse subcutaneous model. The injection of Muc‐gels prevents IVD degeneration in a rat tail IVD degeneration model up to 24 weeks post‐operation. Mechanistic investigations indicate that Muc‐gels attenuate immune cell infiltration into NPs, offering durable protection against immune attack post‐microdiscectomy.

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Physalin A alleviates intervertebral disc degeneration via anti-inflammatory and anti-fibrotic effects

Cited by 13 publications

References 62 publications

Physalin A exerts neuroprotective effects: inhibition of OGD/R-induced cellular pyroptosis and inflammatory responses in nerve cells

Physalin A exerts neuroprotective effects: inhibition of OGD/R-induced cellular pyroptosis and inflammatory responses in nerve cells

Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy

Preserving the Immune‐Privileged Niche of the Nucleus Pulposus: Safeguarding Intervertebral Discs from Degeneration after Discectomy with Synthetic Mucin Hydrogel Injection

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