Ginsenoside Compound K Ameliorates Osteoarthritis by Inhibiting the Chondrocyte Endoplasmic Reticulum Stress-Mediated IRE1α-TXNIP-NLRP3 Axis and Pyroptosis

You, Tian; Feng, Xinyuan; Zhou, Zimo; Qin, Sen; Chen, Senxiang; Zhao, Jihui; Hou, Jianglin; Liu, Da

doi:10.1021/acs.jafc.2c06134

Cited by 11 publications

(9 citation statements)

References 46 publications

(76 reference statements)

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“…Furthermore, prior research has demonstrated that classic PERK/TXNIP/NLRP3 signaling predominantly occurs in OA, which increases SF proliferation, increases collagen deposition and worsens synovial fibrosis ( Liu et al, 2021 ; Tian et al, 2023 ). The endoplasmic reticulum stress-mediated unfolded protein response (UPR) typically involves three receptor proteins: activating transcription factor 6 (ATF-6), protein kinase RNA-like ER kinase (PERK) and inositol requiring enzyme 1α (IRE1α) ( Li et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Targeting overactive canonical PERK/TXNIP/NLRP3 signaling has emerged as a promising treatment strategy for KOA ( Liu et al, 2021 ; Tian et al, 2023 ). In addition, based on the limitations of previous studies, we are also in search of drug monomers that can suppress the NLRP3 inflammasome to mitigate synovitis and fibrosis in KOA ( Zhang et al, 2019b ).…”

Section: Introductionmentioning

confidence: 99%

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Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK/TXNIP/NLRP3 signaling

et al. 2023

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Objective: Synovitis and fibrosis are common pathological features of knee osteoarthritis (KOA). The interaction of synovitis and fibrosis can promote KOA progression. Chrysin (CHR), a natural flavonoid, may treat inflammation and prevent fibrosis. However, the effect and mechanism of CHR in KOA synovitis and fibrosis remains unclear.Methods: The KOA model was established in male SD rats by anterior cruciate ligament transection (ACLT), and histological analysis was used to evaluate synovitis and fibrosis. IL-6, IL-1β and TNF-α mRNA expression in synovial tissue was measured by qRT‒PCR. Immunohistochemistry (IHC) was performed to detect GRP78, ATF-6 and TXNIP expression in vivo. Synovial fibroblasts (SFs) were treated with TGF-β1 to stimulate the inflammatory response and fibrosis. CCK-8 assays were used to detect the viability of CHR-treated SFs. The IL-1β level was detected by immunofluorescence analysis. Coimmunoprecipitation (Co-IP) and double immunofluorescence colocalization were used to detect the physiological interaction between TXNIP and NLRP3. The expression of fibrosis-related mediators and PERK/TXNIP/NLRP3 signaling molecules was detected by western blotting and qRT-PCR.Results: Four weeks after CHR treatment, pathological sections and associated scores showed that CHR improved synovitis and fibrosis in the ACLT model. In vitro, CHR attenuated the TGF-β1-induced inflammatory response and fibrosis in SFs. Moreover, CHR suppressed the expression of synovial fibrosis markers and PERK/TXNIP/NLRP3 signaling molecules in the synovial tissue of rats with ACLT and cultured SFs. More importantly, we found that CHR inhibited TXNIP-NLRP3 interactions in TGF-β-induced SFs.Conclusion: Our findings indicate that CHR can ameliorate synovitis and fibrosis in KOA. The underlying mechanism may be related to the PERK/TXNIP/NLRP3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK/TXNIP/NLRP3 signaling

et al. 2023

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“…A key player in this metabolic transformation is compound K, a secondary metabolite formed through the action of intestinal bacteria on primary ginsenosides such as Rb1 and Rb2. Compound K is particularly noteworthy because it has been shown to exert significant anti-inflammatory, antioxidative, and anticancer effects (Choi and Kim 2023 ; Liu et al 2023b ; Tian et al 2023 ). These effects are often more potent than those of the original ginsenosides, highlighting the importance of gut microbial metabolism in enhancing the pharmacological efficacy of ginseng.…”

Section: Nds and Their Pathogenesismentioning

confidence: 99%

Herbal medicine and gut microbiota: exploring untapped therapeutic potential in neurodegenerative disease management

Guan,

Tang,

et al. 2024

Arch. Pharm. Res.

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The gut microbiota that exists in the human gastrointestinal tract is incredibly important for the maintenance of general health as it contributes to multiple aspects of host physiology. Recent research has revealed a dynamic connection between the gut microbiota and the central nervous system, that can influence neurodegenerative diseases (NDs). Indeed, imbalances in the gut microbiota, or dysbiosis, play a vital role in the pathogenesis and progression of human diseases, particularly NDs. Herbal medicine has been used for centuries to treat human diseases, including NDs. These compounds help to relieve symptoms and delay the progression of NDs by improving intestinal barrier function, reducing neuroinflammation, and modulating neurotransmitter production. Notably, herbal medicine can mitigate the progression of NDs by regulating the gut microbiota. Therefore, an in-depth understanding of the potential mechanisms by which herbal medicine regulates the gut microbiota in the treatment of NDs can help explain the pathogenesis of NDs from a novel perspective and propose novel therapeutic strategies for NDs. In this review, we investigate the potential neuroprotective effects of herbal medicine, focusing on its ability to regulate the gut microbiota and restore homeostasis. We also highlight the challenges and future research priorities of the integration of herbal medicine and modern medicine. As the global population ages, access to this information is becoming increasingly important for developing effective treatments for these diseases.

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“…The effects of ginsenosides on osteoarthritis, both in vitro and in vivo, have been mainly observed in terms of cartilage protection. In some studies, osteoarthritis has been induced using monoiodoacetate (MIA) to reproduce these conditions in animal models [ 16 ]. The effects of ginsenosides on articular cartilage tissue have been classified into four categories: the inhibition of matrix synthesis or the expression of matrix-degrading enzymes in chondrocytes, which play an important role in the destruction and regeneration of articular cartilage, and anti-inflammatory, antioxidant, and anti-pyroptotic activities ( Figure 1 and Figure 2 C).…”

Section: Effects Of Ginsenosides On Osteoarthritismentioning

confidence: 99%

“…Analyses of nuclear factor kappa-κB (NF-κB) and mitogen-activated protein kinase (MAPK) expression and activity in relevant cells serve to elucidate the signaling pathways involved [ 8 , 9 , 10 , 11 ]. Animal models of osteoporosis typically assess changes in bone density; in contrast, those of periodontal disease or osteoarthritis consider inflammatory mediators, connective tissue integrity, connective-tissue-degrading enzymes, and serum metabolic markers [ 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Ginsenosides on Bone Metabolism: A Review of Osteoporosis, Periodontal Disease and Osteoarthritis

2024

IJMS

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Ginsenosides, bioactive compounds from the genus Panax, have potential therapeutic effects on diverse ailments, including diabetes. Emerging evidence suggests their involvement in bone metabolism. The present review summarizes the current understanding of the effects of ginsenosides on osteoporosis, periodontal disease, and osteoarthritis. Their mechanisms of action include effects on osteoblasts, osteoclasts, periodontal ligament fibroblasts (PDLFs), and chondrocytes, which are pivotal in maintaining bone, periodontal tissue, and cartilage homeostasis. Ginsenosides may exert their beneficial effects by enhancing PDLF and osteoblast activity, suppressing osteoclast function, augmenting chondrocyte synthesis in the cartilage matrix, and mitigating connective tissue degradation. Moreover, they possess antioxidant, anti-inflammatory, antimicrobial, and anti-pyroptotic properties. Their efficacy in increasing bone density, ameliorating periodontitis, and alleviating osteoarthritis symptoms has been demonstrated in preclinical studies using animal models. In terms of their mechanism of action, ginsenosides modulate cellular differentiation, activity, and key signaling pathway molecules, such as mitogen-activated protein kinases (MAPKs), while also regulating various mediators. Furthermore, the symptomatic relief observed in animal models lends further credence to their therapeutic utility. However, to translate these preclinical findings into clinical practice, rigorous animal and clinical investigations are imperative to ascertain the safety, efficacy, and optimal dosing regimens in human subjects.

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Ginsenoside Compound K Ameliorates Osteoarthritis by Inhibiting the Chondrocyte Endoplasmic Reticulum Stress-Mediated IRE1α-TXNIP-NLRP3 Axis and Pyroptosis

Cited by 11 publications

References 46 publications

Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK/TXNIP/NLRP3 signaling

Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK/TXNIP/NLRP3 signaling

Herbal medicine and gut microbiota: exploring untapped therapeutic potential in neurodegenerative disease management

Therapeutic Potential of Ginsenosides on Bone Metabolism: A Review of Osteoporosis, Periodontal Disease and Osteoarthritis

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