Picroside II suppresses chondrocyte pyroptosis through MAPK/NF-κB/NLRP3 signaling pathway alleviates osteoarthritis
Open accessAbstract
Background: Picroside II (P-II) is the main bioactive constituent of Picrorhiza Kurroa, a traditional Chinese herb of interest for its proven anti-inflammatory properties. Its beneficial effects have been noted across several physiological systems, including the nervous, circulatory, and digestive, capable of treating a wide range of diseases. Nevertheless, the potential of Picroside II to treat osteoarthritis (OA) and the mechanisms behind its efficacy remain largely unexplored. Aim: This study aims to evaluate the efficacy of Picroside II in the treatment of osteoarthritis and its potential molecular mechanisms. Methods: In vitro, we induced cellular inflammation in chondrocytes with lipopolysaccharide (LPS) and subsequently treated with Picroside II to assess protective effect on chondrocyte. We employed the Cell Counting Kit-8 (CCK-8) assay to assess the impact of Picroside II on cell viability and select the optimal Picroside II concentration for subsequent experiments. We explored the effect of Picroside II on chondrocyte pyroptosis and its underlying molecular mechanisms by qRT-PCR, Western blot (WB) and immunofluorescence. In vivo, we established the destabilization of the medial meniscus surgery to create an OA mouse model. The therapeutic effects of Picroside II were then assessed through Micro-CT scanning, Hematoxylin-eosin (H&E) staining, Safranin O-Fast Green (S&F) staining, immunohistochemistry and immunofluorescence. Results: In in vitro studies, toluidine blue and CCK-8 results showed that a certain concentration of Picroside II had a restorative effect on the viability of chondrocytes inhibited by LPS. Picroside II notably suppressed the expression levels of caspase-1, IL-18, and IL-1β, which consequently led to the reduction of pyroptosis. Moreover, Picroside II was shown to decrease NLRP3 inflammasome activation, via the MAPK/NF-κB signaling pathway. In vivo studies have shown that Picroside II can effectively reduce subchondral bone destruction and osteophyte formation in the knee joint of mice after DMM surgery. Conclusions: Our research suggests that Picroside II can inhibit chondrocyte pyroptosis and ameliorate osteoarthritis progression by modulating the MAPK/NF-κB signaling pathway.
AI snapshot
Written from the paper’s full text.
TL;DR
Picroside II (P-II) reduced LPS-induced chondrocyte pyroptosis and ECM degradation in vitro and attenuated DMM-induced osteoarthritis in mice, with effects linked to inhibition of MAPK/NF-κB signaling and NLRP3 inflammasome activation. The authors conclude P-II may be a potential OA treatment, though clinical safety remains to be studied.
Key findings
- In chondrocytes, P-II at 25 and 50 μM was selected after CCK-8 testing: 100 μM and above inhibited viability, while 50 μM showed the most pronounced protection against LPS-induced viability loss; toluidine blue showed partial restoration of LPS-induced morphology.
- P-II increased Col2 and decreased MMP3 at mRNA/protein levels and by immunofluorescence, indicating reduced ECM degradation.
- P-II decreased NLRP3, caspase-1, IL-1β, and IL-18 in LPS-induced chondrocytes; in vivo immunohistochemistry showed lower NLRP3 and caspase-1 in P-II-treated DMM mice.
- In DMM mice, P-II improved BV/TV, Tb.Th, and Tb.N and decreased Tb.Sp, reduced osteophyte/subchondral bone destruction and OARSI scores; P-II H (50 mg/kg) was more effective than P-II L (25 mg/kg). LPS increased phosphorylation of JNK, ERK, p38, and p65, which P-II reduced.
Methods
- In vitro: chondrocytes from 7-day-old C57BL/6J mice; inflammation induced with 1 μg/mL LPS; P-II tested at 5–200 μM for CCK-8, then 25/50 μM for subsequent assays including toluidine blue, qRT-PCR, Western blot, and immunofluorescence.
- In vivo: 8-week-old male C57BL/6J mice underwent DMM surgery; groups were control (n = 8), model (n = 8), P-II L (25 mg/kg, n = 8), and P-II H (50 mg/kg, n = 8); oral treatment lasted 8 weeks, followed by micro-CT, H&E, Safranin O-Fast Green, immunohistochemistry, immunofluorescence, and OARSI scoring.
- Statistics: mean ± SD, one-way ANOVA, P < 0.05; experiments repeated at least 3 times; SPSS 25.0 and GraphPad Prism 8.4.3 used.
Limitations
- The paper does not include a formal limitations section; it states that safety evaluation for clinical application deserves in-depth study.
- Evident from the text: in vivo experiments used only male C57BL/6J mice, so sex-specific effects are not addressed.
- Evident from the text: the mechanism is inferred from phosphorylation and expression changes; no NLRP3/MAPK/NF-κB loss-of-function or inhibitor experiments are reported to establish causality.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
33 of 43 cited sources checked · 15 supported · 0 flagged · accuracy not yet measured
- Premisecitation
NLRP3 levels in individuals with osteoarthritis exceed those in healthy subjects by a factor of more than five.
“Remarkably, the levels of NLRP3 in individuals with osteoarthritis (OA) have been detected to exceed those in healthy subjects by a factor of more than five [23,24]”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [23] D Clavijo-Cornejo, 2016, The Overexpression of NALP3 Inflammasome in Knee Osteoarthritis Is Associated with Synovial Membrane Prolidase and NADPH Oxidase 2, Oxidative medicine and cellular longevity source
- cites [24] Z Chen, 2019, Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis, Arthritis research & therapy source
The Results section on synovial inflammasome proteins reports higher NLRP3 expression in OA patients than controls, but its stated values (0.12 versus 0.05) amount to 2.4-fold, not more than fivefold. The Results section on clinical samples also reports increased NLRP3 protein and mRNA expression without giving a numerical fold change in the text. (LLM, conf=0.87)
Experimental — accuracy not yet measured
- Premisecitation
Damage-associated molecular patterns accumulate within the articular space in osteoarthritis pathogenesis.
“In the context of OA pathogenesis, it is observed that Damage-associated molecular patterns (DAMPs) accumulate within the articular space [20].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [20] G Wang, 2021, LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger hepatocyte pyroptosis by activating the NLRP3 inflammasome, Cell death discovery source
The Introduction (page unavailable) discusses DAMPs in LPS-induced acute liver injury, and the Results (page unavailable) concern liver damage. Neither addresses osteoarthritis or DAMP accumulation in the articular space; searches for osteoarthritis, articular space, and synovial joints found no relevant passage. (LLM, conf=0.75)
Experimental — accuracy not yet measured
- Premisecitation
Chondrocyte pyroptosis contributes to the progression of osteoarthritis.
“The current study found that chondrocyte pyroptosis, contributes to the progression of OA [14].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [14] L Tong, 2022, Current understanding of osteoarthritis pathogenesis and relevant new approaches, Bone research source
- Premisecitation
The MAPK/NF-κB signaling pathway significantly contributes to the pyroptotic demise of chondrocytes.
“The MAPK/NF-κB signaling pathway significantly contributes to the pyroptotic demise of chondrocytes.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [27] CJ Bradfield, 2023, Biphasic JNK signaling reveals distinct MAP3K complexes licensing inflammasome formation and pyroptosis, Cell death and differentiation source
The Discussion (page unavailable) reports that inhibiting MAP3K5 or deleting Jnk2 limits GSDMD processing needed for pyroptotic cell permeation, supporting a role for MAPK signaling in pyroptosis. The reported experiments concern U937 cells, not chondrocytes, and the paper does not establish that a combined MAPK/NF-κB pathway drives chondrocyte pyroptosis. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
The MAPK pathway leads to the activation of NLRP3 and caspase-1.
“MAPK pathway is an essential cellular signaling mediators that have been shown to lead to the activation of NLRP3 and caspase-1 [44].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [44] R Zhou, 2019, Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis, Journal of neuroinflammation source
The Discussion (page unavailable) links p38 MAPK and ERK signaling to NLRP3/caspase-1-related pyroptosis in neonatal septic rats, supporting a pathway relationship. It does not establish the unqualified claim that MAPK activation leads to activation of both proteins: when the pathways were further activated with U46619, NLRP3 and caspase-1 expression did not significantly increase. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation
The MAPK signaling pathway plays an instrumental role in cartilage differentiation and degradation.
“and it also plays an instrumental role in cartilage differentiation and degradation.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [54] J Yue, 2020, Understanding MAPK Signaling Pathways in Apoptosis, International journal of molecular sciences source
Section 1, “A Simple Introduction to MAPK Cascades” (page not provided), says MAPKs play a pivotal role in cellular differentiation generally. It does not establish a role in cartilage differentiation or degradation; searches for cartilage and chondrocytes found no relevant passage. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Premisecitation
Phosphorylation of p65 elevates NLRP3 by enhancing the transcriptional activity of NF-κB.
“and phosphorylation of p65 achieves elevation of NLRP3 by enhancing the transcriptional activity of NF-κB [27].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [27] CJ Bradfield, 2023, Biphasic JNK signaling reveals distinct MAP3K complexes licensing inflammasome formation and pyroptosis, Cell death and differentiation source
The Introduction (page unavailable) says that priming transcriptionally upregulates inflammasome components, but it does not connect this to p65 phosphorylation or NF-κB activity. Searches for p65, NF-κB, and the claimed transcriptional mechanism found no passage establishing that phosphorylation of p65 elevates NLRP3. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Premisecitation
Inflammation is a central pathogenic mechanism in OA.
“Inflammation is recognized as a central pathogenic mechanism in OA [45].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [45] L Ju, 2020, Huoxuezhitong capsule ameliorates MIA-induced osteoarthritis of rats through suppressing PI3K/ Akt/ NF-κB pathway, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie source
- Premisecitation
Chondrocyte pyroptosis is an important factor in the progression of OA.
“Previous studies have indicated that chondrocyte pyroptosis is an important factor in the progression of OA [50].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [50] W Liu, 2023, Dual-engineered cartilage-targeting extracellular vesicles derived from mesenchymal stem cells enhance osteoarthritis treatment via miR-223/NLRP3/pyroptosis axis: Toward a precision therapy, Bioactive materials source
- Premisecitation
P-II has demonstrated the ability to suppress LPS-induced inflammation by targeting the NF-κB signaling pathway.
“P-II has demonstrated the ability to suppress LPS-induced inflammation by targeting the NF-κB signaling pathway”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [59] S Giridharan, 2018, Mechanisms of NF-κB p65 and strategies for therapeutic manipulation, Journal of inflammation research source
The section on therapeutic targeting of NF-κB p65 reports that other agents inhibit NF-κB signaling in LPS-stimulated cells or reduce LPS-induced endotoxemia (page not available). It does not identify P-II or report that P-II suppresses LPS-induced inflammation, so the agent-specific claim is unsupported. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [60] R Chai, 2023, Tanshinone IIA inhibits cardiomyocyte pyroptosis through TLR4/NF-κB p65 pathway after acute myocardial infarction, Frontiers in cell and developmental biology source
The Discussion (page unavailable) reports that tanshinone IIA inhibits LPS-induced inflammation through a pathway involving NF-κB. The cited paper does not identify tanshinone IIA as P-II or report this effect for P-II; searches for P-II and LPS found no such passage. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Premisecitation
NF-κB is a key signaling molecule for NLRP3 inflammasome activation.
“and is a key signaling molecule for NLRP3 inflammasome activation [58].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [58] B Luo, 2017, NLRP3 Inflammasome as a Molecular Marker in Diabetic Cardiomyopathy, Frontiers in physiology source
- Findingown data
LPS significantly increased the phosphorylation of JNK, ERK, p38, and p65 in the MAPK/NF-κB pathway.
“In this study, LPS significantly increased the phosphorylation of JNK, ERK, p38, and p65 (Fig 5A–5G) in the MAPK/NF-κB pathway.”
Quote in the paperSubstantial claim- Rests on an assumption: Phosphorylation of JNK, ERK, p38, and p65 reflects activation of the MAPK/NF-κB signaling pathway.
- Findingown data
In in vitro experiments, LPS enhanced the expression of IL-1β, IL-18, NLRP3, and caspase-1 in chondrocytes.
“In in vitro experiments, LPS enhanced the expression of IL-1β, IL-18, NLRP3, and caspase-1 in chondrocytes”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Findingown data
P-II treatment decreased MMP3 expression in chondrocytes.
“we found that P-II treatment increased Col2 and decreased MMP3 expression in chondrocytes”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Findingown data
In LPS-induced chondrocytes, MMP3 expression was elevated.
“Col2 expression was decreased, while MMP3 expression was elevated in LPS-induced chondrocytes.”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Findingown data
Treatment with 25μM and 50μM of P-II significantly reduced the phosphorylation levels of JNK, ERK, p38, and p65.
“However, treatment at 25μM and 50μM of P-II significantly reduced the phosphorylation levels of these proteins.”
Quote in the paperSubstantial claim- Rests on an assumption: Phosphorylation of JNK, ERK, p38, and p65 reflects activation of the MAPK/NF-κB signaling pathway.
- Findingown data
P-II attenuated the LPS-induced enhancement of IL-1β, IL-18, NLRP3, and caspase-1 in chondrocytes.
“as we expected, P-II attenuated this response.”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Findingown data
Treatment with different doses of Picroside II improved bone destruction in the subchondral bone.
“as well as treatment with different doses of P-II improved bone destruction in the subchondral bone.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
- Findingown data
Treatment with 25 μM and 50 μM Picroside II partially reversed the adverse LPS effects on chondrocytes.
“These results suggested that treatment with 25μM and 50μM P-II partially reversed these adverse LPS effects on chondrocytes.”
Quote in the paperSubstantial claim - Findingown data
Picroside II decreases NLRP3 inflammasome activation via the MAPK/NF-κB signaling pathway.
“Moreover, Picroside II was shown to decrease NLRP3 inflammasome activation, via the MAPK/NF-κB signaling pathway.”
Quote in the paperSubstantial claim - Findingown data
Picroside II decreased the expression of NLRP3 and caspase-1 in the chondrocytes of the knee joints of mice compared to the model group.
“Likewise, P-II decreased the expression of NLRP3 and caspase-1 in the chondrocytes of the knee joints of mice compared to the model group (Fig 3K–3N),”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
- Findingown data
In vivo, the expression of caspase-1 and NLRP3 was significantly elevated in IHC of bone tissues.
“In vivo experiments, we found that the expression of caspase-1 and NLRP3 was significantly elevated in IHC of bone tissues”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM-induced OA mouse model is a valid model for human osteoarthritis.
- Findingown data
LPS-induced cells increased pyroptosis, characterized by elevated expression of NLRP3, caspase-1, IL-1β and IL-18.
“Based on our in vitro results, we found that compared with controls, LPS-induced cells increased pyroptosis, characterized by elevated expression of NLRP3, caspase-1, IL-1β and IL-18 (Fig 3A–3I)”
Quote in the paperSubstantial claim- Rests on an assumption: LPS-induced chondrocyte inflammation is a valid in vitro model of osteoarthritis chondrocyte pyroptosis.
- Findingown data
Picroside II can effectively reduce subchondral bone destruction and osteophyte formation in the knee joint of mice after DMM surgery.
“In vivo studies have shown that Picroside II can effectively reduce subchondral bone destruction and osteophyte formation in the knee joint of mice after DMM surgery.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
- Findingown data
In LPS-induced chondrocytes, Col2 expression was decreased.
“Col2 expression was decreased, while MMP3 expression was elevated in LPS-induced chondrocytes.”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Findingown data
S&F staining showed that the model group exhibited poor articular surface integrity and uneven contours.
“S&F staining showed that the model group exhibited poor articular surface integrity and uneven contours.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
- Findingown data
At concentrations above 50 μM, Picroside II exhibited inhibitory effects on cell proliferation.
“At concentrations above 50μM, P-II exhibited inhibitory effects on cell proliferation.”
Quote in the paperSubstantial claim - Findingown data
Picroside II treatment decreased the levels of NLRP3, caspase-1, IL-1β and IL-18 in LPS-induced chondrocytes.
“However, the treatment of P-II decreased their levels.”
Quote in the paperSubstantial claim- Rests on an assumption: LPS-induced chondrocyte inflammation is a valid in vitro model of osteoarthritis chondrocyte pyroptosis.
- Findingown data
Toluidine blue staining revealed that Picroside II partially restored LPS-induced morphological changes in chondrocytes.
“Toluidine blue staining revealed that P-II partially restored LPS-induced morphological changes in chondrocytes. (Fig 1D).”
Quote in the paperNot a substantial claim - Findingown data
Picroside II at concentrations of 100 μM and above significantly inhibited chondrocyte viability.
“In this study, we detected significant inhibition of chondrocyte viability at concentrations of P-II of 100μM and above.”
Quote in the paperNot a substantial claim - Findingown data
P-II treatment reduced OA scores in mice, as measured by the OARSI scoring system.
“Additionally, according to the OARSI scoring system, we found that OA scores were reduced in mice in the P-II treatment group (Fig 4I)”
Quote in the paperSubstantial claim - Findingown data
P-II treatment increased Col2 expression in chondrocytes.
“we found that P-II treatment increased Col2 and decreased MMP3 expression in chondrocytes”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Findingown data
P-II inhibited the high expression of caspase-1 and NLRP3 in vivo.
“and reassuringly, P-II again inhibited their high expression.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM-induced OA mouse model is a valid model for human osteoarthritis.
- Findingown data
P-II reversed the LPS-induced elevation of phosphorylation of p65, p38, ERK, JNK.
“but was reversed by P-II”
Quote in the paperSubstantial claim- Rests on an assumption: Phosphorylation of JNK, ERK, p38, and p65 reflects activation of the MAPK/NF-κB signaling pathway.
- Findingown data
In experimental results, phosphorylation of p65, p38, ERK, JNK was significantly elevated in response to LPS induction.
“our experimental results showed that phosphorylation of p65, p38, ERK, JNK was significantly elevated in response to LPS induction”
Quote in the paperSubstantial claim- Rests on an assumption: Phosphorylation of JNK, ERK, p38, and p65 reflects activation of the MAPK/NF-κB signaling pathway.
- Premisecitation
Damage-associated molecular patterns initiate activation of caspase-1 and the NLRP3 inflammasome.
“These molecules initiate the activation of the caspase-1 and NLRP3 inflammasome [21]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] J Xu, 2014, Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis, Cell death and differentiation source
- Premisecitation
Activation of caspase-1 and the NLRP3 inflammasome causes release of IL-18 and IL-1β.
“causing the release of IL-18 and IL-1β [22].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] PG Conaghan, 2019, Therapeutic options for targeting inflammatory osteoarthritis pain, Nature reviews Rheumatology source
- Interpretationown data
Picroside II attenuates bone destruction in the subchondral bone.
“These results suggest that P-II attenuates bone destruction in subchondral bone.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
- Interpretationreasoning
P-II resulted in better preservation of the cartilage matrix.
“suggesting that P-II reduced ECM degradation, resulting in better preservation of the cartilage matrix.”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Interpretationown data
P-II reduced ECM degradation.
“suggesting that P-II reduced ECM degradation, resulting in better preservation of the cartilage matrix.”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Interpretationown data
Picroside II treatment mitigates chondrocyte pyroptosis.
“Drawing on the findings from both in vivo and in vitro studies, it can be concluded that Picroside II treatment mitigates chondrocyte pyroptosis.”
- Also stated in: § Results · plain
“Picroside II notably suppressed the expression levels of caspase-1, IL-18, and IL-1β, which consequently led to the reduction of pyroptosis.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
- Rests on an assumption: LPS-induced chondrocyte inflammation is a valid in vitro model of osteoarthritis chondrocyte pyroptosis.
- Also stated in: § Results · plain
- Interpretationown data
P-II can mitigate the progression of DMM-induced OA in mice.
“indicating that P-II can mitigate the progression of DMM-induced OA.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM-induced OA mouse model is a valid model for human osteoarthritis.
- Premisecitation
The MAPK/NF-κB signaling pathway is essential for activation of the NLRP3 inflammasome.
“and is essential for the activation of the NLRP3 inflammasome [30,31].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Shen et al. showed that P-II can attenuate the inflammatory response by inhibiting NLRP3 inflammasome and the NF-κB signaling pathway.
“In addition, Shen et al. showed that that P-II can attenuate the inflammatory response by inhibiting NLRP3 inflammasome and the NF-κB signaling pathway [52].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [52] B Shen, 2017, Picroside II Protects Rat Lung and A549 Cell Against LPS-Induced Inflammation by the NF-κB Pathway, Inflammation source
- Interpretationown data
P-II can inhibit the activation of NLRP3 inflammasome in vivo and in vitro.
“These results suggested that P-II can inhibit the activation of NLRP3 inflammasome in vivo and in vitro”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Rests on an assumption: The DMM-induced OA mouse model is a valid model for human osteoarthritis.
- Rests on an assumption: Expression of NLRP3 and caspase-1 reflects pyroptosis.
- Interpretationown data
P-II reduces the degradation of ECM during OA development.
“indicating that suggests that P-II reduces the degradation of ECM during OA development.”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Rests on an assumption: The DMM-induced OA mouse model is a valid model for human osteoarthritis.
- Interpretationown data
P-II plays a positive role in improving the construction of the subchondral bone in the progression of OA.
“All these results suggested that P-II plays a positive role in improving the construction of the subchondral bone in the progression of OA.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM-induced OA mouse model is a valid model for human osteoarthritis.
- Interpretationown data
P-II may ameliorate chondrocyte pyroptosis through the MAPK/NF-κB pathway.
“This further confirms our hypothesis and suggests that P-II may ameliorate chondrocyte pyroptosis through the MAPK/NF-κB pathway.”
Quote in the paperSubstantial claim- Rests on an assumption: Phosphorylation of JNK, ERK, p38, and p65 reflects activation of the MAPK/NF-κB signaling pathway.
- Rests on an assumption: Expression of NLRP3 and caspase-1 reflects pyroptosis.
- Interpretationreasoning
The underlying molecular mechanism of P-II's therapeutic effect may be achieved by attenuating chondrocyte pyroptosis through inhibition of the MAPK/NF-κB pathway.
“and the underlying molecular mechanism may be achieved by attenuating chondrocyte pyroptosis through inhibition of the MAPK/NF-κB pathway.”
Quote in the paperSubstantial claim- Rests on an assumption: Phosphorylation of JNK, ERK, p38, and p65 reflects activation of the MAPK/NF-κB signaling pathway.
- Rests on an assumption: Expression of NLRP3 and caspase-1 reflects pyroptosis.
- Interpretationown data
P-II has a therapeutic effect on osteoarthritis.
“In conclusion, we identified for the first time that P-II has a therapeutic effect on osteoarthritis”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Rests on an assumption: The DMM-induced OA mouse model is a valid model for human osteoarthritis.
- Rests on an assumption: The effects of P-II observed in mouse and chondrocyte models translate to human osteoarthritis.
- Interpretationown data
P-II has a role in inhibiting the MAPK/NF-κB signaling pathway.
“suggests that P-II has a role in inhibiting the MAPK/NF-κB signaling pathway.”
Quote in the paperSubstantial claim- Rests on an assumption: Phosphorylation of JNK, ERK, p38, and p65 reflects activation of the MAPK/NF-κB signaling pathway.
- Classified as probably not a substantial claim. 20
- May combine two claims. 24
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationInvestigations delineating the link between osteoarthritis and pyroptosis are still limited in number.
“Despite its biological importance, investigations that delineate the link between OA and pyroptosis are still limited in number [17].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [17] J Yang, 2021, Targeting Cell Death: Pyroptosis, Ferroptosis, Apoptosis and Necroptosis in Osteoarthritis, Frontiers in cell and developmental biology source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationPyroptosis is predominantly dependent on activation of inflammatory caspases, especially caspase-1, and is marked by emission of pro-inflammatory cytokines.
“This process is predominantly dependent on the activation of inflammatory caspases, especially caspase-1, is marked by the emission of numerous pro-inflammatory cytokines [14].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [14] L Tong, 2022, Current understanding of osteoarthritis pathogenesis and relevant new approaches, Bone research source
May combine two claims.
PremisecitationPicroside II has potent anti-inflammatory effects mediated through regulation of the MAPK/NF-κB signaling pathway and suppression of NLRP3 inflammasome activation.
“Additionally, research has confirmed the potent anti-inflammatory effects of Picroside II, which are mediated through the regulation of the MAPK/NF-κB signaling pathway and the suppression of NLRP3 inflammasome activation. [38,39].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [38] P Wu, 2023, Network Pharmacology Study of Bioactive Components and Molecular Mechanisms of the Glycoside Fraction from Picrorhiza scrophulariiflora Against Experimental Colitis, Drug design, development and therapy source
The Discussion and Results identify picroside II as an anti-inflammatory component: it inhibited NO release in macrophage cells and showed predicted binding to MAPK-related proteins. The paper experimentally links MAPK regulation to the glycoside fraction as a whole, not specifically to picroside II, and does not establish NF-κB regulation or NLRP3 inflammasome suppression by picroside II (no page numbers supplied). (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [39] H Yao, 2022, Picroside II alleviates DSS-induced ulcerative colitis by suppressing the production of NLRP3 inflammasomes through NF-κB signaling pathway, Immunopharmacology and immunotoxicology source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPicroside II has been shown to improve liver damage and protect heart muscle cells.
“P-II is a key active ingredient derived from this herb, which has been studied and shown to improve liver damage and protect heart muscle cells [35,36]”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [35] X Piao, 2020, Picroside II Improves Severe Acute Pancreatitis-Induced Intestinal Barrier Injury by Inactivating Oxidative and Inflammatory TLR4-Dependent PI3K/AKT/NF-κB Signaling and Improving Gut Microbiota, Oxidative medicine and cellular longevity source
The Results (§3.2 and §3.5; page numbers unavailable) report that picroside II improved intestinal barrier injury in rats with severe acute pancreatitis. Searches for liver damage, hepatic injury, heart muscle cells, and cardiomyocytes found no passage in our copy addressing either claimed effect. (LLM, conf=0.75)
Experimental — accuracy not yet measured - cites [36] FJ Meng, 2012, Picroside II protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by activating the PI3K/Akt and CREB pathways, International journal of molecular medicine source
Classified as probably not a substantial claim.
PremisecitationDireito et al. noted that P-II exhibits potential to inhibit caspase-1 expression.
“Direito, R. et al. noted that P-II exhibits potential to inhibit caspase-1 expression [53].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [53] R Direito, 2023, Medicinal Plants, Phytochemicals and Regulation of the NLRP3 Inflammasome in Inflammatory Bowel Diseases: A Comprehensive Review, Metabolites source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSurgical interventions, including total joint replacements, are considered the standard of care for advanced osteoarthritis.
“Surgical interventions, including total joint replacements, are considered the standard of care for advanced OA [11].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [11] D Misra, 2019, Risk of Knee Osteoarthritis With Obesity, Sarcopenic Obesity, and Sarcopenia, Arthritis & rheumatology (Hoboken, NJ) source
The Methods (Study sample and Outcome; page not provided) examine risk factors for new-onset radiographic knee osteoarthritis, not treatment of advanced disease. Searches for total joint replacement, arthroplasty, and surgery found no passage stating that surgical intervention is the standard of care for advanced osteoarthritis. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
PremisecitationThe MAPK/NF-κB signaling pathway is a critical intracellular signaling mechanism regulating the inflammatory response.
“which is a critical intracellular signaling mechanism regulating the inflammatory response”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [28] F Zhou, 2019, Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes, Acta pharmaceutica Sinica B source
- cites [29] Y Shi, 2022, Tangeretin suppresses osteoarthritis progression via the Nrf2/NF-κB and MAPK/NF-κB signaling pathways, Phytomedicine: international journal of phytotherapy and phytopharmacology source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationMMP3 plays a significant role in ECM degradation and is connected with inflammatory processes.
“Meanwhile, MMP3 is an enzyme that plays a significant role in ECM degradation and is intimately connected with inflammatory processes [48].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [48] R Qin, 2020, Danshen Attenuates Intervertebral Disc Degeneration via Antioxidation in SD Rats, Oxidative medicine and cellular longevity source
The Discussion (section 4; page unavailable) calls MMP-3 a main catabolic enzyme responsible for ECM degradation. It also discusses inflammation in disc degeneration, and the Results (sections 3.4–3.5; pages unavailable) report increases in both MMP-3 and inflammatory factors after puncture. These passages support an association in this rat model, but do not establish the claimed intimate connection between MMP-3 itself and inflammatory processes. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe financial burden and complexities of postoperative recovery following surgery present additional challenges.
“Nonetheless, the financial burden and the complexities of postoperative recovery following surgery present additional challenges [12].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [12] ST Skou, 2015, A Randomized, Controlled Trial of Total Knee Replacement, The New England journal of medicine source
No passage from our copy matched the claim. Searches for surgical costs, financial burden, postoperative recovery, rehabilitation, and adverse events returned no passages, so the copy does not establish whether the paper discusses these challenges. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
PremisecitationThe classical pathway of cellular pyroptosis is the caspase-1 pathway, which recruits and activates caspase-1 through NLRP3 inflammasome sensing danger, cleaves IL-18, IL-1β, and GSDMD, leading to cellular pyroptosis.
“The classical pathway of cellular pyroptosis is the caspase-1 pathway, which recruits and activates cysteinyl asparagin-1 through NLRP3 inflammasome sensing the danger, which cleaves and activates inflammatory factors such as IL-18, IL-1β and cleaves the N-terminal sequences of the GSDMD so that it binds to the membrane and forms a membrane pore, leading to cellular pyroptosis [51].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [51] L Sun, 2019, Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome, Cell death & disease source
The Introduction describes inflammasome-associated caspase-1 activation, GSDMD cleavage, and maturation of IL-1β and IL-18; the Discussion links danger signals to NLRP3 activation. The Results also report caspase-1-dependent GSDMD cleavage and pyroptosis. Our copy does not describe the claimed N-terminal GSDMD fragment binding the membrane and forming a pore. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe MAPK signaling pathway is acknowledged for its pivotal role in regulating the proliferation and differentiation of inflammatory cells.
“In previous studies, the MAPK signaling pathway is acknowledged for its pivotal role in regulating the proliferation and differentiation of inflammatory cells [54]”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [54] J Yue, 2020, Understanding MAPK Signaling Pathways in Apoptosis, International journal of molecular sciences source
Section 1, “A Simple Introduction to MAPK Cascades” (page not available), says MAPKs play a pivotal role in cellular responses including proliferation and differentiation. It does not establish that role specifically for inflammatory cells; the cited review focuses on apoptosis. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAnti-inflammatory strategies continue to be a mainstay in OA treatment.
“Anti-inflammatory strategies continue to be a mainstay in OA treatment [46].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [46] CH Tang, 2019, Research of Pathogenesis and Novel Therapeutics in Arthritis, International journal of molecular sciences source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPhosphorylation of JNK in the MAPK pathway activates the transcription factor c-Jun.
“For example, phosphorylation of JNK in the MAPK pathway activates the transcription factor c-Jun”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [27] CJ Bradfield, 2023, Biphasic JNK signaling reveals distinct MAP3K complexes licensing inflammasome formation and pyroptosis, Cell death and differentiation source
Classified as probably not a substantial claim.
PremisecitationLee et al. found that P-II has the ability to alleviate inflammation by inhibiting the MAPK signaling pathway.
“And previous explorations by Lee, K et al. found that P-II has the ability to alleviate inflammation by inhibiting the MAPK signaling pathway [56].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [56] K Lee, 2019, Picroside II Isolated from Pseudolysimachion rotundum var. subintegrum Inhibits Glucocorticoid Refractory Serum Amyloid A (SAA) Expression and SAA-induced IL-33 Secretion, Molecules (Basel, Switzerland) source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationZhou et al. states that phosphorylation of JNK/ERK/p38 leads to the development of inflammation and decreased chondrocyte proliferation.
“The study by Zhou et al. states that phosphorylation of JNK/ERK/p38 leads to the development of inflammation and decreased chondrocyte proliferation [28].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [28] F Zhou, 2019, Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes, Acta pharmaceutica Sinica B source
The Discussion links JNK/ERK/p38 MAPK signaling to inflammatory macrophage activity, and the Results report increased phosphorylation of these proteins after LPS and IFN-γ stimulation. The paper separately reports that IL-1β inhibited chondrocyte proliferation, but it does not establish that JNK/ERK/p38 phosphorylation caused that decrease. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim. May combine two claims.
Premisecitationp65 phosphorylation is activated into the nucleus and promotes the expression of a range of inflammation-related genes.
“p65 phosphorylation is activated into the nucleus and promotes the expression of a range of inflammation-related genes55.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [55] W Gao, 2019, Chlorogenic Acid Attenuates Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice through MAPK/ERK/JNK Pathway, BioMed research international source
The Discussion (page not provided) reports increased NF-κB p65 phosphorylation in the DSS-induced colitis model and describes NF-κB as a transcription factor that regulates inflammation. It also says NF-κB activation upregulates TNF-α and IL-1. The copy does not state that phosphorylated p65 moves into the nucleus, so that step of the claim is unsupported. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
Premisecitationp65 phosphorylation is a critical step in NF-κB activation.
“where p65 phosphorylation is a critical step in activation [59,60]”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [59] S Giridharan, 2018, Mechanisms of NF-κB p65 and strategies for therapeutic manipulation, Journal of inflammation research source
- cites [60] R Chai, 2023, Tanshinone IIA inhibits cardiomyocyte pyroptosis through TLR4/NF-κB p65 pathway after acute myocardial infarction, Frontiers in cell and developmental biology source
The Results (§3.3 and §3.5; page not available) measure phosphorylated NF-κB p65 as part of the signaling pathway and discuss changes in p65 activity. The paper does not establish that p65 phosphorylation is a critical step required for NF-κB activation. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationNF-κB is a transcription factor that regulates the immune response and inflammatory response, and regulates gene expression in response to multiple stimuli.
“NF-κB is a transcription factor that regulates the immune response and inflammatory response, and regulates gene expression in response to multiple stimuli [57]”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [57] T Liu, 2017, NF-κB signaling in inflammation, Signal transduction and targeted therapy source
May combine two claims.
Findingown dataPicroside II treatment resulted in less cartilage erosion of the articular surface and a more complete contour.
“The P-II treatment resulted in less cartilage erosion of the articular surface and more complete contour (Fig 4H).”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
May combine two claims.
Findingown dataAfter Picroside II treatment, there was less synovial hyperplasia, lower levels of synovial inflammation, and better surface continuity of the cartilage than before.
“After P-II treatment, There was less synovial hyperplasia in the joints and lower levels of synovial inflammation, along with better surface continuity of the cartilage than before. (Fig 4G).”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
May combine two claims.
Findingown dataPicroside II treatment resulted in a dose-dependent increase in cell viability, with 50 μM Picroside II showing the most pronounced protective effect.
“Surprisingly, P-II treatment resulted in a dose-dependent increase in cell viability, with 50μM P-II showing the most pronounced protective effect.”
- Also stated in: § Results · hedged
“In in vitro studies, toluidine blue and CCK-8 results showed that a certain concentration of Picroside II had a restorative effect on the viability of chondrocytes inhibited by LPS.”
Quote in the paperSubstantial claim- Also stated in: § Results · hedged
May combine two claims.
Findingown dataPicroside II improved BV/TV and increased Tb.Th and Tb.N, while decreasing Tb.Sp.
“Quantitative histologic analyses showed that P-II improved BV/TV and increased Tb.Th and Tb.N, while decreasing Tb.Sp (Fig 4C–4F).”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
May combine two claims.
Findingown dataMMP3 expression in tissue immunofluorescence was higher in the model group compared to the control group and decreased after treatment with Picroside II.
“Similarly, the expression of MMP3 in tissue immunofluorescence was higher in the model group compared to the control group and decreased after treatment with P-II (Fig 2H)”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn the model group compared to the control group, H&E staining showed increased synovial hyperplasia and inflammatory cell infiltration, with a higher degree of surface destruction of cartilage.
“In the model group compared to the control group, H&E staining in the model group showed increased synovial hyperplasia and inflammatory cell infiltration, with a higher degree of surface destruction of cartilage.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
May combine two claims.
Findingown dataLPS decreased the expression of Col2 and increased MMP3 levels at both the protein and mRNA levels in chondrocytes.
“According to the qRT-PCR and Western Blot analysis, we found that LPS decreased the expression of Col2 and increased the MMP3 levels at both the protein levels and mRNA (Fig 2A–2E).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe model group had increased periarticular bone formation and greater loss of subchondral bone mass compared to the control group.
“Analysis of micro-CT scans of mouse tibiae showed that the model group had increased periarticular bone formation and greater loss of subchondral bone mass compared to the control group (Fig 4A and 4B)”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
May combine two claims.
Findingown dataThe Picroside II high-dose group was more effective than the Picroside II low-dose group, with more pronounced bone reconstruction of the subchondral bone.
“Additionally, we found that the P-II H group was more effective than the P-II L group, and the bone reconstruction of the subchondral bone was more pronounced.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
May combine two claims.
PremisecitationPicroside II has shown promise in mitigating pyroptosis and has anti-inflammatory and antioxidant properties.
“also has shown promise in its ability to mitigate pyroptosis, anti-inflammatory and antioxidant [37].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] Y Huang, 2016, Picroside II protects against sepsis via suppressing inflammation in mice, American journal of translational research
May combine two claims.
PremisecitationCurrent medical treatments for osteoarthritis offer limited pain relief and are associated with considerable side effects.
“While these medications can offer some pain relief, their efficacy is limited and they are associated with considerable side effects [10].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] B Abramoff, 2020, Osteoarthritis: Pathology, Diagnosis, and Treatment Options, The Medical clinics of North America source
May combine two claims.
Interpretationown dataPicroside II can inhibit chondrocyte pyroptosis and ameliorate osteoarthritis progression by modulating the MAPK/NF-κB signaling pathway.
“Our research suggests that Picroside II can inhibit chondrocyte pyroptosis and ameliorate osteoarthritis progression by modulating the MAPK/NF-κB signaling pathway.”
Quote in the paperSubstantial claim- Rests on an assumption: The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
- Rests on an assumption: LPS-induced chondrocyte inflammation is a valid in vitro model of osteoarthritis chondrocyte pyroptosis.
May combine two claims.
Interpretationown dataP-II inhibited NLRP3 inflammasome activation and mitigated inflammation by blocking the MAPK/NF-κB signaling pathway.
“These results indicated that P-II inhibited NLRP3 inflammasome activation and mitigated inflammation by blocking the MAPK/NF-κB signaling pathway.”
Quote in the paperSubstantial claim- Rests on an assumption: Phosphorylation of JNK, ERK, p38, and p65 reflects activation of the MAPK/NF-κB signaling pathway.
- Rests on an assumption: Expression of NLRP3 and caspase-1 reflects pyroptosis.
May combine two claims.
InterpretationreasoningP-II can inhibit pyroptosis by suppressing the expression of caspase-1, thereby alleviating the development of OA.
“and that it can inhibit pyroptosis by suppressing the expression of caspase-1, thereby alleviating the development of OA.”
Quote in the paperSubstantial claim- Rests on an assumption: The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
- Rests on an assumption: The DMM-induced OA mouse model is a valid model for human osteoarthritis.
- Rests on an assumption: The effects of P-II observed in mouse and chondrocyte models translate to human osteoarthritis.
- Rests on an assumption: Expression of NLRP3 and caspase-1 reflects pyroptosis.
May combine two claims.
Interpretationown dataPicroside II may have favorable effects in promoting extracellular matrix repair and inhibiting extracellular matrix degradation, thereby slowing the progression of osteoarthritis.
“This suggests that P-II may have some favorable effects in promoting ECM repair and inhibiting ECM degradation, thereby slowing the progression of osteoarthritis.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationMa et al. noted a trend toward degradation of cartilage ECM during OA progression, with decreased Col2 expression and increased MMP3 expression.
“Ma et al. noted a trend toward degradation of cartilage ECM during the progression of OA, that is to say, a decrease in Col2 expression and an increase in MMP3 expression [49].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [49] T Ma, 2023, Oleanolic acid, a small-molecule natural product, inhibits ECM degeneration in osteoarthritis by regulating the Hippo/YAP and Wnt/β-catenin pathways, Food & function source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenEach of the above experiments was repeated at least 3 times.
“Each of the above experiments was repeated at least 3 times and the data were subjected to analysis utilizing SPSS 25.0 software, with results presented as the mean ± standard deviation.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll experimental protocols were approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine.
“All experimental protocols were thoroughly reviewed and were approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (GZTCMF1-20221121, Nov. 21,2022).”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The DMM surgery-induced osteoarthritis mouse model is a valid model of human osteoarthritis.
“Mice excluding the control group underwent DMM surgery to induce an OA model.”
The paper relies on this without support.
LPS-induced chondrocyte inflammation is a valid in vitro model of osteoarthritis chondrocyte pyroptosis.
“Subsequently, we established an inflammatory model in chondrocytes using LPS (1μg/mL).”
The paper relies on this without support.
The LPS-induced chondrocyte inflammation model is a valid model for studying osteoarthritis mechanisms.
“In our study, we used 1μg /mL LPS to establish an inflammation model.”
The paper relies on this without support.
The DMM-induced OA mouse model is a valid model for human osteoarthritis.
“indicating that P-II can mitigate the progression of DMM-induced OA.”
The paper relies on this without support.
The effects of P-II observed in mouse and chondrocyte models translate to human osteoarthritis.
“In conclusion, we identified for the first time that P-II has a therapeutic effect on osteoarthritis”
The paper relies on this without support.
Inflammation is inextricably linked to pyroptosis.
“Furthermore, inflammation is inextricably linked to pyroptosis.”
The paper relies on this without support.
Phosphorylation of JNK, ERK, p38, and p65 reflects activation of the MAPK/NF-κB signaling pathway.
“In this study, LPS significantly increased the phosphorylation of JNK, ERK, p38, and p65 (Fig 5A–5G) in the MAPK/NF-κB pathway.”
The paper relies on this without support.
Expression of NLRP3 and caspase-1 reflects pyroptosis.
“These results suggested that P-II can inhibit the activation of NLRP3 inflammasome in vivo and in vitro, and that it can inhibit pyroptosis by suppressing the expression of caspase-1”
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“Direito, R. et al. noted that P-II exhibits potential to inhibit caspase-1 expression [53].”
BackgroundPicroside II Protects Rat Lung and A549 Cell Against LPS-Induced Inflammation by the NF-κB Pathway
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Flagged first, then by citations
5 of the 67 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Role of Pyroptosis in the Pathogenesis of Osteoarthritis: An Updated Review
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“59,62 Pyroptosis Is Involved in the Pathological Process of OA Both the pathological process of OA and the occurrence of pyroptosis lead to the release of a large amount of inflammatory mediators.”
InfluentialOsteoarthritis: Epidemiology, Pathogenesis, and Treatment
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“Mechanistic analyses reveal its capacity to reverse astrocyte-derived in fl ammatory signaling, evidenced by reduced transcription and translation of pro-in fl ammatory cytokines (IL-1 β , IL-6, TNF-α ) in activated astrocytes [108].”
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“Pic II is a key active component extracted from Picrorhiza Kurroa, has been researched and found to alleviate osteoarthritis by suppressing chondrocyte pyroptosis (Wang et al. 2024a).”
Self-citationPicroside II as a Potential Anti-Inflammatory Agent
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“Wang et al. [57] found that picroside II (:25 mg/kg and 50 mg/kg in OA mouse model; 20 µ M and 50 µ M in cellular experiments) inhibited LPS-induced chondrocyte pyroptosis and attenuated osteoarthritis progression in OA mice by regulating the MAPK/NF-κ B/NLRP3 signaling pathway.”
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“Recently, picroside II suggested suppressing chondrocyte pyroptosis by modulating the MAPK/NF‐κB/NLRP3 signaling axis, contributing to the mitigation of osteoarthritis symptoms (Wang et al. 2024).”
Zhang, L., Xing, X., Zhou, C., et al. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1861567
“Accordingly, growing research efforts have identified candidate compounds that alleviate OA by inhibiting NLRP3 inflammasome-mediated chondrocyte pyroptosis through suppression of NF-κ B activation (Zhang et al., 2024; Wang et al., 2024; Zhou et al., 2024).”
Self-citationYang, J., Song, W., Chen, K., Deng, J., Wang, A., Xu, P., Pan, H., Wang, K., Bian, Z., Chen, S., et al. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158811
- Authors
- Wang, F., Xiao, J., Li, M., He, Q., Wang, X., Pan, Z., Li, S., Wang, H., & Zhou, C.
- Affiliations
- Guangzhou University of Chinese Medicine (CN)
- Corresponding author
- Wang, Haibin
- Zhou, Chi
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2024-08-29
- Volume
- 19
- Issue
- 8
- Pages
- e0308731
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC11361613
- OpenAlex
- W4401989544
- Semantic Scholar
- aae08b584e6079622ae6e82ea26328ab8a509d72
- Cited by
- 9
- References
- 67
- Citations by year
- 2026: 4 · 2025: 5
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82074462)
- Guangdong Provincial Administration of Traditional Chinese Medicine (20233001)
- Guangzhou Municipal Science and Technology Project (2023B03J0056)
- Maoming Science and Technology Bureau (2023SZX022)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Health Sciences › Medicine › Pharmacology › Pharmacological Effects of Medicinal Plants
- Keywords
- picroside II, osteoarthritis, NLRP3 inflammasome, caspase-1, IL-18, IL-1β, lipopolysaccharide-induced inflammation, destabilization of the medial meniscus, subchondral bone destruction, osteophyte formation, Picrorhiza kurroa, anti-inflammatory herbal medicine, chondroprotection
- MeSH terms
- Pyroptosis, NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Cinnamates, Lipopolysaccharides, Male, Mice, Inbred C57BL, Osteoarthritis, Signal Transduction, NF-kappa B, Chondrocytes, MAP Kinase Signaling System, Mice, Iridoid Glucosides
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-13.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-13.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
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