The protective effect of hesperetin in osteoarthritis: an<i>in vitro</i>and<i>in vivo</i>study

Zeng, Lin; Fu, Changchang; Yan, Zijian; Wu, Yifan; Zhan, Jingdi; Lou, Zhiling; Liao, Xin; Pan, Jun

doi:10.1039/c9fo02552a

Cited by 31 publications

(20 citation statements)

References 43 publications

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“…Based on the UPLC analysis, five drug monomers were identified, including Astragaloside, Aucubin, Ginsenoside, Notoginsenoside, and Hesperidin. Previous reports had reported that Hesperidin ( Lin et al, 2020 ), extracted from Pericarpium Citri Reticulatae, attenuated cartilage destruction and reduced IL-1β and TNF-α levels in a surgically-induced OA model. Aucubin ( Wang et al, 2015 , 2019 ) a natural compound isolated from Cortex Eucommiae, had a protective effect on cartilage, slowing OA progression in the OA mice model.…”

Section: Discussionmentioning

confidence: 99%

Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

Ling

Zeng

et al. 2021

Front. Pharmacol.

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Osteoarthritis (OA) is a common disease characterized by cartilage degeneration. In recent years much attention has been paid to Traditional Chinese Medicine (TCM) since its treatments have shown efficacy for ameliorating cartilage degradation with mild side effects. Osteoking is a TCM prescription that has long been used in OA treatment. However, the exact mechanism of Osteoking are not fully elucidated. In the current study, destabilization of the medial meniscus (DMM)-induced OA mice was introduced as a wild type animal model. After 8 weeks of administration of Osteoking, histomorphometry, OARSI scoring, gait analysis, micro-CT, and immunohistochemical staining for Col2, MMP-13, TGFβRII and pSmad-2 were conducted to evaluate the chondroprotective effects of Osteoking in vivo. Further in vitro experiments were then performed to detect the effect of Osteoking on chondrocytes. TGFβRIICol2ER transgenic mice were constructed and introduced in the current study to validate whether Osteoking exerts its anti-OA effects via the TGF-β signaling pathway. Results demonstrated that in wild type DMM mice, Osteoking ameliorated OA-phenotype including cartilage degradation, subchondral bone sclerosis, and gait abnormality. Col2, TGFβRII, and pSmad-2 expressions were also found to be up-regulated after Osteoking treatment, while MMP-13 was down-regulated. In vitro, the mRNA expression of MMP-13 and ADAMTS5 decreased and the mRNA expression of Aggrecan, COL2, and TGFβRII were up-regulated after the treatment of Osteoking in IL-1β treated chondrocytes. The additional treatment of SB505124 counteracted the positive impact of Osteoking on primary chondrocytes. In TGFβRIICol2ER mice, spontaneous OA-liked phenotype was observed and treatment of Osteoking failed to reverse the OA spontaneous progression. In conclusion, Osteoking ameliorates OA progression by decelerating cartilage degradation and alleviating subchondral bone sclerosis partly via the TGF-β signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

Ling

Zeng

et al. 2021

Front. Pharmacol.

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“…Moreover, ROS was suggested to play a role in photoaging via stimulating pro-inflammatory mediators (e.g., TNF-α, IL-6, IL-1β)-mediated signaling cascades including MAPK-AP-1/NF-κB, leading to transcriptional regulation of MMP-1 (Pittayapruek et al, 2016;Subedi et al, 2017). HSP was also reported to possess antiinflammatory effects via downregulation of proinflammatory cytokines (including TNF-α, IL-6, and IL-1β) and NF-κB signaling concomitant with activation of Nrf2 in various in vitro and in vivo models (Parhiz et al, 2015;Li and Schluesener, 2017;Lin et al, 2020). Therefore, anti-photoaging effects and mechanisms of HRF containing HSP could also involve the anti-inflammatory activity against UVA-induced MMP-1 upregulation in dermal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect of Polyherbal Formulation, Harak Formula, on UVA-Induced Photoaging of Human Dermal Fibroblasts and Mouse Skin via Promoting Nrf2-Regulated Antioxidant Defense

et al. 2021

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Polyherbal formulation combining multiple herbs is suggested to achieve enhanced therapeutic effects and reduce toxicity. Harak herbal formula (HRF) extracts were proposed to regulate skin responses to UVR through their ability to suppress UVA-induced matrix metalloproteinase-1 (MMP-1) and pigmentation via promoting antioxidant defenses in in vitro models. Therefore, natural products targeting Nrf2 (nuclear factor erythroid 2-related factor 2)-regulated antioxidant response might represent promising anti-photoaging candidates. Hesperetin (HSP) was suggested as a putative bioactive compound of the HRF, as previously shown by its chemical profiling using the liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). In this study, we explored the anti-photoaging effects of HRF extracts and HSP on normal human dermal fibroblasts (NHDFs) and mouse skin exposed to UVA irradiation. Pretreatment of NHDFs with HRF extracts and HSP protected against UVA (8 J/cm2)-mediated cytotoxicity and reactive oxygen species (ROS) formation. The HRF and HSP pretreatment also attenuated the UVA-induced MMP-1 activity and collagen depletion concomitant with an upregulation of Nrf2 activity and its downstream genes (GST and NQO-1). Moreover, our findings provided the in vivo relevance to the in vitro anti-photoaging effects of HRF as topical application of the extracts (10, 30 and 100 mg/cm2) and HSP (0.3, 1, and 3 mg/cm2) 1 h before UVA exposure 3 times per week for 2 weeks (a total dose of 60 J/cm2) mitigated MMP-1 upregulation, collagen loss in correlation with enhanced Nrf2 nuclear accumulation and its target protein GST and NQO-1 as well as reduced 8-hydroxy-2′-deoxyguanosine (8-OHdG) in irradiated mouse skin. Thus, our findings revealed that HRF extracts and HSP attenuated UVA-induced photoaging via upregulating Nrf2, together with their abilities to reduce ROS formation and oxidative damage. Our study concluded that the HRF and its bioactive ingredient HSP may represent potential candidates for preventing UVA-induced photoaging via restoration of redox balance.

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“…COX-2 is an inducible enzyme of inflammatory cytokines, including interleukin (IL)-1 and tumor necrosis factor-α (TNF-α). Notably, IL-1 and TNF-α have been detected in synovial fluid from patients with KOA ( 40 ). However, the present study failed to investigate whether COX-2 expression was affected by IL-1 or TNF-α, in addition to miR-758-3p.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of cyclooxygenase‑2 in synovium tissues and synovial fluid from patients with knee osteoarthritis is associated with downregulated microRNA‑758‑3p expression

et al. 2021

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Cyclooxygenase-2 (COX-2) is a common factor in inflammation, and its specific regulatory mechanism has not been fully elucidated. The present study aimed to investigate COX-2 mRNA and protein expression levels in synovium tissues and synovial fluid from patients with knee osteoarthritis (KOA), and determine the molecular mechanism by which microRNA (miRNA/miR)-758 regulates KOA via COX-2. A total of 37 patients with KOA and 29 patients with acute knee trauma (control group) were enrolled in the present study. Reverse transcription-quantitative PCR analysis was performed to detect miR-758-3p and COX-2 mRNA expression, while western blotting and ELISA were performed to detect COX-2 protein expression in synovium and synovial fluid, respectively. The dual-luciferase reporter assay was performed to verify the interaction between miR-758-3p and the 3'-untraslated region (UTR) of COX-2 mRNA. Synovial cells were transfected with agomiR-758-3p, and the MTT assay was performed to assess cell proliferation. The results demonstrated that COX-2 expression was higher in patients with KOA than those with acute knee trauma. Conversely, miR-758-3p expression was lower in patients with KOA than those with acute knee trauma. Notably, miR-758-3p interacted with the 3'-UTR of COX-2 mRNA to regulate its expression. Overexpression of miR-758-3p inhibited the expression and release of COX-2, as well as the proliferation of human KOA synovial cells. Taken together, these results suggest that COX-2 expression is upregulated in synovium tissues and synovial fluid from patients with KOA, which is associated with downregulated miR-758-3p expression. In addition, miR-758-3p affects the proliferation of synovial cells and the expression of relevant proteins in these cells, thus promoting the occurrence and development of KOA.

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The protective effect of hesperetin in osteoarthritis: anin vitroandin vivostudy

Abstract: Osteoarthritis (OA), a progressive joint disorder, is principally characterized by the degeneration and destruction of articular cartilage.

Cited by 31 publications

References 43 publications

Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

The Protective Effect of Polyherbal Formulation, Harak Formula, on UVA-Induced Photoaging of Human Dermal Fibroblasts and Mouse Skin via Promoting Nrf2-Regulated Antioxidant Defense

Increased expression of cyclooxygenase‑2 in synovium tissues and synovial fluid from patients with knee osteoarthritis is associated with downregulated microRNA‑758‑3p expression

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