Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway

Shao, Minglei; Lv, Dongwei; Zhou, Kai; Sun, Haijun; Wang, Zhitao

doi:10.1080/13880209.2022.2042327

Cited by 13 publications

(4 citation statements)

References 48 publications

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“…20 Nobiletin, tangeretin, senkyunolide A, glycyrrhetinic acid, and protocatechuate have been shown to have anti-inflammatory and antioxidant effects. [32][33][34][35] Curcumin and demethoxycurcumin have been shown to inhibit inflammation and apoptosis of nucleus pulposus cells, and delay intervertebral disc degeneration. 36,37 In various cell lines, curcumin treatment was reported to decrease CCL2 production.…”

Section: Discussionmentioning

confidence: 99%

Zhiqiao Gancao Decoction Ameliorates Hyperalgesia in Lumbar Disc Herniation via the CCL2/CCR2 Signaling Pathway

Huang¹,

Lu²,

Zhang³

et al. 2023

DDDT

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Purpose The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism. Methods The potential mechanism of ZQGCD’s therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software. Results Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream. Conclusion The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression.

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Section: Discussionmentioning

confidence: 99%

Zhiqiao Gancao Decoction Ameliorates Hyperalgesia in Lumbar Disc Herniation via the CCL2/CCR2 Signaling Pathway

Huang¹,

Lu²,

Zhang³

et al. 2023

DDDT

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“…In the SX mixture, SEA was identified as a key molecule that significantly downregulated the expression of the tumor necrosis factor (TNF)-α-induced CD137, which is a member of the TNF receptor superfamily associated with increased plaque necrosis, macrophage infiltration, and decreased collagen content in the progression of unstable atherosclerotic plaques [55][56] . In a study using an osteoarthritis mouse model, SEA treatment was found to alleviate osteoarthritis progression by inhibiting the expression of multiple inflammatory cytokines and the NLRP3 signaling pathway [57] . Several studies have reported the anti-inflammatory effects of SEA in different cell models, via blocking the release of IL-1βinduced pro-inflammatory mediator nitric oxide (NO), inhibiting the expression of nod-like receptor family pyrin domain-containing 3, and downregulating the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokines (C-C motif chemokine ligand 20) [57][58] .…”

Section: Inhibition Of Inflammatory Reactionmentioning

confidence: 99%

“…In a study using an osteoarthritis mouse model, SEA treatment was found to alleviate osteoarthritis progression by inhibiting the expression of multiple inflammatory cytokines and the NLRP3 signaling pathway [57] . Several studies have reported the anti-inflammatory effects of SEA in different cell models, via blocking the release of IL-1βinduced pro-inflammatory mediator nitric oxide (NO), inhibiting the expression of nod-like receptor family pyrin domain-containing 3, and downregulating the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokines (C-C motif chemokine ligand 20) [57][58] .…”

Section: Inhibition Of Inflammatory Reactionmentioning

confidence: 99%

Research progress on the pharmacological activities of senkyunolides

Li,

Wan,

Zhao

2023

Acupuncture and Herbal Medicine

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Senkyunolides are a group of phthalide molecules that exist in Umbelliferae plants, with the highest abundance in Ligusticum chuanxiong Hort, a medicinal herb with therapeutic applications in various diseases such as coronary heart disease, migraine, and rheumatism. Modern research has highlighted the anti-inflammatory, analgesic, and cardiovascular-protective properties of senkyunolides. Recently, some novel effects, such as antibacterial, anti-osteoporosis, and anti-fibrosis, have been reported for senkyunolides, indicating their diverse biological activities. In addition, because of its high bioavailability and ability to cross the blood-brain barrier (BBB), particularly exemplified by senkyunolide I (SEI), holds promise for the treatment of brain diseases. Multiple signaling pathways have been related to the pharmacological activities of senkyunolides, such as the toll-like receptor 4/nuclear factor-kappa B (NF-κB) signaling, extracellular signal–regulated kinase (ERK) pathway, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) pathways. Here, we review the research progress on the pharmacokinetics and pharmacological effects of senkyunolides, which are promising candidates for future drug development and have significant clinical value in the treatment of various diseases. Graphical abstract: http://links.lww.com/AHM/A66.

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“…Recent pharmacological studies have shown that the active ingredients in the EF–CR pair, namely icariin, epimedin A, epimedin B, epimedin C, icariside I, icariside II, ligustilide, ferulic acid and senkyunolide A, exert anti‐inflammatory and analgesic effects via the modulation of various inflammatory factors and pathways (Du et al, 2021; Lai et al, 2013; Li et al, 2018; Shao et al, 2022; Wang et al, 2020; Zeng et al, 2017; Ziadlou et al, 2019; Zu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Comparative pharmacokinetic study of nine bioactive components in osteoarthritis rat plasma using ultra‐performance liquid chromatography–tandem mass spectrometry after single and combined oral administration of Epimedii Folium and Chuanxiong Rhizoma extracts

Zhang

Chen

et al. 2022

Biomedical Chromatography

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The herb pair Epimedii Folium–Chuanxiong Rhizoma (EF–CR), derived from the classical traditional Chinese medicine ‘Xian Ling Pi San’, has a distinctive compatibility therapeutic profile and is clinically safe and effective. This study aimed to investigate and compare the pharmacokinetic characteristics of nine analytes in osteoarthritis (OA) rat plasma after the oral administration of EF, CR or a combination of these two herbs. We developed an ultra‐performance liquid chromatography method coupled with quadrupole linear ion‐trap mass spectrometry to simultaneously quantify and assess the pharmacokinetics of icariin, epimedin A, epimedin B, epimedin C, icariside I, icariside II, ferulic acid, ligustilide and senkyunolide A of the EF–CR pair in the plasma of osteoarthritic rats. The pharmacokinetic parameters showed that the absorption of multiple components was significantly enhanced and residence time was prolonged in the EF–CR group (P < 0.05) compared to the single‐herb group. These parameters revealed that the combination of EF and CR exhibited synergistic effects of the nine bioactive components, suggesting the potential application of the EF–CR combination for the treatment of OA.

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Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway

Cited by 13 publications

References 48 publications

Zhiqiao Gancao Decoction Ameliorates Hyperalgesia in Lumbar Disc Herniation via the CCL2/CCR2 Signaling Pathway

Zhiqiao Gancao Decoction Ameliorates Hyperalgesia in Lumbar Disc Herniation via the CCL2/CCR2 Signaling Pathway

Research progress on the pharmacological activities of senkyunolides

Comparative pharmacokinetic study of nine bioactive components in osteoarthritis rat plasma using ultra‐performance liquid chromatography–tandem mass spectrometry after single and combined oral administration of Epimedii Folium and Chuanxiong Rhizoma extracts

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