Icariin, a flavonoid with anti-cancer effects, alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner

Gui, Yulong; Zhang, Jie; Chen, Liang; Duan, Shunyuan; Tang, Jing; Xu, Wei; Li, Aiyuan

doi:10.1177/1744806918768970

Cited by 54 publications

(45 citation statements)

References 30 publications

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“…22,41,42 It has been shown that activated neuroglia in spinal cord produce proinflammatory cytokines. 43,44 Moreover, recent work has shown that PTX interacts with and activates TLR4 in the spinal cord, leading to the activation of the NF-κB signaling pathway and the release of pro-inflammatory cytokines, including IL-1β and TNF-α. 41 The link between spinal TLR4 and the production of central and peripheral inflammatory cytokines could contribute to behavioral hypersensitivity following exposure to chemotherapy drugs.…”

Section: Discussionmentioning

confidence: 99%

<p>Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway</p>

Zhao¹,

Yao²,

Li³

et al. 2020

JPR

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Background and Purpose: Neuropathic pain is a major side-effect of paclitaxel (PTX) chemotherapy. Although the precise mechanisms responsible for this pain are unclear, the activation of neuroglia and upregulation of the TLR4/NF-κB pathway are known to be involved. In this study, we determined whether electroacupuncture (EA) could limit mechanical hypersensitivity resulting from the chemotherapeutic drug PTX in rats, and investigated the potential mechanisms involved. Methods: Rats intraperitoneally received a cumulative dose of 8 mg/kg PTX (2 mg/kg per day) or vehicle control on alternate days (day 0, 2, 4 and 6). EA treatment (10 Hz, 1 mA) was applied at bilateral ST36 acupoints in rats once every other day on days 0-14. For sham EA, needles were inserted at ST36 acupoints without electrical stimulation. Mechanical allodynia was measured by mechanical withdrawal latency (MWL) of paws to a mechanical stimulus every 2 days. Protein expression of TLR4 and NF-κB p65, as well as TMEM119 and GFAP (indicators of microglia and astrocytes, respectively) in spinal cord was quantified by Western blot analysis. Levels of inflammatory cytokines IL-1β and TNF-α in spinal cord and serum were detected by ELISA. Results: Mechanical allodynia induced by PTX in both paws (right and left) of rats was significantly attenuated by EA but not sham EA treatment. In addition, EA, but not sham EA, inhibited the activation of both microglia (TMEM119) and astrocytes (GFAP) in lumbar spinal cord. Moreover, Western blot analysis revealed that protein expression of TLR4 and NF-κB in spinal cord was suppressed by EA but not sham EA treatment. PTX significantly increased inflammatory cytokines in spinal cord and serum, which were ameliorated by EA treatment but not by sham EA. Conclusion: These results indicate that EA treatment attenuates PTX-induced mechanical allodynia. The putative mechanism corroborating this finding could be related to the suppression of activated microglia and astrocytes in spinal cord, as well as the inhibition of the activated TLR4/NF-κB signaling pathway by EA treatment.

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Section: Discussionmentioning

confidence: 99%

<p>Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway</p>

Zhao¹,

Yao²,

Li³

et al. 2020

JPR

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“…A previous research disclosed that the drug target of ICA might be related to the increase of cAMP/cGMP ratio (ZHU and LOU, 2006). The related researches uncovered that ICA exerted the antitumor functions mainly in inducing apoptosis and differentiation, prohibiting invasion and metastasis, restraining angiogenesis, and reducing toxicity of radiotherapy and chemotherapy (Yang et al, 2015;Gui et al, 2018;Shi et al, 2014). Among these, the mechanism of SPARC involved in tumorigenesis includes inducing differentiation, inhibiting invasion and metastasis, and restraining angiogenesis of cancer cells (Chen et al, 2012;Ma et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Retracted: Icariin inhibits proliferation, migration, and invasion of medulloblastoma DAOY cells by regulation of SPARC

Yang

2020

Phytotherapy Research

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Icariin (ICA) is obtained from Epimedium brevicornu maxim and exploited to remedy miscellaneous cancers. But the role of ICA in medulloblastoma remains hazy. The research delved into the antitumor activity of ICA in medulloblastoma DAOY cells. ICA with diverse concentrations was utilized to stimulate DAOY cells, and the biological functions of ICA in medulloblastoma DAOY cells were examined. Then, the relative SPARC expression was determined in ICA‐managed DAOY cells, and the pc‐SPARC vector was transfected into DAOY cells to further probe the influence of SPARC and JAK1/STAT3 and PI3K/AKT pathways in ICA‐managed DAOY cells. A xenograft model was established to investigate the function of ICA in vivo. ICA restrained cell viability, expedited apoptosis, prohibited cell migration and invasion, and meanwhile affected the associative factors expression in DAOY cells. Additionally, SPARC expression was declined in ICA‐stimulated DAOY cells. Overexpressed SPARC reversed the functions of ICA in above‐involved cell behaviors of DAYO cells and the correlative protein levels. Besides, ICA notably frustrated JAK1/STAT3 and PI3K/AKT activations in DAOY cells. Beyond that, ICA prohibited tumor formation in vivo. The results concluded that ICA exhibited the antitumor activity in DAOY cells via decreasing SPARC and inactivating JAK1/STAT3 and PI3K/AKT pathways.

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“…A study revealed that HSYA showed neuroprotection through attenuating oxidative stress, inflammatory response, and neural apoptosis (Pei et al, 2017 ). Another study showed that Icariin could be a potential agent for the treatment of paclitaxel-induced neuropathic pain in a SIRT1-dependent manner (Gui et al, 2018 ). Another study suggested that 3,4-DHBA prevented neuronal cell damage by interfering with the increase of Ca 2+ (Ban et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways

Deng

et al. 2018

Front. Pharmacol.

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Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting toxicity of many anti-neoplastic agents, especially paclitaxel, and oxaliplatin. Up to 62% of patients receiving paclitaxel regimens turn out to develop CIPN. Unfortunately, there are so few agents proved effective for prevention or management of CIPN. The reason for the current situation is that the mechanisms of CIPN are still not explicit. Traditional Chinese Medicine (TCM) has unique advantages for dealing with complex diseases. Wen-Luo-Tong (WLT) is a TCM ointment for topical application. It has been applied for prevention and management of CIPN clinically for more than 10 years. Previous animal experiments and clinical studies had manifested the availability of WLT. However, due to the unclear mechanisms of WLT, further transformation has been restricted. To investigate the therapeutic mechanisms of WLT, a metabolomic method on the basis of UPLC- MS was developed in this study. Multivariate analysis techniques, such as principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA), were applied to observe the disturbance in the metabolic state of the paclitaxel-induced peripheral neuropathy (PIPN) rat model, as well as the recovering tendency of WLT treatment. A total of 19 significant variations associated with PIPN were identified as biomarkers. Results of pathway analysis indicated that the metabolic disturbance of pathways of linoleic acid (LA) metabolism and glycerophospholipid metabolism. WLT attenuated mechanical allodynia and rebalanced the metabolic disturbances of PIPN by primarily regulating LA and glycerophospholipid metabolism pathway. Further molecular docking analysis showed some ingredients of WLT, such as hydroxysafflor yellow A (HSYA), icariin, epimedin B and 4-dihydroxybenzoic acid (DHBA), had high affinity to plenty of proteins within these two pathways.

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Icariin, a flavonoid with anti-cancer effects, alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner

Cited by 54 publications

References 30 publications

<p>Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway</p>

<p>Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway</p>

Retracted: Icariin inhibits proliferation, migration, and invasion of medulloblastoma DAOY cells by regulation of SPARC

Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways

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