Honokiol Downregulates Kruppel-Like Factor 4 Expression, Attenuates Inflammation, and Reduces Histopathology After Spinal Cord Injury in Rats

Liu, Jia; Zhang, Changmeng; Liu, Zhi; Zhang, Jianzheng; Xiang, Zimin; Sun, Tiansheng

doi:10.1097/brs.0000000000000758

Cited by 27 publications

(23 citation statements)

References 30 publications

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“…According to the effective therapeutic dose range of honokiol reported in previous studies, a dose of 20 mg/kg (equal to 0.18-0.25 mL of NHNK depending on the weight of individual mouse) was employed in the present study. 15,37 As the encapsulation rate of NHNK was 58.1%, the realistic dose of honokiol carried by nanosomes was 11.6 mg/kg. The immunized mice were randomly distributed into different treatment groups on day 18 and intravenously injected with NHNK (n = 19) or empty nanosomes (vehicle control, NSE; n = 19) twice a week for 3 weeks.…”

Section: Mog-induced Eae and Nhnk Treatmentmentioning

confidence: 99%

“…Honokiol, a natural hydrophobic phytochemical extracted from the Chinese herb Houpu, has been traditionally used to treat many mental and neurological disorders. 12 It has been well documented that honokiol exerts several pharmacological activities, including anti-anxiety, 13 anti-hyperalgesia, 14 anti-inflammation, 15 anti-oxidation, 16 anti-senescence, 17 and neuroprotection. 18 In mouse models, honokiol treatment could ameliorate the symptoms of allergic asthma, postoperative ileus and arthritis by reducing the production of inflammation-related factors, such as TNF, IL-6, and IFN-γ.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21] Intraperitoneal administration of honokiol could attenuate motor dysfunction in hemiparkinsonian mice and neuronal degeneration in mice with traumatic spinal cord injury. 15,22 Additionally, mechanistic investigation revealed that honokiol influenced the activation of microglial cells by modulating the production of nitric oxide (NO), pro-inflammatory and anti-inflammatory cytokines. 23 These results suggest that honokiol is a promising phytochemical to be developed as a potential anti-inflammatory and neuroprotective agent against inflammatory CNS diseases.…”

Section: Introductionmentioning

confidence: 99%

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<p>Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis</p>

Hsiao¹,

Chen²,

Liang³

et al. 2020

IJN

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Background: Honokiol has been reported to possess anti-inflammatory and neuroprotective activities. However, the poor aqueous solubility of honokiol limits its clinical application for systemic administration. Purpose: This study aims to develop a novel formulation of nanosome-encapsulated honokiol (NHNK) for intravenous therapy against mouse experimental autoimmune encephalomyelitis (EAE) that mimics human multiple sclerosis. Methods: Nanosomes and NHNK were prepared by using an ultra-high pressure homogenization (UHPH) method. Mice were treated with NHNK or empty nanosomes during the peak phase of EAE symptoms. Symptoms of EAE were monitored and samples of the spinal cord were obtained for histopathological examinations. Results: The stock of NHNK containing honokiol in the nanosome formulation, which showed the structure of single phospholipid bilayer membranes, was well formulated with the particle size of 48.0 ± 0.1 nm and the encapsulation efficiency 58.1 ± 4.2%. Intravenous administration of NHNK ameliorated the severity of EAE accompanied by a significant reduction of demyelination and inflammation in the spinal cord. Furthermore, NHNK decreased the number of IL-6 + , Iba-1 + TNF + , Iba-1 + IL-12 p40 + , and CD3 + IFN-γ + cells infiltrating the spinal cord. Conclusion: The UHPH method simplified the preparation of NHNK with uniformly distributed nanosize and high encapsulation efficiency. Intravenous administration of NHNK ameliorated the severity of EAE by suppressing the infiltration of activated microglia and Th1 cells into the spinal cord. Collectively, these results suggest that the formulation of NHNK is a prospective therapeutic approach for inflammatory CNS diseases, such as multiple sclerosis.

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Section: Mog-induced Eae and Nhnk Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

<p>Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis</p>

Hsiao¹,

Chen²,

Liang³

et al. 2020

IJN

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“…The score representing severity of SCI was recorded as follows: 0, none or minor; 1, limited; 2, intermediate; 3, prominent; and 4, widespread. 21 …”

Section: Histological Studymentioning

confidence: 99%

Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury

et al. 2016

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Study design: Randomized experimental study. Objectives: To investigate the molecular mechanisms of quercetin in spinal cord injury (SCI) rats. Setting: China. Methods: One hundred female Sprague-Dawley rats were randomly assigned into four groups: sham group, SCI group, SCI+Vehicle (Veh) group, and the SCI+Quercetin (Que) group. The influences of quercetin on proinflammatory cytokine levels, histological changes and locomotion scale were estimated. Results: SCI significantly promoted nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation and increased proinflammatory cytokine productions in the SCI group as compared with the sham group. Quercetin administration significantly decreased reactive oxygen species production, inhibited NLRP3 inflammasome activation and reduced inflammatory cytokine levels. Moreover, quercetin administration attenuated histopathology and promoted locomotion recovery. Conclusion: Quercetin can attenuate tissue damage and improve neurological function recovery, and the mechanism may be related to the inhibition of NLRP3 inflammasome activation.

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“…30 MZF1 is involved in myeloid cell differentiation 31 and is a strong enhancer of cell migration and invasion, 32 thus potentially explaining the origin of the strong CA4 expression in neutrophils. KLF4, in turn, has been shown to be expressed during inflammation 33 and wound healing 34, 35, 36, 37 , and to facilitate cutaneous wound healing. 36 …”

Section: Discussionmentioning

confidence: 99%

Role of carbonic anhydrases in skin wound healing

et al. 2017

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Skin wound closure occurs when keratinocytes migrate from the edge of the wound and re-epithelialize the epidermis. Their migration takes place primarily before any vascularization is established, that is, under hypoxia, but relatively little is known regarding the factors that stimulate this migration. Hypoxia and an acidic environment are well-established stimuli for cancer cell migration. The carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton. On this basis, we explored the possible role of CAs in tissue regeneration using mouse skin wound models. We show that the expression of mRNAs encoding CA isoforms IV and IX are increased (~25 × and 4 ×, respectively) during the wound hypoxic period (days 2–5) and that cells expressing CAs form a band-like structure beneath the migrating epidermis. RNA-Seq analysis suggested that the CA IV-specific signal in the wound is mainly derived from neutrophils. Due to the high level of induction of CA IV in the wound, we treated skin wounds locally with recombinant human CA IV enzyme. Recombinant CA IV significantly accelerated wound re-epithelialization. Thus, CA IV could contribute to wound healing by providing an acidic environment in which the migrating epidermis and neutrophils can survive and may offer novel opportunities to accelerate wound healing under compromised conditions.

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Honokiol Downregulates Kruppel-Like Factor 4 Expression, Attenuates Inflammation, and Reduces Histopathology After Spinal Cord Injury in Rats

Abstract: NA.

Cited by 27 publications

References 30 publications

<p>Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis</p>

<p>Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis</p>

Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury

Role of carbonic anhydrases in skin wound healing

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