The research on the anti-inflammatory activity and hepatotoxicity of triptolide-loaded solid lipid nanoparticle

Mei, Zhinan; Li, Xiaokuan; Wu, Qingqing; Hu, Sheng; Yang, Xiangliang

doi:10.1016/j.phrs.2004.10.007

Cited by 135 publications

(69 citation statements)

References 24 publications

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“…In vivo and in vitro experiments have demonstrated that triptolide has a role in numerous immune disorders, including multiple sclerosis, colitis, lupus nephritis and transplant rejection (6,15,16). The anti-inflammatory activity of triptolide not only activates immune cells, such as T cells and monocytes, Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model but also resident tissue cells (17,18). In the present study, the anti-inflammatory effects of triptolide were investigated, and the mechanisms underlying the action of triptolide in ALI were explored.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model

Xian

Zhang

Duan

et al. 2014

Molecular Medicine Reports

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Abstract.Triptolide is one of the main active components in the Chinese herb Tripterygium wilfordii Hook F, which has been demonstrated to possess anti-inflammatory properties. The aim of this study was to investigate the effects of triptolide on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and to explore the possible mechanisms. Mice were administered LPS intranasally to induce lung injury, and triptolide was administered intraperitoneally 1 h prior to the LPS challenge. Triptolide-treated mice exhibited significantly reduced levels of leukocytes, myeloperoxidase activity and edema of the lung, as well as tumour necrosis factor-α, interleukin (IL)-1β and IL-6 production in the bronchoalveolar lavage fluid compared with LPS-treated mice. Additionally, western blot analysis showed that triptolide inhibited the LPS-induced phosphorylation of nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor-α and nuclear factor κ-light-chain-enhancer of activated B cells-p65 (NF-κB p65) and the expression of Toll-like receptor 4 (TLR4). In conclusion, the results from the present study suggest that the anti-inflammatory effect of triptolide against LPS-induced ALI may be due to its ability to inhibit the TLR4-mediated NF-κB signalling pathway. Triptolide may therefore be a promising potential therapeutic agent for ALI treatment, which may ultimately aid the clinical therapy for patients with ALI.

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Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model

Xian

Zhang

Duan

et al. 2014

Molecular Medicine Reports

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“…The Chinese herbal medicine Tripterygiumwilfordii Hook F, also called Lei gong teng in a Chinese, is used for the treatment of various illnesses for centuries in China (Cameron et It is generally known that triptolide has a narrow therapeutic window and could caused severe toxicity, such as significant hepatotoxicity and reproductive toxicity (Liu et al, 2010;Ni et al, 2008;Mei et al, 2005), which limits its application.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Interaction Between Triptolide and Bovine Serum Albumin (Bsa) by Spectroscopic and Molecular Modeling Methods

Wang¹,

Shi²,

Pang³

et al. 2016

Afr J Tradit Complement Altern Med

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Background: Triptolide is a major active constituent isolated from Tripterygiumwilfordii Hook F, a Chinese herbal medicine. This study investigated the intermolecular interaction between triptolide and bovine serum albumin (BSA). Materials and Methods:The fluorescence, circular dichroism (CD) and molecular docking methods were used to investigate the intermolecular interaction between triptolide and BSA. The binding constant, the number of binding sites, binding subdomain and the thermodynamic parameters were measured. Results: The results of this experiment revealed that the intrinsic fluorescence of BSA was effectively quenched by triptolide via static quenching. The experimental results of synchronous fluorescence and CD spectra showed that the conformation of BSA was changed in the presence of triptolide. Conclusion: It indicated that triptolide could spontaneously bind on site II (subdomain IIIA) of BSA mainly via hydrogen bonding interactions and Van der Waals force.

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“…17,18 In addition, we investigated the influence of SLNs on the toxicity of TP previously. 19,20 Thus, in this work, the characteristics of TP-NLCs (particle size, morphology, encapsulation efficiency, and stability), in vitro release, in vivo pharmacokinetics, and subacute toxicity in male rats were examined and compared, using the optimized TP-loaded SLNs (TP-SLNs) as a contrast.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously studied the protective effect of TP-SLNs against the liver toxicity of TP (400 µg/kg) in male mice. 19 TPNLCs and TP-SLNs can also reduce the liver toxicity of TP (500 µg/kg) in male rats (Figure 9). However, at high doses (650 µg/kg), only TP-NLCs had a significant protective effect on the liver, spleen, and kidneys (Figures 9 and 11).…”

mentioning

confidence: 96%

Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats

Zhang¹,

Fan²,

Liu³

et al. 2014

IJN

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After oral administration in rodents, triptolide (TP), a diterpenoid triepoxide compound, active as anti-inflammatory, immunosuppressive, anti-fertility, anti-cystogenesis, and anticancer agent, is rapidly absorbed into the blood circulation (from 5.0 to 19.5 minutes after dosing, depending on the rodent species) followed by a short elimination half-life (from about 20 minutes to less than 1 hour). Such significant and rapid fluctuations of TP in plasma likely contribute to its toxicity, which is characterized by injury to hepatic, renal, digestive, reproductive, and hematological systems. With the aim of prolonging drug release and improving its safety, TP-loaded nanostructured lipid carriers (TP-NLCs), composed of Compritol® 888 ATO (solid lipid) and Capryol™ 90 (liquid lipid), were developed using a microemulsion technique. The formulated TP-NLCs were also characterized and in vitro release was evaluated using the dialysis bag diffusion technique. In addition, the pharmacokinetics and toxicology profiles of TP-NLCs were compared to free TP and TP-loaded solid lipid nanoparticles (TP-SLNs; containing Compritol 888 ATO only). Results demonstrate that TP-NLCs had mean particle size of 231.8 nm, increased drug encapsulation with a 71.6% efficiency, and stable drug incorporation for over 1-month. TP-NLCs manifested a better in vitro sustained-release pattern compared to TP-SLNs. Furthermore, TP-NLCs prolonged mean residence time (MRT) 0–t ( P <0.001, P <0.001), delayed T max ( P <0.01, P <0.05) and decreased C max ( P <0.01, P <0.05) compared to free TP and TP-SLNs, respectively, which was associated with reduced subacute toxicity in male rats. In conclusion, our data suggest that TP-NLCs are superior to TP-SLNs and could be a promising oral delivery system for a safer use of TP.

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The research on the anti-inflammatory activity and hepatotoxicity of triptolide-loaded solid lipid nanoparticle

Cited by 135 publications

References 24 publications

Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model

Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model

Studies on the Interaction Between Triptolide and Bovine Serum Albumin (Bsa) by Spectroscopic and Molecular Modeling Methods

Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats

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