查找使用阿拉丁产品的科研文献

Assessment of the Effect of Tetrandrine-Loaded Solid Lipid Nanoparticles on Plasma Metabolite Profile Using Metabolomics

Du Chuling,Li Qianwen,Wang Bingyue,Huang Yinghong,Zhang Ronghua,Yang Li,Cai Tiange,Cai Yu

The aim of our study was to characterize the metabolism of Tetrandrine (TET) and Tetrandrine-Loaded Solid Lipid Nanoparticles (TET-SLN). TET-SLN was prepared by high temperature emulsified-low temperature curing method. Composition of prescription was glycerol monostearate, soy lecithin, twain-80 and TET, oil phase organic solvent was anhydrous ethanol. The Box-Behnken response surface analysis determined the optimal prescription: quantity of reagent: 5.71 mg, emulsifier concentration: 3.1%, Soya Lecithin-Glyceryl Monostearate (SL-GMS) ratio: 1.31:1. TET-SLN was translucent liquid and had blue-opalescent obviously. TET-SLN content was determined by High Performance Liquid Chromatography (HPLC) method. Nanoparticles were round or class round solid ball under electron microscopy, and dispersion was good. Particle size was (93.6 ± 2.87) nm, polydispersity index (PDI) was (0.276 ± 0.01), zeta potential was –(18.71 ± 0.85) mV, pH was 7.14. The hemolysis of TET-SLN was measure by rabbit blood, and determined the concentration of injected quality was within 11.42 μg/mL. Ultrafiltration centrifugation method determined encapsulation efficiency and drug loading capacity, encapsulation efficiency was (90.70 ± 0.52)% and drug loading capacity was (1.99 ± 0.01)%. The data indicate that TET-SLN had good physical properties. Finally, we determined the metabolite profile in mice receiving TET-SLN or SLN using Nuclear Magnetic Resonance (NMR). Subsequent Principal Component Analysis (PCA) and Partial Least Squares-Discrimination Analysis (PLS-DA) revealed that both experimental groups were well separated.

Supramolecular solvent-based ultrasound-assisted extraction of fangchinoline and tetrandrine from the roots of Stephaniae tetrandrae

Yingzhen Wang,Bingyue Cao,Shanshan Shi,Shulin Gao,Dandan Ge

A supramolecular solvent (SUPRAS) based ultrasound-assisted extraction method was developed for the extraction of fangchinoline and tetrandrine from Radix Stephaniae tetrandrae. SUPRASs were prepared in aqueous solutions containing hexafluorobutanol (HFB) and alkanols for the first time. HFB was used as a coacervation agent and density-regulating agent for the SUPRAS preparation. The biosurfactants, namely hexanol, octanol, and decanol were selected as the amphiphiles. The possible mechanism of the new SUPRAS formation was studied. The hydrogen-bond and hydrophobic interactions between HFB and alkanols are the main driving forces for the new SUPRAS formation. The crucial parameters influencing the extraction yields of FAN and TET, such as type and content of amphiphile, type and content of coacervation agent, volume of SUPRAS, ultrasound time, and extraction temperature were investigated and optimized. HFB-hexanol SUPRAS was found to be the most effective extraction solvent for the extraction of fangchinoline and tetrandrine from Stephaniae tetrandrae. Under the optimized conditions, HFB-hexanol SUPRAS showed extraction yields of 7.11 and 13.89 mg g-1 for FAN and TET, respectively. The values were higher than those of obtained with other extraction methods. The developed method has a great potential for extracting alkaloids from natural plant materials.

Sequentially Released Liposomes Enhance Anti-Liver Cancer Efficacy of Tetrandrine and Celastrol-Loaded Coix Seed Oil

Yunyan Chen,Ziwei Zhang,Zhilei Qian,Rui Ma,Minna Luan,Yu Sun

Background A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue.Methods TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L.Results TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study.Conclusion Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.

Characterization and Evaluation of a Folic Acid Receptor-Targeted Norcantharidin/Tetrandrine Dual-Drug Loaded Delivery System

Youxiang Xiong,Hongxia Tang,Wenhong Liu,Tingting Zhang,Rui Ma,Chaofeng Mu,Zhihong Zhu,Fanzhu Li

The objective of this study was to construct norcantharidin (NCTD)/tetrandrine (Tet) dual-drug loaded lipid nanoparticles (FA-LP@Tet/(MSNs@NCTD)) based on mesoporous silica nanoparticles (MSNs) for controlling drug release and lowering their systemic toxicity. In this study, MSNs were prepared and used for encapsulating anticancer drug NCTD; then MSNs@NCTD and Tet were loaded into liposomes to construct dual-drug loaded lipid nanoparticles with folic acid (FA) as the targeting moiety. The prepared dual-drug loaded lipid nanoparticles with a uniform particle size distribution of (PDI , zeta potential -), had a visible core-shell structure under transmission electron microscopy; the encapsulation efficiency of NCTD and Tet was 86.62% and 79.19%, respectively, with obvious in vitro sustained release characteristics. The cellular uptake results suggested that FA modification could enhance intracellular distribution of FA-LP@Tet/(MSNs@NCTD). Furthermore, cell apoptosis assays showed FA-LP@Tet/(MSNs@NCTD) had better antitumor ability via reversing multidrug resistance. Therefore, FA-LP@Tet/(MSNs@NCTD) was a promising drug delivery system for combination cancer therapy.

Tetrandrine, a novel inhibitor of ether-à-go-go-1 (Eag1), targeted to cervical cancer development

Xuzhao Wang,Yafei Chen,Junwei Li,Shuai Guo,Xiaoe Lin,Hailin Zhang,Yong Zhan,Hailong An

Mortality-to-incidence ratios in patients with cancer are extremely high, positioning cancer as a major cause of death worldwide. Ether-à-go-go-1 (Eag1) is an ion channel that plays important roles in tumour proliferation, malignant transformation, invasion, metastasis, recurrence, and prognosis. Therefore, identifying potent and specific Eag1 channel inhibitors is crucial. In this study, we identified the first natural inhibitor of Eag1, the traditional Chinese medicine agent tetrandrine, and explored the underlying mechanism. Tetrandrine directly interacted with Eag1 and inhibited the currents in a concentration-dependent manner (IC 50 of 69.97 ± 5.2 μM), and the amino acids Ile 550 , Thr 552 , and Gln 557 in the Eag1 C-linker domain were critical for tetrandrine’s inhibitory effect. Moreover, tetrandrine reduced the proliferation of HeLa cells and Chinese hamster ovary (CHO) cells stably expressing Eag1 in a concentration-dependent manner. Finally, tetrandrine (30 mg/kg/day) inhibited tumor growth in mice, demonstrating a 64.21% inhibitory rate of HeLa cell-transplanted tumors. These results suggest that tetrandrine is a potent and selective Eag1 channel inhibitor, and could act as a leading compound in the development of therapies for Eag1 ion channel dysfunction-induced diseases.

Inhaled biomimetic nanoparticles enhance pulmonary delivery of tetrandrine and pirfenidone for the treatment of idiopathic pulmonary fibrosis

Xinrui Zhang,Ruibing Yu,Xusheng Duan,Tenghan Zhang,Fanyu Cheng,Shan Pan,Dongfang Zhou,Juhong Zhu,Yue Cai,Xuanrong Sun

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease marked by epithelial-mesenchymal transition (EMT) and overactivation of the transforming growth factor-β (TGF-β) signaling pathway, leading to collagen accumulation and macrophage infiltration in the lungs. Here, a bioinspired inhalable nanoplatform (PCMΦ@PPT) was designed and prepared for delivering therapy agents by penetrating the excessive physiological barrier deposited in the lesions and reversing established fibrotic foci in IPF. The nanoplatform was composed of two components: a pirfenidone (PFD) and tetrandrine (TET) co-loaded poly(lactic-co-glycolic acid) (PLGA) core (PPT), as well as a collagen-binding peptide and collagenase functionalized macrophage membrane (PCMΦ) shell. Following inhalation, PCMΦ@PPT has been shown to possess the capacity to target and penetrate the dense collagen barrier with the assistance of functional groups present on PCMΦ. The coating of PCMΦ enables PCMΦ@PPT to evade phagocytosis by macrophages that accumulate at the site of lesions. Meanwhile, the precise co-delivery of PFD and TET to the lesion site not only blocks the TGF-β signaling pathway but also promotes the recovery of damaged autophagy in fibroblasts, thereby alleviating the progression of IPF and partially improved lung function parameters in mice. In summary, this study proposes a novel nano-inhalation formulation for the treatment of IPF. Statement of significance The biomimetic nanoparticle PCMΦ@PPT was designed to recognize and degrade overexpressed extracellular matrix proteins. It is composed of two components: a poly(lactic-co-glycolic acid) core co-loaded with pirfenidone (PFD) and tetrandrine (TET), as well as a collagen-binding peptide and collagenase-functionalized macrophage membrane shell (PCMΦ). Following inhalation, PCMΦ@PPT has been shown to target and penetrate the dense collagen barrier while evading phagocytosis by macrophages, promoting drug retention in the focus. Finally, co-delivery of PFD and TET blocks the TGF-β signaling pathway, promoting recovery of damaged autophagy in fibroblasts and alleviating IPF progression and restoring lung function.

Tetrandrine attenuates the bone erosion in collagen-induced arthritis rats by inhibiting osteoclastogenesis via spleen tyrosine kinase

Yugai Jia,Yumeng Miao,Mengfan Yue,Mei Shu,Zhifeng Wei,Yue Dai

Tetrandrine, a bisbenzylisoquinoline alkaloid, was previously demonstrated to attenuate inflammation and cartilage destruction in the ankles of mice with collagen-induced arthritis (CIA). Here, we explored the underlying mechanism by which tetrandrine prevented arthritis-induced bone erosion by focusing on the differentiation and function of osteoclasts. We found that daily administration of tetrandrine (30 mg/kg) markedly reduced the bone damage and decreased the number of osteoclasts in CIA rats. In vitro , tetrandrine inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis at the early stage and reduced the expressions of osteoclast-related marker genes. In bone marrow-derived macrophages and RAW264.7 cells, tetrandrine inhibited RANKL-induced translocation of NF-κB-p65 and nuclear factor of activated T cell 1 (NFATc1) through suppressing spleen tyrosine kinase (Syk)-Bruton's tyrosine kinase-PLCγ2-Ca 2+ signaling. Of interest, tetrandrine did not affect the phosphorylation of immunoreceptor tyrosine-based activation motifs, the conventional upstream of Syk, but it inhibited the activity of Syk by enhancing its ubiquitination and degradation. The anti–osteoclastogenesis effect of tetrandrine nearly disappeared when it was used in combination with the Syk inhibitor piceatannol or in constitutively activated Syk-overexpressing cells. Taken together, tetrandrine attenuated CIA-induced bone destruction by inhibiting osteoclastogenesis through hindering the translocation of NF-κB-p65 and NFATc1 via reducing the activation of Syk.—Jia Y., Miao, Y., Yue, M., Shu, M., Wei, Z., Dai Y. Tetrandrine attenuates the bone erosion in collagen-induced arthritis rats by inhibiting osteoclastogenesis via spleen tyrosine kinase. FASEB J. 32, 3398–3410 (2018). www.fasebj.org

Tetrandrine and adriamycin reverse multidrug resistance by regulating NLRP3/Caspase-1/GSDMD signaling in human breast cancer cells

Guosong Xin,Yanxiu Hou,Yuhan Liu,Hairu Li

Purpose This study examined the effects and underlying mechanisms of tetrandrine (TET) combined with adriamycin (ADR) in reversing multidrug resistance (MDR) in breast cancer cells. Methods Cell viability, proliferation, and drug resistance were assessed via the MTT assay. Small interfering RNA (siRNA) transfection was used to knock down GSDMD expression in MCF-7/ADR cells. Pyroptosis induction by the combined TET and ADR treatment was evaluated through morphological observations, cytotoxicity assays, and flow cytometry. The expression levels of mRNA and proteins were analyzed using qRT-PCR and western blotting, respectively. Results At non-cytotoxic concentrations, the combined treatment of TET and ADR significantly inhibited the growth of MCF-7/ADR cells, demonstrating a synergistic effect in reversing MDR. This combination effectively reduced MDR protein expression in MCF-7/ADR cells via GSDMD modulation, which diminished efflux activity and promoted ADR accumulation. The increased accumulation of ADR subsequently activated the NLRP3/Caspase-1/GSDMD signaling pathway, leading to elevated LDH release and enhanced pyroptosis rates. Conclusion The combined use of TET and ADR not only suppresses MCF-7/ADR cell growth but also reverses MDR by targeting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These findings propose a promising therapeutic strategy for combatting MDR in breast cancer and highlight the potential for further clinical application of this combination therapy.

Acoustic resonance technology and quality by design approach facilitate the development of the robust tetrandrine nano-delivery system

Xiaoyang Zhang,Xi Wang,Jianlu Qu,Yao Zhang,Cunhao Li,Wei Wu,Wenlong Li

The aim of this study was to develop a sufficiently robust tetrandrine (Tet) nano-delivery system using acoustic resonance (AR) technology and freeze-drying technology. This system can effectively improve the solubility and dissolution properties of Tet, along with high stability and scale-up adaptability. Firstly, 54 stabilizers were screened simultaneously in a high-throughput manner with the help of AR technology to fully explore the optimal prescription space of tetrandrine nanosuspension (Tet-NS). The Plackett-Burman design was used to screen for critical variables severely affecting the quality of Tet-NS. The Box-Behnken design was used to investigate and optimize critical variables to obtain optimal nanosuspensions. The optimal prescription was successfully scaled up by 100 times, which was the initial exploration of its commercial scale production. Solidification studies have shown that formulations with 2.44% fructose as the cryoprotectant have excellent redispersibility. Compared with pure Tet, Tet in Tet-NS showed a significant increase in solubility and dissolution rate in water. Fourier transform infrared (FT-IR) demonstrated that no significant interactions occurred between the drug and excipients in Tet-NS. Powder x-ray diffraction analysis (PXRD) indicated that some of the Tet transformed into amorphous state during the preparation process. In short-term stability study, Tet-NS successfully maintained its physical stability. In summary, under the guidance of the QbD concept, this study rapidly developed Tet-NS using acoustic resonance technology, which can effectively improve the solubility and dissolution properties of Tet. During the development of Tet-NS, AR technology has demonstrated high particle size reduction capability, the ability to process multiple sets of formulations in parallel, and excellent scale-up capability. Meanwhile, the method and concept of this study are not limited to Tet, but also applicable to other poorly water-soluble drugs.

Pharmacokinetic and Pharmacodynamic Study of Folic Acid-Modified Chitosan–Stearic Acid Nanomicelles Loaded with Tetrandrine for Rheumatoid Arthritis

Shuai Ma,Fei Xue,Lan Yang,Long Chen,Pei Liu,Jinhua Chang,Ruxing Wang

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, and it is currently incurable. Tetrandrine (TET) has an obvious curative effect with therapeutic efficacy on RA, but its use is limited due to its poor water-solubility and bioavailability. Therefore, TET-loaded nanomicelles modified with chitosan, stearic acid, and folic acid (FCST) was prepared in the study, and the pharmacokinetics and pharmacodynamics were studied. Methods: The plasma concentrations of FCST and TET were measured by the PLC-MS/MS method at different times, and the pharmacokinetic parameters were calculated. A collagen-induced arthritis (CIA) model was established with rats. On the 16th day after the first immunization, 50 rats were randomized into five groups with 10 rats in each group according to the arthritis score. The drugs were administered by intraperitoneal injection for 30 days. The swelling degree and joint score of the rats were tested during each administration. In addition, the pro-inflammatory factors IL-1β, IL-6, IL-17, and TNF-α in the serum of the rats were tested by an ELISA kit, and their joints were examined by histopathology. Results: Pharmacokinetic studies showed that the AUC0–72hof FCST was 1.93 times that of TET. FCST demonstrated higher bioavailability compared to TET (p< 0.05). Pharmacodynamic studies demonstrated that FCST had significant anti-inflammatory effects, and its anti-inflammatory activity was stronger compared to the same dose of TET, as evidenced by measuring toe thickness and observing toe appearance. It significantly reduced the expression of IL-1, IL-6, IL-17, and TNF-α in rats with rheumatoid arthritis (p< 0.05). Conclusions: FCST can significantly improve bioavailability and has a significant therapeutic effect on rheumatoid arthritis.

Study on preparation, characterization and multidrug resistance reversal of red blood cell membrane-camouflaged tetrandrine-loaded PLGA nanoparticles

Xiao Que,Jing Su,Pengcheng Guo,Zul Kamal,Enge Xu,Siyu Liu,Jieyu Chen,Mingfeng Qiu

Ursolic acid alleviates tetrandrine-induced hepatotoxicity by competitively binding to the substrate-binding site of glutathione S-transferases

Simeng Chu,Yujie Lu,Wenjuan Liu,Xiaoyao Ma,Jiamin Peng,Xiaoying Wang,Min Jiang,Gang Bai

Background Tetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra S. Moore, is the only approved medicine in China for silicosis. However, TET-induced hepatotoxicity has raised safety concerns. The underlying toxic targets and mechanism induced by TET remain unclear; there are no targeted detoxification strategies developed for TET-induced hepatotoxicity. Ursolic acid (UA), a pentacyclic triterpene with liver protective effects, may have detoxification effects on TET-induced hepatotoxicity. Purpose This study aims to explore toxic targets and mechanism of TET and present UA as a potential targeted therapy for alleviating TET-induced hepatotoxicity. Methods A TET-induced liver-injury model was established to evaluate TET toxicity and the potential UA detoxification effect. Alkenyl-modified TET and UA probes were designed to identify potential liver targets. Pharmacological and molecular biology methods were used to explore the underlying toxicity/detoxification mechanism. Results TET induced liver injury by covalently binding to the substrate-binding pocket (H-site) of glutathione S-transferases (GSTs) and inhibiting GST activity. The covalent binding led to toxic metabolite accumulation and caused redox imbalance and liver injury. UA protected the liver from TET-induced damage by competitively binding to the GST H-site. Conclusion The mechanism of TET-induced hepatotoxicity is related to irreversible binding with the GST H-site and GST-activity inhibition. UA, a natural antidote, competed with TET on H-site binding and reversed the redox imbalance. This study revealed the hepatotoxic mechanism of TET and provided a targeted detoxifying agent, UA, to alleviate hepatotoxicity caused by GST inhibition.