JOURNAL OF MICROENCAPSULATION
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2019
·
IF 2.04
Ran Li,Rui Bao,Qiu-Xuan Yang,Qi-Long Wang,Michael Adu-Frimpong,Qiu-Yu Wei,Toreniyazov Elmurat,Hao Ji,Jiang-Nan Yu,Xi-Ming Xu
Aims: The aim was to improve the absorption and bioavailability of [6]-shogaol with β-cyclodextrin (β-CD) prior to in vitro and in vivo evaluation.Methods: [6]-Shogaol/β-CDs inclusion complexes (6-S-β-CDs) were developed using saturated aqueous solution method and characterised with appropriate techniques. The absorption and bioavailability potential of [6]-shogaol was evaluated via in vivo pharmacokinetics and in situ intestinal perfusion.Results: The results of characterisation showed that 6-S-β-CDs (drug loading, 7.15%) were successfully formulated. In vitro release study indicated significantly improved [6]-shogaol release. Pharmacokinetic parameters such as Cmax, AUC0–36 h, and oral relative bioavailability (about 685.36%) were substantially enhanced. The in situ intestinal perfusion study revealed that [6]-shogaol was markedly absorbed via passive diffusion in the intestinal segments, and duodenum followed by ileum and jejunum.Conclusions: Cyclodextrin inclusion technology could enhance the intestinal absorption and oral bioavailability of hydrophobic drugs like [6]-shogaol.
研究领域:
药剂学
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药物代谢动力学
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生物医学工程
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DOI
PubMed
高影响因子
Pharmaceutics
·
2019
·Vol. 11
·期 3
·107
·
IF 4.773
Huiyun Zhang,Qilong Wang,Congyong Sun,Yuan Zhu,Qiuxuan Yang,Qiuyu Wei,Jiaxin Chen,Wenwen Deng,Michael Adu-Frimpong,Jiangnan Yu,Ximing Xu
6-shogaol is a promising anti-cancer and anti-inflammatory agent. However, the treatment effectiveness of 6-shogaol is limited by poor water solubility, poor oral absorption and rapid metabolism. Herein, 6-shogaol loaded in micelles (SMs) were designed to improve 6-shogaol’s solubility and bioavailability. The micelles of a PEG derivative of linoleic acid (mPEG2k-LA) were prepared by the nanoprecipitation method with a particle size of 76.8 nm, and entrapment of 81.6 %. Intriguingly, SMs showed a slower release in phosphate buffer saline (PBS) (pH = 7.4) compared to free 6-shogaol while its oral bioavailability increased by 3.2–fold in vivo. More importantly, the in vitro cytotoxic effect in HepG2 cells of SMs was significantly higher than free 6-shogaol. Furthermore, SMs could significantly improve the tissue distribution of 6-shogaol, especially liver and brain. Finally, SMs showed a better hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo than free 6-shogaol. These results suggest that the novel micelles could potentiate the activities of 6-shogaol in cancer treatment and hepatoprotection.Keywords:6-shogaol;cytotoxic effect;HepG2 cells;micelles;hepatoprotection
研究领域:
药学
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肿瘤学
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肝病学
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产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
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2019
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IF 2.367
Qiuxuan Yang,Qilong Wang,Yingshu Feng,Qiuyu Wei,Congyong Sun,Caleb Kesse Firempong,Michael Adu-Frimpong,Ran Li,Rui Bao,Elmurat Toreniyazov,Hao Ji,Jiangnan Yu,Ximing Xu
The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger (Zingiber officinale Roscoe), has been proved to possess diverse pharmacological activities. However, its poor aqueous solubility usually leads to low bioavailability, and further clinical applications will be greatly discounted. The current study aimed to formulate a 6-shogaol-loaded-Self Microemulsifying Drug Delivery System (SMEDDS) to amend low aqueous solubility and bioavailability orally, as well as, potentiate the hyperuricemic activity of the 6-shogaol. SMEDDS was developed with central composite design established on a two system components viz., 18.62% W/W ethyl oleate (oil phase) and ratio of tween 80 (surfactant) to PEG 400 (co-surfactant) (1.73:1, W/W). Based on quadratic model, the navigation of the design space could generate spherically-shaped and homogenous droplets with respective mean particle diameter, polydispersity and of 20.00 ± 0.26 nm and 0.18 ± 0.02. The 6-shogaol-SMEDDS showed significant elevation of cumulative release compared with the free 6-shogaol and more importantly a 571.18% increment in the relative oral bioavailability of the drug. The predominant accumulation of 6-shogaol-SMEDDS in the liver suggested hepatic-targeting potentiality of the drug. Oral administration of 6-shogaol-SMEDDS in hyperuricemic rats also significantly decreased uric acid level and xanthine oxidase activity. Histological studies confirmed formulation groups indeed could provide better protection of kidney than free drug groups. Collectively, these findings indicated that the SMEDDS hold much promise in enhancing the oral delivery and therapeutic efficacy of 6-shogaol.
研究领域:
药剂学
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代谢病学
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中药学
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DOI
PubMed
高影响因子
RSC Advances
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2018
·Vol. 8
·期 72
·41368-41375
·
IF 2.936
Liangliang He,Jinjin Xu,Qi Wang,Yezi Zhang,Zifei Qin,Yang Yu,Zhengming Qian,Zhihong Yao,Xinsheng Yao
Shogaols, mainly [6]-shogaol (6S), [8]-shogaol (8S) and [10]-shogaol (10S), the predominant and characteristic pungent phytochemicals in ginger, are responsible for most of its beneficial effects. However, poor oral bioavailability owing to extensive glucuronidation limits their application. The present study aimed to characterize the glucuronidation pathways of 6S, 8S and 10S by using pooled human liver microsomes (HLM), human intestine microsomes (HIM) and recombinant human UDP-glucosyltransferases (UGTs). The rates of glucuronidation were determined by incubating shogaols with uridine diphosphate glucuronic acid-supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. Reaction phenotyping assays, activity correlation analyses and relative activity factors were performed to identify the main UGT isoforms. As a result, one mono-4′-O-glucuronide was detected after incubating each shogaol with HLM and HIM. Enzymes kinetic analysis demonstrated that glucuronidation of shogaols consistently displayed the substrate inhibition profile, and the liver showed higher metabolic activity for shogaols (CLint = 1.37–2.87 mL min−1 mg−1) than the intestine (CLint = 0.67–0.85 mL min−1 mg−1). Besides, reaction phenotyping assays revealed that UGT2B7 displayed the highest catalytic ability (CLint = 0.47–1.17 mL min−1 mg−1) among all tested UGTs. In addition, glucuronidation of shogaols was strongly correlated with AZT glucuronidation (r = 0.886, 0.803 and 0.871 for glucuronidation of 6S, 8S and 10S, respectively; p < 0.01) in a bank of individual HLMs (n = 9). Furthermore, UGT2B7 contributed to 40.8%, 34.2% and 36.0% for the glucuronidation of 6S, 8S and 10S in HLM, respectively. Taken altogether, shogaols were efficiently metabolized through the glucuronidation pathway, and UGT2B7 was the main contributor to their glucuronidation.
研究领域:
药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2022
·
IF 2.65
Bin Wang,Xiaoxuan Fan,Qianwen Sun,Qingxiang Zhang,Yue Kong,Qingyan Meng,Dongsheng Zhao,Beibei Mao,Yan Liu,Pan Zhao,Lu Zhang,Peizheng Yan
Asthma is a common chronic respiratory disease characterized by wheezing and shortness of breath. Its risk factors include genetic and acquired factors. The acquired factors are closely related to the environment, especially cold conditions. Autophagy plays a regulatory role in asthma. Therefore, we hypothesized that asthma can be controlled by drug intervention at the autophagy level under cold conditions. The Xiaoqinglong decoction (XQLT) was freeze-dried. The compounds in the freeze-dried powder were identified and quantified using reference standards via the high-performance liquid chromatography method. Ovalbumin (OVA)-sensitized rats were subjected to cold stimulation. The effect of cold stimulation on autophagy levels was determined, and it was confirmed that cold stimulation affected autophagy. The effects and mechanisms of XQLT in an asthmatic rat model (OVA-sensitized rats stimulated with cold) were explored. The concentrations of paeoniflorin, liquiritin, trans-cinnamic acid, glycyrrhizic acid, 6-gingerol, schisandrol A, and asarinin in XQLT freeze-dried powder were 14.45, 3.85, 1.03, 3.93, 0.59, 0.24, and 0.091 mg/g, respectively. Cold stimulation is an important cause of asthma. The inflammatory factors in bronchoalveolar lavage fluid and serum were increased in the model group, accompanied by a decline in autophagy level. The treatment with XQLT increased the expression of autophagy genes and decreased the expression of inflammatory factors. Histological studies showed that XQLT improved inflammatory infiltration and collagen fiber deposition in the lungs of rats. XQLT intervention increased autophagy in asthmatic rats. Autophagy plays a role in phagocytosis and reduces the accumulation of abnormal metabolites in the body to reduce airway inflammation and promote asthma recovery.
研究领域:
药理学
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呼吸医学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA POLONICA
·
2022
·Vol. 69
·期 2
·363-370
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IF 2.349
Jian-li Qiu,Yu-na Chai,Feng-yang Duan,Hui-juan Zhang,Xiao-yan Han,Ling-yan Chen,Fei Duan
Liver fibrosis is a global health problem caused by a number of diseases related to liver damage. 6-Shogaol is a biologically active substance derived from the rhizome of Zingiber officinale Roscoe with anti-tumor, anti-inflammatory, and antioxidant properties. To explore the effects of 6-Shogaol on liver fibrosis, we used a mouse model of the condition in which mice were injected intraperitoneally with carbon tetrachloride (CCl4) at a dose of 2 mL/kg three times per week for a period of 4 weeks. 6-Shogaol was administered orally at two different doses (5 mg/kg, 20 mg/kg) 30 min before CCl4 injection. CCl4 induced severe liver injury and fibrosis, as indicated by significant inflammatory cell infiltration, disordered liver structure, increased activities of aspartate aminotransferase and alanine aminotransferase (liver damage markers) in serum, elevated collagen deposition, and overexpressed alpha-smooth muscle actin (α-SMA, marker of hepatic stellate cells activation) in liver tissues, whereas 6-Shogaol administration rescued those alterations dose-dependently. We found that 6-Shogaol suppressed CCl4-induced inflammatory response by inhibiting macrophage recruitment, release of pro-inflammatory factors, and activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in liver tissues. Additionally, we demonstrated that 6-Shogaol blocked CCl4-induced activation of the nuclear factor-kappa B (NF-κB) pathway, which is a vital transcriptional regulator of the inflammatory response. Altogether, this study demonstrates that 6-Shogaol can prevent CCl4-induced liver fibrosis by suppressing inflammatory response through the NF-κB pathway and suggests that 6-Shogaol can be used for liver fibrosis prevention.
研究领域:
药理学
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肝病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2023
·
IF 3
Ping Huang,Bailu Duan,Deshun Li,Yanfen Duan,Zhenxiang Zhou,Lintao Han,Jingjing Li,Jiajia Wu,Yan Ye,Fengyun Zhang,Ziwen Guo,Qiong Wang,Fang Huang
Xixin-Ganjiang Herb Pair (XGHP), a classic combination treatment to warm the lungs and dissolve phlegm, is widely used in the treatment of various pulmonary diseases. Chronic obstructive pulmonary disease (COPD) refers to a group of chronic obstructive airway diseases that can seriously harm human health. However, the effective components, targets, and pathways that underlie XGHP in the treatment of COPD remain unclear. Therefore, this study initially identified the effective components of XGHP through the use of UPLC–MS/MS and pharmacologic methods of traditional Chinese medicine. Secondly, transcriptomic analysis of the lung tissues of rats revealed the pharmacodynamic transcripts of each group, and metabolomics analysis revealed the differential metabolites associated with XGHP treatment. Finally, molecular docking of effective components with transcriptome genes was performed and western blotting was performed in order to determine the expression of related proteins in rat lung tissue. Overall, 30 effective components of XGHP were identified, including L-asarinin, 6-gingerol, sesamin, kaempferol, and quercetin. Transcriptomic studies demonstrated that expression of 386 genes recovered after XGHP treatment, and that they were mainly enriched in the oxidative phosphorylation and AMPK signaling pathways. According to the metabolomics studies, expression of eight metabolites differed between the COPD and the XGHP groups. These metabolites were mainly involved the biosynthesis of unsaturated fatty acids. Finally, the transcriptomic and metabolomics data were integrated. FASN and SCD in AMPK signaling pathway were directly linked to certain metabolites, including linoleic acid, palmitic acid, and oleic acid. These results indicate that XGHP can inhibit pAMPK expression and negatively regulate FASN and SCD expression during treatment of COPD in order to enhance the biosynthesis of unsaturated fatty acids and maintain energy homeostasis.
研究领域:
药理学
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分子生物学
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中医药学
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慢性肺部疾病
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）