CRYSTENGCOMM
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2017
·Vol. 19
·期 41
·6154-6163
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IF 3.474
Hongyan He,Qi Zhang,Jian-Rong Wang,Xuefeng Mei
It was reported that the alkaloid component piperine (Pip) can drastically improve the bioavailability of the compound resveratrol (RSV) when co-administered. Therefore, cocrystallization experiments of RSV and Pip were attempted, and four cocrystals are successfully obtained from solution evaporation experiments. Their single crystals are acquired and the structural determination reveals that all the cocrystals contain solvent molecules within the crystals. Confirmed by VT-PXRD, the cocrystals transformed into the amorphous state after desolvation. Considering the toxicity of the solvent molecule, only RSV–Pip co-1 was utilized for further dissolution and pharmacokinetic experiments. The dissolution results demonstrate that RSV–Pip co-1 shows lower dissolution and apparent solubility than the RSV constituent under different buffers in the presence of different surfactants. The reduced dissolution and apparent solubility have a strong diminishing impact on the absorption of RSV, thus leading to unfavorable bioavailability, even though the coformer Pip possesses bioenhancer properties.
研究领域:
药物化学
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药理学
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生物化学
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DOI
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Jiahao Li,Sharon Shui Yee Leung,Edwin Ho Yin Chan,Cuiping Jiang,Evelyn Tze Yin Ho,Zhong Zuo
Introduction Piperine, the major component in Piper retrofractum and Piper nigrum, had potential therapeutic effects on central nervous system diseases such as Alzheimer’s disease, Parkinson’s disease, epilepsy and fragile X-associated tremor/ataxia syndrome. However, its low aqueous solubility (0.04 mg/mL) limits brain uptake and pharmacological investigations at higher doses. In the current study, formulation strategies and routes of administration were assessed to enhance systemic and brain uptake of piperine.Methods Formulation of piperine nanoparticles (PIP NPs) was developed to enhance its solubility. PIP NPs were prepared using flash nanoprecipitation via a four-stream Multi-Inlet Vortex Mixer, employing an aqueous solution of poloxamer 188 and an ethanolic solution containing piperine and Eudragit L100-55. The process was optimized using the Design of Experiments to minimize the particle size and maximize the encapsulation efficiency of piperine. Additionally, we investigated the impact of administrating PIP NPs via oral and intranasal routes on its systemic and brain uptake.Results The optimized PIP NPs formulation exhibited a particle size of 171.45±2.38 nm, polydispersity index of 0.27±0.01, zeta potential of −43.71±5.11 mV, encapsulation efficiency of 92.49±1.92% and drug loading of 15.07±0.09%. Fourier-transform infrared spectroscopy confirmed the successful encapsulation of piperine into nanoparticles. The PIP NPs could significantly increase the aqueous solubility of piperine from 0.04 mg/mL to 52.31±0.9 mg/mL and release piperine with a 12.83-fold higher rate than that from piperine suspension. Both oral and intranasal administrations of PIP NPs to C57BL/6 mice at 20 mg/kg demonstrated an increase in AUC0-120min for both plasma (7.9–10 times) and brain (4.7–5.0 times) comparing to that from piperine suspension, with no significant difference between these two routes.Discussion Our findings suggested that increasing solubility rather than changing the administration route served as the most critical step to enhance the brain uptake of piperine.
研究领域:
药剂学
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神经科学
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药物代谢动力学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 1
·94
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IF 6.525
Yanjie Liu,Fan Yang,Xiuhua Zhao,Siying Wang,Qilei Yang,Xiaoxue Zhang
Hesperetin (HES) is a key biological active ingredient in citrus peels, and is one of the natural flavonoids that attract the attention of researchers due to its numerous therapeutic bioactivities that have been identified in vitro. As a bioenhancer, piperine (PIP) can effectively improve the absorption of insoluble drugs in vivo. In the present study, a cocrystal of HES and PIP was successfully obtained through solution crystallization. The single-crystal structure was illustrated and comprehensive characterization of the cocrystal was conducted. The cocrystal was formed by two drug molecules at a molar ratio of 1:1, which contained O–H–O hydrogen bonds between the carbonyl and ether oxygen of PIP and the phenolic hydroxyl group of HES. In addition, a solubility experiment was performed on powder cocrystal in simulated gastrointestinal fluid, and the result revealed that the cocrystal improves the dissolution behavior of HES compared with that of the pure substance. Furthermore, HES’s bioavailability in the cocrystal was six times higher than that of pristine drugs. These results may provide an efficient oral formulation for HES.Keywords:hesperetin;piperine;cocrystal;solubility;bioavailability
研究领域:
药学
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药理学
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化学
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DOI
PubMed
高影响因子
JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY
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2020
·Vol. 96
·期 3
·233-243
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IF 1.56
Liu Kai,Liu Huijun,Li Zhendong,Li Wei,Li Liuxing
The co-evaporation method was used to synthesize the EN-β-CD@Piperine inclusion complex with a molar ratio of 1:1. The properties and structures of the inclusion complex were characterized by various methods to investigate the inclusion mode and interactions between host and guest. The results of molecular modeling were theoretically analyzed to determine the inclusion mechanism of inclusion complexes. Finally, the vitro dissolution release studies showed that the water solubility of piperine was significantly enhanced when EN-β-CD was combined with piperine. Therefore, the EN-β-CD@Piperine inclusion complex provides a promising development for the clinical application of piperine in the future.
研究领域:
药剂学
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药物化学
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产品关联
DOI
高影响因子
Food & Function
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2023
·Vol. 14
·期 14
·6422-6431
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IF 6.1
Di Wu,Xia Hu,Zhangyu Cai,Jing Zhang,Fang Geng,Hui Li
It has been reported in many studies that piperine (PIP) has multiple activity properties, the most prominent of which is antioxidant activity. This work reports the binding behavior and antioxidant activity of the spice extract piperine towards myoglobin (Mb) using spectroscopic and fluorescence spectra analysis, and computational approaches. Antioxidant activity studies have shown that the antioxidant effect of the Mb–PIP complex system depends on the concentration of PIP added. An appropriate concentration of PIP can successfully prevent the release of free iron from Mb. The fluorescence results indicated that the binding of PIP to Mb was via static quenching. After binding to PIP, the α-helix content of Mb decreased by about 5%. Synchronous fluorescence results indicate that PIP is closer to Trp, and MD simulations also demonstrate that PIP enters the hydrophobic cavity of Mb and binds stably. This explains the structural changes in proteins that lead to changes in antioxidant properties. The results of this study provide a reference for the quality control of additives of plant origin in the processing and storage of meat and meat products.
研究领域:
食品科学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
MengYing Lei,Qing Chen,Yang Wang,Gang Wang
Oral absorption of carrier-free self-assembly nanoplatform was limited by mucus barrier, p-gp efflux and liver metabolism. In this study, Pip-Cur-TA nanoparticle were constructed by co-assembly of tannic acid, curcumin and piperine via inter-molecular hydrogen-bonded and π-π interaction to improve the oral chemotherapy. The optimized Pip-Cur-TA nanoparticle showed an average diameter of 60 nm with a drug encapsulation efficiency of 67.02 % and loading capacity of 61.37 %. Pip-Cur-TA nanoparticles showed pH-dependent drug release, mucosal adhesion, inhibition of p-gp and liver metabolism and improved membrane permeability. Oral Pip-Cur-TA nanoparticle produced high oral delivery efficiency and relative oral bioavailability of 12.84 % in rats, and further showed significant tumor inhibition on PC-3 tumor cells. These findings confirmed that Pip-Cur-TA nanoparticle might be a promising oral drug formulation for chemotherapy.
研究领域:
药剂学
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肿瘤学
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产品关联
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
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IF 3.322
Yelin Tang,Wenxin Zhang,Liqin Wu,Bin Bai,Bin Zheng,Mengying Li,Yue Tang,Xiaona Zhu,Yali Zhang,Yi Wang,Bing Zhang
Purpose Acute lung injury (ALI) is a fatal acute inflammatory illness with restricted therapeutic choices clinically. Piperlongumine (PL) is recognized as an alkaloid separated from Piper longum L, which was suggested to exhibit multiple pharmacological activities (e.g., anti-inflammatory activity). However, the effects of PL on LPS-triggered ALI and its anti-inflammatory target remain unclear. This paper intended to assess the roles of PL in LPS-triggered ALI, as well as its underlying mechanism and target. Methods In vivo, ALI was induced by intratracheal injection of LPS to evaluate protective effects of PL and assessed by the changes of histopathological. In vitro, the anti-inflammatory activity and mechanism of PL were investigated by ELISA, RT-qPCR, transcription factor enrichment analysis, Western blotting and Immunofluorescence assay. The binding affinity of PL to MD2 was analyzed using computer docking, surface plasmon resonance , ELISA and immunoprecipitation assay. Results It was reported here that PL treatment alleviated LPS-induced pulmonary damage, inflammatory cells infiltration and inflammatory response in mice. In culture cells, PCR array showed that PL significantly inhibited LPS-induced inflammatory cytokines, chemokines , and type I IFNs genetic expression, along with the inhibition of TAK1 and TBK1 pathway. It is noteworthy that PL is capable of straightly binding to MD2 and inhibiting MD2/TLR4 complex formation and TLR4 dimerization . Conclusions As revealed from this study, PL directly binding to MD2 to block cytokines expression by inhibiting the activation of TAK1 and TBK1 pathway, which then exerted its pulmonary protective activity. Accordingly, PL may act as an underlying candidate for treating LPS-triggered ALI.
研究领域:
药理学
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免疫学
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肺医学
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DOI
PubMed
高影响因子
Biomedicines
·
2023
·Vol. 11
·期 9
·2442
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IF 4.7
Eun-Young Choi,Eun-Ji Han,Su-Ji Jeon,Sang-Woo Lee,Jun-Mo Moon,Soo-Hyun Jung,Ji-Youn Jung
Oral cancer is a malignant tumor that primarily affects areas such as the lips, tongue, buccal mucosa, salivary gland, and gingiva and has a very high malignancy. Piperlongumine (PL), isolated from long pepper (Piper longumL.), is a natural alkaloid with pharmacological effects, such as anti-inflammatory and anti-atherosclerotic effects. The effect and mechanism of PL in oral cancer cell lines has not been explored. Therefore, this study aimed to investigate the mechanism of anticancer effects of PL in the human oral cancer cell lines MC-3 and HSC-4 in vitro. This study demonstrated that PL inhibits cell proliferation by inducing apoptosis and autophagy in human oral cancer cell lines, which was confirmed by the levels of apoptosis- and autophagy-related proteins through Western blotting. Moreover, the pharmacological blockade of autophagy activation by hydroxychloroquine (HCQ), an autophagy inhibitor, significantly improved PL-induced apoptosis in MC-3 cells, suggesting a cytoprotective effect. In addition, activation of the mitogen-activated protein kinase (MAPK) signaling pathway contributed to PL-induced apoptosis. Collectively, the study suggested that combining an autophagy inhibitor with PL treatment can exert effective anticancer properties in oral cancer cells by inducing apoptosis and cytoprotective autophagy via the JNK-mediated MAPK pathway.Keywords:piperlongumine;oral cancer;apoptosis;autophagy;MAPK pathway;anti-cancer agent
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
BIOTECHNOLOGY LETTERS
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2020
·Vol. 42
·期 10
·2049-2058
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IF 1.977
Song Lingyu,Wang Yan,Zhen Yunhuan,Li Dengke,He Xidong,Yang Hong,Zhang Huayang,Liu Qi
Cancer metastasis is the primary cause of death in patients diagnosed with colorectal cancer. Piperine, an active nontoxic ingredient in pepper, has potent anti-inflammatory and anti-cancer properties. However, little is known about the anti-migratory and anti-invasive effects of piperine on colorectal cancer. We demonstrated piperine inhibited the migration and invasion of colorectal cancer cells. Then, we found piperine reversed the biomarker expression of epithelial-to-mesenchymal transition (EMT), and suppressed the EMT regulator Snail. Furthermore, signal transducers and activators of transcription 3 (STAT3) was downregulated by piperine. Finally, STAT3 inhibitors were applied to observe the role of STAT3 in colorectal cancer migration, invasion and EMT. Collectively, piperine inhibits colorectal cancer migratory and invasive capacities through STAT3/Snail mediated EMT. Therefore, piperine could be applied as a possible therapeutic regimen for the prevention of colorectal cancer metastasis.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
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2022
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IF 6.59
Qian Yun-Fang,Yu Jia-Yi,Yu Ying-Jie,Xie Jing,Yang Sheng-Ping
In order to study the effects of the compound preservatives (curcumin and piperine (CP)) and vacuum packaging (VP) on the quality of salmon during cold chain logistics suffered from temperature abuse, the physiochemical indexes (texture, water holding capacity (WHC), total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS), free amino acids (FAA) contents), microbial indicators (total mesophilic bacteria count (MBC), total psychrotrophic bacteria count (PBC), H2S-producing bacteria count (HSBC)) were determined, and the moisture changes were explored by near-infrared (NIR) spectroscopy and low-field nuclear magnetic resonance (LF-NMR). The results showed that the treatment of curcumin and piperine in combination with vacuum packaging could maintain the quality of salmon suffered from temperature abuse most effectively. At the end of storage, the MBC of VP+CP was only 4.95 log CFU/g, which was about 1 log CFU/g lower than the control sample stored at the same condition. The combined treatment also retarded the increase of TVB-N, TBARS, and the decrease of hardness, springiness, and a* value, as well as water migration in salmon, contributing to higher water holding capacity and better appearance. Besides, VP+CP retarded the decrease of free glutamate, which contributed to umami taste. Due to the biological activity and safety of the preserves, the combined treatment could be a promising method for preservation of seafood.
研究领域:
食品科学
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生物化学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
·
IF 5.3
Jinping Ke,Jiawei Yuan,Zunting Pang,Rongrong Huang,Wenjun Miao,Weili Heng
The coamorphous formulations have attracted increasing interest due to enhanced solubility and bioavailability, together with synergistic pharmacological effects. In this study, a ternary coamorphous system of polyphenols was successfully prepared, wherein baicalein (Bai) and resveratrol (Res) were constructed into a single-phase coamorphous system mediated by piperine (Pip). FTIR and ss 13 C NMR spectra together with quantum chemical calculation and molecular dynamics simulation suggested Pip as a molecular bridge connected Bai and Res molecules through π-π stacking and hydrogen bonding interactions. The configuration of coamorphous Bai-Pip-Res could minimize the system energy to facilitate its formation and enhance the stability. The ternary system showed 3.2, 4.3 and 5.3-fold increase in apparent solubilities of Bai, Res and Pip, and maintained the peak concentrations for at least 24 h. Compared to binary coamorphous systems, the ternary system exhibited superior physical stability under temperature and humidity conditions. Furthermore, coamorphous Bai-Pip-Res exhibited enhanced antibacterial activity, significant antioxidant ability and synergistic anti-inflammatory effect. This work offers a promising strategy to construct a ternary coamorphous delivery system with enhanced pharmaceutical properties by incorporating a molecular bridge, especially for components with the lack of intermolecular interactions.
研究领域:
药物化学
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制药工程
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生物医学
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
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IF 6.3
Yeye Hu,Yanting Wang,Haoyang Gao,Guigui Yang,Jing Xie,Ziliang He,Shenghui Lv,Fenglin Gu,Chaoqing Huang,Weicheng Hu
Inflammatory bowel disease (IBD) is a global health concern with limited therapeutic options. Previous studies have demonstrated that piperine exhibited anti-inflammatory effects both in vitro and in vivo. However, its potential to ameliorate colitis in mice through modulation of gut microbiota has not been explored. This study aimed to investigate the role of gut microbiota in the protective effects of piperine against colitis using a dextran sulfate sodium (DSS)-induced mouse model. Mice were administered piperine (12.5 and 25 mg/kg) prior to DSS exposure. Fecal microbiota transplantation (FMT) was then performed, after which we evaluated colitis symptoms, inflammation levels, and intestinal barrier function. Subsequently, 16S rDNA-based high-throughput sequencing was employed to analyze the microbial composition of the mouse cecal contents. Piperine administration increased the colon length, decreased the spleen index, and improved colon histopathology. Furthermore, piperine modulated inflammatory responses by inhibiting NF-κB signaling, thereby reducing the release of pro-inflammatory cytokines and mediators. It also enhanced intestinal barrier integrity by increasing the expression of claudin-1, claudin-3, ZO-1, occludin, and mucin 2. Notably, the 16S rDNA sequencing results revealed that piperine increased the abundance of Dubosiella in the gut. Piperine effectively protected mice from DSS-induced colitis, suppressed inflammation, and improved poor intestinal barrier function. It reshaped the intestinal microbiota, ultimately alleviating DSS-induced colitis in mice. Our research highlighted the significant role of gut microbiota in the piperine-mediated alleviation of intestinal damage and suggested its therapeutic potential for promoting gut health and reducing the risk of colitis.
研究领域:
医学
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微生物学
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免疫学
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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）