JOURNAL OF THE ELECTROCHEMICAL SOCIETY
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2024
·Vol. 171
·期 4
·047503
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IF 3.1
Zhengjie Zhang,Yiheng Zhang,Yangchun Li,Yurong Wang
An electrochemical sensor for the simultaneous detection of magnolol (MAG) and honokiol (HON) was constructed based on the metal-organic framework, UIO-66-NH2, and electroreduced carboxylated graphene oxide (ErGO-GOOH). The UIO-66-NH2@ErGO-COOH coating was characterized by scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. Cyclic voltammetry was applied to investigate the electrochemical behavior of MAG and HON on UIO-66-NH2@ErGO-COOH/GCE. The electroanalytical method for the simultaneous determination of MAG and HON was established using linear sweep voltammetry. Under optimal experimental conditions, a linear range of 0.05 ∼ 8 μM and limits of detection of 16 and 7.0 nm for MAG and HON, respectively, were obtained. The sensor exhibited good repeatability, reproducibility, stability and anti-interference ability. The sensor was successfully applied to the simultaneous detection of MAG and HON in urine and serum samples with good recovery.
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Acta Biomaterialia
·
2017
·
IF 6.319
Ziqi Wang,Xinru Li,Dishi Wang,Yang Zou,Xiaoyou Qu,Chuyu He,Yunqiang Deng,Yao Jin,Yuanhang Zhou,Yanxia Zhou,Yan Liu
To concurrently suppress multidrug resistance (MDR) and metastasis of breast cancer cells, paclitaxel (PTX) and honokiol (HNK) were coencapsulated into pH-sensitive polymeric micelles based on poly(2-ethyl-2-oxazoline)-poly( d , l -lactide) (PEOz-PLA). The physicochemical properties of dual drug-loaded PEOz-PLA micelles were characterized in size, drug loading and in vitro release. The efficiency of MDR reversal for the micelles was testified by synergetic enhancement of cytotoxicity and uptake by MCF-7/ADR cells. The flow cytometry and fluorescence polarization measurement results reinforced the conclusion that down-regulation of P-gp expression and increase of plasma membrane fluidity appeared to be possible mechanisms of MDR reversal by dual drug-loaded PEOz-PLA micelles. Further, the efficient inhibition of tumor metastasis by dual drug-loaded PEOz-PLA micelles was demonstrated by in vitro anti-invasion and anti-migration assessment in MDA-MB-231 cells and in vivo bioluminescence imaging in nude mice . The suppression of MDR and metastasis by the micelles was assigned to synergistic effects of pH-triggered drug release and HNK/PEOz-PLA-aroused P-gp inhibition, and pH-triggered drug release and PTX/HNK-aroused MMPs inhibition, respectively. In conclusion, our findings strengthen the usefulness of co-delivery of PTX and HNK by pH-responsive polymeric micelles for suppression of tumor MDR and metastasis. Statement of Significance Multidrug resistance (MDR) and metastasis are considered to be two of the major barriers for successful chemotherapy. The combination of a chemotherapeutic drug with a modulator has emerged as a promising strategy for efficiently treating MDR cancer and preventing tumor metastasis. Herein, a dual drug (paclitaxel and honokiol)-loaded pH-sensitive polymeric micelle system based on PEOz-PLA was successfully fabricated to ensure that tumor MDR and metastasis could be concurrently suppressed, therefore achieving distinguishing endo/lysosomal pH from physiological pH by accelerating drug release and then enhancing the cytotoxicity of paclitaxel to drug-resistant tumor cells MCF-7/ADR by increasing cellular uptake of paclitaxel, preventing in vitro invasion and migration for MDA-MB-231 cells and in vivo metastasis in nude mice. Further, the mechanism of MDR reversal by dual drug-loaded PEOz-PLA micelles was elucidated to be down-regulation of P-gp expression and increase of plasma membrane fluidity of MCF-7/ADR cells. The present findings strengthen the usefulness of co-delivery of PTX and HNK by pH-responsive polymeric micelles for suppression of tumor MDR and metastasis.
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Oxidative Medicine and Cellular Longevity
·
2020
·
IF 5.076
Ting Zhai,Wei Xu,Yayun Liu,Kun Qian,Yanling Xiong,Yong Chen
Background. Honokiol (HNK) has been reported to possess various beneficial effects in the context of metabolic disorders, including fatty liver, insulin resistance, and oxidative stress which are closely related to nonalcoholic steatohepatitis (NASH), however with no particular reference to CFLAR or JNK. Methods. C57BL/6 mice were fed methionine-choline-deficient (MCD) diet and administered simultaneously with HNK (10 and 20 mg/kg once a day, ig) for 6 weeks, and NCTC1469 cells were pretreated, respectively, by oleic acid (OA, 0.5 mmol/L) plus palmitic acid (PA, 0.25 mmol/L) for 24 h, and adenovirus-down Cflar for 24 h, then exposed to HNK (10 and 20 μmol/L) for 24 h. Commercial kits, H&E, MT, ORO staining, RT-qPCR, and Western blotting were used to detect the biomarkers, hepatic histological changes, and the expression of key genes involved in NASH. Results. The in vivo results showed that HNK suppressed the phosphorylation of JNK (pJNK) by activating CFLAR; enhanced the mRNA expression of lipid metabolism-related genes Acox, Cpt1α, Fabp5, Gpat, Mttp, Pparα, and Scd-1; and decreased the levels of hepatic TG, TC, and MDA, as well as the levels of serum ALT and AST. Additionally, HNK enhanced the protein expression of oxidative stress-related key regulatory gene NRF2 and the activities of antioxidases HO-1, CAT, and GSH-Px and decreased the protein levels of prooxidases CYP4A and CYP2E1. The in vivo effects of HNK on the expression of CLFAR, pJNK, and NRF2 were proved by the in vitro experiments. Moreover, HNK promoted the phosphorylation of IRS1 (pIRS1) in both tested cells and increased the uptake of fluorescent glucose 2-NBDG in OA- and PA-pretreated cells. Conclusions. HNK ameliorated NASH mainly by activating the CFLAR-JNK pathway, which not only alleviated fat deposition by promoting the efflux and β-oxidation of fatty acids in the liver but also attenuated hepatic oxidative damage and insulin resistance by upregulating the expression of NRF2 and pIRS1.
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BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Ruige Yang,Xiangjing Fu,Jiangping Fan,Tingting Wang,Jian Song,Ting Xu,Yong Guo,Sai-Yang Zhang
Honokiol, derived from Magnolia officinalis (a traditional Chinese medicine), has been reported to have anticancer activity. Here, a series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared and evaluated for their anticancer activities against three types of digestive system tumor cells. Biological evaluation showed that honokiol derivative 3k exhibited the best antiproliferative activity against HCT116 cells with an IC 50 value of 6.1 μmol/L, superior to the reference drug 5-fluorouracil (IC 50 : 9.63 ± 0.27 µmol/L). The structure–activity relationships (SARs) indicated that the introduction of –(4-NO 2 )Ph, 3-pyridyl, –(2-F)Ph, –(4-F)Ph, –(3-F)Ph, –(4-Cl)Ph, and –(3-Cl)Ph groups was favorable for enhancing the anticancer activity of the title honokiol thioethers. Further study revealed that honokiol thioether 3k can well inhibit the proliferation of colon cancer cells HCT116, arresting the cells in G1 phase and inducing cell death. Moreover, a preliminary mechanism study indicated that 3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway. Thus, honokiol thioether 3k could be deeply developed for the development of honokiol-based anticancer candidates.
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FISH & SHELLFISH IMMUNOLOGY
·
2026
·
IF 4.2
Le Zhang,Yihuan Chen,Yinghao Zhou,Chen Chen,Yaohuan Wang,Yiming Zheng,Shilin Shang,Maocang Yan,Xuan Dong,Qianjin Zhou,Jiong Chen
Honokiol (HKL) sensitizes Vibrio parahaemolyticus to doxycycline. • HKL–DOX shows additive interaction and reduces culturable bacteria. • HKL–DOX is associated with membrane perturbation and ATP depletion. • Dietary HKL–DOX improves shrimp survival and lowers bacterial burden. • Host and microbiota changes accompany HKL–DOX-mediated protection. Vibrio parahaemolyticus is a major bacterial pathogen in shrimp aquaculture, and the development of new anti-infective strategies is urgently needed due to limited protective options. In this study, we report that the plant-derived compound honokiol (HKL) acts as an effective adjuvant to doxycycline (DOX) against V. parahaemolyticus . Checkerboard assays revealed an additive interaction between HKL and DOX (FICI = 0.5625), accompanied by a 16-fold reduction in the minimum inhibitory concentration (MIC) of DOX from 64 μg/mL to 4 μg/mL. Plate-count-based time-kill analysis showed that the HKL–DOX combination reduced recoverable culturable bacteria to below the detection limit under the tested plating conditions. Mechanistic investigations indicated that HKL acted as an important membrane-active component of the combination, increasing bacterial membrane permeability and perturbing membrane integrity. Under combination conditions, HKL and DOX induced membrane-associated damage and intracellular ATP depletion. In a shrimp infection model, the HKL-DOX combination therapy significantly improved shrimp survival, reduced bacterial load in the hepatopancreas, partially preserved intestinal and hepatopancreatic histoarchitecture, was accompanied by changes in immune- and mucosal barrier-related gene expression and intestinal microbiota diversity and composition. Overall, HKL acts as an effective antibiotic adjuvant, highlighting a promising combination strategy for controlling V. parahaemolyticus infections in aquaculture.
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Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 29
·5845-5853
·
IF 4.543
Ping Zhang,Yang Cao,Huali Chen,Bo Zhou,Wenjing Hu,Liangke Zhang
In this study, a multi-functional drug delivery system, which combines targeted tumor treatment with glycyrrhetinic acid-modified nanodroplets and ultrasound imaging with low-boiling-point phase-change perfluorocarbon, was proposed and validated. The obtained nanodroplets were spherical in shape with an average size of 324.8 ± 183.7 nm and a negative zeta-potential. Low-intensity focused ultrasound (LIFU) was introduced to perform targeted US imaging via acoustic droplet vaporization (ADV) both in vitro and in vivo. The in vitro cytotoxicity and cellular uptake studies conducted on HepG2 cells demonstrated that nanodroplets modified with glycyrrhetinic acid enhanced the selective delivery to cells expressing high levels of glycyrrhetinic acid receptors. Moreover, the glycyrrhetinic acid-modified nanodroplets showed significant antitumor efficacy in HepG2 cell-bearing mice with the assistance of both passive targeting via the EPR effects and active targeting ability of glycyrrhetinic acid. In conclusion, our fabricated multi-functional nanodroplets possess targeted antitumor activity and simultaneous US imaging, providing high potential for targeted tumor theranostics.
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PHYTOMEDICINE
·
2026
·
IF 11.3
Chi Wei,Yujia Guo,Jiaying Zhan,Jinjin Zheng,Bin Yu,Haodong Xu,Yu Yang,Jingwen Bai
Honokiol targets HptA to block G‑6‑P uptake and induce lethal carbon starvation. • Carbon starvation collapses MRSA central metabolism and weakens biofilm formation. • Metabolic inhibition lowers NADPH, amplifies ROS, and drives oxidative damage. • Honokiol reduces MRSA burden, dampens TLR2/NF‑ κ B, and accelerates wound healing. • HptA is absent in mammals, giving HNK high target selectivity and low toxicity. Background Methicillin-resistant Staphylococcus aureus (MRSA) compromises chronic wound healing, and growing antibiotic resistance necessitates novel agents that target unconventional bacterial vulnerabilities. Purpose To investigate the anti-MRSA efficacy of honokiol and to characterize hexose phosphate transport regulatory protein A (HptA), a regulator of alternative carbon source uptake under nutritional stress, as a therapeutic target. Methods Anti-MRSA activity was evaluated in vitro , with MIC determination. HptA protein was purified, and HptA–honokiol interactions were characterized using molecular docking, bio-layer interferometry, and related techniques. Multi-omics analysis were performed to elucidate metabolic responses. Therapeutic efficacy was assessed in mouse model of MRSA-induced wound infection. Results Honokiol exhibited moderate anti-MRSA activity with an MIC of 36 µg/ml. Mechanistically, honokiol allosterically locks HptA into a nonfunctional conformation, blocking glucose-6-phosphate uptake under nutrient-limited wound conditions. This induces carbon starvation, redox imbalance, and a ROS burst, leading to membrane damage, DNA fragmentation, and biofilm eradication. Local bacterial clearance subsequently reduced peptidoglycan-driven TLR2/NF- κ B activation, attenuated inflammation, and significantly accelerated wound healing in vivo . Conclusion HptA is identified as a potential antibacterial target against MRSA. By blocking alternative carbon uptake, honokiol induces carbon starvation‑driven lethal stress; lowered bacterial burden then inhibits TLR2/NF‑ κ B signaling, accelerating wound healing through a localized antibacterial action. Download: Download high-res image (358KB) Download: Download full-size image
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JOURNAL OF CHROMATOGRAPHY A
·
2020
·
IF 4.049
Jingwei Zhou,Yaoyao Hu,Peichun Chen,Hongwu Zhang
In the present study, a novel strategy based on unidirectional freezing and atom transfer radical polymerization combined with activator regenerated by electron transfer (ARGET-ATRP) was applied to synthesizing orderly macroporous monolithic column with restricted-access (RA) property in a 1000μL pipette tip. The RA column was composed of hydrophobic inner column (poly(styrene- co -ethylene glycol dimethacrylate) and hydrophilic outer layer (poly-hydroxyethyl methacrylate chain) which was grafted on the hydrophobic surface by means of the second ARGET-ATRP reaction. The as-prepared RA monolithic tip was connected to a 2mL syringe for directly extracting magnolol and honokiol from rat plasma just by manually pushing operation. The surface morphology and chemical composition of the column were characterized by scanning electronic microscope, infrared spectroscopy and X-ray photoelectron spectroscopy respectively. The determined results of evaluation experiments based on the optimized solid phase extraction conditions showed that the RA column possessed good protein exclusion power, extraction recovery and reusability. The constructed RA-SPE-HPLC/UV method for simultaneously analyzing magnolol and honokiol in rat plasma was validated with quality control (QC) samples at four concentration levels. Good precision (RSDs, 3.39~11.16%) and acceptable accuracy (relative recoveries, 89.52%~108.42%) were obtained for intra- and inter-day assays. The determined results of real rat plasma as well as the standard-addition samples demonstrated the developed method with good accuracy and precision. It can be extrapolated from the experimental results that this simple and cost-efficient RA-SPE method is also suitable for directly extracting other hydrophobic constituents in biological body fluid for therapeutic drug monitoring or pharmacokinetic study.
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