查找使用阿拉丁产品的科研文献

Honokiol-Loaded β-D-Glucan/Chitosan Nanoparticles with Antibacterial and Anti-Inflammatory Activities for Promoting MRSA-Infected Wound Healing

Background:Methicillin-resistantStaphylococcus aureus(MRSA) wound infections are a major clinical concern due to their high prevalence and the growing risk of antimicrobial resistance. Therefore, it is imperative to develop safe and effective therapeutic strategies.Methods: Herein, we fabricated a novel antibiotic-free nanodrug delivery system (HNK/DG-COS NPs) by loading honokiol (HNK), a hydrophobic natural antimicrobial agent, onto a dual-polysaccharide carrier composed of chitosan (COS) and β-D-glucan (DG), for the treatment of MRSA-infected wounds. COS endows the nanoparticles with synergistic antibacterial activity together with HNK, while DG improves their anti-inflammatory and tissue repair capacities. The physicochemical characteristics of nanoparticles, as well as their in vitro antibacterial and anti-inflammatory activities, were systematically evaluated. Furthermore, an MRSA-infected wound model was constructed to verify their therapeutic efficacy.Results: HNK/DG-COS NPs exhibited a spherical morphology with a uniform particle size of approximately 200 nm. In vitro experiments have shown that HNK/DG-COS NPs can significantly kill MRSA and inhibit biofilm formation. Scanning electron microscopy further revealed that the nanoparticles exerted antibacterial effects by disrupting the integrity of bacterial cell membranes. In LPS-stimulated RAW264.7 macrophages, treatment with HNK/DG-COS NPs significantly mitigated pro-inflammatory cytokine levels. Cell migration assays confirmed that nanoparticles effectively enhanced L929 cell migration. In vivo, treatment with HNK/DG-COS NPs significantly accelerated MRSA-infected wound healing in mice, mitigated inflammatory damage, stimulated collagen production and repaired damaged tissues.Conclusions: HNK/DG-COS NPs represent a promising antibiotic-free candidate for intervention against early-stage MRSA-infected wounds.

Targeting Inflammatory Lesions Facilitated by Galactosylation Modified Delivery System Eudragit/Gal-PLGA@Honokiol for the treatment of Ulcerative Colitis

Anqi Wang,Yuanyuan Liu,Wugui Xiong,Wei Li,Jin Li,Zhiqiang Yang,Zhongtao Zou,Yinjia Luo,Zhoujiang Chen,Hanmei Li,Chi Teng Vong,Liang Zou

Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis , and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC. D-galactose was grafted by chemical coupling reactions with PLGA to prepare Gal-PLGA, which was used as a carrier for HNK (Gal-PLGA@HNK nanoparticles (NPs)). To improve the colon targeting efficiency by oral administration of the NPs, Eudragit S100 was used for wrapping on the surface of Gal-PLGA@HNK NPs (E/Gal-PLGA@HNK NPs). Our results showed that the encapsulation efficiency and drug loading capacity of E/Gal-PLGA@HNK NPs were 90.72 ± 0.54% and 8.41 ± 0.02%, respectively. Its average particle size was 242.24 ± 8.42 nm, with a PDI value of 0.135 ± 0.06 and zeta-potential of -16.83 ± 1.89 mV. The release rate of HNK from E/Gal-PLGA@HNK NPs was significantly decreased when compared with that of free HNK in simulated gastric and intestinal fluids, which displayed a slow-releasing property. It was also found that the cellular uptake of E/Gal-PLGA@HNK NPs was significantly increased when compared with that of free HNK in RAW264.7 cells, which was facilitated by D-galactose grafting on the PLGA carrier. Additionally, our results showed that E/Gal-PLGA@HNK NPs significantly improved colonic atrophy, body weight loss, as well as reducing disease activity index (DAI) score and pro-inflammatory cytokine levels in UC mice induced by DSS. Besides, the retention time of E/Gal-PLGA@HNK NPs in the colon was significantly increased when compared with that of other preparations, suggesting that these NPs could prolong the interaction between HNK and the injured colon. Taken together, the efficiency for target delivery of HNK to the inflammatory lesions was significantly improved by galactosylation modification on the PLGA carrier, which provided great benefits for the alleviation of colonic inflammation and injury in mice.

The effect of honokiol on pulmonary artery endothelium cell autophagy mediated by cyclophilin A in hypoxic pulmonary arterial hypertension

Xiaoying Wang,Dandan Xiao,Cui Ma,Lixin Zhang,Qingya Duan,Xiaodong Zheng,Min Mao,Daling Zhu,Qian Li

Abnormal autophagy plays critical roles in the structure and function of the pulmonary vasculature. Cyclophilin A (CyPA) can be secreted from cells in response to hypoxia and oxidative stress, which are involved in inducing autophagy and regulating the function of endothelial cells in pulmonary arterial hypertension. Honokiol is a small molecule natural compound; it has many bioactivities, such as antitumor, anti-inflammatory, antioxidant and antiangiogenic properties, but how honokiol mediates autophagy in pulmonary arterial hypertension is unclear. Rat' lungs gavaged with honokiol were examined for autophagy via western blot and fluorescence microscopy. In addition, western blot, quantitative RT-PCR and immunofluorescence were employed to test the expression of CyPA and autophagy markers in pulmonary artery endothelial cells (PAECs). Small interfering RNA targeting CyPA (si-CyPA) was used to knockdown the expression of CyPA, and then autophagy was tested with mRFP-GFP-LC3 fluorescence microscopy and western blot. We found that honokiol could reduce the expression of CyPA and autophagy markers in vivo and in vitro. Furthermore, autophagy was also down-regulated by si-CyPA. Taken together, we revealed a novel mechanism by which honokiol regulates autophagy. The results revealed that honokiol can alleviate autophagy and pulmonary arterial hypertension regulated by CyPA in PAECs.

A network pharmacology-based method to explore the therapeutic effect of honokiol on diabetes with comorbid depression in mice

Haonan Sun,Yumin Liu,Xuedong Wang,Luan Shu

The effective treatment of diabetes with comorbid depression is a big challenge so far. Honokiol, a bioactive compound from the dietary supplement Magnolia officinalis extract, possesses multiple health benefits. The present study aims to propose a network pharmacology-based method to elucidate potential targets of honokiol in treating diabetes with comorbid depression and related mechanisms. The antidepressant-like efficacy of honokiol was evaluated in high-fat diet (HFD) induced diabetic mice using animal behavior testing, immuno-staining and western blotting assay. Through network pharmacology analysis, retinoid X receptor alpha (RXRα) and vitamin D receptor (VDR) were identified as potential targets related to diabetes and depression. The stable binding conformation between honokiol and RXR/VDR was determined by molecular docking simulation. Moreover, hononkiol effectively alleviated depression-like behaviors in HFD diabetic mice, presented anti-diabetic and anti-neuroinflammatory functions, and protected the hippocampal neuroplasticity. Importantly, honokiol could activate RXR/VDR heterodimer in vivo . The beneficial effects of honokiol on HFD mice were significantly suppressed by UVI3003 (a RXR antagonist), while enhanced by calcitriol (a VDR agonist). Additionally, the disruption of autophagy in the hippocampus of HFD mice was ameliorated by honokiol, which was attenuated by UVI3003 but strengthened by calcitriol. Taken together, the data provide new evidence that honokiol exerts the antidepressant-like effect in HFD diabetic mice via activating RXR/VDR heterodimer to restore the balance of autophagy. Our findings indicate that the RXR/VDR-mediated signaling might be a potential target for treating diabetes with comorbid depression.

Preparation of honokiol nanoparticles by liquid antisolvent precipitation technique, characterization, pharmacokinetics, and evaluation of inhibitory effect on HepG2 cells

Weiwei Wu,Li Wang,Lingling Wang,Yuangang Zu,Siying Wang,Peiyan Liu,Xiuhua Zhao

Background Honokiol is a bioactive lignanoid and has been utilized in traditional Chinese medicine for a long time. It exhibits several pharmacological properties, such as anticancer effects, anti-inflammatory effects, and antianxiety effects. However, the poor aqueous solubility of honokiol has impeded clinical applications.Materials and methods In the present study, we adopted the liquid antisolvent precipitation (LAP) technique to prepare nanoparticles of honokiol for enhancement of solubility and bioavailability. Moreover, the honokiol nanoparticles obtained were investigated and evaluated in terms of morphology, physicochemical properties, saturation solubility, dissolution in vitro, bioavailability in vivo, toxicity, and the inhibitory effect on growth of HepG2 cells.Results The obtained honokiol nanoparticles existed nearly in spherical shape and could be turned into amorphous structure by the LAP method. Moreover, the solubility of the honokiol nanoparticles was extremely higher than that of free honokiol, and the nanoparticle dissolution rate was also higher than that of free honokiol, which was about 20.41 times and 26.2 times than that of free honokiol in artificial gastric juice and in artificial intestinal juice. The area under the curve [AUC(0–t)] value of honokiol nanoparticles was about 6.52 times greater than that of free honokiol; therefore, the honokiol nanoparticles had a higher bioavailability than free honokiol but were innoxious to the organs of rats. Additionally, the honokiol nanoparticles exhibited a higher inhibition of HepG2 cells due to their lower IC50 compared to free honokiol.Conclusion Honokiol nanoparticles have high solubility and bioavailability, and can become a new oral drug formulation and produce a better response for its clinical applications.

Honokiol potentiates low-dose sulfamonomethoxine sodium against antimicrobial-resistant AHPND-causing Vibrio parahaemolyticus through bacterial membrane disruption and host recovery

Yihuan Chen,Liyuan Yi,Le Zhang,Yiming Zheng,Chen Chen,Yaohua Wang,Shilin Shang,Maocang Yan,Qianjin Zhou,Jiong Chen

Acute hepatopancreatic necrosis disease (AHPND), caused by Vibrio parahaemolyticus, poses a severe threat to global shrimp aquaculture. Reduced susceptibility of aquaculture-associated bacterial pathogens to conventional antibiotics, together with concerns regarding antimicrobial input and environmental exposure, highlights the need for dose-sparing therapeutic strategies. This study investigated the antibiotic-potentiating activity of honokiol (HKL), a plant-derived lignan, in combination with sulfamonomethoxine sodium (SMM-Na) against AHPND. Checkerboard and time-kill assays demonstrated that sub-inhibitory HKL concentrations (32–64 μg/mL) markedly enhanced SMM-Na activity, reducing its minimum inhibitory concentration by 8–32-fold and achieving bactericidal effects in combination. The SMM-Na + HKL combination also significantly inhibited biofilm formation and compromised bacterial membrane integrity, as evidenced by enhanced propidium iodide uptake and scanning electron microscopy, while inducing severe ATP depletion. In Penaeus vannamei challenged with V. parahaemolyticus, dietary administration of low-dose SMM-Na (16 mg/kg) and HKL (32 mg/kg) yielded the highest survival rate (86.6%), substantially reduced hepatopancreatic bacterial load, attenuated histopathological damage, and restored total hemocyte counts. The treatment also upregulated a broad spectrum of immune-related genes (e.g., Alf, Tlr, Lec, Crustin, Lzm, CatB) in the hepatopancreas and mucosal barrier genes (e.g., Muc-1, Muc-4, Muc-5AC, Muc-19) in the intestine. Furthermore, 16S rRNA sequencing indicated that the combination therapy was associated with treatment-related shifts in the intestine microbiota, including increased alpha diversity indices, reduced Vibrio abundance, and altered predicted KEGG functional profiles. Collectively, our results identify HKL as a natural-origin antibiotic potentiator that enhances the efficacy of low-dose SMM-Na against AHPND-causing V. parahaemolyticus. These findings provide proof-of-concept evidence for a dose-sparing combination strategy that may reduce therapeutic SMM-Na input while supporting pathogen control and host recovery in shrimp aquaculture.

An environmentally safe formulation of plant derived fungicide: preparation and characterization of inclusion complex of honokiol and methyl-β-cyclodextrin

Zhang Chao,Wen Tingchi,Qiao Lijun,Guo Ming,Li Qihua,Lu Zhenghua,Zhu Zhenyuan,Lu Meiling

Honokiol (HK) is an active compound in the traditional Chinese medicine Magnolia officinalis , which has antibacterial and disease-resistant effects on pathogenic microorganisms. However, due to its poor water solubility, its application is severely limited. In this study, Methyl-β-Cyclodextrin (M-β-CD) was used to encapsulate honokiol to improve its water solubility. The inclusion complex of HK with M-β-CD (HK/M-β-CD IC) were prepared by freeze-drying method, Phase solubility studies indicate that HK with M-β-CD forms inclusion complex in a stoichiometric ratio of 1:1. However, considering that the inclusion process is reversible. In order to obtain inclusion complex with higher encapsulation efficiency, we use response surface optimization to optimize the encapsulation process. The encapsulation efficiency of the obtained inclusion compound is 87.64%.The structure of inclusion complex was characterized by FTIR, TGA, SEM, XRD and NMR. The molecular docking was used to predict the structure of inclusion complex. In addition, compared with free HK, the solubility of the inclusion complex in water was significantly enhanced, about 1228 times that of the free HK. And it enhances the antibacterial activity against Trichoderma koningii .

Non-clinical pharmacokinetics study in rat plasma, tissues and excreta of honokiol derivative HM475 by UPLC-Q-TOF-MS/MS

Jing Zhang,Wenyuan Li,Luming Xie,Changfeng Zhong,Changmei Wang,Lin Chen,Yifan Feng,Xia Wu

To provide the basis for further development and research of drugs, non-clinical pharmacokinetics studies were conducted on HM475, which is composed of natural active molecules honokiol and metformin through cyclization. In this paper, HM475 was studied from six aspects by gavage and intraperitoneal injection: 1) Acute toxicity of HM475 in rats, 2) Pharmacokinetic characteristics of HM475 in rats, 3) Distribution characteristics of HM475 in heart, liver, spleen, lung, and kidney, small intestine, fat and brain of rats, 4) Main metabolic pathways of HM475 in rats, 5) Excretion of HM475 in rats, 6) Determination of protein binding rate of HM475 in bovine plasma, rabbit plasma, and rat plasma. Acute toxicity of HM475 on SD rats was evaluated by maximum dose method. The metabolic analysis method of HM475 in rats was first established by UPLC-Q-TOF-MS/MS technology, and the pharmacokinetic characteristics of oral administration and intraperitoneal injection were studied. Experimental results showed that HM475 had no obvious acute toxicity. The absolute oral bioavailability of HM475 was 38.45 %, and the drug concentration in plasma was higher than that in tissues. Combined with the process characteristics of HM475 in vivo , it is inferred that HM475 has enterohepatic circulation. In this study, non-clinical pharmacokinetics were systematically studied to provide data support for the clinical pharmacokinetics and pharmacodynamics of HM475, to more accurately predict the pharmacokinetic behavior of HM475 in human body and provide scientific data for the compound to enter clinical research.

Honokiol attenuates high glucose-induced peripheral neuropathy via inhibiting ferroptosis and activating AMPK/SIRT1/PGC-1ɑ pathway in Schwann cells

Man Hu,Wen Jiang,Chen Ye,Ting Hu,Qingqing Yu,Moran Meng,Lijuan Sun,Jichao Liang,Yong Chen

Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC-1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC-1 staining results demonstrated that honokiol reduced HG-induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT-qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG-induced inhibition of AMPK/SIRT1/PGC-1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG-induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin-induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG-induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.

Honokiol reduces cadmium-induced oxidative injury and endosomal/lysosomal vacuolation via protecting mitochondrial function in quail (Coturnix japonica) liver tissues

Junzhao Yuan,Xiaoqian Huang,Jianhong Gu,Yan Yuan,Zongping Liu,Hui Zou,Jianchun Bian

Cadmium (Cd) pollution in environment is toxic to birds. This study aimed to assess antagonistic effect of honokiol (HNK) on Cd-induced quail ( Coturnix japonica ) liver tissue damage and Cd-induced vacuolation in hepatocytes. We found that HNK alleviated Cd-induced liver pathological damage marked by elevated serum liver biochemical indicators, disordered antioxidant levels and trace elements in quails. HNK reduced Cd-induced liver cell apoptosis as assessed by western blotting and TUNEL staining. The ultrastructure of hepatocytes under transmission electron microscope revealed that Cd induced mitochondrial damage in addition to abnormal enlargement and increased vacuolar structure of cells. Mitochondrial damage and vacuolization were reduced in the HNK + Cd group. Cd induced an increase in the levels of endosomal/lysosomal-related genes, while HNK treatment reversed this effect. Finally, we demonstrated that vacuolation in buffalo rat liver 3A (BRL 3A) cells occurred primarily due to Cd-induced oxidative stress damage that reduces mitochondrial ATP content and indirectly led to dysfunction of ATP-dependent lipid kinase PIKfyve complex. In summary, we are the first to report that Cd induces abnormal enlargement of endosome/lysosomes in quail liver cells and HNK alleviated this phenomenon by reducing mitochondrial damage and increasing intracellular ATP level. This study demonstrated the toxic effect of Cd pollution on birds and how HNK mitigated these effect at the cellular level. Overall, more research on Cd pollution and HNK use in animal husbandry is warranted.

A Versatile Natural Neolignan as a Potential Pesticide Resource: Synthesis and Insecticidal Evaluation of Honokiol Derivatives Featuring a Bis(benzoxazole) Scaffold

Chun Yang,Jin-Qiu Duan,Hao Fu,Feng Wang,Xin-Yu Zhang,Ying Liu,Yan-Qiong Guo,Xiao-Yan Zhi

Inspired by the insecticidal scaffold honokiol, bis(benzoxazole)-fused analogs were designed and synthesized. Compounds 5h, 7d, 8f, 8m, and 9a exhibited potent oral toxicity (LC50 = 3.2–12.6 mg/L) and antifeedant activity (AFC50 = 1.0–3.3 mg/L) against Plutella xylostella, outperforming honokiol, toosendanin, and rotenone. In greenhouse trials, compound 8f (100 mg/L, 48 h) achieved 51.1% corrected mortality and 75.8% leaf protection. Against Mythimna separata, compounds 5f, 6f, 6n, 7a, and 8g showed pronounced growth inhibition (LC50 = 90–360 mg/L), exceeding honokiol and toosendanin. Acetylcholinesterase (AChE) was identified as a potential target in P. xylostella, and Chitinase inhibition disrupted M. separata development. Negligible cytotoxicity (IC50 > 100 μM) against the human keratinocyte cell line (HaCaT) suggests a favorable safety profile for mammalian exposure. The novel architectures, potent efficacy, and good safety profile highlight the potential of these honokiol-inspired compounds as promising insecticidal candidates.

Concurrently suppressing multidrug resistance and metastasis of breast cancer by co-delivery of paclitaxel and honokiol with pH-sensitive polymeric micelles

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.