查找使用阿拉丁产品的科研文献

The natural compounds, Magnolol or Honokiol, promote adipose tissue browning and resist obesity through modulating PPARα/γ activity

Yi Chu,Sisi Gui,Yazhen Zheng,Jingwu Zhao,Yaxiang Zhao,Yingying Li,Xiaodong Chen

Non-alcoholic fatty liver disease (NAFLD) is closely associated with the body's energy metabolism. A potential strategy to regulate energy metabolism, combat obesity, and reduce NAFLD is by enhancing adipocyte thermogenesis and increasing energy expenditure. In this study, our objective was to examine the effects of phenolic extracts derived from Magnolia officinalis on the regulation of NAFLD. Specifically, we investigated the impact of Magnolol or Honokiol treatment on high-fat diet (HFD)-induced obese C57BL6/J male mice. Firstly, we monitored energy metabolism, dissected tissues, and analyzed tissue sections. Additionally, we conducted experiments on HepG2 and primary adipocytes to gain insights into the roles of Magnolol or Honokiol. To further understand the effects of these compounds on related signaling pathways and marker genes, we performed molecular docking, dual-luciferase assays, and interfered with target genes. Our findings revealed that Magnolol or Honokiol activate the peroxisome proliferator activated receptor alpha (PPARα) signaling pathway, leading to the alleviation of NAFLD. This activation promotes fatty acid oxidation, reduces lipogenesis, and enhances the expression and secretion of FGF21. Notably, Fibroblast growth factor 21 (FGF21), secreted by the liver, plays a crucial role in improving communication between the liver and adipocytes while also promoting the browning of adipose tissue. Additionally, Magnolol or Honokiol activate the peroxisome proliferator activated receptor gamma (PPARγ) signaling pathway, resulting in increased uncoupling protein 1 (UCP1) expression, heightened heat production in adipose tissue, and anti-obesity. Therefore, Magnolol or Honokiol alleviate NAFLD, promote adipose tissue browning and resist obesity through dual activation of PPARα/γ.

Honokiol targeting ankyrin repeat domain of TRPV4 ameliorates endothelial permeability in mice inflammatory bowel disease induced by DSS

Lin Niu,Shilong Wang,Yanyan Xu,Xingwang Zu,Xinyu You,Qiuyang Zhang,Pengwei Zhuang,Min Jiang,Jie Gao,Xiaotao Hou,Yanjun Zhang,Gang Bai,Jiagang Deng

Ethnopharmacological relevance As a classic traditional Chinese medicine , Magnolia officinalis ( M . officinalis ) is widely used in digestive diseases . It has rich gastrointestinal activity including inflammatory bowel disease (IBD) treatment, but the mechanism is not clear. Aim of the study In recent years, there has been a growing interest in investigating the regulatory effects of herbal compounds on transient receptor potential (TRP) channel proteins. Transient receptor potential vanilloid 4 (TRPV4), a subtype involved in endothelial permeability regulation, was discussed as the target of M . officinalis in the treatment of IBD in the study. Based on the targeting effect of TRPV4, this study investigated the active ingredients and mechanism of M . officinalis extract in treating IBD. Materials and methods To reveal the connection between the active ingredients in M . officinalis and TRPV4, a bioactivity-guided high performance liquid chromatography system coupled with mass spectrometry identification was utilized to screen for TRPV4 antagonists. TRPV4 siRNA knockdown experiment was employed to validate the significance of TRPV4 as a crucial target in regulating endothelial permeability by honokiol (HON). The interaction of the active ingredient representing HON with TRPV4 was confirmed by molecular docking, fluorescence-based thermal shift and live cell calcium imaging experiments. The potential binding sites and inhibitory mechanisms of HON in TRPV4 were analyzed by molecular dynamics simulation and microscale thermophoresis. The therapeutic effect of HON based on TRPV4 was discussed in DSS-IBD mice. Results Our finding elucidated that the inhibitory activity of M . officinalis against TRPV4 is primarily attributed to HON analogues. The knockdown of TRPV4 expression significantly impaired the calcium regulation and permeability protection in endothelial cells. The mechanism study revealed that HON specifically targets the Q239 residue located in the ankyrin repeat domain of TRPV4, and competitively inhibits channel opening with adenosine triphosphate (ATP) binding. The immunofluorescence assay demonstrated that the administration of HON enhances the expression and location of VE-Cadherin to protect the endothelial barrier and attenuates immune cell infiltration. Conclusions The finding suggested that HON alleviates IBD by improving endothelial permeability through TRPV4. The discovery provides valuable insights into the potential therapeutic strategy of active natural products for alleviating IBD.

Discovery of honokiol thioethers containing 1,3,4-oxadiazole moieties as potential α-glucosidase and SARS-CoV-2 entry inhibitors

Ting Xu,Jie-Ru Meng,Wanqing Cheng,Jia-Zheng Liu,Junyan Chu,Qian Zhang,Nannan Ma,Li-Ping Bai,Yong Guo

Honokiol, isolated from a traditional Chinese medicine (TCM) Magnolia officinalis , is a biphenolic compound with several biological activities. To improve and broaden its biological activity, herein, two series of honokiol thioethers bearing 1,3,4-oxadiazole moieties were prepared and assessed for their α -glucosidase and SARS-CoV-2 entry inhibitory activities. Among all the honokiol thioethers, compound 7l exhibited the strongest α -glucosidase inhibitory effect with an IC 50 value of 18.9 ± 2.3 µM, which was superior to the reference drug acarbose (IC 50  = 24.4 ± 0.3 µM). Some interesting results of structure–activity relationships (SARs) have also been discussed. Enzyme kinetic study demonstrated that 7l was a noncompetitive α -glucosidase inhibitor, which was further supported by the results of molecular docking. Moreover, honokiol thioethers 7e , 9a , 9e , and 9r exhibited potent antiviral activity against SARS-CoV-2 pseudovirus entering into HEK-293 T-ACE2 h . Especially 9a displayed the strongest inhibitory activity against SARS-CoV-2 pseudovirus entry with an IC 50 value of 16.96 ± 2.45 μM, which was lower than the positive control Evans blue (21.98 ± 1.98 μM). Biolayer interferometry (BLI) binding and docking studies suggested that 9a and 9r may effectively block the binding of SARS-CoV-2 to the host ACE2 receptor through dual recognition of SARS-CoV-2 spike RBD and human ACE2. Additionally, the potent honokiol thioethers 7l , 9a , and 9r displayed relatively no cytotoxicity to normal cells (LO2). These findings will provide a theoretical basis for the discovery of honokiol derivatives as potential both α -glucosidase and SARS-CoV-2 entry inhibitors.

Natural product honokiol exerts anti-methicillin resistant Staphylococcus aureus infection activity by targeting pyruvate kinase to inhibit glucose metabolism

Jingwen Bai,Jinjin Zheng,Chi Wei,Bin Yu,Jingwen Sun,Ziyang Feng,Yu Yang

The global spread of methicillin-resistant Staphylococcus aureus (MRSA) urgently demands novel therapeutic strategies. This study demonstrates that honokiol (HNK), a natural biphenolic compound, is a potent and broad-spectrum agent against MRSA, including clinical isolates. HNK exhibited rapid bactericidal activity, effectively disrupted biofilms, and in a murine abscess model, significantly promoted wound healing while reducing pro-inflammatory cytokines, with excellent biocompatibility. Through an integrated multi-omics, biochemical, and biophysical approach, we identified pyruvate kinase (PYK), the terminal enzyme of glycolysis, as the primary cellular target. Remarkably, HNK employs a dual-targeting strategy, concurrently inhibiting PYK enzyme activity and downregulating pyk gene transcription. Molecular docking, dynamics simulations, and computational mutagenesis delineated the precise binding mode and validated key interaction residues. This concerted attack triggers a catastrophic metabolic cascade severe obstruction of glycolytic flux, impairment of the TCA cycle, profound depletion of ATP/NADH, and oxidative stress ultimately leading to bacterial death and virulence attenuation. Our findings not only elucidate a novel antibacterial mechanism centered on the simultaneous transcriptional and functional inhibition of a metabolic hub but also provide a structural basis for drug design, positioning HNK as a valuable lead compound against multidrug-resistant staphylococcal infections. The definitive genetic validation of PYK as the essential target remains the critical next step to advance this therapeutic strategy.

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 .

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.