Sinusoidal alternating electromagnetic field accelerates fracture healing in rats. / æ­£å¼¦äº¤å˜ç”µç£åœºå¯åŠ é€Ÿå¤§é¼ éª¨æŠ˜æ„ˆåˆ.

OBJECTIVES: To investigate the effect of sinusoidal alternating electromagnetic field (SEMF) on fracture healing and its mechanism. METHODS: Femoral fracture model was established using SPF male Wistar rats, 30 model rats were randomly divided into model control (MC) and SEMF groups with 15 rats in each group. The SEMF group was given 50 Hz 1.8 mT for 90 min every day, and the MC group was not treated. X-ray examinations were performed every two weeks to determine the formation of bone scabs in each group of rats. Three rats were sacrificed after 2 and 4 weeks of treatment in both groups. Protein was extracted from the fractured femurs, and the expression of type Ⅰ collagen (COL-1), Osterix (OSX), Runt-related transcription factor 2 (RUNX2), and vascular endothelial growth factor (VEGF) protein level was detected by immunoblotting. After 8 weeks, the femur on the operated side was taken for micro-CT scanning to observe fracture healing, angiography to observe blood vessel growth, and organs such as hearts, livers, spleens, lungs, and kidneys were taken for safety evaluation by hematoxylin-eosin staining (HE staining). RESULTS: The bone scab scores of the SEMF group were significantly higher than those of the MC group after 2, 4, 6, and 8 weeks of treatment (all P<0.01); the fracture healing of the SEMF group was better than that of the MC group after 8 weeks, and the bone volume scores of the two groups were 0.243±0.012 and 0.186±0.008, respectively, with statistically significant differences (P<0.01); and the number of blood vessels in the SEMF group was also more than that of the MC group after 8 weeks. The results of protein blotting method showed that the protein expression of VEGF, COL-1, RUNX2, and OSX was higher in the SEMF group than in the MC group after 2 and 4 weeks of treatment (all P<0.05), and the HE staining showed that there was no abnormality in histopathological observation of examined organs in both groups. CONCLUSIONS: SEMF can accelerate fracture healing by promoting the expression of osteogenic factors and vascular proliferation without significant adverse effects.

[Combination of shikonin and gefitinib reverses drug resistance in human non-small cell lung cancer and its mechanism].

The occurrence and development of tumors are associated with the cell energy metabolism. Inhibiting energy metabolism of lung cancer cells is an important strategy to overcome drug resistance. Based on the cellular energy metabolism pathway, this study observed the effect of combination of shikonin(SKN) and gefitinib(GFB) on the drug resistance in non-small cell lung cancer and explored the underlying mechanism. The human non-small cell lung cancer line HCC827/GR resistant to gefitinib was used as the cell model in vitro. The CCK-8 assay and flow cytometry were employed to investigate the cell viability and apoptosis, respectively. The high performance liquid chromatography was employed to measure the intracellular accumulation of GFB. A Seahorse XFe96 Analyzer was used to detect the changes of cellular energy metabolism. Western blot was employed to determine the expression of the proteins involved in the drug resistance. The tumor-bearing nude mouse model was used to verify the efficacy of SKN+GFB in overcoming drug resistance in vivo. The results showed that SKN+GFB significantly reduced the IC_(50) of GFB on HCC827/GR cells, with the combination index of 0.628, indicating that the combination of the two drugs had a synergistic effect and promoted cell apoptosis. SKN increased the intracellular accumulation of GFB. SKN+GFB lowered the oxygen consumption rate(OCR) and glycolytic proton efflux rate(GlycoPER) in cell energy metabolism, and down-regulated the overexpression of PKM2, p-EGFR, P-gp, and HIF-1α in drug resistance. The results of reversing drug resistance test in vivo showed that GFB or SKN alone had no significant antitumor effect, while the combination at different doses induced the apoptosis of the tumor tissue and inhibited the expression of PKM2 and P-gp, demonstrating a significant antitumor effect. Moreover, the tumor inhibition rate in the high-dose combination group reached 64.01%. In summary, SKN+GFB may interfere with the energy metabolism to limit the function of HCC827/GR cells, thus reversing the GFB resistance in non-small cell lung cancer.

The interdependent relationship between the nitric oxide signaling pathway and primary cilia in pulse electromagnetic field-stimulated osteoblastic differentiation.

Pulsed electromagnetic fields (PEMFs) have long been recognized being safe and effective in treating bone fracture nonunion and osteoporosis. However, the mechanism of osteogenic action of PEMFs is still unclear. While primary cilia are reported to be a sensory organelle for PEMFs, and nitric oxide (NO) plays an indispensable role in osteogenic effect of PEMFs, the relationship between NO and primary cilia is unknown. In this study, effects of treatment with 50 Hz 0.6 mT PEMFs on osteogenic differentiation and mineralization, NO secretion, and ciliary location of specific proteins were examined in rat calvarial osteoblasts (ROBs) with normal or abrogated primary cilia. It was found that PEMFs stimulated the osteogenic differentiation by activating the NOS/NO/sGC/cGMP/PKG signaling pathway, which need the existence of primary cilia. All components of the signaling pathway including iNOS, eNOS, sGC, PKG-1, and PKG-2 were localized to primary cilia, and eNOS was phosphorylated inside the primary cilia. Besides, primary cilia were elongated significantly by PEMF treatment and changed dynamically with the activation NO/cGMP pathway. When the pathway was blocked by L-NAME, PEMFs could no longer elongate the primary cilia and stimulate the osteoblastic differentiation. Thus, this study for the first time observed activation of the NO/cGMP signaling pathway in ciliary compartment of osteoblasts, and PEMFs could not stimulate the osteoblastic differentiation if the NO signaling pathway was blocked or the ciliogenesis was inhibited. Our findings indicate the interdependent relationship between NO and primary cilia in the PEMF-promoted osteogenesis.

Hyperoside ameliorates cerebral ischaemic-reperfusion injury by opening the TRPV4 channel in vivo through the IP3-PKC signalling pathway.

CONTEXT: Hyperoside (Hyp), one of the active flavones from Rhododendron (Ericaceae), has beneficial effects against cerebrovascular disease. However, the effect of Hyp on vasodilatation has not been elucidated. OBJECTIVE: To explore the effect of Hyp on vasodilatation in the cerebral basilar artery (CBA) of Sprague-Dawley (SD) rats suffering with ischaemic-reperfusion (IR) injury. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into sham, model, Hyp, Hyp + channel blocker and channel blocker groups. Hyp (50 mg/kg, IC50 = 18.3 µg/mL) and channel blocker were administered via tail vein injection 30 min before ischaemic, followed by 20 min of ischaemic and 2 h of reperfusion. The vasodilation, hyperpolarization, ELISA assay, haematoxylin-eosin (HE), Nissl staining and channel-associated proteins and qPCR were analysed. Rat CBA smooth muscle cells were isolated to detect the Ca2+ concentration and endothelial cells were isolated to detect apoptosis rate. RESULTS: Hyp treatment significantly ameliorated the brain damage induced by IR and evoked endothelium-dependent vasodilation rate (47.93 ± 3.09% vs. 2.99 ± 1.53%) and hyperpolarization (-8.15 ± 1.87 mV vs. -0.55 ± 0.42 mV) by increasing the expression of IP3R, PKC, transient receptor potential vanilloid channel 4 (TRPV4), IKCa and SKCa in the CBA. Moreover, Hyp administration significantly reduced the concentration of Ca2+ (49.08 ± 7.74% vs. 83.52 ± 6.93%) and apoptosis rate (11.27 ± 1.89% vs. 23.44 ± 2.19%) in CBA. Furthermore, these beneficial effects of Hyp were blocked by channel blocker. DISCUSSION AND CONCLUSIONS: Although Hyp showed protective effect in ischaemic stroke, more clinical trial certification is needed due to the difference between animals and humans.

B16F10 Cell Membrane-Based Nanovesicles for Melanoma Therapy Are Superior to Hyaluronic Acid-Modified Nanocarriers.

Some cancer cell membrane (CCM)-derived nanovesicles show strong homing effects and are used for targeted cancer therapy. By co-constructing the B16F10 cell membrane with a PEGylated phospholipid membrane, a new nanocarrier with a composite nanocrown structure was developed, which can evade immune recognition and actively target homologous melanoma. The nanocrowns have an encapsulation efficiency of more than 90% for paclitaxel and showed no significant difference (p > 0.05) from the PEGylated phospholipid membrane vesicles. Compared with the hyaluronic acid-modified PEGylated phospholipid membrane vesicles, the biomimetic nanocrowns enhanced the escape of nanovesicles from reticuloendothelial cells in vitro and extended the circulation time in vivo; moreover, the nanocrowns showed superior melanoma-targeted drug delivery capability and improved anticancer effects of paclitaxel as demonstrated by the inhibition of B16F10 cell proliferation and induction of apoptosis by interfering with microtubule formation. In contrast, the modification of hyaluronic acid did not increase the targeting capacity or antitumor effects of the nanocrowns, confirming that the superior targeting capacity was mediated by the exposed homologous CCMs rather than by hyaluronic acid. Our results demonstrate the potential of using biomimetic nanocrowns for active melanoma-targeted therapy.

A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy.

BACKGROUND: A red blood cell membrane (RBCm)-derived drug delivery system allows prolonged circulation of an antitumor treatment and overcomes the issue of accelerated blood clearance induced by PEGylation. However, RBCm-derived drug delivery systems are limited by low drug-loading capacities and the lack of tumor-targeting ability. Thus, new designs of RBCm-based delivery systems are needed. RESULTS: Herein, we designed hyaluronic acid (HA)-hybridized RBCm (HA&RBCm)-coated lipid multichambered nanoparticles (HA&RBCm-LCNPs) to remedy the limitations of traditional RBCm drug delivery systems. The inner core co-assembled with phospholipid-regulated glycerol dioleate/water system in HA&RBCm-LCNPs met the required level of blood compatibility for intravenous administration. These newly designed nanocarriers had a honeycomb structure with abundant spaces that efficiently encapsulated paclitaxel and IR780 for photochemotherapy. The HA&RBCm coating allowed the nanocarriers to overcome the reticuloendothelial system barrier and enhanced the nanocarriers specificity to A549 cells with high levels of CD44. These properties enhanced the combinatorial antitumor effects of paclitaxel and IR780 associated with microtubule destruction and the mitochondrial apoptotic pathway. CONCLUSIONS: The multifunctional HA&RBCm-LCNPs we designed expanded the functionality of RBCm and resulted in a vehicle for safe and efficient antitumor treatment.

Functional oral nanoparticles for delivering silibinin and cryptotanshinone against breast cancer lung metastasis.

BACKGROUND: Breast cancer lung metastasis occurs in more than 60% of all patients with breast cancer, and most of those afflicted by it eventually die of recurrence. The tumor microenvironment plays vital roles in metastasis. Modulating the tumor microenvironment via multiple pathways could efficiently prevent or inhibit lung metastasis. Silibinin and cryptotanshinone are natural plant products that demonstrate anti-metastasis effects and modulate the tumor microenvironment via different pathways. However, they have poor aqueous solubility, membrane permeability, and oral bioavailability. Oral drug administration may help improve the quality of life and compliance of patients with breast cancer, primarily under long-term and/or follow-up therapy. Herein, we developed poly-N-(2-hydroxypropyl) methacrylamide (pHPMA)-coated wheat germ agglutinin-modified lipid-polymer hybrid nanoparticles, co-loaded with silibinin and cryptotanshinone (S/C-pW-LPNs). We assessed their oral bioavailability, and evaluated their anti-metastasis efficacy in a 4T1 breast cancer tumor-bearing nude mouse model. RESULTS: An in vitro mucus diffusion study revealed that pHPMA enhanced W-LPN mucus penetration. After oral administration, pHPMA enhanced nanoparticle distribution in rat jejunum and substantially augmented oral bioavailability. S/C-W-LPNs markedly increased 4T1 cell toxicity and inhibited cell invasion and migration. Compared to LPNs loaded with either silibinin or cryptotanshinone alone, S/C-pW-LPNs dramatically slowed tumor progression in 4T1 tumor-bearing nude mice. S/C-pW-LPNs presented with the most robust anti-metastasis activity on smooth lung surfaces and mitigated lung metastasis foci. They also downregulated tumor microenvironment biomarkers such as CD31, TGF-ß1, and MMP-9 that promote metastasis. CONCLUSIONS: Silibinin- and cryptotanshinone-co-loaded pW-LPNs efficiently penetrate intestinal barriers, thereby enhancing the oral bioavailability of the drug loads. These nanoparticles exhibit favorable anti-metastasis effects in breast cancer-bearing nude mice. Hence, S/C-pW-LPNs are promising oral drug nanocarriers that inhibit breast cancer lung metastasis.

Co-hybridized composite nanovesicles for enhanced transdermal eugenol and cinnamaldehyde delivery and their potential efficacy in ulcerative colitis.

Percutaneous absorption of drugs can be enhanced by ethosomes, which are nanocarriers with excellent deformability and drug-loading properties. However, the ethanol within ethosomes increases phospholipid membrane fluidity and permeability, leading to drug leakage during storage. Here, we developed and characterized a new phospholipid nanovesicles that is co-hybridized with hyaluronic acid (HA), ethanol and the encapsulated volatile oil medicines (eugenol and cinnamaldehyde [EUG/CAH]) for transdermal administration. In comparison with EUG/CAH-loaded ethosomes (ES), the formulation stability and percutaneous drug absorption of EUG/CAH-loaded HA-immobilized ethosomes (HA-ES) were significantly improved. After transdermal administration of HA-ES, the interstitial cells of Cajal in the colon of rats with trinitrobenzene sulfonate-induced ulcerative colitis (UC) were significantly increased, and the stem cell factor/c-kit signaling pathway was partly repaired. Overall, HA-ES possesses excellent deformability and showed improved efficacy against UC compared with ES, which is demonstrated as a promising transdermal delivery vehicle for volatile oil medicines.

Advances in next-generation lipid-polymer hybrid nanocarriers with emphasis on polymer-modified functional liposomes and cell-based-biomimetic nanocarriers for active ingredients and fractions from Chinese medicine delivery.

Recently, functional liposomes modified with versatile polymer and cell-based- biomimetic nanoparticles have emerged as the most advanced lipid-polymer hybrid nanocarriers (LPNs) for drug delivery. This review highlights the advances of these two LPNs in the delivery of active ingredients and fractions from Chinese medicine with promising therapeutic, chemopreventive, or chemosensitive effects. To understand their complete potency, the relationship between the nanoparticle characteristics and their in vitro and in vivo performance characteristics has been discussed. Polymer-modified liposomes and cell-based biomimetic nanoparticles are beneficial for improving absorption, modulating release, targeting and overcoming multidrug resistance, and reducing side effects. The associated challenges, current limitations, and opportunities in this field are also discussed.

Functional lipid polymeric nanoparticles for oral drug delivery: Rapid mucus penetration and improved cell entry and cellular transport.

To improve Biopharmaceutics Classification System class IV drug bioavailability, mucus and underlying intestinal epithelial barriers must be overcome. Hydrophilic nanoparticle coatings may hinder cellular uptake and transport. We integrated hydrophilic, detachable poly(N-(2-hydroxypropyl) methacrylamide) with vitamin B12-modified chitosan into lipid polymeric nanoparticles (H/VC-LPNs) to enhance mucus penetration, intracellular uptake, and transepithelial absorption. Multiple particle tracking revealed accelerated mucus diffusion into porcine mucus in vitro. The nanoparticles increased uptake and intracellular distribution in Caco-2 cells, which may involve intrinsic factor receptor-mediated endocytosis and intercellular tight junctions. Integration of improved mucus penetration and intracellular absorption was confirmed by in vitro internalization kinetics in HT29-MTX/Caco-2 co-cultures and in vivo distribution, transport, and mouse Peyer's patch absorption. H/VC-LPNs substantially increased curcumin bioavailability in rats. A nanocarrier with a dissociable shell, receptor-mediated intracellular penetration, and paracellular transport may be promising for oral curcumin delivery. This study identified the key factors involved in oral bioavailability enhancement.

Regulation of Eclipta prostrata L. components on cigarette smoking-induced autophagy of bronchial epithelial cells via keap1-Nrf2 pathway.

Cigarette smoking extract (CSE)-induced autophagic injury has been regarded as an important contributor to the pathogenesis of lung cancer. We previously found that Eclipta prostrata L. component (CCE) reduced CSE-induced bronchial epithelial cells damage. However, the mechanism remains unknown. Human normal bronchial epithelial cells (NHBE) were exposed to CSE to establish stress model. Nrf2-siRNA and Keap1-siRNA transfection were performed. mRFP-GFP-LC3 dual fluorescence and transmission electron microscopy were used to observe the autophagic characteristics. CCE prevented CSE-induced Nrf2 transfer into cytoplasm and up-regulated Keap1 level of NHBE cells. Furthermore, CCE significantly increased p-p16, p-p21 and p-p53 phosphorylation levels in Nrf2-siRNA- or Keap1-siRNA-transfected cells. As demonstrated by transmission electron microscopy and mRFP-GFP-LC3 dual fluorescence assays, CCE mitigated autophagic injury, and also down-regulated autophagy-related Beclin-1, LC3II/LC3I ratio, Atg5 and ATF4 levels. Our findings showed the attenuation of CCE on CSE-induced NHBE cells injury was associated with Nrf-2-mediated oxidative signaling pathway.

[Individualized clinical treatment from the prospective of hepatotoxicity of non-toxic traditional Chinese medicine].

Traditional Chinese medicine has a long history in clinical application, and been proved to be safe and effective. In recent years, the toxicity and side-effects caused by the western medicine have been attracted much attention. As a result, increasing people have shifted their attention to traditional Chinese medicine. Nonetheless, due to the natural origin of traditional Chinese medicine and the lack of basic knowledge about them, many people mistakenly consider the absolute safety of traditional Chinese medicine, except for well-known toxic ones, such as arsenic. However, according to the clinical practices and recent studies, great importance shall be attached to the toxicity of non-toxic traditional Chinese medicine, in particular the hepatotoxicity. Relevant studies indicated that the toxicity of non-toxic traditional Chinese medicine is closely correlated with individual gene polymorphism and constitution. By discussing the causes and mechanisms of the hepatotoxicity induced by non-toxic traditional Chinese medicine in clinical practices, we wrote this article with the aim to provide new ideas for individualized clinical therapy of traditional Chinese medicine and give guidance for rational and safe use of traditional Chinese medicine.

[Prevention effect of Ligusticum chuanxiong extraction against oxidative stress injury induced by myocardial ischemia through activation of Nrf2 signaling pathway].

Ligusticum chuanxiong is one of the common traditional Chinese medicinal herbs for treating various cardiovascular and cerebrovascular diseases, and a number of previous studies have demonstrated that the extract of L. chuanxiong has strong antioxidative activity. This paper was mainly aimed to investigate the effects and possible mechanisms of L. chuanxiong extraction on oxidative stress induced by myocardial ischemia injury in rats. The rats were subcutaneously injected with isoprenaline hydrochloride to induce myocardial ischemia injury and treated for 2 weeks. Then the cardiac indexes of the rats were recorded. The concentration of malondialdehyde (MDA) and activities of serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were measured by colorimetry. Light microscope was used to observe the morphological changes of myocardium, and the protein expressions of nuclear factor E2 related factor 2 (Nrf2), quinone oxidoreductase (NQO1) and hemeoxygenase-1 (HO-1) in cardiac tissue were evaluated by Western blot. The results showed that L. chuanxiong extraction could decrease cardiac indexes and the values of CK, LDH and AST in blood serum, increase activities of serum SOD and T-AOC, reduce serum MDA concentration, improve myocardium structure after ischemia injury, and up-regulate the protein expressions of Nrf2, NQO1 and HO-1 in cardiac tissue. These findings revealed that the cardioprotective effects of L. chuanxiong extraction may be related to inhibiting oxidative stress through the activation of Nrf2 signaling pathway.

[Discussion on influence factors, mechanism and traditional Chinese medicine pathogenesis of idiosyncratic drug-induced liver injury].

Idiosyncratic drug-induced liver injury (IDILI) is a kind of unique adverse drug reaction with relative high morbidity compared with other idiosyncratic diseases. Its occurrence, however, has nothing to do with pharmacological effects and clinical dosage of drugs administered, and only a small number of susceptible individuals will suffer from it. Especially to deserve to be mentioned, the proportion of TCM-induced IDILI showed an ascending trend year by year. So in this article, the author has reviewed some facts related with TCM-induced IDILI, including the predisposing causes and occurrence mechanism, and tries to provide reference for the prevention, diagnosis and treatment of TCM-induced IDILI through the analysis of characteristics and research status of TCM-induced IDILI and exploration of the internal relationship between Chinese medicine constitution type and IDILI.

[Development ideas of fine pharmaceutical materials of traditional Chinese medicine preparations based on active cluster theory].

The pharmaceutical materials are divided into coarse and fine types in the development of traditional Chinese medicine preparations. Fine materials with clear composition, stable content and high quality control conform to the international development trend of traditional Chinese medicine preparations. In this paper, the status of fine materials was analyzed, and the development ideas were tentatively put forward. On the one hand, the study on simple methods and efficient equipment shall be strengthened for the simultaneous separation of multiple components of traditional Chinese medicine; on the other hand, the knowledge for traditional Chinese medicine shall be broadened to further develop the scientific compatibility of monomers under the guidance of the theory of traditional Chinese medicine.

[Study on nephrotoxicity of ethanol extract from Alismatis Rhizoma in rats and its molecular mechanism].

Female rats were fed with ethanol extraction of Alismatis Rhizoma for 6 months to study its nephrotoxicity and molecular mechanism. HPLC was used to determine the components in ethanol extraction of Alismatis Rhizoma. An assessment of renal pathology was determined by HE staining. Meanwhile Western blot, immunohistochemical assay and q-PCR were used to assess the protein expression and mRNA level of Kim-1, clusterin, LCN2, osteopontin, ceruloplasmin and TIMP1 in rat kidney. Eight components were identified in ethanol extraction of Alismatis Rhizoma. Tubule-interstitial inflammation, renal tubular epithelial cell exfoliation and morphological changes of cell were observed in rat kidney. Comparing with control blank group, the protein expression of clusterin, Kim-1, LCN2, osteopontin and TIMP1 in rat kidney was significantly increased while the protein expression of ceruloplasmin was significantly decreased. The mRNA level of Kim-1, TIMP1, osteopontin, clusterin and LCN2 was significantly increased while the mRNA level of ceruloplasmin was significantly decreased. In this study, it was inferred that there is chronic toxicity in kidney by using high dosage of ethanol extraction of Alismatis Rhizoma for a long time. And the underlying molecular mechanism was related to regulate the protein expression of ceruloplasmin, clusterin, Kim-1, LCN2, osteopontin and TIMP1.

[Metabolism of paeoniflorin by rat intestinal flora in vitro].

In order to clarify the effect of intestinal flora on the absorption and metabolism of paeoniflorin in vivo, the metabolism of paeoniflorin by rat intestinal flora was studied under the in vitro anaerobic condition. Paeoniflorin was incubated with rat anaerobic intestinal flora for 48 h, and UPLC was used to detect the changes of paeoniflorin at different incubation time points under the following chromatographic conditions：WelchromTM C18 chromatographic column (4.6 mm×100 mm, 5 µm), with 0.1% formic acid(A)-acetonitrile(B) as the mobile phase for gradient elution. The flow rate was 0.4 mL•min⁻¹, and column temperature was 30 ℃. UPLC-Q-TOF-MS with positive ion mode(ESI ion source) was applied to investigate the structural characterization of metabolic products. The structures of the metabolites were identified by accurate molecular weight, TOF-MS/MS fragmentation information, combined with retention time and literature data review, and the intestinal metabolic rules were then analyzed. After incubation for 24 h, the paeoniflorin was metabolized completely, and the resulting metabolites(albiflorin, albiflorinaglycone, deacylate albiflorin, deacylate albiflorin aglycone and paeonilactone-B) were detected in rat intestinal flora. The metabolic pathway analysis showed that the isolated rat intestinal flora first transformed peoniflorin into albiflorin, and then further metabolized by glucose removal, phenyl group removal, or four-membered ring pyrolysis and rearrangement. Paeoniflorin was gradually transformed into more hydrophobic metabolites with smaller molecular mass, which were better absorbed by the intestinal tract.

[Simultaneous determination of 8 main compounds in Eclipta Herba by UPLC].

To establish an UPLC method for the simultaneous determination of 8 compounds in Eclipta Herba, such as isoquercitrin, luteoloside, demethylwedelolactone, isochlorogenic acid A, isochlorogenic acid C, luteolin, wedelolactone and apigenin. The experiment was performed with a Waters Acquity UPLC BEH C18 (2.1 mm×100 mm, 1.7 µm) column by gradient elution of 0.1% formic acid in water and acetonitrile: 0-4 min,10%-13% A; 4-10 min, 13%-16% A; 10-13 min, 16%-25% A; 13-17 min, 25%-28% A; 17-20 min,28%-40% A;20-25 min,40%-95% A. The flow rate was 0.3 mL•min⁻¹.. The condition of was the colum temperature was maintained at 35 ℃ and the detected wavelength was set at 350 mm. 8 components were separated clearly by this method. Also a good linearity was obtained between the chosen concentration(r≥0.999 0). The measured data showed that the recovery rate range from 96.60%-103.4% (n=6) and their RSD values were 0.86%-2.4%. The method has high recovery rate, good reproducibility and stability. It provides a scientific basis for the identification and quality evaluation of Eclipta Herba.

Bacteria-targeted magnolol-loaded multifunctional nanocomplexes for antibacterial and anti-inflammatory treatment.

Natural plant-derived small molecules have shown great potential for their antimicrobial and anti-inflammatory properties. In this study, we successfully developed a nanocomplex consisting of magnolol (Mag), a surfactant with an 18 carbon hydrocarbon chain and multi-amine head groups (C18N3), and a peptide (cyclic 9-amino acid peptide (CARG)) with targeting capabilities forStaphylococcus aureus(S. aureus). The obtained Mag/C18N3/CARG nanocomplexes exhibited strong antibacterial activity againstS. aureus. Furthermore, they demonstrated anti-inflammatory effects by reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ßfrom macrophage inflammatory cells. This was achieved through downregulating the activation of NF-κB, KEAP1, and NRF2 signaling pathways. In a murine skin infection model, the Mag/C18N3/CARG nanocomplexes effectively suppressed the growth ofS. aureusin the infected area and promoted wound healing. Additionally, in a mouse model of acute kidney injury (AKI), the nanocomplexes significantly reduced the levels of blood urea nitrogen and creatinine, leading to a decrease in mortality rate. These findings demonstrate the potential of combining natural plant-derived small molecules with C18N3/CARG assemblies as a novel approach for the development of effective and safe antibacterial agents.

Wheat germ agglutinin modified mixed micelles overcome the dual barrier of mucus/enterocytes for effective oral absorption of shikonin and gefitinib.

The combination of shikonin (SKN) and gefitinib (GFB) can reverse the drug resistance of lung cancer cells by affecting energy metabolism. However, the poor solubility of SKN and GFB limits their clinical application because of low bioavailability. Wheat germ agglutinin (WGA) can selectively bind to sialic acid and N-acetylglucosamine on the surfaces of microfold cells and enterocytes, and is a targeted biocompatible material. Therefore, we created a co-delivery micelle system called SKN/GFB@WGA-micelles with the intestinal targeting functions to enhance the oral absorption of SKN and GFB by promoting mucus penetration for nanoparticles via oral administration. In this study, Caco-2/HT29-MTX-E12 co-cultured cells were used to simulate a mucus/enterocyte dual-barrier environment, and HCC827/GR cells were used as a model of drug-resistant lung cancer. We aimed to evaluate the oral bioavailability and anti-tumor effect of SKN and GFB using the SKN/GFB@WGA-micelles system. In vitro and in vivo experimental results showed that WGA promoted the mucus penetration ability of micelles, significantly enhanced the uptake efficiency of enterocytes, improved the oral bioavailability of SKN and GFB, and exhibited good anti-tumor effects by reversing drug resistance. The SKN/GFB@WGA-micelles were stable in the gastrointestinal tract and provided a novel safe and effective drug delivery strategy.