The activator protein-1 complex governs a vascular degenerative transcriptional programme in smooth muscle cells to trigger aortic dissection and rupture.

BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.

Role of toll-like receptors in the pathogenesis of COVID-19: Current and future perspectives.

The coronavirus disease 2019 (COVID-19) pandemic underlines a persistent threat of respiratory tract infectious diseases and warrants preparedness for a rapid response. At present, COVID-19 has had a serious social impact and imposed a heavy global burden on public health. The exact pathogenesis of COVID-19 has not been fully elucidated. Since the outbreak of COVID-19, a renewed attention has been brought to Toll-like receptors (TLRs). Available data and new findings have demonstrated that the interaction of human TLRs and SARS-CoV-2 is a vital mediator of COVID-19 immunopathogenesis. TLRs such as TLR2, 4, 7 and 8 are potentially important in viral combat and activation of immunity in patients with COVID-19. Therapeutics targeting TLRs are currently considered promising options against the pandemic. A number of TLR-targeting immunotherapeutics are now being investigated in preclinical studies and different phases of clinical trials. In addition, innovative vaccines based on TLRs under development could be a promising approach for building a new generation of vaccines to solve the current challenges. In this review, we summarize recent progress in the role of TLRs in COVID-19, focusing the new candidate drugs targeting TLRs, the current technology and potential paths forward for employing TLR agonists as vaccine adjuvants.

A sensitive ratiometric fluorescence probe with a large spectral shift for sensing and imaging of palladium.

Palladium (Pd) is an important heavy metal with excellent catalytic properties and widely used in organic chemistry and the pharmaceutical industry. Efficient and convenient analytical techniques for Pd are urgently needed due to the hazardous effects of Pd on the environment and human health. Herein, we have developed five new ratiometric probes for the selective detection of Pd0 based on the Pd-catalyzed Tsuji-Trost reaction. Among them, the F-substituted probe PF-Pd showed the largest spectral shift (148 nm) and the most sensitive response (detection limit 2.11 nM). PF-Pd was employed to determine Pd0 in tap water or lake water samples, which presented satisfactory accuracy and precision. In addition, profiting from its distinct colorimetric response, visual detection of Pd0 was performed on PF-Pd loaded test strips or in field soil samples. Furthermore, fluorescence imaging of living 4T1 cells demonstrated that PF-Pd is suitable for imaging of intracellular Pd0. The good analytical performance of PF-Pd may enable it to be widely used in the convenient, rapid, sensitive and selective detection of Pd0 in environmental or biological analysis.

A near-infrared and lysosome-targeted BODIPY photosensitizer for photodynamic and photothermal synergistic therapy.

Phototherapy is a promising approach for the treatment of cancers and other diseases. So far, many photosensitizers have been developed for photodynamic therapy (PDT) or photothermal therapy (PTT). However, it remains a challenge to develop a system for synergistic PDT and PTT with specific targeting and real-time fluorescence tracking. Herein, we designed a multifunctional BODIPY derivative, Lyso-BDP, for synergistic PDT and PTT against tumors. Lyso-BDP was composed of three parts: (1) the BODIPY fluorophore was selected as a theranostic core, (2) a morpholine group modified on meso-BODIPY served as a lysosome-targeting unit for enhancing the antitumor effect, and (3) N,N-diethyl-4-vinylaniline was attached to the BODIPY core to extend its wavelength to the near-infrared region. Finally, Lyso-BDP shows near-infrared absorption and emission, photosensitizing activity, lysosomal targeting, and synergistic PDT and PTT effects, and effectively kills cancer cells both in vitro and in vivo. Therefore, our study demonstrates that Lyso-BDP can serve as a promising photosensitizer in the therapy of cancer with potential clinical application prospects.

A simple and sensitive electrochemical sensor for the detection of peptidase activity.

In this work, a simple and sensitive electrochemical sensor was proposed for the detection of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) activity. Firstly, the BACE1 specific peptide was modified onto the Au electrode to graft a single-strand DNA with polycytosine DNA sequence (dC12) via amide bonding between peptide and dC12. Because the dC12 is abundant in phosphate groups, thus it can react with molybdate to form redox molybdophosphate, which can generate electrochemical current. Using BACE1 as a model peptidase, the proposed sensor shows a linear response range from 1 to 15 U/mL and limit of detection down to 0.05 U/mL. The sensor displays good performance for the BACE1 activity detection in human serum samples, which may have potential applications in the clinical diagnostics of Alzheimer's disease.

DAL-1/4.1B promotes the uptake of exosomes in lung cancer cells via Heparan Sulfate Proteoglycan 2 (HSPG2).

DAL-1/4.1B is frequently absent in lung cancer tissues, which is significantly related to the occurrence and development of lung cancer. In this research, we found that DAL-1/4.1B affected the uptake of exosomes by lung cancer cells. When the expression of DAL-1/4.1B increased and decreased, the ability of exosome uptake enhanced and attenuated correspondingly. And we found that when cells were treated with different vesicles uptake inhibitors (chlorpromazine, methyl-ß-cyclodextrin (MßCD), cytochalasin D, chloroquine and heparin) and heparinase (HSPE), only heparin and HSPE counteracted the uptake enhancement effect caused by DAL-1/4.1B. Therefore, we speculated that DAL-1/4.1B might promote the uptake of exosomes through the heparan sulfate proteoglycans (HSPGs) pathway. After screening the expression of HSPGs and HSPE in H292 cells, the expression of heparan sulfate proteoglycan 2 (HSPG2) increased with overexpression of DAL-1/4.1B and decreased with knockdown of DAL-1/4.1B. Meanwhile, exosome uptake decreased with HSPG2 knockdown in H292 and DAL-1/4.1B-overexpressing H292 cells. Moreover, knockdown of DAL-1/4.1B and HSPG2 in lung cancer A549 cells resulted in a similar decrease in exosome uptake, and the expression of HSPG2 was also decreased with DAL-1/4.1B knockdown. These results indicated that HSPG2 directly affected the uptake of exosomes, while DAL-1/4.1B positively affected the expression of HSPG2. Therefore, DAL-1/4.1B may promote cellular adhesion and inhibit migration in cancer cells.

Targeting the tubulin C-terminal tail by charged small molecules.

The disordered tubulin C-terminal tail (CTT), which possesses a higher degree of heterogeneity, is the target for the interaction of many proteins and cellular components. Compared to the seven well-described binding sites of microtubule-targeting agents (MTAs) that localize on the globular tubulin core, tubulin CTT is far less explored. Therefore, tubulin CTT can be regarded as a novel site for the development of MTAs with distinct biochemical and cell biological properties. Here, we designed and synthesized linear and cyclic peptides containing multiple arginines (RRR), which are complementary to multiple acidic residues in tubulin CTT. Some of them showed moderate induction and promotion of tubulin polymerization. The most potent macrocyclic compound 1f was found to bind to tubulin CTT and thus exert its bioactivity. Such RRR containing compounds represent a starting point for the discovery of tubulin CTT-targeting agents with therapeutic potential.

Discovery of 12ß-oxygenated oleanolic acid alkyl esters as potent and selective FXR modulators exhibiting hyperglycemia amelioration in vivo.

Farnesoid X receptor (FXR) ligands have been actively pursued to treat metabolic disorders, liver and bile diseases, among others. Starting from a widely occurring natural product, oleanolic acid (OA), we discovered potent and selective FXR modulator from the 12ß-oxygenated OA alkyl esters, with the assistance of molecular modeling. The representative compound 7b modulated some FXR downstream genes involved in glucose and lipid metabolism in cells, and significantly improved hyperglycemia in KKay fat mice fed with high fat diet, through the reduction of mRNA expression of gluconeogenesis genes PEPCK and G6Pase. This study provides a new series of selective FXR modulator, as well as the in vitro and in vivo evidence for their potential to improve hyperglycemia in diabetic mice through FXR antagonism.

Bacteria-derived outer membrane vesicles engineered with over-expressed pre-miRNA as delivery nanocarriers for cancer therapy.

Outer membrane vesicles (OMVs) of Escherichia coli as nanoscale spherical vesicles have been recently used in cancer therapy as drug carriers. However, most of them need complicated methods to load cargos. Herein, we proposed an inexpensive and potentially mass-produced method for the preparation of OMV engineered with over-expressed pre-miRNA. In this work, we found that OMV can be released and inherit over-expressed tRNALys-pre-miRNA from mother E. coli that directly used for the tumor therapy. The eukaryotic cells infection experiments revealed that the over-expressed pre-miRNA inside OMV could be released and processed into mature miRNAs with the aid of the camouflage of "tRNA scaffold". Moreover, the group in vivo treated with targeted OMVtRNA-pre-miR-126 obviously inhibited the expression of target oncogenic CXCR4, and significantly restrain the proliferation of breast cancer tissues. Together, these findings indicated that the OMV-based platform is a versatile and powerful strategy for personalized tumor therapy directly and specificity.

Chemiluminescence in Combination with Organic Photosensitizers: Beyond the Light Penetration Depth Limit of Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising noninvasive medical technology that has been approved for the treatment of a variety of diseases, including bacterial and fungal infections, skin diseases, and several types of cancer. In recent decades, many photosensitizers have been developed and applied in PDT. However, PDT is still limited by light penetration depth, although many near-infrared photosensitizers have emerged. The chemiluminescence-mediated PDT (CL-PDT) system has recently received attention because it does not require an external light source to achieve targeted PDT. This review focuses on the rational design of organic CL-PDT systems. Specifically, PDT types, light wavelength, the chemiluminescence concept and principle, and the design of CL-PDT systems are introduced. Furthermore, chemiluminescent fraction examples, strategies for combining chemiluminescence with PDT, and current cellular and animal applications are highlighted. Finally, the current challenges and possible solutions to CL-PDT systems are discussed.

Novel Lysosome-Targeting Fluorescence Off-On Photosensitizer for Near-Infrared Hypoxia Imaging and Photodynamic Therapy In Vitro and In Vivo.

Photodynamic therapy (PDT) has emerged as a new antitumor modality. Hypoxia, a vital characteristic of solid tumors, can be explored to stimulate the fluorescence response of photosensitizers (PSs). Considering the characteristics of PDT, the targeting of organelles employing PS would enhance antitumor effects. A new multifunctional cyanine-based PS (CLN) comprising morpholine and nitrobenzene groups was prepared and characterized. It generated fluorescence in the near-infrared (NIR) region in the presence of sodium dithionite (Na2S2O4) and nitroreductase (NTR). The response mechanism of CLN was well investigated, thus revealing that its obtained reduction product was CLNH. The obtained fluorescence and singlet oxygen quantum yield of CLNH were 8.65% and 1.60%, respectively. Additionally, the selective experiment for substrates indicated that CLN exhibited a selective response to NTR. Thus, CLN fluorescence could be selectively switched on and its fluorescence intensity increased, following a prolonged stay in hypoxic cells. Furthermore, fluorescence colocalization demonstrated that CLN could effectively target lysosomes. CLN could generate reactive oxygen species and kill tumor cells (IC50 for 4T1 cells was 7.4 µM under a hypoxic condition), following its response to NTR. NIR imaging and targeted PDT were finally applied in vivo.

A Novel Utilization of Water Extract of Suaeda Salsa in the Pd/C Catalyzed Suzuki-Miyaura Coupling Reaction.

Using biomass-derived solvents in various organic reactions is challenging for the fine chemicals industry. We herein report a Pd/C catalyzed Suzuki-Miyaura reaction in water extract of suaeda salsa (WES) without using external phosphine ligand, base, and organic solvent. The cross-coupling reactions were carried out in a basic WES medium with a broad substrate scope and wide functional group tolerance. Furthermore, the high purity of solid biaryl products can be obtained by column chromatography or filtration.

A Hydroxytricyanopyrrole-Based Fluorescent Probe for Sensitive and Selective Detection of Hypochlorous Acid.

Hypochlorous acid (HOCl) is a reactive substance that reacts with most biomolecules and is essential in physiological and pathological processes. Abnormally elevated HOCl levels may cause inflammation and other disease responses. To further understand its key role in inflammation, HOCl must be detected in situ. Here, we designed a hydroxytricyanopyrrole-based small-molecule fluorescent probe (HTCP-NTC) to monitor and identify trace amounts of HOCl in biological systems. In the presence of HOCl, HTCP-NTC released hydroxyl groups that emit strong fluorescence covering a wide wavelength range from the visible to near-infrared region owing to the resumption of the intramolecular charge transfer process. Additionally, HTCP-NTC demonstrated a 202-fold fluorescence enhancement accompanied by a large Stokes shift and a low detection limit (21.7 nM). Furthermore, HTCP-NTC provided a rapid response to HOCl within 18 s, allowing real-time monitoring of intracellular HOCl. HTCP-NTC exhibited rapid kinetics and biocompatibility, allowing effective monitoring of the exogenous and endogenous HOCl fluctuations in living cells. Finally, based on fluorescence imaging, HTCP-NTC is a potential method for understanding the relationship between inflammation and HOCl.

Molecular mechanism of activation of human musk receptors OR5AN1 and OR1A1 by (R)-muscone and diverse other musk-smelling compounds.

Understanding olfaction at the molecular level is challenging due to the lack of crystallographic models of odorant receptors (ORs). To better understand the molecular mechanism of OR activation, we focused on chiral (R)-muscone and other musk-smelling odorants due to their great importance and widespread use in perfumery and traditional medicine, as well as environmental concerns associated with bioaccumulation of musks with estrogenic/antiestrogenic properties. We experimentally and computationally examined the activation of human receptors OR5AN1 and OR1A1, recently identified as specifically responding to musk compounds. OR5AN1 responds at nanomolar concentrations to musk ketone and robustly to macrocyclic sulfoxides and fluorine-substituted macrocyclic ketones; OR1A1 responds only to nitromusks. Structural models of OR5AN1 and OR1A1 based on quantum mechanics/molecular mechanics (QM/MM) hybrid methods were validated through direct comparisons with activation profiles from site-directed mutagenesis experiments and analysis of binding energies for 35 musk-related odorants. The experimentally found chiral selectivity of OR5AN1 to (R)- over (S)-muscone was also computationally confirmed for muscone and fluorinated (R)-muscone analogs. Structural models show that OR5AN1, highly responsive to nitromusks over macrocyclic musks, stabilizes odorants by hydrogen bonding to Tyr260 of transmembrane α-helix 6 and hydrophobic interactions with surrounding aromatic residues Phe105, Phe194, and Phe207. The binding of OR1A1 to nitromusks is stabilized by hydrogen bonding to Tyr258 along with hydrophobic interactions with surrounding aromatic residues Tyr251 and Phe206. Hydrophobic/nonpolar and hydrogen bonding interactions contribute, respectively, 77% and 13% to the odorant binding affinities, as shown by an atom-based quantitative structure-activity relationship model.

Neuroprotective effects of andrographolide derivative CX-10 in transient focal ischemia in rat: Involvement of Nrf2/AE and TLR/NF-κB signaling.

Ischemic stroke is a major cause of mortality and disability worldwide. To date there is no ideal effective treatment. 3, 14, 19-triacetyl andrographolide (CX-10) is a new molecule entity derived from andrographolide. The aim of the present study was to evaluate the neuroprotection of CX-10 against experimental cerebral ischemia. The anti-inflammation of CX-10 was screened using LPS-induced inflammation in vitro and in vivo. Rats were subjected to 1.5 h of middle cerebral occlusion (MCAO) and then reperfusion for 72 h. The infarct size was evaluated by TTC staining, and the behavioral disturbance was evaluated, and inflammatory cytokines and anti-oxidant enzymes in brain tissues were examined. Western blot was used to analyze the expression of proteins. The results showed that CX-10 exerted potent anti-inflammatory and anti-oxidation activities, which significantly inhibited LPS-induced TNF-α and NO release, lowered TNF-α and IL-1ß levels in the brain, meanwhile increased activities of SOD, CAT and GSH-P × . The effect of CX-10 was equivalent to that of dexamethasone, and was obviously superior to that of andrographolide. CX-10 exhibited a neuroprotective effects, manifested as reducing infarct size, improving neurological function and reducing motor impairments. Furthermore, western blot analysis revealed that treatment with CX-10 down-regulated the expression of TLR4, NF-κB, TNF-α and iNOS, induced Nrf2 and HO-1 expression. Overall, CX-10 has a favorable neuroprotection in ischemic brain injury. The mechanism may involve inhibition of TLR4/NF-κB signaling pathway and upregulation of Nrf2/ARE signaling pathway. All these indicated that CX-10 is likely to be a promising agent for ischemic stroke.

Protective effect of Salvianolic acid A on ischaemia-reperfusion acute kidney injury in rats through protecting against peritubular capillary endothelium damages.

Renal ischaemia-reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Peritubular capillary (PTC) endothelium damages are an important pathogenesis during I/R AKI. Salvianolic acid A (SAA) possesses various pharmacological activities. The study investigated whether SAA ameliorated I/R AKI through protecting against PTC endothelium damages. Male Sprague-Dawley rats were divided into 6 groups: control, sham, I/R, and I/R plus SAA (2.5, 5, 10 mg/kg) groups. Rats were subjected to bilateral renal pedicle clamping for 60 min, and killed at 24 hr after reperfusion. Kidney injury, PTC endothelium damages and factors affecting PTC endothelium were evaluated. SAA significantly decreased blood urea nitrogen and serum creatinine levels, and reduced urine kidney injury molecule-1 concentration. Simultaneously, SAA alleviated histological damages, prevented PTC endothelium damages, preserved the density of PTC and improved renal hypoxia. Furthermore, SAA inhibited platelet activation, elevated Klotho protein expression and up-regulated vascular endothelial growth factor A expression. Overall, SAA has protective effects on AKI induced by I/R. Preventing PTC endothelium damages and preserving PTC integrity to improve the renal hypoxia may be the ways for SAA to ameliorate AKI. All these indicate that SAA is likely to be a promising agent for AKI.

MiR-9 Regulates the Expression of BACE1 in Dementia Induced by Chronic Brain Hypoperfusion in Rats.

BACKGROUND/AIMS: MicroRNA-9 (miR-9) plays important roles in nervous system diseases such as glioblastoma and neurodegenerative disorders. However, how miR-9 contributes to dementia requires further study. In this study, we evaluated the role of miR-9 in dementia and the molecular mechanisms underlying its effects. METHODS: A rat model of dementia was created by occlusion of the bilateral common carotid artery (2VO) for 8 weeks. Learning and memory were assessed using the Morris Water Maze (MWM). MicroRNA expression profiling was performed according to a protocol provided by LC Sciences, and quantitative real-time PCR (qRT-PCR) was used to detect the level of miR-9. Transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining were used to assess pathological changes in brain tissue. Western blot and immunofluorescence were employed to detect the expression of ß-site APP cleaving enzyme 1 (BACE1) and c-AMP response element-binding protein (CREB). RESULTS: Learning and memory were significantly impaired in 2VO rats, and these changes were accompanied by neuronal loss and glial activation in brain tissues. miR-9 was greatly upregulated in both the hippocampus and cortex of rats following 2VO. Knockdown of endogenous miR-9 via lentiviral vector-mediated delivery of its antisense molecule (lenti-pre-AMO-miR-9) reduced the vulnerability to dementia, reversed the increase in BACE1 expression, and ameliorated the reduction in CREB expression triggered by 2VO. BACE1 protein levels were significantly increased, but CREB protein levels were significantly decreased in the presence of miR-9 in cultured neonatal rat neurons (NRNs). AMO-miR-9 rescued the upregulation of BACE1 and downregulation of CREB elicited by miR-9 in rats. Dual luciferase assay experiments showed that overexpression of miR-9 inhibited the expression of CREB by targeting its 3'UTR domain. CREB protein was downregulated by miR-9 overexpression which was reversed by miR-9 inhibition in cultured NRNs. TEM imaging showed that miR-9 caused damage to NRNs, which was reversed by addition of AMO-miR-9. CONCLUSION: We conclude that miR-9 plays an important role in regulating the process of dementia induced by 2VO in rats by increasing BACE1 expression via downregulation of CREB.

Fluorinated Musk Fragrances: The CF2 Group as a Conformational Bias Influencing the Odour of Civetone and (R)-Muscone.

The difluoromethylene (CF2 ) group has a strong tendency to adopt corner over edge locations in aliphatic macrocycles. In this study, the CF2 group has been introduced into musk relevant macrocyclic ketones. Nine civetone and five muscone analogues have been prepared by synthesis for structure and odour comparisons. X-ray studies indeed show that the CF2 groups influence ring structure and they give some insight into the preferred ring conformations, triggering a musk odour as determined in a professional perfumery environment. The historical conformational model of Bersuker and co-workers for musk fragrance generally holds, and structures that become distorted from this consensus, by the particular placement of the CF2 groups, lose their musk fragrance and become less pleasant.

Total Synthesis and Antifungal Activity of Palmarumycin CP17 and Its Methoxy Analogues.

Total synthesis of naturally occurring spirobisnaphthalene palmarumycin CP17 and its methoxy analogues was first achieved through Friedel-Crafts acylation, Wolff-Kishner reduction, intramolecular cyclization, ketalization, benzylic oxidation, and demethylation using the inexpensive and readily available methoxybenzene, 1,2-dimethoxybenzene and 1,4-dimethoxybenzene and 1,8-dihydroxynaphthalene as raw materials. Demethylation with (CH3)3SiI at ambient temperature resulted in ring A aromatization and acetal cleavage to give rise to binaphthyl ethers. The antifungal activities of these spirobisnaphthalene derivatives were evaluated, and the results revealed that 5 and 9b exhibit EC50 values of 9.34 µg/mL and 12.35 µg/mL, respectively, against P. piricola.

Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin.

Geniposide (GE) is the main bioactive component of Gardeniae Fructus. The hepatotoxicity of geniposide limited clinical application. In order to get a new geniposide derivative that has less hepatotoxicity and still possesses the antidepressant activity, a new C-1 hydroxyl methylation derivative named methyl genipin (MG) was synthesized from geniposide. In the present study, we demonstrated that MG did not increase the liver index, alanine aminotransferase (ALT) and aspirate aminotransferase (AST). Histopathological examination suggested that no toxic damages were observed in rats treated orally with MG (0.72 mmol/kg). More importantly, a 7-day treatment with MG at 0.13, 0.26, and 0.52 mmol/kg/day could reduce the duration of immobility. It showed that the antidepressant-like effects of MG were similar to GE in the tail suspension test and the forced swim test. Furthermore, we found MG could be detected in the brain homogenate of mice treated orally with MG 0.52 mmol/kg/day for 1 day by HPLC. The area under the curve (AUC) of MG in the brain homogenate was enhanced to 21.7 times that of GE. The brain amount and distribution speed of MG were improved significantly after oral administration. This study demonstrated that MG possessed the antidepressant effects and could cross the blood-brain barrier, but had less hepatotoxicity.