The OsZIP2 transporter is involved in root-to-shoot translocation and intervascular transfer of cadmium in rice.

Cadmium (Cd) is a toxic metal that poses serious threats to human health. Rice is a major source of dietary Cd but how rice plants transport Cd to the grain is not fully understood. Here, we characterize the function of the ZIP (ZRT, IRT-like protein) family protein, OsZIP2, in the root-to-shoot translocation of Cd and intervascular transfer of Cd in nodes. OsZIP2 is localized at the plasma membrane and exhibited Cd2+ transport activity when heterologously expressed in yeast. OsZIP2 is strongly expressed in xylem parenchyma cells in roots and in enlarged vascular bundles in nodes. Knockout of OsZIP2 significantly enhanced root-to-shoot translocation of Cd and alleviated the inhibition of root elongation by excess Cd stress; whereas overexpression of OsZIP2 decreased Cd translocation to shoots and resulted in Cd sensitivity. Knockout of OsZIP2 increased Cd allocation to the flag leaf but decreased Cd allocation to the panicle and grain. We further reveal that the variation of OsZIP2 expression level contributes to grain Cd concentration among rice germplasms. Our results demonstrate that OsZIP2 functions in root-to-shoot translocation of Cd in roots and intervascular transfer of Cd in nodes, which can be used for breeding low Cd rice varieties.

Expanding individualized therapeutic options via genoproteomics.

Clinical next-generation sequencing (NGS) tests have enabled treatment recommendations for cancer patients with driver gene mutations. Targeted therapy options for patients without driver gene mutations are currently unavailable. Herein, we performed NGS and proteomics tests on 169 formalin-fixed paraffin-embedded (FFPE) samples of non-small cell lung cancers (NSCLC, 65), colorectal cancers (CRC, 61), thyroid carcinomas (THCA, 14), gastric cancers (GC, 2), gastrointestinal stromal tumors (GIST, 11), and malignant melanomas (MM, 6). Of the 169 samples, NGS detected 14 actionable mutated genes in 73 samples, providing treatment options for 43% of the patients. Proteomics identified 61 actionable clinical drug targets approved by the FDA or undergoing clinical trials in 122 samples, providing treatment options for 72% of the patients. In vivo experiments demonstrated that the Mitogen-Activated Protein Kinase (MEK) inhibitor could block lung tumor growth in mice with overexpression of Map2k1 protein. Therefore, protein overexpression is a potentially feasible indicator for guiding targeted therapies. Collectively, our analysis suggests that combining NGS and proteomics (genoproteomics) could expand the targeted treatment options to 85% of cancer patients.

A novel detection technology for early gastric cancer based on Raman spectroscopy.

Despite universal endoscopic screening, early detection of gastric cancer is challenging, led researchers to seek for a novel approach in detecting. Raman spectroscopy measurements as a fingerprint of biochemical structure, enable accurate prediction of gastric lesions non-destructively. This study aimed to evaluate the diagnostic power of Raman spectroscopy in early gastric cancer (EGC), and reveal dynamic biomolecular changes in vitro from normal to EGC. To clarify the biochemical alterations in Correa's cascade, Raman spectra of human normal gastric mucosa, intestinal metaplasia, dysplasia, and adenocarcinoma were compared at tissue and cellular levels based on a self-developed data processing program. For effectively identify EGC, Raman spectroscopy was used combined with multiple machine learning methods, including partial least-squares discriminant analysis (PLS-DA), support vector machine (SVM), and convolutional neural network (CNN) with leave-one-out (LOO) cross validation. A total of 450 Raman spectra were investigated in this study. The upregulation of νsym(O-P-O) backbone (p < 0.001) was identified as a favorable factor for the diagnosis of EGC, the area under the ROC curve (AUC) was up to 0.918. In addition, higher levels of lactic acid (p < 0.001), lipids (p < 0.001), phenylalanine (p = 0.002), and carotenoids (p < 0.001) were detected in EGC. Multivariate machine learning methods for diagnosis of EGC based on Raman spectroscopy, the sensitivity, specificity, accuracy, and AUC were 91.0%, 100%, 94.8%, and 95.8% for SVM, and 84.8%, 92.0%, 88.8%, and 95.5% for CNN, respectively. Raman spectroscopy can be used as a powerful tool for detecting EGC while elucidating biomolecular dynamics in tumorigenesis. (Chictr.org.cn, ChiCTR2200060720.).

Botany, traditional usages, phytochemistry, pharmaceutical analysis, and pharmacology of Eleutherococcus nodiflorus (Dunn) S.Y.Hu: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Eleutherococcus nodiflorus (Dunn) S.Y.Hu (Araliaceae), also called Eleutherococcus gracilistylus, Acanthopanax gracilistylus, and Xi-zhu-wu-jia (Wujiapi or Nan Wujiapi) in Chinese, is a widely used traditional Chinese herb with the effects of dispelling pathogenic wind and eliminating dampness, nourishing liver and kidney, diuresis and detumescence, promoting blood circulation for removing blood stasis, and strengthening the bones and tendons according to the theory of Traditional Chinese Medicine (TCM). It has been used as medicine for the treatment of paralysis, arthritis, rheumatism, lameness, body asthenia, fatigue, edema, beriberi, and liver diseases. Meanwhile, E. nodiflorus (EN, thereafter) has ginseng-like activities known as "ginseng-like herb". AIMS OF THE REVIEW: This review aims to present comprehensive information for the research progress of EN, including taxonomic position, botany, traditional usages, phytochemistry, pharmaceutical analysis, pharmacology and toxicology. Among them, phytochemical and pharmacological studies are mainly focused. MATERIALS AND METHODS: Relevant literature was acquired from scientific databases including Web of Science, PubMed, Google Scholar, Baidu Scholar, SciFinder and Chinese national knowledge infrastructure (CNKI). Monographs and Chinese pharmacopeia were also utilized as references. RESULTS: In the past decade, a great number of phytochemical and pharmaceutical analyses, as well as pharmacological studies on EN have been carried out. Several kinds of chemical compositions have been reported, including essential oil, sesquiterpenes, diterpenes, triterpenes, phenylpropanoids, lignans, caffeoyl quinic acids, flavonoids, steroids, fatty acids, ceramides as well as other compounds, among which, diterpenes and triterpenes were considered to be the most active components. The fingerprint chromatography, qualitative and quantitative analysis were used for the methods of quality control of EN. Considerable pharmacological experiments in vitro and in vivo have demonstrated that EN possessed hypoglycemic, anti-inflammatory, anticancer, anti-ageing, anti-fatigue, immunomodulatory, hepatoprotective, antioxidant, anti-AChE, anti-BuChE, anti-hyaluronidase, and antiobesity activities. CONCLUSIONS: As an important TCM, a large number of investigations have proved that EN and terpenoids isolated from EN have markedly therapeutic efficacy on diabetes, inflammation, and cancer disorders. These research findings provide modern scientific evidence for the traditional uses of EN. Moreover, more novel and active secondary metabolites from EN, as well as the in vivo and clinical in-depth tests are required in the future.

Enantioselective synthesis of atropisomeric indoles via iron-catalysed oxidative cross-coupling.

Heterobiaryl compounds that exhibit axial chirality are of increasing value and interest across several fields, but direct oxidative methods for their enantioselective synthesis remain elusive. Here we disclose that an iron catalyst in the presence of a chiral PyBOX ligand and an oxidant enables direct coupling between naphthols and indoles to yield atropisomeric heterobiaryl compounds with high levels of enantioselectivity. The reaction exhibits remarkable chemoselectivity and exclusively yields cross-coupled products without competing homocoupling. Mechanistic investigations enable us to postulate that an indole radical is generated in the reaction but that this is probably an off-cycle event, and that the reaction proceeds through formation of a chiral Fe-bound naphthoxy radical that is trapped by a nucleophilic indole. We envision that this simple, cheap and sustainable catalytic manifold will facilitate access to a range of heterobiaryl compounds and enable their application across the fields of materials science, medicinal chemistry and catalysis.

Antioxidative and Cytoprotective Effects of Ganoderma applanatum and Fomitopsis pinicola in PC12 Adrenal Phaeochromocytoma Cells.

Considering the impact of oxidative stress on the development of many diseases, together with the role of natural antioxidants in maintaining physiological balance in humans, medicinal mushrooms are potential sources of bioactive compounds against many diseases. In the present work, in vitro evaluation of the biological activities of the alcoholic extracts of two wild tree mushrooms, namely, Ganoderma applanatum and Fomitopsis pinicola, has been performed. Extraction of G. applanatum (GAE) and F. pinicola (FPE) was conducted with 60% ethanol and 100% ethanol sequentially. UPLC-MS/MS identification was conducted on the two mushrooms extracts. A total of 15 substances were identified in GAE, including 3 spiro meroterpenoids and 12 triterpenoids; a total of 14 chemical constituents were iden¬tified in FPE, including 8 triterpenoids, 4 triterpene glycosides, 1 lanosterol, and 1 lanostanoid. The resulting extracts were examined for their in vitro antioxidative and cytoprotective effects against AAPH-induced oxidative damage. Our results demonstrated that both extracts have potent antioxidative activities, when GAE was 0.2 mg/mL, the clearance rates of DPPH and ABTS have reached 93.34% and 99.93%, respectively. When FPE was 1.4 mg/mL and 0.6 mg/mL, the scavenging rates of DPPH and ABTS have reached 91.76% and 100%, respectively. Both the alcoholic extracts of G. applanatum and F. pinicola were able to protect the AAPH-induced damage and could effectively inhibit cell aging via ß-galactosidase (SA ß-gal) staining activity test and scanning electron microscopy analysis.

Eleutheroside K Isolated from Acanthopanax henryi (Oliv.) Harms Inhibits the Expression of Virulence-Related Exoproteins in Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus (S.) aureus (MRSA) is a representative pathogen that produces numerous virulence factors involving manifold cytotoxins and exotoxins. The present study was designed to investigate the influence of Eleutheroside K (ETSK), a single compound isolated from the leaves of Acanthopanax (A.) henryi (Oliv.) Harms, on the exotoxins secreted by MRSA. The transcription and translation of the exotoxins (α-hemolysin and staphylococcal enterotoxins) related to virulence in S. aureus were determined via quantitative RT-PCR and western blot analysis. The effect of ETSK on the production of tumor necrosis factor (TNF)-α was evaluated using enzyme-linked immunosorbent assay. As a result, ETSK at sub-MIC concentrations could reduce the protein expression of α-hemolysin and enterotoxin, and the expression of genes that regulate virulence factors was also inhibited. In addition, the TNF-inducing activity of S. aureus was attenuated by ETSK in a dose-dependent manner. These results revealed that ETSK not only reduced the protein and gene expression levels of related exotoxins but also suppressed the ability of S. aureus to induce macrophages to release cytokines. This study indicated that the inhibition of MRSA infection by ETSK may be achieved by reducing the virulence of S. aureus and highlighted the potential of ETSK as an innovative strategy for the prevention and treatment of MRSA infections.

Acanthopanax henryi: Review of Botany, Phytochemistry and Pharmacology.

Acanthopanax henryi (Oliv.) Harms (Araliaceae), also known as Eleutherococcus henryi and Caoyewujia (Hengliwujia) in Chinese, is a widely used traditional Chinese herb with the effects of expelling wind and removing dampness, relaxing the muscles and stimulating the blood circulation, and regulating the flow of qi to alleviate pain in the theory of Traditional Chinese Medicine. Acanthopanax henryi (AH, thereafter) possesses ginseng-like activities and is known as ginseng-like herb. In the past decade, a great number of phytochemical and pharmacological studies on AH have been carried out. Several kinds of chemical compositions have been reported, including terpenoids (monoterpenoids, diterpenoids, and triterpenoid saponins), phenylpropanoids, caffeoyl quinic acid derivatives, flavonoids, lignans, sterols, fatty acids, etc., among which, triterpenoid saponins were considered to be the most active components. Considerable pharmacological experiments in vitro have demonstrated that AH possessed anti-neuroinflammatory, anti-adipogenic, anti-inflammatory, antibacterial, anti-cancer, anti-oxidation, anti-AChE, anti-BuChE, and antihyaluronidase activities. The present review is an up-to-date and comprehensive analysis of the botany, phytochemistry, and pharmacology of AH.

Nickel-catalyzed Suzuki-Miyaura cross-couplings of aldehydes.

Transition-metal-catalyzed cross-couplings have been extensively used in the pharmaceutical and agrochemical industries for the construction of diverse C-C bonds. Conventional cross-coupling reactions require reactive electrophilic coupling partners, such as organohalides or sulfonates, which are not environmentally friendly and not naturally abundant. Another disadvantage associated with these transformations is the need for an exogenous base to facilitate the key transmetalation step, and this reagent inevitably induces side reactions and limits the substrate scope. Here, we report an unconventional Suzuki-type approach to the synthesis of biaryls, through nickel-catalyzed deformylative cross coupling of aldehydes with organoboron reagents under base-free conditions. The transformation tolerates structurally diverse (hetero)aryl substituents on both coupling partners and shows high reactivity and excellent functional group tolerance. Furthermore, the protocol was carried out on gram scale and successfully applied to the functionalization of complex biologically active molecules. Mechanistic investigations support a catalytic cycle involving the oxidative addition of the nickel into the aldehyde C(acyl)-H bond with subsequent hydride transfer, transmetalation, decarbonylation and reductive elimination processes.

Rubrofusarin-6-ß-gentiobioside inhibits lipid accumulation and weight gain by regulating AMPK/mTOR signaling.

BACKGROUND: Although rubrofusarin-6-ß-gentiobioside (RFG), which is a component of Cassiae tora seed, could likely regulate hyperlipidemia, its anti-obesity effect and related mechanism have not been elucidated. PURPOSE: The aim of this study was to examine whether RFG can ameliorate obesity and the mechanism of lipid accumulation regulated by RFG. STUDY DESIGN: In in vitro experiments, we confirmed the anti-adipogenic effect of RFG using 3T3-L1 cells and human adipose mesenchymal stem cells (hAMSCs). To confirm the anti-obesity effect, High-Fat Diet (HFD)-induced obese mice were selected as a model. METHODS: We investigated anti-adipogenic effects of RFG using MTS assay, Oil Red O Staining, real-time RT-PCR, western blot analysis, and immunofluorescence staining. The anti-obesity effect of RFG was confirmed in HFD-induced mice model using hematoxylin and eosin staining and serum analysis. RESULTS: RFG inhibited lipid accumulation in 3T3-L1 cells and hAMSCs by reducing expression of mammalian targets of rapamycin (mTOR), peroxisome proliferator-activated receptor (PPAR)γ, and CCAAT-enhancer binding protein (C/EBP)α. RFG phosphorylated AMP-activated protein kinase (AMPK) in a liver kinase B (LKB) 1-independent manner. Moreover, the anti-adipogenic effect of RFG was blocked by AMPK inhibitor. These results suggest that RFG inhibits lipid accumulation via AMPK signaling. Furthermore, RFG reduced the body weight, size of epididymal white adipose tissue (eWAT), and fatty liver in the mice. RFG also suppressed levels of adipogenic factors PPARγ, C/EBPα, FAS, LPL, and aP2) by activating AMPK in the eWAT and liver. CONCLUSION: RFG can ameliorate obesity, and thus, could be used as a therapeutic agent for treating obesity.

Chemical Constituents and an Antineuroinflammatory Lignan, Savinin from the Roots of Acanthopanax henryi.

The phytochemical investigation on the roots of Acanthopanax henryi (Araliaceae) resulted in the discovery of twenty compounds whose chemical structures were elucidated by the analysis of 1D-, 2D-NMR, mass spectrometry data, other physicochemical properties, and a comparison of the spectral data with the literature. They were identified as (-)-sesamin (1), helioxanthin (2), savinin (3), taiwanin C (4), 6-methoxy-7-hydroxycoumarin (5), behenic acid (6), 3-O-caffeoyl-quinic acid (7), 5-O-caffeoyl-quinic acid (8), 1,3-di-O-caffeoyl-quinic acid (9), 1,4-di-O-caffeoyl-quinic acid (10), 1,5-di-O-caffeoyl-quinic acid (11), (+)-threo-(7R,8R)-guaiacylglycerol-ß-coniferyl aldehyde ether (12), (+)-erythro-(7S,8R)-guaiacylglycerol-ß-coniferyl aldehyde ether (13), ferulic acid (14), caffeic acid (15), stigmasterol (16), ß-sitosterol (17), adenosine (18), syringin (19), and trans-coniferin (20). Among these isolates, compound 3 showed inhibitory activity against lipopolysaccharide- (LPS-) induced nitric oxide (NO) and prostaglandin E2 (PGE2) production with IC50 values of 2.22 ± 0.11 and 2.28 ± 0.23 µM, respectively. The effects of compound 3 were associated with the suppression of LPS-induced expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. Furthermore, compound 3 negatively regulated the production of interleukin- (IL-) 1ß and tumor-necrosis factor- (TNF-) α at the transcriptional level in LPS-stimulated BV2 microglial cells. These antineuroinflammatory effects of compound 3 were mediated by p38 mitogen-activated protein kinase (MAPK).

Nickel-Catalyzed Csp2-Csp3 Bond Formation via C-F Bond Activation.

A nickel-catalyzed cross coupling of aryl fluorides via C-F bond activation has been developed. The alkylation method allows selective replacement of aryl fluorides by alkyl groups and enables the synthesis of diverse and otherwise difficult to access scaffolds in good yields.

Mutant Huntingtin Causes a Selective Decrease in the Expression of Synaptic Vesicle Protein 2C.

Huntington's disease (HD) is a neurodegenerative disease caused by a polyglutamine expansion in the huntingtin (Htt) protein. Mutant Htt causes synaptic transmission dysfunctions by interfering in the expression of synaptic proteins, leading to early HD symptoms. Synaptic vesicle proteins 2 (SV2s), a family of synaptic vesicle proteins including 3 members, SV2A, SV2B, and SV2C, plays important roles in synaptic physiology. Here, we investigated whether the expression of SV2s is affected by mutant Htt in the brains of HD transgenic (TG) mice and Neuro2a mouse neuroblastoma cells (N2a cells) expressing mutant Htt. Western blot analysis showed that the protein levels of SV2A and SV2B were not significantly changed in the brains of HD TG mice expressing mutant Htt with 82 glutamine repeats. However, in the TG mouse brain there was a dramatic decrease in the protein level of SV2C, which has a restricted distribution pattern in regions particularly vulnerable in HD. Immunostaining revealed that the immunoreactivity of SV2C was progressively weakened in the basal ganglia and hippocampus of TG mice. RT-PCR demonstrated that the mRNA level of SV2C progressively declined in the TG mouse brain without detectable changes in the mRNA levels of SV2A and SV2B, indicating that mutant Htt selectively inhibits the transcriptional expression of SV2C. Furthermore, we found that only SV2C expression was progressively inhibited in N2a cells expressing a mutant Htt containing 120 glutamine repeats. These findings suggest that the synaptic dysfunction in HD results from the mutant Htt-mediated inhibition of SV2C transcriptional expression. These data also imply that the restricted distribution and decreased expression of SV2C contribute to the brain region-selective pathology of HD.

Cross-Coupling of Amides with Alkylboranes via Nickel-Catalyzed C-N Bond Cleavage.

A protocol for the nickel-catalyzed alkylation of amides was established. The use of alkylboranes as nucleophilic partners allowed the use of mild reaction conditions and compatibility of various functional groups with respect to both coupling partners. The catalytic alkylation proceeded selectively at the amides in the presence of other functional groups as well as other carboxylic acid derived moieties.

Inhibitory effects of lupane­type triterpenoid saponins from the leaves of Acanthopanax gracilistylus on lipopolysaccharide-induced TNF­α, IL­1ß and high­mobility group box 1 release in macrophages.

Acanthopanax gracilistylus (AGS) has long been used in traditional Chinese medicine for the treatment of various inflammatory diseases. 3­O­ß­D­glucopyranosyl 3α, 11α­dihydroxylup­20(29)­en­28­oic acid, acantrifoside A, acankoreoside D, acankoreoside B and acankoreoside A are major lupane­type triterpenoid saponins derived from AGS. In the present study, these five saponins were isolated from AGS by chromatography and their anti­inflammatory activities were investigated in lipopolysaccharide (LPS)­treated RAW264.7 macrophages. Cell viability was evaluated by MTT assay. Tumor necrosis factor (TNF)­α, interleukin (IL)­1ß and NF­κB p65 were measured by ELISA. The gene expression levels of TNF­α and IL­1ß was detected by reverse­transcription polymerase chain reaction. And high­mobility group box 1 (HMGB1) were analyzed by western blotting. The results demonstrated that these five saponins significantly suppressed LPS­induced expression of TNF­α and IL­1ß at the mRNA and protein level in RAW264.7 cells. Further analysis revealed that acankoreoside A and acankoreoside B were able to reduce the secretion of HMGB1 and NF­κB activity induced by LPS in RAW264.7 macrophages. Taken together, these results suggested that the anti­inflammatory activity of AGS­derived saponins may be associated with the downregulation of TNF­α and IL­1ß, and the 'late­phase' proinflammatory cytokine HMGB1, via negative regulation of the NF­κB pathway in RAW264.7 cells.

Synthesis of Amidines from Amides Using a Nickel-Catalyzed Decarbonylative Amination through CO Extrusion Intramolecular Recombination Fragment Coupling.

A catalytic synthesis of amidines from amides has been established for the first time. The newly developed CO extrusion recombination process takes advantage of an inexpensive nickel(II) catalyst and provides the corresponding amidines with high efficiency. The intramolecular fragment coupling shows excellent chemoselectivity, starts from readily available amides, and provides a valuable alternative amidine synthesis protocol.

Araliasaponin II isolated from leaves of Acanthopanax henryi (Oliv.) Harms inhibits inflammation by modulating the expression of inflammatory markers in murine macrophages.

Araliasaponin II (AS II) is a bioactive compound isolated from Acanthopanax henryi (Oliv.) Harms, a plant widely used in traditional oriental medicine. The present study investigated the anti­inflammatory effects of AS II using murine macrophages. The effects of AS II on inflammatory mediator and cytokine production in lipopolysaccharide (LPS)­stimulated RAW 264.7 cells was evaluated. Nitric oxide (NO) and cytokine production were determined using the Griess reagent and an ELISA kit. The expression levels of cytokines, inducible NO synthase (iNOS) and cyclooxygenase­2 (COX­2) mRNA were examined by reverse transcription­quantitative polymerase chain reaction. The expression levels of iNOS, COX­2 and toll­like receptor (TLR)­4 protein were examined by western blotting. Translocation of nuclear factor­κB (NF­κB) and TLR­4 expression were visualized by immunofluorescence staining. AS II markedly inhibited the production of NO and prostaglandin E2, and reduced iNOS and COX­2 expression at the transcriptional and translational levels. AS II downregulated the expression of interleukin­6 and tumor necrosis factor­α at the protein and mRNA levels. Furthermore, pre­treatment with AS II significantly suppressed the TLR­4­NF­κB signaling pathway; this effect may be cause by AS II competing with LPS for binding to TLR­4 and subsequently inhibiting translocation of the NF­κB/p65 protein to the nucleus. The results suggested that the anti­inflammatory properties of AS II may result from inhibiting pro­inflammatory mediators by suppressing the initiation of the inflammatory response and inhibiting TLR-4-NF-κB signaling pathways.

Nickel-Catalyzed Synthesis of Primary Aryl and Heteroaryl Amines via C-O Bond Cleavage.

A nickel-catalyzed protocol for the conversion of aryl and heteroaryl alcohol derivatives to primary and secondary aromatic amines via C(sp2)-O bond cleavage is described. The new amination protocol can be applied to a range of substrates bearing diverse functional groups and uses readily available benzophenone imines as an effective nitrogen source.

Selective Reductive Removal of Ester and Amide Groups from Arenes and Heteroarenes through Nickel-Catalyzed C-O and C-N Bond Activation.

An inexpensive nickel(II) catalyst and a hydrosilane were used for the efficient reductive defunctionalization of aryl and heteroaryl esters through a decarbonylative pathway. This versatile method could be used for the removal of ester and amide functional groups from various organic molecules. Moreover, a scale-up experiment and a synthetic application based on the use of a removable carboxylic acid directing group highlight the usefulness of this reaction.

Inhibitory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid on lipopolysaccharide-induced TNF-α, IL-1ß, and the high mobility group box 1 release in macrophages.

We investigated the anti-inflammatory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid (HLEDA)-a lupane-type triterpene isolated from leaves of Acanthopanax gracilistylus W. W.Smith (AGS), as well as the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that HLEDA concentration-dependently reduced the production of nitric oxide (NO), significantly suppressed LPS-induced expression of TNF-α and IL-1ß at the mRNA and protein levels in RAW264.7 cells. Further analysis revealed that HLEDA could reduce the secretion of High Mobility Group Box 1 (HMGB1). Additionally, the results showed that HLEDA efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that HLEDA exerts anti-inflammatory properties in LPS-induced macrophages, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. These results warrant further studies that would concern candidate therapy for diseases, such as fulminant hepatitis and rheumatology of triterpenoids in AGS.