Two spurge species, Euphorbia resinifera O. Berg and Euphorbia officinarum subsp. echinus (Hook.f. & Coss.) Vindt inhibit colon cancer.

BACKGROUND: Colon cancer, a prominent contributor to global cancer-related deaths, prompts the need for innovative treatment strategies. Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp. echinus Hook. f. & Coss Vindt (E. echinus) and their bee-derived products have been integral to traditional Moroccan medicine due to their potential health benefits. These plants have historical use in addressing various health issues, including cancer. However, their effects against colon cancer remain unclear, and the specific mechanisms underlying their anti-cancer effects lack comprehensive investigation. METHODS: The study aimed to assess the potential anti-cancer effects of Euphorbia extract on colon cancer cell lines (DLD-1) through various techniques. The apoptosis, migration, and proliferation of DLD-1 cells were measured in DLD-1 cells. In addition, we conducted High-Performance Liquid Chromatography (HPLC) analysis to identify the profile of phenolic compounds present in the studied extracts. RESULTS: The extracts demonstrated inhibition of colon cancer cell migration. E. resinifera flower and E. echinus stem extracts show significant anti-migratory effects. Regarding anti-proliferative activity, E. resinifera flower extract hindered proliferation, whereas E. echinus flower extract exhibited dose-dependent inhibition. Apoptosis assays revealed E. resinifera flower extract inducing early-stage apoptosis and E. echinus flower extract promoting late-stage apoptosis. While apoptotic protein expression indicated, E. resinifera stem and propolis extracts had minimal impact on apoptosis. CONCLUSION: The findings provide evidence supporting the beneficial effects of E resinifera and E. echinus extracts on colon cancer and exerting anti-cancer properties.

Acer tegmentosum extract-mediated silver nanoparticles loaded chitosan/alginic acid scaffolds enhance healing of E. coli-infected wounds.

This work developed Acer tegmentosum extract-mediated silver nanoparticles (AgNPs) loaded chitosan (CS)/alginic acid (AL) scaffolds (CS/AL-AgNPs) to enhance the healing of E. coli-infected wounds. The SEM-EDS and XRD results revealed the successful formation of the CS/AL-AgNPs. FTIR analysis evidenced that the anionic group of AL (-COO-) and cationic amine groups of CS (-NH3+) were ionically crosslinked to form scaffold (CS/AL). The CS/AL-AgNPs exhibited significant antimicrobial activity against both Gram-positive (G+) and Gram-negative (G-) bacterial pathogens, while being non-toxic to red blood cells (RBCs), the hen's egg chorioallantoic membrane (HET-CAM), and a non-cancerous cell line (NIH3T3). Treatment with CS/AL-AgNPs significantly accelerated the healing of E. coli-infected wounds by regulating the collagen deposition and blood parameters as evidenced by in vivo experiments. Overall, these findings suggest that CS/AL-AgNPs are promising for the treatment of infected wounds.

Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.

Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.

Cellular metabolism and health impacts of dichlorvos: Occurrence, detection, prevention, and remedial strategies-A review.

Dichlorvos (2,2-Dichlorovinyl dimethyl phosphate, [DDVP]) belongs to the class of organophosphates and is widely used as an insecticide in agriculture farming and post-harvest storage units. Extensive research has been conducted to assess the factors responsible for the presence of DDVP in terrestrial and aquatic ecosystems, as well as the entire food chain. Numerous studies have demonstrated the presence of DDVP metabolites in the food chain and their toxicity to mammals. These studies emphasize that both immediate and chronic exposure to DDVP can disrupt the host's homeostasis, leading to multi-organ damage. Furthermore, as a potent carcinogen, DDVP can harm aquatic systems. Therefore, understanding the contamination of DDVP and its toxicological effects on both plants and mammals is vital for minimizing potential risks and enhancing safety in the future. This review aimed to comprehensively consolidate information about the distribution, ecological effects, and health impacts of DDVP, as well as its metabolism, detection, prevention, and remediation strategies. In summary, this study observes the distribution of DDVP contaminations in vegetables and fruits, resulting in significant toxicity to humans. Although several detection and bioremediation strategies are emerging, the improper application of DDVP and the alarming level of DDVP contamination in foods lead to human toxicity that requires attention.

2-Geranyl-1-methoxyerythrabyssin II alleviates lipid accumulation and inflammation in hepatocytes through AMPK activation and AKT inhibition.

A growing proportion of the global adult and pediatric populations are currently affected by nonalcoholic steatohepatitis (NASH), leading to rising rates of liver fibrosis and hepatocellular carcinoma without effective pharmacotherapy. Here, we investigated whether 2-geranyl-1-methoxyerythrabyssin II (GMET), isolated from Lespedeza bicolor, could alleviate lipid accumulation and inflammatory responses in a NASH model. GMET exhibited potent in vitro and in vivo effects against lipid accumulation and attenuated inflammatory responses without cytotoxicity. Mechanistically, GMET inhibits acetyl-CoA carboxylase (ACC), sterol regulatory element-binding proteins-1c (SREBP1), and mammalian target of rapamycin (mTOR), and activates PPARα by activating AMP-activated kinase (AMPK), leading to the alleviation of lipid accumulation. In addition, GMET suppresses the NF-κB pathway by activating AMPK and inhibiting the activated protein kinase B (AKT)/IκB-kinase (IKK) pathway, leading to the inhibition of the inflammatory response in hepatocytes. All these protective effects of GMET on lipid accumulation and inflammation in vivo and in vitro were largely abolished by co-treatment with dorsomorphin, an AMPK inhibitor. In conclusion, GMET alleviated lipid accumulation and inflammation to preserve normal hepatocyte function in steatohepatitis. Thus, GMET is a novel potential multi-targeting compound to improve steatohepatitis.

Inhibitory Effects of Ehretia tinifolia Extract on the Excessive Oxidative and Inflammatory Responses in Lipopolysaccharide-Stimulated Mouse Kupffer Cells.

Ehretia tinifolia (E. tinifolia) L., an evergreen tree with substantial biological activity, including antioxidant and anti-inflammatory effects, has been used in many herbal and traditional medicines. To elucidate its antioxidant and anti-inflammatory activity and the underlying mechanisms, we applied a methanol extract of E. tinifolia (ETME) to lipopolysaccharide (LPS)-stimulated mouse immortalized Kupffer cells. ETME suppressed the LPS-induced increase in nitric oxide, a mediator for oxidative stress and inflammation, and restored LPS-mediated depletion of total glutathione level by stabilizing antioxidative nuclear factor erythroid 2-related factor 2 (Nrf2) and the subsequent increase in heme oxygenase-1 levels. Furthermore, ETME inhibited the LPS-induced production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. The inhibitory effects of ETME on pro-inflammatory responses were regulated by ETME-mediated dephosphorylation of mitogen-activated protein kinases (MAPKs: p38, p44/p42, and stress-associated protein kinase/c-Jun N-terminal kinase) and inhibition of nuclear localization of nuclear factor kappa B (NF-κB). These results suggest that ETME is a possible candidate for protecting Kupffer cells from LPS-mediated oxidative stress and excessive inflammatory responses by activating antioxidant Nrf2/HO-1 and inhibiting pro-inflammatory NF-κB and MAPKs, respectively.

Seven new secondary metabolites isolated from roots of Lespedeza bicolor.

Chemical investigation of a methanol extract obtained from the roots of Lespedeza bicolor identified one new pterocarpene (1), three new pterocarpans (2-4), and three new arylbenzofurans (5-7), and two known compounds (8 and 9). Their structures were determined by interpretations obtained from combined UV, NMR, and HRTOFMS spectroscopic data. Furthermore, the absolute configurations of compounds 2 and 3 were established by the combination of electronic circular dichroism (ECD) calculations and NMR calculations with DP4+ probability analysis. All isolated compounds (1-9) were evaluated for cytotoxicity against the human lung carcinoma cell line A549 and the human hepatoma cell line Huh-7. Compound 4 showed antiproliferative activity against A549 cell line with IC50 value of 24.9 µM. Furthermore, compound 9 exhibited cytotoxicity against Huh-7 cell line with IC50 value of 68.7 µM.

1-Methoxyerythrabyssin II Induces Autophagy in Leukemia Cells via PI3K/Akt/mTOR Pathways.

Leukemia, despite currently being one of the most lethal cancers worldwide, still lacks a focused treatment. The purpose of the present investigation was to evaluate the pharmacological effect of 1-methoxyerythrabyssin II, a pterocarpan identified in the roots of Lespedeza bicolor, on leukemic cells and to explore its underlying mechanism using a network pharmacology strategy. 1-Methoxyerythrabyssin II showed an antiproliferative effect in a concentration-dependent manner and exhibited a higher potency in human acute leukemia T cells (Jurkat). The G1 phase arrest induced by 1-methoxyerythrabyssin II was confirmed using a cell cycle assay, and the downregulation of CDK2 and cyclin D1 was observed using an immunoblot assay. Moreover, 1-methoxyerythrabyssin II-treated cells exhibited higher expression levels of LC3B, Atg-7, and Beclin 1 in addition to an enhanced fluorescence intensity in monodansylcadaverine staining, indicating autophagy induction by 1-methoxyerythrabyssin II. Furthermore, network pharmacology and molecular docking analyses revealed that the PI3K/Akt/mTOR pathway is a potential target of 1-methoxyerythrabyssin II in leukemic cells. In vitro assays further demonstrated that 1-methoxyerythrabyssin II promoted autophagy and suppressed cell proliferation by inhibiting the PI3K/Akt/mTOR pathway in leukemic cells. This discovery will contribute to the development of novel therapeutics and prophylactics against leukemia.

In Vitro Anti-Inflammatory Effects of Symplocos sumuntia Buch.-Ham. Ex D. Don Extract via Blockage of the NF-κB/JNK Signaling Pathways in LPS-Activated Microglial Cells.

Symplocos sumuntia Buch.-Ham. ex D. Don (S. sumuntia) is a traditional medicinal herb used in Asia to treat various pathologies, including cough, stomachache, tonsillitis, hypertension, and hyperlipidemia. Although the anti-inflammatory activity of S. sumuntia has been reported, little is known about its anti-inflammatory activity and molecular mechanisms in microglial cells. Therefore, we investigated the inhibitory effects of S. sumuntia methanol extract (SSME) on the inflammatory responses in lipopolysaccharide (LPS)-treated BV2 cells. The SSME significantly inhibited the LPS-stimulated inducible nitric oxide synthase and cyclooxygenase-2 expression, as well as the production of nitric oxide (NO), a proinflammatory mediator. The production of proinflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-1ß, was suppressed by the SSME in the LPS-induced BV2 cells. The mechanism underlying the anti-inflammatory effects of SSME involves the suppression of the LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) such as JNK. Moreover, we showed that the LPS-stimulated nuclear translocation of the nuclear factor-κB (NF-κB)/p65 protein, followed by IκB degradation, was decreased by the SSME treatment. Collectively, these results showed that the SSME induced anti-inflammatory effects via the suppression of the MAPK signaling pathways, accompanied by changes in the NF-κB translocation into the nucleus. Therefore, SSME may be employed as a potential therapeutic candidate for various inflammatory diseases.

The lysosome as a novel therapeutic target of EGFR-mediated tumor inflammation.

EGFR-mediated tumors have been targeted to overcome several different malignant cancers. EGFR overexpression and mutations are directly related to the malignancy, which makes the therapy more complicated. One reason for the malignancy is the induction of AP1 followed by inflammation via IL-6 secretion. Current therapeutic strategies to overcome EGFR-mediated tumors are tyrosine kinase inhibitors (TKIs), anti-EGFR monoclonal antibodies, and the combination of these two agents with classic chemotherapy or immune checkpoint inhibitors (ICIs). Although the strategies are straightforward and have shown promising efficacy in several studies, there are still hurdles to overcoming the adverse effects and limited efficacy. This study reviews the current therapeutic strategies to target EGFR family members, how they work, and their effects and limitations. We also suggest developing novel strategies to target EGFR-mediated tumors in a novel approach. A lysosome is the main custodial staff to discard unwanted amounts of EGFR and other receptor tyrosine kinase molecules. Targeting this organelle may be a new approach to overcoming EGFR-mediated cancers.

Comparison of the Clinicopathologic Features and T-Cell Infiltration of B7-H3 and B7-H4 Expression in Triple-negative Breast Cancer Subtypes.

Previously we revealed an upregulated expression of B7-H3 and B7-H4 mRNA and protein in breast cancer, including triple-negative breast cancer (TNBC). However, little is known regarding the clinical impact and value of B7-H3 and B7-H4 in TNBC subtypes. Thus, this study evaluated the clinicopathologic effects of B7-H3 and B7-H4 mRNA and protein expression according to the TNBC subtypes. RNAscope in situ hybridization and immunohistochemistry of B7-H3 and B7-H4 was done for 186 TNBC samples using tissue microarray. Immunohistochemistry was also performed for TNBC molecular subtype-surrogate markers, CD3, and CD8. TNBCs were classified into basal-like (BL) (64.5%), luminal androgen receptor (10.8%), and unclassifiable (24.7%) subtypes. Tumor B7-H4 mRNA expression was associated with younger age at the initial diagnosis and with molecular TNBC subtypes. Expression of B7-H3 mRNA and protein in the tumor cells was negatively correlated with CD3+ and CD8+ T-cell infiltration density in the tumor and/or stromal region of TNBCs and their subtypes. High stromal B7-H3 mRNA expression was associated with poor disease-free and overall survival in the TNBCs and with overall survival in the unclassifiable subtype. Stromal B7-H3 mRNA expression was independently associated with overall survival and disease-free survival in the TNBCs and BL subtype, respectively. Our results indicate the importance of the stromal expression of B7-H3 mRNA as a prognostic factor in the TNBCs and BL subtype. The inverse relationship between B7-H3 expression and CD3+ and CD8+ T-lymphocyte infiltration represents a promising target for immunotherapy for the TNBCs, especially the BL subtype.

Narciclasine suppresses esophageal cancer cell proliferation and migration by inhibiting the FAK signaling pathway.

Esophageal cancer (EC) is one of the malignant cancer with pool survival due to the limited therapeutic and drug-resistance. Narciclasine, a natural compound from Lycoris sanguinea possesses antitumor and anti-inflammatory properties. However, the mechanisms underlying the growth-inhibitory effect of narciclasine against EC have not yet been elucidated. Experimental evidences indicated that narciclasine treatment significantly affected the distribution of FAK and its phosphorylation, resulting in proliferation inhibition and migration inhibition of EC. Our study also showed that narciclasine treatment triggered DNA damage and inhibited DNA replication, leading to cell cycle arrest and apoptosis. Further mechanistic studies indicated that narciclasine inhibited EC cell proliferation and migration through FAK/JNK and p38 pathway. Altogether, these findings suggest that narciclasine could be a potential novel chemotherapeutic agent for esophageal cancer cell proliferation and migration.

Fine-Dust-Induced Skin Inflammation: Low-Molecular-Weight Fucoidan Protects Keratinocytes and Underlying Fibroblasts in an Integrated Culture Model.

Prolonged exposure to fine dust (FD) increases the risk of skin inflammation. Stimulated epidermal cells release growth factors into their extracellular environment, which can induce inflammation in dermal cells. Algae are considered rich sources of bioactive materials. The present study emphasized the effect of low-molecular-weight fucoidan isolated from Sargassum confusum (LMF) against FD-induced inflammation in HaCaT keratinocytes and underneath fibroblasts (HDFs) in an integrated culture model. HDFs were treated with media from FD-stimulated HaCaT with LMF treatments (preconditioned media). The results suggested that FD increased the oxidative stress in HaCaT, thereby increasing the sub-G1 phase of the cell cycle up to 587%, as revealed via flow cytometric analysis. With preconditioned media, HDFs also displayed oxidative stress; however, the increase in the sub-G1 phase was insignificant compared with HaCaT. LMF dose-dependently regulated the NF-κB/MAPK signaling in HaCaT. Furthermore, significant downregulation in NF-κB/MAPK signaling, as well as inflammatory cytokines, tissue inhibitors of metalloproteinases, matrix metalloproteinases, and reduction in relative elastase and collagenase activities related to the extracellular matrix degeneration were observed in HDFs with a preconditioned media treatment. Therefore, we concluded that HDFs were protected from inflammation by preconditioned media. Continued research on tissue culture and in vivo studies may reveal the therapeutic potential of LMF.

Inhibition of UBA5 Expression and Induction of Autophagy in Breast Cancer Cells by Usenamine A.

Breast cancer is now the most common type of cancer worldwide, surpassing lung cancer. This issue is further worsened by the lack of effective therapies for the disease. Recent reports indicate that the inhibition of ubiquitin-like modifier-activating enzyme 5 (UBA5) can impede tumor development. However, there have been few reports regarding UBA5-inhibiting compounds. This work studied usenamine A, a natural product from the lichen Usnea longissimi that exhibits UBA5-inhibitory effects. Bioinformatics analysis was performed using public databases, and the anti-proliferative ability of usenamine A in breast cancer cells was examined through MTS and colony formation assays. Flow cytometry and western blot analysis were also conducted to examine and analyze cell cycle arrest and apoptosis. In addition, LC3B-RFP and UBA5 expression plasmids were used for the analysis of usenamine A-induced autophagy. According to the bioinformatics analysis results, UBA5 was upregulated in breast cancer. According to in vitro studies, usenamine A displayed prominent anti-proliferative activity and resulted in G2/M phase arrest in MDA-MB-231 cells. Moreover, usenamine A induced autophagy and endoplasmic reticulum stress in MDA-MB-231 cells. In conclusion, the findings support the potential of usenamine A as an agent that can attenuate the development and progression of breast cancer.

Anticancer Effects of Propionic Acid Inducing Cell Death in Cervical Cancer Cells.

Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics.

Squalene epoxidase expression is associated with breast tumor progression and with a poor prognosis in breast cancer.

Differentially expressed genes (DEGs) have been previously identified using massive parallel RNA sequencing in matched normal, breast cancer (BC) and nodal metastatic tissues. Squalene epoxidase (SQLE), one of these DEGs, is a key enzyme in cholesterol synthesis. The aim of the present study was to investigate the potential involvement of SQLE in the tumorigenic process of BC and to determine its association with the clinical outcome of BC. SQLE mRNA expression was measured using reverse transcription-quantitative PCR in 10 pairs of ductal carcinoma in situ (DCIS) and BC tissues and their adjacent normal tissues. Immunohistochemical staining of SQLE on tissue microarray was performed in 26 normal breast, 79 DCIS and 198 BC samples. The role of SQLE as a prognostic biomarker in patients with BC has been verified using BreastMark. SQLE mRNA expression was significantly increased in DCIS and BC tissues compared with that in their adjacent normal tissues. High SQLE expression was detected in 0, 48.1 and 40.4% of normal breast, DCIS and BC tissues, respectively. SQLE expression in DCIS and BC tissues was significantly higher than that in normal breast tissues. High SQLE expression was observed in DCIS with higher nuclear grade, comedo-type necrosis and HER2 positivity. High SQLE expression in BC was associated with larger tumor size, nodal metastases, higher stage, HER2 subtype and distant metastatic relapse. High SQLE expression was associated with poor disease-free and overall survival, and independently predicted poor disease-free survival in patients with BC. Following BreastMark analysis, high SQLE mRNA expression in BC was significantly associated with a poor prognosis in the 'all', lymph node negative, lymph node positive, luminal A subtype and luminal B subtype groups. Therefore, SQLE expression may be upregulated during the tumorigenic process of BC, and high SQLE expression may be a useful biomarker for predicting a poor prognosis in patients with BC.

Anticancer Activity of Lesbicoumestan in Jurkat Cells via Inhibition of Oxidative Stress-Mediated Apoptosis and MALT1 Protease.

This study explores the potential anticancer effects of lesbicoumestan from Lespedeza bicolor against human leukemia cancer cells. Flow cytometry and fluorescence microscopy were used to investigate antiproliferative effects. The degradation of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) was evaluated using immunoprecipitation, Western blotting, and confocal microscopy. Apoptosis was investigated using three-dimensional (3D) Jurkat cell resistance models. Lesbicoumestan induced potent mitochondrial depolarization on the Jurkat cells via upregulated expression levels of mitochondrial reactive oxygen species. Furthermore, the underlying apoptotic mechanisms of lesbicoumestan through the MALT1/NF-κB pathway were comprehensively elucidated. The analysis showed that lesbicoumestan significantly induced MALT1 degradation, which led to the inhibition of the NF-κB pathway. In addition, molecular docking results illustrate how lesbicoumestan could effectively bind with MALT1 protease at the latter's active pocket. Similar to traditional 2D cultures, apoptosis was markedly induced upon lesbicoumestan treatment in 3D Jurkat cell resistance models. Our data support the hypothesis that lesbicoumestan is a novel inhibitor of MALT1, as it exhibited potent antiapoptotic effects in Jurkat cells.

Inhibition of Jurkat T Cell Proliferation by Active Components of Rumex japonicus Roots Via Induced Mitochondrial Damage and Apoptosis Promotion.

Rumex japonicus Houtt (RJH) is a valuable plant used in traditional medicine to treat several diseases, such as scabies and jaundice. In this study, Jurkat cell growth inhibitory extracts of R. japonicus roots were subjected to bioassay-guided fractionation, resulting in the isolation of three naphthalene derivatives (3-5) along with one anthraquinone (6) and two phenolic compounds (1 and 2). Among these compounds, 2-methoxystypandrone (5) exhibited potent anti-proliferative effects on Jurkat cells. Analysis by flow cytometry confirmed that 2-methoxystypandrone (5) could significantly reduce mitochondrial membrane potential and promote increased levels of mitochondrial reactive oxygen species (ROS), suggesting a strong mitochondrial depolarization effect. Real-time quantitative polymerase chain reaction (qPCR) analysis was also performed, and the results revealed that the accumulation of ROS was caused by reduced mRNA expression levels of heme oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, 2-methoxystypandrone (5) triggered strong apoptosis that was mediated by the arrest of the G0/G1 phase of the cell cycle. Furthermore, 2-methoxystypandrone (5) downregulated p-IκB-α, p-NF-κB p65, Bcl2, and Bcl-xl and upregulated BAX proteins. Taken together, these findings revealed that 2-methoxystypandrone (5) isolated from RJH could potentially serve as an early lead compound for leukemia treatment involving intracellular signaling by increasing mitochondrial ROS and exerting anti-proliferative effects.

Inhibitory Effects of Aucklandia lappa Decne. Extract on Inflammatory and Oxidative Responses in LPS-Treated Macrophages.

Aucklandia lappa Decne., known as "Mok-hyang" in Korea, has been used for the alleviation of abdominal pain, vomiting, diarrhea, and stress gastric ulcers in traditional oriental medicine. We investigated the anti-inflammatory and antioxidative effects of the ethanol extract of Aucklandia lappa Decne. (ALDE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. ALDE significantly inhibited the LPS-induced nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. The production of other proinflammatory mediators, including COX-2, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α, was reduced by ALDE in LPS-stimulated RAW 264.7 cells. The mechanism underlying the anti-inflammatory effects of ALDE was elucidated to be the suppression of LPS-induced nuclear translocation of p65, followed by the degradation of IκB and the inhibition of the phosphorylation of mitogen-activated protein kinases (MAPK). In addition, ALDE showed enhanced radical scavenging activity. The antioxidant effect of ALDE was caused by the enhanced expression of heme oxygenase (HO-1) via stabilization of the expression of the nuclear transcription factor E2-related factor 2 (Nrf2) pathway. Collectively, these results indicated that ALDE not only exerts anti-inflammatory effects via the suppression of the NF-κB and MAPK pathways but also has an antioxidative effect through the activation of the Nrf2/HO-1 pathway.