Jaceosidin attenuates the progression of hepatic fibrosis by inhibiting the VGLL3/HMGB1/TLR4 signaling pathway.

BACKGROUND: Jaceosidin (JA) is a natural flavone extracted from Artemisia that is used as a food and traditional medicinal herb. It has been reported to possess numerous biological activities. However, the regulatory mechanisms underlying amelioration of hepatic fibrosis remain unclear. HYPOTHESIS/PURPOSE: We hypothesized that jaceosidin acid (JA) modulates hepatic fibrosis and inflammation. METHODS: Thioacetamide (TAA) was used to establish an HF mouse model. In vitro, mouse primary hepatocytes and HSC-T6 cells were induced by TGF-ß, whereas mouse peritoneal macrophages received a treatment lipopolysaccharide (LPS)/ATP. RESULTS: JA decreased serum transaminase levels and improved hepatic histological pathology in TAA-treated mice stimulated by TAA. Moreover, the expression of pro-fibrogenic biomarkers associated with the activation of liver stellate cells was downregulated by JA. Likewise, JA down-regulated the expression of vestigial-like family member 3 (VGLL3), high mobility group protein B1 (HMGB1), toll-like receptors 4 (TLR4), and nucleotide-binding domain-(NOD-) like receptor protein 3 (NLRP3), thereby inhibiting the inflammatory response and inhibiting the release of mature-IL-1ß in TAA-stimulated mice. Additionally, JA suppressed HMGB1 release and NLRP3/ASC inflammasome activation in LPS/ATP-stimulated murine peritoneal macrophages. JA decreases the expression of pro-fibrogenic biomarkers related to liver stellate cell activation and inhibits inflammasome activation in mouse primary hepatocytes. It also down-regulated α-SMA and VGLL3 expressions and also suppressed inflammasome activation in HSC-T6 cells. VGLL3 and α-SMA expression levels were decreased in TGF-ß-stimulated HSC-T6 cells following Vgll3 knockdown. In addition, the expression levels of NLRP3 and cleaved-caspase-1 were decreased in Vgll3-silenced HSC-T6 cells. JA enhanced the inhibitory effects on Vgll3-silenced HSC-T6 cells. Finally, Vgll3 overexpression in HSC-T6 cells affected the expression levels of α-SMA, NLRP3, and cleaved-caspase-1. CONCLUSION: JA effectively modulates hepatic fibrosis by suppressing fibrogenesis and inflammation via the VGLL3/HMGB1/TLR4 axis. Therefore, JA may be a candidate therapeutic agent for the management of hepatic fibrosis. Understanding the mechanism of action of JA is a novel approach to hepatic fibrosis therapy.

Jaceosidin induces apoptosis and inhibits migration in AGS gastric cancer cells by regulating ROS-mediated signaling pathways.

Jaceosidin (JAC) is a natural flavonoid with anti-oxidant and other pharmacological activities; however, its anti-cancer mechanism remains unclear. We investigated the mechanism of action of JAC in gastric cancer cells. Cytotoxicity and apoptosis assays showed that JAC effectively killed multiple gastric cancer cells and induced apoptosis in human gastric adenocarcinoma AGS cells via the mitochondrial pathway. Network pharmacological analysis suggested that its activity was linked to reactive oxygen species (ROS), AKT, and MAPK signaling pathways. Furthermore, JAC accumulated ROS to up-regulate p-JNK, p-p38, and IκB-α protein expressions and down-regulate the p-ERK, p-STAT3, and NF-κB protein expressions. Cell cycle assay results showed that JAC accumulated ROS to up-regulate p21 and p27 protein expressions and down-regulate p-AKT, CDK2, CDK4, CDK6, Cyclin D1, and Cyclin E protein expressions to induce G0/G1 phase arrest. Cell migration assay results showed JAC accumulated ROS to down-regulate Wnt-3a, p-GSK-3ß, N-cadherin, and ß-catenin protein expressions and up-regulate E-cadherin protein expression to inhibit migration. Furthermore, N-acetyl cysteine pre-treatment prevented the change of these protein expressions. In summary, JAC induced apoptosis and G0/G1 phase arrest and inhibited migration through ROS-mediated signaling pathways in AGS cells.

Integrative analysis of metabolite and transcriptome reveals biosynthetic pathway and candidate genes for eupatilin and jaceosidin biosynthesis in Artemisia argyi.

Artemisia argyi (A. argyi) is a medicinal plant belonging to the Asteraceae family and Artemisia genus. Flavonoids abundant in A. argyi are associated with anti-inflammatory, anticancer, and antioxidative effects. Eupatilin and jaceosidin are representative polymethoxy flavonoids with medicinal properties significant enough to warrant the development of drugs using their components. However, the biosynthetic pathways and related genes of these compounds have not been fully explored in A. argyi. This study comprehensively analyzed the transcriptome data and flavonoids contents from four different tissues of A. argyi (young leaves, old leaves, trichomes collected from stems, and stems without trichomes) for the first time. We obtained 41,398 unigenes through the de-novo assembly of transcriptome data and mined promising candidate genes involved in the biosynthesis of eupatilin and jaceosidin using differentially expressed genes, hierarchical clustering, phylogenetic tree, and weighted gene co-expression analysis. Our analysis led to the identification of a total of 7,265 DEGs, among which 153 genes were annotated as flavonoid-related genes. In particular, we were able to identify eight putative flavone-6-hydroxylase (F6H) genes, which were responsible for providing a methyl group acceptor into flavone basic skeleton. Furthermore, five O-methyltransferases (OMTs) gene were identified, which were required for the site-specific O-methylation during the biosynthesis of eupatilin and jaceosidin. Although further validation would be necessary, our findings pave the way for the modification and mass-production of pharmacologically important polymethoxy flavonoids through genetic engineering and synthetic biological approaches.

The effects of cisplatin and jaceosidin on SH-SY5Y neuroblastoma cells: an electron microscopic, molecular and biochemical study.

In this study, our aim was to show both the single and combined effects of cisplatin and jaceosidin in SHSY-5Y neuroblastoma cells. For this purpose, we used MTT cellular viability assay, Enzyme-Linked Immunosorbent Assay (ELISA), Transmission Electron Microscopy (TEM), Immunofluorescence Staining Assay (IFA) and Western blotting (WB) assay. According to MTT findings, IC50 dose was detected as 50 µM cisplatin and 160 µM jaceosidin co-application. Therefore, experimental groups were finally selected as control, cisplatin, 160 µM jaceosidin and Cisplatin +160 µM jaceosidin. Cell viability was decreased in all groups, and the IFA findings confirmed the viability analysis. WB data indicated that matrix metalloproteinase 2 and 9 levels, as indicators of metastasis, decreased. While LPO and CAT levels increased in all treatment groups, it was observed that the activity of SOD decreased. When TEM micrographs were investigated, cellular damages were determined. In the light of these results, it can be said that cisplatin and jaceosidin have a potential to increase the effects of each other synergistically.

Jaceosidin inhibits the progression and metastasis of NSCLC by regulating miR-34c-3p/Integrin α2ß1 axis.

Non-coding RNAs are crucial for cancer progression, among which miR-34c-3p has been demonstrated to be a tumor suppressor in non-small cell lung cancer (NSCLC). In this study, we attempt to identify flavonoids that can up-regulate miR-34c-3p expression, evaluate the anticancer activity of the flavonoids and explore its underlying mechanism in NSCLC cells. Six flavonoids were screened by RT-qPCR and we found that jaceosidin significantly increased miR-34c-3p expression in A549 cells. We found that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner, indicated by cell counting kit (CCK-8) assay, wound healing assay, transwell assay and EdU assay, we observed that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner. Further research suggested that miR-34c-3p bound to the transcriptome of integrin α2ß1 and then inhibited its expression, leading to the inhibitory effect on the migration and invasion of NSCLC. Our study sheds some light on anti-tumor of jaceosidin and provides a potential lead compound for NSCLC therapy.

Apoptotic effect of jaceosidin on MCF-7 human breast cancer cells through modulation of ERK and p38 MAPK pathways.

Jaceosidin a flavone abundant in Artemisia species has been used for its beneficial effects. This study investigated the apoptotic effect of jaceosidin treatment on MCF-7 human breast cancer cells at varying concentrations of (0, 10, 20 and 40 µM) for 24 and 48 h treatment times. Jaceosidin treatment induced a significant (p < 0.05) dose-dependent increase in apoptosis of MCF-7 cells. Jaceosidin similarly modulated the expressions of apoptosis-associated proteins, and revealing a coaction between Bax and Bcl-2, striking a balance between cell survival/cell deaths. Besides, a significant increase in pro-apoptotic expression of cleaved PARP which is a key executioner in apoptosis was observed. Apoptosis was confirmed in the cells by flow cytometry which indicated an early apoptosis (7%, 17%), as well as late apoptosis (36%, 40%) of the cells in varying percentages as treatment concentration increased. Thus, this study demonstrates that jaceosidin could be used as a potential treatment for breast cancer.

Jaceosidin: A Natural Flavone with Versatile Pharmacological and Biological Activities.

Nature always remains an inexhaustible source of treasures for mankind. It remains a mystery for every challenge until the completion of the challenge. While we talk about the complicated health issues, nature offers us a great variety of chemical scaffolds and their various moieties packed in the form of natural products e.g., plants, microorganisms (fungi, algae, protozoa), and terrestrial vertebrates and invertebrates. This review article is an update about jaceosidin, a bioactive flavone, from genus Artemisia. This potentially active compound exhibits a variety of pharmacological activities including anti-inflammatory, anti-oxidant, anti-bacterial, antiallergic and anti-cancer activities. The bioactivities and the therapeutic action of jaceosidin, especially the modulation of different cell signaling pathways (ERK1/2, NF-κB, PI3K/Akt and ATM-Chk1/2) which become deregulated in various pathological disorders, have been focused here. The reported data suggest that the bioavailability of this anti-cancer compound should be enhanced by utilizing various chemical, biological and computational techniques. Moreover, it is recommended that researchers and scientists should work on exploring the mode of action of this particular flavone to precede it further as a potent anti-cancer compound.

Jaceosidin Ameliorates Insulin Resistance and Kidney Dysfunction by Enhancing Insulin Receptor Signaling and the Antioxidant Defense System in Type 2 Diabetic Mice.

Emerging evidence has shown that flavonoids extracted from Artemisia have beneficial effects on metabolic disorders. However, whether and how jaceosidin ameliorates insulin resistance and diabetic nephropathy in type 2 diabetes mellitus is largely unknown. For 8 weeks, db/db diabetic mice were fed with or without jaceosidin. Oral jaceosidin supplementation reduced fasting blood glucose levels and insulin resistance through the upregulation of insulin receptor downstream pathways in the liver and skeletal muscles. While jaceosidin did not noticeably alter kidney filtration function, this dietary intervention contributed to attenuating the accumulation of advanced glycation end products in diabetic kidneys. The levels of VEGF-a (vascular endothelial growth factor-a) proteins in the diabetic kidneys were markedly diminished by jaceosidin treatments, which increased the expression and activity of Cu (copper) and Zn-SOD (zinc-superoxide dismutase). Therefore, it is suggested that jaceosidin supplementation elicits antidiabetic effects and treats diabetic nephropathy by augmenting insulin signaling, suppressing fibrosis, and enhancing antioxidant activity.

Seomae mugwort and jaceosidin attenuate osteoarthritic cartilage damage by blocking IκB degradation in mice.

Seomae mugwort, a Korean native variety of Artemisia argyi, exhibits physiological effects against various diseases. However, its effects on osteoarthritis (OA) are unclear. In this study, a Seomae mugwort extract prevented cartilage destruction in an OA mouse model. In vitro and ex vivo analyses revealed that the extract suppressed MMP3, MMP13, ADAMTS4 and ADAMTS5 expression induced by IL-1ß, IL-6 and TNF-α and inhibited the loss of extracellular sulphated proteoglycans. In vivo analysis revealed that oral administration of the extract suppressed DMM-induced cartilage destruction. We identified jaceosidin in Seomae mugwort and showed that this compound decreased MMP3, MMP13, ADAMTS4 and ADAMTS5 expression levels, similar to the action of the Seomae mugwort extract in cultured chondrocytes. Interestingly, jaceosidin and eupatilin combined had similar effects to Seomae mugwort in the DMM-induced OA model. Induction of IκB degradation by IL-1ß was blocked by the extract and jaceosidin, whereas JNK phosphorylation was only suppressed by the extract. These results suggest that the Seomae mugwort extract and jaceosidin can attenuate cartilage destruction by suppressing MMPs, ADAMTS4/5 and the nuclear factor-κB signalling pathway by blocking IκB degradation. Thus, the findings support the potential application of Seomae mugwort, and particularly jaceosidin, as natural therapeutics for OA.

Bidirectional Regulatory Mechanisms of Jaceosidin on Mitochondria Function: Protective Effects of the Permeability Transition and Damage of Membrane Functions.

Many natural products could induce apoptosis through mitochondrial pathways. However, direct interactions between natural products and mitochondria have rarely been reported. In this work, the effects and regulatory mechanisms of Jaceosidin on the isolated rat liver mitochondria have been studied. The results of the experiments which by introducing exogenous Ca2+ illustrated that Jaceosidin has the protective effects on the structure and function of the isolated mitochondria. These protective effects were related to the chelation of Ca2+ with Jaceosidin. Besides, Jaceosidin could scavenge reactive oxygen species produced during electron transport, and weaken the mitochondrial lipid peroxidation rate, which may be attributed to the antioxidant effect of phenolic hydroxyl groups of Jaceosidin. In addition, Jaceosidin has some damage effects on mitochondrial function, such as the inhibition of mitochondrial respiration and the increase of mitochondrial membrane fluidity. These results of this work provided comprehensive information to clarify the mechanisms of Jaceosidin on mitochondria, which may be the bidirectional regulatory mechanisms.

Quality control of eight substances in Changwei San based on quantitative analysis of multi-components by single-marker / 国际药学研究杂志

Objective: To establish a quantitative analysis of multi-components by single marker(QAMS)method for the simultaneous determination of jaceosidin, eupatilin, limoni, evodiamine, rutaecarpine, cinnamyl alcohol, cinnamic acid and cinnamal-dehyde in Changwei San. Methods: The Waters Symmetry C18 column(250 mm×4.6 mm, 5 μm)was used for the separation, and the mobile phase was the acetonitrile(A)and 0.1% phosphoric acid(B)solution in a gradient elution at a flow rate of 1.0 ml/min. The detection wavelengths were set at 345 nm for jaceosidin and eupatilin, 215 nm for limoni, evodiamine and rutaecarpine, and 275 nm for cinnamyl alcohol, cinnamic acid and cinnamaldehyde. With evodiamine as an internal reference standard, the relative correction factors for the other 7 components were established and their contents were calculated with the relative correction factors to achieve the QAMS, and then the differences between the calculated values by QAMS and measured values by the external standard method(ESM) were compared to validate the accuracy and feasibility of the QAMS method. Results: Jaceosidin, eupatilin, limoni, evodiamine, rutaecarpine, cinnamyl alcohol, cinnamic acid and cinnamaldehyde showed good linear relationships within the ranges of 0.98-19.60, 2.67-53.40, 4.06-81.20, 1.98-39.60, 2.69-53.80, 0.56-11.20, 1.49-29.80, and 8.77-175.40 μg/ml(r≥0.9992), whose average recoveries(RSD) were 98.77%(0.96%), 99.38%(1.01%), 100.02%(0.83%), 97.80%(1.40%), 98.91%(1.18%), 96.99% (1.13%), 98.09%(1. 24%)and 99.10%(0.67%), respectively. No significant difference was observed between the calculated values by QAMS and the measured values by ESM. Conclusion: The established QAMS method is simple and accurate, which might be used to evaluate the quality of Changwei San.

The therapeutic effects of Jaceosidin on lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury (ALI) results from various factors including uncontrolled pulmonary inflammation, oxidative damage and the over-activated complement with high mortality rates. Jaceosidin was a flavonoid compound with significant anti-complement activity. We aimed to investigate the therapeutic effects of Jaceosidin on ALI induced by lipopolysaccharide (LPS). Mice were orally administrated with Jaceosidin (15, 30 and 60 mg/kg) after LPS challenge. 24 h after LPS challenge, Jaceosidin could significantly decrease the lung wet-to-dry weight (W/D) ratio and the protein concentration in bronchoalveolar lavage fluid (BALF). Jaceosidin could down-regulate the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), together with up-regulation the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in BALF. Jaceosidin could significantly decrease the levels of myeloperoxidase (MPO), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB), COX-2 mRNA and NF-κB p65 mRNA together with increasing the activity of catalase (CAT). Additionally, Jaceosidin attenuated lung histopathological changes, inhibited the expressions of COX-2 and NF-κB p65 and reduced complement deposition with decreasing the levels of complement 3 (C3) and complement 3c (C3c) in serum. These data suggest that Jaceocidin may dampen the inflammatory response and decrease the levels of complement together with the antioxidant activity following LPS-induced ALI.

Use of Some Asteraceae Plants for the Treatment of Wounds: From Ethnopharmacological Studies to Scientific Evidences.

Severe wounds result in large lesions and/or loss of function of the affected areas. The treatment of wounds has challenged health professionals due to its complexity, especially in patients with chronic diseases (such as diabetes), and the presence of pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. Taking this into consideration, the development of new therapies for wound healing requires immediate attention. Ethnopharmacological studies performed in different countries have shown the use of several plants from the Asteraceae family as wound-healing agents. Evidences gained from the traditional medicine have opened new ways for the development of novel and more efficient therapies based on the pharmacological properties of these plants. In this article, we discuss the literature data on the use of Asteraceae plants for the treatment of wounds, based on the ethnopharmacological relevance of each plant. Special attention was given to studies showing the mechanisms of action of Asteraceae-derived compounds and clinical trials. Ageratina pichinchensis (Kunth) R.M. King and H. Rob. and Calendula officinalis L. preparations/compounds were found to show good efficacy when assessed in clinical trials of complicated wounds, including venous leg ulcers and foot ulcers of diabetic patients. The compounds silibinin [from Silybum marianum (L.) Gaertn.] and jaceosidin (from Artemisia princeps Pamp.) were identified as promising compounds for the treatment of wounds. Overall, we suggest that Asteraceae plants represent important sources of compounds that may act as new and efficient healing products.

Acute and subacute toxicity and chemical constituents of the hydroethanolic extract of Verbena litoralis Kunth.

ETHNOPHARMACOLOGICAL RELEVANCE: Verbena litoralis Kunth is a native species of South America, popularly known as gervãozinho-do-campo or erva-de-pai-caetano. It is used in gastrointestinal disorders, as detoxifying the organism, antifebrile properties and amidaglitis. AIM OF THE STUDY: To identify the chemical constituents of the hydroethanolic extract obtained from the aerial parts of V. litoralis and to evaluate the acute and sub-acute toxicity in male and female rats. MATERIALS AND METHODS: The single dose (2000 mg/kg) of the extract was administered orally to male and female rats. In the subacute study the extract was given at doses of 100, 200 and 400 mg/kg during 28 days orally. Biochemical, hematological and histological analyzes were performed, oxidative stress markers were tested and chemical constituents were identified through UHPLC-ESI-HRMS RESULTS: Six classes of metabolites were identified: iridoids glycosides, flavonoids, phenylpropanoids-derived, phenylethanoid-derived, cinnamic acid-derived and triterpenes. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. Our results demonstrated that subacute administration of the crude extract of V. litoralis at 400 mg/kg resulted in an increase in AST in males, whereas ALT enzyme showed a small increase in males that received 200 mg/kg and 400 mg/kg of the extract. CONCLUSIONS: The extract of the aerial parts of Verbena litoralis did not present significant toxicity when administered a single dose. However, when different doses were administered for 28 days, were observed changes in hematological, biochemical and histological parameters in rats.

Gastro-protective effect of edible plant Artemisia argyi in ethanol-induced rats via normalizing inflammatory responses and oxidative stress.

PHARMACOLOGICAL RELEVANCE: Artemisia argyi, a kind of ethnic drug, has a long-term use on gastric diseases and syndromes. AIM OF THE STUDY: The aim of the study is to validate the traditional uses of A. argyi scientifically and to discover more efficient nature derived gastro-protective ethnomedicine and further elucidate the possible mechanisms. MATERIALS AND METHODS: Sixty rats were randomly divided into control, model (ethanol-induced), reference (omeprazole-treated) and A. argyi extract (AT) (0.3, 0.1, 0.033g/mL) treated groups, respectively. The levels of biochemical indexes in tissues and serum and the activities of pepsin in gastric contents were measured after the sacrifice of rats. Moreover, the anti-inflammatory effects in LPS-induced RAW 264.7 cells of the isolated compounds were determined. RESULTS: The studies indicated that A. argyi extract could exert strong protective effects on gastric mucosa in ethanol-induced rat model by regulating the levels of inflammatory factors, superoxide dismutase, and malonaldehyde, which were superior to those of positive control at 0.3g/mL. The isolated flavonoids could down-regulate the levels of pro-inflammatory cytokines on LPS-induced RAW 264.7 macrophage cells and eliminate free radicals in the anti-oxidative tests. The effects of eupatilin and jaceosidin, which were substituted by additional methoxy groups, were predominant, indicting the importance of methoxy to the activities. CONCLUSION: The results confirmed that A. argyi can protect ethanol-induced rats from gastric mucosal injury through inhibiting inflammatory responses and ameliorating oxidative stress. A. argyi is suitable for people with gastric mucosal injuries or unhealthy dietary habits as a necessary dietary supplement, which will promote the planting and application of A. argyi in both agriculture and food industry.

[Quantative analysis of eupatilin and jaceosidin in folium of Artemisia argyi from different areas in China by RP-HPLC based on ancient medicine books].

In order to evaluate the quality of Artemisia argyi from Qichun, Ningbo, Anguo and Nanyang, the contents of eupatilin and jaceosidin were determined by RP-HPLC. The determination was performed on Agilent Eclipse XDB-C18 (4.6 mm×250 mm, 5 µm) with mobile phase consisted of acetonitrile-0.2% phosphoric acid(35∶65) at the flow rate 1.0 mL•min ⁻¹. The detection wavelength was 350 nm and the column temperature was 25 ℃. The results showed that the amount of eupatilin and jaceosidin had a clear linear relationship in the range of 0.003-0.126 g•L ⁻¹ (r=0.999 9) and 0.005-0.200 g•L ⁻¹ (r=0.999 9), and the average recovery rates for them were 99.14% (n=6, RSD 1.2%) and 99.40% (n=6, RSD=0.73%), respectively. The results showed that RP-HPLC can be used for the quantification of eupatilin and jaceosidin in the folium of A. argyi. With this method, we found there was no significant difference of jaceosidin content within all the samples collected, but the content of eupatilin was significantly higher in samples from Qichun, Ningbo, Xiangyang and Nanyang, located in the south of Huaihe River compared with these from other areas.

Structure-activity relationships for flavone interactions with amyloid ß reveal a novel anti-aggregatory and neuroprotective effect of 2',3',4'-trihydroxyflavone (2-D08).

Naturally-occurring flavonoids have well documented anti-aggregatory and neuroprotective properties against the hallmark toxic protein in Alzheimer's disease, amyloid ß (Aß). However the extensive diversity of flavonoids has limited the insight into the precise structure-activity relationships that confer such bioactive properties against the Aß protein. In the present study we have characterised the Aß binding properties, anti-aggregatory and neuroprotective effects of a discreet set of flavones, including the recently described novel protein sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Quercetin, transilitin, jaceosidin, nobiletin and 2-D08 were incubated with human Aß1-42 for 48h in vitro and effects on Aß fibrillisation kinetics and morphology measured using Thioflavin T (ThT) and electron microscopy respectively, in addition to effects on neuronal PC12 cell viability. Of the flavones studied, only quercetin, transilitin and 2-D08 significantly inhibited Aß1-42 aggregation and toxicity in PC12 cells. Of those, 2-D08 was the most effective inhibitor. The strong anti-amyloid activity of 2-D08 indicates that extensive hydroxylation in the B ring is the most important determinant of activity against ß amyloid within the flavone scaffold. The lack of efficacy of jaceosidin and nobiletin indicate that extension of B ring hydroxylation with methoxyl groups result in an incremental loss of anti-fibrillar and neuroprotective activity, highlighting the constraint to vicinal hydroxyl groups in the B ring for effective inhibition of aggregation. These findings reveal further structural insights into anti-amyloid bioactivity of flavonoids in addition to a novel and efficacious anti-aggregatory and neuroprotective effect of the semi-synthetic flavone and sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Such modified flavones may facilitate drug development targeting multiple pathways in neurodegenerative disease.

A natural compound jaceosidin ameliorates endoplasmic reticulum stress and insulin resistance via upregulation of SERCA2b.

Increased endoplasmic reticulum (ER) stress has emerged as a vital contributor to dysregulated glucose homeostasis, and impaired function of sarco-endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) is one of the central mechanisms underlying ER stress. In this study, we reported that SERCA2b upregulation contributed to the amelioration of ER stress and insulin resistance by a small natural compound jaceosidin. In a model of differentiated C2C12 myotubes, jaceosidin-triggered SERCA2b upregulation enhanced insulin sensitivity and decreased ER stress. Moreover, the activity of Ca2+-ATPase in thapsigargin-treated myotubes was also augmented by jaceosidin. Furthermore, jaceosidin significantly suppressed blood glucose levels, improved glucose tolerance and lowered body weight, but did not alter food intake in insulin-resistant obese mice. In addition, this compound markedly reduced lipid accumulation, suppressed the expression of lipogenic genes in liver and ameliorated liver injury. The ameliorative effects of jaceosidin were due to its ability to reduce ER stress via increasing the expression of SERCA2b in the muscles of obese mice. Taken together, jaceosidin could improve ER stress and attenuate insulin resistance via SERCA2b upregulation in mice skeletal muscles.

Antibacterial activity of fractions from three Chumash medicinal plant extracts and in vitro inhibition of the enzyme enoyl reductase by the flavonoid jaceosidin.

We have investigated the in vitro antibacterial bioactivity of dichloromethane-soluble fractions of Artemisia californica, Trichostema lanatum, Salvia apiana, Sambucus nigra ssp. cerulea and Quercus agrifolia Née against a ΔtolC mutant strain of Escherichia coli. These plants are traditional medicinal plants of the Chumash American Indians of Southern California. Bioassay-guided fractionation led to the isolation of three flavonoid compounds from A. californica: jaceosidin (1), jaceidin (2), and chrysoplenol B (3). Compounds 1 and 2 exhibited antibacterial activity against E. coli ΔtolC in liquid cultures. The in vitro activity of 1 against the enoyl reductase enzyme (FabI) was measured using a spectrophotometric assay and found to completely inhibit FabI activity at a concentration of 100 µM. However, comparison of minimum inhibitory concentration values for 1-3 against E. coli ΔtolC and an equivalent strain containing a plasmid constitutively expressing fabI did not reveal any selectivity for FabI in vivo.

Quantative analysis of eupatilin and jaceosidin in folium of Artemisia argyi from different areas in China by RP-HPLC based on ancient medicine books / 中国中药杂志

In order to evaluate the quality of Artemisia argyi from Qichun, Ningbo, Anguo and Nanyang, the contents of eupatilin and jaceosidin were determined by RP-HPLC. The determination was performed on Agilent Eclipse XDB-C₁₈ (4.6 mm×250 mm, 5 μm) with mobile phase consisted of acetonitrile-0.2% phosphoric acid(35∶65) at the flow rate 1.0 mL•min ⁻¹. The detection wavelength was 350 nm and the column temperature was 25 ℃. The results showed that the amount of eupatilin and jaceosidin had a clear linear relationship in the range of 0.003-0.126 g•L ⁻¹ (r=0.999 9) and 0.005-0.200 g•L ⁻¹ (r=0.999 9), and the average recovery rates for them were 99.14% (n=6, RSD 1.2%) and 99.40% (n=6, RSD=0.73%), respectively. The results showed that RP-HPLC can be used for the quantification of eupatilin and jaceosidin in the folium of A. argyi. With this method, we found there was no significant difference of jaceosidin content within all the samples collected, but the content of eupatilin was significantly higher in samples from Qichun, Ningbo, Xiangyang and Nanyang, located in the south of Huaihe River compared with these from other areas.