Scrophularia Buergeriana Research Articles

Synthesis, Crystal Structure, Hirshfeld Surface Analyses and Biological Activity of Novel Cinnamide Derivatives as Neuroprotective Drugs

The p-methoxycinnamoyl group contained in the compounds extracted from Scrophularia buergeriana, which is a traditional medicinal herb in China, exhibits a remarkable neuroprotective effect. Based on the p-methoxycinnamoyl group, these two cinnamide derivatives, namely, (E)-3-(4-bromophenyl)-1-(4-(4-chlorobenzyl)piperazin-1-yl)prop-2-en-1-one (6a) and (E)-1-(4-(4-chlorobenzyl)piperazin-1-yl)-3-(4-chlorophenyl)prop-2-en-1-one (6b), were designed and synthesized. The target compounds were represented by High-resolution mass spectra, 1H NMR spectra, 13C NMR spectra, and single-crystal X-ray diffraction. According to the results of single-crystal X-ray diffraction, indicating that compound 6a crystallizes in the monoclinic system and compound 6b crystallizes in the triclinic system, and they both have a stacked-layer 3-D structure. Hirshfeld surface indicated that compounds 6a and 6b exist H…H, O…H, C…H, and π…π intermolecular interactions. Furthermore, their neuroprotective effects were further evaluated against glutamate-induced PC12 cell injury. These results indicate that the target compounds exhibit potent activities against glutamine-induced neurotoxicity in PC12 cells. In vivo experiments demonstrated that compounds 6a and 6b have good protective effects in high doses on bilateral common carotid artery ligation.

Effects of Scrophularia buergeriana Extract (Brainon®) on Aging-Induced Memory Impairment in SAMP8 Mice

Alzheimer's disease (AD) is a worldwide problem. Currently, there are no effective drugs for AD treatment. Scrophularia buergeriana Miquel (SB) is a traditional herbal medicine used in Korea to treat various diseases. Our previous studies have shown that ethanol extract of SB roots (SBE, Brainon®) exhibits potent anti-amnesic effects in Aβ1-42- or scopolamine-treated memory impairment mice model and neuroprotective effects in a glutamate-induced SH-SY5Y cell model. In this study, we evaluated the therapeutic effects of Brainon® and its mechanism of action in senescence-accelerated mouse prone 8 (SAMP8) mice. Brainon® (30 or 100 mg/kg/day) was orally treated to six-month-old SAMP8 mice for 12 weeks. Results revealed that Brainon® administration effectually ameliorated cognitive deficits in Y-maze and passive avoidance tests. Following the completion of behavioral testing, western blotting was performed using the cerebral cortex. Results revealed that Brainon® suppressed Aβ1-42 accumulation, Tau hyperphosphorylation, oxidative stress, and inflammation and alleviated apoptosis in SAMP8 mice. Brainon® also promoted synaptic function by downregulating the expression of AChE and upregulating the expression of p-CREB/CREB and BDNF. Furthermore, Brainon® restored SAMP8-reduced expression of ChAT and -dephosphorylated of ERK and also decreased AChE expression in the hippocampus. Furthermore, Brainon® alleviated AD progression by promoting mitophagy/autophagy to maintain normal cellular function as a novel finding of this study. Our data suggest that Brainon® can remarkably improve cognitive deficiency with the potential to be utilized in functional food for improving brain health.

A mixture of Panax ginseng and Scrophularia buergeriana improves immune function in an immunosuppressed murine model

BackgroundImmunomodulatory drugs are currently used for immunosuppressed individuals, but adverse side effects have been reported. Although Panax ginseng and Scrophularia buergeriana are known to have respective pharmacological properties, the potential of a mixture of Panax ginseng and Scrophularia buergeriana (Isam-Tang, IST) as an immunomodulatory drug has not yet been studied. PurposeThe present study was designed to assess the immunomodulatory activity of IST and p-coumaric acid (pCA), an active compound of IST, in the immune system. MethodsThe levels of immunostimulatory cytokines, nitrite, inducible nitric oxide synthase (iNOS), NF-kB activation, and proliferation were examined in RAW264.7 cells, primary splenocytes and splenic NK cells isolated from normal mouse spleen, and in cyclophosphamide-induced immunosuppressed mice using ELISA, quantitative real-time PCR, Western blotting, and immunofluorescence staining. ResultsIST or pCA treatment increased the production of immunostimulatory cytokines and nitrite and the expression of iNOS in RAW264.7 cells and splenocytes. IST or pCA also induced NF-κB signaling activation and promoted the phagocytic activity of RAW264.7 cells. In addition, the splenocyte proliferation and splenic NK activity were enhanced by IST or pCA. IST or pCA increased the levels of immunostimulatory cytokines in immunosuppressed mice and ameliorated splenic tissue damage. ConclusionThese findings suggest that IST supplementation may be used to enhance immune function.

Scrophulariae Radix: An Overview of Its Biological Activities and Nutraceutical and Pharmaceutical Applications.

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.

Complete Genome Sequence and Characterization of Beet Western Yellows Virus in Figwort

Background: Figwort (Scrophularia buergeriana Miq.) is a biennial plant, whose dried root has been used in traditional medicine. Here, we investigated a viral disease in S. buergeriana, characterized the disease symptoms, and sequenced the complete genome of the identified virus.<BR>Methods and Results: Disease symptoms and growth characteristics were compared between two groups of plants, that is, those that were grown from rootlets and those cultivated from seeds. Leaf samples were collected from both groups for RNA sequencing analysis. Primers were designed based on the obtained contig, and the complete genome sequence was determined via reverse transcription polymerase chain reaction and cloning. Viral symptoms were confirmed in figwort plants. The highest incidence of infections was observed at the end of July. The complete genome of Beet western yellows virus (BWYV) ADHS comprised 5,878 nucleotides and seven open reading frames. Phylogenetic analysis based on the nucleotide sequence of the complete genome confirmed that the BWYV ADHS isolate was related most closely to the LS isolate from Korea.<BR>Conclusions: This study is the first report of BWYV infection in figwort worldwide. The virus affects plant height and root weight. Control methods should be developed to minimize virus damage in figwort culture.

Scrophularia buergeriana Extract (Brainon) Improves Scopolamine-Induced Neuronal Impairment and Cholinergic Dysfunction in Mice through CREB-BDNF Signaling Pathway

We evaluated the effectiveness of Scrophularia buergeriana extract (Brainon) on cognitive dysfunction and determined its underlying mechanisms in a scopolamine (SCO)-treated mouse model of memory impairment. Brainon treatment for 28 days ameliorated the symptoms of memory impairment as indicated by the results of both passive avoidance performance and the Morris water mazes. Brainon lowered acetylcholinesterase activity and raised acetylcholine levels in the hippocampus. The treatment elevated the protein levels of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding (CREB). Additionally, the excessive generation of SCO-induced reactive oxygen species (ROS) and subsequent oxidative stress were suppressed by the enhancement of superoxide dismutase (SOD)-1 and SOD-2 proteins. mRNA levels of upregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, as well as the apoptotic protein Bcl-2-associated X protein (Bax), cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase (PARP) expression after SCO injection were downregulated by Brainon treatment. Collectively, these findings suggested that Brainon possesses anti-amnesic effects through the CREB-BDNF pathway. Moreover, it exerted antioxidant, anti-inflammatory, and anti-apoptotic effects in SCO-induced mice exhibiting cognitive impairment and memory loss.

Scrophularia buergeriana Extract Improves Memory Impairment via Inhibition of the Apoptosis Pathway in the Mouse Hippocampus

Scrophularia buergeriana (SB) Miq. (Scrophulariaceae) has been used to help cure swelling and fever and has reported antioxidant and neuro-protective effects. However, few mechanism–based studies have evaluated the memory-improving effects in a beta-amyloid induced memory loss model. As a result of Scrophularia buergeriana extract (SBE) administration (30 and 100 mg/kg) for 28 days significantly recovered beta-amyloid-induced amnesia in the passive avoidance test and improved the impairment of spatial memory in the Morris Water Maze (MWM) task. Furthermore, SBE up-regulated superoxide dismutase-1 (SOD)-1, SOD-2, glutathione peroxidase-1, and B-cell lymphoma (Bcl)-2 protein expression levels. Additionally, SBE downregulated Bcl-2-associated X protein, cleaved caspase-9, cleaved poly (adenosine diphosphate-ribose) polymerase, and Aβ protein expression levels and inhibited the phosphorylation of the tau protein of Aβ-treated mice hippocampus. These results demonstrate that SBE improved memory impairment by reducing beta-amyloid induced neurotoxicity and regulated oxidative stress, anti-apoptotic pathways.

Isolation and quantitative analysis of metabolites from Scrophularia buergeriana and their hepatoprotective effects against HepG2 Cells

현삼(Scrophularia buergeriana) 뿌리를 80% Methanol수용액으로 추출한 뒤, 감압 농축한 추출물을 EtOAc, n-BuOH과 H2O층으로 계통 분획을 실시하였다. n-BuOH분획에 대하여 silicagel, octadecyl SiO2 column chromatograph 및 중압분취(MPLC)장비를 반복 실시하여 4종의 phenylethanoid glycoside 및 iridoid glycoside계의 화합물을 분리하였다. NMR 및 Mass데이터를 해석하여, harpagoside (1), angoroside C (2), aucubin (3) 및 acetoside (4)로 구조 동정하였다. 분리한 4종의 화합물에 대하여 HPLC 분석법을 이용하여 정량분석한 결과, 11.5mg/g (1), 7.6 mg/g (2), 41.2 mg/g (3), 및 4.8 mg/g (4) 이현삼 뿌리에 함유된 것을 확인하였다. 현삼으로부터 분리된 화합물 중 angoroside C 및 acetoside는 에탄올에 의해 저해된 세포 성장률을 검증한 결과, 간암세포종인 HepG2세포에 대해서 간세포를 보호하는 효과가 있음을 확인하였다.

Abstract 4404: E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl ester (MCR) increases Nrf2 stability by inhibiting ubiquitination in HaCaT cells

Abstract The nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator of gene expression during oxidative stress and drug detoxification. Thus, identifying Nrf2 activators to protect from possible cell damage is necessary. In this study, we investigated whether E-p-methoxycinnamoyl-α-l-rhamnopyranosyl ester (MCR), a phenylpropanoid isolated from Scrophularia buergeriana, can activate Nrf2 signaling in human keratinocytes (HaCaT). First, we determined the dose- and time-dependent effects of MCR on the expression and activity of Nrf2. The antioxidant response element-luciferase reporter assay and western blot analysis results showed that MCR markedly induced Nrf2 activity and its protein expression, respectively. Further, MCR increased both the mRNA and protein levels of heme-oxygenase-1, one of the Nrf2 target genes, in the cells. Interestingly, we found that Nrf2 stability was remarkably enhanced by MCR. Furthermore, ubiquitin-dependent proteasomal degradation of Nrf2 was significantly reduced by MCR. Thus, MCR might afford skin protection by enhancing Nrf2 stability or by blocking its proteasomal degradation. Citation Format: Jiwon Jeong, Lilik D. Wahyudy, Heejung Yang, Jung-Hwan Kim. E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl ester (MCR) increases Nrf2 stability by inhibiting ubiquitination in HaCaT cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4404.

E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes.

The nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator of gene expression during oxidative stress and drug detoxification. Thus, identifying Nrf2 activators to protect from possible cell damage is necessary. In this study, we investigated whether E-p-methoxycinnamoyl-α-l-rhamnopyranosyl ester (MCR), a phenylpropanoid isolated from Scrophularia buergeriana, can activate Nrf2 signaling in human keratinocytes (HaCaT). First, we determined the dose- and time-dependent effects of MCR on the expression and activity of Nrf2. The antioxidant response element-luciferase reporter assay and western blot analysis results showed that MCR markedly induced Nrf2 activity and its protein expression, respectively. Further, MCR increased both the mRNA and protein levels of heme-oxygenase-1, one of the Nrf2 target genes, in the cells. Interestingly, we found that Nrf2 stability was remarkably enhanced by MCR. Furthermore, ubiquitin-dependent proteasomal degradation of Nrf2 was significantly reduced by MCR. Thus, MCR might afford skin protection by enhancing Nrf2 stability or by blocking its proteasomal degradation.

Effect of Storage Condition on the Germination of Scrophularia buergeriana and Scrophularia takesimensis

Background: This study was conducted to investigate the effects of germination temperature, storage container and storage temperature on Scrophularia buergeriana and Scrophularia takesimensis seeds. Methods and Results: Seed lengths of both species were 0.8 ㎜, while seed width differed, with S. buergeriana measuring 0.5 ㎜ and S. takesimensis measuring 0.4 ㎜. The seeds of S. buergeriana were packaged in paper containers under room temperature (15℃), cold temperature (4℃), and freeze temperature (−20℃). These seeds exhibited around 80% germination rate at temperatures between 15℃ and 30℃. The germiantion rate of S. takesimensis, on the other hand, differed significantly at different germination temperatures. Seeds of S. takesimensis which were packaged in vinyl and paper containers and stored under room and cold temperatures, exhibited around 80% germination rate at 15℃. However, the germination rate of freeze-stored seeds were decreased to lower than 20% at germination temperatures of 15℃, 25℃ and 30℃ germiantion conditions. The rate of germination showed a low positive to a significantly negativie correlation with the other factor that were determined to evaluate the germination performance. Conclusions: This study elucidates the most suitable germination and storage conditions to increase the germination rate for the two species of Scrophularia buergeriana and Scrophularia takesimensis needs to be stored in paper containers under cold temperature and requires a temperature of 20℃ for germination. On the other hand, S. takesimensis in vinyl containers need to be stored at room temperature and those in paper containers at cold temperature, and a temperature of 15℃ is required for germination.

English

This study determined the effect of 30% ethanol extract of plant mixture (EPM: Glycyrrhiza uralensis, Angelica gigas, Acorus calamus, Cnidium officinale, Panax ginseng, Camellia sinensis, Salvia miltiorrhiza, Zanthoxylum schinifolium, Carthamus tinctorius, Prunus persica and Scrophularia buergeriana) on promotion of hair growth in human hair dermal papilla cells and C57BL/6J mice. EPM significantly increased the proliferation of human hair dermal papilla cells in a dose- and time- dependent manner (p < 0.05 and p < 0.01). EPM also enhanced mRNA and protein levels of growth factors such as IGF-1, VEGF, KGF and HGF. Moreover, photographical and histological observation showed that application of EPM resulted in the early onset and prolongation of the anagen phase of the hair cycle. In addition, the EPM was revealed to possess potent inhibitory effect on the 5α-reductase activity. Taken together, these results suggest that EPM has hair growth promoting potential and can be used for hair growing products. Key words: Hair growth, extract of plant mixture, growth factors, steroid 5α-reductase.

A study on the glucose‐regulating enzyme activities of water extracts from Korea medicinal herbs (959.18)

We selected Korea medicinal herbs having potential anti‐diabetic effects by activation of hepatic glucose‐regulating enzymes, such as glucokinase (GK). The glucokinase(GK) activity using the cytosol fraction in liver of a type II diabetic animal (GK rat, Goto‐kakizaki) was measured by spectrometric procedure. The selected Korea medicinal herbs were CM(Cordyceps militaris), MWY(Paeonia suffruticosa Andrews), SSY(Cornus officinalis), JSY (Perilla sikokiana), MWR(Angelica utilis Makino), SJH(Rehmannia glutinosa), DMH(Scrophularia buergeriana MIQUEL), JGP(Lycium Chinense), JC(Panax notoginsengs), YSB(Pyrus pyrifolia), PBG(Chamaecyparis obtusa), CWJ(Cucumis melon L. ), GSO(Acanthopanax senticosun), SY(Discorea Japonica Thunb.), YM(Coix Lachryma‐jobi L.) and DS(Salvia miltriorrhiza Bunge). Additionally, glucose‐uptake activity was measured by detection of 2DG accumulation in HepG2 cell. As a results of study, the GK activity in cytosol fraction of liver was higher at the 1mg/ml CM(2.99 fold induction) water extract than the control, and glucose‐uptake effect was higher at the MWY, CJW and MWR water extracts than at the control.

경동맥 혈전 유발 동물모델을 이용한 한약재 추출물의 효능 검색

Objectives : The aim of this study was to examine anti-thrombotic effect of traditional herbal extracts in a rat model of ferric chloride (<TEX>$FeCl_3$</TEX>)-induced carotid arterial thrombosis. Methods : Thirty minutes prior to a 35% <TEX>$FeCl_3$</TEX> application, Sprague Dawley(SD) rats were injected with the 10 types of traditional herbal extracts (100mg/kg, intraperitoneal injection), respectively. The effect of these herbal extracts was examined for time to occlusion(TTO) using the Laser doppler flow meter and measured for thrombus weight (TW) in <TEX>$FeCl_3$</TEX>-induced thrombosis model. Results : In the TTO, Salvia miltiorrhiza (Sm, <TEX>$2.30{\pm}0.28$</TEX> min, p<0.001) and Santalum album (Sa, <TEX>$2.19{\pm}0.19$</TEX> min, p<0.001) showed significantly delayed TTO more than twice compared with Saline-treated group. Cnidium officinale (Co), Psoralea corylifolia (Pc), Scutellatia baicalensis (Sba), Panax notoginseng (Pn), Angelica tenuissima (At), Scrophularia buergeriana (Sbu), Rhus verniciflua (Rv) and Picrasma quassioides (Pq), except for Rhus verniciflua (Rv) also meaningfully impeded TTO more than one fold. In addition, Salvia miltiorrhiza, Santalum album, Cnidium officinale, Psoralea corylifolia and Scutellatia baicalensis significantly reduced TW more than 10% compared with Saline-treated group. Especially, Salvia miltiorrhiza and Santalum album showed the most excellent anti-thrombotic effect among the 10 herbal extracts tested on the restoration of altered TTO and TW. Conclusions : These results suggest that Sm and Sa extracts have outstanding anti-thrombotic effect in <TEX>$FeCl_3$</TEX>-induced thrombosis model and is potentially useful as herbal medicines for the treatment and prevention of thrombosis.

Scrophularia buergeriana regulates cytokine production in vitro

The Scrophularia buergeriana (SB) has long been used to treat various diseases an account of its antimicrobial and anti-virus activity. However, it is unclear how SB regulates the immune responses. This study investigated the effect of SB on the production of cytokines in a human T-cell line, MOLT-4 cells, and mouse peritoneal macrophages. The MOLT-4 cells were cultured for 24 h in the presence or absence of SB plus concanavalin (con) A. SB plus con A significantly increased the level of interleukin (IL)-2, IL-4 and interferon (IFN)-γ production compared with that of con A alone (approximately 1.79-fold for IL-2, 2-fold for IL-4, and 1.85-fold for IFN-γ, p < 0.05). SB plus recombinant IFN-γ (rIFN-γ) increased the level of IL-12 and NO production compared with rIFN-γ alone. In addition, SB plus rIFN-γ increased the level the iNOS expression on mouse peritoneal macrophages. Overall, SB may have an immune-enhancement effect through cytokine production.

Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice

The cognitive-enhancing activities of E-harpagoside and 8-O-E-p-methoxycinnamoylharpagide (MCA-Hg) isolated from Scrophularia buergeriana were evaluated in scopolamine-induced amnesic mice by the Morris water maze and by passive avoidance tests [1, 2]. E-harpagoside and MCA-Hg significantly improved the impairment of reference memory induced by scopolamine in the Morris water maze test. The mean escape latency, the mean path length and swimming movement were also improved by both compounds. In passive avoidance test, E-harpagoside and MCA-Hg (2mg/kg body weight, p.o.) significantly ameliorated scopolamine-induced amnesia by as much as 70% of the level found in normal control mice. Donepezil, an acetylcholinesterase inhibitor and the most widely used drug for AD treatment was employed as a positive control [3]. The activity of acetylcholinesterase was inhibited significantly by E-harpagoside or MCA-Hg within the cortex and hippocampus to a level similar to that observed in mice treated with donepezil (2mg/kg body weight, p.o.). Moreover, treatment with E-harpagoside or MCA-Hg to scopolamine-induced amnesic mice significantly decreased TBARS level which was accompanied by an increase in the activities or contents of glutathione reductase, SOD and reduced GSH. We believe these data demonstrate that E-harpagoside or MCA-Hg exerted potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidant mechanisms.

Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice

The cognitive-enhancing activities of E-harpagoside and 8- O- E- p-methoxycinnamoylharpagide (MCA-Hg) isolated from Scrophularia buergeriana were evaluated in scopolamine-induced amnesic mice by the Morris water maze and by passive avoidance tests. E-harpagoside and MCA-Hg significantly improved the impairment of reference memory induced by scopolamine in the Morris water maze test. The mean escape latency, the mean path length and swimming movement were also improved by both compounds. In passive avoidance test, E-harpagoside and MCA-Hg (2 mg/kg body weight, p.o.) significantly ameliorated scopolamine-induced amnesia by as much as 70% of the level found in normal control mice. Donepezil, an acetylcholinesterase inhibitor and the most widely used drug for AD treatment was employed as a positive control. The activity of acetylcholinesterase was inhibited significantly by E-harpagoside or MCA-Hg within the cortex and hippocampus to a level similar to that observed in mice treated with donepezil (2 mg/kg body weight, p.o.). Moreover, treatment with E-harpagoside or MCA-Hg to scopolamine-induced amnesic mice significantly decreased TBARS level which was accompanied by an increase in the activities or contents of glutathione reductase, SOD and reduced GSH. We believe these data demonstrate that E-harpagoside or MCA-Hg exerted potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidant mechanisms.

Cognitive-enhancing activities of iridoid glycosides isolated from Scrophularia buergeriana

Cognitive-enhancing activities of iridoid glycosides isolated from Scrophularia buergeriana