KD-501, a standardized extract of Scrophularia buergeriana has both cognitive-enhancing and antioxidant activities in mice given scopolamine.
Jeong Eun Ju,Ma Choong Je,Lee Ki Yong,Kim Seung Hyun,Sung Sang Hyun,Kim Young Choong
Journal of ethnopharmacology
AIM OF THE STUDY:The cognitive-enhancing and antioxidant activities of KD-501, a standardized extract of the roots of Scrophularia buergeriana Miquel (Scrophulariceae) were investigated. MATERIALS AND METHODS:KD-501 was orally administered to amnesic mice induced by scopolamine and we performed passive avoidance and the Morris water maze tests. To elucidate the mechanism of cognitive-enhancing activity, the effects of KD-501 on the activities of acetylcholinesterase and antioxidant enzymes within the cortex and hippocampus of mice were evaluated. RESULTS:Acute and prolonged oral administration of KD-501 significantly ameliorated scopolamine-induced amnesia in passive avoidance test. In the Morris water maze test, acute and prolonged administration of KD-501 improved the impairment of spatial memory induced by scopolamine indicated by the formation of reference and working memories. The activity of acetylcholinesterase was significantly inhibited by KD-501 within the cortex and hippocampus. Moreover, the reduced activities or contents of glutathione reductase, superoxide dismutase (SOD) and reduced GSH within the cortex and hippocampus caused by scopolamine were elevated by the treatment of KD-501. CONCLUSIONS:Taken together, it could be postulated that KD-501 may exert its potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidative actions.
10.1016/j.jep.2008.10.006
Scrophularia lucida L. as a valuable source of bioactive compounds for pharmaceutical applications: In vitro antioxidant, anti-inflammatory, enzyme inhibitory properties, in silico studies, and HPLC profiles.
Journal of pharmaceutical and biomedical analysis
The genus Scrophularia has received much interest with regards to its traditional uses against eczema, psoriasis, and mastitis. Yet, the medicinal properties of some species still need to be scientifically validated. The present study was designed to investigate into the biological properties of various solvent extracts (ethyl acetate, methanol, and aqueous) of the roots and aerial parts of Scrophularia lucida based on its antioxidant, anti-inflammatory, and enzyme inhibitory activities together with phytochemical screening. Our results revealed that the solvent extracts differed in their biological effectiveness. The root ethyl acetate extract showed the highest ABTS scavenging, FRAP, CUPRAC, and inhibitory activity against AChE and α-glucosidase. The ethyl acetate extract of the aerial parts displayed the highest BChE and α-amylase inhibition and antioxidant effect in the phosphomolybdenum assay, while the methanol extracts of both parts were the most effective DPPH scavengers and tyrosinase inhibitors. The methanol extracts of the root and aerial parts also inhibited NO production in lipopolysaccharide (LPS)-stimulated murine leukemic monocyte-macrophage cell (4.99% and 10.77%, respectively), at 31.25 μg/mL concentration. The highest TPC (34.98 mg GAE/g extract) and TFC (48.33 mg RE/g extract) were observed in the ethyl acetate extract of the root and aerial parts, respectively. The most abundant compounds in the root ethyl acetate extract were luteolin (852 μg/g extract), rosmarinic acid (522 μg/g extract), and hesperidin (394 μg/g extract) while kaempferol was most abundant in the ethyl acetate extract of the aerial parts (628 μg/g extract). In silico experiments were conducted on tyrosinase and the higher docking values were observed for rosmarinic acid and hesperidin. The present findings provide base line information which tend to support the potential use of S. lucida in the management of several chronic diseases, including Alzheimer's disease and diabetes mellitus.
10.1016/j.jpba.2018.09.035
Harpagoside variation is positively correlated with temperature in Scrophularia ningpoensis Hemsl.
Yang Shuting,Li Jinghui,Zhao Yunpeng,Chen Binlong,Fu Chengxin
Journal of agricultural and food chemistry
Scrophularia ningpoensis Hemsl. is an important Chinese medicinal herb with a history of domestication of over 1000 years. Phytochemical variation of S. ningpoensis in response to environmental gradients remains an attractive topic with both practiceal and theoretical significances. In the current study, HPLC fingerprinting and four major bioactive compounds of S. ningpoensis, that is, harpagoside, angroside C, acteoside, and cinnamic acid, were determined to explore its correlations with climatic, geographic, and soil factors. The present data confirmed the approximate three-group pattern of phytochemical differentiation among the five production regions, the population of Zhejiang (ZJ), the population of Hubei (HB), and the rest three populations of Chongqing, Hunan, and Shaanxi (CQ, HN, and SX). Harpagoside, the dominant bioactive compound of S. ningpoensis, contributed most to the phytochemical differentiation and displayed a significant positive correlation with monthly and annual average temperature and negative correlations with altitude and latitude. It was concluded that harpagoside variation was strongly positively correlated with environmental changes of temperature.
10.1021/jf104702u
Three Species (, , and ) Inhibit RANKL-Induced Osteoclast Differentiation in Bone Marrow-Derived Macrophages.
Nam Hyeon-Hwa,Lee A Yeong,Seo Yun-Soo,Park Inkyu,Yang Sungyu,Chun Jin Mi,Moon Byeong Cheol,Song Jun-Ho,Kim Joong-Sun
Plants (Basel, Switzerland)
Scrophulariae Radix, derived from the dried roots of Hemsl. or Miq, is a traditional herbal medicine used in Asia to treat rheumatism, arthritis, and pharyngalgia. However, the effects of , , and on osteoclast formation and bone resorption remain unclear. In this study, we investigated the morphological characteristics and harpagoside content of , , and , and compared the effects of ethanol extracts of these species using nuclear factor (NF)-κB ligand (RANKL)-mediated osteoclast differentiation. The harpagoside content of the three species was analyzed by high-performance liquid chromatography-mass spectrometry (HPLC/MS). Their therapeutic effects were evaluated by tartrate-resistant acid phosphatase (TRAP)-positive cell formation and bone resorption in bone marrow-derived macrophages (BMMs) harvested from ICR mice. We confirmed the presence of harpagoside in the species. The harpagoside content of , , and was 1.94 ± 0.24 mg/g, 6.47 ± 0.02 mg/g, and 5.50 ± 0.02 mg/g, respectively. Treatment of BMMs with extracts of the three species inhibited TRAP-positive cell formation in a dose-dependent manner. The area of hydroxyapatite-absorbed osteoclasts was markedly decreased after treatment with the three species extracts. Our results indicated that the three species of the genus might exert preventive effects on bone disorders by inhibiting osteoclast differentiation and bone resorption, suggesting that these species may have medicinal and functional value.
10.3390/plants9121656
Harpagide alleviate neuronal apoptosis and blood-brain barrier leakage by inhibiting TLR4/MyD88/NF-κB signaling pathway in Angiotensin II-induced microglial activation in vitro.
Chemico-biological interactions
Angiotensin II, the effector peptide of the renin-angiotensin system, is not only a pivotal peptide implicated in the regulation of blood pressure but also a key mediator of the inflammatory processes that play an important role in the pathology of hypertension-related cSVD. Harpagide is the major bioactive constituent of Scrophulariae Radix widely used in traditional Chinese medicine for numerous diseases including hypertension. The present study aimed to investigate the effect of harpagide on Ang II-induced neuroinflammation and the potential mechanism. Pretreated with harpagide or resatorvid (the TLR4 pathway inhibitor), BV2 cells were treated with Ang II or LPS (the TLR4 activator). NO, pro-inflammatory cytokines, the proteins on TLR4/MyD88/NF-κB signaling pathway and the expression of CD86, CD206, TREM2 in BV2 cells were detected respectively. Subsequently, the effects of harpagide on neurotoxicity and BBB destruction triggered by Ang II-induced neuroinflammation were investigated in the co-cultures of BV2 microglia/HT22 hippocampal neurons, BV2 microglia/bEnd.3 endotheliocyte and BV2 microglia/BBB monolayer model. We found that Ang II converted microglia into M1 state and resulted in neuroinflammation through activating TLR4/MyD88/NF-κB signaling pathway. It also triggered the imbalance of TLR4/TREM2 in microglia. Ang II-mediated inflammation microglia further led to neuronal apoptosis and BBB damage. Harpagide showed the effect of alleviating Ang II-mediated neuroinflammation as well as the resulting neurotoxicity and BBB destruction through inhibiting the TLR4/MyD88/NF-κB pathway. The anti-inflammatory and neuroprotective effect of harpagide suggested that it might be a potential therapeutic strategy in hypertensive cSVD.
10.1016/j.cbi.2021.109653
Optimization of Extraction of Four Components from Radix Scrophulariae with Natural Deep Eutectic Solvents and Evaluation of Extract's Antioxidant Activity.
Journal of chromatographic science
In this research, eight natural deep eutectic solvents (NaDESs) consisting of food-grade ingredients were screened for the extraction of four bioactive compounds (acteoside, cinnamic acid, angoroside C and harpagoside) from radix scrophulariae (RS). Among these NaDESs, Proline-Glycerol NaDES with higher comprehensive score was selected. The Criteria Importance Through Intercriteria Correlation (CRITIC) was applied to calculate the information entropy and the weight of indexes, and figured out a comprehensive score. The weights of acteoside, cinnamic acid, angoroside C and harpagoside were 0.369, 0.172, 0.241 and 0.218, respectively. Response surface methodology (RSM) mathematical model was used to optimize the extraction parameters. The optimal extraction parameters were as follows: extraction time with 42.21 min, NaDES concentration with 52.89%, solid-to-liquid ratio with 1 : 37.05 g/mL and the predicted value of comprehensive score was 0.885. Under the optimal condition, the comprehensive score was 0.903 ± 0.005. Finally, the antioxidant activity experiment revealed that the 1,1-Diphenyl-2-picrylhydrazyl · radical scavenging activity and hydroxyl radical scavenging activity of the extract at 2.0 mg/mL and 1.5 mg/mL were approximately equal to those of ascorbic acid, respectively. The results showed that the extraction condition optimized by RSM combined with CRITIC was reasonable and dependable, and the extract of radix scrophulariae exhibited good antioxidant activity.
10.1093/chromsci/bmae037
SRVF, a novel herbal formula including Scrophulariae Radix and Viticis Fructus, disrupts focal adhesion and causes detachment-induced apoptosis in malignant cancer cells.
Kim Aeyung,Im Minju,Ma Jin Yeul
Scientific reports
When cells lose adhesion, they undergo detachment-induced apoptosis, known as anoikis. In contrast, tumor cells acquire resistance to anoikis, enabling them to survive, even after separating from neighboring cells or the ECM. Therefore, agents that restore anoikis sensitivity may serve as anti-cancer candidates. In this study, we constructed a novel herbal formula, SRVF, which contains Scrophulariae Radix (SR) and Viticis Fructus (VF). SRVF rapidly decreased cell adhesion, altered the cell morphology to round, and induced cell death; however, SR, VF, or their co-treatment did not. SRVF arrested HT1080 cells in G/M phase, increased the levels of pro-apoptotic proteins, and decreased the levels of anti-apoptotic proteins. Furthermore, SRVF efficiently reduced cell-cell and cell-ECM interactions by disrupting the F-actin cytoskeleton and down-regulating the levels of focal adhesion-related proteins, suggesting that SRVF efficiently triggers detachment-induced apoptosis (i.e., anoikis) in malignant cancer cells. In xenograft mouse models, daily oral administration of 50 or 100 mg/kg SRVF retarded tumor growth in vivo, and repeated administration of SRVF did not cause systemic toxicity in normal mice. These data collectively indicate that SRVF induces cancer cell death by restoring anoikis sensitivity via disrupting focal adhesion. Therefore, SRVF may be a safe and potent anti-cancer herbal decoction.
10.1038/s41598-017-12934-y
An integrated metabolomics and 16S rRNA gene sequencing approach exploring the molecular pathways and potential targets behind the effects of Radix Scrophulariae.
RSC advances
To assess the impact of the caecal microbiota on faecal metabolic phenotypes in the presence of Radix Scrophulariae (Chinese name: ), an integrated approach involving 16S rRNA gene sequencing combined with ultrahigh-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS)-based faecal metabolomics was applied to Radix Scrophulariae-treated rats. Interestingly, Radix Scrophulariae led to significant gut microbiota changes at the phylum and genus levels in treated rats compared to control rats. Additionally, distinct changes in faecal metabolites, including linoleic acid (LA), guanosine, inosine, hypoxanthine, xanthine, 4-hydroxycinnamic acid, cholic acid, -acetyl-d-glucosamine, l-urobilinogen and uridine, were observed in Radix Scrophulariae-treated rats. Of these, seven metabolites were up-regulated, and the remaining three metabolites were down-regulated. Moreover, there were substantial associations between altered levels of gut microbiota genera and discrepant levels of faecal metabolites, particularly for compounds involved in LA and purine metabolism. These results demonstrated that the gut microbiota is altered in association with faecal metabolism following treatment with Radix Scrophulariae. Our findings suggest that further application of this 16S rRNA gene sequencing and UHPLC/TOF-MS-based metabolomics approach will facilitate the assessment of the pharmacological action of Radix Scrophulariae and thus expand the scope of this herb.
10.1039/c9ra03912k
Neuroprotective Effects of Radix Scrophulariae on Cerebral Ischemia and Reperfusion Injury via MAPK Pathways.
Molecules (Basel, Switzerland)
Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R). Ischemia and reperfusion-induced injury or apoptosis inhibition in human brain tissue may exert an irreplaceable protective effect on ischemic nerves. This process has particular significance for the treatment of stroke patients. However, the development of neuroprotective drugs remains challenging. Radix Scrophulariae, traditionally considered a valuable medicine, has been discovered to have neuroprotective effects. To explore the neuroprotective effects of an aqueous extract of Radix Scrophulariae (RSAE) on cerebral ischemia/reperfusion and their underlying mechanisms, oxygen-glucose deprivation and reperfusion (OGD/R)-induced PC12 cells were used, and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. In vitro results showed that 12.5 μg/mL RSAE markedly improved cell viability; inhibited LDH leakage; increased SOD, GSH-Px and CAT enzyme activity; stabilized the mitochondrial membrane potential; and reduced OGD-induced cell injury and apoptosis. Additionally, in vivo results preliminarily suggested that in MCAO/R model mice, RSAE treatments attenuated infarct volume; reduced brain water content and nitric oxide (NO) and malondialdehyde (MDA) concentrations; inhibited I/R-induced neurological deficits; reduced the levels of lactate dehydrogenase (LDH) leakage release; improved antioxidant capacity by upregulating SOD, GSH-Px and CAT enzyme activity; and reduced neuronal apoptosis, necrosis and loss of neurons. Moreover, it was found that RSAE upregulated the expression of Bcl-2 and downregulated the expression of Bax. In addition, the phosphorylation levels of MAPK signal pathways were elucidated via western blot analysis and immunohistochemical evaluation. In summary, this study investigated the neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R injury in mice. Radix Scrophulariae has been previously identified as a potential neuroprotective natural plant. Hence, our results may offer insight into discovering new active compounds or drugs for the treatment of ischemic stroke. Many new natural active chemicals in this extract may be discovered by chemical separation and identification and may provide new insights into therapeutic targets in stroke patients.
10.3390/molecules23092401
Molecular Insights into the Macrophage Immunomodulatory Effects of Scrophulariae Radix Polysaccharides.
Chemistry & biodiversity
Scrophulariae Radix (SR) has been widely used in Chinese herbal compound prescriptions, health care products and functional foods. The present study aimed to investigate the immunomodulatory activity of polysaccharides from SR (SRPs) in macrophages and explore the potential mechanisms. The results showed that four SRPs fractions (SRPs40, SRPs60, SRPs80 and SRPs100) had similar absorption peaks and monosaccharide compositions, but the intensities of absorption peaks and monosaccharide contents were distinguished. All SRPs fractions significantly enhanced the pinocytic activity, promoted the production of NO and TNF-α, increased the mRNA expressions of inflammatory factors (IL-1β, IL-6, TNF-α and PTGS2) and TLR2, and elevated the phosphorylation levels of p38, ERK, JNK, p65 and IκB. Moreover, the production of NO and TNF-α stimulated by SRPs was dramatically suppressed by anti-TLR2 antibody. These results indicated that SRPs activated macrophages through MAPK and NF-κB signaling pathways via recognition of TLR2.
10.1002/cbdv.202301180
[Chemical constituents of Scrophulariae Radix and their antitumor activities in vitro].
Zhou Meng-Nan,Liu Peng,Jing Shu-Jin,Sun Meng,Li Xiang,Zhang Wei,Liu Bin
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
The present study investigated the chemical constituents of Scrophulariae Radix and their antitumor activities in vitro. The compounds in the ethyl acetate extract were separated and purified by conventional column chromatographies(such as silica gel, Sephadex LH-20, and ODS column) and semi-preparative high-performance liquid chromatography(HPLC), and their structures were identified by various spectral techniques such as nuclear magnetic resonance(NMR) and mass spectrometry(MS). Twenty-three compounds were isolated and identified as benzyl-β-D-(3',6'-di-O-acetyl) glucoside(1), 5-O-p-methoxybenzoyl kojic acid(2), 5-O-methoxybenzoyl kojic acid(3), 7-O-methylbenzoyl kojic acid(4), 5-O-benzoyl kojic acid(5), methyl ferulate ethyl ether(6), trans-ferulic acid(7), trans-isoferulic acid(8), trans-caffeic acid(9), trans-caffeic acid methyl ester(10), caffeic acid ethyl ester(11), trans-cinnamic acid(12), trans-p-methoxycinnamic acid(13), trans-p-hydroxycinnamic acid(14), trans-p-hydroxycinnamic acid methyl ester(15), 2-(3,4-dihydroxyphenethyl) alcohol(16),(p-hydroxyphenyl) propanoic acid(17), coniferaldehyde(18), sinapaldehyde(19), benzyl β-primeveroside(20), 5-(hydroxymethyl) furfural(21), furan-2-carboxylic acid(22), and decanedioic acid(23). Among them, compound 1 is a new benzyl glucoside, compounds 2-4 are new pyranone compounds, compound 5 is a new natural product of pyranone. The NMR data of compounds 5 and 6 are reported for the first time. Compounds 6 and 20 were isolated from the Scrophularia plant for the first time. Compounds 8, 11, 14, 16, 18, 19, 22, and 23 were isolated from this plant for the first time. The in vitro cytotoxic activities of these compounds against three tumor cell lines(HepG2, A549, and 4 T1) were evaluated. The results showed that compounds 10 and 15 showed cytotoxic activities against HepG2 cells with IC_(50) values of(19.46±0.48) μmol·L~(-1) and(46.10±1.21) μmol·L~(-1).
10.19540/j.cnki.cjcmm.20211126.201
Scrophulariae Radix-Atractylodes sinensis pair and metformin inhibit inflammation by modulating gut microbiota of high-fat diet/streptozotocin-induced diabetes in rats.
Frontiers in microbiology
Introduction:Type 2 mellitus (T2DM), a chronic metabolic disorder, causes severe impairment of patients' quality of life and has attracted global attention. Many studies have suggested the importance of the gut microbiota in the occurrence of T2DM. The Scrophulariae Radix and Atractylodes sinensis (XC) pair, recommended in traditional Chinese medicine (TCM), have been used for treating diabetes for many years. However, research on the role of the XC pair in modulating gut microbial communities is lacking, but it is important to elucidate the underlying mechanism. Methods:In this study, we detected bacterial communities by high-throughput 16S rRNA gene sequencing. Results:The results showed that XC + MET reduced postprandial hyperglycemia and inflammatory response in diabetic rats more effectively than metformin (MET) alone. The XC + MET treatment reshaped the intestinal microbial composition of diabetic rats. XC can help MET regulate carbohydrate, amino acid, and lipid metabolism, particularly the insulin signaling pathway. Discussion:This research would help elucidate potential mechanisms and the treatment methods.
10.3389/fmicb.2022.900021
Radix: An Overview of Its Biological Activities and Nutraceutical and Pharmaceutical Applications.
Lee Hae-Jin,Kim Hae-Lim,Lee Dong-Ryung,Choi Bong-Keun,Yang Seung-Hwan
Molecules (Basel, Switzerland)
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 (SB) and (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.
10.3390/molecules26175250