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
Responses to lead stress in : insights into antioxidative defence mechanisms and changes in flavonoids profile.
Functional plant biology : FPB
Lead (Pb) induces oxidative stress in plants, which results in different responses, including the production of antioxidants and changes in the profile of secondary metabolites. In this study, the responses of Scrophularia striata exposed to 250mgL-1 Pb (NO3 )2 in a hydroponic environment were determined. Growth parameters, oxidative and antioxidative responses, redox status, and the concentration of Pb were analysed in roots and shoots. Malondialdehyde and hydrogen peroxide (H2 O2 ) levels in the roots were significantly increased and reached their highest value at 72h after Pb treatment. Superoxide dismutase, catalase, and peroxidase, as an enzymatic antioxidant system, were responsible for reactive oxygen species scavenging, where their activities were increased in the shoot and root of Pb-treated plants. Enzymatic antioxidant activities were probably not enough to remove a significant H2 O2 content in response to Pb treatment. Therefore, other defence responses were activated. The results stated that the flavonoid components of S. striata progressed towards the increase of isoflavone, flavanol, and stilbenoid contents under Pb treatment. In general, S. striata stimulates the enzymatic defence system and activates the non-enzymatic system by modulating the profile of flavonoids toward the production of flavonoids with high antioxidant activity, such as quercetin and myricetin in response to Pb stress.
10.1071/FP23236
Fast repairing of oxidized OH radical adducts of dAMP and dGMP by phenylpropanoid glycosides from Scrophularia ningpoensis Hemsl.
Li Y M,Han Z H,Jiang S H,Jiang Y,Yao S D,Zhu D Y
Acta pharmacologica Sinica
AIM:To investigate the antioxidative activity of the constituents of the roots of Scrophularia ningpoensis (Chinese name: Xuanshen). METHODS:The main compounds from the roots of Scrophularia ningpoensis were isolated and identified by chromatography and FABMS, NMR etc. Using the techniques of pulse radiolysis, the electron transfers from iridoid glycosides (IG) or phenylpropanoid glycosides (PG) to oxidized OH radical adducts of 2'-deoxyadenosine-5'-monophosphate acid (dAMP) or 2'-deoxyguanosine-5'-monophosphate acid (dGMP) were observed. RESULTS:Two IG: harpagoside and harpagide, two PG: angoroside C and acteoside were obtained as the main hydrophilic constituents of the plant. At 0.1 mmol/L concentration, angoroside C and acteoside were able to repair the oxidized OH adducts dAMP and dGMP significantly. However, harpagoside and harpagide had no such effect. The electron transfer rate constants of angoroside C with dAMP and dGMP were 4.2 x 10(8) and 10.3 x 10(8) L.mol-1.s-1; the electron transfer rate constants of acteoside with dAMP and dGMP were 5.3 x 10(8) and 20.2 x 10(8) L.mol-1.s-1. CONCLUSION:PG from Scrophularia ningpoensis have a potent antioxidative activity for reducing of the oxidized OH adducts of dAMP and dGMP.
Hypouricemic effects of phenylpropanoid glycosides acteoside of Scrophularia ningpoensis on serum uric acid levels in potassium oxonate-pretreated Mice.
Huang Cai Guo,Shang Yan Jun,Zhang Jun,Zhang Jian Rong,Li Wen Jie,Jiao Bin Hua
The American journal of Chinese medicine
Phenylpropanoid glycoside acteoside was extracted from the traditional Chinese medicine Scrophularia ningpoenis Hemsl. In the present study, we investigated the effects of acteoside administration on serum uric acid levels in mice rendered hyperuricemic with the uricase inhibitor potassium oxonate. When administered orally for 3 days at doses of 50, 100 and 150 mg/kg, acteoside reduced serum uric acid levels by 15.2, 23.8 and 33.1%, respectively, relative to vehicle-treated hyperuricemic mice. Importantly, in non-hyperuricemic mice, the serum uric acid levels were not affected by acetoside treatment. Acteoside also inhibited mouse liver xanthine dehydrogenase XDH and xanthine oxidase XO activity at all three doses. These results suggest that the hypouricemic action of acteoside may be attributable to its inhibition of XDH/XO activity.
10.1142/S0192415X08005667
Hepatoprotective phenylpropanoids from Scrophularia buergeriana roots against CCl(4)-induced toxicity: action mechanism and structure-activity relationship.
Lee Eun Ju,Kim So Ra,Kim Jinwoong,Kim Young Choong
Planta medica
Phenylpropanoids isolated from the roots of Scrophularia buergeriana MIQ. (Scrophulariaceae) protected primary cultures of rat hepatocytes from toxicity induced by carbon tetrachloride (CCl(4) ). In this report, we show that two of these phenylpropanoids, 4-O-E- p-methoxycinnamoyl-alpha-L-rhamnopyranoside ester ( 1) and p-methoxycinnamic acid ( 3) have significant hepatoprotective activity; another phenylpropanoid used for comparison, isoferulic acid ( 11), was equally active. To determine the mechanism(s) by which these three phenylpropanoids exerted their hepatoprotective activity, we measured activities of enzymes involved in the glutathione (GSH) redox system and assayed the level of hepatic mitochondrial GSH. The GSH levels in primary cultures of rat hepatocytes were significantly reduced with CCl(4) insult, but were significantly preserved by the treatment with these three phenylpropanoids. The activities of glutathione disulfide reductase and glutathione-S-transferase which normally decrease in CCl(4) -injured rat hepatocytes were significantly preserved by the treatment with these three phenylpropanoids. In addition, in CCl(4) -injured rat hepatocytes, the increased formation of malondialdehyde, a byproduct of lipid peroxidation, was reduced by the treatment with these phenylpropanoids. We determined the essential structural moiety within these three phenylpropanoids needed to exert hepatoprotective activity. The alpha,beta-unsaturated ester moiety seemed to be essential for exerting hepatoprotective activity.
10.1055/s-2002-32081
In Vitro Propagation, Phytochemical Analysis, and Evaluation of Free Radical Scavenging Property of Scrophularia kakudensis Franch Tissue Extracts.
Manivannan Abinaya,Soundararajan Prabhakaran,Park Yoo Gyeong,Jeong Byoung Ryong
BioMed research international
The current study deals with in vitro propagation, antioxidant property estimation, and assessment of acacetin content in Scrophularia kakudensis Franch. Adventitious shoot induction was achieved from the nodal explant with the highest number of adventitious shoots per explant (17.4) on Murashige and Skoog's (MS) medium fortified with 2.0 mg·L(-1) 6-benzyladenine (BA) and 0.5 mg L(-1) indole-3-acetic acid (IAA). Maximum number of roots per plant (16.5) was noted in half strength MS medium supplemented with 0.5 mg·L(-1) IAA. The regenerated plants displayed successful survival ratio (95%) in the greenhouse. The highest content of acacetin, a pharmaceutically important flavonoid, was observed in the shoot extracts (in vitro: 32.83 µg·g(-1) FW; in vivo: 30.05 µg·g(-1) FW) followed by root extracts. Total phenol and flavonoid contents along with free radical scavenging assays revealed the occurrence of larger amount of antioxidants in shoot extract in comparison with callus and root extracts of S. kakudensis. Thus, the outcome of the present study can be highly beneficial for the germplasm conservation and commercial cultivation of S. kakudensis for therapeutic purposes.
10.1155/2015/480564
Iridoids from Scrophularia buergeriana attenuate glutamate-induced neurotoxicity in rat cortical cultures.
Kim So Ra,Koo Kyung Ah,Sung Sang Hyun,Ma Choong Je,Yoon Jeong Seon,Kim Young Choong
Journal of neuroscience research
In previous work, we isolated 7 neuroprotective iridoid glycosides from the 90% MeOH fraction of Scrophularia buergeriana (Scrophulariaceae). We therefore investigated the mode of action of 8-O-E-p-methoxycinnamoyl-harpagide (8-MCA-Harp), the most potent neuroprotective iridoid, and its aglycone, harpagide (Harp) using primary cultures of rat cortical cells in vitro. 8-MCA-Harp only revealed its neuroprotective activity in a pretreatment paradigm; this iridoid had more selectivity in protecting neurons against N-methyl-D-aspartate (NMDA)-induced neurotoxicity as opposed to that induced by kainic acid (KA). On the other hand, Harp exerted significant neuroprotective activity when it was administered either before or after glutamate insult and protected cultured neuronal cells from neurotoxicity induced by NMDA or KA. Furthermore, Harp significantly prevented the decrease of glutathione, an antioxidative compound in the brain, in our cultures. Finally, 8-MCA-Harp and Harp could successfully reduce the overproduction of nitric oxide and the level of cellular peroxide in cultured neurons. Collectively, these results suggested that Harp and 8-MCA-Harp protected primary cultured neurons against glutamate-induced oxidative stress primarily by acting on the antioxidative defense system and on glutamatergic receptors, respectively.
10.1002/jnr.10828
Neuroprotective phenylpropanoid esters of rhamnose isolated from roots of Scrophularia buergeriana.
Kim S R,Kim Y C
Phytochemistry
Four phenylpropanoid esters of rhamnose, buergerisides A1, B1, B2 and C1 were isolated from roots of Scrophularia huergeriana MIQ. (Scrophulariaceae), and were characterized as 2-O-acetyl-3,4-di-O-(E)-p-methoxycinnamoyl-alpha-L-rhamnopyranosid e, 2-O-acetyl-3-O-(E)-p-methoxycinnamoyl-alpha-L-rhamnopyranoside, 2-O-acetvl-3-O-(Z)-p-methoxycinnamoyl-alpha-L-rhamnopyranosi de and 4-O-(E)-p-methoxycinnamoyl-alpha-L-rhamnopyranoside, respectively. In addition, six known phenylpropanoids were authenticated as: (E)-cinnamic acid, (E)-p-methoxycinnamic acid, (E)-p-methoxycinnamic acid methyl ester, (E)-p-coumaric acid, (E)-caffeic acid, (E)-ferulic acid and a phenylalcohol, 2-(3-hydroxy-4-methoxyphenyl)ethanol. These ten phenylpropanoids all attenuated glutamate-induced neurotoxicity when added to primary cultures of rat cortical cells in a dose-dependent manner. These results demonstrate that phenylpropanoids isolated from S. buergeriana may exert significant protective effects against glutamate-induced neurodegeneration in primary cultures of cortical neurons.
Anti-amnestic activity of E-p-methoxycinnamic acid from Scrophularia buergeriana.
Kim So Ra,Kang So Young,Lee Ki Yong,Kim Seung Hyun,Markelonis George J,Oh Tae H,Kim Young Choong
Brain research. Cognitive brain research
We previously reported that phenylpropanoids isolated from the roots of Scrophularia buergeriana Miquel (Scrophulariaceae) protected cultured cortical neurons against glutamate-induced neurotoxicity [Kim and Kim, Phytochemistry, 54 (2000) 503-509; Kim et al., Br. J. Pharmacol. 135 (2002) 1281-1291]. In the present study, we examined the anti-amnestic activities of phenylpropanoids in mice with amnesia induced in vivo by scopolamine. Among the phenylpropanoids tested through passive avoidance tasks, buergeriside A1, buergeriside C1, E-p-methoxycinnamic acid (E-p-MCA) and E-isoferulic acid significantly improved the deficit of memory induced by scopolamine. This suggested that the alpha,beta-unsaturated carboxyl moiety and the para-methoxy group in phenylpropanoids (E-p-MCA) might be a crucial component in their cognition-enhancing activity. Indeed, E-p-MCA (0.01-2 mg/kg body weight, i.p.), given in pre- or post-treatment paradigms, significantly ameliorated scopolamine-induced amnesia as determined by passive avoidance tasks and prevented or aided in the recovery of memory to a level that was about 60% of control. In addition, E-p-MCA (0.1-1.0 mg/kg body weight, i.p.) significantly improved impairments of spatial learning and memory induced by scopolamine; the compound reduced deficits in both long- and short-term memories as measured by the Morris water maze test. We suggest, therefore, that E-p-MCA may ultimately hold significant therapeutic value in alleviating certain memory impairments observed in dementia.
10.1016/s0926-6410(03)00161-7
[Antifungal effects of three medicinal crops on Phytophthora nicotianae].
He Da-Min,Chen Yang,Yang Shui-Ping,Zhang Xue,Zhao Jian,Mo Jing-Jing,Zhang Dong-Yan,Zhao Xin-Mei,Chen Da-Xia,Ding Wei
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
Tobacco black shank is one of the most harmful soil-borne diseases infected by Phytophthora parasitica. In order to probe the control method to this disease, in this study, the mycelial growth rate method was employed to investigate the antifungal effects of extracts from stem-leaf and root, root exudates, and their combination of Scrophularia ningpoensis, Chuanmingshen violaceum and Pinellia ternata The results showed that: ①Stem-leaf and root extracts of S. ningpoensis, C. violaceum and P. ternata exhibited different antifungal activities, and the inhibition increased with the increase of extract concentration. The antifungal effect of S. ningpoensis extracts at 0.5 g•mL⁻¹ was the strongest than other medicinal plants, the inhibition rate of steam-leaf and root extracts reached 74.88%, 69.27%, respectively. The inhibitory effect of C. violaceum and P. ternata was relatively lower, however, there is a significant gain effect after combination of steam-leaf and root extracts of C. violaceum. ②The root exudates of S. ningpoensis, C. violaceum and P. ternata showed fungistasis to Phytophthora nicotianae, and fungistasis was enhanced with the increase of root exudate concentration. The antifungal effect in the order of C. violaceum > S. ningpoensis > P. ternata. ③The antifungal activity of combination of extract and root exudate from S. ningpoensis was similar with the effect of C. violaceum, they were both stronger than P. ternata, and the antifungal activity for three combination were located between the antifungal activity of their extracts and root exudates. S. ningpoensis and C. violaceum can be potentially applied to prevent and control the tobacco black shank.
10.19540/j.cnki.cjcmm.20170814.010
[Effects of extracts of Radix Scrophulariae on blood pressure in spontaneously hypertensive rats and the underlying mechanisms].
Chen Chan,Chen Chang-xun,Wu Xi-min,Wang Rui,Li Yi-ming
Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine
OBJECTIVE:To explore the effects of extracts of Radix Scrophulariae (ERS) on blood pressure, vasoconstrictors and morphology of artery in spontaneously hypertensive rats (SHRs). METHODS:Fifty SHRs were randomly divided into SHR, SHR plus 40 mg/kg of captopril, SHR plus 70 mg/kg of ERS, SHR plus 140 mg/kg of ERS and SHR plus 280 mg/kg of ERS groups. Wistar-Kyoto (WKY) rats were randomly divided into two groups, namely, WKY and WKY plus 140 mg/kg of ERS groups. The rats were orally administered with the corresponding drugs or drinking water once a day for 20 weeks. The blood pressure was determined every three weeks. At the 21st week, the concentrations of noradrenaline (NA), angiotensin II (Ang II), thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F(1α) in serum and endothelin-1 (ET-1) were detected by enzyme-linked immunosorbent assay. The morphological changes in abdominal aorta were observed under an optical microscope with hematoxylin and eosin staining. The ratio of intima-media thickness/lumen radius of abdominal aorta was calculated. RESULTS:ERS significantly lowered the blood pressure of SHRs from the 3rd to the 21st week; ERS also reduced the levels of NA, Ang II, ET-1 and TXB(2), decreased the intima-media thickness of abdominal aortal wall and improved the morphological changes in abdominal aorta in SHRs. In addition, ERS did not significantly change blood pressure and vasoactive substances in WKY rats. CONCLUSION:ERS possesses beneficial effects in inhibiting hypertension and attenuating arteriosclerosis. The underlying mechanism may be associated with restraining the release of vasoconstrictors, such as NA, Ang II, ET-1 and TXB(2).
Anti-inflammatory secondary metabolites from .
Renda Gülin,Kadıoğlu Mine,Kılıç Merve,Korkmaz Büşra,Kırmızıbekmez Hasan
Human & experimental toxicology
The species belonging to genus grow mainly in Irano-Turanian and Mediterranean regions and have been used as folk remedy for inflammatory-related diseases since ancient times. The present study was aimed to evaluate the anti-inflammatory activity of the extracts of as well as the isolated compounds. The aerial parts and the roots of the plant were separately extracted with methanol. Anti-inflammatory activities of both extracts were evaluated with formalin test in mice. As the methanolic extract of the aerial parts significantly ( < .05) inhibited inflammation, it was then submitted to successive solvent extractions with -hexane, dichloromethane, ethyl acetate and -butanol to yield subextracts. Anti-inflammatory activities of the subextracts were evaluated within the same test system. Among the subextracts tested, the -butanol subextract produced a significant ( < .05) anti-inflammatory activity at all doses (5, 10, and 30 mg/kg, ip.). Sequential chromatographic separation of the -butanol subextract yielded 8-O-acetyl-4--()--coumaroylharpagide, 8--acetyl-4--()--coumaroylharpagide, β-sitosterol 3--β-glucopyranoside, apigenin 7--β-glucopyranoside, apigenin 7--rutinoside, luteolin 7--β-glucopyranoside and luteolin 7--rutinoside. The anti-inflammatory activities of the isolates were evaluated at 5 mg/kg dose. Luteolin 7--β-glucopyranoside and apigenin 7--rutinoside caused a significant ( < .05) inhibition of oedema formation.
10.1177/09603271211058889
[Protective effect of iridoid glycosides of radix scrophulariae on endoplasmic reticulum stress induced by oxygen-glucose deprivation and reperfusion model].
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences
OBJECTIVE:To investigate the regulatory effect of iridoid glycoside of radix scrophulariae (IGRS) on endoplasmic reticulum stress induced by oxygen-glucose deprivation and reperfusion model. METHODS:Rat pheochromocytoma PC12 cells were pretreated with IGRS (50, 100, 200 μg/mL) for 24h, and the model of oxygen-glucose deprivation/reoxygenation (OGD/R) was applied. The cell viability was determined by MTT and lactate dehydrogenase (LDH) assay. The apoptotic rate was detected by flow cytometry. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), C/EBP homologous protein (CHOP), caspase-12 protein, and glucose-regulated protein-78(GRP78)were detected by Western blotting. The mRNA expression levels of sarco/endoplasmic reticulum Ca-ATPase2 (SERCA2), 1, 4, 5-triphosphate inositol receptor 1 (IPR1), and ryanodine receptor 2 (RyR2)were detected by real-time RT-PCR. Free Ca concentration [Ca] was determined by using laser scanning confocal microscopy. RESULTS:The damage caused by OGD/R to PC12 cells was significantly reduced by IGRS, with significant effect on increasing survival rate and reducing LDH release (all <0.01). The expression of GRP78, CHOP, Bax, and caspase-12 were down-regulated (all <0.01), and the expression of Bcl-2 and Bcl-2/Bax ratio was up-regulated (all <0.01); IGRS increased the expression of SERCA2 mRNA in PC12 cells after OGD/R injury (<0.01), decreased [Ca] and down-regulated the expression of RyR2 mRNA and IPR1 mRNA. CONCLUSIONS:IGRS has neuroprotective effect, which may alleviate cerebral ischemia-reperfusion injury by regulating SERCA2, maintaining calcium balance, and inhibiting endoplasmic reticulum stress-mediated apoptosis.
10.3785/j.issn.1008-9292.2020.12.05
Iridoid glycosides from Radix Scrophulariae attenuates focal cerebral ischemia‑reperfusion injury via inhibiting endoplasmic reticulum stress‑mediated neuronal apoptosis in rats.
Chen Yanyue,Zhang Lei,Gong Xueyuan,Gong Hengpei,Cheng Rubin,Qiu Fengmei,Zhong Xiaoming,Huang Zhen
Molecular medicine reports
Iridoid glycosides of Radix Scrophulariae (IGRS) are a group of the major bioactive components from Radix Scrophulariae with extensive pharmacological activities. The present study investigated the effects of IGRS on cerebral ischemia‑reperfusion injury (CIRI) and explored its potential mechanisms of action. A CIRI model in rats was established by occlusion of the right middle cerebral artery for 90 min, followed by 24 h of reperfusion. Prior to surgery, 30, 60 or 120 mg/kg IGRS was administered to the rats once a day for 7 days. Then, the neurological scores, brain edema and volume of the cerebral infarction were measured. The apoptosis index was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling. The effects of IGRS on the histopathology of the cortex in brain tissues and the endoplasmic reticulum ultrastructure in the hippocampus were analyzed. Finally, the expression of endoplasmic reticulum stress (ERS)‑regulating mediators, endoplasmic reticulum chaperone BiP (GRP78), DNA damage‑inducible transcript 3 protein (CHOP) and caspase‑12, were detected by reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The volume of cerebral infarction and brain water content in the IGRS‑treated groups treated at doses of 60 and 120 mg/kg were decreased significantly compared with the Model group. The neurological scores were also significantly decreased in the IGRS‑treated groups. IGRS treatment effectively decreased neuronal apoptosis resulting from CIRI‑induced neuron injury. In addition, the histopathological damage and the endoplasmic reticulum ultrastructure injury were partially improved in CIRI rats following IGRS treatment. RT‑qPCR and western blot analysis data indicated that IGRS significantly decreased the expression levels of GRP78, CHOP and caspase‑12 at both mRNA and protein levels. The results of the present study demonstrated that IGRS exerted a protective effect against CIRI in brain tissue via the inhibition of apoptosis and ERS.
10.3892/mmr.2019.10833
Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity.
Sheu Shiow-Yunn,Hong Yi-Wen,Sun Jui-Sheng,Liu Man-Hai,Chen Ching-Yun,Ke Cherng-Jyh
BMC complementary and alternative medicine
BACKGROUND:Hypoxia could lead to microglia activation and inflammatory mediators' overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced microglia activation. METHODS:In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O2 for 3 h). Harpagoside had been shown to be no cytotoxicity on microglia cells by MTT assay. The scavenger effect of harpagoside on hypoxia-enhanced microglial cells proliferation, associated inflammatory genes expression (COX-II, IL-1β and IL-6 genes) and NO synthesis were also examined. RESULTS:Hypoxia enhances active proliferation of microglial cells, while harpagoside can scavenge this effect. We find that harpagoside could scavenge hypoxia-enhanced inflammatory genes expression (COX-2, IL-1β and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1α (HIF-1α) significantly increase, while the cytosol IκB-α content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease IκB-α protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-κB activation and reduce the HIF-1α generation. CONCLUSION:These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-κB signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-α pathway.
10.1186/s12906-015-0842-x
The protective effect of harpagoside on angiotensin II (Ang II)-induced blood-brain barrier leakage in vitro.
Lu Yun Wei,Hao Ren Juan,Wei Yu Yan,Yu Gu Ran
Phytotherapy research : PTR
Hypertension and its associated dysfunction of the blood-brain barrier (BBB) contribute to cerebral small vessel disease (cSVD). Angiotensin II (Ang II), a vasoactive peptide of the renin-angiotensin system (RAS), is not only a pivotal molecular signal in hypertension but also causes BBB leakage, cSVD, and cognitive impair. Harpagoside, the major bioactive constituent of Scrophulariae Radix, has been commonly used for the treatment of multiple diseases including hypertension in China. The effect of harpagoside on Ang II-induced BBB damage is unclear. We employed an immortalized endothelial cell line (bEnd.3) to mimic a BBB monolayer model in vitro and investigated the effect of harpagoside on BBB and found that harpagoside alleviated Ang II-induced BBB destruction, inhibited Ang II-associated cytotoxicity in a concentration-dependent manner and attenuated Ang II-induced reactive oxygen species (ROS) impair by downregulation of Nox2, Nox4, and COX-2. Harpagoside prevented Ang II-induced apoptosis via keeping Bax/Bcl-2 balance, decreasing cytochrome c release, and inactivation of caspase-8, caspase-9, and caspase-3 (the mitochondria-dependent and death receptor-mediated apoptosis pathways). Moreover, harpagoside can alleviate Ang II-induced BBB damage through upregulation of tight junction proteins and decrease of caveolae-mediated endocytosis. Thus, harpagoside might be a potential drug to treat Ang II-induced cSVD.
10.1002/ptr.7269
Evaluation of in vivo analgesic activity of Scrophularia kotscyhana and isolation of bioactive compounds through activity-guided fractionation.
Renda Gülin,Korkmaz Büşra,Kılıç Merve,Duman Mine Kadıoğlu,Kırmızıbekmez Hasan
Natural product research
The present study was undertaken to evaluate the in vivo analgesic activities of the extracts prepared from the aerial parts and roots of Scrophularia kotscyhana and to isolate the bioactive metabolites from the most active extract. Analgesic activities of all extracts and subextracts at the doses of 5, 10 and 30 mg/kg (i.p.) were examined using hot plate test in mice. Among the tested extracts, MeOH extract prepared from the aerial parts and the n-butanol subextract prepared thereof displayed the best analgesic activity at all doses. Phytochemical studies on n-butanol subextract led to the isolation of two new iridoid glycosides as an inseparable mixture, 8-O-acetyl-4'-O-(E)-(p-coumaroyl)-harpagide (1) and 8-O-acetyl-4'-O-(Z)-(p-coumaroyl)-harpagide (2) along with five known secondary metabolites, β-sitosterol 3-O-β-glucopyranoside (3), apigenin 7-O-β-glucopyranoside (4), apigenin 7-O-rutinoside (5), luteolin 7-O-β-glucopyranoside (6) and luteolin 7-O-rutinoside (7). The iridoid mixture (1 and 2), 3 and 4 elicited significant inhibition of pain at 5 mg/kg dose.
10.1080/14786419.2017.1356829
Four new neuroprotective iridoid glycosides from Scrophularia buergeriana roots.
Kim So Ra,Lee Ki Yong,Koo Kyung Ah,Sung Sang Hyun,Lee Na-Gyong,Kim Jinwoong,Kim Young Choong
Journal of natural products
Four new iridoid glycosides were isolated from a 90% MeOH extract of Scrophularia buergeriana roots and characterized as 8-O-E-p-methoxycinnamoylharpagide (1), 8-O-Z-p-methoxycinnamoylharpagide (2), 6'-O-E-p-methoxycinnamoylharpagide (3), and 6'-O-Z-p-methoxycinnamoylharpagide (4), respectively. In addition, three known iridoids were identified as E-harpagoside (5), Z-harpagoside (6), and harpagide (7). Compounds 1-7 significantly attenuated glutamate-induced neurotoxicity when added to primary cultures of rat cortical cells at concentrations ranging from 100 nM to 10 microM. The results obtained indicate that the iridoid glycosides isolated from S. buergeriana have significant protective effects against glutamate-induced neurodegeneration in primary cultures of rat cortical neurons.
Screening and identification of neuroprotective compounds from Scrophularia buergeriana using cell extraction coupled with LC-MS.
Shin Hyeji,Medriano Carl Angelo,Park Byoungduck,Park Youngja H,Lee Ki Yong
Journal of pharmaceutical and biomedical analysis
In the cell extraction_LC-MS method, when cells are incubated with natural product extracts, bioactive compounds selectively bind to extracellular or intracellular targets. The extracts and major compounds (phenylpropanoids and iridoid glycosides) of Scrophularia buergeriana Miquel have been reported to show neuroprotective effects both in vitro and in vivo. In this study, the cell extraction_LC-MS strategy was applied to screen and identify potential neuroprotective compounds from S. buergeriana by using immortalized mouse hippocampal HT22 cells. The results showed that two known compounds from S. buergeriana selectively bound HT22 cells. Additionally, metabolomics analyses were performed using the Mass Profiler Professional and Limma differential expression package of R to identify significant differences between HT22 cells treated with S. buergeriana and untreated cells. The cell extraction approach more accurately reflects in vivo conditions compared with other methods and can be readily used for screening bioactive components from natural products.
10.1016/j.jpba.2017.10.018
[Effects of Scrophulariae Radix and Split Component on Isoproterenol-Induced Ventricular Remodeling in Rat].
Lu Fang,Yu Hui,Li Zi-hui,Zhang Ning,Dong Wan-ru,Liu Shu-min
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials
Objective:To explore the effects and mechanism of Scrophulariae Radix and split component on experimental ventricular remodeling. Methods:The rats were injected subcutaneously by 10,5 mg / kg ISO for 2 d and then 3 mg / kg ISO as maintenance dose for 7 d to build the the ventricular remodeling. After 21 days’ treatment,the left ventricular mass index( LVMI) and heart mass index( HMI) were measured. The content of atrial natriuretic peptide( ANP),endothelin-1( ET-1) and angiotensinⅡ( Ang II) were determined by enzyme linked immunosorbent assay( ELISA),and the pathological changes of myocardial tissue were also observed. Results:LVMI,HMI were improved by total composition components and small polar iridoid glycosides components,and the content of ANP,ET-1 and AngⅡwas decreased remarkably; The polysaccharide components could only decline the content of Ang Ⅱ and ET-1. Conclusion:The pharmacological effects of Scrophulariae Radix inhibit ventricular remodeling may be related to the small polar iridoid glycosides components and the polysaccharide components. And the mechanism may be related to regulating the over expression neurohumor factors and inhibiting the release of ANP and ET-1,Ang Ⅱ.