A metabolism-based study of the mechanism of action of Scrophularia ningpoensis Hemsl. on nephrogenic edema.

Nephrogenic edema (NE) is a type of edema with hypoproteinemia and water and sodium retention as a result of renal injury. Traditional Chinese medicine has proved that Scrophularia ningpoensis Hemsl. has an effect on NE, but its mechanism is not clear. In this study, the main components and blood components of S. ningpoensis were identified using ultra-high-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS). Pathological section and blood biochemical analysis were used to estimate the therapeutic effect of S. ningpoensis on NE. Network pharmacology was used to predict the potential pathways of S. ningpoensis. The metabolomics method was used to study the changes in small-molecule metabolites in the body. The results showed that S. ningpoensis could relieve NE by regulating relative to renal function and body edema, and its mechanism may be related to the regulation of energy metabolism, recovery of renal injury, and reduction in inflammation. The active component harpagoside may be one of the important compounds of S. ningpoensis in the treatment of NE. We confirmed that S. ningpoensis has a therapeutic effect on NE, which provides a solid scientific research basis for the clinical application of S. ningpoensis.

[Chemical constituents, pharmacological activities, processing and clinical application of traditional Chinese medicine Scrophulariae Radix: a review].

Traditional Chinese medicine Scrophulariae Radix, which is also called Yuan Shen, black Shen, is the dried root of Scrophularia ningpoensis of the Scrophulariaceae family. Research has indicated that the chemical constituents of Scrophulariae Radix mainly include terpenoids, phenylpropanoids, organic acids, volatile oils, steroids, sugars, flavonoids, alkaloids and phenols, among which iridoids and phenylpropanoids were the main active constituents. It has been reported that extracts of Scrophulariae Radix or its active substances have anti-inflammatory, antioxidant, hepatoprotective, anti-tumor, anti-fatigue, uric acid-lowering, anti-depression, myocardial cell-protective and other pharmacological activities, and can regulate cardiovascular system, central nervous system and immune system. This paper reviewed the present research achievements of Scrophulariae Radix in chemical constituents, pharmacological activities, processing methods, toxicity and other aspects, and the clinical application of Scrophulariae Radix in ancient and modern times was illustrated. This paper aimed to provide reference for further research of Scrophulariae Radix and facilitated its clinical application.

Comprehensive quality evaluation of processed Scrophulariae Radix from different regions of China using HPLC coupled with chemometrics methods.

INTRODUCTION: Scrophulariae Radix (SR) has been extensively used in traditional Chinese medicine (TCM) for thousands of years. However, the processing methods and production areas of Scrophularia ningpoensis have undergone notable historic changes. Thus, their effects on the bioactive constituents of SR still need to be studied further. OBJECTIVES: This study aimed to establish an objective and comprehensive method to identify the correlation of bioactive constituents of SR with variety, place of origin and processing method for evaluating their qualities. METHODOLOGY: An accurate and rapid high-performance liquid chromatography-diode array detector (HPLC-DAD) method for the simultaneous determination of 11 marker components (aucubin, harpagide, 6-O-methyl-catalpol, harpagoside, verbascoside, isoverbascoside, angoroside C, cinnamic acid, l-tyrosine, l-phenylalanine, and l-tryptophan) was established to evaluate the quality of SR for the first time. In addition, the effects of different production areas and processed methods on the target compounds were studied by analysing 66 batches of SR samples with chemometrics methods, including similarity evaluation of chromatographic fingerprints of TCM, principal component analysis (PCA), and partial least squares-discriminant analysis (PLS-DA). RESULTS: Compared with "sweating", short-term "steaming" and "slice-drying" could largely preserve the bioactive constituents of SR. When using the model established through PLS-DA, five components were identified as the most significant variables for discrimination. Furthermore, the score plots of PCA and the similarity evaluation revealed that variety had a more notable influence on the quality of SR than the place of origin. CONCLUSION: An objective approach of HPLC fingerprint coupled with chemometrics analysis and quantitative assessment could be applied to discriminate different processed SR and evaluate the qualities of SR rapidly.

The in vitro and in vivo antibacterial activities of uniflorous honey from a medicinal plant, Scrophularia ningpoensis Hemsl., and characterization of its chemical profile with UPLC-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Compendium of Materia Medica, honey has been used as a traditional medicine in treatment against mucositis, tinea, hemorrhoids and psoriasis. In complementary medicine, due to its significant antimicrobial activity, honey has been widely used as a remedy for skin wounds and gastrohelcosis for thousands of years. AIM OF THE STUDY: This study is aimed at exploring the antimicrobial activity and mechanisms of honey sourced from medicinal plants, and revealing the composition-activity relationship, to facilitate their complementary and alternative application in the therapy of bacterial infectious diseases. MATERIALS AND METHODS: Eight kinds of medicinal plant-derived uniflorous honey, native to China, were gathered. Their antimicrobial activities were evaluated in vitro, and then in vivo with the systemically infected mouse model and the acute skin infection model. SYTOX uptake assay, scanning electron microscopy, DNA binding assay, and quantitative real-time PCR, were carried out to elucidate the antibacterial mechanisms. This was followed by an investigation of the componential profile with the UPLC-MS/MS technique. RESULTS: It was found that Scrophularia ningpoensis Hemsl. (figwort) honey (S. ningpoensis honey) exhibited broad-spectrum and the strongest antibacterial potency (MICs of 7.81-125.00%, w/v), comparable to manuka honey. In the in vivo assays, S. ningpoensis honey significantly decreased the bacterial load of the muscles under the acute MRSA-infected skin wounds; the sera level of TNF-α in the S. aureus and P. aeruginosa-infected mice decreased by 45.38% and 51.75%, respectively, after the treatment of S. ningpoensis honey (125 mg/10 g). It was capable of killing bacteria through disrupting the cell membranes and the genomic DNA, as well as down-regulating the expression of genes associated with virulence, biofilm formation and invasion, including icaA, icaD, eno, sarA, agrA, sigB, fib and ebps in S. aureus, and lasI, lasR, rhlI, rhlR and algC in P. aeruginosa. Apart from H2O2, some other nonperoxide compounds such as adenosine, chavicol, 4-methylcatechol, trehalose, palmitoleic acid and salidroside, might play a vital role in the antibacterial properties of S. ningpoensis honey. CONCLUSIONS: This is the first study to thoroughly investigate the antibacterial activity, mode of action, and componential profile of S. ningpoensis honey. It suggested that S. ningpoensis honey might be a potential supplement or substitute for manuka honey, for the prevention or treatment of bacterial infections. It will facilitate the precise application of medicinal plant-sourced honey, provide a new thread for the development of antibacterial drugs, and assist in the distinction of different kinds of honey.

[Chemical constituents of Scrophulariae Radix and their antitumor activities in vitro].

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-ß-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 ß-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).

Simultaneous Determination of Iridoid Glycosides, Phenylpropanoid Glycosides, Organic Acids, Nucleosides and Amino Acids in Scrophulariae Radix Processed by Different Processing Methods by HPLC-QTRAP-MS/MS.

Scrophulariae Radix is one of the widely used traditional Chinese medicines. In this study, a high-performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry method was established for the simultaneous determination of multiple bioactive constituents including four iridoid glycosides, two phenylpropanoid glycosides, six organic acids, 11 nucleosides and 16 amino acids in Scrophulariae Radix. The validated method was used to analyze nine Scrophulariae Radix samples processed by different processing methods. In addition, Grey relational analysis and DTOPSIS were used to evaluate the samples according to the content of 39 ayalytes. The results showed that the quality of Scrophulariae Radix processed by cutting into slices, sun drying and "sweating" methods were better. All the results proved that the developed method was available and could be used to evaluate the quality of Scrophulariae Radix.

Remarkable positive effects of figwort (Scrophularia striata) on improving growth performance, and immunohematological parameters of fish.

This study was conducted to investigate the effect of figwort on the growth and immunohematological parameters of common carp (14.20 ± 0.53 g). Four experimental diets were developed to feed fish for eight weeks: control, Figw10 (10 g/kg figwort), Figw20 (20 g/kg figwort), and Figw30 (30 g/kg figwort). The results showed that fish fed dietary Figw10 gained more weight (38.25 g) than control (P < 0.05). Regarding immunohematological parameters, fish fed dietary Figw30 had a higher level of white blood cells (31.2 103/mm3), hematocrit (35.82%), blood performance (14.63), total protein (1.96 g/dL), albumin (0.79 g/dL), globulin (1.17 g/dL), lymphocyte (70.53%), monocyte (3.03%), alternative hemolytic complement activity (ACH50) (147.76 u/mL), lysozyme (62.19 u/mL), and bactericidal activities (135.24) than the control group (P < 0.05). After 14 days of the challenge with Aeromonas hydrophila, the Figw30 treatment had the highest survival ratio (61.76%) compared to the control with 26.46%. Further, after the challenge, fish fed dietary Figw30 had a higher value of immunoglobulin M (42.00 µg/mL), antibody titer (19.23), complement component 3 (296.39 µg/mL), and complement component 4 (97.91 µg/mL) when compared with those fed control diet (P < 0.05). In conclusion, the optimum dosage for providing the best immune response was 30 g/kg in diet.

4-Methoxycinnamic acid attenuates schizophrenia-like behaviors induced by MK-801 in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophularia buergeriana has been used for traditional medicine as an agent for reducing heat in the blood and for nourishing kidney 'Yin'. Therefore, S. buergeriana might be a potential treatment for mental illness, especially schizophrenia, which may be attenuated by supplying kidney Yin and reducing blood heat. In a pilot study, we found that S. buergeriana alleviated sensorimotor gating dysfunction induced by MK-801. AIM OF THE STUDY: In the present study, we attempted to reveal the active component(s) of S. buergeriana as a candidate for treating sensorimotor gating dysfunction, and we identified 4-methoxycinnamic acid. We explored whether 4-methoxycinnamic acid could affect schizophrenia-like behaviors induced by hypofunction of the glutamatergic neurotransmitter system. MATERIALS AND METHODS: Mice were treated with 4-methoxycinnamic acid (3, 10, or 30 mg/kg, i.g.) under MK-801-induced schizophrenia-like conditions. The effect of 4-methoxycinnamic acid on schizophrenia-like behaviors were explored using several behavioral tasks. We also used Western blotting to investigate which signaling pathway(s) is involved in the pharmacological activities of 4-methoxycinnamic acid. RESULTS: 4-Methoxycinnamic acid ameliorated MK-801-induced prepulse inhibition deficits, social interaction disorders and cognitive impairment by regulating the phosphorylation levels of PI3K, Akt and GSK-3ß signaling in the prefrontal cortex. And there were no adverse effects in terms of catalepsy and motor coordination impairments. CONCLUSION: Collectively, 4-methoxycinnamic acid would be a potential candidate for treating schizophrenia with fewer adverse effects, especially the negative symptoms and cognitive dysfunctions.

Chemical constituents of Scrophulariae Radix and their antitumor activities in vitro / 中国中药杂志

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).

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.

Effects of Scrophularia striata hydroalcoholic extract in comparison to salinomycin on growth performance, intestinal health and immunity in broiler chickens following a mixed-species Eimeria challenge.

Poultry coccidiosis is an important disease affecting performance which is characterized by intestinal epithelium damageand increased mortality and is caused by the protozoa parasites of the genus Eimeria. This study evaluated the growth-promoting (experiment 1), protective, and immunostimulatory effects (experiment 2) of salinomycin and Scrophularia striata hydroalcoholic extract (SSE) against coccidiosis in broilers. Two experiments were conducted with 300 1-day-old broiler chickens, which were randomly assigned to 5 treatments with 6 replicate pens of 10 birds (experiment 1) or 10 replicate cages of 6 birds (experiment 2). In both experiments, treatments were: negative control (NC: untreated, and uninfected); positive control (PC: untreated, infected); or PC supplemented with salinomycin (Sal); 200 mg/kg of SSE (SSE200); or 400 mg/kg of SSE (SSE400). All these groups (except NC) were challenged via oral gavage with of sporulated oocysts of Eimeria species (Eimeria acervulina, Eimeria maxima, and Eimeria tenella) on d 10 (experiment 1) or d 14 (experiment 2). In the first trial, all treatments improved growth and feed conversion compared with the PC group, where the best values were noticed in the NC, SAL, and SSE400 groups throughout the entire experimental period (d 1-42). Further, a lower mortality rate (P < 0.05) was observed in the NC, Sal, and SSE400 groups as compared to that in the PC group. In the second trial, intestinal lesion scores and total oocyst numbers were reduced in the Sal and SSE400 groups compared to the PC group, although all coccidiosis-challenged groups had higher intestinal lesion scores (P < 0.05) compared to NC group. Immune responses revealed that among challenged birds, those fed diets Sal and SSE400 had significantly higher Eimeria-specific cecum IgG and IgM levels, but lower serum IFN-γ concentration than the PC group. Among the experimental treatments, broiler chickens fed diet SSE400 had greater (P < 0.05) Eimeria-specific serum IgG and TGF-ß levels, but lower (P < 0.05) serum IL-6 concentration than those fed the PC diet at d 24. Considering the results, dietary SSE, especially at high levels of inclusion in broiler diet (400 mg/kg), could result in a comparable growth performance and a better immune response, compared to a salinomycin supplement under coccidiosis challenge.

Scrophularia ningpoensis Hemsl: a review of its phytochemistry, pharmacology, quality control and pharmacokinetics.

OBJECTIVES: Scrophularia ningpoensis Hemsl (SNH) is a commonly used medicinal plant in East Asia. Scrophulariae Radix (SR) is the dried roots of SNH, and is one of the most commonly used medicinal parts of SNH, and is an essential traditional medicine and widely used in East Asia for more than 2000 years. SR is used for clearing away heat and cooling blood, nourishing Yin and reducing fire, detoxicating and resolving a mass. The purpose of this paper is to systematically review the phytochemistry, pharmacology, quality control and pharmacokinetics of SNH based on the surveyed and summarized literature. KEY FINDINGS: Up to now, iridoids, phenolic glycosides, phenolic acids, alkaloids, flavonoids, triterpenes and other compounds have been isolated and identified from SNH. The extract and chemical components of SNH exerts multiple pharmacological effects, such as hepatoprotective effect, anti-inflammatory effect, neuroprotective effect, anti-ventricular remodeling effect and other activities. Various methods have been developed for the quality control of SNH, mainly for SR. Some bioactive compounds in SNH exhibited different pharmacokinetic behaviours and individual metabolic transformation profiles. SUMMARY: This review will contribute to understanding the correlation between the pharmacological activities and the traditional usage of SNH, and useful to rational use and drug development in the future.

Determination of bioactive compounds in the nonmedicinal parts of Scrophularia ningpoensis using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry and chemometric analysis.

Although Scrophulariae Radix (root of Scrophularia ningpoensis) has received much attention, little is known about the nonmedicinal parts of S. ningpoensis. A comprehensive evaluation of the multibioactive constituents in the flowers, rhizomes, leaves, and stems of S. ningpoensis during different growth stages would be of value to fully understand the potential medicinal properties of all parts of the plant. Ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry was performed for accurately determining nine compounds in S. ningpoensis. The results indicated the content of total analytes in S. ningpoensis was in the order of flowers (81.82 mg/g) > roots (31.95 mg/g) > rhizomes (26.68 mg/g) > leaves (16.86 mg/g) > stems (14.35 mg/g). The chemometric analysis showed that these plant parts were rich in iridoids and should not be discarded during the processing of medicinal materials. Dynamic accumulation analysis suggested that the early flowering stage was the optimum time for harvesting flowers and appropriate amounts of stems and leaves. Moreover, considering the accumulation of constituents and biomass of medicinal materials, the medicinal parts should be harvested around December with the rhizomes attached. This research provides a theoretical basis and scientific evidence for comprehensive development and utilization of S. ningpoensis resources.

Targeted characterization of acylated compounds from Scrophulariae Radix using liquid chromatography coupled with Orbitrap mass spectrometry and diagnostic product ion-based data analysis.

Acylated compounds are often present in herbal medicines. In this study, a diagnostic product ion-based strategy was established to comprehensively characterize acylated compounds in Scrophulariae Radix. After untargeted data acquisition using ultra-high performance liquid chromatography coupled with Orbitrap mass spectrometry, the data were processed by three-stage diagnostic product ions. First, diagnostic product ions corresponding to the acyl groups (cinnamoyl, p-coumaroyl, feruloyl, and caffeoyl) were used to search 90 compounds. Second, these compounds were divided into three categories using diagnostic product ions for phenylethanoid glycosides, iridoid glycosides, and phenylpropanoids, respectively. Last, the linkage position of the acyl group to iridoid glycosides was discriminated via the third-stage diagnostic product ions. As a result, 90 acylated compounds were characterized, and 37 of them were reported from Scrophulariae Radix for the first time.

A trisaccharide phenylethanoid glycoside from Scrophularia flava Grau with potential anti-type 2 diabetic properties by inhibiting α-glucosidase enzyme and decreasing oxidative stress.

The Scrophularia genus is a rich source of phenylethanoid glycosides, with diverse biological activities including anti-diabetic properties. This study investigated anti-type 2 diabetic potential and active component of Scrophularia flava Grau. A new phenylethanoid glycoside was isolated from aerial parts of the plant and identified as 2-(4-hydroxy-3-methoxyphenyl) ethyl 6-deoxy-3-O-[(2E)-3-(3 hydroxy-4-methoxyphenyl) prop-2-enoyl]-α-rhamnopyranosyl-(1 â†’ 3)-[α-rhamnopyranosyl-(1 â†’ 6)]-4-O-[(2E)-3-(4-hydroxy-3-methoxyphenyl) prop-2-enoyl]-ß-glucopyranoside. It was named flavaioside. The structure of flavaioside was identified based on 1H NMR, 13C NMR, DEPT-HSQC, COSY, HMBC, NOESY and LC-ESI-MS-MS. Total methanol extract, fractions (A-F) and specific main phenylethanoid glycoside (flavaioside), were assessed for inhibitory effects against the α-glucosidase enzyme (in vitro anti-type 2 diabetic assay). The antioxidant activities of methanol extracts, all fractions and isolated flavaioside were identified based on 2, 2'-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activity, 2, 2'-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid radical cation (ABTS+) scavenging activity, phosphomolybdenum method, and metal chelating activity. In comparison to the other fractions, the best antioxidant result was observed in fraction E and its main compound, flavaioside, in DPPH (IC50 = 4.26, 2.57 µg/mL) and ABTS+ (EC50 = 55.45, 6.34 µg/mL) scavenging activities. Flavaioside showed significantly stronger activities than α-tocopherol and ascorbic acid in DPPH and ABTS+ assays. Furthermore, flavaioside showed a potent inhibitory activity on the α-glucosidase enzyme which was comparable with the known anti-type 2 diabetic drug, acarbose (91.85%, and 92.87%, respectively). Fraction E and flavaioside showed α-glucosidase inhibitory activities with IC50 values, 65.05 and 6.50 µg/mL. The plant and its isolated flavaioside can possess acceptable anti-type 2 diabetic potential and anti-oxidant activity.

Middle Eastern Plant Extracts: An Alternative to Modern Medicine Problems.

Middle Eastern countries are primarily known for their dry sand deserts; however, they have a wider physiographic range which includes upland plateau and mountain ranges. The Middle East is home to various types of plants, such as Phoenix dactylifera (date palm tree), Scrophularia striata (herbaceous plants), and Opuntia ficus-indica (cactus). These plants have been found to have various types of bioactivities, such as antimicrobial activities against both bacteria and fungi, in addition to exhibiting anti-inflammatory effects and anti-cancer characteristics which can be utilized in the clinical setting for treatment. Due to limited reviews focusing on plant extracts from the Middle East, we aim to provide a discourse on plants from this region which have various bioactivities and to provide information on the compounds that can be identified from these plants. This is to enhance our understanding to improve modern medicine problems such as antimicrobial resistance and to find an alternative cure for cancer. It is hoped that the collation of information from this review will enable an assessment of the direct role of Middle Eastern plants in providing therapeutic options to address the predicaments in the medical field.

Harpagide from Scrophularia protects rat cortical neurons from oxygen-glucose deprivation and reoxygenation-induced injury by decreasing endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Harpagide is the main ingredient in Scrophularia ningpoensis Hemsl which is used for the therapeutic purpose of treating encephalopathy. Harpagide has shown promise in the treatment of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced brain injury. However, the underlying mechanisms remain unclear. AIM OF STUDY: In this study, we aimed to determine the neuroprotective effect of harpagide on rat cortical neurons under OGD/R conditions that induce the development of ischaemia-reperfusion (I/R). MATERIALS AND METHODS: To explore the biological function of harpagide in cerebral ischaemia-reperfusion injury (CIRI), The CIRI model was established by oxygen-glucose deprivation and reoxygenation (OGD/R) on rat cortical neurons. It tested cell survival rate by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, apoptosis by flow cytometry, intracellular Ca2+ concentration [Ca2+] i by cofocal laser, and expressions related to endoplasmic reticulum stress (ERS) by RT-PCR and Western blot. RESULTS: We found that pretreatment with harpagide (50 µM) prevented OGD/R-induced apoptotic cell death. Harpagide also significantly decreased the gene expression levels and protein production of ERS-related proteins. We found that harpagide also exerted a neuroprotective effect on TG-induced apoptosis in rat cortical neurons and decreased the gene expression levels and protein production of GRP78, caspase-12 and CHOP. We also measured the intracellular calcium ion concentration ([Ca2+]i) in neurons and found that harpagide significantly decreased the [Ca2+]i induced by OGD/R and TG. CONCLUSION: These results suggest that harpagide protects against OGD/R-induced cell apoptosis, likely by decreasing ERS. Collectively, harpagide was demonstrated to be a prominent suppressor of ERS and prevented the apoptosis of rat cortical neurons. Based on the results, harpagide could potentially serve as a therapeutic agent of ischaemia-like injury associated with excessive ERS and apoptosis.

Antidiabetic and protective effects of Scrophularia striata ethanolic extract on diabetic nephropathy via suppression of RAGE and S100A8 expression in kidney tissues of streptozotocin-induced diabetic rats.

Background The present study was conducted to examine the antidiabetic effects of Scrophularia striata ethanolic extract and to evaluate its effects on oxidative stress markers and RAGE and S100A8 gene expressions in the kidney of type 1 diabetic rats. Methods A total of 36 rats (weight 200-250 g) were randomly assigned into six groups as follows: Cnt, Cnt + S. striata 100, and Cnt + S. striata 200 that received normal saline, 100 mg/kg bw, and 200 mg/kg bw of ethanol extract of S. striata, respectively; and group Dibt, Dibt + S. striata 100, and Dibt + S. striata 200 that received normal saline, 100 mg/kg bw, and 200 mg/kg bw of ethanol extract of S. striata, respectively. Type 1 diabetes was induced in rats by a single injection of streptozotocin (55 mg/kg bw). After 60 days of treatment, biochemical factors and oxidative stress markers (superoxide dismutase [SOD] and malondialdehyde [MDA]) were measured using spectrophotometric methods. RAGE and S100A8 gene expressions were analyzed using real-time polymerase chain reaction. Results Diabetes significantly impairs serum and urine fasting blood glucose (FBG), lipid profile, creatinine, urea, and albumin parameters. After the treatment with S. striata extract, these parameters are close to the normal range. It was shown that the S. striata extract significantly decreased the kidney expression levels of RAGE and S100A8 genes and improved oxidative stress markers (SOD and MDA) in the kidney tissues when compared with the diabetic control group. It was also found that the beneficial effects of the S. striata were dose dependent. Conclusions The ethanolic extract of S. striata has beneficial antidiabetic effects. Moreover, by reducing RAGE and S100A8 gene expressions and by improving oxidative stress, S. striata might be used as adjuvant treatment for diabetic complications.

Scrophularia buergeriana attenuates allergic inflammation by reducing NF-κB activation.

BACKGROUND: Scrophularia buergeriana Miq. (Scrophulariaceae) (SB) has been used as an oriental medicine for the treatment of inflammatory diseases, such as neuritis and pharyngolaryngitis. PURPOSE: We explored the therapeutic effects of S. buergeriana ethanol extract (SBE) on airway inflammation in ovalbumin (OVA)-induced asthmatic mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. METHODS: Mice were intraperitoneally injected with OVA on days 0 and 14 to elevate the immune response. On days 21 to 23, the mice were challenged with OVA solution and SBE (20 and 40 mg/kg) was administered daily by oral gavage from days 18 to 23. RAW264.7 cells were pretreated with SBE 1 h before LPS stimulation. RESULTS: SBE administration effectively suppressed inflammatory cell infiltration, the expression of interleukin (IL)-5, IL-13, and IL-17, immunoglobulin E, and airway hyperresponsiveness in an OVA-induced allergic asthma model. A reduction in histological alterations, including airway inflammation and mucus hypersecretion, was observed. These effects of SBE were accompanied by a decrease in matrix metalloproteinase-9 (MMP-9) expression and nuclear factor kappa B (NF-κB) phosphorylation. These responses were observed in LPS-stimulated RAW264.7 cells. SBE treatment reduced the mRNA expression of tumor necrosis factor (TNF)-α, IL-6, and MMP-9, and NF-κB phosphorylation, in LPS-stimulated RAW264.7 cells. CONCLUSION: Our results indicated that SBE effectively attenuated airway inflammation in an OVA-induced allergic asthma model. These properties of SBE were thought to be involved in the suppression of NF-κB phosphorylation, suggesting that the material has the potential to regulate the development of allergic asthma.

Effects of ecological factors on the antioxidant potential and total phenol content of Scrophularia striata Boiss.

Scrophularia striata, commonly known as figwort, is one of the most important medicinal plants that mainly grows in cold regions of the Zagros Mountains (West of Iran). Although the chemical composition of this plant species has not yet been explored, people living in Ilam province (W Iran) have used it for many years to treat different illnesses. The present study aims to analyze the effect of some ecological factors on the antioxidant potential and the amount of phenol present in this plant species, using a random factorial design with two factors (elevation and region) and three replicates. The fruits of the plant were gathered from three different elevations. They were collected from three regions of the Ilam province (Badreh, Dareshahr, and Dehloran) in June 2016, when the fruits appear. Moreover, to analyze different soil chemical and physical features, soil samples were gathered from a depth of 0.5 m under the shrubs. The antioxidant action of the methanol extract from the plant samples and the total amount of phenol compounds were measured using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the Folin-Ciocalteu method, respectively. The results showed that the effects of site and elevation, and the interaction between these factors, on the antioxidant potential and total phenol amount were significant with a probability of error of 1%. The maximum extract efficiency (19.37 ± 3.07%), antioxidant potential (126.5656 ± 0.96 µg/mL), and total amount of phenol (55.7689 ± 3.17 µg/mL) were obtained from Dareshahr at an elevation of 600 m above mean sea level. The minimum amount of total phenol (24.6544 ± 3.21 µg/ml) was recorded at the lowest elevation of Badreh, at which phosphorus, potassium, organic carbon, organic material, nitrogen, acidity, lime, and silt were present at the lowest amount. However, the antioxidant activity and total amount of phenol had a strong direct correlation in the two districts of Dareshahr and Badreh, but were reversely and strongly correlated in Dehloran. Therefore, it can be stated that Scrophularia striata has the potential for antioxidant activity, however, the complexity of the effect of ecological factors on one hand, and the emergence of different chemical processes in the plant under such effects on the other hand, has led to the synthesis of different compounds with antioxidant potential in the plant in different regions.