Bioactive nanofibrous mats constructs: Separate efficacy of Lawsonia inermis and Scrophularia striata extracts in PVA/alginate matrices for enhanced wound healing.

The study explores the use of electrospinning technology to create advanced wound dressing materials by integrating natural extracts from Lawsonia inermis (LI) and Scrophularia striata (SS) into nanofibrous matrices composed of Polyvinyl Alcohol (PVA) and Alginate (ALG). These macromolecular complexes aim to leverage the unique properties of the botanical extracts for wound healing purposes. The research assesses the physical, chemical, and mechanical attributes of the nanofibrous constructs as well as their antimicrobial activities and ability to promote wound repair. Evaluation of Cellular Viability and Cytotoxicity (MTT) tests showed high biocompatibility of the nanofibrous mats, with cell viability percentages of 92 % for LI-loaded mats and 89 % for SS-loaded mats. The antibacterial rate of extract-containing mats was 70 % higher than non-extract-containing mats. In vivo assessments on rat models with burn injuries demonstrated that mats containing LI and SS extracts substantially accelerate tissue regeneration and overall healing. Nanofibrous mats containing LI extract showed a 45 % faster wound healing process than the control, while those containing SS extract showed a 40 % improvement. Overall, the study highlights the potential of PVA/ALG nanofibrous mats augmented with LI and SS extracts as effective platforms for wound management, offering enhanced properties for superior healing outcomes.

Migration Patterns and Potential Risk Assessment of Trace Elements in the Soil-Plant System in the Production Area of the Chinese Medicinal Herb Scrophularia ningpoensis Hemsl.

Scrophularia ningpoensis Hemsl. holds a prominent place among Chinese medicinal herbs. Assessing the soil-plant system of its origin is crucial for ensuring medication safety. Although some trace elements are essential for the normal functioning of living organisms, exposure to higher concentrations is harmful to humans, so in order to assess the possible health risk of trace elements in the soil-plant system of Scrophularia ningpoensis Hemsl. origin for human assessment, we used non-carcinogenic risk (HI) and carcinogenic risk (CR) for their evaluation. In this paper, the following trace elements were studied in the soil-Scrophularia ningpoensis Hemsl. system: manganese (Mn), iron (Fe), cobalt (Co), zinc (Zn), selenium (Se), molybdenum (Mo), arsenic (As) and lead (Pb). Correlation and structural equation analyses showed that the effect of soil in the root zone on the plant was much greater than the effect of soil in the non-root zone on the plant. The single-factor pollution index (Pi) showed that the soil in the production area of Scrophularia ningpoensis Hemsl. was polluted to a certain extent, notably with Pb showing the highest average Pi values of 0.94 and 0.89 in the non-root and root zones, respectively. Additionally, the Nemerow composite pollution indices (PN) for both zones indicated an alert range. Regarding health risks, exposure to soil in the non-root zone posed higher non-carcinogenic risk (HI) and carcinogenic risk (CR) compared to the root zone, although neither zone presented a significant carcinogenic risk. The potential non-carcinogenic risk (HI) and carcinogenic risk (CR) from consuming Scrophularia ningpoensis Hemsl. leaves and stems were more than ten times higher than that of roots. However, the carcinogenic risk (CR) values for both the soil and plant of interest in the soil- Scrophularia ningpoensis Hemsl. system did not exceed 10-4, and therefore no significant carcinogenic risk existed.

Vertebrate Pollination of Angiosperms in the Mediterranean Area: A Review.

For a long time, it was considered that entomogamy was the only pollination mechanism in the Mediterranean area. However, data recorded in this review prove that ornithogamy and saurogamy also take place. With the exception of the nectarivorous Cinnyris osea (Nectariniidae) which pollinates the mistletoe Picosepalus acaciae in Israel, all birds responsible for the pollination of several plant species in this area are primarily insectivorous, sedentary, or migrating passerine birds, particularly Sylvia atricapilla, S. melanocephala, Phylloscopus collibita and Parus caeruleus. They contribute, together with insects, to the pollination of Anagyris foetida, three species of Scrophularia with big flowers, Rhamnus alaternus, Brassica oleracea, and some other plants. The lacertid lizard Podarcis lilfordi acts as a pollinating agent on several W Mediterranean islands, where it effectively pollinates Euphorbia dendroides, Cneorum tricocum, and presumably Rosmarinus officinalis and Chrithmum maritimum. The flowers of some other plant species are visited by birds or by Podarcis species in the Mediterranean area, where they could also contribute to their pollination.

Metabolomics distinguishes different grades of Scrophularia ningpoensis hemsl: Towards a biomarker discovery and quality evaluation.

In managing unique complexities associated with Chinese medicinal quality assessment, metabolomics serves as an innovative tool. This study proposes an analytical approach to assess differing qualities of Scrophularia ningpoensis （S. ningpoensis）Hemsl by identifying potential biomarker metabolites and their activity with the corresponding secondary metabolites. The methodology includes four steps; first, a GC-MS based metabolomics exploration of the Scrophularia ningpoensis Hemsl. Second, a multivariate statistical analysis (PCA, PLS-DA, OPLS-DA) for quality assessment and biomarker identification. Third, the application of ROC analysis and pathway analysis based on identified biomarkers. Finally, validation of the associated active ingredients by HPLC. The analysis showed distinct metabolite profiles across varying grades of S. ningpoensis Hemsl, establishing a grading dependency relationship. Select biomarkers (gluconic Acid, d-xylulose, sucrose, etc.) demonstrated robust grading performances. Further, the Pentose Phosphate Pathway, deemed as most influential in grading, was tied to the synthesis of key constituents (iridoids, phenylpropanoids). HPLC validation tests affirm a decreasing trend in harpagoside and cinnamic acid levels between first and third-grade samples. In conclusion, this GC-MS based metabolomics combined HPLC method offers a sound approach to assess and distinguish quality variations in S. ningpoensis Hemsl samples.

An Integrative Study of Scrophularia takesimensis Nakai in an Ovalbumin-Induced Murine Model of Asthma: The Effect on T Helper 2 Cell Activation.

Scrophularia have traditionally been used as herbal medicines to treat neuritis, sore throats, and laryngitis. In particular, S. takesimensis, a Korean endemic species with restricted distribution on Ulleung Island, holds significant resource and genetic value. However, its pharmacological properties have not been thoroughly evaluated. Thus, we provide detailed morphological characteristics and genomic information for S. takesimensis in this study. Moreover, its pharmacological activity was evaluated in an ovalbumin-induced asthma rat model, using extracts of S. takesimensis roots (100 or 200 mg/kg). The distinguishing features of S. takesimensis from related species include the presence or absence of stem wings, leaf shape, and habitat. The chloroplast (cp) genome of this species is 152,420 bp long and exhibits a conserved quadripartite structure. A total of 114 genes were identified, which included 80 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. The gene order, content, and orientation of the S. takesimensis cp genome was highly conserved and consistent with the general structure observed in S. buergeriana and S. ningpoensis cp genomes. Confirming the anti-inflammatory effects of S. takesimensis extract (STE) using an established mouse model of ovalbumin-induced asthma, we observed reduced asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and suppression of T helper 2 (Th2) cell. Furthermore, STE treatment reduced Th2 cell activation and differentiation. This study underscores the medicinal value of S. takesimensis. The importance of preserving S. takesimensis was revealed and crucial insights were provided for further research on its utilization as a medicinal resource.

The impact of non-environmental factors on the chemical variation of Radix Scrophulariae.

Radix Scrophulariae is a commonly used Chinese herb derived from the dried root of Scrophularia ningpoesis Hemsl. (S. ningpoensis). It is difficult to accurately estimate the dosage of Chinese medicinal materials used in the prescription because of the chemical variation caused by various factors. To analyze the non-environmental factors affecting the chemical variation of Radix Scrophulariae, we planted nine different cultivated varieties of S. ningpoensis in the same plantation. Based on sequence-related amplified polymorphism (SRAP), simple sequence repeats (SSR) markers and high-performance liquid chromatography (HPLC) analysis, we found that the materials from the cultivated varieties could be divided into two groups, the Zhejiang group, and the southwest China group. The genetic distance based on molecular data between the two groups was above 0.3882, and the Euclidean distance based on chemical data between the two groups was above 5.312. The correlation analysis between the genetic distance matrix based on SRAP and the Euclidean distance matrix based on 18 HPLC peaks of the whole underground part revealed that the genetic differentiation and chemical variation were positively related, r = 0.7196 (p < 0.05). The genetic background, different part of the roots and the different development of the roots are the three non-environmental factors causing the chemical variation. The coefficient of variation (C.V) of chemical composition of Radix Scrophulariae with different genetic background reached to 93.62 %, the C.V of the chemical composition of Radix Scrophulariae derived from the same variety reached to 64.21 %, the C.V of the chemical composition of Radix Scrophulariae derived from the middle part of the roots of S. ningpoensis from the same variety reached to 45.55 %. The C.V of chemical composition of Radix Scrophulairae produced in the same plantation could be controlled to 38.43 % by using the same variety of roots with the approximate mass derived from the middle part of the roots under 20 g. Our findings provided insights to decrease the chemical variation of Chinese medicinal materials by controlling non-environmental factors.

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.

Hydroalcoholic extract of Scrophularia striata has a significant therapeutic effect on thioacetamide-induced liver cirrhosis in rats.

OBJECTIVES: Liver cirrhosis is one of the most important causes of death from liver diseases. Nowadays, the use of herbal medicines has increased due to its availability, less side effects and cheapness for the treatment of liver diseases. The present study was conducted to examine therapeutic effects of hydroalcoholic extract of Scrophularia striata (S. striata) on thioacetamide-induced liver cirrhosis in rats through evaluate its effects on oxidative stress markers and the expression of metalloproteinase 1 (TIMP 1), toll-like receptor-4 (TLR-4), and Mitofusin (MFN2) genes. METHODS: 24 male rats were selected by simple random sampling. Rats were randomly assigned to four groups: group I: healthy rats, group II: thioacetamide (TAA) injected rats, group III: TAA injected rats+100 mg/kg bw of S. striata and group IV: TAA injected rats+200 mg/kg bw of S. striata. Liver cirrhosis was induced in rats by a 300 mg/kg bw TAA administration twice with an interval of 24 h. After 8 weeks of treatment by S. striata at doses of 100 and 200 mg/kg bw, biochemical factors and oxidative stress markers (SOD, TAC, GPX, CAT and MDA) were measured using spectrophotometric methods. Also, gene expression of TIMP 1, TLR-4, and MFN2 were analyzed using real-time PCR. ANOVA and Bonferroni post hoc test analysis were applied to evaluate the data. RESULTS: The results showed the S. striata extract significantly improve the serum ALT, AST and ALP levels, TIMP 1, TLR-4, and MFN2 genes and oxidative stress markers (SOD, TAC, GPX, CAT and MDA) in the liver tissues when compared to control group (p<0.05). Also, it was found that the beneficial effects of the S. striata were dose-dependent. CONCLUSIONS: Based on the results obtained S. striata by reducing the expression of TIMP 1, TLR-4, and MFN2 genes and improving oxidative stress might be used as adjuvant treatment for liver cirrhosis.

Molecular Insights into the Macrophage Immunomodulatory Effects of Scrophulariae Radix Polysaccharides.

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-1ß, 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.

Simultaneous application of salicylic acid and silicon in aerial parts of Scrophularia striata L. in response to drought stress.

Plants respond to water shortage by regulating biochemical pathways which result in the biosynthesis of osmotic compounds. Active metabolites and compatible osmolytes control the inhibition of oxygen free radicals and dehydration. The physiological response of scrophularia striata to drought stress, a factorial completely randomized design (FCRD) experiment was conducted in three replication. Drought stress was induced at two levels (100% and 50% field capacity), and salicylic acid (SA) and silicon (Si) and Ecotype were also used at two levels of (0 and 100 PPM), (0 and 1 g/L) and (Ilam and Abdanan) respectively. Data analysis results indicated that the H2O2 content, Malondialdehyde (MDA), glycine betaine (GB) and the activity of the enzyme glutathione reductase (GR; EC 1.6.4.2) of aerial parts increased during the entire stress exposure period. Although the SA + Si + stress + ecotype interaction increased the content of soluble carbohydrate s and the GR activity in aerial parts of Ilam and Abdanan ecotypes, this interaction led to a decrease in MDA, H2O2 in Ilam ecotypes. The interaction between the stress + SA + Si + ecotype led to an increase in the phenylalanine ammonialyase (PAL; EC 4.3.1.5) activity in the Abdanan ecotype, but no important difference was observed. As compared to the control treatment, the content of Polyphenol increased, The interaction between ecotype + stress + Si caused to increased the of proline content in the Abadanan ecotype. The results showed that the increase in antioxidant defense and compatible osmolytes due to the use of SA and Si can improve the drought tolerance in S.striata.

P2X7-Receptor Pathway Involvement in the Anti-Inflammatory Activity of Medicinal Plants.

Medicinal plants used in European folk medicine attached to Lamiales, Gentianales or Asterales orders are used to treat inflammatory disorders. Many targets have been identified but to date, implication of purinergic receptor P2X7 activation has not yet been investigated. We managed to evaluate the protective effect on P2X7 activation by plant extracts used as anti-inflammatory in European folk medicine by the YO-PRO-1 uptake dye in vitro bioassay. Results revealed that among our selected plants, species from Scrophularia and Plantago genus were able to decrease significantly P2X7 activation (>50 % at 0.1 and 1 µg/mL). UPLC/MS, dereplication and metabolomic analysis of Scrophularia extracts, allowed us to identify the cinnamoyl-iridoid harpagoside as putative inhibitor of P2X7 activation. These results open a new research field regarding the anti-inflammatory mechanism of cinnamoyl-iridoids bearing plants, which may involve the P2X7 receptor.

Scrophularia amplexicaulis increases anti-cancer potential of doxorubicin in gastric cancer cells.

Increased drug resistance has reduced efficiency of chemotherapic drugs such as Doxorubicin (Dox). Scrophularia amplexicaulis (Scr) is one of the most important medicinal plants in Iran that has anti-cancer activity. The aim of this study was to investigate a novel approach to enhance therapeutic efficacy of Dox (as a chemotherapeutic agent) by co-administration of Scr (as a bioactive herbal compound) in gastric cancer treatment. In the present study, effects of Dox, Scr, and their combinations (Scr-Dox) were evaluated on viability and proliferation of two gastric cancer cell lines (AGS and MKN28). Moreover, morphological changes, invasion, migration, colony formation, and apoptosis rate in the treated cancer cells were evaluated. Expression of BAX, BCL2, SAMC, SURVIVIN, CASP9, P53, MMP9, and MMP2 in the treated cancer cells and untreated controls were evaluated by Real-Time PCR method. Treatments of cancer cells by Scr, Dox, and Scr-Dox significantly decreased proliferation, invasion, migration, and colony formation of gastric cancer cells. Treatments of cancer cells by Scr, Dox, and Scr-Dox significantly increased apoptosis rate as well as decreased cells mobility through modification of apoptosis- and metastasis-related genes expression. However, anti-cancer activity of Scr-Dox combination was significantly more than Scr and Dox treatments alone. In general, we demonstrated that Scr-Dox combination therapy exerts more profound anti-cancer effects on AGS and MKN28 cell lines than Scr and Dox monotherapy.

Ameliorative Effect of Aqueous and Hydroalcoholic Extracts of Scrophularia striata Boiss. on Murine Model of Experimental Colitis.

Background: Scrophularia striata Boiss. (S. striata) is a flowering plant with several therapeutic properties including antiinflammatory, antioxidant, antimicrobial, and wound-healing activity. Regarding the side effects of drugs conventionally used for inflammatory bowel disease (IBD) treatment, we investigated the anticolitis properties of aqueous (SSAE) and hydroalcoholic (SSHE) extracts of S. striata on experimental colitis. Materials and Methods: The colitis was induced using acetic acid (3%) and 2 h before ulcer induction, each group of rats received orally three doses (150, 300, and 600 mg/kg, p.o.) of SSAE or SSHE for the next 5 days. Dexamethasone (1 mg/kg, i.p.) and mesalazine (100 mg/kg, p.o.) were used as reference drugs. Different parameters including weight of colon/height, ulcer index, total colitis index, levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were investigated. Results: Total phenolic contents were 4.3 ± 0.2 and 7.1 ± 0.4 mg/g equivalent to gallic acid for SSAE and SSHE respectively. Three applied doses of SSHE and the highest dose of SSAE (600 mg/kg) could reduce all the macroscopic and pathologic indices of colitis and the levels of MPO and MDA. Two lesser doses of SSAE (150, 300 mg/kg) however, couldn't diminish the histopathologic features of colitis and the values of MPO and MDA. Conclusions: S. striata, especially SSHE, which also contained more phenolic compounds, had an ameliorating effect on ulcerative colitis and possibly exerts this effect through its antioxidant, antiinflammatory and wound healing properties. Further investigations are required to introduce this plant as a novel alternative herbal drug for colitis treatment.

Scrophularia peyronii Post. from Jordan: Chemical Composition of Essential Oil and Phytochemical Profiling of Crude Extracts and Their In Vitro Antioxidant Activity.

The genus Scrophularia is one of the largest genera belonging to the Scrophulariaceae family. Different members of the genus exhibit an interesting, wide spectrum of bioactivities. Accordingly, the current study aimed to investigate, for the first time, the chemical composition of the essential oil of Scrophularia peyronii Post. from Jordan. Additionally, extracts obtained from the aerial parts with solvents of different polarities were assayed for their phytochemical constituents and in vitro antioxidant activities. The major constituents detected in the essential oil, as revealed by GC/MS analysis, contained mainly Z,Z-farnesyl acetone (11.04%), ß-elemene (6.36%), n-octanal (5.98%), and spathulenol (4.58%). Each of the aqueous methanol (Sp-M) and butanol (Sp-B) extracts contained flavonoids, saponins, anthraquinone, and glycosides. Both extracts were evaluated for their total phenolic content (TPC), total flavonoid content (TFC), and their in vitro antioxidant activity, which were assayed using the DPPH radical scavenging activity and ABTS radical scavenging methods. Additionally, the two extracts were then subjected to LC-ESI-MS/MS for the qualitative determination of their secondary metabolite content, especially in flavonoids and phenolic compounds. The results showed that the Sp-B extract of S. peyronii had the highest contents of both phenolic compounds and flavonoids and showed high radical scavenging activity, as determined by the two assay methods, when compared with the Sp-M extract. The LC-ESI-MS/MS analysis resulted in the detection of 21 compounds, including 8 flavonoids, 6 phenolic acids, 6 iridoids, and 2 acids. Although the majority of compounds were detected in both extracts, it was noticed that scropolioside B, 6'-O-cinnamoylharpagide, isoferulic acid, and 6-O-methylcatapol were only detected in the Sp-M fraction.

Characterization and Comparative Analysis of Chloroplast Genomes of Medicinal Herb Scrophularia ningpoensis and Its Common Adulterants (Scrophulariaceae).

Scrophularia ningpoensis, a perennial medicinal plant from the Scrophulariaceae family, is the original species of Scrophulariae Radix (SR) in the Chinese Pharmacopoeia. This medicine is usually deliberately substituted or accidentally contaminated with other closely related species including S. kakudensis, S. buergeriana, and S. yoshimurae. Given the ambiguous identification of germplasm and complex evolutionary relationships within the genus, the complete chloroplast genomes of the four mentioned Scrophularia species were sequenced and characterized. Comparative genomic studies revealed a high degree of conservation in genomic structure, gene arrangement, and content within the species, with the entire chloroplast genome spanning 153,016-153,631 bp in full length, encoding 132 genes, including 80 protein-coding genes, 4 rRNA genes, 30 tRNA genes, and 18 duplicated genes. We identified 8 highly variable plastid regions and 39-44 SSRs as potential molecular markers for further species identification in the genus. The consistent and robust phylogenetic relationships of S. ningpoensis and its common adulterants were firstly established using a total of 28 plastid genomes from the Scrophulariaceae family. In the monophyletic group, S. kakudensis was determined to be the earliest diverging species, succeeded by S. ningpoensis. Meanwhile, S. yoshimurae and S. buergeriana were clustered together as sister clades. Our research manifestly illustrates the efficacy of plastid genomes in identifying S. ningpoensis and its counterfeits and will also contribute to a deeper understanding of the evolutionary processes within Scrophularia.

Study on material basis and anti-hypertensive metabolomics of different extraction methods of the Uncaria rhynchophylla Scrophularia Formula.

Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Uncaria rhynchophylla Scrophularia Formula (URSF), a medical institution preparation of the affiliated Hospital of Shandong University of Traditional Chinese Medicine, is effective for essential hypertension. However, the efficacy of URSF for hypertension remains unclear. We aimed to clarify the anti-hypertensive mechanism of the URSF. The material basis of URSF was identified by the LC-MS. We also evaluated the antihypertensive efficacy of URSF on SHR rats by body weight, blood pressure and biochemical indicators. The LC-MS spectrometry-based serum non-targeted metabolomics was used to seek potential biomarkers and relevant pathways for URSF in the treatment of SHR rats. 56 biomarkers were metabolically disturbed in SHR rats in the model group compared with the control group. After URSF intervention, 13 biomarkers showed a recovery in the optimal method compared with the other three groups. We identified 3 metabolic pathways in which URSF is involved: the arachidonic acid metabolism pathway, the niacin and nicotinamide metabolism pathway, and the purine metabolism pathway. These discoveries offer a basis for the study of URSF for the treatment of hypertension.

Scrophularia buergeriana Extract (Brainon) Attenuates Neuroinflammation in BV-2 Microglia Cells and Promotes Neuroprotection in SH-SY5Y Neuroblastoma Cells.

Microglia-induced neuroinflammation is one of the causative factors in cognitive dysfunction and neurodegenerative disorders. Our previous studies have revealed several benefits of Scrophularia buergeriana extract (Brainon®) in the central nervous system, but the underlying mechanism of action has not been elucidated. This study is purposed to investigate the anti-inflammatory and neuroprotective mechanisms of Brainon in the BV-2 condition SH-SY5Y model. Lipopolysaccharide (LPS)-induced BV-2 conditioned media (CM) were used to treat SH-SY5Y cells to investigate neuroprotective effects of the extract against microglial cytotoxicity. Results demonstrated that pretreated Brainon decreased nitric oxide release, the inducible nitric oxide synthase expression level, and expression of cytokines like interleukin-6, interleukin-1ß, and tumor necrosis factor-α by blocking expression of TLR4/MyD88 and NLRP3 and suppressing nuclear factor κB/AP-1 and p38/JNK signaling pathways in LPS-induced BV-2 cells. In addition, when SH-SY5Y cells were treated with CM, pretreatment with Brainon increased neuronal viability by upregulating expression of antioxidant proteins like as SODs and Gpx-1. Increased autophagy and mitophagy-associated proteins also provide important clues for SH-SY5Y to prevent apoptosis by Brainon. Brainon also modulated mTOR/AMPK signaling to clear misfolded proteins or damaged mitochondria via auto/mitophagy to protect SH-SY5Y cells from CM. Taken together, these results indicate that Brainon could reduce inflammatory mediators secreted from BV-2 cells and prevent apoptosis by increasing antioxidant and auto/mitophagy mechanisms by regulating mTOR/AMPK signaling in SH-SY5Y cells. Therefore, Brainon has the potential to be developed as a natural product in a brain health functional food to inhibit cognitive decline and neuronal death.

Chemometric-guided chemical marker selection: A case study of the heat-clearing herb Scrophularia ningpoensis.

The selection of medicinal plants' chemical markers focuses on bioactivity as the primary goal, followed by the nature of secondary metabolites, their stability, and availability. However, herbal medicines are valued for their complex and holistic pharmacological effects. A correct chemical marker can be carefully selected by a systematic clarification of their chemical-biological relationships. In the current study, the multi-informative molecular networking (MIMN) approach was employed to construct the anti-inflammatory metabolomic pattern of a heat-clearing herb, Scrophularia ningpoensis Hemsl. (S. ningpoensis). The MIMN molecular families characterized by cinnamic acid glycosides showed a higher bioactivity score compared with the other two major chemical classes (iridoid glycosides and iridoid-cinnamic acid glycosides). The Global Natural Product Social Molecular Networking (GNPS) and Reaxys database were used to assist in the putative annotation of eighteen metabolites from the bioactive and non-bioactive molecular families. The anti-inflammatory validation step was based on the detection of reactive oxygen species (ROS) generation by activated human neutrophils. All compounds from the bioactive MIMN molecular families dose-dependently inhibited the total ROS generation promoted by fMLF (IC50: 0.04-0.42 µM), while the compounds from non-bioactive MIMN clusters did not show any significant anti-inflammatory effect. The ROS-dependent anti-inflammatory activity of these cinnamic acid glycosides was attributed to their oxygen radical scavenging ability. The most abundant cinnamic acid glycoside, angoroside C (IC50: 0.34 µM) was suggested to be selected as a chemical marker for S. ningpoensis. In this study, the MIMN platform was applied to assist in the chemical marker selection of S. ningpoensis. The correct selection of markers will aid in the compilation and revision of herbal monographs and pharmacopeias resulting in the precise analysis and classification of medicinal plants on a scientific basis.

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

Alzheimer's disease (AD) is a worldwide problem. Currently, there are no effective drugs for AD treatment. Scrophularia buergeriana Miquel (SB) is a traditional herbal medicine used in Korea to treat various diseases. Our previous studies have shown that ethanol extract of SB roots (SBE, Brainon®) exhibits potent anti-amnesic effects in Aß1-42- or scopolamine-treated memory impairment mice model and neuroprotective effects in a glutamate-induced SH-SY5Y cell model. In this study, we evaluated the therapeutic effects of Brainon® and its mechanism of action in senescence-accelerated mouse prone 8 (SAMP8) mice. Brainon® (30 or 100 mg/kg/day) was orally treated to six-month-old SAMP8 mice for 12 weeks. Results revealed that Brainon® administration effectually ameliorated cognitive deficits in Y-maze and passive avoidance tests. Following the completion of behavioral testing, western blotting was performed using the cerebral cortex. Results revealed that Brainon® suppressed Aß1-42 accumulation, Tau hyperphosphorylation, oxidative stress, and inflammation and alleviated apoptosis in SAMP8 mice. Brainon® also promoted synaptic function by downregulating the expression of AChE and upregulating the expression of p-CREB/CREB and BDNF. Furthermore, Brainon® restored SAMP8-reduced expression of ChAT and -dephosphorylated of ERK and also decreased AChE expression in the hippocampus. Furthermore, Brainon® alleviated AD progression by promoting mitophagy/autophagy to maintain normal cellular function as a novel finding of this study. Our data suggest that Brainon® can remarkably improve cognitive deficiency with the potential to be utilized in functional food for improving brain health.

Comparative proteomic analysis reveals novel insights into the continuous cropping induced response in Scrophularia ningpoensis.

BACKGROUND: Scrophularia ningpoensis is a well-known medicinal crop. Continuous cropping seriously affects the yield and quality, but little is known about the influence of continuous cropping on metabolic pathways. In this study, the difference in protein abundance between continuous cropping and non-continuous cropping of S. ningpoensis roots was studied by proteomics, and the molecular mechanism that protects S. ningpoensis against continuous cropping was explored. RESULTS: The results suggested that continuous cropping in S, ningpoensis altered the expression of proteins related to starch and sucrose metabolism, glycolysis/gluconeogenesis, pentose phosphate pathway, citric acid cycle, phenylalanine, tyrosine and tryptophan biosynthesis, phenylpropanoid biosynthesis, terpenoid backbone biosynthesis, monoterpenoid biosynthesis, sesquiterpenoid and triterpenoid biosynthesis, and steroid biosynthesis. Among these processes, the most affected were phenylpropanoid biosynthesis and starch and sucrose metabolism, which may be important for continuous cropping resistance. CONCLUSION: The effect of continuous cropping on S. ningpoensis was demonstrated at the proteome level in this work, and identified candidate proteins that may cause continuous cropping reactions. The paper provides the theoretical foundation and scientific reference for enhancing the continuous cropping resistance of S. ningpoensis. © 2022 Society of Chemical Industry.