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.

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.

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.

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.

Aqueous extract of Scrophularia ningpoensis improves insulin sensitivity through AMPK-mediated inhibition of the NLRP3 inflammasome.

BACKGROUND: Scrophularia ningpoensis Hemsl. is a commonly used medicinal plant in China for the treatment of diabetes mellitus (DM), but its mechanism of action remains poorly described. Type 2 diabetes mellitus (T2DM) accounts for > 90% of all DM cases and is characterized by insulin resistance. PURPOSE: The aim of this study was to investigate whether the insulin sensitivity can be improved by treatment with aqueous extract of S. ningpoensis (AESN) and further explore its mechanism(s) of activity. METHODS: Primary mouse hepatocytes and human HepG2 hepatocytes were used to investigate the effects of AESN on cell viability, AMP-activated protein kinase (AMPK) activation and glucose output under normal culture conditions. To mimic hyperglycemia and insulin resistance in vitro, hepatocytes were exposed to high glucose (HG), and the influences of AESN on AMPK phosphorylation, NLRP3 inflammation activation, insulin signaling, lipid accumulation and glucose output were investigated. Increasing doses of AESN (50, 100 and 200 mg/kg/day) were administered by gavage to db/db mice for 8 weeks, and then biochemical analysis and histopathological examinations were performed. RESULTS: AESN significantly activated AMPK and inhibited glucose output in hepatocytes, but did not impact cell viability under normal culture conditions. Moreover, in HG-treated hepatocytes, AESN protected against aberrant AMPK activity, NLRP3 inflammasome activation, insulin signaling, and lipid accumulation. AMPK inhibition abolished the regulatory effects of AESN on the NLRP3 inflammasome, insulin signaling, lipid accumulation, and glucose output of hepatocytes following HG exposure. Furthermore, AESN administration reduced blood glucose and serum insulin levels, improved lipid profiles and insulin resistance, and corrected the aberrant AMPK activity and NLRP3 inflammasome activation in liver tissues. CONCLUSION: AESN improves insulin sensitivity via AMPK-mediated NLRP3 inflammasome inhibition.

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.

Pharmacology, phytochemistry, and traditional uses of Scrophularia ningpoensis Hemsl.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophularia ningpoensis Hemsl. (known as Xuanshen) has been used in China for centuries as a traditional medicinal plant to treat numerous diseases including inflammation, hypertension, cancer, and diabetes. AIM OF REVIEW: In this review, we provide an update on the botany, pharmacology, phytochemistry, pharmacokinetics, traditional uses, and safety of S. ningpoensis to highlight future research needs and potential uses of this plant. MATERIALS AND METHODS: All information on S. ningpoensis was obtained from scientific databases including ScienceDirect, Springer, PubMed, Sci Finder, China Knowledge Resource Integrated Database from the China National Knowledge Infrastructure (CNKI), Google Scholar, and Baidu Scholar. Additional information was collected from Chinese herbal medicine books, Ph.D. dissertations, and M.Sc. Theses. Plant taxonomy was verified by "The Plant List" database (http://www.theplantlist.org). RESULTS: S. ningpoensis displays fever reducing, detoxifying, and nourishing 'Yin' effects in traditional Chinese medicine (TCM). More than 162 compounds have been identified and isolated from S. ningpoensis, including iridoids and iridoid glycosides, phenylpropanoid glycosides, organic acids, volatile oils, terpenoids, saccharides, flavonoids, sterols, and saponins. These compounds possess a diverse variety of pharmacological properties that affect the cardiovascular, hepatic, and nervous systems, and protect the body against inflammation, oxidation, and carcinogenesis. CONCLUSIONS: Modern pharmacological studies have confirmed that S. ningpoensis is a valuable Chinese medicinal herb with many pharmacological uses in the treatment of cardiovascular, diabetic, and liver diseases. Most of the S. ningpoensis activity may be attributed to iridoid glycosides and phenylpropanoid glycosides; however, detailed information on the molecular mechanisms, metabolic activity, toxicology, and structure-function relationships of active components is limited. Further comprehensive research to evaluate the medicinal properties of S. ningpoensis is needed.

Chemical Constituents from the Roots of Scrophularia ningpoensis Hemsl and Their Anti-inflammatory Activities / 中国药学杂志

OBJECTIVE: To study the chemical constituents in the roots of Scrophularia ningpoensis Hemsl. METHODSE: Compounds were isolated by chromatographic techniques and their structures were elucidated by spectral methods. The anti-inflammatory activities of all isolated compounds were evaluated by lipopolysaccharides (LPS)-stimulated BV2 cells model. RESULTS: Eighteen compounds were isolated and identified as 2'''-acetyl angroside C (1), saccatoside (2), 6-O-α-L-(2″-O-feruloyl)rhamnopyranosylcatalpol (3), scrophularioside (4), harprocumbide A (5), 6″-O-β-D-glucopyranosylharpagoside (6), harpagoside (7), 8-O-(p-coumaroyl)-harpagide (8), 8-O-feruloylharpagide (9), 6-O-α-D-galactopyranosylharpagoside (10), 6'-O-cinnamoylharpagide (11), angoroside B (12), angoroside C (13), scrophuloside B1 (14), 2-(3-hydroxy-4-methoxyphenyl)ethyl-O-α-L-arabinopyranosyl-(1→6)-O-α-L-rhamnopyranosyl-(1→3)]-β-D-glucopyranoside (15), darendoside B (16), 6-O-caffeoyl-β-D-fructofuranosyl-(2→1)-α-D-glucopyranoside (17), and sibirioside A (18). CONCLUSION: Compound 1 is new compound, and compounds 2-4, 12, 14, and 17 are isolated from this plant for the first time. Compounds 1, 12, and 13 show significant inhibition against nitric oxide production in LPS-stimulated BV2 cells model.

Comparative study on distribution of endophytic fungi in Scrophularia ningpoensis from different habitats / 中草药

Objective: To analyze the distribution of endophytic fungi in Scrophularia ningpoensis from different habitats. Methods: The endophytic fungi in S. ningpoensis from six localities (Pan’an of Zhejiang Province, Ankang of Shaanxi Province, Wuxue of Hubei Province, Shaodong of Hunan Province, Dazhou of Sichuan Province, and Bozhou of Anhui Province) were isolated, identified, and analyzed according to the morphology and ITS sequences. Results: A total of 3 052 strains of endophytic fungi were isolated from S. ningpoensis in six localities. A total of 84 fungal taxa were identified according to the morphology and ITS sequences, these strains were belong to 25 genera. Thereinto Diaporthe, Fusarium, Nigrospora, Alternaria, Phoma, Corynespora, Epicoccum, and Cladosporium were common genera to S. ningpoensis from six localities, but the dominant genus was different: Fusarium was the dominant genus from Anhui, Hubei, Hunan, and Shaanxi; Alternaria was the dominant genus from Sichuan; Diaporthe was the dominant genus from Zhejiang. According to the similarity coefficient, the composition of the endophytic fungi was distinctly different between six localities. The Shannon-wiener diversity index and Simpson index of endophytic fungi in S. ningpoensis from Zhejiang were found higher than others. The diversity of endophytic fungi in S. ningpoensis from Sichuan was lower than others. Conclusion: Systematic studying the diversity and community structure of endophytic fungi in S. ningpoensis and clarifying their distribution regularity in plant tissues can offer basic data and scientific basis for their development and utilization.

Optimization of steaming technology for decoction pieces of Scrophularia ningpoensis by D-optimal response surface methodology based on AHP- entropy weight method / 中草药

Objective :To determine the weight coefficient and optimize the steaming technology of decoction pieces of Scrophularia ningpoensis (SN). Methods The contents of harpagide, harpagoside, aucubin, acteoside, angoroside C, and cinnamic acid were simultaneously determined by HPLC. The weight coefficient of each component was evaluated by AHP-entropy (analyitc hierarchy process) method. With composite score as index, D-optimal response surface methodology was adopted to investigate the effects of soaking time, steaming time, and drying temperature on the quality of processed products and optimize the processing technology of decoction pieces of SN. Results :Optimal processing parameters were as follows: soaking time was 15.63 min, steaming time was 85 min, drying temperature was 60 ℃, and the synthetical mark was 97.20. Considering the actual situation, the optimum processing technology of SN was obtained by fine-turning the soaking time. The soaking time was 15 min, the steaming time was 85 min, and the drying temperature was 60 ℃. Also, the synthetical mark were 98.53, 99.39, 98.86, and its RSD was 0.47% through the obtained conditions in parallel with three batches of samples. Conclusion: The optimized steaming technology is simple and feasible, which can provide a reference for the steaming of decoction pieces of SN. The method established to simultaneously determine the contents of six components in decoction pieces of SN is rapid and reliable for controlling the quality of decoction pieces of SN.

A new iridoid glycoside and a new cinnamoyl glycoside from Scrophularia ningpoensis Hemsl.

A new iridoid glycoside, namely 8-O-(threo-2, 3-dihydroxyl-3-phenyl-propionoyl)-harpagide (1), along with a new cinnamoyl glycoside named as cis-sibirioside A (2), were isolated from Scrophularia ningpoensis Hemsl. Their chemical structures were completely established by spectroscopic methods and comparison with related literatures. Compound 1 exhibited moderate antifouling effect against the settlement of Balanus amphitrite larvae with IC50 being 13.5 µg/mL and LC50 > 25 µg/mL.

Iridoid and phenylpropanoid glycosides from Scrophularia ningpoensis Hemsl. and their α-glucosidase inhibitory activities.

A new phenylpropanoid glycoside, designated Scrophuside (1) and two new iridoid glycosides, respectively named Ningposide I (2) and Ningposide II (3), along with twelve known (4-15) iridoid and phenylpropanoid glycosides were obtained from the roots of Scrophularia ningpoensis Hemsl. by various chromatographic techniques and their structures were established through chemical methods and spectroscopic analyses. Most of the obtained compounds have been screened for α-Glucosidase inhibitory activity, in which compounds 4, 5, 7, 11, 12, 13, and 14 show significant activity.

Genetic structure analysis of cultivated Scrophularia ningpoensis in Zhejiang Province / 中草药

Objective To observe the genetic structure of cultivated Scrophularia ningpoensis in Zhejiang Province.Methods The genetic structures of six typical S.ningpoensis populations were analyzed by fluorescence AFLP marker.Results Bands(12 552) were generated by seven pairs of AFLP primer combinations,of which 8 808 were polymorphic,and the polymorphic rate was 70.17%.The variety ranges of PPB among different populations were 41.67%—55.56%,and 47.30% in average.I was between 0.190 8—0.238 3,and 0.221 8 in average.Ne was between 1.201 4—1.280 6,and 1.236 9 in average.Gst was 0.127 1,Nm was 3.432 4.UPGMA Cluster analysis showed that the six populations can be divided into two clusters,as that of Tiantai,Jinyun,and Jingning were one sub-cluster,and Dongyang,Pan′an,and Xianju were another one sub-cluster.Conclusion There is a relative high genetic diversity level in cultured S.ningpoensis of Zhejiang Province.Genetic differentiation exists among populations,but it exists in population mostly.There is a relative high genetic intercommunion among populations.The genetic distance is not related to the geographic environment.