Two Undescribed Coumarins from Notopterygium incisum with Anti-inflammatory Activity.

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.

Chemical constituents from Notopterygium incisum and their anti-neuroinflammatory activity.

Phytochemical research on an extract of Notopterygium incisum yielded fifteen compounds (1-15), including four previously undescribed compounds (10-13). The structures of the unreported compounds were elucidated by spectroscopic and spectrometric data analysis such as 1D and 2D NMR, IR and HR-ESI-MS. Compounds 1-5 and 10-14 were isolated from N. incisum for the first time. 7S⁎,8R⁎-Phenethyl-(7-methoxy-8-isoeugenol)-ferulate (10), 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) are the undescribed ferulic acid derivatives. Additionly, the anti-neuroinflammatory effects of compounds were evaluated in lipopolysaccharide (LPS)-induced BV2 cells. The pharmacological results showed that 6ß,10ß-epoxy-4α-hydroxy-guaiane (6), teuclatriol (7) and 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) inhibited the production and expression of nitric oxide (NO) in the LPS-induced BV2 cells in a concentration-dependent manner. Acorusnol (4), teucladiol (9), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) only inhibited the release of NO at concentration of 20 µM. Moreover, 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) reduced the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated BV2 cells. The results demonstrated 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) could be a potential anti-neuroinflammatory agent and is worthy of further study.

[Morphological and biochemical characterization during seed development of Notopterygium incisum].

This study aimed to examine the morphological, physiological, and biochemical alterations occurring in Notopterygium incisum seeds throughout their developmental stages, with the objective of establishing a theoretical foundation for the cultivation of superior quality seeds. The experimental materials utilized in this study were the seeds of N. incisum at various stages of development following anthesis. Through the employment of morphological observation and plant physiology techniques, the external morphology, nutrients, enzyme activity, and endogenous hormones of the seeds were assessed. The results revealed a transition in seed coat color from light green to brown during the growth and development of N. incisum seeds. Additionally, as the seeds matured, a decrease in water content was observed. Conversely, starch content exhibited a progressive increase, while sucrose content displayed fluctuations. At 7 days after anthesis, the soluble sugar content attained its highest level of 4.52 mg·g~(-1), whereas the soluble protein content reached its maximum of 6.00 mg·g~(-1) at 14 days after anthesis and its minimum of 4.94 mg·g~(-1) at 42 days after anthesis. The activity of superoxide dismutase(SOD) exhibited an initial increase, followed by a decrease, and eventually reached a stable state. Conversely, the activities of catalase(CAT) and peroxidase(POD) demonstrated a decrease initially, followed by an increase, and then another decrease. The levels of the four endogenous hormones, namely gibberellin(GA_3), zeatin riboside(ZR), auxin(IAA), and abscisic acid(ABA), in the seeds displayed significant variations, with IAA and ABA exhibiting considerably higher levels compared to the other hormones. The levels of plant growth-promoting hormones, represented by IAA, generally displayed a pattern of initial increase followed by a subsequent decrease during seed development, while the plant growth-inhibiting hormone ABA showed the opposite trend. The findings indicate that the alterations in nutrient composition, antioxidant enzyme activity, and endogenous hormone levels vary throughout the maturation process of N. incisum seeds. These observations hold relevance for the cultivation of N. incisum seeds.

Active metabolites and potential mechanisms of Notopterygium incisum against obstructive sleep apnea Syndrome (OSAS): network analysis and experimental assessment.

Background: Notopterygium incisum K.C. Ting ex H.T. Chang, a synonym of Hansenia weberbaueriana (Fedde ex H. Wolff) Pimenov & Kljuykov, is an anti-inflammatory medicinal plant. Although abrnotopterol has been reported to be its primary active metabolite, the other metabolites and their mechanisms of action remain unclear. This study aims to investigate the potential mechanisms by which its active metabolites treat Obstructive Sleep Apnea Syndrome (OSAS) through network analysis and experimental assessment. Methods: The metabolites and potential targets of Notopterygium incisum were extracted from public databases. We searched for OSAS-related genes in the Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Cytoscape 3.9.0 was used to construct the drug-target-disease network and screen for hub genes. Human bronchial epithelial (HBE) cells were cultivated in normoxia and chronic intermittent hypoxia (CIH) medium for 24 h. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) were quantified using enzyme-linked immunosorbent assay (ELISA). Prostaglandin-endoperoxide synthase 2(PTGS2) mRNA was detected using RT-qPCR, while PTGS2 and nuclear factor-kappa B (NF-κB) proteins were identified using Western blot analysis. Co-Immunoprecipitation (CoIP) and Western blotting were utilized to evaluate the ubiquitination of PTGS2 in HBE cells. Results: Pterostilbene and notopterol, isolated from Notopterygium incisum, had potential therapeutic effects on OSAS. The PTGS2 and estrogen receptor alpha (ESR1) hub genes were associated with OSAS. The pathway enrichment analysis focuses on the NF-κB, apoptosis, and HIF-1A pathways. In response to CIH, pterostilbene and notopterol decreased IL-6, TNF-α, and PGE2 levels. The NF-κB pathway was activated by an increase in PTGS2 levels. Pterostilbene promoted proteasome-mediated ubiquitination of PTGS2 protein and reduced PTGS2 levels, inhibiting the NF-κB pathway. Conclusion: This study reveals the active metabolites of Notopterygium incisum and hub genes involved in treating OSAS, which provide a basis for the follow-up development and exploitation of the botanical drug.

Structure Characterization and Anti-Rheumatoid Arthritis Activity of a Polysaccharide from Notopterygium incisum.

SCOPE: Notopterygium incisum is a traditional Chinese medicine that is commonly used to treat rheumatoid arthritis. Polysaccharides from N. incisum can be one of its main active components. However, there have been little investigations on N. incisum polysaccharides. METHODS AND RESULTS: A novel polysaccharide named NIP is extracted from N. incisum with a molecular weight of 2.34 × 106  Da. NIP, composed of arabinose, galactose, glucose, and galacturonic acid, is linked by methyl esterified 1,4-linked α-galacturonic acid, 1,6-linked ß-galactose, 1,5-linked α-arabinose, and 1,4,6-linked ß- glucose. In vitro, NIP can inhibit the NO production of LPS-stimulated RAW264.7 cells. In vivo, NIP relieves toe redness and swelling of AIA rats, reduces the release of inflammatory factors in the serum, and inhibits the activation of NF-κB and JAK/STAT3 signaling pathways. In addition, NIP can effectively decrease oxidative stress, reverse intestinal flora imbalance, and promote butyric acid-producing bacteria's proliferation to exert anti-RA activity. CONCLUSION: NIP may be recommended as a functional food that can alleviate the damage of rheumatoid arthritis.

Water extract of Notopterygium incisum alleviates cold allodynia in neuropathic pain by regulation of TRPA1.

ETHNOPHARMACOLOGICAL RELEVANCE: Neuropathic pain can be debilitating and drastically affects the quality of life of those patients suffering from this condition. The Chinese herb Notopterygium incisum Ting ex H.T. Chang has long been used to disperse "cold". One under examined clinical feature of neuropathic pain is sensitivity to cold. Patients with neuropathic pain or arthritis usually describe a worsening of symptoms during the winter. AIMS OF THIS STUDY: We proposed to test the hypothesis that Notopterygium incisum has a positive effect on the cold sensitivity found in neuropathic pain. MATERIALS AND METHODS: In this study, we established chronic constriction injury (CCI) and cisplatin induced neuropathic pain mice models. Behavioral experiments and physiological examination methods were employed to investigate the effect of water extract of Notopterygium incisum (WN) on cold pain. RESULTS: We found WN reduced cold pain and allyl isothiocyanate (AITC, Transient Receptor Potential A1 (TRPA1 agonist)) induced pain. WN inhibited AITC induced calcium response in HEK 293 cells transfected with TRPA1 and dorsal root ganglion (DRG) neurons. Moreover, we found that oral administration of WN reduced cold allodynia and mechanical allodynia caused by (CCI) and cisplatin induced neuropathic pain. We also observed that oral administration of WN decreased responses to AITC in DRG neurons as well as expression of TRPA1 in the WN treated neuropathic pain model. CONCLUSIONS: The present study provide evidence that Notopterygium incisum alleviates cold allodynia in CCI and cisplatin induced neuropathic pain mouse models. WN alleviated neuropathic pain induced cold allodynia via directly modulating TRPA1. Our findings identify WN as a promising candidate for treating neuropathic pain that highlights a new mechanism of Notopterygium incisum on 'disperse cold'.

Notopterygium incisum Root Extract (NRE) Alleviates Epileptiform Symptoms in PTZ-Induced Acute Seizure Mice.

BACKGROUND: Epilepsy is a common neurological disorder affecting more than 70 million people worldwide. Despite numerous efforts on new antiepileptic drugs, approximately one-third of epilepsy patients suffer from uncontrolled seizures. It leads to serious psychosocial consequences, cognitive problems, and decreased quality of life. OBJECTIVE: Our previous studies have shown that N. incisum root extract (NRE) can improve cognitive dysfunction in Alzheimer's disease (AD) mice. In addition, our research shows that AD and epilepsy have pathological mechanisms overlapping. Therefore, we tried to investigate whether NRE can ameliorate the seizures of epileptic mice in this study. METHODS: NRE-treated mice group was given an oral administration with 1 g/kg/d for 7 days. On the 8th day, mice were exposed to PTZ (i.p. injection) to induce epilepsy. Then the cognitive tests of mice in the water maze were carried out, and the biochemical indexes and pathological tests were carried out after the mice were sacrificed. RESULTS: SOD level in the NRE group was significantly higher than that in the PTZ group, while MDA, TNF-α, and IL-1ß levels were decreased. The cognitive ability of NRE-treated mice was significantly improved compared with the PTZ group. Immunohistochemistry (IHC) results showed that the activation of microglia and astrocytes in the hippocampus and cortex of NRE mice were inhibited. CONCLUSION: This study suggests that NRE can alleviate epilepsy and improve cognitive function in mice with epilepsy, and its mechanism may be through reducing inflammation and enhancing antioxidant defense.

A hypothesis that Notopterol may be effective in COVID-19 via JAK/STAT and other signaling pathways.

COVID-19 is a rapidly spreading disease, causing a global pandemic. It is circulating in multiple countries and causing a series of respiratory infections. Due to the uncertain safety and efficacy of the vaccines and lack of specific medicines, it's important to investigate new pharmacological procedures and find out new drugs that help us eradicate this pandemic. We suggest the hypothesis that Notopterol (NOT), the main Secondary metabolite of Notopterygium incisum Ting ex H.T (a common Chinese medicinal herb), may have the potential benefits on SARS-CoV2 infection for this reasons: (a) NOT exhibits anti-inflammatory, anticancer, and anti-angiogenic properties, (b) NOT indicates a significant reduction in cytokines and chemokines releasing including TNFa, IL-6, interferon-γ, which may decrease COVID-19 cytokine storm (c) NOT can suppress the expression of genes which leads to inflammation via Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway. It is exactly acting like tocilizumab, (an approved drug against COVID-19) and (d) Notopterygium incisum has antiviral activity against influenza virus, it can reduce the viral-induced oxidative stress. By these explanations, it is hopeful that NOT may be effective in COVID-19 infections which needs further investigations to examine Notopterol as a beneficial agent against the SARS-CoV2 infection.

Nitric oxide inhibitory phenolic constituents isolated from the roots and rhizomes of Notopterygium incisum.

Fourteen phenolic constituents, notopheninetols A-E (1-5), notoflavinols A and B (6 and 7), and (2R)-5,4'-dihydroxy-7-O-[(E)-3,7-dimethyl-2,6-octadienyl]flavanone (8a), along with 12 known analogues (8b and 9-19) were isolated from the roots and rhizomes of Notopterygium incisum. Compounds 1-4 and 6-8 were seven pairs of enantiomers, and they were separated by chiral HPLC to obtain the optically pure compounds. The structures of the new compounds were elucidated based on detailed analyses of 1D and 2D NMR and HRESIMS data, and the absolute configurations were determined by quantum chemical calculations of the electronic circular dichroism (ECD) spectra, comparison of the experimental ECD data with those reported, and chemical methods. Compounds 1 and 2 possessed a 1-benzyl-2-methyl-indane skeleton, which was unprecedented in natural source. All of the isolated compounds were evaluated for their nitric oxide (NO) inhibitory effects on RAW264.7 cells induced by LPS, and compounds 6a/6b, 7a, 8a/8b, and the hydrogenated products 6'a and 7'a showed moderate inhibitory activities with IC50 values in the range of 6.2-20.6 µM. Moreover, the interactions of these bioactive compounds with inducible nitric oxide synthase (iNOS) were explored by employing molecular docking simulation.

[Effect of intercropping with Vicia faba on secondary metabolites and rhizosphere soil microbial diversity of Notopterygium incisum].

Rhizosphere soil microbial community and its diversity are important for the structure and functions of medicinal plant ecosystem. In this study, based on high-throughput sequencing, rhizosphere soil microbial diversity, and yield and quality of rhizome and root of Notopterygium incisum cultivated alone(control, CK) and intercropped with Vicia faba(QH) were analyzed, which is expected to lay a basis for optimization of the cultivation mode and ecological production of N. incisum. RESULTS:: showed that the rhizosphere soil bacteria of N. incisum were dominated by Proteobacteria and Bacteroides, with the relative abundance of 50.38%-51.95% and 16.36%-17.02%, respectively. Soil bacterial community at the phylum level was not significantly different between CK and QH. At the genus level, the relative abundance of MND1(3.54%), Spinstomonas(3.50%), Nitrospira(1.53%), and Rhizobacter(1.05%) was significantly higher and that of Gemmatimonas, Candidatus＿Solibacter, and Bryophytes was lower in QH treatment than in the CK. The plant height, leaf length, leaf width, and petiole length of N. incisum in QH treatment was significantly increased and the underground biomass rose by 71.43% compared with those in the CK. Thus, intercropping with V. faba promoted the aboveground growth of N. incisum and improved the yield of root and rhizome. Moreover, the content of notopterol and isoimperatorin increased by 37.96% and 4.09% in QH treatment, respectively, indicating that the intercropping with V. faba boosted the accumulation of secondary metabolites in N. incisum. Pearson's correlation analysis showed that the soil bacterial community was mainly influenced by the soil factors including the content of soil available nutrients, soil organic matter, pH value, and soil water. The influence was in the order: total potassium>total nitrogen>pH>organic matter>available potassium>soil water content>available nitrogen>available phosphorus. In conclusion, the intercropping with V. faba altered soil microenvironment and also increased the yield and accumulation of secondary metabolites of N. incisum, which is a promising ecological planting model for N. incisum.

Falcarindiol Isolated from Notopterygium incisum Inhibits the Quorum Sensing of Pseudomonas aeruginosa.

Quorum sensing (QS) is employed by the opportunistic pathogen Pseudomonas aeruginosa to regulate physiological behaviors and virulence. QS inhibitors (QSIs) are potential anti-virulence agents for the therapy of P. aeruginosa infection. During the screening for QSIs from Chinese herbal medicines, falcarindiol (the major constituent of Notopterygium incisum) exhibited QS inhibitory activity. The subinhibitory concentration of falcarindiol exerted significant inhibitory effects on the formation of biofilm and the production of virulence factors such as elastase, pyocyanin, and rhamnolipid. The mRNA expression of QS-related genes (lasB, phzH, rhlA, lasI, rhlI, pqsA, and rhlR) was downregulated by falcarindiol while that of lasR was not affected by falcarindiol. The transcriptional activation of the lasI promoter was inhibited by falcarindiol in the P. aeruginosa QSIS-lasI selector. Further experiments confirmed that falcarindiol inhibited the las system using the reporter strain Escherichia coli MG4/pKDT17. Electrophoretic mobility shift assay (EMSA) showed that falcarindiol inhibited the binding of the transcription factor LasR and the lasI promoter region. Molecular docking showed that falcarindiol interacted with the Tyr47 residue, leading to LasR instability. The decrease of LasR-mediated transcriptional activation was responsible for the reduction of downstream gene expression, which further inhibited virulence production. The inhibition mechanism of falcarindiol to LasR provides a theoretical basis for its medicinal application.

Imperatorin Interferes with LPS Binding to the TLR4 Co-Receptor and Activates the Nrf2 Antioxidative Pathway in RAW264.7 Murine Macrophage Cells.

Imperatorin (IMP) could downregulate several inflammatory transcription factor signaling pathways. Some studies have pointed out that IMP could interfere with toll-like receptor 4 (TLR4) signaling. This study evaluates how IMP interferes with the TLR4 co-receptors signaling through the protein-ligand docking model, Western blotting, immunofluorescence (IF), and atomic force microscopy (AFM) assays in lipopolysaccharide (LPS) stimulated macrophage-like RAW264.7 cells in vitro. The results of the protein-ligand docking demonstrate that IMP interferes with LPS binding to the LPS-binding protein (LBP), the cluster of differentiation 14 (CD14), and the toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD-2) co-receptors in LPS-stimulated RAW264.7 cells. Compared with TLR4 antagonist CLI-095 or dexamethasone, IMP could suppress the protein expressions of LBP, CD14, and TLR4/MD-2 in LPS-stimulated cells. Furthermore, the three-dimensional (3D) image assay of the AFM showed IMP could prevent the LPS-induced morphological change in RAW264.7 cells. Additionally, IMP could activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, and it increased the antioxidative protein expression of heme oxygenase-1 (HO-1), superoxidase dismutase (SOD), and catalase (CAT). Our results are the first to reveal that the anti-inflammatory effect of IMP interferes with LPS binding to TLR4 co-receptor signaling and activates the antioxidative Nrf2 signaling pathway.

[Comparison of soil hydraulic properties in wild and cultivated areas of Notopterygium incisum].

To clarify the difference of soil moisture characteristics between mixed broad leaf-conifer forest soil and artificial cultivation of Notopterygium incisum, the HYPROP system and the dew point potential meter were used to determine soil water retention curves(SWRC) for samples of two horizons(i.e. 2-7 cm, 10-15 cm). The basic physical and chemical properties of soil and its water characteristic parameters were also determined. The result showed as fllows:①The bulk density of mixed coniferous-broad leaf forest soil was between 0.33 and 0.52 g·cm~(-3), significantly lower than the corresponding value of field soil(1.01-1.18 g·cm~(-3))(P<0.05), While the organic matter content was significantly higher than the corresponding value of field soil(P<0.05). ②The saturated water content(θ_s), field water holding capacity(θ_(FC)) and Water that can be effectively utilized by plants(θ_(PAC)) of mixed coniferous-broadleaved forest soil were significantly higher than the corresponding value of field soil(P<0.05), while the retained water content(θ_r) value that cannot be effectively utilized by plants was significantly lower than that of field soil(P<0.05). ③The values of structural porosity(0.13-0.24 cm~3·cm~(-3)) and Matrix porosity(0.34-0.44 cm~3·cm~(-3)) of mixed coniferous-broadleaved forest soil were higher than the corresponding values of field soil. Therefore, with low bulk density and high content of organic matter, mixed coniferous-broadleaved forest soil can store more water in soil in the form of effective water to meet the needs of plants for water, thus possibly forming high quality medicinal materials of Notopterygii Rhizoma et Radix. In conclusion, the results of this study can provide theoretical basis guidance for soil structure improvement and water management to form high quality medicinal materials in the artificial cultivation of N. incisum.

Structural analyses of the HG-type pectin from notopterygium incisum and its effects on galectins.

In the manuscript, water-soluble polysaccharides WPNI was extracted from notopterygium incisum roots and separated into two homogeneous fractions WPNI-A-a and WPNI-A-b. WPNI-A-a was an arabinogalactan (AG). WPNI-A-b belonged to HG type pectin. The structure of WPNI-A-b was analyzed by FT-IR, NMR, enzymatic hydrolysis (Endo-PG) and UPLC-FLD-MSn. WPNI-A-b was dominated by HG domain, covalently linked with AG and RG-II domains. Oligogalacturonides produced by Endo-PG from HG domain were non-, mono-, di- or tri-methyl esterified with degree of polymerization (DP) from 1 to 6. The distribution of methyl-ester groups was in a block-wise manner. The interaction of WPNI-A-b and its enzymatic hydrolysis products with galectin-1, galectin-3, galectin-7 and galectin-8 showed that AG domain exhibited stronger binding avidity to galectins than RG-II and HG domain, while oligogalacturonides showed no binding activities to galectins. The results would be useful for the application of the pectin from notopterygium incisum.

[Correlation between growth characteristics and quality of rhizomes of Notopterygium incisum under wild tending].

Study the growth and development process of rhizomes(bamboo-like part) of Notopterygium incisum and the changes of carbohydrate, endogenous hormones and secondary metabolites, and provide theoretical guidance for the formation of high-quality N. incisum medicinal commodities under artificial cultivation. The One-year-old seedlings were transplanted to the original habitat,and the growth and physiological characteristics of N. incisum were dynamically monitored. The results showed that: ① Seedlings transplanted to the original habitat in spring could form rhizomes(bamboo-like part) in the same year. ② After 60 days of transplantation, the root length and root diameter of underground part of N. incisum had increased rapidly, and carbohydrate content in roots and rhizomes had accumulated rapidly. After 120 days of transplantation, the roots and rhizomes of underground part had grown slowly, and starch content in roots and rhizomes increased continuously, while sucrose and total soluble sugar content decreased gradually. ③ The content of abscisic acid(ABA) in rhizomes decreased firstly and then increased, while the indole acetic acid(IAA) content stabilized firstly and then increased rapidly, and the contents of gibberellin(GA_3) and zeatin riboside(ZR) continued to increase. ④ The content of notopterol in rhizomes was higher than that in roots, while the content of isoimperatorin was lower than that in roots, but the total content of the both in rhizomes was higher than that in roots. Therefore, N. incisum can form rhizomes with high content of secondary metabolites under wild tending, and the growth and development of rhizomes are closely related to changes in carbohydrates and are regulated by related endogenous hormones.

Potential distribution of Notopterygium incisum Ting ex H. T. Chang and its predicted responses to climate change based on a comprehensive habitat suitability model.

Notopterygium incisum Ting ex H. T. Chang is a rare and endangered traditional Chinese medicinal plant. In this research, we built a comprehensive habitat suitability (CHS) model to analyze the potential suitable habitat distribution of this species in the present and future in China. First, using nine different algorithms, we built an ensemble model to explore the possible impacts of climate change on the habitat distribution of this species. Then, based on this model, we built a CHS model to further identify the distribution characteristics of N. incisum-suitable habitats in three time periods (current, 2050s, and 2070s) while considering the effects of soil and vegetation conditions. The results indicated that the current suitable habitat for N. incisum covers approximately 83.76 × 103 km2, and these locations were concentrated in the Tibet Autonomous Region, Gansu Province, Qinghai Province, and Sichuan Province. In the future, the areas of suitable habitat for N. incisum would significantly decrease and would be 69.53 × 103 km2 and 60.21 × 103 km2 in the 2050s and 2070s, respectively. However, the area of marginally suitable habitat would remain relatively stable. This study provides a more reliable and comprehensive method for modelling the current and future distributions of N. incisum, and it provides valuable insights for highlighting priority areas for medicinal plant conservation and resource utilization.

Rapid discrimination of Notopterygium incisum and Notopterygium franchetii based on characteristic compound profiles detected by UHPLC-QTOF-MS/MS coupled with multivariate analysis.

INTRODUCTION: The herbs Notopterygium incisum (NI) and N. franchetii (NF) are referred to as "Qianghuo" in the Chinese Pharmacopeia and are popular for treatment of certain conditions, including headaches, rheumatoid arthritis and the common cold. Recently, several adulterations of NI and NF have been found in the Chinese herbal market. OBJECTIVE: The aim of this study was to rapidly identify the unique characteristic compounds of NI and NF, to discriminate Qianghuo from its adulterations. METHODOLOGY: Twenty-four batches of NI and NF samples with different origins were collected and extracted with methanol. The extracts were analysed using ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS). Principal component analysis (PCA) and orthogonal partial squared discriminant analysis (OPLS-DA) were then used to distinguish between NI and NF and to identify their potential characteristic markers. RESULTS: Fifty compounds were identified or tentatively characterised according to the retention time, m/z value and MS/MS fragment analysis. Six compounds were selected as potential markers of NI and NF by PCA and OPLS-DA. They were successfully applied to authenticate 17 kinds of Chinese patent medicines containing Qianghuo. The markers could not be detected in three of the Chinese patent medicines, indicating that they were counterfeit products. CONCLUSION: The UHPLC-QTOF-MS/MS coupled with the multivariate analysis method could discriminate NI and NF from their adulterations. Moreover, the data clearly demonstrated significant differences in the chemical compositions of NI and NF. Further research is needed to examine the relationship between therapeutic efficacy and the chemical constituents of NI and NF.

Notopterygium incisum extract (NRE) rescues cognitive deficits in APP/PS1 Alzhneimer's disease mice by attenuating amyloid-beta, tau, and neuroinflammation pathology.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a frequently occurring disease of the elderly, and "deficiency" is the root of AD. Most famous experts of traditional Chinese medicine believe that the disease is based on deficiency, and the deficiency of kidney essence is the basis. Notopterygium incisum (Qiang huo) is beneficial to bladder, liver, and kidneys. It is used to treat liver and kidney deficiency, language difficulties, and mental coma. Qiang huo yu feng tang has been used to treat liver and kidney deficiency, unclear language and mental paralysis in many traditional Chinese medicine books and records. In modern times, it has been used to treat AD and exhibited favourable efficacy. AIM OF THE STUDY: This study attempts to investigate the effects of furocoumarins from Notopterygium incisum (NRE) on the Aß cascade, tau pathology and inflammatory pathology of AD. MATERIALS AND METHODS: In this study, we reported a detailed protocol for stabilizing HEK APPswe293T cells with lentivirus for the first time. This cell line can secrete high concentration of Aß. In addition, we treated N2a cells with AKT/PKC specific inhibitors (wortmannin/GF-109203X) and established a tau pathological cell model (AKT/PKC N2a) by activating GSK3ß and triggering hyperphosphorylation of tau. The Aß levels and the expression of phosphorylated tau were detected by ELISA and Western blot. The cognitive ability of NRE on APP/PS1 mice was detected using a Morris water maze (MWM) assay and Aß contents were also evaluated. RESULTS: In HEK APPswe293T cells, NRE (10, 20, 40 µg/mL) significantly inhibited the secretion and production of Aß in dose dependent manner. In addition, NRE also suppressed the expression of phosphorylated tau in wortmannin/GF-109203X treated N2a cells. Furthermore, NRE ameliorated the cognitive impairment of APP/PS1 mice, and the contents of Aß, IL-1ß and TNF-α were significantly depressed in hippocampus and cortex. CONCLUSION: In conclusion, our results demonstrated that NRE has a potential anti-AD effect via the inhibition of the Aß cascade, tau pathology and neuroinflammation in vitro and in vivo.

Correlation between growth characteristics and quality of rhizomes of Notopterygium incisum under wild tending / 中国中药杂志

Study the growth and development process of rhizomes(bamboo-like part) of Notopterygium incisum and the changes of carbohydrate, endogenous hormones and secondary metabolites, and provide theoretical guidance for the formation of high-quality N. incisum medicinal commodities under artificial cultivation. The One-year-old seedlings were transplanted to the original habitat,and the growth and physiological characteristics of N. incisum were dynamically monitored. The results showed that: ① Seedlings transplanted to the original habitat in spring could form rhizomes(bamboo-like part) in the same year. ② After 60 days of transplantation, the root length and root diameter of underground part of N. incisum had increased rapidly, and carbohydrate content in roots and rhizomes had accumulated rapidly. After 120 days of transplantation, the roots and rhizomes of underground part had grown slowly, and starch content in roots and rhizomes increased continuously, while sucrose and total soluble sugar content decreased gradually. ③ The content of abscisic acid(ABA) in rhizomes decreased firstly and then increased, while the indole acetic acid(IAA) content stabilized firstly and then increased rapidly, and the contents of gibberellin(GA_3) and zeatin riboside(ZR) continued to increase. ④ The content of notopterol in rhizomes was higher than that in roots, while the content of isoimperatorin was lower than that in roots, but the total content of the both in rhizomes was higher than that in roots. Therefore, N. incisum can form rhizomes with high content of secondary metabolites under wild tending, and the growth and development of rhizomes are closely related to changes in carbohydrates and are regulated by related endogenous hormones.

Coumarins from Notopterygium incisum and their inhibitory effect against lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells / 中草药

Objective: To study coumarins from Notopterygium incisum and their anti-inflammatory effect. Methods: Coumarins were separated and purified by repeated column chromatography on silica gel and HPLC, and their chemical structures were determined by spectral data analyses of MS and NMR. Lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells accompanying overproduction of pro-inflammatory mediator nitric oxide (NO) were applied to investigate the anti-inflammatory effect of these purified coumarins. Results: Twenty-four coumarins were obtained and identified as isoimperatorin (1), angenomalin (2), psoralen (3), bergapten (4), capillarin (5), osthenol (6), 5-dehydronotopterol (7), anhydronotopoloxide (8), 7'-O-methylnotoptol (9), bergamottin (10), 7-isopentenyloxy-6-methoxy-coumarin (11), pabulenol (12), notopterol (13), demethylfuropinarine (14), notoptol (15), cnidilin (16), 6-isopentenyloxyumbelliferone (17), nodakenitin (18), isopimpinellin (19), nodakenin (20), decuroside V (21), decuroside I (22), marmesin-11-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (23), and forbesoside (24), respectively. Coumarins 7-10, 13, and 15 exhibited potent inhibitory activity against LPS-induced NO production in RAW 264.7 cells with half maximal inhibitory concentration values from 8.50 to 35.12 μmol/L. Conclusion: Compound 7 is a new natural product; compound 17 is obtained from the roots and rhizomes of N. incisum for the first time; Unsaturated double bond on C-5 in the aromatic ring significantly improved the anti-inflammatory activity of coumarins.