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A novel trimeric monoterpenoid indole alkaloid, vincarostine A (1) consisting of an aspidosperma-iboga-aspidosperma type skeleton, was isolated from the whole plant of Catharanthus roseus. The structure including absolute stereochemistry was elucidated on the basis of 2D NMR data and CD spectrum. Vincarostine A (1) showed anti-malarial activity., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

A new dimeric indole alkaloid, vincazalidine A consisting of an aspidosperma type and a modified iboga type with 1-azatricyclo ring system consisting of one azepane and two piperidine rings coupled with an oxazolidine ring was isolated from Catharanthus roseus, and the structure including absolute stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Vincazalidine A induced G2 arrest and subsequent apoptosis in human lung carcinoma cell line, A549 cells., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

We examined ammonium glycyrrhizate listed in the monographs of the European Pharmacopoeia (EP) and United States Pharmacopoeia (USP) as well as in the reagents and solutions used in the general test of the Japanese Pharmacopoeia by performing HPLC on their sample standards or reference reagents under reported and modified conditions. Comparative experiments involving five authentic samples, namely, 18β-glycyrrhizin (1), 18α-glycyrrhizin (2), licorice-saponin G2 (3), licorice-saponin H2 (4), and galacturonic acid-replaced glycyrrhizin (the 4″-epimer of 18β-glycyrrhizin) (5), led us to propose the revision of the peak assignment of 18α-glycyrrhizin (2) and postscript a possible co-existence of galacturonic acid-replaced glycyrrhizin (5) as a hidden component in the EP and USP. We also proposed that the α-configuration used in the nomenclature of the glycosidic bond between aglycone and the sugar units of ammonium glycyrrhizate and impurities in the EP and USP should be revised to the β-configuration., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Cliniatines A-C (1-3), three new Amaryllidaceae alkaloids, consisting of 2,6-dimetylpyridine and lycorine-type and/or galanthamine-type were isolated from Clivia miniata (Lindl.) Bosse. The structures and absolute configurations of 1-3 were elucidated based on spectroscopic data and chemical correlation. Cliniatines A-C showed moderate inhibitory activity against acetylcholinesterase., (© 2021. The Japanese Society of Pharmacognosy.)

A novel Lycopodium alkaloid, complanadine F (1), seco-complanadine A type was isolated from the club moss Lycopodium complanatum. The planar structure and relative configuration were elucidated based on spectroscopic data.

Saposhnikoviae Radix (SR), derived from the dried root and rhizome of Saposhnikovia divaricata, is a popular crude drug used in traditional Chinese and Japanese medicine. To evaluate the metabolites of S. divaricata roots from Mongolia and to investigate their geographical variation, we developed the HPLC method, determined the contents of 9 chromones and 4 coumarins, and conducted multivariate statistical analysis. All Mongolian specimens contained prim-O-glucosylcimifugin (1) and 4'-O-β-D-glucosyl-5-O-methylvisamminol (3), and their total amount (5.04-25.06 mg/g) exceeded the criterion assigned in the Chinese Pharmacopoeia. Moreover, the content of 1 (3.98-20.79 mg/g) was significantly higher in the Mongolian specimens than in Chinese SR samples. The specimens from Norovlin showed the highest contents of 1 and 3. The total levels of dihydropyranochromones were higher in the specimens from Bayan-Uul. The orthogonal partial least squares-discriminant analysis revealed that the Mongolian specimens tended to be separated into three groups based on growing regions, in which several chromones contributed to each distribution. Furthermore, 1 H NMR analysis revealed that Mongolian specimens had less amount of sucrose and a substantial amount of polyacetylenes. Thus, in this study, the chemical characteristics of Mongolian S. divaricata specimens were clarified and it was found that the specimens from the northeast part of Mongolia, including Norovlin, had the superior properties due to higher amounts of major chromones.

Previously, we established a 1 H NMR metabolomics method using reversed-phase solid-phase extraction column (RP-SPEC), and succeeded in distinguishing wild from cultivated samples of Saposhnikoviae radix (SR), and between SR and its substitute, Peucedanum ledebourielloides root (PR). Herein, we performed LC-HR/MS metabolomics using fractions obtained via RP-SPEC to identify characteristic components of SR and PR. One and three characteristic components were respectively found for SR and PR; these components were isolated with their m/z values and retention times as a guide. The characteristic component of SR was identified as 4'-O-β-D-glucosyl-5-O-methylvisamminol (1), an indicator component used to identify SR in the Japanese Pharmacopoeia. In contrast, the characteristic components of PR were identified as xanthalin (2), 4'-O-β-D-apiosyl (1 → 6)-β-D-glucosyl-5-O-methylvisamminol (3), and 3'-O-β-D-apiosyl (1 → 6)-β-D-glucosylhamaudol (4) based on spectroscopic data such as 1D- and 2D-NMR, MS, and specific optical rotation. Among them, 4 is a novel compound. For the correlation between the NMR metabolomics results in the present and our previous report, only 1 and 2 were found to correlate with the chemical shifts, and the other compounds had no correlation. As the chemical shifts for compounds 1, 3, and 4 were similar to each other, especially for the aglycone moiety, they could not be distinguished because of the sensitivity and resolution of 1 H NMR. Accordingly, combining NMR and LC/MS metabolomics with their different advantages is considered useful for metabolomics of natural products. The series of methods used in our reports could aid in quality evaluations of natural products and surveying of marker components.

1 H NMR-based metabolomics has been applied in research on food, herbal medicine, and natural products. Although excellent results were reported, samples were directly extracted with a deuterated solvent (e.g., methanol-d 4 or D 2 O) in most reports. As primary metabolites account for most of the results, data for secondary metabolites are partially reflected. Consequently, secondary metabolites tend to be excluded from factor loading analysis, serving as a significant unfavorable feature of 1 H NMR-based metabolomics when investigating biologically active or functional components in natural products and health foods. Reversed-phase solid-phase extraction column (RP-SPEC) was applied for sample preparation in 1 H NMR-based metabolomics to overcome this feature. The methanol extract from Saposhnikoviae radix (SR), an important crude drug, was fractionated with RP-SPEC into 5% methanol-eluting fractions, and the remaining fraction was collected. Each fraction was subjected to 1 H NMR-based metabolomics and compared to results from conventional 1 H NMR-based metabolomics. Based on principal component analysis (PCA) and partial least squares projections to latent structures discriminant analysis (PLS-DA), the 5% methanol fraction and conventional method reflected the amount of saccharides such as sucrose on the PC1/PLS1 axes, and wild and cultivated samples were discriminated along those axes. The remaining fraction clearly distinguished SR from Peucedanum ledebourielloides root. The compounds responsible for this discrimination were deemed falcarindiol derivatives and other unidentified secondary metabolites from the s-plot on PLS-DA. The secondary metabolites from original plants were, therefore, presumed to be concentrated in the remaining fraction by RP-SPEC treatment and strongly reflected the species differences. The developed series is considered effective to perform quality evaluation of crude drugs and natural products.

Ephedra Herb is a crude drug defined as the terrestrial stem of Ephedra sinica, E. intermedia, or E. equisetina. It is often used to treat headaches, bronchial asthma, nasal inflammation, and the common cold. In this study, we isolated characteristic non-alkaloidal constituents from the extracts and identified them in relation to the habitat of Ephedra Herb. Extracts were prepared from Ephedra Herb collected from Inner Mongolia and Gansu. High-performance liquid chromatography was performed to quantitatively analyse the amount of ephedrine alkaloids in each extract. We compared the chemical compositions of the extracts by thin layer chromatography (TLC) to find spot characteristics depending on the habitat. 1 H-NMR, 13 C-NMR, and 2D-NMR spectra of the samples were also examined. The ephedrine content of all extracts satisfied the quality standard stated in the Japanese Pharmacopoeia. Nonetheless, we found each notable constituent characteristic to the Ephedra Herbs from both habitats. In order to identify them, Ephedra Herb extracts were separated by column chromatography, resulting in the isolation of (±)-α-terpineol-β-D-O-glucopyranoside (1) and (E)-7-hydroxy-3,7-dimethyloct-2-en-1-yl-β-D-O-glucopyranoside (2) as the characteristic constituents in Ephedra Herb from Inner Mongolia. Epheganoside (3), a new eudesmane-type sesquiterpene glycoside, and scopoletin (4) were found to be the characteristic constituents in Ephedra Herb from Gansu. The results obtained from this study can be used to distinguish between the habitats of Ephedra Herb.

As part of our continuing study of ephedrine alkaloids-free Ephedra Herb extract (EFE) in pursuit of its approval as a crude drug preparation, we identified two quantitative markers for the quality control of the manufacturing process of EFE and sought to establish cost-effective and simple methods for quantitative analyses. We analysed Ephedra Herb extracts grown in different habitats and collection years by liquid chromatography/high-resolution mass spectrometry (LC/HRMS) and detected two notable peaks common to each extract. These peaks were identified as vicenin-2 (1) and isovitexin 2″-O-rhamnoside (2). Quantitative analyses using the isocratic condition of LC/MS showed that the content percentages of 1 and 2 in EFE were 0.140-0.146% and 0.350-0.411%, respectively. We concluded that 1 and 2 were adequate quality control markers for quantitative analysis of EFE. Furthermore, we quantitatively analysed apigenin (3), an aglycon common to 1 and 2, and found that the conversion factors of 1 to 3 and 2 to 3 were 1.3 and 1.5, respectively. Therefore, we concluded that 3 was a secondary standard for quantifying the contents of 1 and 2 in EFE. A series of results obtained from this study will be valuable for the quality control of EFE.

Delayed coil migration after endovascular treatment with detachable coils, particularly several months after treatment, is extremely rare. In this report, the authors describe a 77-year-old female in whom delayed coil migration to the anterior cerebral artery and posterior communicating artery (PCoA) developed 3 months after an uncomplicated aneurysm embolization. The patient was successfully retreated with a closed-cell stent. Computational fluid dynamics (CFD) revealed high wall shear stress (WSS) and multiple vortices in the residual cavity of the initially treated aneurysm. CFD could be useful to detect and predict this complication, and a stent-assisted technique could be an important treatment option.

This is the first report on the mechanism of pseudoaneurysm formation after withdrawal of a stent retriever. A 79-year-old woman developed cardiogenic embolization of the distal middle cerebral artery (M2). The deployed stent retriever bent because of vessel tortuosity. After withdrawal of the stent with strong resistance, complete revascularization was achieved, but an extravasation was detected at the site. Eight hours after disappearance of the extravasation, re-bleeding occurred with aneurysm-like pooling of contrast media. Direct surgical observation confirmed a pseudoaneurysm formation. The pseudoaneurysm was likely formed by avulsion of a fine vessel during withdrawal of the stent retriever at a tortuous vessel.

Background: Arteriovenous shunting visualized by angiography is one of the major features of glioblastomas, and the visualization is dependent on the presence of extensive shunting. Extensive arteriovenous shunting is associated with the risk of poorly controlled intraoperative bleeding. When a tumor with extensive arteriovenous shunting is located in close proximity to the eloquent regions of the brain, a meticulous surgical procedure is necessary. In the present study, the site-oriented visualization of angiographical arteriovenous shunting was evaluated from the perspective of surgical treatment, with a particular focus on the perisylvian region that is in close proximity to motor and language regions (dominant hemisphere), as well as large arteries and veins., Methods: Twenty-six consecutive patients underwent a resection of glioblastoma between February 2007 and September 2012. All patients were presurgically examined using digital subtraction angiography. The patients were subdivided into the following two groups based on the location of the tumor: 1) perisylvian glioblastoma (18 patients) and 2) non-perisylvian glioblastoma (eight patients). Angiography to detect the arteriovenous shunting was performed. In addition, the number of intratumoral vessels, tumor proliferative activity (MIB-1 labeling index), and volume of intraoperative bleeding were evaluated and compared between the two groups., Results: Angiographical arteriovenous shunting was definitively visualized in 13 of 18 (72 %) perisylvian glioblastomas, in contrast to only one of eight (13 %) non-perisylvian glioblastomas (p = 0.007). There were no significant differences between the two groups with respect to the number of intratumoral vessels, MIB-1 labeling index, and volume of intraoperative bleeding. However, massive intraoperative bleeding of > 2,000 mL occurred in one perisylvian glioblastoma patient., Conclusions: Glioblastomas in the perisylvian region tend to be associated with extensive arteriovenous shunting that can be definitively visualized by performing an angiography. Because arteriovenous shunting carries the risk of intraoperative bleeding, perisylvian glioblastomas-particularly in the dominant hemisphere-should be resected with a meticulous surgical procedure and strategy.

High-grade (World Health Organization grades II and III) meningiomas grow aggressively and recur frequently, resulting in a poor prognosis. Assessment of tumor malignancy before treatment initiation is important. We attempted to determine predictive factors for high-grade meningioma on magnetic resonance (MR) imaging before surgery. We reviewed 65 meningiomas (39 cases, benign; 26 cases, high-grade) and assessed four factors: (1) tumor-brain interface (TBI) on T1-weighted imaging (T1WI), (2) capsular enhancement (CapE), i.e., the layer of the tumor-brain interface on gadolinium-enhanced T1WI (T1Gd), (3) heterogeneity on T1Gd, and (4) tumoral margin on T1Gd. All four factors were useful in distinguishing high-grade from benign meningiomas, according to univariate analysis. On multivariate regression analysis, unclear TBI and heterogeneous enhancement were independent predictive factors for high-grade meningioma. In meningiomas with an unclear TBI and heterogeneous enhancement, the probability of high-grade meningioma was 98%. Our data suggest that this combination of factors obtained from conventional sequences on MR imaging may be useful to predict high-grade meningioma.

Here, we report the case of a patient with cerebellar high-grade glioma that developed after the patient underwent treatment for medulloblastoma. A 34-year-old man visited our hospital with complaints of dizziness and truncal ataxia. Magnetic resonance image showed a cerebellar tumor with multiple cavernomas and two lesions that were suspected to be meningiomas. The cerebellar tumor was surgically removed. According to pathological examination, the tumor was a high-grade glioma that was positive for methylated O-6-methylguanine-DNA methyltransferase promoter. In the past, he had received radiotherapy at the age of 5, after which he was operated for desmoplastic medulloblastoma in his right cerebellar hemisphere. Seven years after the initial therapy, cavernoma-induced intracerebral hemorrhage of the right temporal lobe was noted. To our knowledge, this is the first case of radiation-induced double intracranial tumors accompanied by symptomatic cavernoma.

Although there are many reports on the clinical use of the MIB-1 labeling index (LI), which is a measure of proliferative activity in astrocytomas; its significance varies between studies. There are no known molecules that are directly linked to the MIB-1 LI in astrocytomas. We evaluated the clinical value of the MIB-1 LI in our human glioblastoma cases and determined the molecules that possibly influenced the MIB-1 LI. An immunohistochemical study of the MIB-1 protein was performed and MIB-1 LIs of 38 glioblastomas were determined. In the same cases, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-alpha (PDGFRA), and sphingosine-1-phosphate receptor type 1 (S1P(1)), which are known regulators of glioma cell proliferation, were detected and quantified by quantitative real-time-PCR or western blotting. Kaplan-Meier survival curves for 38 patients with glioblastomas showed that a high MIB-1 LI correlated with poor survival (P < 0.05). Among the molecules tested, only the low expression of S1P(1) was significantly correlated with the high MIB-1 LI in glioblastomas (P < 0.05). Multivariate analysis revealed that the S1P(1) expression level was a significant prognostic factor. Our results indicate that the MIB-1 LI is an important prognostic factor in human glioblastomas. Furthermore, downregulation of S1P(1) expression increases proliferative activity, and thus enhances the malignancy of glioblastomas, resulting in a poor survival.