Journal of Natural Medicines最新文献

Ferroptosis is a unique programmed cell death driven by iron-dependent phospholipid peroxidation. Tumor cells that escape from the conventional therapies appear more sensitive to ferroptosis. Therefore, it is extremely urgent to find safe and efficient active ingredients that induce ferroptosis in tumor cells. Herein, we identified that angelic acid, as a potent anti-tumor active ingredient in Angelica sinensis, profoundly sensitizes CRC cells to ferroptosis via a natural compound library screen. We revealed that angelic acid treatment is sufficient to predispose CRC cells to ferroptosis phenotype, evidenced by malondialdehyde (MDA) accumulation, lipid peroxidation, and upregulation of ferroptosis-associated markers CHAC1 and PTGS2, which is abolished by ferroptosis inhibitor Fer-1. Moreover, the results of network pharmacology showed that NRF2 is critical for angelic acid-mediated CRC cell ferroptosis. Mechanistically, angelic acid exerted its ferroptosis induction via directly binding and facilitating the degradation of NRF2. In addition, the syngeneic mouse models revealed that angelic acid boosts CRC cell sensitivity to ferroptosis inducer sulfasalazine with essentially no toxicity in vivo. Collectively, our findings highlighted a previously unrecognized anti-tumor mechanism of angelic acid and represented an appealing therapeutic strategy for CRC treatment.

The inhibition of amyloid β (Aβ) aggregation and degradation of Aβ aggregates are promising approaches for treating and preventing Alzheimer's disease. In our search for Aβ42 aggregation inhibitors, we isolated seven undescribed meroterpenoids, sargasilides A (1)‒G (7), from brown alga (Sargassum siliquastrum) collected at Noto Peninsula in Japan. We structurally elucidated the isolated meroterpenoids using spectroscopic data and evaluated their activities using Thioflavin T assay and transmission electron microscopy. Among the seven compounds isolated, sargasilide B had the strongest inhibitory activity. From the comparison of structure and activity, the geometric isomerism of olefins and length of isoprene side chains are important for the activity of meroterpenoids isolated from brown alga.

Epilepsy, characterized by recurrent seizures, often accompanies neurocognitive impairments and is associated with increased oxidative stress and inflammation. This study investigates the possible neuroprotective properties of glycitin, a soy isoflavone, on memory impairment, its impact on oxidative stress responses, and inflammatory gene expression in a chronic epileptic rat model induced by pentylenetetrazol (PTZ). Glycitin was administered at varying doses to evaluate its potential neuroprotective impact on memory, oxidative stress, and inflammation in this model. Behavioural assessments, memory retention and recall capabilities, histopathological examinations, measurements of oxidative stress biomarkers, and molecular assessments were employed for comprehensive evaluation. The results demonstrated that glycitin significantly improved memory impairment and reduced oxidative stress in epileptic rats. Additionally, glycitin treatment decreased the expression of tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-κB), indicating its potential to modulate the inflammatory response associated with epilepsy. These observations underscore the potential of glycitin as a therapeutic candidate for mitigating memory impairments linked to chronic epilepsy due to its antioxidant and anti-inflammatory properties, offering insights into novel avenues for the development of targeted interventions aimed at preserving cognitive function and ameliorating oxidative damage and inflammation in epileptic conditions.

As crude drugs are natural products, their quality may vary. However, the degradation of the active ingredients in the compositional changes that occur during processing and preparation also affects the medicinal properties of the Kampo formula, which uses herbal medicines; therefore, a detailed investigation of the effects of compositional changes during preparation is required. Plant constituents vary in content depending on the year of cultivation and the plant part; however, detailed studies have rarely been reported for some crude drugs. Liquid chromatography-nuclear magnetic resonance/mass spectrometry revealed the degradation process of saponins, which are unstable components of the crude drug "Achyranthes root." The presence of diterpenes unstable with respect to drying temperature in the leaves of the crude drug "Leonurus herb" was revealed and their structures were elucidated. At the examination stage of the degradation process of perillaldehyde, the characteristic aromatic component of Perilla herb, it was elucidated that some specimens contained a small amount of perillaldehyde and that they contained more α-asarone. A trend toward lower ephedrine content was observed toward the tip of the above-ground branching of the Ephedra herb. Multivariate analysis was also introduced into the quality assessment of crude drugs and was established as a tool to identify bioactive compounds using the component diversity of crude drugs and to elucidate component differences due to the cultivation environment.

Lysiphyllum binatum (Blanco) de Wit in the Fabaceae family, despite its traditional medicinal uses, has not been the subject of prior scientific inquiry into its chemical and biological profile. The dichloromethane and MeOH extracts of its roots exhibited notably similar antioxidant activity, while the dichloromethane extract of the vine stems showed aromatase inhibition. This study aimed to identify the bioactive components responsible for these activities. Chemical investigation of the roots led to the isolation of six new metabolites, named lysiphans A-F (1-6), along with eight known compounds (7-14). The vine stem yielded lysiphan C (3) and compound 7, as well as five known isolates (15-19). The structures of these metabolites were determined through NMR spectral analysis, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and Mosher's modifications to establish their absolute configurations. The biogenetic relationships between the new compounds were proposed. Several of the isolates were evaluated for their antioxidant, anti-aromatase, and cytotoxic properties. Lysiphan B (2) exhibited significant antioxidant activity, with an IC₅₀ value of 28.8 ± 0.4 μM in the diphenyl picrylhydrazyl radical (DPPH) assay, 3.5 ± 0.2 μM in the xanthine/xanthine oxidase (XXO) assay, and 1.5 ± 0.0 ORAC units in oxygen radical absorbance capacity (ORAC) assay. Additionally, compounds 12, 13, and 16 exhibited very strong aromatase inhibitory activity with IC₅₀ values of 0.3 ± 0.2, 4.7 ± 0.1, and 0.9 ± 0.2 µM, respectively. Compound 16 also demonstrated strong ORAC activity of 1.9 ± 0.1 ORAC units.

Abstract

Previously, we reported that azamollugin, an aza-derivative of mollugin, exhibited potent inhibitory activity on NO production in LPS-stimulated RAW 264.7 cells. Further investigations in this study revealed that azamollugin not only suppressed iNOS gene expression regulated by NF-κB, but also inhibited LPS-induced IFN-β expression, which is known to be regulated by IRF3. Azamollugin exhibited an inhibitory activity on LPS-induced IRAK1 activation, suggesting inhibitory effect on the MyD88-dependent pathway. Furthermore, azamollugin inhibited LPS-induced phosphorylation of IRF3 and its upstream factor, TBK1/IKKε, suggesting an inhibitory effect on the TRIF-dependent pathway via TLR4. In addition, azamollugin also suppressed poly(I:C)-induced phosphorylation of TBK1 and IRF3, suggesting an inhibitory effect on the TRIF-dependent pathway via TLR3. These results suggest that azamollugin has inhibitory activity against both the MyD88-dependent and TRIF-dependent pathways, respectively.

Graphical abstract

Macrocyclization of peptides reduces conformational flexibilities, potentially leading to improved drug-like properties. However, side reactions such as epimerization and oligomerization often pose synthetic challenges. Peptide-cyclizing biocatalysts in the biosynthesis of non-ribosomal peptides (NRPs) have remarkable potentials as chemoenzymatic tools to facilitate more straightforward access to complex macrocycles. This review highlights the biocatalytic potentials of NRP cyclases, especially those of cis-acting thioesterases, the most general cyclizing machinery in NRP biosynthesis. Growing insights into penicillin-binding protein-type thioesterases, a relatively new group of trans-acting thioesterases, are also summarized.

Microscopic examination is one of the important identification methods for crude drug test described in the 18th Japanese Pharmacopoeia. This method is useful for identification because it can be used for small amounts of samples regardless of their storage conditions; however, this method requires a lot of technical skill in sectioning intricate and/or small samples and is time-consuming. High-resolution X-ray computed tomography (HRXCT) is a novel method for observing the internal morphology of materials. Previously, we used HRXCT to visualize the internal morphology of the Ephedra Herb, obtaining observations that closely match those obtained via microscopic examination. HRXCT employs a low-energy X-ray source and the permeation distance of the X-rays is very short. Therefore, HRXCT can be used for elucidating the morphology of small herbal medicines. In this study, Artemisia Capillaris Flower (capitulum with a diameter of approximately 2 mm) and Plantago Seed (seeds with a length of approximately 2 mm) were examined. The results showed that HRXCT examination was sufficient to illustrate the internal independent organs of Artemisia Capillaris Flower and that their inflorescences remained intact. When observing Plantago Seed, the internal morphology of more than one seed can be depicted simultaneously. Therefore, observation using HRXCT was easy, simple, and effective to illustrate the internal morphology of herbal medicines, which is typically time-consuming and requires advanced microscopy skills.

Uncaria rhynchophylla (Miq.) Miq. (Rubiaceae) is widely used as a botanical raw material for traditional Japanese and Chinese medicines. However, not all of its potentially bioactive constituents have been isolated and characterized. Herein, one new indole alkaloid triglucoside (1), nine known alkaloids (2-10) and thirteen known non-alkaloids (11-23) were isolated from the aqueous extract of Uncaria rhynchophylla hook and structurally characterized ¹H and ¹³C NMR and high-resolution electrospray ionization mass spectrometry. The absolute configurations of isolated compounds (1, 2 and 3) were determined by the X-ray diffraction analysis of their single crystals obtained using a micro-drop crystallization technique. This technique allows single crystals to be obtained from samples as small as 50 µg, thus providing detailed structural information even on minor constituents and enabling the accurate quality monitoring of botanical raw materials more accurately.