Skip to content

Bioactive Terpenoids and Steroids from Astragalus complanatus Seeds underlie Its Potent Neuroprotective Efficacy In Vitro and In Vivo

Aug 2026 · Journal of Agricultural and Food Chemistry · Vol 74, pp. 26311-26331 · 0 citations · 50 references

TL;DR

In APP/PS1 mice, compound 11 dose-dependently improved cognitive function, reduced Aβ plaques, and attenuated glial inflammation, supporting its promising neuroprotective potential.

Abstract

An investigation of the seeds of Astragalus complanatus (SAC), a homologous food-medicine plant in China, yielded 29 compounds, including four new terpenoids, astranoids A–D (1, 2, 6, 23), and one new stigmastane steroid, astrasteroid (12). Structural elucidation was achieved using NMR, HRESIMS, quantum-chemical ECD, and NMR computations, and X-ray crystallography. Astranoid A (1) features a novel 5/6/6/6/5 pentacyclic skeleton with cis-fused A/B rings. All isolates were evaluated for nitric oxide inhibition in LPS-stimulated BV-2 cells. 7-oxo-β-sitosterol (11) demonstrated potent antineuroinflammatory activity with an IC50 of 6.09 ± 0.49 μM. This compound suppressed proinflammatory cytokines, NF-κB translocation, and iNOS/COX-2 expression, activated Nrf2/HO-1 in HT22 cells, and protected neurons from Aβ-induced inflammatory injury. In APP/PS1 mice, compound 11 dose-dependently improved cognitive function, reduced Aβ plaques, and attenuated glial inflammation, supporting its promising neuroprotective potential.

View source

Similar papers

Jul 2026

Structurally diverse flavonoids from the seeds of Astragalus complanatus with ferroptosis regulation via the NOX4/Nrf2 axis in neural cells.

The seeds of Astragalus complanatus R. Br. (SAC), a medicinal food homologous resource, are widely distributed and utilized in China. A phytochemical investigation of the seeds of SAC afforded 47 flavonoids, including eight previously undescribed ones, designated as complanatin A (2), and neocomplanatosides A-G (38, 39, and 43-47). Among them, 43 and 44 are phenylpropanoid-esterified flavonoid glycosides, while 45-47 represent a rare class of sesquiterpene-esterified flavonoid glycosides. Their structures were elucidated by the NMR and HRESIMS spectroscopic data, and ECD calculations. Biological evaluation demonstrated that rhamnocitrin (15) inhibited ferroptosis in erastin-induced HT22 cells (EC50 = 7.79 ± 0.44 μM) by suppressing NOX4 expression and activating the SLC7A11/Nrf2 pathway. Molecular dynamics simulations confirmed its stable binding to NOX4 (RMSD < 0.4 nm; ΔGbind = - 47.92 kJ/mol), and competitive inhibition with GLX351322 further confirmed NOX4 as the direct target. These findings indicate that flavonoids from SAC, particularly rhamnocitrin (15), are promising natural neuroprotective candidates for food-based health applications.

Kangxian Zhao, Xu-Tong Fang, Yue-Tong Zhu et al. · 2 citations
Aug 2026

Chemical Constituents of the Roots and Rhizomes of Rubia yunnanensis and Their Neuroprotective Activity.

Twelve previously undescribed compounds, including 10 naphthalene derivatives (1, 3-11), one benzo[b]oxepine derivative (2) and one anthraquinone analogue (12) were isolated from the CH2Cl2 extract of the roots and rhizomes of Rubia yunnanensis, together with 27 known ones (13-39). Their structures were elucidated on the basis of extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Angeloylgomisin O (31) exhibited anti-neuroinflammatory activity by inhibiting lipopolysaccharide (LPS)-induced overproduction of nitric oxide (NO) in BV-2 microglial cells. Furthermore, angeloylgomisin O (31) exhibited notable neuroprotective effects against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injuries in SH-SY5Y cells. These investigation results suggested that angeloylgomisin O (31) may contribute to the anti-inflammatory effects of Rubia yunnanensis and may provide valuable insights into the discovery of novel protective agents against ischemic neuronal or microglial injuries.

Fengbei Gong, Pei-Kun Tian, Ning-Yuan Gong et al. · 0 citations
Jul 2026

Phytochemical and anti-inflammatory profiling of Amomum maximum Roxb. Fruits reveal undescribed diarylheptanoids and labdane diterpenoids.

It is demonstrated that diarylheptanoids are the major anti-inflammatory components in A. maximum fruits, which not only validates the ethnopharmacological use of this herb, but also provides new anti-inflammatory agents derived from natural products.

Jinna Zhao, Shu-Fei Yu, Yan-Jun Ding et al. · 0 citations
Jul 2026

Isolation, structural elucidation, and biological evaluation of anti-inflammatory and cytotoxic compounds from Ligusticum wallichii.

Ligusticum wallichii Franch., an oriental medicinal herb widely used throughout East Asian countries, is well recognized for its therapeutic potential in treating cardiovascular, inflammatory, and neurodegenerative diseases. In this study, phytochemical investigation of the methanol extract of L. wallichii roots led to the isolation and structural elucidation of four previously undescribed compounds (1-4), and eight known analogues (5-12). Their structures were determined through extensive spectroscopic analyses, including 1D and 2D NMR, HR-ESI-MS, and CD spectroscopy, supported by quantum chemical ECD calculations. All isolated compounds were evaluated for anti-inflammatory and cytotoxic activities. Compounds 1, 3, 7, 9, and 12 significantly inhibited nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Regarding pro-inflammatory cytokine modulation, compounds 1, 9 and 12 significantly reduced both TNF-α and IL-6 levels by more than 40% at 10 μM. Moreover, compounds 2, 3, 5-7, and 9 showed significant cytotoxic activity with IC50 values ranging from 2.8 to 13.2 μM. Mechanistic investigations in PC9 cells revealed that the cytotoxic effects of selected compounds (2, 3, 5-7, 9) were mediated via apoptosis induction. Their dual functional properties position them as promising anti-inflammatory and anti-cancer agents, which prompt further research and potential following development step in targeting inflammation-associated cancer.

Ninh Khac Thanh Tung, Nguyễn Thị Tú Oanh, T. H. Giáp et al. · 0 citations
Jul 2026

Diverse bioactive metabolites from Callicarpa longifolia var. floccosa: terpenoids, polyketide, and callilongiflocin A as a potent anti-inflammatory diterpenoid targeting IL-17/TNF-α/MAPK signaling with anti-psoriatic activity.

Seven previously undescribed compounds comprising four diterpenoids (1-4), two sesquiterpenoids (5, 6), and one polyketide (7), together with four known diterpenoids (8-11), were isolated from Callicarpa longifolia Lamk. var. floccosa Schauer. Their structures and absolute configurations were established using HRESIMS, UV, IR, NMR and ECD calculations. All isolated compounds (1-11) were evaluated for anti-inflammatory activity by LPS-induced RAW264.7 cells. While all compounds inhibited nitric oxide (NO) release to varying degrees, callilongiflocin A (1) exhibited the most potent effects, significantly suppressing the production of NO, pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and the overexpression of inducible NO synthase (iNOS) in a concentration-dependent manner. Proteomics sequencing revealed that compound 1 modulates IL-17 and TNF signaling pathways. This regulation was further validated by Western blotting, demonstrating 1's inhibition of the common downstream mitogen-activated protein kinase (MAPK) pathway. Furthermore, in an IL-17A plus TNF-α-induced keratinocyte HaCaT model of psoriasis, compound 1 effectively suppressed the inflammatory cytokine IL-6, C-C motif chemokine ligand 20 (CCL-20), and the protein expression of intercellular cell adhesion molecule-1 (ICAM-1), suggesting its potential anti-psoriatic activity.

Ting Liu, Xiao-Lu Wu, Lianchun Li et al. · 0 citations
Open access

Alkaloid constituents from the stems of Dendrobium nobile and their anti-inflammatory activities

A phytochemical investigation of the stems of Dendrobium nobile Lindl. led to the isolation of six nitrogen-containing compounds, including one previously undescribed quinoline–aspartic acid hybrid alkaloid, dendronobiline A (1), together with five known alkaloid-related constituents (2–6). The structure of compound 1 was elucidated by comprehensive spectroscopic analyses, including HRESIMS, 1D and 2D NMR experiments, and its absolute configuration was assigned by comparison of experimental and calculated ECD spectra. Structurally, compound 1 features a quinoline-derived unit connected to a dimethyl aspartate moiety through an amide linkage. All isolated compounds were evaluated for their inhibitory effects on LPS-induced nitric oxide production in RAW264.7 macrophages. Among them, compound 1 displayed the most potent anti-inflammatory activity, with an IC50 value of 9.05 ± 1.60 μM, comparable to that of the positive control dexamethasone. These findings enrich the chemical diversity of D. nobile alkaloids and suggest that its stems are a promising source of anti-inflammatory natural products.

Jing-Yi Yue, Yu-Jia Lu, Yang Yu et al. · 0 citations