Lysidrhodosides A-I, acylphloroglucinol glucosides with anti-inflammatory activities from the leaves of Lysidice rhodostegia.

Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.

Undescribed matrine-type alkaloids from Sophora alopecuroides with anti-inflammatory activity.

A phytochemical investigation on the alkaloid fractions of Sophora alopecuroides L. led to the production of 11 undescribed matrine-type alkaloids, sophaloseedlines I-S (1-11), 12 known analogs (12-23), and an unexpected artificial matrine-derived Al(III) complex (24). The corresponding structures were elucidated by the interpretation of spectroscopic analyses, quantum chemical calculation, and six instances (1-4, 18, and 24), verified by X-ray crystallography. The biological activities screening demonstrated that none of the isolates exhibited cytotoxicity against four human cancer cell lines (HepG2, A549, THP-1, and MCF-7) and respiratory syncytial virus (RSV) at 50 µM, while moderate anti-inflammatory activity with IC50 value from 15.6 to 47.8 µM was observed. The key structure-activity relationships of those matrine-type alkaloids for anti-inflammatory effects have been summarized. In addition, the most potent 7-epi-sophoramine (19) and aluminum sophaloseedline T (24) could effectively inhibit the release of pro-inflammatory factors (TNF-α, IL-6, and IL-1ß), as well as the expression of iNOS and COX-2 proteins.

Diterpenoid Alkaloids from Delphinium ajacis and Their Anti-inflammatory Activity.

Three novel diterpenoid alkaloids, comprising two C19 -diterpenoid alkaloids (1 and 2) and one C20 -diterpenoid alkaloid (3), were isolated from Delphinium ajacis, alongside the six known compounds (4-9). Their structures were elucidated by spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and chemical properties. Simultaneously, the anti-inflammatory properties of all compounds (1-9) was conducted, focusing on nitric oxide (NO) production in LPS-induced BV-2 cells. The results indicated compounds 1-3, 7, and 8 have potential anti-inflammatory activity.

Lindenane sesquiterpenoid dimers from Chloranthus holostegius with anti-neuroinflammatory activities in BV-2 microglia.

Fifteen undescribed lindenane-type sesquiterpenoid dimers, designated chloranholides F-T (1-15), together with twenty-five known analogs (16-40), were isolated from the whole plants of Chloranthus holostegius. The isolate structures were elucidated by analysis of spectroscopic data and chemical methods, and their absolute configurations were determined by X-ray crystallography and electronic circular dichroism spectra. In anti-neuroinflammatory assays, all isolates were evaluated by examination of their inhibitory effect on nitric oxide (NO) in LPS-stimulated BV-2 cells, and the results showed that 21-24, 26, 30, 32 and 36 significantly inhibited the production of the inflammatory mediator NO, with IC50 values ranging from 3.18 to 11.46 µM, which was better than that of quercetin. Structure-activity relationship analysis revealed that two essential functional groups played an indispensable role in the anti-inflammatory effects. Moreover, 22 and 24 inhibited the LPS-induced upregulation of iNOS and COX-2 enzymes in BV-2 microglia at the protein level.

Sesquiterpenoids from the whole plants of Elephantopus mollis with cytotoxicity activities.

Five new sesquiterpenoids (1-5), elephantmollides A-E, along with four known compounds (6-9), were isolated from the whole plants of E. mollis. Their planar structures were elucidated using the spectroscopic methods, including HRESIMS, IR, UV, and NMR (1H, 13C, DEPT, HSQC, HMBC, 1H-1H COSY). The relative configurations of them were partially deduced by the NOESY experiment, and the absolute configurations were assigned by comparing the calculated electronic circular dichroism (ECD) results with the experimental data. In addition, cytotoxic activities of 1-9 against HepG2 cells ware tested, and compounds 1-9 exhibited cytotoxic activities with IC50 values ranging from 6.7 to 25.8 µM.

Lycopodium Alkaloids from Huperzia serrata and Their Anti-acetylcholinesterase Activities.

One new fawcettimine-type alkaloid (1), one new miscellaneous-type alkaloid (2), four new lycodine-type alkaloids (3-6), and eight known ones (7-14) were isolated from the whole plants of Huperzia serrata. Their structures and absolute configurations were elucidated based on spectroscopic data, X-ray diffraction, ECD calculation and Mosher's method. Compound 1 was a rare C18 N2 -type Lycopodium alkaloid, possessing serratinine skeleton with an amide side chain in C-5. The absolute configuration of the 18-OH of compounds 4-6 were first determined by Mosher's method. Moreover, compounds 1-14 were assayed anti-acetylcholinesterase effect in vitro, and compound 7 showed significant anti-acetylcholinesterase activity with an IC50 value of 16.18±1.64 µM.

Undescribed phloroglucinol derivatives with antiviral activities from Dryopteris atrata (Wall. Ex Kunze) Ching.

Nine undescribed phloroglucinol derivatives (dryatraols A-I) with five different backbones and three known dimeric acylphloroglucinols were isolated from the rhizome of Dryopteris atrata (Wall. Ex Kunze) Ching (Dryopteridaceae). Dryatraol A contains an unprecedented carbon skeleton-a butyrylphloroglucinol and a rulepidanol-type sesquiterpene are linked via a furan ring to form a 6/5/6/6 ring system. Dryatraols B and C are the first examples of monomeric phloroglucinols coupled with the aristolane-type sesquiterpene through the C-C bond. Dryatraol D features a rare spiro [benzofuran-2',5″-furan] backbone. Dryatraols E-I are five undescribed adducts with a butyrylphloroglucinol or filicinic acid incorporated into the germacrene-type sesquiterpene via a pyran ring. These undescribed structures were determined by comprehensively analysing the spectroscopic data, X-ray diffraction results, and electronic circular dichroism calculations. The result of in vitro antiviral activity evaluation indicated that dryatraol C displayed the strongest antiviral effect against both respiratory syncytial virus and influenza A virus (H1N1), with IC50 values of 11.9 µM and 5.5 µM, respectively. Dryatraols F-H exhibited considerable inhibitory activity against herpes simplex virus type 1 (HSV-1), with IC50 values ranging from 2.6 to 6.3 µM. Analysis of the inhibitory mechanism using a time-of-addition assay revealed that dryatraol G may inhibit the replication of HSV-1 by interfering with the late stage of the viral life cycle.

Three new compounds isolated from the whole plants of Salsola collina pall.

One new alkaloid, 6, 7-dimethoxyisoquinoline-N-oxide (1), one new benzofuran derivative, 3,7-dimethyl-6-acetyl-8-benzofuranol (2) and one new lignan, salsolains A (3), along with seven known compounds (4-10), were isolated from the whole plant of Salsola collina Pall. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1 D and 2 D NMR), and their absolute configurations were determined by the X-ray crystallography and ECD calculation. The activities of compounds 1-10 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, especially, compound 5 (50 µM) exhibited the most significant anti-inflammatory activity with the secretion levels of IL-6 and TNF-α at 3.87% and 4.03%, respectively.

Two new clerodane diterpenoids and a new pyran-2-one derivative with anti-neuroinflammatory activities from Croton crassifolius.

Two new clerodane diterpenoids (1 and 2), a new pyran-2-one derivative (3), along with five known compounds (4‒8), were isolated from Croton crassifolius. Notably, crassifolin X (1) is a novel clerodane diterpenoid, characterized with a peculiar δ-lactone core being formed between C-1 and C-4. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (UV, IR, HRESIMS and NMR), and circular dichroism experiments. In addition, all compounds were evaluated for their anti-neuroinflammatory activities based on the expression of TNF-α and IL-6 levels on LPS-induced BV2 cells, and compounds 1‒3 and 5 showed potential anti-neuroinflammatory activity.

Three new sesquiterpene lactones from the whole plants of Elephantopus scaber.

Three new sesquiterpene lactones, named scabertopinolides H - J (1 - 3), along with four known ones, desacylisodeoxyelephantopin 2-methylbutyrate (4), iso-17,19-dihydrodeoxyelephantopin (5), scabertopinolide D (6) and (2R,6R,7R,8S)-8-tigloyloxy-1(10),4(5),11(13)-germacratrien-2,15,6,12-diolide (7) were isolated from the whole plants of Elephantopus scaber. Their structures were elucidated by extensive analysis of spectroscopic data (including IR, UV, HRESIMS, 1 D and 2 D NMR) and single-crystal X-ray. These isolated compounds showed effective anti-inflammatory effects on LPS-stimulated RAW 264.7 cells with IC50 values of 6.27 ± 0.18 to 18.31 ± 1.38 µM.

Water-soluble matrine-type alkaloids with potential anti-neuroinflammatory activities from the seeds of Sophora alopecuroides.

A phytochemical investigation on the alkaloids from water-soluble part of Sophora alopecuroides led to obtain forty matrine-type alkaloids (1-40) including eighteen new ones (1-18), which covers almost all positions of the oxygen substitution in matrine-type structure. Notably, eight compounds (1-8) belong to rare bis-amide matrine-type alkaloid. The new structures were determined based on extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and six instances, verified by X-ray crystallography. Most of isolates showed anti-neuroinflammatory activities based on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BV2 microglia cells. Especially, compound 39 can suppress those two mediator secretions in a dose-dependent manner with IC50 values of 21.6 ± 0.5 and 16.7 ± 0.8 µM, respectively. Further mechanistic study revealed that 39 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF-κB signaling pathway.

Stilbene dimer xylosides and flavanols from the roots of Lysidice rhodostegia and their antioxidant activities.

Eight new stilbene dimer xylosides (1-8) and one new flavanol (9), along with seven known ones (10-16) were isolated from the roots of Lysidice rhodostegia. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1D and 2D NMR), ECD calculations and acid hydrolysis. Compounds 1-16 were evaluated for their antioxidant activities using DPPH radical-scavenging assay. Especially, compounds 9 and 10 exhibited stronger antioxidant effects than the positive control (vitamin E), with IC50 values of 9.57 ± 1.30 and 13.60 ± 1.47 µM, respectively.

Five matrine-type alkaloids from Sophora tonkinensis.

Five matrine-type alkaloids (1‒5) including two new compounds (1 and 3) and a new natural product (2) were isolated from the roots of Sophora tonkinesis. Their structures were identified by extensive spectroscopic analysis (UV, IR, HRESIMS and NMR). The absolute configurations of 2 and 3 were determined by X-ray diffraction. Compounds 1‒5 were evaluated their activity against inflammatory cytokines TNF-α and IL-6 levels on LPS-induced RAW 264.7 macrophages, and compound 1 showed the most significant activity, potent than that of matrine, the representative ingredient from Sophora plants.

Two new isoquinoline alkaloids from the seeds of Nandina domestica.

Two new isoquinoline alkaloids, 6 R,6aS-N-nantenine Nß-oxide (1), 6S,6aS-N-nantenine Nα-oxide (2), along with nine known alkaloids, nantenine (3), oxonantenine (4), protopine (5), nornantenine (6), N-methyl-laurotetanine (7), isocorydine (8), O-methyflavinantine (9), N-methyl-2,3,6-trimethoxymorphinan-dien-7-one Nß-oxide (10) and (+)-10-O-methylhernovine Nß-oxide (11) were isolated from the seeds of Nandina domestica. Their structures were elucidated by extensive analyses of spectroscopic data (IR, UV, HRESIMS, 1 D and 2 D NMR), ECD calculation and comparison with the related literatures. In addition, the cytotoxicity against A549 cells of these alkaloids was determined by the MTT assay.

One new sesquiterpene pyridine alkaloid from the stems and leaves of Euonymus fortunei.

A new sesquiterpene pyridine alkaloid (1), along with four known compounds (2-5), were isolated from the stems and leaves of Euonymus fortunei. The new structure was determined by extensive spectroscopic analyses (IR, UV, NMR, HRESIMS and ECD). In addition, compound 3 showed a stronger anti-respiratory syncytial virus (RSV) activity with an IC50 value of 1.20 ± 0.10 µM than the positive control ribavirin with an IC50 value of 5.62 ± 0.49 µM.[Formula: see text].

ß-Carboline Alkaloids from the Seeds of Peganum harmala and Their Anti-HSV-2 Virus Activities.

Pegaharines A-G (1-6), six novel ß-carboline alkaloids representing three types of skeleton, were isolated from the seeds of Peganum harmala. Compound 1 is a peculiar ß-carboline alkaloid characterized by the unprecedented carbon skeleton of an azepine-indole system. Compounds 3-6 represent the first examples of heterodimers constructed from rare tetracyclic ß-carboline and classic tricyclic ß-carboline alkaloids. Compounds 1 and 2 were characterized by X-ray crystallography. Compound 4 exhibited strong antiviral activity against HSV-2, with an IC50 value of 2.12 ± 0.14 µM.

Chemical constituents from the thorns of Gleditsia sinensis and their cytotoxic activities.

A new aromatic glycoside (1) and a new natural product, neolignan (2), along with twenty-three known compounds (3-25), were isolated from the thorns of Gleditsia sinensis. According to the spectroscopic analyses (IR, UV, HRESIMS, NMR and ECD), the structures of isolates were elucidated. Herein, compounds 4, 6-8, 10-13, 15, 16, 18, 20, 23 were isolated from the plant of G. sinensis for the first time. Moreover, compounds 4, 6, 15 and 24 showed cytotoxic effects on human ovarian cancer (SKOV-3) cells with IC50 values of 24.83 ± 4.90, 48.86 ± 9.11, 80.13 ± 5.62, 15.38 ± 2.21 µM, respectively. [Formula: see text].

Quinolizidine alkaloids from Sophora tonkinensis and their anti-inflammatory activities.

Two new quinolizidine-based alkaloids (2 and 12), along with ten known ones (1, 3-11) were isolated from the roots of S. tonkinensis. Their structures were determined by spectroscopic data (including NMR, MS, IR, and UV), X-ray single crystal diffraction, electronic circular dichroism analyses (ECD), and comparing with related literatures. Compounds 1, 3-12 at non-toxic concentrations exhibited potent anti-inflammatory activities according to in vitro and in vivo anti-inflammatory tests. Among them, (-)-anagyrine (4), sophocarpine (8), 14ß-hydroxymatrine (10), and 7ß-sophoramine (12) showed more potent in vitro anti-inflammatory activities, and 5α,14ß-dihydroxymatrine (2), (-)-anagyrine (4), sophocarpine (8), and 5α-hydroxymatrine (9) exhibited better in vivo anti-inflammatory effects.

Psiguadiols A-J, Rearranged Meroterpenoids as Potent PTP1B Inhibitors from Psidium guajava.

Psiguadiols A-J (1-10), new meroterpenoids with rearranged skeletons, were isolated from the leaves of Psidium guajava. Compounds 1-3 represent the first examples of 6,8-diformyl-5,7-dihydroxy-4-phenylchromane-coupled sesquiterpenoids with an unprecedented C-8-spiro-fused 6/6/9/4 tetracyclic ring system. Compounds 4 and 5 represent two unusual scaffolds featuring 1ß,6ß- and 3α,5α-epoxy rings, respectively. The combination of spectroscopic data analyses, comparison of experimental and calculated ECD data, and single-crystal X-ray diffraction data of 1, 6, and 8 allowed for the assignment of the structures. A putative biosynthetic pathway for 1-10 is discussed. Compounds 1, 7, and 8 exhibited inhibitory activities against PTP1B with IC50 values of 4.7, 6.2, and 9.2 µM, respectively. In addition, molecular docking was performed to investigate the mechanism of action.

Alopecuroides A-E, Matrine-Type Alkaloid Dimers from the Aerial Parts of Sophora alopecuroides.

Five new matrine-type alkaloid dimers, alopecuroides A-E, were isolated from the aerial parts of Sophora alopecuroides. Alopecuroides A and B represent the first dimeric matrine-type alkaloids possessing a cyano group and an epoxy moiety. Alopecuroides C and D are dimeric matrine-type alkaloids connected via C-2-C-9' and C-10-C-3' bonds, respectively. The chemical structures of alopecuroides A-E were elucidated by spectroscopic methods combined with single-crystal X-ray diffraction analysis. The anti-inflammatory effects of alopecuroides A-E were evaluated, and alopecuroide B exhibited the most significant activity, better than that of matrine, the representative compound from S. alopecuroides.