Anti-osteoporotic and antioxidant activities of chemical constituents of the aerial parts of Ducrosia ismaelis

A new pterocarpan glycoside, glycinol-3-O-β-d-glucopyranoside (1), and a new dihydrochalcone glycoside, ismaeloside A (2), were isolated together with 13 known compounds, including several flavonoids (3–8), lignans (9–11), and phenolic compounds (12–15), from the methanol extract of the aerial parts of Ducrosia ismaelis. The chemical structures of these compounds were elucidated from spectroscopic data and by comparison of these data with previously published results. The anti-osteoporotic and antioxidant activities of the isolated compounds were assessed using tartrate-resistant acid phosphatase (TRAP), oxygen radical absorbance capacity (ORAC), and reducing capacity assays. Compound 15 exhibited a dose-dependent inhibition of osteoclastic TRAP activity with a TRAP value of 86.05 ± 6.55% of the control at a concentration of 10 μM. Compounds 1, 3–5, and 8 showed potent peroxyl radical-scavenging capacities with ORAC values of 22.79 ± 0.90, 25.57 ± 0.49, 20.41 ± 0.63, 26.55 ± 0.42, and 24.83 ± 0.12 μM Trolox equivalents (TE) at 10 μM, respectively. Only compound 9 was able to significantly reduce Cu(I) with 23.44 μM TE at a concentration of 10 μM. All of the aforementioned compounds were isolated for the first time from a Ducrosia species.     

Bioactive chemical constituents from the root bark of Morus australis

Two new pyranoflavonoids, morustralins A (1) and B (2), a new natural benzene derivative, one benzenoid (Z)-1-hydroxy-4-(2-nitroethenyl)benzene (3), and thirty known compounds were isolated and characterized from the root bark of Morus australis. The structures of the new compounds were established from spectroscopic and spectrometric analyses. Ten isolates (1–10) were examined for inhibitory effects on adenosine diphosphate (ADP)-, arachidonic acid (AA)-, and platelet-aggregating factor (PAF)-induced platelet aggregation. Among the tested compounds, compound 3 displayed the most significant inhibition of ADP- and AA-induced platelet aggregation with IC₅₀ values of 9.76 ± 5.54 and 9.81 ± 2.7 μM, respectively. In addition, eight purified compounds (3–10) were examined for inhibition of nitric oxide (NO) production in RAW 264.7 cells and six compounds (3–8) displayed significant inhibitory effects with IC₅₀ values ranging from 2.1 ± 0.3 to 6.3 ± 0.6 μM.     

Bioactive 2-pyrone metabolites from an endophytic Phomopsis asparagi SWUKJ5.2020 of Kadsura angustifolia

Five new 2-pyrone metabolites, phomaspyrones A–E (1–5) along with three known compounds, macommelin-8,9-diol (6), macommelin-9-ol (7), and macommelin (8), were isolated from the culture broth of an endophytic fungus Phomopsis asparagi SWUKJ5.2020 of medicinal plant Kadsura angustifolia by sequentially purification over silica gel, Sephadex LH-20 column chromatography and preparative HPLC. Their structures were elucidated on the basis of spectroscopic analysis, including two-dimensional (2D) NMR and HRMS (ESI-TOF) data. Among them, compounds 3–5 exhibited notable cytotoxicity against HL-60 and K562 cells with IC₅₀ values of below 10 μg/mL better than those of the other isolated metabolites (IC₅₀ = 10.6–26.6 μg/mL). The results showed that the keto or hemiketal functionality might play an important role in cytotoxic activity of this class of compounds.     

Tirucallane triterpenoids from the stem bark of Araliopsis synopsis

Two new tirucallane triterpenoids, 21-methoxy-21,23-epoxy-tirucalla-7,24-dien-3α-ol (1) and 21-methoxy-21,23-epoxy-tirucalla-7,24-diene-1α,3α-diol (2), together with thirteen known compounds were isolated from the CH₂Cl₂ extract of the stem bark of Araliopsis synopsis. The structures of the compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data and comparison with previously known analogs. Compounds 1–10 were tested against bacteria, fungi and plant pathogen oomycetes by the paper disk agar diffusion assay resulting in missing to low activities corresponding with MICs > 1 mg/mL. However, compounds 5–10 exhibited high cytotoxic activity against the human Caucasian prostate adenocarcinoma cell PC-3 line, with IC₅₀ 8.5–12.5 μM compared to the standard Doxorubicin with IC₅₀ = 0.9 μM, while compounds 1, 3 and 4 showed low activity.     

A new megastigmane from Kalanchoe tubiflora (Harvey) Hamet

One new megastigmane, (6S,7R,8R,9S)-6-oxaspiro-7,8-dihydroxymegastigman-4-en-3-one (1) (tubiflorone, 1), and ten known compounds were isolated and characterized from the EtOH extract of Kalanchoe tubiflora (Harvey) Hamet. Structures of these isolates were assigned based on spectroscopic analyses that included 1D and 2D NMR techniques, such as HMQC, HMBC, and NOESY. The anti-inflammatory activities of selected isolated compounds (1–6 and 9–11) were evaluated as inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cell lines. Compounds 1–4, 6, 9, and 11 possessed nitric oxide inhibitory activity with IC₅₀ values ranging from 15.1 ± 0.9 to 98.9 ± 1.3 μM.     

Acylated iridoid glycosides and acylated rhamnopyranoses from Gmelina arborea flowers

Nine acylated iridoid glycosides (1–9), five acylated rhamnopyranoses (10–14) and verbascoside (15) were isolated from Gmelina arborea flowers, including 5 new compounds (1, 2, and 10–12). The cytoprotective activity of 11 selected compounds (1–8, 10, 11, and 15) against CCl₄-induced cytotoxicity on liver was determined. Compounds 1, 2, 4, 7, 8 and 15 displayed hepatoprotective activity. 6-O-α-l-(2″, 3″-di-O-trans-p-hydroxycinnamoyl)rhamnopyranosylcatalpol (2) exhibited the most potent cytoprotective effect with an EC₅₀ value of 42.5 μM (SI = 19.3) compared with biphenyldimethylesterate (DDB, EC₅₀ = 277.3 μM, SI = 9.8) and bicylo-ethanol (EC₅₀ = 279.2 μM, SI = 12.2). Among the acylated iridoid glycosides, the compounds (2 and 8) containing phenolic hydroxy groups were more active than were those lacking them.     

Anti-inflammatory components of Euphorbia humifusa Willd.

Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3–26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10–21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC₅₀ values as low as 18.05 ± 1.17, 18.64 ± 1.83, and 17.23 ± 0.84 μM, respectively. In addition, the effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compounds 3–6, 8, 18, 20–23, and 25–26 inhibited the production of both NO and TNF-α, with IC₅₀ values ranging from 11.1 ± 0.9 to 45.3 ± 1.6 μM and 14.4 ± 0.5 to 44.5 ± 1.2 μM, respectively.     

Osteogenic activity of constituents from Butea monosperma

Phytochemical investigation from the stem bark of Butea monosperma, led to the isolation and identification of three new compounds named buteaspermin A (1), buteaspermin B (2) and buteaspermanol (3), along with 19 known compounds. The structure of compounds 1–22 were established on the basis of their spectroscopic data. The isolated compounds 2–17 were evaluated using neonatal (1–3 day old) rat calvaria derived primary osteoblast cultures. Five of these compounds 7, 10–13 showed promising osteogenic activity, attributed to increased osteoblast proliferation, differentiation and mineralization as evidenced by marked increase in expression of alkaline phosphatase, an early phase differentiation marker, and alizarin Red S staining of osteoblasts cultured for 48 h and von Kossa silver staining of nodules formed 15 days after culture with these compounds. Quantification of mineralization by optical density measurement of Alizarin Red S extracted from stained osteoblasts cultured for 7 days in presence of these compounds showed significant (P < 0.05, vs corresponding vehicle control group) increase in mineralization. On the basis of biological results, structure–activity relationships are discussed.     

Geranylated tetraoxygenated xanthones from the pericarp of Garcinia pedunculata

Three new xanthones, pedunxanthones D-F (1–3), along with ten known compounds, were isolated from a chloroform extract of the pericarp of Garcinia pedunculata. Their structures were determined using spectroscopic techniques. Cytotoxicity against HeLa and NCI-H460 cells of the isolated compounds using an SRB assay was evaluated with pedunxanthone D (1) as the most active compound (IC₅₀ 24.9 ± 0.4 and 26.1 ± 1.5 μg/ml, respectively).     

A new lignan and a new alkaloid,and α-glucosidase inhibitory compounds from the grains of Echinochloa utilis Ohwi & Yabuno

A new lignan, utilisin (1), and a new alkaloid, echinoutilin (2), together with eleven known compounds 3–13 were isolated from the grains of Echinochloa utilis Ohwi & Yabuno. Their structures were identified through the analysis of spectroscopic data. The absolute configuration of 2 was determined by Mosher’s method. These compounds were evaluated for α-glucosidase inhibitory activity. Among them, compounds 2, 3 and 6 exhibited considerable α-glucosidase inhibitory activity with IC₅₀ values of 42.1 ± 1.3, 58.9 ± 3.7, and 40.9 ± 1.1 μM, respectively. The results indicate that the grains of E. utilis will be useful in the treatment of diabetes control agents.     

Daphnane-type diterpenes with inhibitory activities against human cancer cell lines from Daphne genkwa

Four new daphnane-type diterpenes, genkwadanes A–D (1–4), together with 19 known ones, were isolated from ethanol extract of the flower buds of Daphne genkwa. Their structures were determined on the basis of extensive spectroscopic data. Among them, daphnane-type diterpene with a 1,10-double bond (1) was isolated from this plant for the first time. The cytotoxicity of all compounds 1–23 against the 10 selected human cancer cell lines was assayed. A number of compounds exhibited significant activities against the 10 cancer cell lines (IC₅₀ < 9.56 μM). and most interestingly, all the compounds revealed preferred cytotoxicities on the HT-1080 cell line and displayed much stronger inhibitory activities (IC₅₀ < 29.94 μM) compared with positive control 5-fluorouracil (IC₅₀ = 35.62 μM), particularly, compounds 9–11, 13, 16 and 19 exhibited the strongest cytotoxicity activities against the HT-1080 cell line (IC₅₀ < 0.1 μM).     

Seven new benzeneacetic acid derivatives and their quinone reductase activity from Eurycorymbus cavaleriei

From the twigs of Eurycorymbus cavaleriei, seven new benzeneacetic acid derivatives cavaol A–G (1–7) were isolated. The structures were elucidated on the basis of the results of spectroscopic (NMR, IR, UV and MS) analysis. In the present study, the quinone reductase (QR) induction activities of compounds 1–7 were assayed. Compounds 3 and 4 showed moderate QR induction with concentrations to double the enzyme activity (CD) of 9.9 ± 0.3 and 7.9 ± 0.5 μg/mL, respectively. LC-MS-MS analysis revealed that the quinone reductase induction activity of compounds 3 and 4 was not due to alkylating the sulfhydryl groups of Keap1. There must be some other pathways for compounds 3 and 4 to induce quinone reductase.     

Two new rotenoids from the roots of Millettia speciosa

Two new rotenoids, named millettiaosas A–B (1–2), together with four known compounds were isolated from the roots of Millettia speciosa. Their structures were elucidated on the basis of spectroscopic analysis including 1D and 2D NMR techniques and HRESIMS. Evaluation of the two new compounds for cytotoxicity against four human cancer cell lines (MCF-7, HCT-116, A549 and HepG-2) showed moderate activities (10 μM < IC₅₀ < 26 μM).     

Four new sesquiterpenoids as natural nitric oxide (NO) inhibitors from the rhizomes of Curcuma phaeocaulis

A new norsesquiterpene named phaeocaulisin N (1), and three new guaiane-type sesquiterpenes named phaeocaulisins O–Q (2–4), together with a known norsesquiterpene (5) were isolated from the rhizomes of Curcuma phaeocaulis. Their structures were established based on extensive spectroscopic analysis. Compounds 1 and 5, as far as we know, are the first example of 13-norguaiane-type sesquiterpenes isolated from the genus Curcuma. All of the isolated compounds were tested for inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages. Compound 1 showed strong inhibitory activity on nitric oxide production with IC₅₀ value of 3.58 ± 0.17 μM.     

Isolation,structural characterization and neuraminidase inhibitory activities of polyphenolic constituents from Flos caryophylli

Neuraminidase (NA) is one of the key surface proteins of the influenza virus, which is an important target for anti-influenza therapy. In the present study, bioassay-guided fractionation led to isolation of two new compounds, rhamnetin-3-O-β-d-glucuronide-6″-methyl ester (1) and rhamnazin-3-O-β-d-glucuronide-6″-methyl ester (2), along with seventeen known compounds (3-19), from the MeOH extract of Flos Caryophylli using in vitro NA inhibition assay. These isolated compounds exhibited significantly inhibitory effects on the NA with IC₅₀ values ranging from 8.4 to 94.1 μM and were found to protect MDCK cells from A (H1N1) influenza infections (EC₅₀ = 1.5–84.7 μM) with very low cytotoxicity to the host cells (CC₅₀ = 374.3–1266.9 μM)), with selective index (SI) ranging from 7 to 297. The primary structure-relationships of these isolates were also discussed.     

New phenolic glycosides with cyclooxygenase inhibition from the roots of Tecoma mollis

Three new phenolic glycosides (1–3) together with nine known ones were isolated from the roots of Tecoma mollis using DPPH radical scavenging bioassay-guided chromatographic separation. The structures of the new compounds were established using extensive spectroscopic data and HR-MS. The antioxidant, COX-2 inhibition, and cytotoxic activities were evaluated for the isolated compounds. Compound 4 displayed the strongest radical scavenging activity relative to ascorbic acid with IC₅₀ 8.7 μM. Compounds 5, 6, and 10 showed promising COX-2 inhibitory action, IC₅₀ values of 11.3 μM, 9.4 μM, and 13.4 μM, respectively. All compounds exhibited weak cytotoxic activity against Hela and A549 cancer cell lines.     

Anti-HIV-1 integrase diterpenoids from Dichrocephala benthamii

Five new clerodane diterpenoid dichrocephnoids A–E (1,2, 6–8) together with three known analogues were isolated from the whole herb of Dichrocephala benthamii C.B. Clarke. Their structures were elucidated on the basis of spectroscopic analyses (UV, IR, MS, 1D and 2D NMR). The relative configurations of the new compounds were established by NOESY correlations, and the absolute configuration of 1 was determined on the basis of CD methods. Dichrocephnoid A (1) possesses a very rare pentacyclic ring system with highly oxygenated functionalities. All of the isolated compounds exhibited inhibitory activity against HIV-1 integrase, however, dichrocephnoid C (6) showed the most promising inhibition of the enzyme with IC₅₀ value of 12.35 ± 1.27 μM.     

Prenylated C6–C3 compounds from the roots of Illicium henryi

Eleven prenylated C₆–C₃ compounds, illihenryifunones A, B (1, 2), illihenryifunol A (3), illihenryipyranol A (4), illihenryiones A−G (5–11), and three known prenylated C₆–C₃ compounds (12–14), were isolated from the roots of Illicium henryi. Structures of 1–11 were elucidated by spectroscopic methods including NMR, HRESIMS, and CD. The absolute configuration of the 11,12-diol moiety in 5 was determined by observing its induced circular dichroism after addition of Mo₂(OAc)₄ in DMSO. The absolute configuration of C-11 in 4 was determined as S based on the Rh₂(OCOCF₃)₄-induced CD data; the absolute configuration of 3 was determined as R by comparison of its experimental and calculated electronic circular dichroism (ECD). The antioxidant activities of compounds 1–14 were also evaluated. Compound 4 exhibited strong antioxidant activity with an IC₅₀ value of 2.97 ± 1.30 μM, whereas compounds 3 and 8 showed antioxidant activities with IC₅₀ values of 44.36 ± 0.30 and 48.00 ± 2.01 μM, respectively.     

Triterpenoid saponins and C-glycosyl flavones from stem bark of Erythrina abyssinica Lam and their cytotoxic effects.

Six new compounds including two oleanane-type triterpenoid saponins (1, 2) and four C-glycosyl flavones (3–6), along with a known saponin (7), three di-C-glycosyl flavones (8–10) and a glycosyl auronol (11), were isolated from the stem bark of Erythrina abyssinica Lam. The structures of the new compounds, identified as 3-O-[α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 2)-β-d-glucuronopyranosyl]-22-O-β-d-glucopyranosyl sophoradiol (1), 3-O-[α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl-(1 → 2)-β-d-glucuronopyranosyl]-22-O-β-d-glucopyranosyl sophoradiol (2), 6-C-β-glucopyranosyl-8-C-β-quinovopyranosyl apigenin (3), 6-C-β-quinovopyranosyl-8-C-β-glucopyranosyl apigenin (4), 8-C-[6″-O-α-l-rhamnopyranosyl-(1‴ → 6″)]-β-glucopyranosyl 7,4′-dihydroxyflavone (5) and 8-C-[6″-O-β-d-xylopyranosyl-(1‴ → 6″)]-β-glucopyranosyl 7,4′-dihydroxyflavone (6), were determined by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry and acid hydrolysis. These new compounds together with the known saponins 7 were evaluated for their cytotoxic activity against MCF-7 (estrogen dependent) and MDA-MB-231 (estrogen independent) cell lines. The new saponin 2 exhibited the highest cytotoxic activity among tested compounds, exerting a selective inhibitory effect against the proliferation of MCF-7 cells, with lower IC₅₀ value (12.90 μM) than that of the positive control, resveratrol (13.91 μM). Structure–activity relationship of these compounds is also discussed.