Melanogenesis inhibitory pregnane glycosides from Cynanchum atratum

Bioassay-guided fractionation of the methanolic extract from the roots of Cynanchum atratum has resulted in the isolation of three new pregnane glycosides (1–3) along with four known compounds (4–7). Their structures were identified by analysis of the spectroscopic data including extensive 2D NMR. All of the isolates were evaluated for their potential to inhibit the melanin production in α-melanocyte stimulating hormone (α-MSH)-activated B16 melanoma cells. Of these, compounds 4–7 dose-dependently inhibited the melanin production with the IC₅₀ values ranging from 4?μM to 33?μM.     

Pseudo-disesquiterpenoids from seeds of Vernonia anthelmintica and their biological activities

Three new pseudo-disesquiterpenoids, vernodalidimer F – H (1 – 3), which are formed by esterification of two sesquiterpenoids, along with a new sesquiterpenoid (4) and two known sesquiterpeonids (5, 6) were isolated from the seeds of Vernonia anthelmintica. Their structures were elucidated by NMR data. The absolute configurations of 1–3 and 5 were determined by comparison of the experimental and calculated electronic circular dichroism spectra. Cytotoxicity of the isolated compounds against four human tumor cell lines were assayed. 5 exhibited strong cytotoxicity against HCT-15, PC-3, A549 and Hela cells lines with IC₅₀ values of 5.3, 5.6, 6.2, and 8.2 μM, respectively. 2 showed non-concentration dependent cytotoxicity against HCT-15, PC-3, and A549 cells lines with inhibition rate of 56.1%, 55.3%, and 50.1%, respectively. 1 and 3 showed moderate cytotoxicity against four cell lines with IC₅₀ values ranging from 12.2 ± 5.1 to 28.6 ± 2.5 μM. The influence of melanin content in B16 melanoma cells of 1, 5, and 6 were tested, and they increased melanin content by 43.6%, 28.1%, and 37.0% higher than positive control 8-methoxypsoralen.     

Iridoid glucosides from the leaves of Vitex negundo var. cannabifolia

Five new iridoid glucosides, cannabifolisides A–E (1 – 5), together with nine analogues (6 – 14), were isolated from the leaves of Vitex negundo var. cannabifolia. Their structures were elucidated by spectroscopic data (NMR, UV, IR, and MS) analyses and comparison of their spectroscopic and physical data with the literature values. The protective effect of isolated compounds on human gastric epithelial cells were evaluated by measuring the enhanced cell viability of GES-1 cell insulted by TCA. Among these, compounds 4, 6, 8, 10, 12, and 14 remarkably increased the cell viability in a concentration-depend manner.     

The isolation,absolute configuration and activities of 18(4 → 3)-abeo-abietane lactones from Tripterygium wilfordii

Phytochemical studies on the leaves of Tripterygium wilfordii led to the isolation of seven new 18(4 → 3)-abeo-abietane lactones, triptergulides E – K (1 – 7). The structure of the new compounds was elucidated on the basis of their spectroscopic analysis, and the absolute configurations of compounds were confirmed by ECD, calculated ECD, and X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. Some compounds showed moderate inhibitory activities against NO, IL-6, and TNF-α production in LPS RAW 264.7 macrophage in vitro.     

Synthesis of quercetin glycosides and their melanogenesis stimulatory activity in B16 melanoma cells

4′-O-β-d-Glucopyranosyl-quercetin-3-O-β-d-glucopyranosyl-(1→4)-β-d-glucopyra-noside (3) was isolated from Helminthostachys zeylanica root extract as a melanogenesis acceleration compound and was synthesized using rutin as the starting material. Related compounds were also synthesized to understand the structure–activity relationships in melanin biosynthesis.Melanogenesis activities of the glycosides were determined by measuring intracellular melanin content in B16 melanoma cells. Among the synthesized quercetin glycosides, quercetin-3-O-β-d-glucopyranoside (1), quercetin-3-O-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside (2), and 3 showed more potent intracellular melanogenesis acceleration activities than theophyline used as positive control in a dose-dependent manner with no cytotoxic effect.     

Tyrosinase activity of Greyia flanaganii (Bolus) constituents

Hyper-pigmentation of the skin is a common problem that is prevalent in middle aged and elderly people. It is caused by over production of melanin. Tyrosinase is known to be the key enzyme in melanin production. Ethanolic extract of Greyia flanaganii leaves showed significant (P < 0.05) antityrosinase activity exhibiting the IC₅₀ of 32.62 μg/ml. The total extract was further investigated for its toxicity and effect on melanin production by melanocytes cells, and showed significant inhibition (P < 0.05) (20%) of melanin production at 6.25 μg/ml and low levels of cytotoxicity (IC₅₀ < 400 μg/ml). The amount of antioxidants necessary to decrease the initial DPPH absorbance by 50% (EC₅₀) by the total ethanolic extract was found to be 22.01 μg/ml. The effect of G. flanaganii against acne causing bacteria, Propionibacterium acnes, was investigated using microdilution assay. The MIC of the extract of G. flanaganii was found to be 250 μg/ml. Bioassay-guided fractionation led to the isolation of (3S)-4-hydroxyphenethyl 3-hydroxy-5-phenylpentanoate (1), 2′,4′,6′-trihydroxydihydrochalcone (2), 2′,6′,4-trihydroxy-4′-methoxydihydrochalcone (3), 2′,6′-dihydroxy-4′-methoxydihydrochalcone (4), 5,7-dihydroxyflavanone [(2S)-pinocembrin] (5), 2′,6′-dihydroxy-4′,4-dimethoxy dihydrochalcone (6) and (2R,3R)-3,5,7-trihydroxy-3-O-acetylflavanone (7). The isolated compounds were tested for their antioxidant, cytotoxicity, tyrosinase inhibition and antibacterial activities. Compound 2 exhibited significant (P < 0.05) antityrosinase activity exhibiting the IC₅₀ of 69.15 μM. The isolated compounds showed low toxicity of the cells with reduction of melanin content of the cells. All compounds tested showed good radical scavenging activity. These data indicates that G. flanaganii extract and its isolated phenolic constituents could be possible skin lightening agents.     

Two new antimicrobial steroids and other constituents from the whole plant of Ludwigia abyssinica

The genus Ludwigia belongs to the Onagraceae family and it encompasses seventy-five species of aquatic plants. The chemistry of this genus is scarcely investigated, although some studies have demonstrated the potential of Ludwigia leptocarpa to produce important bioactive compounds. Herein, we describe the phytochemical investigation of Ludwigia abyssinica A. Rich. Two new steroids named 3β-formyloxy-5α,6α-dihydroxysitostane (Ludwigiaformyl A, 1) and 3β,6α-diformyloxy-5α-hydroxysitostane (Ludwigiaformyl B, 2), along with six known compounds, 3β-formyloxysitost-5-en (3), 5α,6β-dihydroxysitosterol (4), maslinic acid (5), oleanolic acid (6) and a mixture of two iridoids: linearin (7) and 1-epilinearin (8) were obtained from whole plant of L. abyssinica. The structures of the isolated compounds were established by extensive analysis of their spectroscopic and spectrometric data, which included HR-TOF-ESIMS, ¹D NMR (¹H, ¹³C) and ²D NMR (¹H–¹H COSY, HSQC, HMBC and ROESY) and by comparison with data reported in the literature. The antimicrobial activities of extracts, fractions, and new compounds (1) and (2) were evaluated using broth microdilution method against fungi and bacteria strains. The MeOH extract and the ethyl acetate fraction displayed different degrees of antibacterial and antifungal activities (MIC = 32 – 512 µg/mL; MMC = 64 – 512 µg/mL) whereas compounds 1 and 2 showed moderate antimicrobial activities against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Shigella flexneri and Cryptococcus neoformans (MIC = 8 – 32 µg/mL; MMC = 8 – 64 µg/mL).     

Corrigendum to “A new phenylethyl glycoside and a new dibenzocyclooctadiene lignan from the leaves of Kadsura coccinea (Lem.) A. C. Smith” [Phytochem. Lett. 45 (2021) 57–62]

A new phenylethyl glycoside (1), (S)-1-phenylethyl-6-α-L-arabinopyranosyl-β-D-glucopyranoside), and a new dibenzocyclooctadiene lignan (7), Kasuracin A, together with seven known compounds, were isolated and identified from the leaves of Kadsura coccinea. Their structures were determined by analysis of multinuclear and multidimensional nuclear magnetic resonance (NMR), circular dichroism (CD), mass spectrometry, hydrolysis analysis, or comparison to those reported in the literature. Then, all the isolates 1‒9 were evaluated for their inhibitory eff ;ects against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among them, compounds 2 and 3 were isolated for the first time from this plant and compounds 3, 7, 8, and 9 significantly inhibited NO production with IC₅₀ values of 36.4, 10.2, 12.3, and 21.7 μM, respectively.     

Inhibitory effects of phloroglucinols from the roots of Dryopteris crassirhizoma on melanogenesis

Two new phloroglucinols (7 and 10), along with 12 known derivatives (1-6, 8-9, and 11-14), were isolated from the roots of Dryopteris crassirhizoma (Aspiadaceae). Their chemical structures were elucidated by various spectroscopic methods (¹H NMR, ¹³C NMR, COSY, HMQC, and HMBC) and high-resolution mass spectrometry. All isolates (1-14) were tested for their inhibitory effects on melanin production in B16F10 murine melanoma cells. Norflavaspidic acid AB (8), norflavaspidic acid PB (9), and flavaspidic acid PB (12) inhibited melanin production with IC₅₀ values of 181.3, 35.7, and 38.9 μM, respectively. Compound 9 was also shown to inhibit tyrosinase activity in a dose-dependent manner and melanogenesis with an IC₅₀ value of 5.9 μM in B16F10 cells stimulated with 3-isobutyl-1-methylxanthine (IBMX).     

Flavonoids and arylbenzofurans from the rhizomes and roots of Sophora tonkinensis with IL-6 production inhibitory activity

Three new compounds (1–3) and 20 known compounds were isolated from the rhizomes and roots of Sophora tonkinensis, and all the isolates were tested for their inhibitory activity against IL-6 production in HMC-1 cells stimulated by PMA plus ionophore, A23187. Of the tested compounds, compounds 1, 5, 9, and 21 were found to potently inhibit IL-6 production with IC₅₀ values of 1.62, 0.73, 3.01, and 4.02 μM, respectively.     

Anti-inflammatory isoflavones and isoflavanones from the roots of Pongamia pinnata (L.) Pierre

A phytochemical study on the roots of Pongamia pinnata afforded five new isoflavone and isoflavanone derivatives (1–5), including two previously undescribed phenylisoflavones possessing an 1,2-oxetane ring, along with 21 known compounds (6–26) among which compound 18 is the first time to be isolated from nature. The structures of the isolated compounds were determined on the basis of 1D, 2D NMR, and HRESIMS. The absolute configurations of the compounds were assigned via analysis of the specific rotations and circular dichroism (CD) spectra, as well as by comparison of the calculated and experimental electronic circular dichroism (ECD) data. All the isolated compounds were evaluated for their inhibitory effects on NO production in LPS-stimulated BV-2 microglial cells. Twelve compounds exhibited different levels of inhibitory effects against NO production, and compound 1 showed the best activity with an IC₅₀ value at 9.0?μM.     

Two new limonoids from the roots of Trichilia connaroides with inhibitory activity against nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells

Two new rearranged limonoids, trichiliton I (1) and 12-deacetoxyltrijugin A (2) along with four previously reported compounds (3–6) were isolated from the roots of Trichilia connaroides. Their structures were established on the basis of extensive spectroscopic analysis including HR-ESI–MS and 1D and 2D NMR. The new compounds 1 and 2 exhibited weak inhibitory effects on lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 cells in a dose-dependent manner.     

Bioactive monoterpene indole alkaloids from Nauclea officinalis

Two new monoterpene indole alkaloids, naucleaoffines A (1) and B (2), together with six known alkaloids (3–8), were isolated from the stems and leaves of Nauclea officinalis. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. All isolated compounds were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1–8 exhibited significant inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC₅₀ values comparable to that of hydrocortisone. In addition, compounds 1–8 showed significant anti-HIV-1 activities with EC₅₀ ranged from 0.06 to 2.08 µM. These findings suggest that the discoveries of these indole alkaloids with significant anti-inflammatory activities and anti-HIV-1 activities isolated from N. officinalis could be of great importance to the development of new anti-inflammatory and anti-HIV agents.     

Nitric oxide inhibitory constituents from Siegesbeckia pubescens

Two new sesquiterpenoids (1 and 2) and a new ent-pimarane type diterpenoid (3), together with eighteen known compounds (4–21), were isolated from the whole plants of Siegesbeckia pubescens. The structures of the new compounds were determined on the basis of 1D-, 2D NMR and HRESIMS data. All compounds were evaluated for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages. Of these, highly oxygenated germacrane type sesquiterpenoids (1–2 and 13–14) showed significant inhibitory effects with IC₅₀ values ranging from 3.9 to 16.8 μM.     

Inhibitory constituents of the heartwood of Dalbergia odorifera on nitric oxide production in RAW 264.7 macrophages

Two new isoflavanones (1 and 13), along with 25 known compounds (2–12, 14–27), were isolated from the EtOAc-soluble fraction of the heartwood of Dalbergia odorifera by following their potential to inhibit the LPS-induced nitric oxide production in RAW 264.7 cells. The structures of the isolated compounds were established by spectroscopic data such as ¹D, ²D NMR and MS spectrometry. Among the isolated compounds, (2S)-pinocembrin (26), showed the most potent inhibitory effect with IC₅₀ value of 18.1 μM.     

Two new phenolic compounds from the white flower of Impatiens balsamina

During the course of our continuing search for biologically active compounds from Korean medicinal sources, we investigated the white flower of Impatiens balsamina. From the MeOH extract, two new phenolic compounds (1–2) containing a nitrile group and eleven known phenolic compounds (3–13) were isolated. The chemical structures of new compounds (1–2) were determined through NMR, HRMS, and CD data. We tested the isolated compounds (1–13) for their cytotoxic activities by determining their inhibitory effects on human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15) in vitro using the sulforhodamine B (SRB) assay. We also investigated their neuroprotective activity by determining their effects on nerve growth factor (NGF) secretion in C6 cells, and anti-neuroinflammatory activity by measuring nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV-2 cells.     

Steroidal components from the roots and rhizomes of Helleborus thibetanus

Three new steroidal components hellebogenins A and B (1 – 2) and thibetanoside I (3) together with four know ones (4 – 7) were isolated from the roots and rhizomes of Helleborus thibetanus. Their structures were elucidated by chemical methods and spectroscopic analysis. Among them, compound 1 possessed three double bonds at the positions of 1(2), 5(6) and 25(27), while compound 2 had an α, β unsaturated ketone carbonyl on the A ring. In addition, compounds 1 and 2 showed cytotoxic activities against HCT116 cells with IC₅₀ values of 42.0 ± 1.3 μM and 67.3 ± 1.5 μM, respectively.     

Strophasterols E and F: Rearranged ergostane-type sterols from Pleurotus eryngii

Strophasterols E (1) and F (2) were isolated from the fruiting bodies of Pleurotus eryngii, together with four new ergostane-type sterols (3–6). Single-crystal X-ray diffraction analysis performed on the tris-p-bromobenzoate derivatives of compounds 1 and 2 allowed these two compounds to be identified as the structurally rare (22S,23R)- and (22S,23S)-5α,6α-epoxy-3β,7β,23-trihydroxy-15(14 → 22)-abeo-ergost-8-en-14-one, respectively. The inhibitory effects on nitric oxide production of the six new steroids thus isolated from the fruiting bodies of P. eryngii were also evaluated.     

Anti-neuroinflammatory diarylheptanoids from the rhizomes of Dioscorea nipponica

In a continuing search for bioactive constituents from Dioscoreaceae medicinal plants, two new cyclic diarylheptanoids, diosniponol A (1) and B (2), together with 10 known compounds (3–12) were isolated from the rhizomes of Dioscorea nipponica. The structures of these new compounds were determined by spectroscopic analyses, including extensive two-dimensional nuclear magnetic resonance, high-resolution mass spectrometry, and optical rotation. All isolated compounds 1–12 were evaluated for their effects on nitric oxide (NO) production in murine microglia cell line BV-2. Compounds 8 and 11 showed potent inhibitory activities on NO production (IC₅₀ 13.36 and 14.36 μM, respectively) without cell toxicity in lipopolysaccharide-activated BV-2 cells.     

Chrysoeriol derivatives and other constituents from Glandularia selloi

Glandularia selloi (Verbenaceae) presents phenylethanoids, iridoids and flavone glycosides as the main constituents. Two novel chrysoeriol derivatives, selloiside A (1) and selloiside B (2) were isolated from the methanolic extract of the aerial parts. Both flavones are acylated disaccharides. Two known compounds, verbascoside (3) and 6β-hydroxy-ipolamiide (4), were isolated from the methanolic extract of the roots. The structures were elucidated using 1D, 2D NMR and MS. Acylflavones have taxonomic significance since they occur mainly is species from the order Lamiales, specifically from the family Lamiaceae, closely related to Verbenaceae. The compounds 1 – 4 and the methanolic extract were investigated for antichemotactic activity.