Glucoconjugated monoterpene indole alkaloids with xanthine oxidase inhibitory activity from Ophiorrhiza japonica.

Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1-5), ophiorglucidines A-E, and seven known analogues (6-12) from the water-soluble fraction of Ophiorrhiza japonica. The structures were elucidated based on spectroscopic data and quantum calculations as well as X-ray crystallographic analysis. The structure of 1 was characterized as a hexacyclic skeleton including a double bridge linking the indole and the monoterpene moieties, which is the first report of a single crystal with this type of structure. Moreover, the inhibitory effect of zwitterionic indole alkaloid glycosides on xanthine oxidase was found for the first time. The alkaloids 2 and 3, both of which have a pentacyclic zwitterionic system, were more active than the reference inhibitor, allopurinol (IC50 = 11.1 µM) with IC50 values of 1.0 µM, and 2.5 µM, respectively. Structure-activity relationships analyses confirmed that the carbonyl group at C-14 was a key functional group responsible for the inhibitory effects of these alkaloids.

Decoding Evolution of Rubioideae: Plastomes Reveal Sweet Secrets of Codon Usage, Diagnostides, and Superbarcoding.

Galium genus belongs to the Rubiaceae family, which consists of approximately 14,000 species. In comparison to its well-known relatives, the plastomes of the Galium genus have not been explored so far. The plastomes of this genus have a typical, quadripartite structure, but differ in gene content, since the infA gene is missing in Galium palustre and Galium trfidum. An evaluation of the effectiveness of using entire chloroplast genome sequences as superbarcodes for accurate plant species identification revealed the high potential of this method for molecular delimitation within the genus and tribe. The trnE-UUC-psbD region showed the biggest number of diagnostides (diagnostic nucleotides) which might be new potential barcodes, not only in Galium, but also in other closely related genera. Relative synonymous codon usage (RSCU) appeared to be connected with the phylogeny of the Rubiaceae family, showing that during evolution, plants started preferring specific codons over others.

Chemical constituents of the aerial parts of Mitracarpus hirtus (L.) DC (Rubiaceae).

A phytochemical investigation of the aerial parts of Mitracarpus hirtus afforded thirteen compounds, including a new naphthoquinone di-glycoside (1), three isopentenyl isoflavones (2-4), four flavonoids (5-8), three iridoid glycosides (9 - 11) and two coumarins (12 and 13). Their structures were elucidated based on extensive spectroscopic analyses, chemical methods, and the comparison with the literature. Among them, compound 1 possesses a 2-(3-methylnaphthalen-2-yl)acetic acid core with two glucosyl groups, compounds 2-4 are the first three representatives from the Rubiaceae family, and compounds 9-11 and 13 were isolated from Mitracarpus genus for the first time. Additionally, compounds 2-4 displayed potent antibacterial activities against Helicobacter pylori G27/HP159/JRES00015 (MIC = 4-16 µg/mL) , comparable to metronidazole. To date, wighteone (2) is the most active isoflavone with favourable predicted ADMET properties reported against H. pylori.

Thliphthisasapphus (Rubiaceae, Rubieae), a new species from Lefkada (Ionian Islands, Greece) and its ecological position.

The new species, Thliphthisasapphussp. nov. (Rubiaceae, Rubieae), a narrow endemic of the white cliffs of Lefkátas on the southwest coast of Lefkada (Greece) is described and illustrated and an IUCN assessment is presented. Vegetation relevés were performed at the single known locality, limestone cliffs facing the sea and revealed a new association, the Thliphthisasapphus-Lomelosietumdallaportae. The chromosome number of Thliphthisasapphus was determined as 2n = 4x = 44, being the single tetraploid species in the genus to date. The species also differs markedly morphologically from its morphologically closest relatives, two Greek steno-endemic oreophytes, Th.baenitzii and Th.muscosa by the following characters: densely setose mericarps and corolla, tetraploidy and by its distribution. An identification key for the Greek species of Thliphthisa is provided. Th.sapphus constitutes the westernmost outpost of a group of Greek steno-endemics, highlighting the importance of coastal habitats and their protection as refugia for poorly competitive chamaephytes.

Spermacosides a and B, two new triterpenoid saponins from Spermacoce ocymoides burm.f.

Two new triterpenoid saponins, named spermacosides A-B (1 - 2), together with two known oleanane-type triterpenoid saponins, 3-O-ß-D-xylopyranosyl-(1→3)-ß-D-glucopyranosylbayogenin (3) and 3-O-ß-D-glucopyranosylbayogenin (4), were isolated from the ethyl acetate extract of Spermacoce ocymoides Burm.f. in a phytochemical investigation. Their chemical structures were elucidated by spectroscopic data analysis (1D and 2D NMR, and HR-ESI-MS), as well as comparison with reported data. All these compounds were evaluated for inhibiting nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. Among them, 1 showed a slight effect with an IC50 value of 108.65 ± 7.91 µM, and compounds 2-4 were inactive.

Antinociceptive iridoid glycosides from the aerial parts of Paederia foetida.

Two previously undescribed iridoid glycosides, 6'-O-trans-feruloyl-(4S,6R)-3,4-dihydro-3ß-ethoxypaederoside (1) and 6'-O-trans-caffeoyl-(4S,6R)-3,4-dihydro-2'-O-3α-paederoside (2), were isolated from the 90% EtOH extract of the air dried aerial parts of Paederia Foetida. Structural elucidation of all the compounds was performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. The two isolated iridoid glycosides were tested in vivo for their antinociceptive properties. As a result, 2 showed potent antinociceptive effect and its ID50 value (53.4 µmol/kg) was 2-fold less than those of the positive control drugs aspirin and acetaminophen.

Ophiorrhizareflexa (Rubiaceae), a new species from a karst region in Guangxi, China.

Ophiorrhizareflexa, a new species from Guangxi, China, is described and illustrated in this study. It is morphologically similar to O.alatiflora due to the branched inflorescence, distylous flowers and the tubular-funnelform corolla with five longitudinal wings. The new species can be distinguished from O.alatiflora by its erect inflorescence, its smaller and equal-sized calyx lobes 0.5-0.7 mm long, its corolla tubes winged to the middle and the wings straight and its strongly reflexed corolla lobes at anthesis. Ophiorrhizareflexa is assessed as least concern (LC) according to IUCN Categories and Criteria.

Triterpenoids from the hook-bearing stems of Uncaria rhynchophylla.

An unprescribed nortriterpenoid with an aromatic E ring, uncanortriterpenoid A (1), together with fourteen known triterpenoids (2-15), were isolated from the hook-bearing stems of Uncaria rhynchophylla Miq. Based on extensive spectroscopic analyses, the NMR data of 2, 5, and 10 in CD3OD were assigned for the first time, and the wrongly assigned δC of C-27 and C-29 of 2 were revised. Among the known compounds, 7, 13, and 15 were isolated from this species for the first time, and 15 represents the first lanostane triterpenoid bearing an extra methylidene at C-24 for the Rubiaceae family. Additionally, compounds 6 and 14 exhibited moderate ferroptosis inhibitory activity, with an EC50 value of 14.74 ± 0.20 µM for 6 and 23.11 ± 1.31 µM for 14.

Guettarda uruguensis (Rubiaceae): antioxidant and anti-inflammatory plant with quercetin and esters of p-coumaric acid.

Guettarda (Rubiaceae) is a genus known for its diverse range of bioactive compounds, with demonstrated anti-inflammatory and antioxidant properties. Guettarda uruguensis Cham. & Schltdl., commonly known as 'jasmim uruguaio' or 'veludinho,' is a native species of the Atlantic Forest that get interested in its potential therapeutic applications. In this study, we evaluated the phenolic content and antioxidant activity of the crude ethanol extract obtained from G. uruguensis leaves (EBGF) and fractions, as well as the antinociceptive, anti-inflammatory, and toxicity activity of the EBGF. Our findings revealed that the EBGF and its fractions contain polyphenolic compounds, including long-chain esters of p-coumaric acid and quercetin, which contribute to their potent antioxidant activity. The EBGF exhibited significant anti-inflammatory and antinociceptive effects, highlighting its potential as a natural product for treating pain and inflammation. Our study supports G. uruguensis as a promising source of bioactive compounds with pharmacological potential.

Anti-inflammatory monoterpenes from morinda (Morinda officinalis How.).

Morinda (Morinda officinalis How.) is widely consumed as a functional food owing to its potential to promote health. This study investigated the anti-inflammatory phytochemicals of morinda and isolated 30 monoterpenes, including 6 undescribed iridoids (1, 6, 9-11 and 25), 2 undescribed acyclic monoterpenoids (28, 29), a known acyclic monoterpenoid and 21 known iridoids. Their chemical and stereo-structures were elucidated based on HR-ESI-MS, NMR, 13C-NMR calculations, ECD data and ECD calculations. Notably, compounds 11, 12 and 20 exerted pronounced inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values of 28.51 ± 1.70, 25.45 ± 4.17 and 29.17 ± 3.71 µM respectively (indomethacin, IC50 of 33.68 ± 2.19 µM). The same compounds exert anti-inflammatory effects by blocking nuclear translocation of nuclear factor κ-B, and down-regulating the expression of inflammatory cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1ß and interleukin-6 at mRNA and protein levels in a dose-dependent manner. These results suggest that moderate consumption of morinda helps prevent and reduce the occurrence of inflammatory-related diseases.

Previously undescribed tetrahydroanthraquinones from Prismatomeris tetrandra (roxb.) K. Schum with antitumor cell proliferation activities.

To find structurally previously undescribed compounds with pharmacological effects from Prismatomeris tetrandra (Roxb.) K. Schum (Rubiaceae), thirteen undescribed tetrahydroanthraquinones (1⎼13) named prisconnatanones J⎼V and seven known anthraquinones (14⎼20) were isolated and characterized. The structures of these compounds were elucidated by detailed spectroscopic analyses, and their absolute configurations were established by modified Mosher's method and ECD calculations. The antitumor cell proliferative activities of prisconnatanones J⎼V were determined. Among them, prisconnatanones J possessed high antitumor cell proliferation in HGC27 cells (IC50, 0.792 µM) by blocking HGC27 cells in the S phase and significantly inducing apoptosis in HGC27 cells. Prisconnatanone J has no cytotoxicity to normal gastric cells line (GES-1) at 10 µM and showed a considerable selectivity for HGC27 cells. Prisconnatanone J can potentially inhibit tumor cell proliferation and should be further investigated.

Six new iridoid glycosides from the whole plants of Hedyotis diffusa.

Six new iridoid glycosides were isolated from the ethyl acetate fraction of the whole plants of Hedyotis diffusa Willd. They were identified as E-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (1), Z-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (2), E-6-O-caffeoyl scandoside methyl ester (3), E-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (4), Z-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (5), and E-6-O-p-coumaroyl-4'-O-acetyl scandoside methyl ester (6). The structures of them were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, and NMR). They were screened for anti-inflammatory effect, antioxidant effect, antitumor effect, and neuroprotective effect and did not show potent activities.

Hedscandines A-C, three undescribed indole alkaloids from Hedyotis scandens with their anti-MRSA activity.

Hedscandines A-C (1-3), three undescribed indole alkaloids were isolated from Hedyotis scandens Roxb, a traditional Chinese medicine widely used in the treatment of respiratory ailments. Their structures were elucidated by extensive spectroscopic data and electronic circular dichroism calculation. Hedscandine A (1), possessed a unique carbon skeleton with a 1,4-oxazonin-2(3H)-one core system and displayed a rapid bactericidal activity against MRSA with a MIC value of 16 µg/mL. Mechanistic studies showed that compound 1 could disrupt the integrity of bacterial cell membranes and thus lead to bacterial death.

Chemical constituents from the aerial parts of Rubia cordifolia L. with their NO inhibitory activity.

A new naphthoquinone derivative (1) together with twenty-three known compounds (2-24), were isolated from the aerial parts of Rubia cordifolia L. Their structures were elucidated on the basis of NMR and HR-ESIMS data. Compounds 1-13 were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 2-6 exhibited significant inhibitory activities with IC50 values of 21.37, 13.81, 24.56, 20.32, and 30.08 µmol·L-1, respectively.

Minor alkaloids from an aqueous extract of the hook-bearing stem of Uncaria rhynchophylla.

Seven new monoterpene alkaloids (1 - 7), along with 16 known analogues, were isolated from an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). Their structures were determined by spectroscopic data analysis, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are stereoisomers belonging to a novel type of pseudoindoxyl monoterpene alkaloids, 3 is the first monoterpene furoindole alkaloid from nature, and 4 - 7 are derivatives of the known monoterpene alkaloids featuring different structures.

The genus Canthium: A comprehensive summary on its traditional use, phytochemistry, and pharmacological activities.

Canthium Lam. is a genus of flowering plants of the Rubiaceae family with about 80-102 species mainly distributed in Asia, tropical and subtropical Africa. The genus is closely related to Keetia E. Phillips and Psydrax Gaertn. and plants of this genus are used in folk medicine for the treatment of diarrhea, worms, leucorrhoea, constipation, snake bites, diabetes, hypertension, venereal diseases, and malaria. The present review covers a period of 52 years of biological and chemical investigations into the genus Canthium and has resulted in the isolation of about 96 secondary metabolites and several reported biological properties. For the Rubiaceae family, iridoids were reported as being the chemotaxonomic markers of this genus (∼25%). Other reported classes of compounds include alkaloids, flavonoids, phenolic compounds, cyanogenic glycosides, coumarins, sugar alcohols, lignans, triterpenoids, and benzoquinones. The main reported pharmacological properties of most species of this genus include antioxidant, antiplasmodial, antipyretic, anti-inflammatory, antidiabetic, neuroprotective and antimicrobial activities with the latter being the most prominent. Considering the diversity of compounds reported from plants of this genus and their wide range of biological activities, it is considered to be worthy to further investigate them for the discovery of potentially new and cost effective drugs.

Genome mining of metabolic gene clusters in the Rubiaceae family.

The Rubiaceae plant family, comprising 3 subfamilies and over 13,000 species, is known for producing significant bioactive compounds such as caffeine and monoterpene indole alkaloids. Despite an increase in available genomes from the Rubiaceae family over the past decade, a systematic analysis of the metabolic gene clusters (MGCs) encoded by these genomes has been lacking. In this study, we aim to identify and analyze metabolic gene clusters within complete Rubiaceae genomes through a comparative analysis of eight species. Applying two bioinformatics pipelines, we identified 2372 candidate MGCs, organized into 549 gene cluster families (GCFs). To enhance the reliability of these findings, we developed coexpression networks and conducted orthology analyses. Using genomic data from Solanum lycopersicum (Solanaceae) for comparative purposes, we provided a detailed view of predicted metabolic enzymes, pathways, and coexpression networks. We bring some examples of MGCs and GCFs involved in biological pathways of terpenes, saccharides and alkaloids. Such insights lay the groundwork for discovering new compounds and associated MGCs within the Rubiaceae family, with potential implications in developing more robust crop species and expanding the understanding of plant metabolism. This large-scale exploration also provides a new perspective on the evolution and structure-function relationship of these clusters, offering opportunities for the highly efficient utilization of these unique metabolites. The outcome of this study contributes to a broader comprehension of the biosynthetic pathways, elucidating multiple aspects of specialized metabolism and offering innovative avenues for biotechnological applications.

Two new anthraquinone derivatives from Saprosma crassipes H. S. Lo.

Two new anthraquinone derivatives sapranquinones A and B (1 and 2) together with two known biogenetically related anthraquinone derivatives (3 and 4) were isolated from the stems of Saprosma crassipes H. S. Lo. The structures of these compounds were elucidated using comprehensive spectroscopic methods. Compounds 1-4 were evaluated for their antibacterial activities and compounds 1 and 3 had a broad spectrum antibacterial activity against Staphylococcus albus, Escherichia coli, Bacillus cereus, Micrococcus tetragenus, and Micrococcus luteus with MIC values ranging from 1.25 to 5 µg/mL.

Seventeen undescribed iridoid derivatives with anti-inflammatory effects from Hedyotis diffusa and their structure-activity relationships.

Seventeen undescribed iridoid derivatives (1-17) and four known compounds (18-21) were isolated from the whole plant of Hedyotis diffusa Willd. Their structures were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, CD, and 1D and 2D NMR). It is noteworthy that compounds 1-8, which possess unique long-chain aliphatic acid moiety, were reported for the first time among the iridoid natural products. All compounds were evaluated for their anti-inflammatory activities in lipopolysaccharide-induced RAW 264.7 cells. Compounds 2, 4, and 6 showed significant suppression effects on nitric oxide production, with IC50 values of 5.69, 6.16, and 6.84 µM, respectively. The structure-activity relationships of these compounds indicated that long-chain aliphatic moieties at C-10 might be the key group for their anti-inflammatory activities. The therapeutic properties of these iridoid derivatives could give an insight into utilizing H. diffusa as a natural source of anti-inflammatory agents.

Constituents of Uncaria lanosa f. philippinensis and their anti-amyloidogenic activity.

The aggregation of amyloid-ß (Aß) remains the most acceptable pathological hallmark of Alzheimer's disease (AD). In search for natural products exhibiting anti-amyloidogenic effects, phytochemical analyses were conducted on Uncaria lanosa f. philippinensis leading to the purification of oxindole alkaloid uncarine E (isopteropodine) (1), the phenylethanoid tyrosol (2), the megastigmane vomifoliol (3), and the previously reported alkaloids mitraphylline and isomitraphylline. This is the first report of compounds 1-3 in the title plant, and tyrosol (2) from the genus Uncaria. Assessment of the anti-amyloidogenic potential using Thioflavin T assay showed 91% (at 50 µM) and 70% (at 25 µM) inhibitions for compound 1. Tyrosol (2) gave 76% (at 50 µM) and 63% (at 25 µM) inhibitions. These compounds may be further tested to elucidate their mechanism in the prevention of Aß aggregation. To the best of our knowledge, this is the first report on the anti-amyloid aggregation activity of compounds 1 and 2.