New Iridoids and Acyclic Monoterpenoids from the Roots and Rhizomes of Valeriana officinalis var. latifolia.

Five new iridoids, valeralides A-E (1-5), two new acyclic monoterpenoids, valeralides F (6) and G (7), together with two known iridoids (8 and 9), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated based on 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. The absolute configuration of compounds 1-4 were elucidated based on electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their inhibition on nitric oxide production, cytotoxicity and anti-influenza A virus activity.

Iridoids and other constituents from the leaves and stems of Valeriana officinalis var. latifolia.

Fifty-nine compounds, including nineteen previously undescribed iridoids (valeriananols A-S) and an undescribed alkaloid (5'-isovaleryl uridine), were isolated from the leaves and stems of Valeriana officinalis var. latifolia. Their structures were elucidated based on Mass spectrometry and NMR spectroscopy. The absolute configuration of valeriananols A-C, E-N, P, Q and S was determined by experimental and calculated electronic circular dichroism. Structurally, valeriananols A and B were two 1,3-seco-iridoids with a 3,6-epoxy moiety, valeriananols K and L were a pair of C-4 epimers, while valeriananol S was a 4'-deoxy iridoid glycoside. In addition, valeriananol P, stenopterin A and patriscabioin C exhibited significant inhibition on nitric oxide production with IC50 values of 10.31, 3.93 and 8.69 µM, respectively. Furthermore, stenopterin A and patriscabioin C showed anti-proliferation activity on the MCF-7 cell line with IC50 values of 17.28 and 13.89 µM, respectively.

Comparative genomics of the medicinal plants Lonicera macranthoides and L. japonica provides insight into genus genome evolution and hederagenin-based saponin biosynthesis.

Lonicera macranthoides (LM) and L. japonica (LJ) are medicinal plants widely used in treating viral diseases, such as COVID-19. Although the two species are morphologically similar, their secondary metabolite profiles are significantly different. Here, metabolomics analysis showed that LM contained ~86.01 mg/g hederagenin-based saponins, 2000-fold higher than LJ. To gain molecular insights into its secondary metabolite production, a chromosome-level genome of LM was constructed, comprising 9 pseudo-chromosomes with 40 097 protein-encoding genes. Genome evolution analysis showed that LM and LJ were diverged 1.30-2.27 million years ago (MYA). The two plant species experienced a common whole-genome duplication event that occurred ∼53.9-55.2 MYA before speciation. Genes involved in hederagenin-based saponin biosynthesis were arranged in clusters on the chromosomes of LM and they were more highly expressed in LM than in LJ. Among them, oleanolic acid synthase (OAS) and UDP-glycosyltransferase 73 (UGT73) families were much more highly expressed in LM than in LJ. Specifically, LmOAS1 was identified to effectively catalyse the C-28 oxidation of ß-Amyrin to form oleanolic acid, the precursor of hederagenin-based saponin. LmUGT73P1 was identified to catalyse cauloside A to produce α-hederin. We further identified the key amino acid residues of LmOAS1 and LmUGT73P1 for their enzymatic activities. Additionally, comparing with collinear genes in LJ, LmOAS1 and LmUGT73P1 had an interesting phenomenon of 'neighbourhood replication' in LM genome. Collectively, the genomic resource and candidate genes reported here set the foundation to fully reveal the genome evolution of the Lonicera genus and hederagenin-based saponin biosynthetic pathway.

The Anti-Acne Potential and Chemical Composition of Knautia drymeia Heuff. and Knautia macedonica Griseb Extracts.

The treatment of acne and other seborrheic diseases has arisen as a significant clinical challenge due to the increasing appearance of multi-drug resistant pathogens and a high frequency of recurrent lesions. Taking into consideration the fact that some Knautia species are valuable curatives in skin diseases in traditional medicine, we assumed that the thus far unstudied species K. drymeia and K. macedonica may be a source of active substances used in skin diseases. The purpose of this study was to evaluate the antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities of their extracts and fractions. An LC-MS analysis revealed the presence of 47 compounds belonging to flavonoids and phenolic acids in both species while the GC-MS procedure allowed for the identification mainly sugar derivatives, phytosterols, and fatty acids and their esters. The ethanol as well as methanol-acetone-water (3:1:1) extracts of K. drymeia (KDE and KDM) exhibited great ability to scavenge free radicals and good capacity to inhibit cyclooxygenase-1, cyclooxygenase-2, and lipoxygenase. Moreover, they had the most favorable low minimal inhibitory concentration values against acne strains, and importantly, they were non-toxic toward normal skin fibroblasts. In conclusion, K. drymeia extracts seem to be promising and safe agents for further biomedical applications.

Erysiphe lonicerigena sp. nov., a Powdery Mildew Species Found on Lonicera harae.

A powdery mildew (Erysiphaceae) has been continuously collected on the leaves of Lonicera harae in the southern part of the Korean Peninsula, where this shrub is indigenous. Microscopic examination of the asexual morphs revealed that the current collections are differentiated from the all known Erysiphe species on Lonicera spp. by its longer conidiophores and longer conidia. Although the morphology of the chasmothecia is reminiscent of Erysiphe ehrenbergii and E. lonicerae, the specimens on L. harae differ from them in having smaller ascospores. A phylogenetic tree generated from a combined dataset of the internal transcribed spacer region and 28S rDNA gene sequences demonstrates that sequences obtained from three powdery mildew collections on L. harae clustered together as an independent species clade with high bootstrap values distant from other Erysiphe species on Lonicera, representing a species of its own. Based on morphological differences and molecular-phylogenetic results, the powdery mildew on L. harae is proposed as a new species, Erysiphe lonicerigena, and the holomorph of the fungus is described and illustrated in this study.

Secondary metabolites from the underground parts of Valeriana sisymbriifolia Vahl. and their in vitro cytotoxic activities.

Cytotoxic activity-guided isolation studies on the underground parts of Valeriana sisymbriifolia Vahl. led to the isolation of 12 secondary metabolites including two undescribed iridoids, sisymbriifolivaltrate and sisymbriifolioside, and two unreported sesquiterpene lactones, sisymbriifolins A and B. Chemical structures of the isolates were established by extensive 1D and 2D NMR analyses as well as HR-ESI-MS. The in vitro cytotoxic activities of the extract, sub-fractions and isolates on lung (A549), breast (MCF7), gastric (HGC27) and prostate (PC3) cancer cell lines were evaluated by MTS assay. Sisymbriifolivaltrate, didrovaltrate, valtrate, 7-homovaltrate and 1-α-acevaltrate exhibited promising cytotoxic activity on MCF7 cell line with IC50 values ranging from 2.5 to 12.3 µM, while valtrate demonstrated the best cytotoxicity against A549 cells with the IC50 value of 7.5 µM. Valtrate and 7-homovaltrate were found to exert noteworthy cytotoxicity towards HGC27 cell line (IC50 values: 2.3 and 3.7 µM, respectively), whereas valtrate, 7-homovaltrate and 1-α-acevaltrate (IC50 values: 2.3-9.7 µM) were found to be potent cytotoxic against PC3 cells. Among the tested compounds, particularly valepotriate-type iridoids were found to be the main cytotoxic principles of V. sisymbriifolia.

A new acylated iridoid and other chemical constituents from Valeriana jatamansi and their biological activities.

A new acylated iridoid, valejatadoid H (1), along with fourteen known compounds, were obtained from the n-BuOH extract of the roots and rhizomes of Valeriana jatamansi, and their structures were elucidated by various spectroscopic methods. Among them, compounds 8, 11 and 13 exhibited potent inhibition on NO production, with IC50 values of 4.21, 6.08 and 20.36 µM, respectively. In addition, compounds 14 and 15 showed anti-influenza virus activities, among which compound 14 exhibited significant effect with an IC50 value of 0.99 µM.

Iridoids and sesquiterpenoids from Valeriana officinalis and their bioactivities.

Twenty-six iridoids, including six undescribed ones (iridoidvols A-F) and an undescribed natural one, along with ten known sesquiterpenoids were isolated from the roots and rhizomes of Valeriana officinalis. Structurally, iridoidvol A is the first example of iridoid with sesquiterpenoid acid ester. In addition, all of the isolates were evaluated for anti-inflammatory and anti-influenza virus activities. Among them, isovaltrate isovaleroyloxyhydrin exhibited a significant inhibitory effect on NO production with an IC50 value of 19.00 µM.

Scabiosa atropurpurea: A rich source of iridoids with α-glucosidase inhibitory activity evaluated by in vitro and in silico studies.

Scabiosa atropurpurea L. subsp. maritima (L.) Arc. (Caprifoliaceae) is a plant widely distributed in the Mediterranean region and represented by 32 taxa in the flora of Turkey. In the present study, an in-depth phytochemical investigation of S. atropurpurea methanol extract of the whole plant was carried out using a combination of LC-ESI-FT-MS and NMR analysis. This approach allowed the isolation and structural elucidation of 28 compounds: 17 iridoids, 7 flavonoids, and 4 phenolic acids. Among these compounds, three previously unreported iridoids named secologanin-methyl-hemiacetal, atropurpurin A, and atropurpurin B were identified. The methanol extract of S. atropurpurea was assayed for its antioxidant and antihyperglycemic activity, showing a potent α-glucosidase inhibitory activity (IC50 = 100 µg/mL), higher than that exerted by acarbose (IC50 = 196 µg/mL), used as the positive control. Thus, the most abundant iridoids were selected to be tested for their antihyperglycemic activity, and molecular docking experiments were carried out to assess the possibility for selected compounds to form complexes with α-glucosidase enzyme active site.

Lignans from the root of Valeriana jatamansi and their biological evaluation.

Investigation on the chemical components of Valeriana jatamansi Jones (Caprifoliaceae), a new lignan with pyran-ring, dipsalignan G (1), along with eight known compounds (2-9) were isolated. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HR-ESI-MS spectroscopic data. Additionally, possible biosynthetic pathway of 1 was proposed. Finally, biological evaluation results showed that 8 had significant scavenging ability to ABTS and DPPH free radicals, with IC50 values of 1.35 ± 0.01 and 2.94 ± 0.01 µg/ml, respectively.

Effects of the compound extracts of Caprifoliaceae and Scutellaria baicalensis Georgi on the intestinal microbiota and antioxidant function.

According to the Chinese encyclopedia "Ben Cao Gang Mu" (AD 1552-1578), Caprifoliaceae and Scutellaria baicalensis Georgi are used in traditional Chinese medicine to clear heat, detoxify, and treat wind-heat colds, upper respiratory tract infections, and pneumonia. However, the mechanism and the effects of the compound extracts of Caprifoliaceae and Scutellaria baicalensis Georgi on intestinal health remain unclear. From the perspective of intestinal microbes, this study assessed the antioxidant, anti-inflammatory, and intestinal protective properties of Caprifoliaceae and Scutellaria baicalensis Georgi. Mice received diets with or without Caprifoliaceae and Scutellaria baicalensis Georgi extractive (BCA) for 2 weeks in this study. The results showed that BCA increased body weight gain, feed intake, and catalase (CAT) content in the mice but reduced γ-glutamyl transpeptidase (γ-GT) content in the serum (p < 0.05). BCA improved the Sobs, Chao, and Ace indices, as well as the number of Campylobacterota, Patercibacteria, and Desulfobacterota in the colon microbiota, while it decreased the Firmicutes phylum (p < 0.05). At the genus level, BCA increased Candidatus_Saccharimonas, Helicobacter, unclassified_f_Lachnospiraceae, Alistipes, norank_f_norank_o_Clostridia_vadinBB60_group, norank_f_Ruminococcaceae, unclassified_f_Ruminococcaceae, etc. abundance (p < 0.05), but it significantly decreased Lactobacillus and Lachnospiraceae_UCG_001 abundance (p < 0.05). Moreover, BCA improved the concentration of acetic acid, butyric acid, propionic acid, valeric acid, and isovaleric acid and diminished the concentration of isobutyric acid (p < 0.05). Correlation analysis shows that the changes in short-chain fatty acids and antioxidant and inflammatory indices in the serum were significantly correlated with the BCA-enriched microbiota. This study supplemented a database for the application of Caprifoliaceae and Scutellaria baicalensis Georgi in clinical and animal production.

Evaluation of Lonicera etrusca var. etrusca Santi (Caprifoliaceae) Stem and Leaf in Terms of Anatomical Structures and Some Phenolic Compounds.

Objectives: The genus Lonicera includes medicinally important plants. Two varieties of L. etrusca have been recorded in Türkiye. Anatomical structures and phytochemical contents are important in the diagnosis and identification of medicinal plants. This study included stem and leaf anatomy of L. etrusca var. etrusca and high performance liquid chromatography (HPLC) analysis of the methanol extracts obtained from these parts. Materials and Methods: Plant materials were collected from Ankara. Methanol extracts were prepared from the stems and leaves by ultrasonic bath. The amounts of chlorogenic acid and caffeic acid that are major compounds in the stem and leaves, were determined by HPLC. For anatomical studies, specimens were preserved in 70% alcohol. Transverse and surface sections were prepared by hand. Detection of tissues was performed using Sartur reagent. Anatomical specimens were examined using a light microscope and microphotographed. Results: In HPLC analysis, the highest amount of chlorogenic acid was determined in the leaf (1.148%), and the highest amount of caffeic acid (0.156%) was determined in the stem. In the anatomical analysis, it was observed that the stem was disc-shaped and hollow; pericycle is in a ring form, consists of fibre-like cells with thick walls and wide lumina; cork occurs adjoining pericyclic fibers; thin-walled pith cells containing dense druse crystals. The leaf lamina is bifacial in the transverse section; palisade and spongy parenchyma, both contain abundant starch grains; solitary druse crystals are sparse in the leaf mesophyll; the stomata were observed only on the lower surface with 3-5 subsidiary cells. With this study, L. etrusca var. etrusca has been clarified in terms of its anatomical structures and phenolic compounds. Conclusion: The chemical contents and anatomical structures of the plant may contain important information that can be used in classification. This study may support in taxonomically classification for the L. etrusca var. etrusca.

Activity-Guided Isolation of Cytotoxic Non-Glycosidic Ester Iridoids from Valeriana alliariifolia Adams and Unravelling Their Cell Death Mechanisms.

The aim of this study was to isolate the cytotoxic compounds from V. alliariifolia via activity-guided isolation and to determine the mechanism of actions of the most potent ones. The crude EtOH extract as well as CHCl3 and AcOEt subextracts demonstrated remarkable cytotoxic activities against A549, MCF7, HGC27 and PC3 cancer cells. Sequential chromatographic separations on active subextracts yielded 14 secondary metabolites, including 11 iridoids (1-11) most of which belong to non-glycosidic ester iridoids, two phenylpropanoids (12 and 13) and one lignan (14). The chemical structures of purified compounds were elucidated by NMR and MS analysis. Among the isolates, 7-deisovaleroylvaltrate (3) was isolated for the first time as a natural product. According to the cytotoxic assay compounds, 2, 4-6 and 8 were found to be the potent cytotoxic compounds (IC50 <10 µM) against at least one of the tested cancer cell lines. Thus, 2, 4-6 and 8 were investigated for their effects on apoptotic, necrotic and autophagic pathways as well as cell cycle progression. They exerted anticancer activities by inducing different cell death mechanisms depending on the cancer cells. The results demonstrated that 2, 4-6 and 8 could be potential anticancer drug leads that deserve further in vivo and clinical studies on the way to discover novel natural compounds with anticancer properties.

Complete plastome sequence of Lonicera gynochlamydea Hemsl. (Caprifoliaceae).

We report and characterize the complete plastome of Lonicera gynochlamydea Hemsl. L. gynochlamydea is a shrub, belonging to the family Caprifoliaceae. Our results show that the length of the complete plastome is 154,643 bp, including 131 genes consisting of 84 protein-coding genes, 39 tRNA genes, and eight rRNA genes. The plastome exhibits the typical quadripartite structure and gene content of angiosperms, composed of two inverted repeats (IRs) regions of 23,846 bp, a large single-copy (LSC) region of 88,298 bp, and a small single-copy (SSC) region of 18,653 bp. The total G/C content in L. gynochlamydea plastome is 38.4%. The complete plastome sequence of L. gynochlamydea will make contributions to the conservation genetics of this species as well as to phylogenetic studies in Caprifoliaceae.

Jatavaleridoids A-H, eight new iridoids from the roots and rhizomes of Valeriana jatamansi Jones.

Eight new iridoids, jatavaleridoids A-H (1-8), were isolated from the roots and rhizomes of Valeriana jatamansi. Their structures and absolute configurations were elucidated based on NMR and HRESIMS spectroscopic data, as well as quantum chemical calculation. Structurally, compounds 1-5 and 8 were rare iridoids with long-chain fatty acid esters at C-10. In addition, compound 7 showed cytotoxicity, while compounds 1 and 2 exhibited inhibition on NO production.

Stability of valeriana-type iridoid glycosides from rhizomes of Nardostachys jatamansi and their protection against H2O2-induced oxidative stress in SH-SY5Y cells.

Nardostachys jatamansi is close to Valerian in consideration of their same psychoactive effects, such as sedation and neuroprotection. Valeriana-type iridoids are major active components of Valerian, but few valeriana-type iridoids have been isolated from N. jatamansi. Iridoid-targeting chemical investigation of the rhizomes of N. jatamansi resulted in the isolation of seven valeriana-type iridoid glycosides, four of which are previously undescribed. Their structures were determined through NMR spectroscopy, high-resolution mass spectrometry, and optical rotation experiments. In addition, the inaccurate configurations of patrinalloside and 6″-acetylpatrinalloside from previous reports were corrected. These compounds, unstable due to alcoholic solvents, were more stable in the mixtures than in purified forms, as monitored by the qNMR method, supporting the use of natural products as mixtures. Furthermore, the isolates, as well as crude and solvent partition extracts, were found to have a protective effect against hydrogen-peroxide-induced toxicity in human neuroblastoma cells, as confirmed by assays for cell viability and antioxidation. These findings suggest the potential therapeutic application of the valeriana-type iridoid glycosides isolated herein with improved biochemical stability.

Two new triterpenoid saponins from the underground parts of Weigela x "Bristol Ruby".

Two new triterpenoid saponins, 3-O-ß-D-xylopyranosyl-(1→4)-[ß-D-xylopyranosyl-(1→3)]-ß-D-glucopyranosyl-(1→4)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-ß-D-arabinopyranosyloleanolic acid (1) and 3-O-ß-D-xylopyranosyl-(1→4)-[α-L-arabinopyranosyl-(1→3)]-ß-D-glucopyranosyl-(1→4)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-ß-D-xylopyranosyloleanolic acid (2), were isolated and elucidated from the underground parts of Weigela x "Bristol Ruby". Their structures were established by interpretation of spectroscopic data (1 D and 2 D NMR) and mass spectrometry (MS).

Development and Characterization of 20 Genomic SSR Markers for Ornamental Cultivars of Weigela.

Weigela (Caprifoliaceae) is a genus of ornamental plants popular for its phenotypic variation and hardiness, that includes species hybridized to produce the commercially available cultivars. Despite its popularity, limited genetic resources exist for the genus. Twenty genomic simple sequence repeat (gSSR) markers distributed across the genome were developed using low coverage whole-genome sequencing data of Weigela Spilled Wine®. A cross-amplification evaluation with these 20 gSSR markers on a collection of 18 Weigela cultivars revealed a total of 111 unique alleles, including 36 private alleles. A diagrammatic key was constructed to identify cultivars using only six of the gSSR markers, demonstrating the newly developed gSSR markers are immediately useful for cultivar identification. Future uses could include breeding with marker-assisted selection, determining the history of hybridization of the current cultivated lines, aiding in the construction of genetic maps, and assessing the patterns of population genetic structure of Weigela spp.

The complete chloroplast genome of Lonicera acuminata Wall. and its phylogenetic analysis.

Lonicera acuminata Wall. is a medicinal and edible homologous plant in folk medicine that displays excellent pharmacological activities. However, the phylogenetic relationship between L. acuminata and other related family members remains unclear. In this study, we assembled the chloroplast genome of L. acuminata. The circular chloroplast genome was 154,282 bp in size, including a large single-copy region of 88,373 bp and a small single-copy region of 18,455 bp, which were separated by two inverted repeat regions (23,727 bp each). A total of 128 genes were predicted, including 8 ribosomal RNAs, 37 transfer RNAs and 83 protein-coding genes. The phylogenetic analysis revealed that L. acuminata was clustered together with L. pampaninii, L. macranthoides and L. hypoglauca.

Iridoids and sesquiterpenoids from Valeriana jatamansi and their anti-influenza virus activities.

Twenty-one new iridoids, jatamansidoids A-U (1-12, 21-26, 32, 35 and 36), two new natural ones, jatamansidoids V (37) and W (38), eighteen known ones (13-20, 27-31, 33 and 34), together with three patchoulol-type sesquiterpenoids (39-41), were isolated from the roots and rhizomes of Valeriana jatamansi. Structurally, compounds 1-7 were the first examples of iridoids from V. jatamansi with unique α, ß, γ, δ-unsaturated aldehyde fragment between C-11, C-4, C-5, C-9 and C-8; compound 8 was an unprecedented iridoid derivative with a methyl group (Me-10) at C-1, rather than C-8, and its plausible biogenetic pathway was proposed in this paper; compounds 22 and 23 were the first examples of Δ4(5)-iridoids simultaneously replaced by oxygen-containing groups at C-3, C-6 and C-7; compound 24 was the first iridoid with both 6,7- and 1,10-epoxy fragments. The structures and absolute configurations of new compounds were elucidated based on extensive spectroscopic techniques and quantum chemical calculation. Furthermore, compounds 13-15 and 39-41 exhibited potent anti-influenza virus activities with H1N1 and H3N2 strains, with IC50 values of 0.21-1.48 µM.