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Iridoids are a large family of monoterpenoids found in traditional medicinal plants and show significant effects for the human species. In addition to their wide range of biological activities, such as neuroprotective and antitumor activities, the cis‐fused bicyclic ring systems of iridoids are still attractive as synthetic targets to apply novel synthetic methodologies. Accordingly, recent progress regarding the biosynthesis and chemical synthesis of iridoids is covered in this minireview. Identification of new enzymes for the iridoid biosynthesis in Catharanthus roseus and ingenious synthetic strategies for the construction of the iridoid skeleton are described. [ABSTRACT FROM AUTHOR]

Nepetalactol, an iridoid with four chiral carbons, is a crucial component of aphid sex pheromones that have been employed with great success to control the insect-related diseases. Despite of agricultural usage as end products, iridoids are fundamental biosynthetic intermediates for pharmaceutically important monoterpenoid indole alkaloids such as camptothecin (CAM) and vinca alkaloids. Herein we characterized 10-hydroxygeraniol oxidoreductase (10HGO) and iridoid synthase (IS) from Camptotheca acuminata , a CAM-producing plant, and reported their application in biological preparation of nepetalactol. Ca10HGO and CaIS were respectively cloned from C. acuminata , overexpressed in Escherichia coli , and purified to homogeneity. Ca10HGO catalyzes the oxidation of 10-hydroxygeraniol into 10-oxogeranial, in which NADP+ was reduced to NADPH. CaIS catalyzes nepetalactol formation from 10-oxogeranial using NADPH cofactor. The net outcome of the two reactions generate nepetalactol from 10-hydroxygeraniol efficiently, indicating NADP+ - NADPH recycling. Ca10HGO and CaIS were co-overexpressed in E. coli under optimized fermentation conditions to prepare cell-based catalysts that catalyze the conversion of 10-hydroxygeraniol into nepetalactol. The present work shows the enzymatic conversion of 10-hydroxygeraniol into nepetalactol involved in CAM biosynthesis. Co-overexpression of Ca10HGO and CaIS in E. coli is an alternative valuable cell-based biotransformation process with regenerating recycling of NADP+ - NADPH cofactors for nepetalactol preparation. • Ca10HGO and CaIS were cloned from camptothecin-producing plant Camptotheca acuminata. • Ca10HGO and CaIS were expressed in Escherichia coli and functionally characterized. • In vitro combinatory assays of Ca10HGO and CaIS verified recycling of NADP+ - NADPH. • 10-Hydroxygeraniol was converted into nepetalactol by E. coli expressing Ca10HGO-IS. [ABSTRACT FROM AUTHOR]

The influences of freezing pretreatment, thermal pretreatments (water blanching and steam blanching) and their combinations on hot-air drying kinetics of Vaccinium bracteatum Thunb (VBT) leaves at 60°C and key quality attributes were investigated. Generally, all the applied pretreatments accelerated VBT leaf drying process. The sequential freezing (8 h) and water blanching (1 min) pretreatments shortened the drying time by 65.5%. The diffusion modeling results revealed that all the pretreatments intensified water diffusion and external water exchange with hot air during drying. Freezing pretreatments had no preservative effect on phenolics, iridoids, and antioxidant capacity of VBT leaves after dehydration, whereas both thermal pretreatments significantly improved dried VBT leaf quality in these three aspects. On the contrary, thermal pretreatments had destructive effects on activities of polyphenol oxidase and β-glucosidase. Due to the low β-glucosidase activity in dried VBT leaves with thermal pretreatments that participated in the transformation of iridoids to generate dark colorants eventually, the extracts from dried VBT leaves with only thermal pretreatments had weak ability to dye glutinous rice. However, this problem was fixed once extra β-glucosidase was added before rice cooking. Overall, the obtained results can provide guidance for the preservation and drying of VBT leaves that has been poorly studied. [ABSTRACT FROM AUTHOR]

Morinda genus of Rubiaceae has been widely used in medicine at home and abroad. Many parts of Morinda tree are utilized in research, mainly including roots, stems, leaves, branches and seeds. Through the research of online databases, the chemical components and biological activities of the iridoids in Morinda genus were summarized in this paper. Up to now, more than 50 kinds of iridoids have been identified. In addition, more and more studies proved that Morinda iridoids might benefit human via such anti-inflammatory, antinociceptive, anti-oxidation, anti-tumor and bone protection. The theoretical basis was provided for the further development and utilization of the iridoids in Morinda genus. [ABSTRACT FROM AUTHOR]

Four ursane-type triterpenoid glycosides (1-4), two benzophenone glycosides (5 and 6), and one iridoid glucoside (7) were isolated and characterized from the dried roots of Vangueria agrestis. Compounds 1 (3-O-[α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl]pomolic acid 28-O-β-D-glucopyranosyl ester) and 5 (2-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyl]-6,4′-dihydroxy-4-methoxy benzophenone) were found to be new metabolites. The identity of all compounds has been accomplished, primarily, based on 1 D and 2 D NMR and HRESMS analysis. Compounds 6 and 2, showed inhibitory effect against Trypanosoma brucei with IC50 22.3 µM for 6 and IC50 11.1 µM, IC90 12.3 µM for 2. [ABSTRACT FROM AUTHOR]

• 10 compounds were isolated from Adenosma caeruleum aerial parts. • Structures of 3 new iridoids adenocaeroids A−C and 7 known analogs were identified. • NO inhibitory effects of the isolated compounds were evaluated in BV2 cells. • PTP1B inhibitory effects of the isolated compounds were examined. Three new iridoids, adenocaeroids A−C (1 − 3), and seven known analogs, umbellatolide B (4), pedicularis-lactone (5), iridolactone (6), artselaenin C (7), eucommiol (8), rehmaglutin D (9), and 3-deoxy-artselaenin C (10) were isolated from the aerial parts of Adenosma caeruleum. Their chemical structures were identified by the comprehensive spectroscopic methods, including 1D and 2D NMR and HRESI mass spectra. The relative configurations of 1−3 were established by analyzing their NOESY spectra as well as by DFT-GIAO NMR calculations followed by ML- J -DP4, DP4+, and DU8 methods. The absolute configurations of 1−3 were determined by comparing experimental and calculated ECD spectra and specific optical rotation values. All of the compounds, except 7 and 10 , inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV2 microglial cells in a dose-dependent manner, with IC 50 values ranging from 28.4−61.8 µM. However, none of the compounds showed inhibitory effect on protein-tyrosine phosphatase 1B (PTP1B) activity. [Display omitted] [ABSTRACT FROM AUTHOR]

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 IC 50 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. Seventeen undescribed iridoid derivatives were identified from H. diffusa. And three of them exhibited potent nitric oxide (NO) inhibitory effects in LPS-stimulated RAW264.7 cells with IC 50 values of 5.69, 6.16, and 6.84 μM, respectively. [Display omitted] • Seventeen undescribed iridoid derivatives were identified from Hedyotis diffusa. • Eight compounds possess unique long-chain aliphatic acid moiety. • Compounds 2, 4, and 6 showed significant suppression effects on NO production in LPS-induced RAW264.7 cells. • The long-chain aliphatic moieties at C-10 might be the key group for their anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl−), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.

Background/Aims: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, and it is usually characterized by chronic inflammation, oxidative stress, and altered microRNA expression. The aim of this study is to investigate how the effects of iridoids with genipin stem nucleus inhibit PCOS complications. The interactions between iridoids were investigated, as well. Methods: The chronic inflammation cell model was induced using lipopolysaccharide (LPS) in the RAW 264.7 and KGN cell lines. Levels of mRNA and protein expression were quantified using real time-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The target of the iridoids was identified using the drug affinity responsive target stability (DARTS) method. The ability to scavenge free radicals was evaluated using the DPPH radical scavenging method and the ultra oxygen anion (O2-) radical scavenging method. Results: The cells recovered from the inflammatory conditions and showed significantly decreased levels of interleukins after treatment with iridoids. The iridoids were demonstrated to target NF-κB, inhibit the phosphorylation and degradation of IκB, inhibit the nuclear entry of NF-κB, and inhibit the expression of inflammatory factors. Though only genipin showed an efficient ability to scavenge O2-, the iridoids, IκB inhibitor (BAY 11-7085), and NF-κB inhibitor (PDTC) could inhibit LPS-induced oxidative stress on the cells, indicating that the iridoids exert their anti-oxidant effects via the NF-κB pathway. The expression levels of microRNAs (miRNAs) were also altered by LPS, but the iridoids could scarcely rescue the abnormal condition. Conclusion: Chronic inflammation may be an important incentive for oxidative stress and abnormal microRNA expression in PCOS, and iridoids can protect patients from inflammatory damage by regulating the NF-κB pathway.

Some herbivorous insects sequester chemicals from their host plants, which can serve as a defense against predators. However, sequestration can also be costly, impacting immunological responses important for other types of natural enemies, such as parasites and pathogens. These costs could also vary across herbivorous insect development, as both immune function and sequestration abilities change, although few studies have assessed variation in the cost of sequestration across life stages. The buckeye, Junonia coenia (Nymphalidae), is a specialist butterfly that sequesters iridoid glycosides from its host plants, including the introduced weed, Plantago lanceolata (Plantaginaceae). To determine the immunological costs of sequestration and how the immune response varies with host plant and across development, we reared caterpillars on a native host plant, Mimulus guttatus (Phrymaceae), which does not contain iridoid glycosides, and on P. lanceolata, which does. We assayed immune function across 3rd, 4th, and 5th instar caterpillars, estimating both hemocyte density and the ability of hemocytes to encapsulate foreign bodies by challenging the immune system with nylon filaments. For caterpillars reared on P. lanceolata, we then explored the relationships between iridoid glycoside sequestration and immune function across instars. We found that while hemocyte density tended to increase with instar regardless of host plant, caterpillars reared on P. lanceolata had lower encapsulation ability, and encapsulation decreased with increasing sequestration of iridoid glycosides, though patterns varied between instars and experimental periods. Interestingly, immune challenged caterpillars sequestered more iridoid glycosides than unchallenged caterpillars, suggesting that caterpillars responded to immune challenge by sequestering or retaining more iridoids, even though that may decrease their ability to encapsulate. These results suggest that sequestration can have important consequences for immune function across caterpillar development, and that the incorporation of novel hosts may affect defense against natural enemies.

Iridoids, which are a class of monoterpenoids, are attractive synthetic targets due to their diversely substituted cis-fused cyclopenta[c]pyran skeletons. Additionally, various biological activities of iridoids raise the value of synthetic studies on this class of compounds. Here, our synthetic efforts toward 11-noriridoids; (±)-umbellatolide B (6), (±)-10-O-benzoylglobularigenin (9) and 1-O-pentenylaucubigenin (34) are described. For the efficient synthesis of target compounds, common synthetic intermediates (tricyclic enones 17 and 26) were prepared by the Pauson-Khand reaction. The cleavage of the acetal bond on the tricyclic enones and 1,2-reduction introduced the two hydroxy groups on the cyclopentane ring of the core scaffold. Furthermore, the C3-C4 olefin part was constructed by the syn-elimination of a thiocarbonate moiety to obtain 34. The developed synthetic routes for 6, 9, and 34 will be useful for the preparation of iridoid analogs that have a polyfunctionalized core skeleton.

Extracts from the plants Phlomis umbrosa and Dipsacus asperoides—which are widely used in Korean and Chinese traditional medicine to treat osteoarthritis and other bone diseases—were used to treat experimental osteoarthritis (OA) rats. Genome-wide differential methylation regions (DMRs) of these medicinal-plant-treated rats were profiled as therapeutic evidence associated with traditional medicine, and they need to be investigated further using detailed molecular research to extrapolate traditional practices to modern medicine. In total, 49 protein-encoding genes whose expression is differentially regulated during disease progression and recovery have been discovered via systematic bioinformatic analysis and have been approved/proposed as druggable targets for various bone diseases by the US food and drug administration. Genes encoding proteins involved in the PI3K/AKT pathway were found to be enriched, likely as this pathway plays a crucial role during OA progression as well as during the recovery process after treatment with the aforementioned plant extracts. The four sub-networks of PI3K/AKT were highly regulated by these plant extracts. Overall, 29 genes were seen in level 2 (51–75%) DMRs and were correlated highly with OA pathogenesis. Here, we propose that these genes could serve as targets to study OA; moreover, the iridoid and triterpenoid phytochemicals obtained from these two plants may serve as potential therapeutic agents.

Phytochemical investigation on the 70% aqueous EtOH extract from the roots of Patrinia scabra led to the isolation and characterization of five new non-glycosidic iridoids, patriscabrins F–J (1–5), along with a known iridoid 11-ethoxyviburtinal (6). The structures of the new compounds 1–5 were determined by interpretation of spectroscopic data, particularly by 1D- and 2D-NMR and ECD studies. Thereafter, the isolates 1–6 were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. Of these, patriscabrin F (1) exhibited the most potent inhibitory effect with observed IC50 value of 14.1 μM. In addition, patriscabrin G (2) and 11-ethoxyviburtinal (6) showed IC50 values 24.6 and 35.5 μM, respectively. [ABSTRACT FROM AUTHOR]

Five new iridoids (1-5), jiohenrins A-E, together with sixteen known compounds (6-21), were isolated from the whole plants of Rehmannia henryi. The structures of these compounds were elucidated on the basis of their spectroscopic data. [ABSTRACT FROM AUTHOR]

• One new sesquiterpene, one new iridoid derivative and 10 known compounds were isolated from the whole plants of Valeriana amurensis. • 1 was determined by single-crystal X-ray diffraction analysis with Cu-Kα irradiation. • Compound 12 displayed significant anti-inflammatory activity with IC 50 value of 1.97 μM. One new sesquiterpene 1 S , 3 S , 4 S , 7 S 3,4-dihydroxy-bisabolol (1), one new iridoid amurensin A (2) and 10 known compounds were isolated from the whole plants of Valeriana amurensis. Their structures were established on the basis of extensive spectroscopic analysis and the absolute stereochemistry of compound 1 was assigned by X-ray diffraction analysis with Cu-Kα irradiation. All of compounds were evaluated for their inhibitory effects on NO production in LPS-induced RAW264.7 macrophages. Compound 12 displayed significant anti-inflammatory activity with IC 50 value of 1.97 μM. [ABSTRACT FROM AUTHOR]

Summary: Despite the phylogenetic distance between plants and insects, these two groups of organisms produce some secondary metabolites in common. Identical structures belonging to chemical classes such as the simple monoterpenes and sesquiterpenes, iridoid monoterpenes, cyanogenic glycosides, benzoic acid derivatives, benzoquinones and naphthoquinones are sometimes found in both plants and insects. In addition, very similar glucohydrolases involved in activating two‐component defenses, such as glucosinolates and cyanogenic glycosides, occur in both plants and insects. Although this trend was first noted many years ago, researchers have long struggled to find convincing explanations for such co‐occurrence. In some cases, identical compounds may be produced by plants to interfere with their function in insects. In others, plant and insect compounds may simply have parallel functions, probably in defense or attraction, and their co‐occurrence is a coincidence. The biosynthetic origin of such co‐occurring metabolites may be very different in insects as compared to plants. Plants and insects may have different pathways to the same metabolite, or similar sequences of intermediates, but different enzymes. Further knowledge of the ecological roles and biosynthetic pathways of secondary metabolites may shed more light on why plants and insects produce identical substances. [ABSTRACT FROM AUTHOR]

Eight new iridoids (1–8) and an ionone glucoside (9), together with 31 known compounds (10–40), were isolated from the whole plants of Rehmannia henryi. The structures of these compounds were elucidated on the basis of their spectroscopic data and chemical evidence. [ABSTRACT FROM AUTHOR]

A new iridoid glycoside, named camptoside (1), together with three known compounds as dehydrodiconiferyl alcohol-9′- O - β - d -glucopyranoside (2), aesculetin (3) and vajicoside (4), have been isolated from Camptosorus sibiricus Rupr. (Aspleniaceae). Their structures were established on the basis of spectroscopic analysis, especially 1D- and 2D-NMR data, and by comparison of their spectroscopic and physical data with those reported in the literature. Compounds 1–3 exhibited inhibitions of nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophages with IC 50 values of 11.2, 8.3 and 9.4 μM, respectively. Unlabelled Image [ABSTRACT FROM AUTHOR]

One new and three known compounds were isolated from the ethanol extract of Psychotria prainii aerial parts. By means of spectroscopic methods, their structures were elucidated to be deacetylasperulosidic acid 6-ethyl ether (1), asperulosidic acid (2), asperuloside (3) and obtucarbamates C (4). The isolated compounds were evaluated for their inhibitory effect on NO production in LPS-stimulated RAW264.7 cells. Among them, compounds 2 and 4 exhibited strong effect with the IC50 values of 5.75 ± 0.85 and 6.92 ± 0.43 μM, respectively. This is the first report for the chemical composition and biological activity of P. prainii. [ABSTRACT FROM AUTHOR]

Caryopincaolide M (1), a new rearranged abietane diterpenoid with an unusual pent-4-enoic acid group on a 6/6/5 tricyclic ring system, and 7-epi-8-dehydroxypatriscabrol (3), a new iridoid, together with 17 known compounds, have been isolated from the whole plant of Caryopteris incana (Thunb.) Miq. Their structures were elucidated on the basis of 1-D and 2-D NMR, IR, and mass spectroscopic data. Compounds 1-5 were evaluated for their inhibitory activities against enzyme α-glucosidase, and the results showed that only 1 has moderate inhibitory activity against enzyme α-glucosidase with IC50 at 528.3 ± 12.37 mg/L. [ABSTRACT FROM AUTHOR]

Ten previously undescribed iridoid constituents, viburnshosins A−E (1 − 5) and viburnshosides A−E (6 − 10), together with one known analogue (11), were isolated from the branches of Viburnum chinshanense. Their structures were unambiguously elucidated by a comprehensive analysis of 1D and 2D NMR data, together with HRESIMS spectroscopic data. The absolute configurations of compounds 1 − 10 were assigned by means of the calculated ECD spectra. Interestingly, compounds 2 and 3 are the first iridoids with an unusual C-3−C-7 oxo bridge. Compounds 4 , 5 , and 10 displayed remarkable inhibitory effects against α -amylase (IC 50 : 38.42, 37.65, and 21.64 μM, respectively) and α -glucosidase (IC 50 : 12.97, 19.34, and 25.71 μM, respectively), comparable to those of the positive control acarbose (IC 50 : 39.75 and 23.66 μM, respectively). The interaction modes of compounds 4 and 10 with two enzymes were analyzed by molecular modeling. The study on the chemical constituents of Viburnum chinshanense led to the isolation of ten previously undescribed iridoids and one known analogue, and their inhibition against α -amylase and α -glucosidase was evaluated in vitro and in silico. [Display omitted] • Ten previously undescribed iridoid constituents were isolated from V. chinshanense. • Viburnshosins B and C are two iridoids with an unusual C-3–C-7 oxo bridge. • Compounds 4 , 5 , and 10 showed potent inhibition on α -amylase and α -glucosidase. • The binding modes of compounds 4 and 10 with two enzymes were simulated. [ABSTRACT FROM AUTHOR]

The asymmetric synthesis of a compound with the cyclopentan[c]pyran core of iridoid natural products in four steps and 40% overall yield is reported. Our methodology includes a one-pot tandem domino reaction which provides a trisubstituted cyclopentane with five new completely determined stereocenters, which were determined through 2D homo and heteronuclear NMR and n.O.e. experiments on different compounds specially designed for this purpose, such as a dioxane obtained from a diol. Due to their pharmaceutical properties, including sedative, analgesic, anti-inflammatory, CNS depressor or anti-conceptive effects, this methodology to produce the abovementioned iridoid derivatives, is an interesting strategy in terms of new drug discovery as well as pharmaceutical development.

The roots and rhizomes of Valeriana jatamansi have long been used as folk medicine in Asia and usually named as “Zhizhuxiang” in Chinese for the treatment of abdominal distention and pain. However, its active ingredients and molecular targets for treatment of abdominal pain remain unrevealed. Inhibitors of Cav2.2 N-type voltage-gated calcium channels (VGCCs) are actively sought after for their potential in treating pain, especially chronic pain. As far as we know, the method used for seeking analgesic active ingredient from plant material has rarely been reported. The analgesic potentials of the EtOH extract (0.01 mg/ml) of the roots and rhizomes of V. jatamansi and its EtOAc, n-BuOH and H2O soluble parts (0.01 mg/ml, respectively) were tested herein on Cav2.2, using whole-oocyte recordings in vitro by tow-electrode voltage clamp. The results indicated that the EtOAc-soluble part exhibited the most potent inhibition of Cav2.2 peak current (20 mv). The EtOAc-soluble part was then subjected to silica gel column chromatography (CC) and giving 9 fractions. Phytochemical studies were carried out by repeated CC and extensive spectroscopic analyses after the fraction (0.01 mg/ml) was identified to be active and got seventeen compounds (1–17). All isolates were then sent for further bioactive verification (1 and 3 at concentration of 10 μM, others at 30 μM). In addition, the selectivity of the active compounds 1 and 3 were tested on various ion channels including Cav1.2, Cav2.1 and Cav3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. The results indicated that compound 1 and 3 (an abundant compound) inhibited Cav2.2 with an EC50 of 3.3 and 4.8 μM, respectively, and had weaker or no effect on Cav1.2, Cav2.1 and Cav3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. Compounds 1 and 3 appear to act as allosteric modulators rather than pore blockers of Cav2.2, which may play crucial role in attenuating nociception. The results of present research indicated that the ethnopharmacological utilization of V. jatamansi for relieving the abdominal distention and pain may mediate through Cav2.2 channel. Our work is the first demonstration of inhibition of Cav2.2 by iridoids, which may provide a fresh source for finding new analgesics.

On continuation of the phytochemical investigation of the MeOH extract of Cyperus rotundus L. Rhizomes, four compounds namely, methyl 3,4-dihydroxy benzoate (1), ipolamiide (2), 6β-hydroxyipolamiide (3), and rutin (4) were isolated. Their structures were established on the basis of 1D and 2D NMR spectroscopic analyses as well as ESIMS spectral data. Compounds 2 and 3 are reported here for the first time from the genus Cyperus and 1 for the first time from the plant. Co-treatment of CCl4 hepatic injured rats with the total MeOH extract (TME) and EtOAc fraction significantly restored the hepatic marker enzymes and total bilirubin to near-normal values compared to silymarin (reference drug).

Context: Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disease caused by excessive proliferation and abnormal differentiation of hematopoietic stem cells. Asperuloside (ASP) is considered to have good biological activity and may be a good anti-CML drug., Objective: This study aimed to explore the effects and possible mechanisms of ASP on the biological behavior of K562 cells based on RNA-seq., Materials and Methods: The IC 50 of ASP in K562 cells was calculated by the concentration-effect curve. Cell viability, apoptosis, and differentiation were detected by CCK8, flow cytometry, benzidine staining, and WB analysis, respectively. Further, RNA-seq was used to analyze the possible mechanism of ASP regulating K562 cells., Results: ASP significantly inhibited the proliferation, and promoted apoptosis and differentiation of K562 cells. A total of 117 differentially expressed genes were screened by RNA-seq, mainly involved in the RAS/MEK/ERK pathway. PD98059 was used to inhibit the RAS/MEK/ERK pathway in K562 cells, and results confirmed that PD98059 could not only inhibit the RAS/MEK/ERK pathway, but also inhibit the regulation of ASP on the proliferation and differentiation of K562 cells., Conclusion: ASP inhibited the proliferation, promoted apoptosis and differentiation of K562 cells by regulating the RAS/MEK/ERK pathway, and played a good anti-CML role., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A 1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 μg/mL. At concentration of 20 μM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9)., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Three new iridoids, namely neonanin A (1), neonanin B (2) and neoretinin A (3), as well as twelve known compounds, 6-hydroxy-7-methyl-1-oxo-4-carbomethoxyoctahydrocyclopenta[c]pyran (4), 4-epi-alyxialactone (5), loganetin (6), loganin (7), phenylcoumaran-α'-aldehyde (8), cleomiscosin A (9), ficusal (10), balanophonin (11), vanillic acid (12), p-coumaric acid (13), cis,trans-abscisic acid (14), and trans,trans-abscisic acid (15) were isolated from the stems of Neonauclea reticulata (Havil.) Merr. These new structures were determined by the detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1-13 were evaluated using an in-vitro MTT cytotoxic assay for hepatocellular carcinoma (HCC) cells, and the preliminary results showed that ficusal (10), balanophonin (11), and p-coumaric acid (13) exhibited moderate cytotoxic activity, with EC50 values of 85.36 ± 4.36, 92.63 ± 1.41, and 29.18 ± 3.48 µg/mL against Hep3B cells, respectively. [ABSTRACT FROM AUTHOR]

The evolution of chemical complexity has been a major driver of plant diversification, with novel compounds serving as key innovations. The species-rich mint family (Lamiaceae) produces an enormous variety of compounds that act as attractants and defense molecules in nature and are used widely by humans as flavor additives, fragrances, and anti-herbivory agents. To elucidate the mechanisms by which such diversity evolved, we combined leaf transcriptome data from 48 Lamiaceae species and four outgroups with a robust phylogeny and chemical analyses of three terpenoid classes (monoterpenes, sesquiterpenes, and iridoids) that share and compete for precursors. Our integrated chemical–genomic–phylogenetic approach revealed that: (1) gene family expansion rather than increased enzyme promiscuity of terpene synthases is correlated with mono- and sesquiterpene diversity; (2) differential expression of core genes within the iridoid biosynthetic pathway is associated with iridoid presence/absence; (3) generally, production of iridoids and canonical monoterpenes appears to be inversely correlated; and (4) iridoid biosynthesis is significantly associated with expression of geraniol synthase, which diverts metabolic flux away from canonical monoterpenes, suggesting that competition for common precursors can be a central control point in specialized metabolism. These results suggest that multiple mechanisms contributed to the evolution of chemodiversity in this economically important family. [ABSTRACT FROM AUTHOR]

Screening of EtOAc soluble fraction of Plantago asiatica (Plantaginaceae) using HPLC–MS/MS coupled DPPH online assay suggested the presence of antioxidant compounds, which characterized as phenylethanoid glycosides. Twenty-nine compounds including three new compounds, plantalides A–C, a phenylethanoid ( 1 ), a phenolic compound ( 9 ) and an iridoid ( 10 ), were isolated from P. asiatica. Consistent with HPLC–MS/MS analysis, seven phenylethanoid glycosides ( 1–7 ) including a new phenylethanoid glycoside ( 1 ) showed antioxidant with ranging IC 50 values of 22.9–88.5 μM. These results suggested that phenylethanoid glycosides were contributed to the antioxidant activity of P. asiatica and HPLC–MS/MS coupled online assay is powerful tool for predicting active compounds with short time and limited amounts. [ABSTRACT FROM AUTHOR]

The extract of the aerial and underground parts of Phlomis likiangensis afforded two new iridoid derivatives, namely as phloloside H ( 1 ) and phloline ( 2 ), along with four known compounds ( 3 – 6 ), and compound 2 was a novel normonoterpene. Their structures were elucidated on the basis of spectroscopic studies and chemical methods. Six compounds were assayed for cytotoxic, antibacterial and antioxidative activities, but were either inactive or very weakly active. [ABSTRACT FROM AUTHOR]

The genus Pentas belongs to the Rubiaceae family, which contains approximately 40 species. Several Pentas species were reported to be used as a folk treatment by African indigenous people in treating some diseases such as malaria, tapeworms, dysentery, gonorrhea, syphilis and snake poisoning. This article covers the period from 1962 to 2017 and presents an overview of the biological activity of different Pentas species and describes their phytochemical traits. As a conclusion, the main secondary metabolites from Pentas species are quinones, highly oxygenated chromene-based structures, and iridoids. Pentas species are widely used in folk medicine but they have to be more investigated for their medicinal properties. [ABSTRACT FROM AUTHOR]

Gardeniae Fructus is a widely used Traditional Chinese Medicines in treating various diseases. However, the absorbed components and metabolites of its main bioactive iridoid ingredients from iridoid extract of the fruits of Gardeniae Fructus in rat plasma need further study. In this study, a systematic method based on ultra-performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) technique was developed to speculate the absorbed components and metabolites of iridoid extract in rat plasma after oral administration. A total of 19 compounds, including 9 prototype components and 10 metabolites were identified in plasma. 5 metabolites containing 4 new metabolites (M1, M2, M7, M10) were tentatively determined in rat plasma. Besides, Microdialysis-intensity-fading mass spectrometry (MD-IF-MS) method was originally employed to reveal the binding affinities with α-glucosidase for in-vivo prototype components and their metabolites. Finally, the absorbed constituents and the corresponding target proteins were used to generate compound-target network to find the related diseases and action pathways by a network pharmacology method. The results provide useful information for further study of pharmacology and in vivo mechanism of action of iridoid extract from the fruits of Gardeniae Fructus. [ABSTRACT FROM AUTHOR]

Nepetalactones are iridoid monoterpenes with a broad range of biological activities produced by plants in the Nepeta genus. However, none of the genes for nepetalactone biosynthesis have been discovered. Here we report the transcriptomes of two Nepeta species, each with distinctive profiles of nepetalactone stereoisomers. As a starting point for investigation of nepetalactone biosynthesis in Nepeta , these transcriptomes were used to identify candidate genes for iridoid synthase homologs, an enzyme that has been shown to form the core iridoid skeleton in several iridoid producing plant species. Iridoid synthase homologs identified from the transcriptomes were cloned, heterologously expressed, and then assayed with the 8-oxogeranial substrate. These experiments revealed that catalytically active iridoid synthase enzymes are present in Nepeta, though there are unusual mutations in key active site residues. Nevertheless, these enzymes exhibit similar catalytic activity and product profile compared to previously reported iridoid synthases from other plants. Notably, four nepetalactone stereoisomers with differing stereochemistry at the 4α and 7α positions – which are generated during the iridoid synthase reaction – are observed at different ratios in various Nepeta species. This work strongly suggests that the variable stereochemistry at these 4α and 7α positions of nepetalactone diastereomers is established further downstream in the iridoid pathway in Nepeta . Overall, this work provides a gateway into the biosynthesis of nepetalactones in Nepeta . [ABSTRACT FROM AUTHOR]

The potential of electrophoretic mobility and dynamic light scattering (DLS) was investigated to assess pigment formation in aqueous solution after the genipin reaction with different amino acids by separate. Absorbance, mobility, hydrodynamic size, polydispersity index, and conductivity of the aqueous solutions were measured after the reaction. Only complexes derived from genipin and leucine, tyrosine, arginine, lysine, and glycine developed dark blue colors. From all measured variables, complex size was correlated with their blue color intensity, and darkest blue complexes showed the highest hydrodynamic size (1073–4179 nm). Moreover, size pigments below 1 µm were obtained for all amino acids at different concentrations of genipin and amino acid, except for arginine. A partial least squares (PLS) model for size was built and exhibited a good ability to describe the distribution in blue complexes formed after the reaction of genipin and excess of amino acid (mM): (R2 adj = 0.88; RMSE = 0.94). Electrophoretic mobility and DLS coupled with multivariate analysis is a useful tool as it can give reliable assessment of the physical properties of aqueous solutions of genipin pigments. [Display omitted] [ABSTRACT FROM AUTHOR]

Noni (Morinda citrifolia L.) fruit juice (NFJ) has an unpleasant flavor but is highly bioactive, so it is necessary to improve the quality of NFJ by exploring a novel strategy. The effects of eight lactic acid bacteria (LAB) on the antioxidant, phenolic, iridoid, and flavor properties of NFJ were investigated in the present study. The results showed that antioxidant activity was improved after NFJ fermentation by LAB and that L. rhamnosus had the highest free radical scavenging activity. The highest total phenolic content and total flavonoid content were in L. brevis- fermented NFJ (78.85 mg gallic acid equivalent/100 mL and 37.12 mg rutin equivalent/100 mL, respectively). Bioconversion of iridoid revealed that deacetylasperulosidic acid can be deacetylated from asperulosidic acid. Furthermore, LAB fermentation presented a significant decrease in unpleasant butanoic acid, with the lowest content found in L. fermentum- fermented NFJ. This research provides progressive information on the application of LAB culture in NFJ fermentation. • Antioxidant activity was improved after noni fruit juice fermented by LAB. • Rutin was increased in noni fruit juice fermented by LAB. • Deacetylasperulosidic acid content increased after LAB fermentation. • Unpleasant butanoic acid was significantly reduced after fermented by LAB. [ABSTRACT FROM AUTHOR]

Three iridoid glycoside lamiide(I), Ipolamiide(II) and ipolamiide(III) were isolated from N-butanol fractions obtained from the column chromatography of methanol extract from the aerial parts of Phlomis tuberosa. In addition, iridoid cyclopenta[c]pyran-4-carboxylic acid, 7-methyl-, methyl ester and phenol, 4-(3-hydroxy-1-propenyl)-2-methoxy were determined from the chloroform fraction of methanol extract of aerial parts from Phlomis tuberosa. Isolation and structural elucidation of compounds were accomplished by PTLC, TLC, CC and spectroscopic methods (UV, 13C and 1H NMR and DEPT, GC-MS). DOI: http://dx.doi.org/10.5564/mjc.v14i0.192 Mongolian Journal of Chemistry 14 (40), 2013, p20-24