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Cyperus rotundus L. (Cyperaceae) is a species widely used in traditional medicine in various regions of the world, mainly in Asian countries such as India and Pakistan. The anticancer potential of this species has been reported in the literature, indicating that its chemical compounds may be effective against different tumor cell lines. The present work aimed to carry out a systematic review on the traditional uses, chemical composition, toxicity, and anticancer potential of C. rotundus. Scientific articles were searched in Google Scholar, PubMed®, ScienceDirect®, and SciELO. Only works published in the last twenty years (2000-2020) were eligible. A total of 85 articles were included in the review. According to the scientific documents analyzed, C. rotundus is widely used for stomach disorders (11%), diarrhea and/or dysentery (11%), fever (10%), menstrual problems (9%), diuresis (9%), and worms (8%). Regarding the in vivo and in vitro anticancer potential, the extracts, fractions, and essential oils from C. rotundus were effective against colorectal, breast, prostate, ovarian, endometrial, liver and cervical cancer, leukemia, and neuroblastoma cell lines. A total of 49 chemical compounds belonging to the classes of sesquiterpenes, iridoid glycosides, and phenolics were identified in this review. Extracts obtained from C. rotundus did not show toxicity in preclinical tests. The pharmacological investigation of the chemical compounds isolated from this plant is important to elucidate the mechanisms of action against cancer cell lines.

Rehmannia glutinosa, the fresh or dried root of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & Mey., and Gardenia, the fruit of Gardenia jasminoides Ellis from Rubiaceae, both are famous traditional Chinese medicines that have been traditionally used in China. Catalpol and geniposide, as two kinds of iridoid glycosides with high activities, are the main bioactive components in Rehmannia glutinosa and Gardenia jasminoides Ellis, respectively. Over the past few decades, catalpol and geniposide have been widely studied for their therapeutic effects. The preclinical experiments demonstrated that they possessed significant neuroprotective activities against Alzheimer's disease, Parkinson's disease, stroke, and depression, etc. In this paper, the pharmacological effects and mechanisms of catalpol and geniposide on Alzheimer's disease and Parkinson's disease from 2005 to now were systematically summarized and comprehensively analyzed. At the same time, the pharmacokinetic characteristics of the analyzed compounds were also described, hoping to provide some enlightenment for the design, research, and development of iridoid glycosides.

Two new iridoids (1-2) together with eight known iridoid glycosides (3-10) were isolated from the 70% EtOH extract of the dried leaves of Vitex negundo var. heterophylla. Their structures were elucidated by extensive spectroscopic analyses. Iridoid aglycones were found for the first time from this plant. All of these compounds were tested for their antioxidant activities. Among them, compound 9 showed moderate radical-scavenging effect on the stable free radical, 1,1-diphenyl-2-picrylhydrazyl, with IC50 values of 26.95 μM.

Lonicerae Japonicae Flos (LJF), a kind of traditional Chinese medicines (TCMs), has functions of detoxifying and evacuating heat. In the study, a method based on ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was developed for the chemical constituent analysis of organic acids, flavonoids, iridoids and new-generated compounds in sulfur-fumigated LJF (SF-LJF). Based on the accurate mass measurement (< ± 5 ppm), chromatographic behavior and diagnostic product ions (DPIs), 113 constituents were unambiguously or tentatively characterized from SF-LJF extract, including 46 chlorogenic acids, 19 flavonoids, 29 iridoid glycosides and 19 newly-generated compounds (including 17 sulfur-containing derivatives). In addition, 5-CQA (5-caffeoylquinic acid, chlorogenic acid) was chosen to be sulfur-fumigated for the result validation. It was found that the most significant change of LJF after sulfur fumigation was the occurrence of sulfate or sulfite esterification reactions, which resulted in the emergence of many new sulfur-containing components. Our results demonstrated that the established method was a useful and efficient analytical tool to comprehensively characterize the material basis of SF-LJF, and also an excellent guidance of quality control about LJF.

Three new secoiridoid glycosides, named lonijapoglycol A (1), aldosecolohanin C (2) and aldosecolohanin B (3), together with three known ones (4-6), have been isolated from the flower the buds of Lonicera japonica. All the structures were identified by spectroscopic analyses. Lonijapoglycol A (1) expressed significant anti-inflammatory activity to inhibit the release of β-glu-curonidase induced by platelet-activating factor in rat polymorphonuclear leukocytes with an IC50 value of 3.76 μmol·L-1.

Asthma is a chronic airway disorder with a hallmark feature of airflow obstruction that associated with the remodeling and inflammation in the airway wall. Effective therapy for controlling both remodeling and inflammation is still urgently needed. Leonuride is the main pharmacological component identified from Bu-Shen-Yi-Qi-Tang (BSYQT) which has been traditionally used in treatment of lung diseases. However, no pharmacological effects of leonuride in asthma were reported.Here we aimed to investigated whether leonuride provided a therapeutic efficacy in reversing asthma airway remodeling and inflammation and uncover the underlying mechanisms.Mouse models of chronic asthma were developed with ovalbumin (OVA) exposure for 8 weeks. Respiratory mechanics, lung histopathology and asthma-related cytokines were examined. Lung tissues were analyzed using RNA sequencing to reveal the transcriptional profiling changes.After oral administration with leonuride (15 mg/kg or 30 mg/kg), mice exhibited a lower airway hyperresponsiveness in comparison to asthmatic mice. Leonuride suppressed airway inflammation evidenced by the significant reductions in accumulation of inflammatory cells around bronchi and vessels, leukocyte population counts and the abundance of type 2 inflammatory mediators (OVA specific IgE, IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). On the other hand, leonuride slowed down the process of active remodeling as demonstrated by weaker goblet cell metaplasia and subepithelial fibrosis in lung histopathology and lower transforming growth factor (TGF)-β1 levels in serum and BALF in comparison to mice treated with OVA only. Furthermore, we uncovered transcriptional profiling alternations in lung tissue of mice after OVA exposure and leonuride treatment. Gene sets belonging to type-2 cytokine/chemokine activity stood out in leonuride target transcripts. Those upregulated (Bmp10, Ccl12, Ccl22, Ccl8, Ccl9, Cxcl15, Il13, Il33, Tnfrsf9, Il31ra, Il5ra, Il13ra2 and Ccl24) or downregulated (Acvr1c and Il18) genes in asthmatic mice, were all reversely regulated by leonuride treatment.Our results revealed the therapeutic efficacy of leonuride in experimental chronic asthma for the first time, and implied that its anti-inflammatory and antifibrotic properties might be mediated by regulation of type-2 high cytokine/chemokines responses.

Six new isolates including three new alkaloids (1-3), one new secoiridoid glycoside (4) and one new 11-delactonization-secoiridoid glycoside (5), and one new organic acid (6) were identified from the leaves of Lonicera japonica, among which 1 and 2 assigned as a pair of configurational isomers possessed two oxazolidin-2-one fragments connected through NN bond. The structures were elucidated by the NMR data and ICD analysis. All the compounds (1-6) were tested for their antioxidant and hepatoprotective activities using cell models of ABAP-induced HepG

Therapeutic failure and drug resistance are common sequelae to insulin resistance associated with type 2 diabetes mellitus (T2DM). Consequently, there is an unmet need of alternative strategies to overcome insulin resistance associated complications.To demonstrate whether Kutkin (KT), iridoid glycoside enriched fraction of Picrorhiza kurroa extract (PKE) has potential to increase the insulin sensitivity vis à vis glucose uptake in differentiated adipocytes.Molecular interaction of KT phytoconstituents, picroside-I (P-I)picroside- II (P-II) with peroxisome proliferator-activated receptor gamma (PPARγ), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) were analyzed in silico. Cellular viability and adipogenesis were determined by following 3-(4, 5-Dimethylthiazol-2-Yl)-2, 5-Diphenyltetrazolium bromide (MTT) assay and Oil Red-O staining. Further, ELISA kit based triglycerides and diacylglycerol-O-Acyltransferase-1 (DGAT1) were assessed in differentiated adipocytes. ELISA based determination were performed to check the levels of adiponectin and tumor necrosis factor alpha (TNF-α). However, Flow cytometry and immunofluorescence based assays were employed to measure the glucose uptake and glucose transporter 4 (glut4) expression in differentiated adipocytes, respectively. Further to explore the targeted signaling axis, mRNA expression levels of PPARγ, CCAAT/enhancer binding protein α (CEBPα), and glut4 were determined using qRT-PCR and insulin receptor substrate-1 (IRS-1), Insulin receptor substrate-2 (IRS-2), PI3K/Akt, AS160, glut4 followed by protein validation using immunoblotting in differentiated adipocytes.In silico analysis revealed the binding affinities of major constituents of KT (P-IP-II) with PPARγ/PI3K/Akt. The enhanced intracellular accumulation of triglycerides with concomitant activation of PPARγ and C/EBPα in KT treated differentiated adipocytes indicates augmentation of adipogenesis in a concentration-dependent manner. Additionally, at cellular level, KT upregulated the expression of DAGT1, and decreases fatty acid synthase (FAS), and lipoprotein lipase (LPL), further affirmed improvement in lipid milieu. It was also observed that KT upregulated the levels of adiponectin and reduced TNFα expression, thus improving the secretory functions of adipocytes along with enhanced insulin sensitivity. Furthermore, KT significantly promoted insulin mediated glucose uptake by increasing glut4 translocation to the membrane via PI3/Akt signaling cascade. The results were further validated using PI3K specific inhibitor, wortmannin and findings revealed that KT treatment significantly enhanced the expression and activation of p-PI3K/PI3K and p-Akt/Akt even in case of treatment with PI3K inhibitor wortmannin alone and co-treatment with KT in differentiated adipocytes and affirmed that KT as activator of PI3K/Akt axis in the presence of inhibitor as well.Collectively, KT fraction of PKE showed anti-diabetic effects by enhancing glucose uptake in differentiated adipocytes via activation of PI3K/Akt signaling cascade. Therefore, KT may be used as a promising novel natural therapeutic agent for managing T2DMand to the best of our knowledge, this is the first report, showing the efficacy and potential molecular mechanism of KT in enhancing insulin sensitivity and glucose uptake in differentiated adipocytes.

Hairy root lines were established through the infection of Agrobacterium rhizogenes strain (A4) from shoot tips and leaves of Rehmannia elata N. E. Brown ex Prain (Orobanchaceae). Seven lines of hairy roots were selected on the basis of morphology and biomass increase in liquid Woody Plant Medium (WPM) supplemented with sucrose (30 g/L) without growth regulators. The transgenic status of the roots was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR) using rolB and rolC specific primers. After 30 days of growth the highest fresh weight (FW) and dry weight (DW) were determined in the S1 hairy root line (9.97 g/flask and 0.88 g/flask, respectively). UHPLC was then used to measure the accumulation of iridoid glycosides (aucubin, harpagide, harpagoside) and phenylethanoid glycosides (verbascoside and isoverbascoside) in selected hairy root lines. Among the iridoid glycosides, the highest amounts of aucubin (0.2 mg/g DW) and harpagide (1.57 mg/g DW) were detected in the S1 line, and harpagoside (0.09 mg/g DW) in the L14 line. Among the phenylethanoid glycosides, the highest levels of verbascoside (17.35 mg/g DW) and isoverbascoside (˜ 2 mg/g DW) were identified in the S1 root line. Catalpol, catalposide and loganin could not be detected in any tested hairy root line.

Two new iridoid tetramers with four glucosides, dipsanosides H (1) and I (2), as well as one new bis-iridoid glucosides dipsanosides J (3), along with four known polymer iridoid glycosides dipsanosides A (4) and B (5), pterocephaline (6), triplostoside A (7) were isolated from Dipsacus asper. Their structures were determined by analysis of 1D and 2D NMR data. All of them were found to be inactive in anti-inflammatory activity.

Iridoid compounds have been reported to be accumulated in the dried fruits of Gardenia jasminoides (Rubiaceae), which are used in traditional Chinese medicine. These compounds exhibit obvious pharmacological activities, including effective protective effects on the liver and therapeutic efficacy for cardiovascular diseases. However, the biosynthetic pathway of iridoid remains uninvestigated. In this study, 12 transcriptomes from four tissues (lower leaves, top leaves, flowers, and fruits) were analyzed to characterize the accumulation of active constituents and to identify the corresponding genes involved in iridoid biosynthesis. Almost all genes in the mevalonate (MVA) pathway and the 2-C-methyl- d -erythritol-4-phosphate (MEP) pathway were found in our transcriptome database; these pathways comprise upstream pathways of iridoid compounds (monoterpene derivatives), most of which are abundant in flowers and fruits. Geraniol synthase (GES), which is involved in the first branch step in the iridoid biosynthetic pathway, was cloned, and quantitative real-time PCR (qRT-PCR) revealed that GjGES showed a similar expression pattern to that in the transcriptome in terms of reads per kilobase per million (RPKM) mapped reads. The recombinant GjGES protein efficiently converted geranyl diphosphate (GPP) to geraniol. Subsequently, the metabolic profiling of seven iridoids and iridoid glycosides, namely geniposide, gardenoside, genipin, geniposidic acid, genipin-1-β-gentiobioside, shanzhiside, and shanzhiside methyl ester, revealed that these compounds were highly accumulated in fruits. Consequently, the metabolites and speculated unigenes involved in iridoid metabolic pathways enabled the identification of glucosyltransferase, hydroxylase, and O-methyltransferase candidate genes responsible for the biosynthesis of iridoid and iridoid glycosides. The results of the present study can serve as a reference for the functional characterization of enzyme-coding genes and are beneficial for the engineering of biosynthetic pathways of iridoids and iridoid glycosides in the future.

The purpose of this study was to analyze the HPLC-DAD-ESI-Q-TOF-MS/MS profile of the methanolic extract obtained from the aerial parts of Verbascum blattaria L. and develop efficient high-performance countercurrent chromatography (HPCCC) methods for isolation of its major iridoid glycosides. Additionally, the potential anti-inflammatory activities of the extract and two of the isolated compounds were evaluated using a human neutrophil model. LC–MS analysis led to the identification of 35 constituents, of which 18 iridoids, eight saponins, three phenylethanoids, four flavonoids and two phenolic acids. Scropolioside F (A, 2 mg), scrophuloside A3 (B, 16 mg) and gmelinoside L (C, 13 mg) were obtained from 300 mg of the crude methanolic extract by HPCCC with the help of two different biphasic solvent systems: n-hexane/ethyl acetate/n-butanol/water (1/2/1/2; v/v/v/v) and n-hexane/ethyl acetate/methanol/water (1/19/1/19; v/v/v/v). The crude methanolic extract (100 μg/mL) down-regulated lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF-α) release in a comparable extent to dexamethasone (25 μM). Gmelinoside L (50 μM) was more active than scrophuloside A3, producing inhibition percentages of 43.52% and 41.28% on interleukin 8 (IL-8) and TNF-α level, respectively. The HPCCC methods developed in the current work may serve to large scale isolation of iridoid glycosides from Verbascum species or other iridoid abundant-genera.

In traditional folk medicine, Verbascum species have been used since ancient times to treat respiratory disorders, hemorrhoids, diarrhea, wounds, eczema and other types of inflammatory skin conditions. Despite the fact that more than 200 bioactive constituents (phenylethanoids, flavonoids, neolignan glycosides, phenolic acids, iridoids, saponins and polysaccharides) have been previously isolated from various Verbascum species, to date preparative high-performance countercurrent chromatography (HPCCC) has never been employed for this purpose. Therefore, in this study, simple HPCCC methods were successfully developed with the aim to primarily isolate acylated iridoid diglycosides from Verbascum ovalifolium Donn ex Sims (oval-leaved mullein). By the use of several biphasic solvent systems containing n-hexane, ethyl acetate, n-butanol/methanol and water, premnacorymboside B (3, 4 mg, 95.4% purity), saccatoside (4, 6 mg, 95.7% purity), premnacorymboside A (7, 6 mg, 98.3%), scorodioside (8, 11 mg, 96.0%) and 6-O-(3′',4′'-di-O-trans-cinnamoyl)-α-L-rhamnopyranosylcatalpol (9, 8 mg, 95.3%) were afforded; compounds 7, 8 and 9 have not been previously reported in Verbascum genus. Additionally, two phenolic acids (1, 2), two flavonoids (6, 10) and verbascoside (5) were secondarily isolated. Evaluation of interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α) inhibitory properties of the acylated iridoid diglycosides proved that these compounds down-regulated TNF-α release more efficiently than IL-8 secretion. The activity might be dependent on the degree of esterification, as diacyl derivatives showed more potent effects than monoesters. The HPCCC methods herein developed could serve to large scale isolation of constituents from Verbascum genus for extensive biological investigations.

Discovering novel compounds with higher activities is a key aim of natural products research. Gardenia jasminoides Ellis is a herb with anti-inflammatory properties. Iridoid glycosides (mainly geniposide) and crocetin derivatives (crocins) are the two major active constituents in this herb and are considered its active ingredients. However, which components are responsible for the anti-inflammatory properties of gardenia have remained to be investigated.Here, we prepared total iridoid glycocides (TIG) and total crocins (TC) from G. jasminoides Ellis, determined their main chemical constituents, and performed animal studies to evaluate their anti-adjuvant arthritis activities, thus, proposing a reasonable mechenism to explain the anti-inflammatory activities of the active components in this herbal remedy.TIG and TC were prepared by using HPD-100 macroporous resin, and characterized by UHPLC-DAD-MS and UV-Vis spectrophotometer. Then, freund's complete adjuvant-injected rats underwent drug treatments with TIG (160 mg/kg) and TC (160 mg/kg) for 14 days, and their ankle diameters were measured. Moreover, X-ray radiographs of the adjuvant injected hind paws were evaluated. Finally, histopathological examinations of the ankle joints, spleens and thymus were carried out to evaluate inflammatory reactions, and immunohistochemical measurements were conducted to evaluate TNF-α and TGF-β1 expression in the ankle joint of the rats.The chemical composition determination of the current study showed that TIG was mainly composed of geniposide and TC was a fraction predominantly with crocin-1, crocin-2 and crocin-3. Calculation of results showed that TIG and TC contained 58.2% total iridoid glycosides and 54.7% total crocins, respectively. Our study suggested TIG and TC treatments markedly decreased paw swelling and ankle diameters of AA rats (both p0.05). The radiological analysis showed that administration of TIG and TC ameliorated bone destruction, and reduced the radiological bone destruction scores (TIG p0.05, TC p0.05). Moreover, data from histological assessment demonstrated considerable mitigation of inflammation in the joints (both p0.01), spleen and thymus of AA rats treated with TIG and TC. TNF-α and TGF-β1 protein expression according to immunohistochemistry staining also supported the anti-arthritis activities of TIG and TC (TNF-α: TIG p0.01 and TC p0.05, TGF-β1: TIG p0.01 and TC p0.05).In the current study, fractionation of gardenia prior to further in vivo investigation has for the first time provided reasonable explanation for the anti-inflammatory activity of this herbal remedy. Our study showed that both TIG and TC from gardenia have anti-inflammatory properties. Overall, these experimental findings suggest that gardenia could be regarded as a potential therapeutic target for arthritis. However, as geniposide has a higher content than crocins in this herbal drug, TIG (mainly geniposide) seems to be primarily responsible for the anti-inflammatory properties of gardenia. Taken together, this maiden attempt demonstrated that TIG (mainly geniposide) is more important in evaluating the anti-inflammatory activity of G. jasminoides Ellis.

One specific group of MMPs; gelatinases A (MMP-2) and B (MMP-9) are of precise interest in view of the development and progression of cancer. In the current work, an attempt was made to investigate the enzymatic inhibitory activity of Kutkin (KT), Kutkoside (KS), and Picroside I (PS) by inhibition assay and to further check the downregulation of the expression of mRNA levels of MMP-2 and -9. Further in silico docking studies were performed to investigate the interaction of KT, KS and PS with MMP-2 and MMP-9. The results revealed a dose dependent cytotoxic activity of the compounds under investigation and showed a significant inhibition of MMP-9 in comparison to the activity against MMP-2. In addition, a considerable decrease in expression of mRNA levels (MMP-9) was observed in KT, KS, and PS-treated MDA-MB-231 and MDA-MB-435 cancer cells as was detected by reverse transcriptase polymerase chain reaction (semi-quantitative RT-PCR). The molecular docking studies between KT, KS, PS with MMPs revealed that KT, KS, PS occupied the active site of MMP-9 and showed better binding interactions in comparison to MMP-2. The binding energies of the complexes were –7.4, –7.1 and –7.2 kJ/mol for KT, KS and PS with MMP-9, respectively and –8.9, –8.0 and –8.0 kJ/mol for KT, KS and PS with MMP-2, respectively. The findings from the in vitro studies revealed that KT, KS and PS exhibited significant anti-proliferative effects on both MDA-MB-231 and MDA-MB-435 breast cancer cells. In addition, the results of inhibition assay showed that MMP-9 activity was significantly inhibited by KT, KS and PS and the results were consistent with in silico assay.

A comprehensive chemical profiling of traditional Chinese medicine is the basic issue for further pharmacological research and quality assessment. To facilitate chemical identification and potential components discovery, the present study proposed an integrated identification strategy guided by a self-built component database constructed from literatures to carry out the global profiling of complex matrixes. Lanqin Oral Liquid was applied as example to validate the feasibility of this strategy. Based on LQL Component Database containing 710 compounds, modified MDF windows was established to extract the interested analogues, isoquinoline alkaloids, flavonoids and iridoid glycosides, according to their regular integral masses and mass defect. For compounds with characteristic substructures, such as quinic acids, crocins and some glycoside derivatives, the associated neutral losses and diagnostic fragment ions were collected to assist in profiling. Directly matching the m/z or formulas in database was proposed to components with limited regularity of accurate masses and substructures, like indole alkaloids, sesquiterpenes and some nucleosides. Eventually, 170 ions of 1038 precursor ions were identified or temporarily deduced, including 59 alkaloids, 36 flavonoids, 48 terpenoids, 24 organic acids and their derivatives, 2 oligosaccharides, and 1 lignans. Among them, 52 putative compounds were confirmed by chemical standards. The results indicated that the database-oriented identification strategy could locate potential components quickly and eliminate interfering ions, which have the potential for in-depth analysis of compounds.

This study attempts to develop a reproducible protocol for in vitro adventitious root regeneration for enhanced biomass production from nodal segments of Allamanda cathartica L., which may be of use as an alternative source for production of iridoid glycosides. Allamanda cathartica (Apocynaceae) is a medicinally rich vine, used in the treatment of human carcinoma, human immunodeficiency virus (HIV), jaundice and malaria. The roots of the plant are the main reservoir of secondary metabolites. The main active constituent in root is iridoid glycosides. The explant for root initiation was cultured in ½ strength Murashige and Skoog (MS) liquid medium augmented with different levels of Indole-3-butyric acid. 0.5 μM Indole-3-butyric acid with 4% sucrose resulted in 1.810 ± 0.049 g and 0.376 ± 0.053 g fresh and dry weight respectively. Among different levels of sodium chloride (80, 100, 120 and 150 mM) added to optimized media, 120 mM sodium chloride treatment increased the root biomass considerably compared with Indole-3-butyric acid alone and other combination, and recorded the fresh weight 2.090 ± 0.049 g and dry weight 0.400 ± 0.005 g after 12 weeks of incubation. The phytochemical investigations using high performance thin-layer liquid chromatography (HPTLC) and mass spectrometry (MS) analysis revealed concentration dependent modulation of selected iridoids in the cultures treated with sodium chloride. The protocol developed can be utilized as an alternative source for production of iridoid glycosides and the findings may be explored on industrial scale.

Three new iridoid glycosides, namely umbrosides A–C (1–3); ten known iridoid glycosides (4–8 and 16–20); and seven known phenylethanoid glycosides (9–15) were isolated from Scrophularia umbrosa Dumortier, and their structures were established through spectroscopic methods including 1D and 2D NMR experiments and ESIMS analysis. The inhibitory activities of the isolated compounds on LPS-stimulated nitric oxide (NO) production in RAW 264.7 cells were investigated. Compounds 1–3, 7, 9–10, 13–16, and 19–20 inhibited NO production, with IC50 values ranging from 9.0 to 40.3 μM. Their structure–activity relationships are preliminarily discussed in this paper.

Three hitherto unknown valeriana-type iridoid glycosides (1−3) were isolated from Viburnum punctatum, and their structures were elucidated by extensive spectroscopic analysis. The new compounds, designated as viburpunosides A − C (1−3), are characterized by having a mono- or triacylated α- l -rhamnopyranosyl-(1→2)-β- d -glucopyranosyl moiety linked to C-11. This is the second report of an iridoid attached to a disaccharide other than glucose in this genus. The absolute configuration of new compounds was briefly discussed.

Six new secoiridoids, syrretosides E-J (1-6) and four known secoiridoids (7-10), were isolated from the stem barks of Syringa reticulata. Their structures were established by the 1D and 2D NMR spectra, HR-ESI-MS, and comparison with the literature. The cytotoxicity of the isolated monomeric compounds against RAW264.7 cells was investigated by the CCK8 assay, and the results showed that the individual compounds were not cytotoxic to RAW264.7. The anti-inflammatory activity of these compounds was evaluated using the LPS-induced RAW264.7 inflammatory cell model and the results showed that compounds 3-7 and 9 showed varying degrees of anti-inflammatory activity.

Lonicerae flos, a widely used traditional Chinese medicine (TCM), has been used for several thousand years in China. As a famous traditional Chinese herbal medicine, it was used as heat-clearing drug and alexipharmic agent and was widely cultivated in Hunan province. L. flos mainly contains biologically active compounds such as caffeic acid derivatives, essential oil, flavonoids, iridoid glycosides and terpenoids. A range of biological activities has been reported from plant extracts including anti-inflammatory, antitumor, antioxidant, antiallergy, immunomodulating and antibacterial activity. In this study, the author investigated ancient books of TCM and nowadays reports, summarized the chemical constituents, biological activity of L. flos to provide a comprehensive systematic review. Keywords: Caprifoliaceae, Lonicerae flos, Chemical constituents, Biological activity, Lonicera macranthoides, Lonicera cofusa

New iridoid glycoside derivatives from durantoside I, the latter from the dried flowers and leaves of Citharexylum spinosum, were synthesized by variously modifying a sugar moiety by silylation or acetylation and/or removal of cinnamate group at C-7 position and subsequent screening for comparative cytotoxicity against several cancer cell lines. Addition of alkylsilane to durantoside I and removal of cinnamate group were most effective in improving cytotoxicity.

Radix Dipsaci (RD), the dried root of Dipsacus asper, is used in traditional Chinese medicine as a remedy for bone fractures, traumatic hematoma, threatened abortion, and uterine bleeding. A novel ultra high-performance liquid chromatography coupled with quadrupole-time-of-flight tanderm mass spectrometry (UHPLC-Q-TOF/MS) approach was performed to rapidly characterize the chemical constituents of RD. Consequently, 21 compounds, including 12 iridoid glycosides (IGs), 4 furofuran lignans (FLs), and 5 phenolic acids (PAs) were discovered and identified from RD. Among these compounds, 3 IGs were previously unreported. Furthermore, a rapid and reliable UHPLC-DAD-based method was developed. The linearity (R2 > 0.999), repeatability (RSDs

In the cell extraction_LC-MS method, when cells are incubated with natural product extracts, bioactive compounds selectively bind to extracellular or intracellular targets. The extracts and major compounds (phenylpropanoids and iridoid glycosides) of Scrophularia buergeriana Miquel have been reported to show neuroprotective effects both in vitro and in vivo. In this study, the cell extraction_LC-MS strategy was applied to screen and identify potential neuroprotective compounds from S. buergeriana by using immortalized mouse hippocampal HT22 cells. The results showed that two known compounds from S. buergeriana selectively bound HT22 cells. Additionally, metabolomics analyses were performed using the Mass Profiler Professional and Limma differential expression package of R to identify significant differences between HT22 cells treated with S. buergeriana and untreated cells. The cell extraction approach more accurately reflects in vivo conditions compared with other methods and can be readily used for screening bioactive components from natural products.

The medicinal benefits of Plantago major have been acknowledged around the world for hundreds of years. This plant contains a number of effective chemical constituents including flavonoids, alkaloids, terpenoids, phenolic acid derivatives, iridoid glycosides, fatty acids, polysaccharides and vitamins which contribute to its exerting specific therapeutic effects. Correspondingly, studies have found that Plantago major is effective as a wound healer, as well as an antiulcerative, antidiabetic, antidiarrhoeal, anti-inflammatory, antinociceptive, antibacterial, and antiviral agent. It also combats fatigue and cancer, is an antioxidant and a free radical scavenger. This paper provides a review of the medicinal benefits and chemical constituents of Plantago major published in journals from year 1937 to 2015 which are available from PubMed, ScienceDirect and Google Scholar.

Two new iridoid glycosides, named 6 β - O -methyl-unedoside ( 1 ) and 6 β - O -methyl-5-deoxythunbergioside ( 2 ) along with two known phenyl propanoid glucoside compounds dolichandroside A ( 3 ) and verbascoside ( 4 ) were isolated from the aerial parts of Odontonema cuspidatum (Nees) Kuntze (Acanthaceae). Structure elucidation of the new compounds was established by interpretation of their 1D and 2D-NMR spectral data by comparing with literatures, HRESIMS and optical activity measurement. The isolated compounds were tested for their in vitro antimicrobial and antimalarial activities. Compound 4 showed a moderate antimicrobial activity against E. coli with IC 50 value of 17.5 μM in comparing with Vancomycin and Cefotaxime.

Siphonoids A–C (1–3), among which siphonoids A-B (1–2) are rare (E)-p-coumaroyl iridoids, were isolated from Siphonostegia chinensis along with ten known iridoids (4–13) and four lignans (14–17). The structures of the compounds were established by 1D- and 2D-NMR spectroscopy and mass spectrometry. Most of the iridoids isolated from S. chinensis were found to possess (E)-p-coumaroyl iridoid subtype skeletons. Hence, this type of iridoid could be regarded as a chemotaxonomic marker of S. chinensis. The inhibition activities for the NF-κB pathway of iridoids (1–6) were detected. The present results showed that compounds 1–2 and 4–6 processed moderate activity towards the inhibition of NF-κB.

Exploring processing chemistry, in particular the chemical transformation mechanisms involved, is a key step to elucidate the scientific basis in traditional processing of herbal medicines. Previously, taking Rehmanniae Radix (RR) as a case study, the holistic chemome (secondary metabolome and glycome) difference between raw and processed RR was revealed by integrating hyphenated chromatographic techniques-based targeted glycomics and untargeted metabolomics. Nevertheless, the complex chemical transformation mechanisms underpinning the holistic chemome variation in RR processing remain to be extensively clarified. As a continuous study, here a novel strategy by combining chemomics-based marker compounds mining and mimetic processing is proposed for further exploring the chemical mechanisms involved in herbal processing. First, the differential marker compounds between raw and processed herbs were rapidly discovered by untargeted chemomics-based mining approach through multivariate statistical analysis of the chemome data obtained by integrated metabolomics and glycomics analysis. Second, the marker compounds were mimetically processed under the simulated physicochemical conditions as in the herb processing, and the final reaction products were chemically characterized by targeted chemomics-based mining approach. Third, the main chemical transformation mechanisms involved were clarified by linking up the original marker compounds and their mimetic processing products. Using this strategy, a set of differential marker compounds including saccharides, glycosides and furfurals in raw and processed RR was rapidly found, and the major chemical mechanisms involved in RR processing were elucidated as stepwise transformations of saccharides (polysaccharides, oligosaccharides and monosaccharides) and glycosides (iridoid glycosides and phenethylalcohol glycosides) into furfurals (glycosylated/non-glycosylated hydroxymethylfurfurals) by deglycosylation and/or dehydration. The research deliverables indicated that the proposed strategy could advance the understanding of RR processing chemistry, and therefore may be considered a promising approach for delving into the scientific basis in traditional processing of herbal medicines.

Angiotensin II, the effector peptide of the renin-angiotensin system, is not only a pivotal peptide implicated in the regulation of blood pressure but also a key mediator of the inflammatory processes that play an important role in the pathology of hypertension-related cSVD. Harpagide is the major bioactive constituent of Scrophulariae Radix widely used in traditional Chinese medicine for numerous diseases including hypertension. The present study aimed to investigate the effect of harpagide on Ang II-induced neuroinflammation and the potential mechanism. Pretreated with harpagide or resatorvid (the TLR4 pathway inhibitor), BV2 cells were treated with Ang II or LPS (the TLR4 activator). NO, pro-inflammatory cytokines, the proteins on TLR4/MyD88/NF-κB signaling pathway and the expression of CD86, CD206, TREM2 in BV2 cells were detected respectively. Subsequently, the effects of harpagide on neurotoxicity and BBB destruction triggered by Ang II-induced neuroinflammation were investigated in the co-cultures of BV2 microglia/HT22 hippocampal neurons, BV2 microglia/bEnd.3 endotheliocyte and BV2 microglia/BBB monolayer model. We found that Ang II converted microglia into M1 state and resulted in neuroinflammation through activating TLR4/MyD88/NF-κB signaling pathway. It also triggered the imbalance of TLR4/TREM2 in microglia. Ang II-mediated inflammation microglia further led to neuronal apoptosis and BBB damage. Harpagide showed the effect of alleviating Ang II-mediated neuroinflammation as well as the resulting neurotoxicity and BBB destruction through inhibiting the TLR4/MyD88/NF-κB pathway. The anti-inflammatory and neuroprotective effect of harpagide suggested that it might be a potential therapeutic strategy in hypertensive cSVD.

Eucommia ulmoides (EU) Oliver seeds are rich in oil and serve as a potential edible oil, but little is known about its phytochemical substances. In this study, the sterol profiles of the supercritical CO2 fluid extracted EU seed oil and its contents were first evaluated by GC-MS analysis, and fifteen sterols and three triterpene alcohols were determined. β-sitosterol was detected as the most abundant phytosterol in the seed oil. Additionally, seven iridoid glycosides (1–7), namely aucubin (1), bartsioside (2), linaride (3), geniposidic acid (4), one dimer scyphiphin D (5), two trimers ulmoidoside A (6) and ulmoidoside B (7) were identified from the defatted seed flour, and the compound 3 was reported in E. ulmoides for the first time. Natural and two acetylated compounds (1–9) were evaluated for their inhibitory effects on NO production in the lipopolysaccharide (LPS)-stimulated microglial cells, and 1–3 exerted significant inhibition of NO generation with IC50 values of 3.60, 7.09, and 10.52 μM, respectively. The structure-activity relationships (SARs) of these iridoids indicated that OH groups on C-10 and C-6 were more effective and the COOH group at C-4 position was highly detrimental to the activity. The results suggest that the edible EU seeds could be a potential dietary source of aucubin and β-sitosterol for reducing the risk of neurodegenerative diseases.

UDP-glycosyltransferases (UGTs) are an important and functionally diverse family of enzymes involved in secondary metabolite biosynthesis. Coumarin is one of the most common skeletons of natural products with candidate pharmacological activities. However, to date, many reported GTs from plants mainly recognized flavonoids as sugar acceptors. Only limited GTs could catalyze the glycosylation of coumarins. In this study, a new UGT was cloned from Cistanche tubulosa, a valuable traditional tonic Chinese herb, which is abundant with diverse glycosides such as phenylethanoid glycosides, lignan glycosides, and iridoid glycosides. Sequence alignment and phylogenetic analysis showed that CtUGT1 is phylogenetically distant from most of the reported flavonoid UGTs and adjacent to phenylpropanoid UGTs. Extensive in vitro enzyme assays found that although CtUGT1 was not involved in the biosynthesis of bioactive glycosides in C. tubulosa, it could catalyze the glucosylation of coumarins umbelliferone 1, esculetine 2, and hymecromone 3 in considerable yield. The glycosylated products were identified by comparison with the reference standards or NMR spectroscopy, and the results indicated that CtUGT1 can regiospecifically catalyze the glucosylation of hydroxyl coumarins at the C7-OH position. The key residues that determined CtUGT1's activity were further discussed based on homology modeling and molecular docking analyses. Combined with site-directed mutagenesis results, it was found that H19 played an irreplaceable role as the crucial catalysis basis. CtUGT1 could be used in the enzymatic preparation of bioactive coumarin glycosides.

Ethnopharmacological relevance In traditional Chinese medicine (TCM) and modern pharmacodynamics, dried Rehmannia Radix (DRR) possesses prominent anti-thrombotic activity that decreases after processing by nine steaming and drying cycles to develop processed Rehmannia Radix (PRR). Due to the complexity of the DRR components, the chemical mechanism leading to efficacy changes of DRR caused by processing is still unclear. Aim of study This study aimed to trace the anti-thrombotic active compounds of DRR and different degrees of processed RR (PRR) and to evaluate the synergistic effects among different active components. Materials and methods The anti-thrombotic active chemical fraction of DRR extracts was evaluated. Targeted fractions of the processed products of RR were prepared at different processing stages. The changes in monosaccharides, oligosaccharides and secondary metabolites during processing were characterized by multidimensional high-performance liquid chromatography (HPLC). The anti-thrombotic effects of targeted fractions of different RR samples were evaluated by analyzing the length of tail thrombus (LT) and serum biochemical indicators in carrageenan-induced tail-thrombus mice. The spectrum-effect relationships were investigated by partial least squares regression (PLSR) analysis and gray correlation analysis (GRA). Finally, the active compounds were screened by spectrum-effect relationship analysis and validated in vivo, and their synergistic effects were determined by Webb's fraction multiplication method. Results Six ingredients highly associated with anti-thrombotic activities were screened out by the spectrum-effect relationship analysis, of which oligosaccharides (stachyose, sucrose and raffinose) and iridoid glycosides (catalpol, leonuride and melitoside) possessed a synergistic effect on tumor necrosis factors (TNF-α), interleukin 1β (IL-1β) and plasminogen activator inhibitor 1 (PAI-1)/tissue-type plasminogen activator (t-PA) ratio in vivo with synergistic coefficient (SC) > 1. Conclusion The main material basis of the anti-thrombotic activities of DRR is oligosaccharide components of stachyose, raffinose and sucrose, iridoid glycosides components of catalpol, leonuride and melittoside. The two kinds of components exert synergistic anti-thrombotic effects by inhibiting the expression of inflammatory factors and regulating the balance of the fibrinolysis system.

Two new iridoid glycosides, scrophularosides A and B (1–2), two phenylethanoid glycosides, scrophularosides C-D (3–4) and eight known compounds (5-12) were isolated from the roots of Scrophularia ningpoensis. Their structures were elucidated via the interpretation of spectroscopic methods, especially 2D NMR and mass analyses. Compound 1 was a novel iridoid glycoside which possessed a 5/6/7/6 ring system with an unprecedented trioxabicyclo [4.3.1] decane core. The anti-inflammatory potential of new compounds 1–4 was evaluated by determining their ability to inhibit lipopolysaccharide (LPS) induced NO production in RAW 264.7 macrophage cells.

Phytochemical investigation of the stems and leaves of Lonicera hypoglauca Miq. led to the isolation of one novel methoxylated flavone, acunminatin (7,2′,4′-trihydroxyl-5,5′- methoxyflavone) (1), and fourteen known compounds (2–15), including six flavonoids (mearnsetin 2, kaempferol 3, acacetin 4, 5,7,3′,4′-tetramethoxyflavone 5, tricin 6, and 5,7,3′,4′,5′-pentamethoxyflavone 7), two coumarins (umbelliferone 8 and scopoletin 9), two phenylpropanoids (trans-ferulic acid 10 and chlorogenic acid 11), two iridoid glycosides (loganin 12 and sweroside 13), and two triterpenoids (uvaol 14 and ursolic acid 15). The structures of the compounds were identified by spectroscopic analysis and by comparing their spectral data with those reported in the literature. Five of these compounds (1, 2, 4, 5, and 7) were isolated from the L. genus for the first time, and compounds 6–8 and 14–15 were isolated for the first time from L. hypoglauca. The chemotaxonomic significance of the isolated compounds in the L. genus and the Caprifoliaceae family are discussed herein.

Introduction Odontites serotina is a medicinal plant primarily distributed in northern China. To the best of our knowledge, no previous study has investigated the bioactivities of this plant. The present study investigated the active constituent contents and bioactivities of the 95% ethanol crude extract (ECE) of O. serotina and its fractions. Methods The total phenol/flavonoid/iridoid glycoside contents were examined by spectrophotometric methods. DPPH/ABTS assays were used to evaluate the antioxidant activities. α-Glycosidase/α-amylase/AChE/BChE-inhibitory assays were performed to evaluate antidiabetic and anticholinergic activities. Correlations were determined via Pearson's correlation analyses. Results The total phenol/flavonoid contents of the ethyl acetate fraction (EAF) and n-butanol fraction (NBF) and the total iridoid glycoside content of the NBF were determined to be significantly higher than those of the ECE. The EAF and NBF exhibited strong antioxidant and potent inhibitory effects on acetylcholinesterase (AChE), and they also exhibited butylcholinesterase (BChE)/α-glucosidase-inhibitory effects. No sample demonstrated any effects against α-amylase. The correlation analyses indicated strong positive correlations between total phenol content and antioxidant activity and between total flavonoid content and antioxidant/AChE/BChE/α-glucosidase-inhibitory activities. The isolation of the EAF resulted in the acquisition of acteoside (1), emodin (2), benzoic acid (3) and β-sitosterol (4). Acteoside showed moderate antioxidant and BChE/α-glucosidase-inhibitory activities, and emodin exhibited moderate BChE-inhibitory activity. Conclusion The EAF and NBF are rich in phenols, flavonoids and iridoid glycosides and have antioxidant and dual AChE/BChE and selective α-glycosidase-inhibitory activities. O. serotina has potential in the development of new drugs to treat Alzheimer's disease (AD) and diabetes.

The iridoid profile of four Vaccinium species was investigated using UHPLC-MS to obtain further information about this group of species for phytochemical characterization. Fruits of bog bilberry (Vaccinium uliginosum L.) showed 14 different iridoid glycosides with a total amount of 20mg/kg fresh weight (FW), whereas bilberry (Vaccinium myrtillus L.) contained 11 iridoid glycosides and a total amount of 127mg/kg FW. Highbush blueberry (Vaccinium corymbosum L.) and lowbush blueberry (Vaccinium angustifolium L.) contained none of the investigated iridoid glycosides. Among the different iridoids, the isomers scandoside and deacetylasperulosidic acid as well as a dihydro derivative thereof were described for the first time in the Ericaceae family. The p-coumaroyl isomers of scandoside, deacetylasperulosidic acid and dihydromonotropein are reported for the first time in V. myrtillus and V. uliginosum. Monotropein and its p-coumaroyl isomers were found for the first time in V. uliginosum. The comparison of iridoid profiles in bilberry fruit and juice samples revealed constant proportions throughout the juice processing. Quantification and profile determination of iridoids may be used for species differentiation and thus for authentication purposes.

Gentiana, a cosmopolitan and important genus of the Gentianaceae family, comprises 400 species distributed among the world. Based on the studies of Iranian traditional medicine texts, there are some promising bioactivities for this genus that is unknown in modern medicine and some of them are still the basis of new remedies. In traditional medicine texts, Gentiana's different exclusive forms of preparations are effective for treatment of some disorders such as menstrual over-bleeding, conjunctivitis, vitiligo, animals venom poisoning, injuries, infected wounds, pain and swelling of liver, spleen, stomach and sprains of muscles. There are some activities that are the same in traditional and modern medicine such as anti-inflammatory, hepatoprotective and diuretic effects. Phytochemical investigations on the title genus have led to characterization many secondary metabolites. Secoiridoidal and iridoid glycosides such as gentiopicroside, xanthones, monoterpene alkaloid; polyphenol and flavones are the constituents that have been shown the pharmacological activities in different gentian species. This article studies the Gentiana according to the Iranian traditional and modern medicine., Graphical abstract

Three new alkaloids, rehmanalkaloid A-C (1-3), and a new iridoid glycoside, rehmaglutoside L (4), together with nine known compounds, including (8S)-7,8-dihydrogeniposid (5), diglycoside (6), monomelittoside (7), mussaenoside (8), darendoside A (9), syringing (10), phenyl-6-O-β- d -xylopyranosyl-O-β- d -glucopyranoside (11), (7R, 8S)-4,9-dihydroxy-3,3′-dimethoxy-7,8-dihydrobenzofuran-1′-propanalneolignan (12), and trans-liovil (13), were isolated from a 95% EtOH extract of dried roots from Rehmannia glutinosa. Their structures were determined by extensive spectroscopic (UV, IR, HR-ESI–MS, and 1D and 2D NMR) analyses. Additionally, compounds 4-8 (iridoid glycosides) were evaluated for their protective effects on H714444444444444444444466666666669c2 cardiocytes impaired by doxorubicin. Among them, compounds 4-8 exhibited protective effects against DOX-induced cardiotoxicity.

A previously undescribed nor-dammarane, 3β,20,23-trihydroxy-24,25,26,27-tetranordammarane; three previously undescribed secoiridoid glycosides, ligujaponosides A-B, and iso-oleonuzhenide; and twenty three known compounds, were isolated from the fruits of Ligustrum japonicum Thunb. Their chemical structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, and HRMS. The isolated compounds were screened for immunosuppressive effects on T activated cells by evaluating interleukin-2 (IL-2) production. Among them, sesamin inhibited IL-2 production in Jurkat T cells with an IC50 value of 38 ± 2 μM. In addition, sesamin inhibited the phosphorylation of extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase (MAPK) family, in phorbol 12-myristate 13-acetate (PMA)/A23187-stimulated T cells. Therefore, sesamin was demonstrated to inhibit T cell activation via regulation of MAPK phosphorylation pathway.

Vitex negundo L. var. heterophylla (Franch.) Rehd. is widely accepted as a functional and medicinal food in China because of the presence of bioactive components which improve the physical condition. In the present study, the bioactive constituents, antioxidant, α -glucosidase and DPP-IV inhibitory activities of V. negundo var. heterophylla were investigated. Two new coumarin glycosides, vitexnegheteroins I-J ( 1 – 2 ), and two new iridoid glycosides, vitexnegheteroins K-L ( 3 – 4 ), were isolated from the leaves and seeds of V. negundo var. heterophylla , together with twenty known compounds. Seven compounds presented stronger antioxidant activities than l -ascorbic acid in both DPPH and ABTS assays. Among them, isoorientin-6″- O -caffeate ( 22 ) also exhibited more potent α -glucosidase inhibitory activity than acarbose with an IC 50 value of 0.24 ± 0.02 μM. These findings further revealed the bioactive components of this edible aromatic plant and disclosed the potency of it to be developed as new antioxidant and α -glucosidase inhibitory agents.

Chemical study on the aerial parts of Phlomis likiangensis unearthed six new iridoid glycosides, phlolosides A–F ( 1 – 6 ), together with six known analogues ( 7 – 12 ). In the light of a combination of spectroscopic data, acid hydrolysis and single crystal X-ray diffraction analysis, the structures of 1 – 6 were determined. This is the first discovery of iridoid glycosides assembling a carbonate ester substituent group. All isolated compounds were assayed for cytotoxic and antibacterial activities, but were either inactive or very weakly active.

An efficient, accurate and sensitive method for the determination of five iridoid glycosides (IGs) in Cornus officinalis fructus using molecularly imprinted solid phase extraction (MISPE) coupled with high performance liquid chromatography (HPLC) has been developed. Water-compatible molecularly imprinted beads (MIBs) were synthesized by precipitation polymerization, using alkenyl glycosides glucose as the hydrophilic functional monomer. Scanning electron microscopy showed that the MIBs had a narrow particle size distribution, with diameters in the range 7.5-9.3μm. The special molecular recognition by the MIBs of IGs in aqueous media was verified by static adsorption, kinetic adsorption, and selectivity experiments. The newly prepared MIBs were used as sorbents in solid phase extraction (SPE) for the selective recognition of five IGs (loganin, morroniside, loganic acid, 7-O-ethyl-morroniside and 7-O-methyl morroniside) in Cornus officinalis fructus. When optimized, the MISPE-HPLC method had good linearity (0.02-100mgg-1), with correlation coefficient (R)≥0.994. Recoveries at three spiked levels were in the range 80.0%-94.0%. Because of its excellent specificity and hydrophilicity, SPE based on monodisperse MIBs provides a promising pretreatment strategy for the analysis of active components in natural products, especially for the quality control of traditional Chinese medicines.

Nardonaphthalenones A and B (1-2), one new apo-α-carotenone (3) and four new monoterpenoids (4, 8-9 and 11), along with six known compounds (5-7, 10, 12-13) were isolated from the dried roots and rhizomes of Nardostachys chinensis Batal. Their structures were elucidated by analysis of the spectroscopic data including NMR, HRESIMS and circular dichroism data. Furthermore, the serotonin transporter (SERT)-regulating activities of these isolates were evaluated, among them compound 3 showed the strongest enhancement activity while compound 12 showed a moderate inhibition activity on SERT.

Chemical study of the aerial parts of Anthospermum emirnense led to the isolation of one original iridoid glycoside (1) along with six known iridoids (2–7), three lignans (8–10), two flavonoids (11–12), one coumarin (13), two anthraquinones (14–15), two benzoic acids (16–17) and three triterpenoids (18–20). These results are the first chemical data on non-volatile constituents of this genus. The chemotaxonomic significance of these compounds is discussed.

Ethnopharmacological relevance Cornus officinalis (CO) has been widely used as a traditional Chinese medicine for treating diabetes mellitus (DM) and its complications. Iridoid glycoside from C. officinalis (IGCO) can resist apoptosis, hyperglycemia, oxidation and so on. The aim of this study was to investigate the therapeutic effects of IGCO on DM-induced testicular damage through inhibition of the AGEs/RAGE/p38 MAPK signaling pathway. Materials and methods A DM model of male Wistar rats was induced with streptozotocin injection (30 mg/kg, i.p.) and high-fat diet. The DM rats were administrated with IGCO at low and high doses (15 and 30 mg/kg, p.o.) for 12 weeks. Testicular damage was evaluated by estimating relative testicular weights, testicular pathohistology, sperm count, live sperm rate, endogenous sex hormone level and activity of testicular marker enzymes. Besides, general diabetic symptoms, renal function, oxidative stress parameters and testicular apoptosis marker were also determined. Finally, the mechanism was explored based on the AGEs/RAGE/p38 MAPK pathway. Results IGCO effectively mitigated the general symptoms of DM rats including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose level and low serum insulin level. Nourishing the kidney evidently, IGCO reduced serum creatinine, urea nitrogen and urine protein excretion, and also markedly protected against DM-induced testicular damage by increasing testis/body weight ratio and live sperm rate, improving the histomorphology of testes, upregulating testosterone, LH, FSH and GnRH levels and preventing the decrease of testicular marker enzymes LDH, ACP and γ-GT. Moreover, IGCO showed considerable anti-oxidative and anti-apoptotic effects, which downregulated the increase of ROS and MDA levels, restored SOD and CAT activities, and decreased spermatogenic cell apoptosis and Bax/Bcl-2 ratio. In the end, the increased AGEs, RAGE and p-p38 MAPK protein levels in DM rats were also reversed by IGCO significantly. Conclusions The kidney tonic IGCO well protected DM rats from testicular damage, which may be related to suppression of the AGEs-RAGE-p38 MAPK pathway.

Ethnopharmacological relevance Veronica ciliata Fisch. is a traditional medical herb that present in more than 100 types of Tibetan medicine prescriptions, most of which are used for liver disease therapy. Iridoid glycosides have been identified as the major active components of V.ciliata with a variety of biological activities. Aims of the study: The aim of this study is to explore the protective effect and potential mechanism of n-Butanol extract (BE) and iridoid glycosides (IG) from V.ciliata against ɑ-naphthyl isothiocyanate (ANIT)-induced hepatotoxicity and cholestasis in mice. Materials and methods Mice were intragastrically (i.g.) given BE and IG at different dose or positive control ursodeoxycholic acid (UCDA) once a day for 14 consecutive days, and were treated with ANIT to cause liver injury on day 12th. Serum levels of hepatic injury markers and cholestasis indicators, liver index and liver histopathology were measured to evaluate the effect of BE and IG on liver injury caused by ANIT. The protein levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B(NF-κB), interleukin-6 (IL-6), Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and the levels of oxidative stress indicators in liver tissue were investigated to reveal the underlying protective mechanisms of BE and IG against ANIT-induced hepatotoxicity and cholestasis. Results The n-Butanol extract (BE) and iridoid glycosides (IG) isolated from V.ciliata significantly decreased serum level of cholestatic liver injury markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), and direct bilirubin (DBIL) in ANIT-treated mice. Histopathology of the liver tissue showed that pathological damages were relieved upon BE and IG treatment. Meanwhile, the results indicated BE and IG notably restored relative liver weights, inhibited oxidative stress induced by ANIT through increasing hepatic level of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and decreasing hepatic content of malondialdehyde (MDA). Western blot revealed that BE and IG inhibited the expression of pro-inflammatory factors TGF-α, IL-6 and NF-κB. Furthermore, the decreased protein expression of bile acid transporters NTCP, BSEP, MRP2 were upregulated by BE and IG in a dose-dependent manner. Conclusion The results have demonstrated that BE and IG exhibited a dose-dependently protective effect against ANIT-induced liver injury with acute intrahepatic cholestasis in mice, which might be related to the regulation of oxidative stress, inflammatory response and bile acid transport. In addition, these findings pointed out that iridoid glycosides as main active components of V.ciliata play a critical role in hepatoprotective effect of V.ciliata.

Ethnopharmalogical relevance Callicarpa nudiflora Hook. & Arn. is a perennial evergreen shrub or low arbor in the Genus Callicarpa. Its dried aerial parts are used as traditional Chinese herbal medicine, Luo-hua-zi-zhu (Callicarpa nudiflora), which has been widely used in anti-bacteria and anti-ulcer in China (Commission, 2015; Development, 1994; Ming-Sheng, 2008). Aim of the study The present paper reviewed findings in phytochemistry and pharmacology of Callicarpa nudiflora. Methods Chinese and English studies on Callicarpa nudiflora were collected from databases including Web of Science, SciFinder, PubMed, Elsevier, and CNKI (Chinese), and the phytochemical and pharmacological studies of Callicarpa nudiflora were reviewed. Results A total of 300 small molecules, 173 of which are volatile oils, have been isolated from Callicarpa nudiflora. These small molecules could be divided into seven structural types — phenylpropanoids, flavonoids, triterpenes, diterpenes, iridoid glycosides, volatile oils, and other small molecules. Different types of compounds in Callicarpa nudiflora were summarized as follow: a) diterpenoid compounds can inhibit the generation of nitric oxide (NO) for exerting the function of anti-inflammation; b) triterpene compounds can play a role of anti-thrombus via inhibiting platelet aggregation and oleanane type and arbutane type pentacyclic triterpenes have the hepatoprotective activities; c) iridoid glycosides have cytotoxicity to tumor cells, and phenylpropanoids compounds have an antioxidant effect and could improve the function of memory. Our group further studied the antiviral activities of Callicarpa nudiflora finding that it has significant effects on RSV, EV71, COXB5, and HSV-1.

The seed kernels and hulls of Paeonia lactiflora Pall. (Chinese peony) contain numerous bioactive compounds. We extracted monoterpene glycosides and oligostilbenes from three varieties of P. lactiflora seed kernels and hulls, and analysed the bioactive compounds in these samples. The results indicated that seed kernels contained significant concentrations of monoterpene glycosides, whilst seed hulls contained high concentrations of oligostilbene compounds. The profiles of monoterpene glycosides and oligostilbene compounds in extracts were significantly dependent on the P. lactiflora variety. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and reference to literature data enabled 96 compounds to be tentatively characterised, including 24 monoterpene glycosides, 16 oligostilbene compounds, and several phenolic compounds, iridoid glycosides, diterpenoids and triterpenoids. This is the first study to find most of these compounds in P. lactiflora seed kernels and hulls. Paeoniflorin (1779.61 ± 10.33 mg/100 g) was the predominant monoterpene glycoside in seed kernels, whilst hulls had the highest concentrations of sufruticosol A (791.93 ± 25.09 mg/100 g) and trans-e-viniferin (607.4 ± 16.22 mg/100 g). All of the results confirmed that P. lactiflora seed kernels and hulls contain substantial concentrations of natural products. These products may be useful as medicines or as ingredients in functional foods.

Picroside I and II, iridoid glycosides, are the major active markers of roots and rhizomes of Picrorhiza kurroa (family: Scrophulariaceae). The rhizomes of P. kurroa have been traditionally used to treat worms, constipation, low fever, scorpion sting, asthma and ailments affecting the liver. Various Ayurvedic and herbal preparations are available in the market which contains P. kurroa e.g. Arogyavadhini vati, Tiktadi kwath , Picrolax capsules and suspension. These preparations are used without any significant pharmacokinetics data. Previously, we have reported that oral bioavailability of picroside I and II is low. Most of the iridoid glycosides are primarily metabolized by intestinal microbial flora. So, it is necessary to determine the metabolic profile of picroside I and II and check the correlation with lower bioavailability. Therefore, this study was designed to check metabolic ( in vitro and in vivo ) profile along with pharmacokinetic profile of picroside I and II. For this, a sensitive and selective LC-ESI-MS method was developed and validated for simultaneous determination of picroside I and II in rat plasma. Chromatographic separations were performed on C18 column. The mobile phase consisted of acetonitrile: 10 mM ammonium acetate buffer [90:10 v/v], pH 3.5. In-vitro Metabolic study was performed on rat liver microsomes and primary hepatocytes. In-vivo pharmacokinetic and metabolic profile of picroside I and II was generated after oral administration of Kutkin (mixture of picroside I and II) to Sprague-Dawley rats. Various pharmacokinetic parameters viz . C max , T max , AUC (0−t) were determined. In metabolic study, eight metabolites of picroside I and six metabolites of picroside II were identified in vitro , out of which four metabolites for each picroside I and picroside II were identified in vivo .

YinHuang drop pill (YHDP) is a new preparation, derived from the traditional YinHuang (YH) decoction. Since drop pills are one of the newly developed forms of Chinese patent drugs, not much research has been done regarding the quality and efficacy. This study aims to establish a comprehensive quantitative analysis of the chemical profile of YHDP. ultra high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was used to identify 34 non-sugar small molecules including 15 flavonoids, 9 phenolic acids, 5 saponins, 1 iridoid, and 4 iridoid glycosides in YHDP samples, and 26 of them were quantitatively determined. Sugar composition of YHDP in terms of fructose, glucose and sucrose was examined via a high performance liquid chromatography-evaporative light scattering detector on an amide column (HPLC-NH2P-ELSD). Macromolecules were examined by high performance gel permeation chromatography coupled with ELSD (HPGPC-ELSD). The content of the drop pill's skeleton component PEG-4000 was also quantified via ultra-high performance liquid chromatography coupled with charged aerosol detector (UHPLC-CAD). The results showed that up to 73% (w/w) of YHDP could be quantitatively determined. Small molecules accounted for approximately 5%, PEG-4000 represented 68%, while no sugars or macromolecules were found. Furthermore, YHDP showed no significant differences in terms of daily dosage, compared to YinHuang granules and YinHuang oral liquid; however, it has a higher small molecules content compared to YinHuang lozenge.