Iridoids with anti-inflammatory effect from the aerial parts of Morinda officinalis How.

Morinda officinalis How was widely applied to alleviate symptom like impotence, menstrual disorders, osteoporosis, and rheumatoid arthritis. To expand resources usage, phytochemistry of the aerial parts was studied and the structures of compounds were elucidated based on NMR, HRESIMS, IR and UV. Moreover, the anti-inflammatory effect and possible mechanism were investigated by Griess kit, RT-qPCR, ELISA, western blot and molecular docking on LPS-induced inflammation in RAW 264.7 cells. Herein, we isolated and identified 16 iridoid derivatives, including seven new iridoids officinaloside A-G (1-7) and nine known iridoids. All the compounds were safe to RAW 264.7 cells. Luckily, compounds 5 and 6 showed inhibitory effect on production of NO, and decreased the expression of inflammatory cytokines at mRNA and protein levels in a dose-dependent way. The possible mechanism of their anti-inflammation may be the affinity interaction between 5 with COX-2 protein, and 6 with iNOS protein. Overall, compounds 5 and 6 exert promising effects in inhibiting inflammatory cytokines, indicating that they could be used as lead compounds for developing health products or clinical practice for inflammation, which provides a scientific basis for further sustainable development and usage of the aerial parts of Morinda officinalis How.

Antidepressant effects of total iridoids of Valeriana jatamansi via the intestinal flora-blood-brain barrier pathway.

CONTEXT: Valeriana jatamansi Jones [syn. V. wallichii DC, (Valerianaceae)] (VJJ) is used to treat depression. OBJECTIVE: To explore the effects of total iridoids of VJJ extract (TIV) on chronic unpredictable mild stress (CUMS) in mice. MATERIALS AND METHODS: VJJ roots and rhizomes were extracted with 70% ethanol. CUMS rats were treated daily with fluoxetine (2.6 mg/kg, i.g.) or TIV (5.7, 11.4, and 22.8 mg/kg, i.g.) for 14 days. Male Kun Ming mice on normal chow and 0.5% CMC-Na solution were used as a control. Behavioural tests included the tail suspension (TST) and sucrose preference tests (SPT). Evans blue staining was used to evaluate blood-brain barrier (BBB) permeability. Western blotting was used to measure zonula occludens-1 (ZO-1) and occludin expression. 16S rRNA sequencing was used to analyse intestinal flora abundance. Tax4Fun was used to predict KEGG metabolic pathways. RESULTS: TIV treatment reduced TST time (117.35 ± 8.23 or 108.95 ± 6.76 vs. 144.45 ± 10.30 s), increased SPT (55.83 ± 7.24 or 53.12 ± 13.85 vs. 38.98 ± 5.43%), increased the abundance of phylum Firmicutes (86.99 ± 0.03 vs. 60.88 ± 0.19%) and genus Lactobacillus (75.20 ± 0.19 vs. 62.10 ± 0.13%), reduced the abundance of phylum Bacteroidetes (6.69 ± 0.06 or 11.50 ± 0.09 vs. 25.07 ± 0.20%). TIV increased carbohydrate metabolism (14.50 ± 3.00 × 10-3 or 14.60 ± 2.00 × 10-3 or 14.90 ± 2.00 × 10-3 vs.13.80 ± 4.00 × 10-3%), replication and repair functions (5.60 ± 1.00 × 10-3 or 5.60 ± 1.00 × 10-3 vs. 5.10 ± 4.00 × 10-3%), reduced the frequency of infectious disease (1.60 ± 2.00 × 10-4 or 1.90 ± 5.00 × 10-4 or 1.80 ± 3.00 × 10-4 vs. 2.20 ± 7.00 × 10-3%), BBB permeability (0.77 ± 0.30 vs. 1.81 ± 0.33 µg/g), and up-regulated the expression of ZO-1 (1.42-fold, 1.60-fold, 1.71-fold) and occludin (1.79-fold, 2.20-fold). CONCLUSIONS: TIV may modulate the intestinal flora, thereby inducing the expression of ZO-1 and occludin, protecting the BBB and exerting an antidepressant effect.

Iridoid compounds from the aerial parts of Swertia mussotii Franch. with cytotoxic activity.

One new secoiridoid compound swertiamarin B (1), along with a known compound lytanthosalin (2), were isolated from ethanol extract of the aerial parts of Swertia mussotii. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. All compounds were first isolated from the Swertia genus. Their antitumor activities were evaluated for four human tumor cell lines (HCT-116, HepG2, MGC-803 and A549). Compounds 1 and 2 showed excellent cytotoxic activities toward the MGC-803 cell lines with IC50 values 3.61 and 12.04 µM, respectively.

Modulation of the 5-HT3A receptor current by desacylbaldrinal.

The serotonin (5-hydroxytryptamine) type 3 receptor is an important target in the control of digestive dysfunction such as anorexia and bulimia, and 5-HT3 receptor antagonists are effective against eating disorder and the early-phase chemotherapy and radiotherapy evoked vomiting. Our previous research of Valeriana jatamansi revealed the presence of iridoids, which showed potent antitumor activities. Here, we explored the effects of 10π aromatic iridoid desacylbaldrinal isolated from V. jatamansi on the 5-HT3 receptor current. We performed whole cell recordings of 5-HT3A receptor currents in the presence of the compound. The result indicated that desacylbaldrinal inhibited the 5-HT-mediated 5-HT3A receptor current.

Anticonvulsant activity of Valeriana edulis roots and valepotriates on the pentylenetetrazole-induced seizures in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: For many centuries, Mexican Valerian (Valeriana edulis ssp. procera) has been an important plant in folk medicine. It has been considered useful to control epilepsy; however, electroencephalographic evidence of its anticonvulsant activity is missing in literature. AIM OF THE STUDY: In the present study, in situ electroencephalographic (EEG) analysis was performed along with administration of a crude ethanol extract of V. edulis and its valepotriate fraction on the pentylenetetrazole (PTZ)-induced convulsive behavior in rats. MATERIALS AND METHODS: Experiments were performed using male Wistar rats with nail-shaped electrodes implanted in the frontal and parietal cortices for EEG recording. All animals received a single dose of PTZ (35 mg/kg, i.p.) to test the anticonvulsant activity of V. edulis crude extract and valepotriate fraction (100 mg/kg, i.p.) 15 and/or 30 min after administration. EEG recordings were obtained from the cortices and were evaluated to assess ictal behavior over 60-75 min. Chromatographic analysis of the valepotriate fraction and in silico predictions of pharmacodynamic properties were also explored. The latency, frequency and duration of seizures evaluated using EEG recordings from the frontal and parietal cortices of rats showed significant changes demonstrating the inhibition of paroxystic activity. RESULTS: The spectral analysis confirmed the reduction of excitatory activity induced by V. edulis extract, which was improved in the presence of the valepotriate fraction as compared to that induced by ethosuximide (a reference anticonvulsant drug). The presence of valepotriates such as: isodihydrovaltrate (18.99%), homovaltrate (13.51%), 10-acetoxy-valtrathydrin (4%) and valtrate (1.34%) was identified by chromatographic analysis. Whereas, not only GABAA receptor participation but also the cannabinoid CB2 receptor was found to be likely involved in the anticonvulsant mechanism of action after in silico prediction. CONCLUSIONS: Our data support the anticonvulsant properties attributed to this plant in folk medicine, due to the presence of valepotriates.

Iridoids from Gardeniae fructus ameliorates depression by enhancing synaptic plasticity via AMPA receptor-mTOR signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Gardeniae fructus is a traditional Chinese herb which exerts antidepressant effect. However, its effective constituent and potential mechanism are still unknown. AIM OF THE STUDY: To examine whether iridoids, a type of monoterpenoids from Gardeniae fructus (IGF), exerts antidepressant effect by enhancing synaptic plasticity via AMPA receptor-mTOR signaling. MATERIALS AND METHODS: The antidepressant effect of IGF (15 mg/kg; 30 mg/kg; 45 mg/kg) was investigated in spatial restraint stress (SRS)-induced mice. The expression levels of AMPA receptor-mTOR signaling and synaptic proteins were measured by Western blot, dendritic spine density was observed in Golgi staining. AMPA receptor (AMPAR) inhibitor NBQX and mTOR inhibitor Rapamycin were employed to determine the roles of AMPAR and mTOR signaling in IGF-induced antidepressant effects. RESULTS: After IGF administration, the expression of the AMPA glutamate receptor Glutamate Receptor 1 (GluA1) was inhibited in SRS mice. We also observed a trend toward the up-regulation of the mammalian target of Rapamycin (mTOR) protein kinase, p70 ribosomal protein S6K (P70S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). The protein levels of Synapsin-1 and PSD-95 were decreased after SRS challenge, along with declined dendritic spine density, which were all reversed with IGF treatment. Furthermore, the treatment efficacy of IGF were blocked with AMPA receptor inhibitor NBQX or mTOR inhibitor Rapamycin. CONCLUSION: IGF exerted antidepressive-like effects by stimulating AMPAR-mTOR signaling regulated synaptic plasticity enhancement. This work provided an important basis for developing IGF and Gardeniae fructus as potential anti-depressants.

Olive Pâté by Multi-Phase Decanter as Potential Source of Bioactive Compounds of Both Nutraceutical and Anticancer Effects.

In the oil sector, a novelty in the centrifugal extraction system is represented by the multi-phase decanters (DMF) that work without adding process water and with the advantage of recovering a dried pomace and a by-product, called "pâté", consisting of the pulp and its vegetation water, without traces of stone. The pâté has a high content of phenolic compounds, mainly represented by secoiridoids and verbascoside. The present work investigated the efficacy of two different ways of debittering (by sequential filtrations and spontaneous fermentation) of DMF pâté from three olive cultivars (Olea europaea L. "Leccino", "Carboncella" and "Tortiglione") to make the pâté edible, and, contemporary, investigated also the effect of its phenolic bioactive extracts on pathogenic bacteria and colon cancer cell model. Daily filtrations of pâté of the three cultivars have been shown to be more efficient in phenolic degradation. The activity of the indigenous microflora on the other hand takes a longer time to degrade the phenolic component and therefore to de-bitter it. None of pâté showed antibacterial activity. Colorimetric assay MTS for cell viability and metabolic activity tested on colon cancer cells CaCo2 and HCT116 suggest a potential beneficial effect of the dried extracts probably related to the modulation of gene expression under these treatments.

Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice.

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.

Geniposide in Gardenia jasminoides var. radicans Makino modulates blood pressure via inhibiting WNK pathway mediated by the estrogen receptors.

OBJECTIVES: To investigate the effects of geniposide in an iridoid found in Gardenia jasminoides var. radicans Makino (GJRM) in spontaneous hypertensive rat (SHR) and explore the possible mechanisms. METHODS: In this study, we detected the content of geniposide in GJRM by high-performance liquid chromatography (HPLC). Then, we used acute diuretic experiments to determine whether geniposide has diuretic effect. Moreover, we carried out experiments on SHR to further study the mechanism of hypertension, while real-time PCR, Western blot and immunohistochemistry were used for the experiments in vivo test. Hypotonic model was used for in vitro test. KEY FINDINGS: Our data showed that the content of geniposide in the extract of GJRM is 27.54%. Meanwhile, 50 mg/kg geniposide showed the strongest effect on promoting urine volume. Further study indicated that the extract of GJRM and geniposide could significantly reduce blood pressure and promote the excretion of urine and Na+ in SHR. In addition, geniposide significantly inhibited the activation of the with-no-lysine kinase (WNK) signalling pathway and significantly increases the protein expressions of estrogen receptor α (ERα), estrogen receptor ß (ERß) and G protein-coupled receptor 30 (GPR30) in SHR. In hypotonic model, geniposide significantly inhibits the phosphorylation of NKCC and NCC and could be antagonistic to estrogen receptor antagonists. CONCLUSIONS: Collectively, we would suggest that geniposide may potentially be utilized as an adjunct to existing thiazide and thiazide-like diuretics to control hypertension, mainly through inhibiting the activation of the WNK signalling pathway mediated by the estrogen receptor.

Elucidation of the active ingredients of Lamiophlomis herba against hemorrhage based on network pharmacology and tail snipping model in mice.

This study aimed to elucidate the active ingredients of Lamiophlomis herba (LH), the overground part of Lamiophlomis rotata (Benth.) Kudo, against hemorrhage based on network pharmacology and tail snipping model in mice. A total of 118 hemorrhage-related target genes were identified by retrieving public databases, and 39 genes were identified as the hub genes of hemorrhage based on protein-protein interaction and module analyses. The interactions between 67 potentially active ingredients in LH and 7 genes in the 39 hub genes were established and analyzed through molecular docking and Cytoscape. A total of 21 ingredients were involved in the interactions, and were divided into three categories: iridoid (15 ingredients), flavonoid (2 ingredients) and other category (4 ingredients). Based on the "multi-ingredient, multi-target" characteristic of traditional Chinese medicines (TCMs), the results of network pharmacology indicated that iridoid might be the key active ingredient group of LH against hemorrhage. The contribution of iridoid to the hemostatic effect of LH was investigated by the tail snipping model in mice. The results showed that iridoid was the key active ingredient group of LH against hemorrhage, which confirmed the prediction in network pharmacology. Additionally, the previous reports also supported this prediction. In conclusion, the finding of the present study indicates that iridoid is the key hemostatic ingredient group of LH. This work provides valuable references for investigation of the hemostatic ingredients of LH based on the holistic theory of TCMs. Meanwhile, this work also provides further insight into the development of hemostatic drugs based on LH.

Antifungal activity of Allamanda polyantha seed extract and its iridoids promote morphological alterations in Cryptococcus spp.

Cryptococcosis, caused by Cryptococcus spp., is an invasive fungal infection of the central nervous system, associated with high mortality, affecting mainly immunocompromised patients. Due to the development of resistance to the current therapy, there is an urgent need for less toxic and more effective antifungal agents. In this study, we describe the antifungal activity against Cryptococcus spp. of an aqueous seed extract from Allamanda polyantha (ASEAP) and two iridoids, plumieride and plumieridine, isolated from this extract with an antifungal activity. The capsule formation and the morphological alterations were evaluated using fluorescent microscopy. The cytotoxic activity was also investigated. The minimal inhibitory concentration (MIC) values of ASEAP for Cryptococcus gattii were 70 and 36 µg/ml (for the R265 and R272 strains, respectively) and 563 µg/ml for Cryptococcus neoformans H99. ASEAP inhibited C. neoformans H99 capsule formation, an important virulence factor, and decreased the cell body size for both the C. gattii strains. H99 cells also presented morphological alterations, with defects in bud detachment and nuclear fragmentation. Plumieride and plumieridine presented higher MIC values than ASEAP, indicating that other compounds might contribute to antifungal activity and/or that combination of the compounds results in a higher antifungal activity.

Phytochemical analysis of olive flowers' hydroalcoholic extract and in vitro evaluation of tyrosinase, elastase and collagenase inhibition activity.

Olea europaea L. is historically one of the most important trees of the Mediterranean countries. Increasing scientific interest regarding its fruits, leaves and olive oil has led to the elucidation of several phytochemical and biological characteristics. However, the phytochemical and biological studies regarding olive flowers remain limited. The aim of the present study was the phytochemical characterization of olive flowers' hydroalcoholic extract from Greek variety Lianolia, the effective isolation of the major secondary metabolites and evaluation of their inhibition activity against tyrosinase, elastase and collagenase. UPLC-HRMS/MS analysis was used to investigate the chemical composition of hydroalcoholic extract resulting in the identification of sixty-three secondary metabolites witch mainly belong to phenilethanoids, triterpenoids, flavonoids and secoiridoids. The orthogonial combination of Centrifugal Partition Chromatography and preparative HPLC in the same purification process led to the isolation of nine major compounds of the extract including two triterpenic acids, two flavonoid glycosides and five secoiridoid derivatives. From them, oleofloside A and oleofloside B are new natural products. Although, the hydroalcoholic extract and isolated secoiridoids exhibited weak or no inhibition activity towards tyrosinase and elastase, they exhibit remarkable anti-collagenase activity with 2΄-ethoxyoleuropein being the most active compound.

Viburnumfocesides A - D, 1-O-isovaleroylated iridoid 11-O-alloside derivatives from Viburnum foetidum var. ceanothoides.

Viburnumfocesides A - D, four undescribed 1-O-isovaleroylated iridoid 11-O-allosides modified with (Z / E)-p-coumaric acid, were isolated from the aqueous EtOH extract of the twigs of Viburnum foetidum var. ceanothoides, together with seven known natural products. Their structures were identified on the basis of the spectroscopic data interpretation and chemical derivation studies. Cell-based estrogen biosynthesis assays indicated that viburnumfoceside D (4), (2S,3R)-2,3-dihydro-3-hydroxymethyl-7-methoxy-2-(4-hydroxy-3-methoxyphenyl)-5-benzofuranpropanol-3a-O-α-L-rhamnopyranoside (8), and (-)-eriodictyol (11) inhibit estrogen biosynthesis with IC50 values of 5.8, 1.5, and 1.1 µM, respectively, in human ovarian granulosa-like KGN cells via decreasing the expression level of aromatase.

Health Properties and Composition of Honeysuckle Berry Lonicera caerulea L. An Update on Recent Studies.

Lonicera caerulea L., also known as haskap or honeysuckle berry, is a fruit commonly planted in eastern Europe, Canada and Asia. The fruit was registered as a traditional food from a third country under European Union regulations only on December 2018. It is resistant to cold, pests, various soil acidities and diseases. However, its attractiveness is associated mostly with its health properties. The fruit shows anticancer, anti-inflammatory, and antioxidant activity-important factors in improving health. These features result from the diverse content of phytochemicals in honeysuckle berries with high concentrations of phytocompounds, mainly hydroxycinnamic acids, hydroxybenzoic acids, flavanols, flavones, isoflavones, flavonols, flavanones and anthocyanins but also iridoids, present in the fruit in exceptional amounts. The content and health properties of the fruit were identified to be dependent on cultivar, genotype and the place of harvesting. Great potential benefits of this nutritious food are its ability to minimize the negative effects of UV radiation, diabetes mellitus and neurodegenerative diseases, and to exert hepato- and cardioprotective activity.

Iridoids of Valeriana fauriei contribute to alleviating hepatic steatosis in obese mice by lipophagy.

Nonalcoholic fatty liver disease (NAFLD) is a common risk factor for metabolic syndrome that increases the risk of future cardiovascular disease, stroke, and diabetes. Recently, autophagy has been proposed as a means to prevent NAFLD. We investigated whether substances with autophagy-inducing activity alleviate NAFLD. The Valeriana fauriei (V. fauriei) was selected as a potential autophagy inducer among various natural materials using a Cyto-ID autophagy detection kit. V. fauriei 70 % ethanol extract (VFE) increased LC3II levels in the presence of the lysosomal inhibitor and reduced the GFP/mCherry puncta ratio, suggesting that VFE enhanced autophagy. VFE reduced oleic acid (OA)-induced lipid accumulation and increased the number of autophagosome in hepatocytes. Autophagy induction by VFE is due to inhibition of mTORC1 activity. VFE supplementation reduced fatty liver by downregulating lipogenesis-related genes and increased the autophagy, as revealed by TEM and IHC analysis in the fatty liver. We identified iridoids as main compounds of VFE; didrovaltrate (DI), valeriotriate B (VAL B), valeriotetrate C (VAL C), valtrate (VAL), and valechlorine (VC) were shown to enhance autophagy. These compounds also reduced OA-induced lipid accumulation in an Atg5-dependent manner. Taken together, VFE and its iridoids might be effective in alleviating fatty liver by acting as autophagy enhancers to break down LDs.

Iridoids and Amino Acid Derivatives from the Paraguayan Crude Drug Adenocalymma marginatum (ysypó hû).

The crude drug ysypó hû (Adenocalymma marginatum DC., Bignoniaceae) is used traditionally by the Guarani of Eastern Paraguayan as a male sexual enhancer. The aim of the present study was to identify the main constituents of the crude drug and to evaluate the in vitro inhibitory activity towards the enzyme phosphodiesterase-5 (PDE-5). The main compounds were isolated by counter-current chromatography (CCC). The metabolites were identified by spectroscopic and spectrometric means. The chemical profiling of the extracts was assessed by high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS). The crude extract and main isolated compounds were tested for their PDE-5 inhibitory activity using commercial kits. The iridoid theviridoside and 4-hydroxy-1-methylproline were isolated as the main constituent of the crude drug. Four chlortheviridoside hexoside derivatives were detected for the first time as natural products. Chemical profiling by HPLC-MS/MS led to the tentative identification of nine iridoids, six phenolics, and five amino acids. The crude extracts and main compounds were inactive towards PDE-5 at concentrations up to 500 µg/mL. Iridoids and amino acid derivatives were the main compounds occurring in the Paraguayan crude drug. The potential of ysypó hû as a male sexual enhancer cannot be discarded, since other mechanisms may be involved.

Chemical Constituents from Fraxinus hupehensis and Their Antifungal and Herbicidal Activities.

The phytochemical investigation of Fraxinus hupehensis led to the isolation and characterization of ten compounds which were identified as fraxin (1), fraxetin (2), esculetin (3), cichoriin (4), euphorbetin (5), kaempferol-3-O-ß-rutinoside (6), oleuropein (7), linoleic acid (8), methyl linoleate (9), and ß-sitosterol (10). Structures of the isolated constituents were characterized by 1H NMR, 13C NMR and HRMS. All the compounds, except compounds 3 and 4, were isolated for the first time from this plant. Further, this was the first report for the occurrence of compound 5 in the Fraxinus species. Antifungal activity evaluation showed that compound 2 exhibited significant inhibitory effects against Bipolaris maydis, Sclerotium rolfsii, and Alternaria solani with EC50 values of 0.31 ± 0.01 mmol/L, 10.50 ± 0.02 mmol/L, and 0.40 ± 0.02 mmol/L respectively, compared to the positive control, Carbendazim, with its EC50 values of 0.74 ± 0.01 mmol/L, 1.78 ± 0.01 mmol/L and 1.41 ± 0.00 mmol/L. Herbicidal activity tests showed that compounds 8-10 had strong inhibitory effects against the roots of Echinochloa crus-galli with EC50 values of 1.16 ± 0.23 mmol/L, 1.28 ± 0.58 mmol/L and 1.33 ± 0.35 mmol/L respectively, more potently active than that of the positive control, Cyanazine, with its EC50 values of 1.56 ± 0.44 mmol/L. However, none of the compounds proved to be active against the tested bacteria (Erwinia carotovora, Pseudomonas syringae, and Ralstonia solanacearum).

Linaburiosides A-D, acylated iridoid glucosides from Linaria buriatica.

Four previously undescribed acylated iridoid glucosides, linaburiosides A‒D, one undescribed iridoid, 7-deoxyiridolactonic acid, and one known acylated iridoid glucoside, iridolinarin C, were isolated from the aerial parts of a Mongolian traditional herbal medicine, Linaria buriatica. Linaburiosides A‒D had an acyl moiety corresponding to 7-deoxyiridolactonic acid. Detailed spectroscopic analyses of linaburiosides A‒D and 7-deoxyiridolactonic acid led to the assignment of their structures. The absolute configuration of 7-deoxyiridolactonic acid was elucidated by application of the PGME method; those of linaburiosides A‒D were assigned on the basis of chemical conversions, as well as application of the modified Mosher's method. The absolute configuration of iridolinarin C was also elucidated in this study. Anti-inflammatory and antiproliferative activities of isolated compounds and their derivatives were evaluated.

Valtrate from Valeriana jatamansi Jones induces apoptosis and inhibits migration of human breast cancer cells in vitro.

Valtrate is a principle compound isolated from Valeriana jatamansi Jones, a traditional Chinese folk medicine originally used to treat various nervous disorders. Here, we found that valtrate exhibited significant anti-cancer activity in vitro, especially in human breast cancer cells, while displayed relatively low cytotoxicity to normal human breast epithelial cells (MCF 10A). Valtrate induced cell cycle arrest at G2/M stage and apoptosis in MDA-MB-231 and MCF-7 cells, with reduced expression of p-Akt (Ser 473), cyclin B1 and caspase 8, and increased expression of p21, p-cdc2, cleaved-caspase 3, cleaved-caspase 7 and poly (ADP-ribose) polymerase (PARP). In addition, valtrate inhibited cell migration through down-regulation of MMP-9 and MMP-2 expression. These results demonstrate that valtrate possesses anti-breast cancer activities via cell cycle arrest, apoptosis, and inhibition of cell migration, thus supporting valtrate as a potential antitumor agent.

Loganin ameliorates cartilage degeneration and osteoarthritis development in an osteoarthritis mouse model through inhibition of NF-κB activity and pyroptosis in chondrocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Loganin is a major iridoid glycoside and one of the quality control indexes of CF. In TCM clinical practice, prescription containing CF is commonly used to treat osteoarthritis (OA), but the underlying mechanisms of loganin are not yet utterly understood. AIM OF THE STUDY: The aims of the present study are to confirm the therapeutic effects of loganin in an OA mouse model and to determine the mechanisms involved in the OA protective effects. MATERIALS AND METHODS: The destabilization of the medial meniscus (DMM) procedure was performed on the right knee of 8-week-old C57BL/6 male mice. 30 or 100 µg/ml of loganin was then injected into articular space twice a week for 8 and 12-week. Safranin O/Fast green staining, H&E staining, micro-CT analysis were performed to analyze structural and morphological changes. The protein expression of collagen type II (Col2), metalloproteinase-3 (Mmp3), matrix metalloproteinase 13 (Mmp13) collagen type X (Col10), cryopyrin and caspase-1 were detected by immunochemistry staining. Immuno-fluorescence assay was performed to assess changes in expression of CD31, endomucin, p65 and p-I-κB. RESULTS: Results of histomorphometry showed that loganin delays the progression of OA in the DMM model. In cartilage, loganin decreased the OARSI score, increasing hyaline cartilage (HC) thickness and decreasing calcified cartilage (CC) thickness. Moreover, loganin inhibited osteophyte formation, reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th) and increased trabecular separation (Tb.Sp) in subchondral bone. Mechanistically, loganin increased the expressions of Col2, decreases the expression of Mmp3, Mmp13, Col10, cryopyrin and caspase-1 in cartilage. In parallel, loganin inhibited the expression of CD31 and endomucin in subchondral bone. Furthermore, loganin suppressed nuclear translocation of p65 protein, and decreased the amount of p-I-κB in chondrocytes. CONCLUSIONS: In summary, these results uncovered that loganin inhibits NF-κB signaling and attenuates cartilage matrix catabolism and pyroptosis of chondrocytes in articular cartilage. Loganin may serve as a potential therapeutic agent for OA treatment.