A new phenolic glycoside from Trollius chinensis Bunge with anti-inflammatory and antibacterial activities.

A undescribed phenolic glycoside, trochinenol A (1), was isolated from the flowers of Trollius chinensis Bunge and the structure was identified by spectroscopic methods. Its anti-inflammatory and antibacterial effects were investigated by broth microdilution and NF-κB reporter gene assays. Consequently, compound 1 exhibited an appreciable effect against Staphylococcus aureus with the MIC value of 6.25 µg/mL. Besides, it showed moderate effect against TNFα-induced activation of NF-κB pathway.

The antiviral mechanism of the crude extract from the flowers of Trollius chinensis based on TLR 3 signaling pathway.

The effects of crude extract from the flowers of Trollius chinensis on expressions of mRNA and proteins related to vital genes (TLR 3, TBK 1, IRF 3 and IFN ß) in TLR 3 signaling pathway were investigated in the presence/absence of Polyinosinic acid-polycytidylic acid (PolyI: C) to ascertain the antiviral mechanism of these flowers. Real-time PCR and western blot were applied to determine the expressions of mRNA and proteins, respectively, and immunofluorescence assay was employed to study the effect on IRF 3 distribution between nuclei and cytoplasma. In the absence of PolyI:C, the crude extract reduced the mRNA expression of TLR 3, IRF 3 and IFN ß and the protein expression of TLR 3, and increased the protein expression of IRF 3 and the distribution of IRF 3 in nuclei. In the presence of PolyI:C, the extract reduced the mRNA and protein expressions of TLR 3 and the mRNA expression of IFN ß, meanwhile inhibited the translocation of IRF 3 into nuclei. The antiviral mechanism of the crude extract from the flowers of T. chinensis is to protect the host from inflammatory damage through intervening the TLR 3 signaling pathway and reducing the secretion of inflammatory factors.

Diterpenoid glycosides from the flower of Trollius chinensis Bunge and their nitric oxide inhibitory activities.

Trolliusditerpenosides A-Q (1-17), seventeen new labdane-diterpenoid glycosides, were isolated from the dried flowers of Trollius chinensis Bunge, a plant that has been commonly used as both an anti-inflammatory folk medicine and a healthcare tea for its therapeutic and anti-viral and antibacterial properties. Their structures were corroborated via comprehensive spectroscopic analysis, ECD calculations, and single-crystal X-ray diffraction analysis. Furthermore, the inhibitory activities on lipopolysaccharide (LPS)-induced NO production in RAW 264.7 macrophages of all compounds (1-17) were evaluated in vitro. Compounds 3, 6, 7, and 11 displayed significant inhibitory activities against NO production, with IC50 values ranging from 1.6 ± 0.1 to 14.4 ± 0.2 µM. In addition, compounds 3, 6, 7, and 11 all down-regulated the mRNA expression of iNOS, COX-2, and IL-1ß in RAW 264.7 cells mediated by LPS. These findings not only support the chemical context of genus Trollius but also the exploration of new chemical entities with pharmacological significance from this genus.

Metabolite Profiling Based on UPLC-Q-TOF-MS/MS and the Biological Evaluation of Medicinal Plants of Chinese Dichocarpum (Ranunculaceae).

The genus Dichocarpum is endemic to East Asia, and many species have been used to treat various diseases. However, phytochemical researches of this genus have been limited to date. In the present study, a metabolomic approach based on UPLC-Q-TOF-MS/MS was used to explore the phytochemical profiles of 10 Chinese Dichocarpum species, and cannabinoid receptor (CB1/CB2) agonistic activities evaluation of these plants was performed. A total of 128 features were putatively annotated, belonging to alkaloids, flavonoids, triterpenes saponins, phenolic acids, and others. Semi-quantitative statistics demonstrated that alkaloids and flavonoids were widely distributed, with the former the most abundant, whereas triterpenes saponins were mainly distributed in D. fargesii and D. wuchuanense. The phylogenetic results obtained from DNA sequencing assigned the 10 species to three groups. Further results of in silico annotation revealed three chemical families and helped determine the characteristic features of the three groups. In addition, the plant extracts of nine species from this genus showed agonistic activity on CB2 receptors. This comprehensive analysis revealed the chemotype distribution and pharmacophylogenetic relationship, to provide clues for the prospective resource utilization of the medicinal plants from the genus Dichocarpum.

In vitro anti-Acanthamoeba activity of flavonoid glycosides isolated from Delphinium gracile, D. staphisagria, Consolida oliveriana and Aconitum napellus.

Acanthamoeba spp. are widely distributed in the environment and cause serious infections in humans. Treatment of Acanthamoeba infections is very challenging and not always effective which requires the development of more efficient drugs against Acanthamoeba spp. The purpose of the present study was to test medicinal plants that may be useful in the treatment of Acanthamoeba spp. Here we evaluated the trophozoital and cysticidal activity of 13 flavonoid glycosides isolated from Delphinium gracile, D. staphisagria, Consolida oliveriana and from Aconitum napellus subsp. Lusitanicum against the amoeba Acanthamoeba castellanii. AlamarBlue Assay Reagent® was used to determine the activity against trophozoites of A. castellanii, and cytotoxic using Vero cells. Cysticidal activity was assessed on treated cysts by light microscopy using a Neubauer chamber to quantify cysts and trophozoites. Flavonoids 1, 2, 3 and 4 showed higher trophozoital activity and selectivity indexes than the reference drug chlorhexidine digluconate. In addition, flavonoid 2 showed 100% cysticidal activity at a concentration of 50 µm, lower than those of the reference drug and flavonoid 3 (100 µm). These results suggest that flavonoids 2 and 3 might be used for the development of novel therapeutic approaches against Acanthamoeba infections after satisfactory in vivo evaluations.

Anticoccidial effect of toltrazuril and Radix Sophorae Flavescentis combination: Reduced inflammation and promoted mucosal immunity.

An anticoccidial model of chicken infected with Eimeria tenella was established to investigate the effect of toltrazuril (Tol) combined with the Radix Sophorae Flavescentis (RSF) on coccidiosis. The anticoccidial index (ACI) was evaluated, and the cecal developmental parameters (i.e., villus height, [VH], crypt depth, [CD], and VH/CD) were determined. The distributions of glycoproteins and goblet cells in the cecal tissue were determined through the Periodic Acid-Schiff (PAS) and Alcian blue PAS staining methods, respectively. The mRNA expression levels of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, and IL-17 of the cecal tissue were determined through quantitative real-time PCR. The moderate ACI was obtained using the combination of Tol and RSF. Compared with the normal control (NC) group, the infected control (IC) group showed remarkably lower VH and VH/CD at five and seven days postinfection. Compared with the IC group, the IC + RSF and IC + TolRSF groups showed remarkably higher VH and VH/CD at five and seven days postinfection. Compared with the NC group, the IC group contained fewer glycoproteins and goblet cells, but the Tol and RSF treatment promoted more glycoproteins and goblet cells at five and seven days postinfection. The mRNA expression levels of IL-1ß, IL-2, IL-4, IL-6, IL-10, and IL-17 in the IC group were upregulated (P < 0.01) compared with those in the NC group. The IC + RSF and IC + TolRSF groups had downregulated mRNA expression levels of IL-1ß, IL-6, and IL-17 cytokines (P < 0.01), and upregulated mRNA expression levels of IL-2 and IL-4 cytokines (P < 0.01) compared with the IC group. Results showed that the combination of Tol and RSF exerts anticoccidial effect by reducing inflammation and promoting intestinal mucosal immunity.

Investigation of Chemical Constituents of Eranthis longistipitata (Ranunculaceae): Coumarins and Furochromones.

Aqueous-ethanol extracts (70%) from the leaves of Eranthis longistipitata Regel. (Ranunculaceae Juss.)-collected from natural populations of Kyrgyzstan-were studied by liquid chromatography with high-resolution mass spectrometry (LC-HRMS). There was no variation of the metabolic profiles among plants that were collected from different populations. More than 160 compounds were found in the leaves, of which 72 were identified to the class level and 58 to the individual-compound level. The class of flavonoids proved to be the most widely represented (19 compounds), including six aglycones [quercetin, kaempferol, aromadendrin, 6-methoxytaxifolin, phloretin, and (+)-catechin] and mono- and diglycosides (the other 13 compounds). In the analyzed samples of E. longistipitata, 14 fatty acid-related compounds were identified, but coumarins and furochromones that were found in E. longistipitata were the most interesting result; furochromones khelloside, khellin, visnagin, and cimifugin were found in E. longistipitata for the first time. Coumarins 5,7-dihydroxy-4-methylcoumarin, scoparone, fraxetin, and luvangetin and furochromones methoxsalen, 5-O-methylvisammioside, and visamminol-3'-O-glucoside were detected for the first time in the genus Eranthis Salisb. For all the above compounds, the structural formulas are given. Furthermore, detailed information (with structural formulas) is provided on the diversity of chromones and furochromones in other representatives of Eranthis. The presence of chromones in plants of the genus Eranthis confirms its closeness to the genus Actaea L. because chromones are synthesized by normal physiological processes only in these members of the Ranunculaceae family.

Evaluation of anti-inflammatory and analgesic activities of aqueous methanolic extract of Ranunculus muricatus in albino mice.

Ranunculus muricatus (Ranunculaceae) is commonly used by inhabitants of Pakistan for the treatment of gout and rheumatism, both of which are inflammatory disorders. The present study attempts to evaluate the anti-inflammatory and analgesic activities of aqueous methanolic extract of R. muricatus in mice. The plant extract at doses of 50, 100 and 150 mg/kg was tested for anti-inflammatory activity against carrageenan and egg albumin induced paw edema in mice and analgesic activity was appraised against acetic acid induced writhing and formalin induced paw licking in mice models. The results designate that extract at the highest dose of 150 mg/kg significantly (p<0.001) and dose dependently inhibited carrageenan induced and egg albumin induced paw edema. Similarly, extract at the same dose of 150 mg/kg showed potent and dose dependent (p<0.001) suppression of formalin induced paw licking and abdominal constrictions / stretching of hind limbs induced by acetic acid. The anti-inflammatory and analgesic activity of plant extract was comparable to standard drug ibuprofen in all models. This study thus supports the use of R. muricatus in traditional medicine for conditions associated with inflammation and analgesia which might be attributed to its previously proven high alkaloid, flavonoids, phenol, tannins content and free radical scavenging activity.

Herbal drink formulation optimization of Trollius chinensis Bunge by sensory fuzzy comprehensive evaluation.

BACKGROUND: Trollius chinensis Bunge is a common herbal plant used for pharmaceutical and food resources in China. The dry flowers of Trollius chinensis Bunge are also treated as a traditional Chinese tea for daily drinking, yet the Trollius chinensis Bunge tea will exhibit a bitter taste in a certain concentration range and is not always accepted among consumers. The aim of the study was to design a herbal drink with a good flavor and optimize the formulation. METHODS: Trollius chinensis Bunge was purchased and ground. The sensory fuzzy comprehensive evaluation method and the orthogonal test were applied to optimize the formulation of the Trollius chinensis Bunge herbal drink. RESULTS: The results showed that the optimum formulation was as follows: an addition amount of Trollius chinensis Bunge extract solution of 30%; an addition amount of mint extract solution of 4%; an addition amount of liquorice extract solution of 7%; an addition amount of sugar of 3%; an addition amount of citric acid of 0.15%. The polysaccharide content decreased with an increase in storage time; the stability of the polysaccharides was not significantly affected by storage temperature (P > 0.05). The pH value of the samples was significantly affected by storage temperature (P < 0.01), which was basically unchanged at 4°C and 25°C, and relatively large at 37°C; the stability of color was significantly affected by temperature (0.01 < P < 0.05). CONCLUSIONS: Sensory fuzzy comprehensive evaluation is an useful evaluation method in optimizing the formulation of a herbal drink. These results provide some theoretical basis for the food product development of Trollius chinensis Bunge.

Anti-influenza A virus mechanism of three representative compounds from Flos Trollii via TLRs signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Flos Trollii is the dried flowers of Trollius chinensis. It has been used as a traditional herbal medicine for the treatment of upper respiratory tract infection, tonsillitis and pharyngitis in China for a long history. Veratric acid, vitexin, and trolline are the representative compounds of phenolic acids, flavonoids and alkaloids in this herbal medicine. All of these three compounds show antiviral activity which is related to the efficacy of Flos Trollii. AIM OF THE STUDY: To investigate the anti-influenza A virus mechanism of the three representative compounds from the perspective of regulating TLRs signaling pathways, so as to understand the relevant efficacy of Flos Trollii. MATERIALS AND METHODS: Influenza A virus A/FM/1/47 (H1N1) and mouse peritoneal macrophages (RAW264.7) were used in the whole process of investigation. MTT assay was conducted to select the appropriate experimental concentrations of the three compounds on RAW264.7 cells. Western blot, RT-PCR, and ELISA assays were performed to determine the protein and mRNA expression of key factors and related inflammatory factors of TLRs signaling pathways. Griess method was employed to detect the production of NO. RESULTS: The three representative compounds reduced the inflammatory factors including NO, IL-6, and TNF-α and enhanced the production of IFN-ß through dynamically regulating the TLRs 3, 4 and 7 pathways. Veratric acid significantly down-regulated the protein expression of TLR3 and IRF3 as well as the mRNA expression of TBK1 and TRIF. Vitexin significantly down-regulated the protein expression of TBK1 and IRF3 as well as the mRNA expression of TLR3, TBK1, TRIF and IRF3 while up-regulated the protein expression of TLR4 and IKKα. Trolline significantly down-regulated the protein expression of TLR7 whereas significantly up-regulated the protein expression of TLR4, IKKα and TAK1. CONCLUSIONS: The three representative compounds from Flos Trollii play their parts in anti-H1N1 viral effect through partially down-regulating TLRs 3 and 7 pathways and up-regulating TLR4 pathway. They counteract the inflammatory injury caused by excessive production of NO, IL-1, IL-6, and TNF-α induced by virus infection and enhance the production of IFN-ß so as to eliminate the virus.

CPF impedes cell cycle re-entry of quiescent lung cancer cells through transcriptional suppression of FACT and c-MYC.

Blockade of cell cycle re-entry in quiescent cancer cells is a strategy to prevent cancer progression and recurrence. We investigated the action and mode of action of CPF mixture (Coptis chinensis, Pinellia ternata and Fructus trichosanthis) in impeding a proliferative switch in quiescent lung cancer cells. The results indicated that CPF impeded cell cycle re-entry in quiescent lung cancer cells by reduction of FACT and c-MYC mRNA and protein levels, with concomitant decrease in H3K4 tri-methylation and RNA polymerase II occupancy at FACT and c-MYC promoter regions. Animals implanted with quiescent cancer cells that had been exposed to CPF had reduced tumour volume/weight. Thus, CPF suppresses proliferative switching through transcriptional suppression of FACT and the c-MYC, providing a new insight into therapeutic target and intervention method in impeding cancer recurrence.

Iridoid glycosides from Radix Scrophulariae attenuates focal cerebral ischemia­reperfusion injury via inhibiting endoplasmic reticulum stress­mediated neuronal apoptosis in rats.

Iridoid glycosides of Radix Scrophulariae (IGRS) are a group of the major bioactive components from Radix Scrophulariae with extensive pharmacological activities. The present study investigated the effects of IGRS on cerebral ischemia­reperfusion injury (CIRI) and explored its potential mechanisms of action. A CIRI model in rats was established by occlusion of the right middle cerebral artery for 90 min, followed by 24 h of reperfusion. Prior to surgery, 30, 60 or 120 mg/kg IGRS was administered to the rats once a day for 7 days. Then, the neurological scores, brain edema and volume of the cerebral infarction were measured. The apoptosis index was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling. The effects of IGRS on the histopathology of the cortex in brain tissues and the endoplasmic reticulum ultrastructure in the hippocampus were analyzed. Finally, the expression of endoplasmic reticulum stress (ERS)­regulating mediators, endoplasmic reticulum chaperone BiP (GRP78), DNA damage­inducible transcript 3 protein (CHOP) and caspase­12, were detected by reverse transcription quantitative polymerase chain reaction (RT­qPCR) and western blot analysis. The volume of cerebral infarction and brain water content in the IGRS­treated groups treated at doses of 60 and 120 mg/kg were decreased significantly compared with the Model group. The neurological scores were also significantly decreased in the IGRS­treated groups. IGRS treatment effectively decreased neuronal apoptosis resulting from CIRI­induced neuron injury. In addition, the histopathological damage and the endoplasmic reticulum ultrastructure injury were partially improved in CIRI rats following IGRS treatment. RT­qPCR and western blot analysis data indicated that IGRS significantly decreased the expression levels of GRP78, CHOP and caspase­12 at both mRNA and protein levels. The results of the present study demonstrated that IGRS exerted a protective effect against CIRI in brain tissue via the inhibition of apoptosis and ERS.

Immunomodulatory Effects of Phosphorylated Radix Cyathulae officinalis Polysaccharides in Immunosuppressed Mice.

This research aimed to investigate the immunomodulatory effects of phosphorylated Radix Cyathulae officinalis Kuan polysaccharides (pRCPS) in immunosuppressed mice, improving their cellular and humoral immune function. Our results showed that pRCPS increased serum immunoglobulin (IgG, IgA, IgM) concentrations significantly, enhanced splenocyte proliferation, and the thymus and spleen indices. pRCPS also promoted phagocytosis in peritoneal macrophages and enhanced cytokine (IFN-γ, IL-2, -4, -5, -6, and -10) serum levels. Importantly, pRCPS increased the proportions of selected T cell subpopulations (CD3+, CD4+, and the CD4+ to CD8+ ratio). Our results revealed that phosphorylation of the polysaccharides promoted their immune-enhancing effects. Thus, pRCPS can enhance cellular and humoral immunity and could be used as an immune-enhancing agent to overcome cyclophosphamide (CY)-induced immunosuppression.

Ultrasonic Extraction of Tropane Alkaloids from Radix physochlainae Using as Extractant an Ionic Liquid with Similar Structure.

In this research, tropane alkaloids in Radix physochlainae were extracted by tropine-type ionic liquid (IL) aqueous solutions under ultrasound assistance, and N-propyltropine hexafluorophosphate ([C3Tr][PF6]) was found to be the most ideal IL in this extraction mode after comprehensive screening. When 0.03 mol/L [C3Tr][PF6] aqueous solution was chosen as the extraction solvent, the solid-liquid ratio of raw material powders and ionic liquid aqueous solution was 1:20 (g/mL), ultrasonic power was 90 W and extraction time was 30 min, the extraction efficiency of tropane alkaloids has reached 121.3%. Compared with common heating extraction, it can further shorten the extraction time, improve extraction efficiency and decrease IL consumption. Furthermore, extraction mechanism together with potential toxicity of IL have been explored and discussed.

Network pharmacology-based identifcation of potential targets of the flower of Trollius chinensis Bunge acting on anti-inflammatory effectss.

The flower of Trollius chinensis Bunge was widely used for the treatment of inflammation-related diseases in traditional Chinese medicine (TCM). In order to clarify the anti-inflammatory mechanism of this Chinese herbs, a comprehensive network pharmacology strategy that consists of three sequential modules (pharmacophore matching, enrichment analysis and molecular docking.) was carried out. As a result, Apoptosis signal-regulating kinase 1 (ASK1), Janus kinase 1 (JAK1), c-Jun N-terminal kinases (JNKs), transforming protein p21 (HRas) and mitogen-activated protein kinase 14 (p38α) that related to the anti-inflammatory effect were filtered out. In further molecular dynamics (MD) simulation, the conformation of CID21578038 and CID20055288 were found stable in the protein ASK1 and JNKs respectively. The current investigation revealed that two effective compounds in the flower of Trollius chinensis Bunge played a crucial role in the process of inflammation by targeting ASK1 and JNKs, the comprehensive strategy can serve as a universal method to guide in illuminating the mechanism of the prescription of traditional Chinese medicine by identifying the pathways or targets.

Protective effect of polysaccharides from Radix Hedysari on gastric ulcers induced by acetic acid in rats.

The dry root of Hedysarum polybotrys Hand.-Mazz., commonly known as "Hong Qi", has a variety of health benefits. The present study was undertaken to explore the anti-gastric ulcer potential effect of Hedysarum polysaccharides (HPS; HPS-50, HPS-80), the principal active fraction of Radix Hedysari (RH). The anti-gastric ulcer effects of HPS were evaluated using an animal model of ulcerative lesions induced by acetic acid. The effects of antioxidant factors, anti-inflammatory cytokines, and mucosal blood flow regulatory factor levels in the gastric tissue homogenate of rats were analyzed for the bioactivities of HPS. The results showed that, compared with the acetic acid-induced ulcerated group, the ulcer inhibition rate of HPS-treated rats was significantly increased. The pathological findings suggested that mucosal regeneration, cell migration, and inflammatory cell infiltration were decreased, and collagen fibers were significantly reduced. Extensive granulation tissue proliferation indicated the healing stage was initiated, suggesting a good prognosis. The oxidative stress status of the gastric ulcer rats was improved, the levels of TNF-α and IL-6 were significantly decreased, and the levels of PGE-2 and NO were increased (P < 0.05). HPS-80-H may be a promising ingredient for incorporation into functional foods or nutritional supplements for the prevention of gastric ulcers.

[Study on Ranunculaceae herbal decoction pieces using X-ray diffraction].

The powder X-ray diffraction(PXRD) technique was used to investigate fourteen kinds of Ranunculaceae herbal decoction pieces(RHDP) recorded in Chinese Pharmacopoeia and to explore a novel PXRD quality control method for RHDP. The results indicated that only three RHDP-Paeoniae Radix Alba, Paeoniae Radix Rubra, and Moutan Cortex, contained calcium oxalate monodydrate(COM), whereas no COM existed in other eleven kinds of RHDP. The difference in PXRD for Paeoniae Radix Alba and Paeoniae Radix Rubra from different growing areas were investigated. The quantitative analysis method for COM was discussed by considering the water-boiling manufacturing process of herbal decoction pieces. The water-boiling experiments revealed that the PXRD peaks from COM crystals in RHDP were enhanced significantly after boiling. Paeoniae Radix Alba, Paeoniae Radix Rubra, Moutan Cortex, Aconiti Lateralis Radix Praeparata, Aconiti Radix, Aconiti Kusnezoffii Radix, and Anemone Raddeanae Rhizoma exhibited a similar series of broader peaks in the 2θ region of 15° to 35°, whose origins were discussed on the basis of chemical constituents RHDP reported by other researchers. These diffraction broader peaks most likely originated from periodic orientation of benzene ring in organic molecular crystals of aconitine-and paeonolum-based alkaloids and glycosides chemical constituents, subsequently, possibly from some other organic constituents. The PXRD technique can be used to rapidly identify Cimicifuga heracleifolia with an amorphous dispersion peak and C. dahurica with a sharp-peak feature. Climatidis Radix et Rhizoma exhibited a series of sharp PXRD peaks. The PXRD method can provide a valuable quality control method for RHDP.

Two new noroleanane-type triterpenoid saponins from the stems of Stauntonia chinensis.

Two new noroleanane-type triterpenoid saponins, 3ß,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 24-O-ß-L-fucopyranosyl-(1→2)-[ß-D-xylopyranosyl-(1→3)]-ß-D-glucopyranoside (1) and 3ß,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 24-O-ß-D-glucopyranosyl-(1→2)-[α-L-arabinopyranosyl-(1→3)]-ß-D-glucopyranoside (2) were isolated from the stems of Stauntonia chinensis DC., together with three known compounds, brachyantheraoside B2 (3), eupteleasaponin Ⅷ (4) and fargoside B (5). Their structures were elucidated by spectroscopic and chemical methods. The cytotoxic activities of compounds 1 and 2 were evaluated against five human tumor cell lines (HCT-116, HepG2, BGC-823, NCI-H1650, and A2780). Compounds 1 and 2 showed moderate cytotoxic activities toward the tested cell lines with IC50 values ranging from 12.71 to 32.04 µM.

Potential anti-inflammation nor-oleanane triterpenoids from the fruits of Stauntonia brachyanthera.

The studies on Stauntonia brachyanthera led to the isolations of 7 normal and nor-oleanane triterpenoids, including 2 new ones. Compounds 1 and 3 showed moderate inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with the IC50 values of 16.09 and 20.19 µM, respectively, which were stronger than that of positive control. A primary structure-activity relationship was also discussed, which revealed the anti-inflammation abilities of three types triterpenoids and their potential possibilities as the candidate compounds for the treatment of inflammation.

Modulation of transporter activity of OATP1B1 and OATP1B3 by the major active components of Radix Ophiopogonis.

Radix Ophiopogonis is often an integral part of many traditional Chinese formulas, such as Shenmai injection used to treat cardio-cerebrovascular diseases. This study aimed to investigate the influence of the four active components of Radix Ophiopogonis on the transport activity of OATP1B1 and OATP1B3. The uptake of rosuvastatin in OATP1B1-HEK293T cells were stimulated by methylophiopogonanone A (MA) and ophiopogonin D' (OPD') with EC50 calculated to be 11.33 ± 2.78 and 4.62 ± 0.64 µM, respectively. However, there were no remarkable influences on rosuvastatin uptake in the presence of methylophiopogonanone B (MB) or ophiopogonin D (OPD). The uptake of atorvastatin in OATP1B1-HEK293T cells can be increased by MA, MB, OPD and OPD' with EC50 calculated to be 6.00 ± 1.60, 13.64 ± 4.07, 10.41 ± 1.28 and 3.68 ± 0.85 µM, respectively. The uptake of rosuvastatin in OATP1B3-HEK293T cells was scarcely influenced by MA, MB and OPD, but was considerably increased by OPD' with an EC50 of 14.95 ± 1.62 µM. However, the uptake of telmisartan in OATP1B3-HEK293T cells was notably reduced by OPD' with an IC50 of 4.44 ± 1.10 µM, and barely affected by MA, MB and OPD. The four active components of Radix Ophiopogonis affect the transporting activitives of OATP1B1 and OATP1B3 in a substrate-dependent manner.