S-adenosyl-L-methionine supplementation alleviates damaged intestinal epithelium and inflammatory infiltration caused by Mat2a deficiency.

Methionine is important for intestinal development and homeostasis in various organisms. However, the underlying mechanisms are poorly understood. Here, we demonstrate that the methionine adenosyltransferase gene Mat2a is essential for intestinal development and that the metabolite S-adenosyl-L-methionine (SAM) plays an important role in intestinal homeostasis. Intestinal epithelial cell (IEC)-specific knockout of Mat2a exhibits impaired intestinal development and neonatal lethality. Mat2a deletion in the adult intestine reduces cell proliferation and triggers IEC apoptosis, leading to severe intestinal epithelial atrophy and intestinal inflammation. Mechanistically, we reveal that SAM maintains the integrity of differentiated epithelium and protects IECs from apoptosis by suppressing the expression of caspases 3 and 8 and their activation. SAM supplementation improves the defective intestinal epithelium and reduces inflammatory infiltration sequentially. In conclusion, our study demonstrates that methionine metabolism and its intermediate metabolite SAM play essential roles in intestinal development and homeostasis in mice.

3D Microfluidic System for Evaluating Inhibitory Effect of Chinese Herbal Medicine Oldenlandia diffusa on Human Malignant Glioma Invasion Combined with Network Pharmacology Analysis.

OBJECTIVE: To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD). METHODS: The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach. RESULTS: Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization. CONCLUSIONS: ]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.

Dietary folate drives methionine metabolism to promote cancer development by stabilizing MAT IIA.

Folic acid, served as dietary supplement, is closely linked to one-carbon metabolism and methionine metabolism. Previous clinical evidence indicated that folic acid supplementation displays dual effect on cancer development, promoting or suppressing tumor formation and progression. However, the underlying mechanism remains to be uncovered. Here, we report that high-folate diet significantly promotes cancer development in mice with hepatocellular carcinoma (HCC) induced by DEN/high-fat diet (HFD), simultaneously with increased expression of methionine adenosyltransferase 2A (gene name, MAT2A; protein name, MATIIα), the key enzyme in methionine metabolism, and acceleration of methionine cycle in cancer tissues. In contrast, folate-free diet reduces MATIIα expression and impedes HFD-induced HCC development. Notably, methionine metabolism is dynamically reprogrammed with valosin-containing protein p97/p47 complex-interacting protein (VCIP135) which functions as a deubiquitylating enzyme to bind and stabilize MATIIα in response to folic acid signal. Consistently, upregulation of MATIIα expression is positively correlated with increased VCIP135 protein level in human HCC tissues compared to adjacent tissues. Furthermore, liver-specific knockout of Mat2a remarkably abolishes the advocating effect of folic acid on HFD-induced HCC, demonstrating that the effect of high or free folate-diet on HFD-induced HCC relies on Mat2a. Moreover, folate and multiple intermediate metabolites in one-carbon metabolism are significantly decreased in vivo and in vitro upon Mat2a deletion. Together, folate promotes the integration of methionine and one-carbon metabolism, contributing to HCC development via hijacking MATIIα metabolic pathway. This study provides insight into folate-promoted cancer development, strongly recommending the tailor-made folate supplement guideline for both sub-healthy populations and patients with cancer expressing high level of MATIIα expression.

Versatile polarization manipulation in vanadium dioxide-integrated terahertz metamaterial.

Broadband and switchable versatile polarization metamaterial is crucial in the applications of imaging, sensing and communication, especially in the terahertz frequency. Here, we investigated versatile polarization manipulation in a hybrid terahertz metamaterial with bilayer rectangular rods and a complementary vanadium dioxide (VO2) layer. The VO2 phase transition enables a flexible switching from dual-band asymmetric transmission to dual-band reflective half-wave plate. The full width half maximum (FWHM) bandwidths of dual-band asymmetric transmission are 0.77 and 0.21 THz, respectively. The polarization conversion ratio (PCR) of the reflective metamaterial is over 0.9 in the frequency ranges of 1.01-1.17 THz and 1.47-1.95 THz. Angular dependences of multiple polarization properties are studied. The proposed switchable polarization metamaterial is important to the development of multifunctional polarization devices and multichannel polarization detection.

Dietary ω-3 polyunsaturated fatty acids are protective for myopia.

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.

Machine learning based strategy surpasses the traditional method for selecting the first trial Lens parameters for corneal refractive therapy in Chinese adolescents with myopia.

PURPOSE: Return zone depth (RZD) and landing zone angle (LZA) are important parameters of corneal refractive therapy (CRT) lenses. A new machine learning algorithm is proposed for prescribing CRT lens parameters in Chinese adolescents with myopia. METHODS: This is a retrospective study. In total, 1037 Chinese adolescents with myopia (1037 right eyes) were enrolled. A calculation model based on corneal elevation maps was constructed to calculate RZD and LZA for the four quadrants. Furthermore, multiple linear regression and optimized machine learning models were established to predict RZD and LZA values for different combinations of age, sex, and ocular parameters. The four methods (sliding card, linear regression, calculation and optimized machine learning) were then compared to the parameters of the final ordered lens. RESULTS: The optimized machine learning pipeline achieved the best performance. Age, sex, horizontal visible iris diameter (HVID), spherical equivalent refraction degree (SER), eccentricity (e), keratometric (K) readings, corneal astigmatism (CA), axial length (AL), AL/corneal curvature ratio (AL/MK), and anterior chamber depth (ACD) were significant to the machine learning model. The R values for the nasal, temporal, superior and inferior LZA based on machine learning were 0.843, 0.693, 0.866 and 0.762, respectively, and those for the RZD were 0.970, 0.964, 0.975 and 0.964, respectively. CONCLUSIONS: The feasibility and efficiency of an optimized machine learning method to predict LZA and RZD parameters has been demonstrated. The advantage of the proposed method is that it is more accurate, easier to use and faster to implement than the traditional sliding card method.

A photothermal-hypoxia sequentially activatable phase-change nanoagent for mitochondria-targeting tumor synergistic therapy.

To enhance the specificity and efficiency of anti-tumor therapies, we have designed a multifunctional nanoparticle platform for photochemotherapy using fluorescence (FL) and photoacoustic (PA) imaging guidance. Nanoparticles (NPs) composed of a eutectic mixture of natural fatty acids that undergo a solid-liquid phase transition at 39 °C were used to encapsulate materials for the rapid and uniform release of the hypoxia-activated prodrug tirapazamine (TPZ) and the photosensitizer IR780, which targets the mitochondria of tumor cells and can be used to induce hypoxic cell death via photodynamic therapy and photothermal therapy. In vitro, the NPs containing TPZ and IR7890 exhibited appreciable cell uptake and triggered drug release when irradiated with a NIR laser. In vivo, photochemotherapy of the NPs achieved the best anti-tumor efficacy under PA and FL imaging guidance and monitoring. By combining IR780 mitochondria-targeting phototherapy with TPZ, we observed improved anti-tumor effectiveness and this has the potential to reduce the side effects of traditional chemotherapy. Herein, we demonstrate a new intracellular photochemotherapy nanosystem that co-encapsulates photosensitizers and hypoxia-activated drugs to enhance the overall anti-tumor effect precisely and efficiently.

Synergistic Chemotherapy and Photodynamic Therapy of Endophthalmitis Mediated by Zeolitic Imidazolate Framework-Based Drug Delivery Systems.

Endophthalmitis, derived from the infections of pathogens, is a common complication during the use of ophthalmology-related biomaterials and after ophthalmic surgery. Herein, aiming at efficient photodynamic therapy (PDT) of bacterial infections and biofilm eradication of endophthalmitis, a pH-responsive zeolitic imidazolate framework-8-polyacrylic acid (ZIF-8-PAA) material is constructed for bacterial infection-targeted delivery of ammonium methylbenzene blue (MB), a broad-spectrum photosensitizer antibacterial agent. Polyacrylic acid (PAA) is incorporated into the system to achieve higher pH responsiveness and better drug loading capacity. MB-loaded ZIF-8-PAA nanoparticles are modified with AgNO3 /dopamine for in situ reduction of AgNO3 to silver nanoparticles (AgNPs), followed by a secondary modification with vancomycin/NH2 -polyethylene glycol (Van/NH2 -PEG), leading to the formation of a composite nanomaterial, ZIF-8-PAA-MB@AgNPs@Van-PEG. Dynamic light scattering, transmission electron microscopy, and UV-vis spectral analysis are used to explore the nanoparticles synthesis, drug loading and release, and related material properties. In terms of biological performance, in vitro antibacterial studies against three kinds of bacteria, i.e., Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus, suggest an obvious superiority of PDT/AgNPs to any single strategy. Both in vitro retinal pigment epithelium cellular biocompatibility experiments and in vivo mice endophthalmitis models verify the biocompatibility and antibacterial function of the composite nanomaterials.

Collaborative networks and thematic trends of research on the application of complementary and alternative medicine in cancer patients: A bibliometric analysis.

BACKGROUND: and purpose: Complementary and Alternative Medicine(CAM) has been greatly used in cancer patients. This research aimed to explore the research priorities of CAM for cancer patient's treatment. METHODS: Web of Science(WoS), HistCite, BibExcel, GunnMap and VOSviewer were used to extract and visualize information. RESULTS: 2768 articles published in 789 journals were indexed in the WoS from 1989 to 2018. The USA(n = 1009) and Technion-Israel Institute Technology(n = 58) were the most prolific country and institution, respectively. Keywords co-occurrence analysis indicated that the research hotspots around the world formed five clusters, so did the author co-citation analysis. The research priorities of the top-five countries, the top-three prolific authors and the co-citation core authors were also discussed, which reveals the differences and similarities among them. CONCLUSION: This study delineates a framework for better understanding the situational use of CAM in cancer patients, which could help health care workers to prioritize and organize future research.

Evaluating the Efficacy and Adverse Effects of Clearing Heat and Removing Dampness Method of Traditional Chinese Medicine by Comparison with Western Medicine in Patients with Gout.

Objective. In China, the method of clearing heat and removing dampness medicine of Chinese traditional medicine has been widely used on gout. However, the clinical effects are various and not summarized systematically. Methods. In this study, a large number of randomized controlled clinical trials were reviewed and analyzed and the clinical efficacy and adverse reactions of traditional Chinese medicine with clearing heat and removing dampness effects for the treatment of gout were systematically evaluated. A comprehensive search of databases including pubMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, Wanfang Data, and SinoMed was performed. Results. There are 69 randomized controlled trials with 5915 sample sizes meeting the criteria in the study. The results of the meta-analysis indicate that the effects of clearing heat and removing dampness medicine were slightly better than western medicine in the treatment of gout based on the following parameters: serum uric acid (standardized mean difference (SMD):-62.14, 95% confidence interval (CI): -78.12 to-46.15), C reactive protein (SMD: -4.21, 95% CI: -6.19 to -2.23), erythrocyte sedimentation rate (SMD: -6.23, 95% CI: -8.39 to-4.06), and overall clinical response (relative risk (RR): 1.11, 95% CI: 1.08 to 1.15) and, in the profile of adverse drug reactions, the clearing heat and removing dampness medicine showed less adverse reactions than traditional Western medicine (RR: 0.18, 95% CI: 0.10 to 0.32). Conclusions. Through a systemic evaluation of the clinical efficacy of the clearing heat and removing dampness medicine of traditional Chinese medicine and western medicine on gout, the clearing heat and removing dampness medicine and western medicine possessed similar clinical efficacy, but traditional Chinese medicine treatments are superior to western medicine in controlling adverse reactions.

Therapeutic Angiogenesis of Chinese Herbal Medicines in Ischemic Heart Disease: A Review.

Ischemic heart disease (IHD) is one of the primary causes of death around the world. Therapeutic angiogenesis is a promising innovative approach for treating IHD, improving cardiac function by promoting blood perfusion to the ischemic myocardium. This treatment is especially important for targeting patients that are unable to undergo angioplasty or bypass surgery. Chinese herbal medicines have been used for more than 2,500 years and they play an important role alongside contemporary medicines in China. Growing evidence in animal models show Chinese herbal medicines can provide therapeutic effect on IHD by targeting angiogenesis. Identifying the mechanism in which Chinese herbal medicines can promote angiogenesis in IHD is a major topic in the field of traditional Chinese medicine, and has the potential for advancing therapeutic treatment. This review summarizes the progression of research and highlights potential pro-angiogenic mechanisms of Chinese herbal medicines in IHD. In addition, an outline of the limitations of Chinese herbal medicines and challenges they face will be presented.

Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases.

Cardiovascular diseases (CVDs) are considered as the major reason for mortality and morbidity worldwide. Substantial evidence suggests that increased oxidative stress plays a significant role in the pathogenesis of CVDs, including atherosclerosis, hypertension, vascular endothelial dysfunction and ischemic heart disease. Cellular oxidative stress results in the release of toxic free radicals by endothelial cells and vascular smooth muscle cells that interact with cell components such as protein, DNA or lipid resulting in cardiovascular pathology. Silymarin has antioxidant activities against CVDs and offers protection against oxidative stress-induced hypertension, atherosclerosis and cardiac toxicity. We present a comprehensive review regarding the oxidative stress and protective effects of silymarin in CVDs management. We also aim to provide mechanistic insight of the mechanisms of silymarin action in oxidative stress-induced CVDs.

Two new phenolic acids from the fruits of Forsythia suspense.

Two new phenolic acids forsythiayanoside C (1) and forsythiayanoside D (2), were isolated from the fruits of Forsythia suspense (Thunb.) Vahl. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses, HRESIMS and CD spectrometry. The cytotoxic and antioxidant activities testing showed that compound 2 exhibited free radical scavenging activity.

[Research ontherapeutics effect of extract of Ornithogalum caudatum on liver fibrosis].

Rat models of liver fibrosis were made by carbon tetrachloride, and the serum levels of AST, ALT, γ-GT, MDA, GSH-px, SOD were detected, serum markers of PCⅢ, IV-C, LN, HA were detected by ELISA method. HE and Masson staining were conducted in hepatic tissues to observe pathological variations. Collagen Ⅲ, TGF-ß, α-SMA, E-cadherin were detected by Western blot. The curative effect of the extract of Ornithogalum caudatum on rat liver fibrosis induced by CCl4was observed and the mechanism was discussed. The experiment results showed that the extract of O. caudatum (50, 150, 500 mg•kg⁻¹) obviously decreased the serum levels of AST, ALT, γ-GT, MDA, increased the serum levels of GSH-px, SOD, decreased the expression of serum markers of PCⅢ, IV-C, LN, HA, and improved the liver pathological variations of fibrotic rats. The experiment proved that the extract of O. caudatum could treat the liver fibrogenesis induced by CCl4 in rats. The positive medicine may inhibit accumulation of extracellular and activate hepatic stellate cell and epithelial-mesenchymal transition.

Comparative evaluation of cultivars of Chrysanthemum morifolium flowers by HPLC-DAD-ESI/MS analysis and antiallergic assay.

A multicomponent quantification fingerprint based on HPLC coupled with diode array detection and electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI/MS) technique has been established for the analysis of phenolic compounds in 12 samples originated from 5 different cultivars of Chrysanthemum morifolium flowers in China. Four caffeoylquinic acids and 15 flavonoids in the capitulum were identified by comparing the retention times and ultraviolet spectra as well as the mass spectrum and/or matching the empirical molecular formula with that of reference compounds, and the contents of these compounds have been determined simultaneously. The samples from three medicinal cultivars significantly differed in the quality and quantity of flavonoid aglycones and glycosides compared with those from two edible cultivars, which allows the possibility of showing the chemical distinctness of these cultivars and may be useful in their standardization. Moreover, the antiallergic effects of these cultivars were comparatively assayed for the first time. A representative medicinal cultivar, 'huaiju', showed potential activity on the inhibition of antigen-induced degranulation from RBL-2H3 cells and compound 48/80-induced scratching in mice, whereas the in vitro and in vivo antiallergic activities of two edible cultivars were weak. The results suggested that the quality and quantity of some active flavonoid aglycones should be responsible for the pharmacological profiles of these cultivars.

Phytochemical investigation and cytotoxic evaluation of the components of the medicinal plant Ligularia atroviolacea.

A phytochemical investigation of the roots of Ligularia atroviolacea resulted in the isolation of 24 compounds including seven new eremophilanoids named eremophila-3,7(11),8-triene-12,8;14,6alpha-diolide (1), 3beta-(angeloyloxy)eremophil-7(11)-en-12,8beta-olid-14-oic acid (2), 1alpha-chloro-10beta-hydroxy-6beta-(2-methylpropanoyloxy)-9-oxo-7,8-furoeremophilane (3), (10betaH)-8-oxoeremophila-3(4),6(7)-diene-12,14-dioic acid (4), (10alphaH)-8-oxoeremophila-3(4),6(7)-diene-12,14-dioic acid (5), 8beta-[eremophila-3',7'(11')-diene-12',8'alpha;14',6'alpha-diolide]eremophila-3,7(11)-diene-12,8alpha;14,6alpha-diolide (6), and ligulatrovine A (7), eleven known eremophilanoids, 8-18, four steroids, one glucose derivative, and one fatty acid. The structures of these compounds were elucidated by spectroscopic methods including 2D-NMR experiments. The structure of 3 was also established by an X-ray diffraction study. The in vitro cytotoxicity evaluation of selected compounds was performed on seven cultured tumor cell lines, i.e., KB, BEL-7404, A549, HL-60, HeLa, CNE, and P-388D1. The preliminary taxonomy of this species was also discussed, and the possible biogenesis of a dimer possessing a new noreremophilanoid type skeleton, 7, is presented in a preliminary form.

[Antioxidative and cytotoxic properties of diarylheptanoids isolated from Zingiber officinale].

OBJECTIVE: To investigate the antioxidant and cytotoxic properties of five diarylheptanoids (1-5) isolated from the rhizomes of Zingiber officinale. METHOD: Various models such as scavenging superoxide anions and 1,1-diphenyl-2- picrylhydrazyl (DPPH) radicals, inhibiting lipid peroxidation, as well as protecting of rat pheochromocytoma (PC12) cells induced by hydrogen peroxide (H2O2) were employed to assay the antioxidative effects of the diarylheptanoids. The cytotoxicities of compounds 1-5 were measured with MTT assays. RESULT: The test compounds (1-5) showed promising DPPH inhibitory activities, and compound 5 exhibited the strongest DPPH scavenging activity with an IC50 value of (22.6+/-2.4) micromol x L(-1). Compounds 1, 3 and 4 showed potential anti-peroxidative effects with inhibitory rates of (66.3+/-15.4)%, (68.7+/-15.8)% and (72.2+/-10.6)%, respectively, at 100 microg x mL(-1). It could be observed that compounds 1, 3 and 4 demonstrated significant neuroprotective activities in a dose-dependent manner. Moreover, compound 3 exhibited certain cytotoxicities against human chronic myelogenous leukemia cells (K562) and its adriamycin-resistant cells (K562/ADR) with IC50 values of (34.9+/-0.6), (50.6+/-23.5) micromol x L(-1), respectively. CONCLUSION: In vitro results demonstrated that five diarylheptanoids (1-5) isolated from the roots of Z. officinale were capable of scavenging radicals, inhibiting lipid peroxidation and protecting PC12 cells against the insult by H2O2. Additionally, compound 3 could inhibit the growth of K562 and K562/ADR cells.

Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis.

The disaccharide trehalose is a key element involved in anhydrobiosis (the capability of surviving almost complete dehydration) in many organisms. Its presence also confers resistance to desiccation and high osmolarity in bacterial and human cells by protecting proteins and membranes from denaturation. The present study used a novel murine dry eye model induced by controlled low-humidity air velocity to determine whether topically applied trehalose could heal ocular surface epithelial disorders caused by ocular surface desiccation. In addition, the efficacy of 87.6 mM trehalose eyedrops was compared with that of 20% serum, the efficacy of which has been well documented. Mice ocular surface epithelial disorders were induced by exposure of murine eyes to continuous controlled low-humidity air velocity in an intelligently controlled environmental system (ICES) for 21 days, which accelerated the tear evaporation. The mice were then randomized into three groups: the control group received PBS (0.01 M) treatment; a second group received 87.6 mM trehalose eyedrops treatment; and the third group received mice serum eyedrops treatment. Each treatment was administered as a 10 microl dose every 6 h for 14 days. The resultant changes in corneal barrier function and histopathologic examination of cornea and conjunctiva were analyzed and the level of apoptosis on the ocular surface was assessed using active caspase-3. After 14 days of treatment, the corneal fluorescein staining area, the ruffling and desquamating cells on the apical corneal epithelium, as well as the apoptotic cells on ocular surface epithelium had significantly reduced in eyes treated with trehalose compared with those treated with serum and PBS. In contrast, after 14 days of treatment, improvements in the thickness of the corneal epithelium, the squamous metaplasia in conjunctival epithelium and the number of goblet cells of the conjunctiva were less marked in eyes treated with trehalose compared with serum. These results demonstrated that trehalose could improve the appearance of ocular surface epithelial disorders due to desiccation through suppression of apoptosis. Trehalose produces some of the same responses as serum upon topical application and can maintain corneal health.

[Studies on chemical constituents from herbs of Taraxacum mongolicum].

OBJECTIVE: To investigate the chemical constituents of the herbs of Taraxacum mongolicum. METHOD: The chemical constituents were isolated by various column chromatographic methods and their structures elucidated mainly by NMR and MS evidences. RESULT: Forty-four components were obtained and identified were as artemetin (1), quercetin (2), quercetin-3', 4', 7-trime-thyl ether (3), luteolin (4), luteolin-7-O-beta-D-glucopyranoside (5), luteolin-7-O-beta-D-galactopyranoside (6), genkwanin (7), isoetin (8), hesperetin (9), genkwanin-4'-O-beta-D-lutinoside (10), hesperidin (11), quercetin-7-O-[beta-D-glucopyranosyl (1-->6) -beta-D-glucopyranoside (12), quercetin-3, 7-O-beta-D-diglucopyranoside (13), isoetin-7-O-beta-D-glucopyranosyl- 2'-O-alpha-L-arabinopyranoside (14), isoetin-7-O-beta-D-glucopyranosyl-2'-O-alpha-D-glucopyranoside (15), isoetin-7- O-beta-D-glucopyranosyl-2'-O-beta-D-xyloypyranoside (16), caffeic acid (17), furulic acid (18), 3-O-caffeoylquinic acid (19), 3, 5-di-O-caffeoylquinic acid (20), 3, 4-di-O-caffeoylquinic acid (21), 4, 5-di-O-caffeoylquinic acid (22), 1-hydroxymethyl-5-hydroxy-phenyl-2-O-beta-D-glucopyranoside (23), p-hydroxybenzoic acid (24), p-coumaric acid (25), 3, 5-dihydroxylbenzoic acid (26), gallic acid (27), gallicin (28), syringic acid (29), 3, 4-dihydroxybenzoic acid (30), caffeic acid ethyl ester (31), esculetin (32), rufescidride (33), mongolicumin A [6, 9, 10-trihydroxy-benzoxanthene-1, 2-dicarboxylic acid] (34), mongolicumin B [1 l-hydroxy-2-oxo-guaia-1 (10), 3, 5-trien-8, 12-lactone] (35), isodonsesquitin A (36), taraxacin (37), sesquiterpene ketolactone (38), taraxasteryl acetate (39), phi-taraxasteryl acetate (40) and lupenol acetate (41), palmitic acid (42), beta-sitosterol (43), and stigmasterol (44). CONCLUSION: Four compounds (14, 15, 34 and 35) were new compounds, compounds 1, 3, 6-13, 20-22, 30 and 31 were isolated from this genus for the first time, while compounds 18, 23-29, 32 and 37-42 were obtained from this species for the first time.