Amelioration effects of α-viniferin on hyperuricemia and hyperuricemia-induced kidney injury in mice.

BACKGROUND: α-Viniferin, the major constituent of the roots of Caragana sinica (Buc'hoz) Rehder with a trimeric resveratrol oligostilbenoid skeleton, was demonstrated to possess a strong inhibitory effect on xanthine oxidase in vitro, suggesting it to be a potential anti-hyperuricemia agent. However, the in vivo anti-hyperuricemia effect and its underlying mechanism were still unknown. PURPOSE: The current study aimed to evaluate the anti-hyperuricemia effect of α-viniferin in a mouse model and to assess its safety profile with emphasis on its protective effect on hyperuricemia-induced renal injury. METHODS: The effects were assessed in a potassium oxonate (PO)- and hypoxanthine (HX)-induced hyperuricemia mice model by analyzing the levels of serum uric acid (SUA), urine uric acid (UUA), serum creatinine (SCRE), serum urea nitrogen (SBUN), and histological changes. Western blotting and transcriptomic analysis were used to identify the genes, proteins, and signaling pathways involved. RESULTS: α-Viniferin treatment significantly reduced SUA levels and markedly mitigated hyperuricemia-induced kidney injury in the hyperuricemia mice. Besides, α-viniferin did not show any obvious toxicity in mice. Research into the mechanism of action of α-viniferin revealed that it not only inhibited uric acid formation by acting as an XOD inhibitor, but also reduced uric acid absorption by acting as a GLUT9 and URAT1 dual inhibitor as well as promoted uric acid excretion by acting as a ABCG2 and OAT1 dual activator. Then, 54 differentially expressed (log2 FPKM ≥ 1.5, p ≤ 0.01) genes (DEGs) repressed by the treatment of α-viniferin in the hyperuricemia mice were identified in the kidney. Finally, gene annotation results revealed that downregulation of S100A9 in the IL-17 pathway, of CCR5 and PIK3R5 in the chemokine signaling pathway, and of TLR2, ITGA4, and PIK3R5 in the PI3K-AKT signaling pathway were involved in the protective effect of α-viniferin on the hyperuricemia-induced renal injury. CONCLUSIONS: α-Viniferin inhibited the production of uric acid through down-regulation of XOD in hyperuricemia mice. Besides, it also down-regulated the expressions of URAT1 and GLUT9 and up-regulated the expressions of ABCG2 and OAT1 to promote the excretion of uric acid. α-Viniferin could prevent hyperuricemia mice from renal damage by regulating the IL-17, chemokine, and PI3K-AKT signaling pathways. Collectively, α-viniferin was a promising antihyperuricemia agent with desirable safety profile. This is the first report of α-viniferin as an antihyperuricemia agent.

Spectrum-effect relationship of antioxidant and anti-inflammatory activities of Laportea bulbifera based on multivariate statistical analysis.

Laportea bulbifera, named Hong He Ma in Chinese, is a Chinese herbal medicine commonly used by the Miao nationality of China. In this study, 43 batches of L. bulbifera were collected from different origins in China. Ethanol, ethyl acetate and petroleum ether were used to prepare different extracts of the plant. UHPLC technique was used to establish the fingerprints, whereas DPPH assay and RAW264.7 inflammatory cell models were used to evaluate the antioxidant and anti-inflammatory activities, respectively. Moreover, the spectrum-effect relationship between relative peak area of common peaks and efficacy value was set up by multivariate statistical analysis. Furthermore, 10 batches were selected randomly for validation of those models. The results showed that ethyl acetate and petroleum ether extracts possess excellent antioxidant and anti-inflammatory activities, respectively. Peaks A6 and A7 demonstrated the greatest antioxidant activity, while peak A17 showed the strongest anti-inflammatory activity. After a verified experiment, the result was obtained and illustrated that the spectrum-effect relationship which we established could reliably infer antioxidant and anti-inflammatory compounds of the Chinese herbal medicine.

Simultaneous Determination of Five Alkaloids by HPLC-MS/MS Combined With Micro-SPE in Rat Plasma and Its Application to Pharmacokinetics After Oral Administration of Lotus Leaf Extract.

An environment-friendly and efficient method for simultaneous determination of five alkaloids (nunciferine, O-nornuciferin, liriodenine, armepavine, and pronuciferine) in rat plasma was established by HPLC-MS/MS associated with micro-solid phase extraction (micro-SPE). The plasma sample was pretreated by using micro-SPE columns filled with polymer materials PEP-2 and eluted by little organic solvent (400 µl acetonitrile). The five alkaloids were separated with acetonitrile and 0.1% formic acid aqueous solution on Eclipse plus C18 column. The mode of positive electrospray ionization was used to measure the analytes in multiple-reaction monitoring (MRM). The determination coefficients (R2) of the five alkaloids were greater than 0.99. The lower limit of quantification (LLOQ) of O-nornuciferin, liriodenine, and armepavine was 0.5 ng·ml-1, and that of nunciferine and pronuciferine was 1 ng·ml-1. The validated method was effectively used for the pharmacokinetics of the five orally administrated alkaloids of lotus leaf extract in rat plasma.

An Established HPLC-MS/MS Method for Evaluation of the Influence of Salt Processing on Pharmacokinetics of Six Compounds in Cuscutae Semen.

A sensitive and effective method was developed for clarifying the pharmacokinetic properties of six compounds (including hyperin, chlorogenic acid, neochlorogenic acid, p-coumaric acid, astragalin, and isoquercitrin) in two processed Cuscutae Semen samples by high performance liquid chromatography mass spectrometry (HPLC-MS/MS). The six compounds were separated by acetonitrile and 0.1% formic acid-water on an Agilent Eclipse plus C18 column (4.6 mm × 100 mm, 1.8 µm). All compounds were analyzed with negative ion mode in multiple reaction monitoring (MRM). The lower limits of quantification (LLOQ) of hyperin, astragalin, neochlorogenic acid, chlorogenic acid, isoquercitrin, and p-coumaric acid were 1, 0.1, 4, 0.1, 2, and 4 ng·mL-1, respectively. The validated approach was effectively used for the pharmacokinetics of six compounds of two processed Cuscutae Semen samples after oral administration to rat. The results indicated that salt processing could improve the adsorption and bioavailability of astragalin in Cuscutae Semen.

A network pharmacology integrated pharmacokinetics strategy for uncovering pharmacological mechanism of compounds absorbed into the blood of Dan-Lou tablet on coronary heart disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Dan-Lou tablet (DLT) is developed from the traditional Chinese medicine (TCM) formula Gualou Xiebai Baijiu Tang which has been used for at least 2000 years in China. DLT has been widely used in clinical practice to treat cardiovascular diseases. AIM OF THE STUDY: This study aimed to uncover the pharmacological mechanism of the compounds absorbed into the blood of Dan-Lou tablet (DLT) on coronary heart disease (CHD) using a network pharmacology integrated pharmacokinetics strategy. MATERIALS AND METHODS: A rapid and sensitive method was developed for the simultaneous determination of the six compounds (puerarin, formononetin, calycosin, paeoniflorin, cryptotanshinone and tanshinone IIA) in rat plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS). Then, the pharmacology network was established based on the relationship between five compounds absorbed into the blood targets (puerarin, formononetin, calycosin, cryptotanshinone and tanshinone IIA) and CHD targets. RESULTS: The intra-and inter-day precision were less than 11% and the accuracy ranged from 88.2% to 112%, which demonstrated that the LC-MS/MS method could be used to evaluate the pharmacokinetic feature of the six compounds in rats after oral administration of DLT. The pathway enrichment analysis revealed that the significant bioprocess networks of DLT on CHD were positive regulation of estradiol secretion, negative regulation of transcription from RNA polymerase II promoter, lipopolysaccharide-mediated signaling pathway and cytokine activity. CONCLUSION: The proposed network pharmacology integrated pharmacokinetics strategy provides a combination method to explore the therapeutic mechanism of the compounds absorbed into the blood of multi-component drugs on a systematic level.

Simultaneous Extraction and Determination of Compounds With Different Polarities From Platycladi Cacumen by AQ C18-Based Vortex-Homogenized Matrix Solid-Phase Dispersion With Ionic Liquid.

This study presented a rapid, simple and environmentally friendly method of employing AQ C18-based vortex-homogenized matrix solid-phase dispersion with ionic liquid (AQ C18-IL-VHMSPD) for the extraction of compounds with different polarities from Platycladi Cacumen (PC) samples by ultra high-performance liquid chromatography with PDA detection. AQ C18 (aqua C18) and ionic liquid ([Bmim]BF4) were used as the adsorbent and green elution reagent in vortex-homogenized MSPD procedure. The AQ C18-IL-VHMSPD conditions were optimized by studying several experimental parameters including the type of ionic liquid, the type of adsorbent, ratio of sample to adsorbent, the concentration and volume of ionic liquid, grinding time and vortex time. The recoveries of the target compounds were in the range of 96.9-104% with relative standard deviation values no more than 2.8%. The limits of detection and limits of quantitation were in the range of 0.2-1.2 and 1.0-5.4 ng mL-1, respectively. Compared with the traditional ultrasonic-assisted extraction, the developed AQ C18-IL-VHMSPD method required less sample, reagent and time. It was concluded that the AQ C18-IL-VHMSPD method was a powerful method for the extraction and quantification of the high polarity and low polarity compounds in traditional Chinese medicines samples.