The Angelica dahurica: A Review of Traditional Uses, Phytochemistry and Pharmacology.

Angelica dahurica (A. dahurica) root is a famous edible medicinal herb that has been used in China for thousands of years. To date, more than 300 chemical constituents have been discovered from A. dahurica. Among these ingredients, coumarins and volatile oils are the major active compounds. Moreover, a few other compounds have also been isolated from the root of A. dahurica, such as alkaloids, phenols, sterols, benzofurans, polyacetylenes and polysaccharides. Modern pharmacological studies demonstrated that the root of A. dahurica and its active components displayed various bioactivities such as anti-inflammation, anti-tumor, anti-oxidation, analgesic activity, antiviral and anti-microbial effects, effects on the cardiovascular system, neuroprotective function, hepatoprotective activity, effects on skin diseases and so on. Based on these studies, this review focused on the research publications of A. dahurica and aimed to summarize the advances in the traditional uses, phytochemistry and pharmacology which will provide reference for the further studies and applications of A. dahurica.

Dietary natural flavonoids treating cancer by targeting aryl hydrocarbon receptor.

The role of aryl hydrocarbon receptor (AhR) as a ligand-activated transcription factor in the field of cancer has gradually been unveiled. A strong body of evidence indicated that AhR is implicated in cell proliferation and apoptosis, immune metabolism and other processes, which further affected tumor growth, survival, migration, and invasion. Therefore, AhR targeted therapy may become a new method for cancer treatment and provide a new direction for clinical tumor treatment. Astonishingly, the largest source of exposure of animals and humans to AhR ligands (synthetic and natural) comes from the diet. Myriad studies have described that various natural dietary chemicals can directly activate and/or inhibit the AhR signaling pathway. Of note, numerous natural products contribute to AhR active, of which dietary flavonoids are the largest class of natural AhR ligands. As interest in AhR and its ligands increases, it seems sensible to summarize current research on these ligands. In this review, we highlight the role of AhR in tumorigenesis and focus on the double effect of AhR in cancer therapy. We explored the molecular mechanism of AhR ligands on cancer through a few AhR agonists/antagonists currently in clinical practice. Ultimately, we summarize and highlight the latest progression of dietary flavonoids as AhR ligands in cancer inhibition, including the limitations and deficiencies of it in clinical research. This review will offer a comprehensive understanding of AhR and its dietary ligands which may dramatically pave the way for targeted cancer treatment.

Natural products for the prevention and treatment of kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is one of the common causes resulting in a high morbidity and mortality. Renal fibrosis is the main pathological features of CKD. Natural products have begun to gain widely popularity worldwide for promoting healthcare and preventing CKD, and have been used as a conventional or complementary therapy for CKD treatment. PURPOSE: The present paper reviewed the therapeutic effects of natural products on CKD and revealed the molecular mechanisms of their anti-fibrosis. METHODS: All the available information on natural products against renal fibrosis was collected via a library and electronic search (using Web of Science, Pubmed, ScienceDirect, Splinker, etc.). RESULTS: Accumulated evidence demonstrated that natural products exhibited the beneficial effects for CKD treatment and against renal fibrosis. This review presents an overview of the molecular mechanism of CKD and natural products against renal fibrosis, followed by an in-depth discussion of their molecular mechanism of natural products including isolated compounds and crude extracts against renal fibrosis in vitro and in vivo. A number of isolated compounds have been confirmed to retard renal fibrosis. CONCLUSION: The review provides comprehensive insights into pathophysiological mechanisms of CKD and natural products against renal fibrosis. Particular challenges are presented and placed within the context of future applications of natural products against renal fibrosis.

Metabolomics in dyslipidemia.

Hyperlipidemia is an important public health problem with increased incidence and prevalence worldwide. Current clinical biomarkers, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol lack the necessary specificity and sensitivity and only increase significantly after serious dyslipidemia. Therefore, sensitive biomarkers are needed for hyperlipidemia. Hyperlipidemia-specific biomarkers would improve clinical diagnosis and therapeutic treatment at early disease stages. The aim of metabolomics is to identify untargeted and global small-molecule metabolite profiles from cells, biofluids, and tissues. This method offers the potential for a holistic approach to improve disease diagnoses and our understanding of underlying pathologic mechanisms. This review summarizes analytical techniques, data collection and analysis for metabolomics, and metabolomics in hyperlipidemia animal models and clinical studies. Mechanisms of hypolipemia and antilipemic drug therapy are also discussed. Metabolomics provides a new opportunity to gain insight into metabolic profiling and pathophysiologic mechanisms of hyperlipidemia.

Diuretic and anti-diuretic activities of fractions of Alismatis rhizoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in China and Japan. In this paper, we report the diuretic activities of the petroleum ether fraction, the ethyl acetate fraction, the n-buthanol fraction, and the remaining fraction, of the ethanol extract of Alismatis rhizoma (AR). MATERIALS AND METHODS: The single dose of the petroleum ether fraction, the ethyl acetate fraction, the n-buthanol fraction, and the remaining fraction, of the ethanol extract of AR were orally administered to rats. Urinary excretion rate, pH and electrolyte excretion were measured in the urine of saline-loaded rats. RESULTS: In this study, the 100 and 400mg/kg doses of the ethyl acetate fraction and the 12.5, 25 and 50mg/kg doses of the n-butanol fraction all produced an increase in urine volume excretion, and all produced a remarkable increase in urine electrolyte excretion. Although the 800mg/kg doses of the ethyl acetate fraction, the 75 and 100mg/kg doses of the n-butanol fraction and the 12.5, 25 and 50mg/kg doses of the remaining fraction significantly decreased the urine output in 6h, the urine Na(+) and Cl(-) excretion were markedly decreased with the n-butanol fraction (75 and 100mg/kg doses) and the remaining fraction (12.5, 25 and 50mg/kg doses) while the ethyl acetate fraction at 800mg/kg doses had slight effect on urine electrolyte excretion. The petroleum ether fraction did not show remarkable diuretic activity in comparison with control group. CONCLUSIONS: Our present study determined that the ethyl acetate fraction and the n-butanol fraction present notable diuretic effects, and we found a dual effect on renal function showed by AR, including promoting diuretic activity and inhibiting diuretic activity. The components with strong polarities in AR may have anti-diuretic activities, which might be an effect of promoting the sodium-chloride co-transporter in the distal tubule.

Diuretic and anti-diuretic activities of the ethanol and aqueous extracts of Alismatis rhizoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in Asia and Europe. In this paper, we report the diuretic activities of the ethanol extract (EE) and the aqueous extract (AE) of A. rhizoma (AR). MATERIALS AND METHODS: The EE and AE were orally administered to rats. The urinary excretion rate and pH, and electrolyte excretion were measured in the urine of saline-loaded rats. RESULTS: The results showed that EE could increase the urine output at 2.5, 5 and 10mg/kg doses but decrease the urine output at 20, 40 and 80mg/kg doses compared with the control group. The 5 and 10mg/kg doses of EE increased the urine electrolyte excretion, but the effects on Na(+)/K(+) values were too weak to reach statistical significance. The Na(+) excretion and Cl(-) excretion were markedly decreased with the 20, 40 and 80mg/kg doses of EE, but the effect on K(+) excretion was notably slight. All of the tested doses of AE produced an increase in urinary excretion, but the increase did not reach statistical significance. CONCLUSIONS: This study identified that EE but not AE presents a notable diuretic effect, and EE had diuretic and anti-diuretic effects, which appears to be related to the sodium-chloride co-transporter in the renal distal convoluting tubule. This study demonstrated for the first time that the EE of AR has a dual effect on renal function, including promotion of diuretic activity at lower doses and inhibiting diuretic activity at higher doses, and the AR dose should be given more attention in clinical applications. This study will play a critical and guiding role in the dosing of AR as a diuretic drug in clinical applications.

Diuretic activity of some fractions of the epidermis of Poria cocos.

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos Wolf (Polyporaceae) is a well-known medicinal fungus, the epidermis ("Fu-Ling-Pi" in Chinese) of the sclerotia is used as a diuretic for treating oedema and promoting the diuretic process. In this paper we report on the diuretic activity in rats of petroleum ether, ethyl acetate, n-butanol and the remaining fractions of the ethanol extract from the epidermis of Poria cocos. MATERIALS AND METHODS: Petroleum ether, ethyl acetate, n-butanol and the remaining fractions of the ethanol extract of Fu-Ling-Pi were orally administered to rats. The urinary excretion rate and the pH and electrolyte excretion were measured in the urine of saline-loaded rats. RESULTS: In this study, all the tested fractions of Fu-Ling-Pi increased the urinary excretion rate. The three doses of the ethyl acetate fraction all produced remarkable urinary output in 6h, and all produced a remarkable increase in Na(+) excretion and Cl(-) excretion. The Na(+)/K(+) value in the experimental group was significantly enhanced compared with that of the control group, but the three doses of the ethyl acetate fraction had no effect on the K(+) excretion. The 25-mg/kg and 50-mg/kg doses of the n-butanol fraction showed notable urinary output and produced a remarkable increase of Na(+) excretion and Cl(-) excretion, but the two doses did not produce a remarkable effect on the Na(+)/K(+) value. The petroleum ether and remaining fractions did not show remarkable diuretic activities compared with the control group. CONCLUSIONS: This study confirmed that the ethyl acetate and n-butanol fractions present a remarkable diuretic effect, showing that they are the diuretic bioactive fractions of Fu-Ling-Pi. This finding appears to indicate at least two mechanisms for the observed diuretic activity, and the K(+)-saving diuretic effect may be related to the triterpenoid components of intermediate polarity contained in this fungus, particularly the lanostanes tetracyclic triterpenoids.

[Chemical constituents of surface layer of Poria cocos and their pharmacological properties (I)].

The surface layer of the sclerotia of Poria cocos, named Fu-Ling-Pi, is used as a diuretic in traditional Chinese medicine to treat edema and urinary dysfunction. Recent studies have showed that the triterpenes (lanostane and 3,4-secolanostane skeletons) and polysaccharides (beta-pachyman) are the main components of Fu-Ling-Pi and they exhibited various biological activities, such as anti-tumor, antibacterial and antioxidant, etc. This review was focused on the chemistry, pharmacology, and clinical uses of this drug and it may provide scientific foundation for further development and utilization of Fulingpi.

Renal metabolic profiling of early renal injury and renoprotective effects of Poria cocos epidermis using UPLC Q-TOF/HSMS/MSE.

Poria cocos epidermis is one of ancient traditional Chinese medicines (TCMs), which is usually used for the treatment of chronic kidney disease (CKD) for thousands of years in China. A metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight high-sensitivity mass spectrometry (UPLC Q-TOF/HSMS) and a mass spectrometry(Elevated Energy) (MS(E)) data collection technique was developed to obtained a systematic view of the development and progression of CKD and biochemistry mechanism of therapeutic effects of P. cocos epidermis (Fu-Ling-Pi, FLP). By partial least squares-discriminate analysis, 19 metabolites were identified as potential biomarkers of CKD. Among the 19 biomarkers, 10 biomarkers including eicosapentaenoic acid, docosahexaenoic acid, lysoPC(20:4), lysoPC(18:2), lysoPC(15:0), lysoPE(20:0/0:0), indoxyl sulfate, hippuric acid, p-cresol sulfate and allantoin were reversed to the control level in FLP-treated groups. The study indicates that FLP treatment can ameliorate CKD by intervening in some dominating metabolic pathways, such as fatty acid metabolism, phospholipid metabolism, purine metabolism and tryptophan metabolism. This work was for the first time to investigate the FLP therapeutic effect based on metabonomics technology, which is a potentially powerful tool to study the TCMs.

Urinary metabonomic study of the surface layer of Poria cocos as an effective treatment for chronic renal injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos Wolf (Polyporaceae) is a well-known medicinal fungus. The epidermis of the sclerotia ("Fu-Ling-Pi" in Chinese) is used as a diuretic and traditionally used for promoting urination and reduce edema. AIM OF THE STUDY: Traditional Chinese medicines (TCM) treat many diseases through multi-components, multi-ways and multi-targets. However, the molecular mechanisms of TCM are not yet well understood. In the present work, ultra performance liquid chromatography-based metabonomics analysis was applied to investigate the urinary metabolite profiling of the renoprotective effect of FLP on adenine-induced chronic kidney disease (CKD) rat model and involved possible mechanism. MATERIAL AND METHODS: A metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight high-sensitivity mass spectrometry and a novel mass spectrometry(Elevated Energy) data collection technique was developed. The resulting dataset was analyzed by principal component analysis and partial least squares discriminant analysis. The identification of all potential biomarkers was performed using reference standard by comparing their mass spectra, MS(E) fragments information, isotopic pattern and MassLynx i-FIT algorithm. RESULTS: By partial least squares-discriminate analysis, 15 biomarkers in rat urine were identified and 11 of them were related to the pathway of adenine metabolism and amino acid metabolism. Among these biomarkers, eight biomarkers like adenine, L-acetylcarnitine, 8-hydroxyadenine, hypoxanthine, creatine, methionine, phytosphingosine and phenylalanine were reversed to the control level in FLP-treated group and six biomarkers like 2,8-dihydroxyadenine, indole-3-carboxylic acid, 3-methyldioxyindole, ethyl-N2-acetyl-L-argininate, 3-O-methyldopa and xanthurenic acid were reversed to high control group by FLP, which indicates that the urinary metabolic pattern significantly changed after FLP treatment. CONCLUSIONS: Our study indicates that FLP treatment can ameliorate CKD by intervening in some dominating metabolic pathways, such as adenine metabolism and amino acid metabolism. The metabonomic results not only supplied a systematic view of the development and progression of CKD and mechanism studies of FLP but also provided the theoretical basis for the prevention or treatment of CKD.

Ultra performance liquid chromatography-based metabonomic study of therapeutic effect of the surface layer of Poria cocos on adenine-induced chronic kidney disease provides new insight into anti-fibrosis mechanism.

The surface layer of Poria cocos (Fu-Ling-Pi, FLP) is commonly used in traditional Chinese medicine and its diuretic effect was confirmed in rat. Ultra performance liquid chromatography/quadrupole time-of-flight high-sensitivity mass spectrometry and a novel mass spectrometry(Elevated Energy) data collection technique was employed to investigate metabonomic characteristics of chronic kidney disease (CKD) induced from adenine excess and the protective effects of FLP. Multiple metabolites are detected in the CKD and are correlated with progressive renal injury. Among these biomarkers, lysoPC(18∶0), tetracosahexaenoic acid, lysoPC(18∶2), creatinine, lysoPC (16∶0) and lysoPE(22∶0/0∶0) in the FLP-treated group were completely reversed to levels in the control group which lacked CKD. Combined with biochemistry and histopathology results, the changes in serum metabolites indicate that the perturbations of phospholipids metabolism, energy metabolism and amino acid metabolism are related to adenine-induced CKD and to the interventions of FLP on all the three metabolic pathways. FLP may regulate the metabolism of these biomarkers, especially their efficient utilization within the context of CKD. Furthermore, these biomarkers might serve as characteristics to explain the mechanisms of FLP.

Pharmacokinetics of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside in rat using ultra-performance LC-quadrupole TOF-MS.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (THSG) from Polygoni multiflori has been demonstrated to possess a variety of pharmacological activities, including antioxidant, anti-inflammatory and hepatoprotective activities. Ultra-performance LC-quadrupole TOF-MS with MS Elevated Energy data collection technique and rapid resolution LC with diode array detection and ESI multistage MS(n) methods were developed for the pharmacokinetics, tissue distribution, metabolism, and excretion studies of THSG in rats following a single intravenous or oral dose. The three metabolites were identified by rapid resolution LC-MS(n). The concentrations of the THSG in rat plasma, bile, urine, feces, or tissue samples were determined by ultra-performance LC-MS. The results showed that THSG was rapidly distributed and eliminated from rat plasma. After the intravenous administration, THSG was mainly distributing in the liver, heart, and lung. For the rat, the major distribution tissues after oral administration were heart, kidney, liver, and lung. There was no long-term storage of THSG in rat tissues. Total recoveries of THSG within 24 h were low (0.1% in bile, 0.007% in urine, and 0.063% in feces) and THSG was excreted mainly in the forms of metabolites, which may resulted from biotransformation in the liver.

Diuretic activity of the ethanol and aqueous extracts of the surface layer of Poria cocos in rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos Wolf (Polyporaceae) is a well-known traditional East-Asian medicinal fungus. the epidermis ("Fu-Ling-Pi" in Chinese) of the sclerotia is used as a diuretic. This study was conducted to evaluate of ethanol extract (EE) and aqueous extract (AE) of the diuretic activity of Fu-Ling-Pi in saline-loaded rats. MATERIAL AND METHODS: The EE and AE were orally administered to rats. Urinary excretion rate, pH and electrolyte excretion were measured in the urine of saline-loaded rats. RESULTS: Urinary excretion rates were significantly increased by the EE. The three doses of AE only produced a slight increase urinary output. The EE had little or no effect on K(+) excretion, but did indeed induce a notable excretion of Na(+), that was in agreement with the urinary excretion. The three doses of AE produced an increase Na(+) and K(+) excretion, but did not arrive at statistical significance. CONCLUSIONS: The present study confirmed that the not aqueous but ethanol extracts of the epidermis of Poria cocos presents a remarkable diuretic effect.