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Purpose: 6-Shogaol, an active phenolic compound from ginger (Zingiber officinale), can inhibit the growth of a variety of human cancer cells. Nevertheless, its underlying molecular mechanisms in cervical cancer remain unclear. In this study, we systematically examine the inhibitory effect of 6-shogaol on cervical cancer in vitro and in vivo. Methods: Cell proliferation was assessed by CCK8 assay and colony formation assay in HeLa and SiHa cells. We analyzed cell cycle and apoptosis through flow cytometry. GFP-LC3 puncta and transmission electron microscopy were used to observe autophagic bodies. Wound-healing assay and transwell assay were used for evaluating the migration of cells. Western blot was applied to detect protein expression levels. Results: 6-Shogaol could suppress cell proliferation and migration, cause cell cycle arrest in the G2/M phase in HeLa and SiHa cells. Moreover, 6-shogaol triggered the apoptosis process through the mitochondrial pathway by downregulating the expression levels of p-PI3K, p-Akt and p-mTOR. Further research indicated that the induction of apoptosis by 6-shogaol was remarkably decreased after the treatment of ROS scavenger and PI3K agonist. Additionally, 6-shogaol increased the number of LC3-positive puncta and autophagic bodies per cell in both HeLa and SiHa cells. Pretreatment of cells with Bafilomycin A1, an autophagy inhibitor, accelerated 6-shogaol mediated cell apoptosis, suggesting that induction of autophagy by 6-shogaol is suppressive to apoptosis. Furthermore, in vivo data revealed that 6-shogaol significantly inhibited tumor growth and cell proliferation in tumor tissues. Conclusion: These findings suggested that 6-shogaol could be developed as a functional food ingredient, which is potentially used as therapeutic agents for patients with cervical cancer. [ABSTRACT FROM AUTHOR]

Objectives. Opiate analgesics are the most effective treatments for severe pain, but their clinical utility is often hampered by the development of analgesic tolerance. There are striking similarities between morphine actions and neuropathic pain. We have demonstrated that B vitamins can attenuate neuropathic pain after peripheral nerve injury, sensory neuron inflammation/compression, and transient spinal cord ischemia. Given this similarity, the present study investigated whether B vitamins might be able to modify the antinociceptive effect of morphine as well as morphine tolerance in mice. Methods. Cell signaling was assayed byWestern blot and immunohistochemistry. Antinociception was assessed in ICR mice using the tail flick. The effects of B vitamins on acute morphine-induced antinociception and chronic morphine tolerance were studied. Results. 1) Co-administration of B vitamins with morphine potentiates acute morphine antinociception. 2) B vitamins attenuate the development of antinociceptive tolerance to chronic morphine administration and inhibit morphine-induced p-NR1, p-PKC in the spinal cord. 3) Morphine induces microglial activation, as evidenced by increased p38 MAPK phosphorylation, IBA1, and IL-1β in the spinal cord, and these changes are inhibited by B vitamins. 4) Treatment of B vitamins alone shows no notable effects on pain threshold and activity of microglia in vivo. Conclusions. B vitamins potentiate acute morphine antinociception and attenuate chronic morphine tolerance. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Huang-Lian-Jie-Du-Decotion (HLJDD, Hwangryun-Hae-Dok-Decotion in Japan), an ancient antipyretic and detoxifying traditional Chinese medicine formula, was reported to have protective effect on ischemic stroke. Aim of the research: To investigate the therapeutic effect of HLJDD on ischemic stroke and explore its mode of action. Material and methods: A model of ischemic stroke in the rat was established after transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Rats were assigned randomly to groups of control, sham, transient ischemia/reperfusion (I/R), and three treatment groups by HLJDD at 2.5, 5.0, 10.0mg/kg. The neurological deficit, the cerebral infarct size, morphology abnormality, biochemical parameters were examined, and the levels of relevant proteins were determined by immunoblotting analysis to evaluate the protective effects of HLJDD on ischemic stroke and explore the underlying mechanism. Results: Compared with I/R group, HLJDD significantly ameliorated neurological deficit and histopathology changes, decreased infarct area, and restored the levels of biochemical indicators including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), total superoxide dismutase (T-SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase (GSH-PX). HLJDD also notably elevated the levels of microtubule-associated protein1 light chain 3 (LC3), Beclin-1, and other autophagy related genes (Atgs), promoted the activation of extracellular signal-regulated kinases (ERK), protein kinase B (Akt), 3-phosphoinositide-dependent kinase (PDK1), and inhibited the activation of mammalian target of rapamycin (mTOR), c-Jun N-terminal protein kinases (JNK), p38, phosphatase and tensin homolog (PTEN). Conclusion: HLJDD showed neuroprotective effects on ischemic stroke, at least in part to the induced protective autophagy via the regulation of mitogen-activated protein kinase (MAPK) signals. This Akt-independent protective autophagy is favorable in the treatment of stroke, avoiding unfavorable side-effects associated with the inactivation of Akt. The efficacy of HLJDD on ischemic stroke and its safety warranted by its long-term clinical use in traditional Chinese medicine favored further study to develop HLJDD as an effective therapeutic agent to treat ischemic stroke. [Copyright &y& Elsevier]

A novel lindenane sesquiterpene with an unprecedented 18-membered triester ring, named chlorafortulide (1), along with one known lindenane sesquiterpene (2) and nine known lindenane sesquiterpene dimers (3–11), was isolated from the whole plant of Chloranthus fortunei. Their structures and relative configurations were elucidated on the basis of spectroscopic analysis. All the isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. Henriol D (4), shizukaols E (8), G (9), M (10), and O (11) showed significant anti-inflammatory activities with IC50 values of 1.90, 3.68, 1.95, 7.01, and 1.95 μM, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Huang-Lian-Jie-Du decoction (HLJDD) (Oren-gedoku-to in Japanese) as a famous traditional Chinese recipe is composed of Rhizoma coptidis, Radix scutellariae, Cortex phellodendri and Fructus gardeniae. It has been used to treat inflammation for nearly two thousand years. Aim of the study: To explore the material base for the anti-inflammatory activity of formula HLJDD, its extract was fractionated on D101 macroporous resin to afford two fractions, HLJDD-1 and HLJDD-2. The whole formula, HLJDD-1 and HLJDD-2, and four typical component compounds were then evaluated for their effects on inflammation-related parameters using lipopolysaccharide (LPS)-induced RAW264.7 cells as a model system. Materials and methods: The effect of HLJDD on carrageenan-induced mice paw edema was first evaluated. A series of inflammation-related parameters including malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) were then measured in LPS-induced RAW264.7 cells treated with HLJDD, its two fractions, and four typical component compounds (geniposide, baicalin, berberine and baicalein). Results: With the help of principal component analysis (PCA) technique, the data obtained revealed that the two fractions and the major group of compounds in HLJDD (iridoids, flavonoids and alkaloids) complement each other with particular emphasis to synergistically exert anti-inflammatory effects. Conclusions: This study demonstrated that HLJDD exhibited anti-inflammatory effect as a “whole”, which justified the combined use of the four component herbs forming the compound prescription and suggested quality control of HLJDD based on its three types of components. [Copyright &y& Elsevier]

Abstract: Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, is clinically used for the treatment of vascular dementia (VD). This study compared the pharmacokinetics of paeoniflorin, the main active ingredients in Paeonia lactiflora Pall, in VD and normal rats administrated with DSS or pure paeoniflorin. The absorptions of paeoniflorin in both VD and normal group of rats were better when orally administrated with DSS than that with pure paeoniflorin, which justified the combined use as formula DSS. Moreover, a better absorption of paeoniflorin in rats of the VD than in normal group was observed, which is helpful for the treatment of VD. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Glycyrrhizae uralenis (GU) is often prescribed together with Cortex daphnes (CD) in traditional Chinese medicinal practice to increase the efficacy of CD on the treatment of rheumatoid arthritis (RA), but the reasons were still unknown. In order to clarify the rationality of herbaceous compatibility between CD and GU, the comparative evaluations on pharmacokinetic behaviors of daphnetin (a predominantly active ingredient in CD) after intragastric administration of CD and CD–GU (combination of CD and GU) extract were studied. In addition, the effects of glycyrrhizin and liquiritin, active ingredients of Glycyrrhiza triterpenes and Glycyrrhiza flavones respectively, on the pharmacokinetics of daphnetin were also investigated. Materials and methods: Five groups of rats were orally administered with CD extract, CD–GU extract, pure daphnetin, co-administration of daphnetin and glycyrrhizin as well as co-administration of daphnetin and liquiritin at the same single dose of daphnetin (20mg/kg). The rat plasma concentrations of daphnetin were determined by our developed UPLC–MS/MS method. The pharmacokinetics of daphnetin in above groups were investigated and compared. Results: Comparing with oral administration of CD extract, AUC and T max of daphnetin significantly increased after giving CD–GU (p<0.05). In addition, in comparison to daphnetin alone, co-administration of daphnetin with liquiritin significantly increased the AUC and C max of daphnetin for ~1.5-fold, while co-administered with glycyrrhizin showed limited impact on the pharmacokinetics of daphnetin. Conclusions: In this study, it was found that liquiritin, one of the major components of GU, significantly enhanced the bioavailability of the main component daphnetin in CD. In addition, the bioavailability of daphnetin in the CD–GU prescription was also significantly higher than that in CD alone, which could be due to liquiritin. Such results explained the mechanism of the increased efficacy in treating RA with the combined use of CD and GU. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Radix Aconiti Lateralis (Fuzi in Chinese, derived from the lateral roots of Aconitum Carmichaeli Debx.) is widely used for the treatment of heart failure, internal cold, arthralgia, diarrhea and edema for thousands of years. It was usually prescribed in combination with Rhizoma Zingiberis (Ganjiang in Chinese, derived from the dry rhizome of Zingiber officinale Rosc.) to decrease toxicity and increase efficacy. Aim of the study: In order to investigate the influence of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA), in Fuzi−Ganjiang herb couple, the comparative pharmacokinetics of six Aconitum alkaloids after oral administration of Fuzi and Fuzi−Ganjiang aqueous extract was carried out. Materials and methods: A sensitive, specific and rapid LC−MS/MS method was developed to determine the six analytes in plasma. Then the rats were randomly divided into two groups and orally administered with Fuzi and Fuzi−Ganjiang aqueous extract. At designated time points after oral administration, the concentrations of the six Aconitum alkaloids in rat plasma were determined, and main pharmacokinetic parameters were investigated using 3P97 (Practical Pharmacokinetics Program Version 1.0). Results: Comparing with Fuzi group, both T 1/2 and AUC0−t of AC and HA decreased (P<0.05), while T 1/2, AUC0−t and C max of BAC, BHA increased (P<0.05) in Fuzi−Ganjiang group, which indicated that Ganjiang could promote the elimination of AC and HA and enhance the absorption of BAC, BHA and BMA. Conclusion: The differences of pharmacokinetics of Aconitum alkaloids in rat plasma could support those of pharmacologics and toxicity in previous reports between Fuzi and Fuzi−Ganjiang herb couple. The results might be helpful in explaining the mechanism of combination of Fuzi−Ganjiang to decrease toxicity and increase efficacy. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The root of Peucedanum praeruptorum Dunn (PPD) is a commonly used traditional Chinese medicine for the treatment of asthma. Its major constituents, coumarins, were presumed to be responsible for its efficacy. Aim of the study: The potential of coumarins from PPD (CPPD) as anti-asthma agent was investigated. Materials and methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic airway inflammation. CPPD was administered intragastrically before every OVA challenge. Airway reactivity to the intravenous administration of acetylcholine chloride was measured 48h after final OVA inhalation. Airway inflammation was evaluated by leukocyte counts of bronchoalveolar lavage fluid (BALF) and histopathological analysis of lung lesions. Levels of interleukin (IL)-4, IL-5, IL-10, IL-13 and IFN-γ in BALF and OVA-specific immunoglobulin (Ig) E in serum, and activity of eosinophil peroxidase (EPO) in lung was measured. The percentage of CD4+CD25+Foxp3+ regulatory T cells among CD4+ T cells in spleen was analyzed by flow cytometry. Results: Compared with model group, CPPD significantly reduced airway hyperreactivity and airway eosinophilic inflammation, improved pathologic lesion of the lungs, reduced levels of IL-4, IL-5, IL-13 in BALF and OVA-specific IgE in serum, inhibited the activities of EPO in lung, and up-regulated levels of IL-10 and IFN-γ in BALF as well as the percentage of CD4+CD25+Foxp3+ regulatory T cells in spleen. Conclusion: CPPD can significantly suppress OVA-induced airway inflammation, airway hyperreactivity and Th2 predominant response in mice, showing great therapeutic potential for the treatment of allergic asthma. [Copyright &y& Elsevier]

Abstract: Salviae miltiorrhizae is one of the most commonly used herbal plants in the treatment of numerous ailments including cardiovascular diseases for hundreds of years. According to the theory of traditional Chinese herbal medicine, S. miltiorrhizae is always used in combination with borneol to obtain better pharmacological effects. The purpose of this study was to investigate the effects of borneol on the pharmacokinetic and bioavailability of S. miltiorrhizae. The pharmacokinetics studying on rosmarinic acid, salvianolic acid A and salvianolic acid B which are the main active compounds of S. miltiorrhizae in rat plasma, was achieved using a optimal high-performance liquid chromatographic technique coupled with liquid–liquid extraction method. After administration of either single salvianolic acids or salvianolic acids in combination with borneol, plasma concentrations of rosmarinic acid, salvianolic acid A and salvianolic acid B of male Sprague–Dawley rats were determined at different time points (5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, and 360min). In comparison with salvianolic acid extract alone, there were statistically significant differences in pharmacokinetic parameters of rosmarinic acid, salvianolic acid B and salvianolic acid A, and the bioavailability of the three salvianolic acids increased by different degrees when the salvianolic acid extract and borneol were administered together. These results indicated that borneol could enhance the intestinal absorption, decrease the distribution and inhibit the metabolism of salvianolic acids. [Copyright &y& Elsevier]

Objective Head elevation at an angle of 30° during cardiopulmonary resuscitation (CPR) was hemodynamically beneficial compared to supine position in a previous porcine cardiac arrest experimental study. However, survival benefit of head-up elevation during CPR has not been clarified. This study aimed to assess the effect of head-up tilt position during CPR on 24-hour survival in a porcine cardiac arrest experimental model. Methods This was a randomized experimental trial using female farm pigs (n=18, 42±3 kg) sedated, intubated, and paralyzed on a tilting surgical table. After surgical preparation, 15 minutes of untreated ventricular fibrillation was induced. Then, 6 minutes of basic life support was performed in a position randomly assigned to either head-up tilt at 30° or supine with a mechanical CPR device, LUCAS-2, and an impedance threshold device, followed by 20 minutes of advanced cardiac life support in the same position. Primary outcome was 24-hour survival, analyzed by Fisher exact test. Results In the 8 pigs from the head-up tilt position group, one showed return of spontaneous circulation (ROSC); all eight pigs expired within 24 hours. In the eight pigs from the supine position group, six had the ROSC; six pigs survived for 24 hours and two expired. The head-up position group showed lower 24-hour survival rate and lower ROSC rate than supine position group (P

Abstract Ethnopharmacological relevance Polygonum multiflorum Thund., a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating hypertension, hyperlipidemia, premature graying of hair, and etc., has aroused wide concern for its reported potential liver toxicity. Due to its various active ingredients, the mechanisms underlying the hepatotoxicity of raw Polygonum multiflorum Thund (RPM) remain largely unknown. Aim of the study 1H NMR metabolomics was used to study the mechanism of RPM induced hepatotoxicity and disclosed the existence of hepatotoxicity and hepatoprotection conversion during RPM administration in mice. Materials and Methods Three dosages of RPM were administered by gavage to mice for consecutive 28 days. The serum and liver samples were collected and then subjected for histopathology observation, biochemical measurement and 1H NMR metabolic profiling. Results RPM caused oxidative stress and mitochondria dysfunction in mice, resulting in significant disturbance in energy metabolism, amino acid metabolism and pyrimidine metabolism and also inducing inflammatory responses. RPM induced hepatotoxicity in an apparent non-linear manner: the most severe in low dosage group, and to a less extent in medium group according to metabolomics analysis. The attenuation of liver injury in mice livers might result from the therapeutic effects, such as anti-oxidative capacity of RPM components. Conclusion RPM exerted a complicated non-linear manner in healthy recipients, switching between hepatoxicity and hepatoprotection dependent on the dosage and status of the body. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Herpetospermum caudigerum Wall. (HCW) is a traditional Tibetan medicine, which has been used to ameliorate liver injuries in the folk. Aim of the study Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis/hepatocarcinoma and even to death in the end. This study aims to demonstrate the protective effect of HCW against CCl 4 -induced liver injury in rats and to explore the underlying mechanisms. Materials and methods Hepatic fibrosis was induced by intraperitoneal injection of CCl 4. Liver function markers, fibrosis markers, serum anti-oxidation enzymes as well as elements levels were determined. Serum and liver tissues were subjected to NMR-based metabolomics and multivariate statistical analysis. Results HCW could significantly reduce the elevated levels of fibrosis markers such as hyaluronidase, laminin, Type III procollagen and Type IV collagen in the serum, improve the activities of the antioxidant enzymes, and effectively reverse the abnormal levels of elements in liver fibrosis rats. Correlation network analysis revealed that HCW could treat liver fibrosis by ameliorating oxidative stress, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. Conclusion This integrated metabolomics approach confirmed the validity of the traditional use of HCW in the treatment of liber fibrosis, providing new insights into the underlying mechanisms. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Treating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the β-catenin-dependent pathway in the spinal cord and the β-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats. Sciatic nerve injury causes a rapid-onset and long-lasting expression of Wnt3a, Wnt5b, and Ryk receptors in primary sensory neurons, and dorsal horn neurons and astrocytes. Spinal blocking of the Wnt/Ryk receptor signaling inhibits the induction and persistence of neuropathic pain without affecting normal pain sensitivity and locomotor activity. Blocking activation of the Ryk receptor with anti-Ryk antibody, in vivo or in vitro, greatly suppresses nerve injury-induced increased intracellular Ca and hyperexcitability of the sensory neurons, and also the enhanced plasticity of synapses between afferent C-fibers and the dorsal horn neurons, and activation of the NR2B receptor and the subsequent Ca-dependent signals CaMKII, Src, ERK, PKCγ, and CREB in sensory neurons and the spinal cord. These findings indicate a critical mechanism underlying the pathogenesis of neuropathic pain and suggest that targeting the Wnt/Ryk signaling may be an effective approach for treating neuropathic pain. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Ascending and descending theory is a core principle of traditional Chinese medicine (TCM) theories. It plays an essential role in TCM clinical applications. Some TCM medicine has specific properties, which could alter the inclination and direction of their actions. The properties of the ascending and floating process of one herbal medicine are affected by means of herb processing. Wine-processing, which is sautéing with rice wine, is one of the most popular technologies of herb processing. Wine-processing increases the inclination and direction of its actions, thereby producing or strengthening their efficacy in cleaning the upper-energizer heat. Radix scutellariae, the dried roots of Scutellaria baicalensis Georgi, is a well-known TCM used for the treatment of inflammation, pyrexia, jaundice, etc. Recently, wine-processed Radix scutellariae was normally applied in clinical studies for the treatment of upper-energizer syndrome. In order to investigate the effects of wine-processing on ascending and descending of Radix scutellariae, the comparative study of distribution of flavonoids in rat tissues of triple energizers (SanJiao-upper, middle, lower jiao) after oral administration of crude and wine-processed Radix scutellariae aqueous extracts was carried out. Materials and methods The rats were randomly assigned to two groups and orally administered with crude and wine-processed Radix scutellariae aqueous extracts, respectively. At different pre-determined time points after administration, the concentrations of compounds in rat tissue homogenate were determined, and the main tissue pharmacokinetic parameters were investigated. Tissue pharmacokinetic parameters including AUC0-t, t1/2, Tmax and Cmax were calculated using DAS 2.0. An unpaired Student t-test was used to compare the differences in tissue pharmacokinetic parameters between the two groups. All the results were expressed as arithmetic mean±S.D. Results The parameters of Cmax and AUC0-t of some flavonoids in wine-processed Radix scutellariae were remarkably increased (p<0.05, p<0.01, p<0.001) in the rat upper-energizer tissues (lung and heart) compared with those of the crude group. However, in the rat middle- and lower-energizer tissues (spleen, liver and kidney), the Cmax and AUC0-t of some flavonoids were significantly decreased (p<0.05, p<0.01) compared with the crude group. The main explanation for these differences seems to the effects of wine-processing on ascending and descending theory. Conclusions All of these differences in the distribution of triple energizers after oral administration of crude and wine-processed Radix scutellariae aqueous extracts may lead to the increase of efficacy on the upper-energizer tissues and were in compliance with the ascending and descending theory. Therefore, wine-processing was recommended when Radix scutellariae was used for cleaning the upper-energizer heat and humidity. The obtained knowledge can be used to evaluate the impact of these differences on the efficacy of both the drugs in clinical applications and might be helpful in explaining the effects of wine-processing on ascending and descending theory. [ABSTRACT FROM AUTHOR]

Abstract: Two new compounds, a neolignan (1), and a benzofuran derivative (2), along with 6 known compounds (3–8), were isolated from the aerial parts of Leontopodium leontopodioides. The structures of the new compounds were elucidated as (7R,8S)-3,5′-dimethoxy-4′,7-epoxy-8,3′-neolignane-5,9,9′-triol (1) and (2R)-12-hydoxy-4-methoxy-tremeton (2) on the basis of their spectroscopic data, respectively. All of the isolates were evaluated for their effects on the inhibition of nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 macrophages and compounds 1 and 8 exhibited inhibitory activity with IC50 values of 35.80 and 24.41μM, respectively. [Copyright &y& Elsevier]

25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity. Aim of the study : To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys. [Display omitted] • The drug safety of turquoise and 25 flavors of the turquoise pill in rats were firstly studied by 1H NMR-based metabolomics. • 25 flavors of the turquoise pill can promote the aerobic respiration of the kidney and liver in rats. • Considering the large dosage used in this experiment, both 25 flavors of the turquoise pill and turquoise are safe. [ABSTRACT FROM AUTHOR]

Wu-Zi-Yan-Zong-Wan (WZYZW) is a commonly used Chinese medicinal recipe for oligozoospermia. Oligozoospermia is a common disease that harms human fertility, there is no effective therapeutic medicine at present. However, the underlying pharmacological mechanism remains unclear. Methods : Oligozoospermia rats model induced by Tripterygium glycosides (TG) was established to inspect the efficiency of WZYZW in the treatment of oligozoospermia by traditional pharmacodynamics combined with NMR-based metabolomics. Multivariate statistics were used to extracted the underlying biomarkers and metabolic pathways of WZYZW in the treatment of oligozoospermia. The results showed that TG disturbed many metabolites and metabolic pathways such as oxidative stress (choline, O -phosphocholine, betaine and ascorbate), energy metabolism in mitochondria (glucose, lactate, succinate, fumarate, 3-hydroxybutyrate and alanine), mitochondrial apoptosis markers (Bax and Bcl-2) and amino acids metabolisms (arginine, branched-chain amino acids, taurine and myo -inositol). WZYZW could significantly reverse the disturbed metabolites to their normal status by their abilities of anti-oxidation, anti-apoptosis, balancing the osmotic pressure regulatory molecules and regulating the amino acids metabolism. This study provides pharmacological basis and guidance for the clinical usage of WZYZW. Image 1 [ABSTRACT FROM AUTHOR]

Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means. Image 1 [ABSTRACT FROM AUTHOR]