[Effects of Huoxiang Zhengqi Oral Liquid on intestinal barrier function in rats with dampness obstructing spleen-stomach syndrome].

The aim of this paper was to investigate the effect of Huoxiang Zhengqi Oral Liquid on intestinal barrier functions in rats with dampness obstructing spleen-stomach syndrome and primarily explore the mechanism. The rat model of dampness obstructing spleen-stomach syndrome was established, and then the modeled rats were randomly divided into the model control group, Huoxiang Zhengqi Oral Liquid high and low dose groups, and natural recovery group according to gender and body weight, with 10 rats in each group. Another 10 rats were taken as blank control group. After each group received the corresponding treatment for 7 days, rat serum was isolated. D-lactic acid content was detected by the MTT method, and diamine oxidase(DAO) activity was detected by the rate method. Colon tissues of the rats were isolated to detect Na~+-K~+-ATPase activity and Ca~(2+)-Mg~(2+)-ATPase activity by phosphate determination method, glutathione peroxidase(GSH-Px) activity was detected by spectrophotometry, catalase(CAT) activity was detected by ammonium molybdate, superoxide dismutase(SOD) activity was detected by hydroxylamine, the expression of occludin protein and ZO-1 protein was detected by immunofluorescence, and the expression levels of occludin protein and ZO-1 protein were detected by Western blot. RESULTS:: showed that low dose Huoxiang Zhengqi Oral Liquid could improve the body weight, diet, stool and urine state of rats with dampness obstructing spleen-stomach syndrome obviously. The D-lactic acid content and the DAO activity in the serum of rats with dampness obstructing spleen-stomach syndrome were reduced obviously. The activities of Na~+-K~+-ATPase, Ca~(2+)-Mg~(2+)-ATPase, GSH-Px, CAT and SOD in rat colon tissues were increased obviously. The occludin proteins and ZO-1 protein expression levels in rat colon tissues were raised obviously. The differences in the above indexes between Huoxiang Zhengqi Oral Liquid group and the model control group were statistically significant(P<0.05). Huoxiang Zhengqi Oral Liquid could effectively restore the intestinal barrier function in rats with dampness obstructing spleen-stomach syndrome and its mechanism may be related to the repair of intestinal mechanical barrier function.

Analysis of Panax ginseng miRNAs and Their Target Prediction Based on High-Throughput Sequencing.

Panax ginseng has been widely and effectively used as medicine for thousands of years. However, only limited studies have been conducted to date on ginseng miRNAs. In the present study, we collected 3 ginseng samples from the Changbai Mountain in China. Small RNA libraries were constructed and sequenced on the Illumina HiSeq platform. Sequencing analyses identified 3798 miRNAs, including 298 known miRNAs and 3500 potentially novel miRNAs. The miR166, miR159, and miR396 families were among the most highly expressed miRNAs in all libraries. The results of miRNA expression analyses were validated by qRT-PCR. Target gene prediction through computational and pathway annotation analyses revealed that the primary pathways were related to plant development, including metabolic processes and single-organism processes. It has been reported that plant miRNAs might be one of the hidden bioactive ingredients in medicinal plants. Based on the combined use of RNAhybrid, Miranda, and TargetScan software, a total of 50,992 potential human genes were predicted as the putative targets of 2868 miRNAs. Interestingly, the enriched KEGG pathways were associated with some human diseases, especially cancer, immune system diseases, and neurological disorders, and this could support the clinical use of ginseng. However, the human targets of ginseng miRNAs should be confirmed by further experimental validation. Our results provided valuable insight into ginseng miRNAs and the putative roles of these miRNAs.

The Effect of Prim-O-Glucosylcimifugin on Tryptase-Induced Intestinal Barrier Dysfunction in Caco-2 Cells.

The intestinal barrier dysfunction is a critical pathological change in irritable bowel syndrome (IBS). The objective of this study was to evaluate the effect of Prim-O-glucosylcimifugin (POG) on intestinal barrier dysfunction and reveal possible molecular mechanisms. Human colon adenocarcinoma cell line (Caco-2) cell monolayers induced by tryptase (TRYP) were used to establish an intestinal barrier dysfunction model. Caco-2 cell monolayers from both functional and dysfunctional samples were treated with POG (30, 60 and 120 µg/mL) for 2, 8, 24, 36, 48 and 72 h. The Caco-2 cell monolayers were assessed by measurement of trans-epithelial electrical resistance (TEER) and percentage of fluorescein permeation (PFP). The expression of Protease Activated Receptor 2 (PAR-2) and myosin light chain kinase (MLCK) mRNA was analyzed by RT-PCR and the level of Zonula Occludens-1 (ZO-1) protein expression was determined by Western blot. In addition, the impact of POG on the distribution of the tight juction protein of Occludin was performed by immunofluorescence. Our results showed that POG elevated the TEER and decreased the PFP of the functional Caco-2 cell monolayers, as well as the dysfunctional Caco-2 cell monolayers. Furthermore, POG inhibited the expression of PAR-2 mRNA and MLCK mRNA and increased the level of ZO-1 protein expression in dysfunctional Caco-2 cells. The distribution of the Occludin proteins was ameliorated simultaneously. This study demonstrates that POG can enhance the intestinal barrier function of Caco-2 cell monolayers by inhibiting the expression of PAR-2 and MLCK and up-regulating the expression of ZO-1 protein, and ameliorated the distribution of Occludin protein.

[Effect of processed Polygonum multiflorum on mRNA expression level of five subtypes of CYP450 enzymes in rat liver].

To observe the effect of processed Polygonum multiflorum on mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. SD rats were randomly divided into the normal control group, processed P. multiflorum high dose and low dose groups (5.40 g•kg⁻¹ and 1.08 g•kg⁻¹). The rats in administration groups were continuously given with processed P. mutiflorum for 7 days by ig administration, and the rats in normal control group were given with the same volume of distilled water. After successive administration of 7 days, the serum biochemical indications were detected, and Real-time quantitative PCR technology was used to detect the mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. Experimental results showed that AST was decreased significantly in both low and high dose groups. ALT was significantly decreased in low dose group and significantly increased in high dose group. The mRNA expression levels of five subtypes of CYP450 enzymes in rat liver were decreased in high dose and low dose groups in a dose-dependent manner. Especially the high dose processed P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in rats. The study showed that high dose P. multiflorum water extract had hepatotoxicity, and the degree of liver damage was increased with the increase of dose. It shall be noted that 5.40 g•kg⁻¹ water extract of P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in the liver of rats.

[Intervention effects of Jiaotai pills on PCPA-induced insomnia in rats].

To elucidate the intervention effects of Jiaotai pills(JTP) on p-chlorophenylalanine (PCPA)-induced insomnia in rats and its underlying mechanism, the insomnia model was established by single intraperitoneal injection with PCPA in rats. The locomotor activity of rats was observed, and the levels of nerve growth factor(NGF) in hypothalamus, hippocampus, prefrontal cortex and serum of rats were determined by using ELISA. Moreover, a proton nuclear magnetic resonance(¹H-NMR)-based metabonomic approach was developed to profile insomnia-related metabolites in rat serum and hippocampus and analyze the intervention effects of JTP on changes in underlying biomarkers related to locomotor activity, NGF and insomnia. According to the results, JTP could significantly suppress the locomotor activity of insomnia rats, and increase the NGF levels in hypothalamus, hippocampus, prefrontal cortex and serum of rats with insomnia. The disturbed metabolic state associated with PCPA-induced insomnia in rat serum and hippocampus could be intervened by JTP. Meanwhile, six and five potential biomarkers related to insomnia in rat serum and hippocampus were reversed by administration of JTP. In conclusion, the current study demonstrated that JTP had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of NGF level and metabolism of amino acids, lipids and choline.

[Metabonomics Study on Urine 1H-NMR in Chronic Superficial Gastritis Patients with Pi-qi Deficiency Syndrome/Pi-Wei Dampness-heat Syndrome].

OBJECTIVE: To observe metabolomic changes in urine of chronic superficial gastritis (CSG) patients with Pi-qi deficiency syndrome (PQDS) or Pi-Wei dampness-heat syndrome (PWDHS), thereby providing scientific evidence for syndrome typing of them. METHODS: Urine samples were collected from CSG patients with PQDS/PWDHS and healthy volunteers, 10 in each group. Proton nuclear magnetic resonance spectroscopy (1H-NMR) based metabonomic analysis was performed on urine samples. Contents of related biomarkers were analyzed by principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), and urivariate statistical analysis. RESULTS: PLS-DA analysis showed that metabolites among CSG patients with PQDS/PWDHS and healthy volunteers could be mutually distinguished. Seven differentially identified metabolites were screened from urines of CSG patients with PQDS and healthy volunteers included glutamate, methionine, α-oxoglutarate, dimethylglycine, creatinine, taurine, and glucose. Four differentially identified metabolites were screened from urines of CSG patients with PWDHS and healthy volunteers included 2-hydroxybutyric acid, trimethylamine oxide, taurine, and hippuric acid. Eleven differentially identified metabolites were screened from urines of CSG patients with PQDS and PWDHS included fucose, ß-hydroxybutyric acid, alanine, glutamate, methionine, succinic acid, citric acid, creatinine, glucose, hippuric acid, and lactic acid. CONCLUSION: The metabolic differences of CSG patients PQDS and PWDHS mainly manifested in glycometabolism, lipid metabolism, and amino acids catabolism, and 1H-NMR based metabonomics may be used in classified study of Chinese medical syndrome typing.

The Therapeutic Potential of Hemp Seed Oil in D-Galactose-Induced Aging Rat Model Was Determined through the Combined Assessment of 1H NMR Metabolomics and 16S rRNA Gene Sequencing.

Aging is an irreversible process of natural degradation of bodily function. The increase in the aging population, as well as the rise in the incidence of aging-related diseases, poses one of the most pressing global challenges. Hemp seed oil, extracted from the seeds of hemp (Cannabis sativa L.), possesses significant nutritional and biological properties attributed to its unique composition of polyunsaturated fatty acids and various antioxidant compounds. However, there is limited knowledge regarding the anti-aging mechanism of hemp seed oil. This study aimed to evaluate the beneficial effects and potential mechanisms of hemp seed oil in a D-galactose (D-gal)-induced aging rat model through a combined analysis of metabolomics and 16S rRNA gene sequencing. Using nuclear magnetic resonance (NMR)-based metabolomics, significant alterations in serum and urine metabolic phenotypes were observed between the D-gal-induced aging rat model and the healthy control group. Eight and thirteen differentially expressed metabolites related to aging were identified in serum and urine, respectively. Treatment with hemp seed oil significantly restored four and ten potential biomarkers in serum and urine, respectively. The proposed pathways primarily included energy metabolism, amino acid metabolism, one-carbon metabolism, and lipid metabolism. Furthermore, 16S rRNA gene sequencing analysis revealed significant changes in the gut microbiota of aged rats. Compared to the model group, the hemp seed oil group exhibited significant alterations in the abundance of 21 bacterial taxa at the genus level. The results indicated that hemp seed oil suppressed the prevalence of pathogenic bacterial genera such as Streptococcus, Rothia, and Parabacteroides. Additionally, it facilitated the proliferation of the genera Lachnospirace_NK4B4_group and Lachnospirace_UCG_001, while also enhancing the relative abundance of the genus Butyricoccus; a producer of short-chain fatty acids (SCFAs). These findings provided new insights into the pathogenesis of aging and further supported the potential utility of hemp seed oil as an anti-aging therapeutic agent.

[Urine metabonomic study of intervention effects of Morinda officinalis how. on 'kidney-yang deficiency syndrome'].

To investigate the intervention effects of Morinda officinalis How. on 'Kidney-yang deficiency syndrome' induced by hydrocortisone in rats, the metabolic profiles of rat urine were characterized using proton nuclear magnetic resonance and principal component analysis (PCA) was applied to study the trajectory of urinary metabolic phenotype of rats with 'Kidney-yang deficiency syndrome' under administration of M. officinalis at different time points. Meanwhile, the intervention effects of M. officinalis on urinary metabolic potential biomarkers associated with 'Kidney-yang deficiency syndrome' were also discussed. The experimental results showed that in accordance to the increased time of administration, an obvious tendency was observed that clustering of the treatment group moved gradually closed to that of the control group. Eight potential biomarkers including citrate, succinate, alpha-ketoglutarate, lactate, betaine, sarcosine, alanine and taurine were definitely up- or down-regulated. In conclusion, the effectiveness of M. oficinalis on 'Kidney-yang deficiency syndrome' is proved using the established metabonomic method and the regulated metabolic pathways involve energy metabolism, transmethylation and transportation of amine. Meanwhile, the administration of M. officinalis can alleviate the kidney impairment induced by 'Kidney-yang deficiency syndrome'.

Integration of transcriptomics and metabonomics revealed the protective effects of hemp seed oil against methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in mice.

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease with few therapeutic options available currently. Hemp seed oil extracted from the seeds of hemp (Cannabis sativa L.) has significant nutritional and biological properties due to the unique composition of polyunsaturated fatty acids and various antioxidant compounds. However, little is known about the beneficial effects and molecular mechanisms of hemp seed oil on NASH. Here, the hepatoprotective effects of hemp seed oil on methionine-choline-deficient (MCD) diet-induced NASH in C57BL/6 mice were explored via integration of transcriptomics and metabolomics. Hemp seed oil could improve hepatic steatosis, inflammation and fibrosis in mice with MCD diet-induced NASH. In a nuclear magnetic resonance (NMR)-based metabonomic study, the hepatic and urinary metabolic profiles of mice supplemented with hemp seed oil showed a tendency to recover to healthy controls compared to those of NASH mice. Eight potential biomarkers associated with NASH in both liver tissue and urine were restored to near normal levels by administration of hemp seed oil. The proposed pathways were mainly involved in pyrimidine metabolism, one-carbon metabolism, amino acid metabolism, glycolysis and the tricarboxylic acid (TCA) cycle. Hepatic transcriptomics based on Illumina RNA-Seq sequencing showed that hemp seed oil exerted anti-NASH activities by regulating multiple signaling pathways, e.g., downregulation of the TNF signaling pathway, the IL-17 signaling pathway, the MAPK signaling pathway and the NF-κB signaling pathway, which played a pivotal role in the pathogenesis of NASH. In particular, integration of metabonomic and transcriptomic results suggested that hemp seed oil could attenuate NASH-related liver fibrosis by inhibition of glutaminolysis. These results provided new insights into the hepatoprotective effects of hemp seed oil against MCD diet-induced NASH and hemp seed oil might have potential as an effective therapy for NASH.

Identification of microRNA and analysis of target genes in Panax ginseng.

Objective: Ginsenosides, polysaccharides and phenols, the main active ingredients in Panax ginseng, are not different significantly in content between 3 and 5 years old of ginsengs called Yuan ginseng and more than ten years old ones called Shizhu ginseng. The responsible chemical compounds cannot fully explain difference in efficacy between them. According to reports in Lonicerae Japonicae Flos (Jinyinhua in Chinese) and Glycyrrhizae Radix et Rhizoma (Gancao in Chinese), microRNA may play a role in efficacy, so we identified microRNAs in P. ginseng at the different growth years and analyzed their target genes. Methods: Using high-throughput sequencing, the RNA-Seq, small RNA-Seq and degradome databases of P. ginseng were constructed. The differentially expressed microRNAs was identified by qRT-PCR. Results: A total of 63,875 unigenes and 24,154,579 small RNA clean reads were obtained from the roots of P. ginseng. From these small RNAs, 71 miRNA families were identified by bioinformatics target prediction software, including 34 conserved miRNAs, 37 non-conserved miRNA families, as well as 179 target genes of 17 known miRNAs. Through degradome sequencing and computation, we finally verified 13 targets of eight miRNAs involved in transcription, energy metabolism, biological stress and disease resistance, suggesting the significance of miRNAs in the development of P. ginseng. Consistently, major miRNA targets exhibited tissue specificity and complexity in expression patterns. Conclusion: Differential expression microRNAs were found in different growth years of ginsengs (Shizhu ginseng and Yuan ginseng), and the regulatory roles and functional annotations of miRNA targets in P. ginseng need further investigation.

[Metabonomic study of intervention effects of Morinda officinalis on 'kidney-yang deficiency syndrome'].

OBJECTIVE: To investigate the metabolic profile of hydrocortisone-induced 'Kidney-yang deficiency syndrome'in rats and the intervention effects of Morinda officinalis. METHOD: Proton nuclear magnetic resonance (1H-NMR) technique was used to analyze the rat metabonome in serum. Orthogonal partial least squares discriminant analysis (OPLS-DA) were processed to analyze the metabonome difference between the control and hydrocortisone treated samples. Twelve potential biomarkers were selected, via the parameter of variable importance in the projection (VIP). Principal components analysis (PCA) was employed to process the data from the M. officinalis. treatment group and the intervention effects of M. officinalis, was investigated through the selected potential biomarkers. RESULT: After hydrocortisone treatment, the energy metabolism, amino acids metabolism and gut microflora environment were seriously disturbed and transmethylation was surpressed. M. officinalis could effectively alleviate the disturbance of energy and amino acids metabolism and enhance transmethylation, but could not modulate the gut microflora environment. CONCLUSION: The results obtained suggested that metabonomic studies could better reflect the whole status of metabolism in bio-systems, and could be treated as a potential powerful approach in pharmacological studies and investigation of the essence of 'syndrome' in traditional Chinese medicine.

Therapeutic potential of puerarin against methionine-choline-deficient diet-induced non-alcoholic steatohepatitis determined by combination of 1H NMR spectroscopy-based metabonomics and 16S rRNA gene sequencing.

Previously published studies have revealed the protective effect of puerarin against non-alcoholic steatohepatitis (NASH), but the definite mechanism of this effect still remains unclear. The present work was an attempt to assess the beneficial effects and the underlying mechanisms of puerarin on methionine-choline-deficient (MCD) diet-induced NASH in C57BL/6 mice by using a combination of metabonomics and 16S rRNA gene sequencing technology. Nuclear magnetic resonance (NMR)-based metabonomics showed significant hepatic and urinary metabolic phenotype changes between MCD-diet fed mice and the healthy controls. A total of eight and thirteen metabolites were identified as differential metabolites associated with NASH in liver tissue and urine of mice, respectively. The proposed pathways mainly included pyrimidine metabolism, one-carbon metabolism, amino acid metabolism, glycolysis, tricarboxylic acid (TCA) cycle and synthesis and degradation of ketone bodies. Furthermore, 16S rRNA gene sequencing analysis delineated remarkable variations in gut microbiota profiles in response to MCD diet in mice and forty differential bacterial taxa related to NASH were found between the control and model group. Puerarin could improve hepatic steatosis and inflammation in NASH mice via partially ameliorating metabolic disorders and rebalancing the gut flora. Specifically, puerarin could inhibit lipopolysaccharide (LPS)-producing genus Helicobacter, and promote butyrate-producing genus Roseburia. These findings offered novel insights into the in-depth understanding of the pathogenesis of NASH and provided further evidence for the potential use of puerarin as an anti-NASH agent.

NMR-Based Metabonomic Study Reveals Intervention Effects of Polydatin on Potassium Oxonate-Induced Hyperuricemia in Rats.

Previous studies have disclosed the antihyperuricemic effect of polydatin, a natural precursor of resveratrol; however, the mechanisms of action still remain elusive. The present study was undertaken to evaluate the therapeutic effects and the underlying mechanisms of polydatin on potassium oxonate-induced hyperuricemia in rats through metabonomic technology from a holistic view. Nuclear magnetic resonance (NMR) spectroscopy was applied to capture the metabolic changes in sera and urine collected from rats induced by hyperuricemia and polydatin treatment. With multivariate data analysis, significant metabolic perturbations were observed in hyperuricemic rats compared with the healthy controls. A total of eleven and six metabolites were identified as differential metabolites related to hyperuricemia in serum and urine of rats, respectively. The proposed pathways primarily included branched-chain amino acid (BCAA) metabolism, glycolysis, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, purine metabolism, and intestinal microflora metabolism. Additionally, some metabolites indicated the risk of renal injury induced by hyperuricemia. Polydatin significantly lowered the levels of serum uric acid, creatinine, and blood urea nitrogen and alleviated the abnormal metabolic status in hyperuricemic rats by partially restoring the balance of the perturbed metabolic pathways. Our findings shed light on the understanding of the pathophysiological process of hyperuricemia and provided a reference for revealing the metabolic mechanism produced by polydatin in the treatment of hyperuricemia.

Verification of miRNAs in ginseng decoction by high-throughput sequencing and quantitative real-time PCR.

Panax ginseng C. A. Meyer is a precious traditional Chinese medicine that has been clinically used for over thousands of years. In general, ginseng needs to be prepared to ginseng decoction before taking it. MicroRNAs are a class of small (18-24 nt), single-stranded molecules that regulate gene expression at the post-transcriptional level. Considering that ginseng miRNAs may be bioactive compounds, we used Illumina high-throughput sequencing and quantitative real-time PCR (qRT-PCR) to validate the existence of miRNAs in fresh ginseng decoction which have been boiled at high temperature. Our previous studies have demonstrated that there are several miRNAs in fresh ginseng. The roots of fresh Panax ginseng were prepared according to routine methods, from which miRNAs were extracted and sequenced. A total of 43 miRNAs were identified from water decoction by Illumina high-throughput sequencing, belonging to 71 miRNA families. The target genes of these miRNAs were predicted by sequencing, and were annotated by GO, KEGG and Nr databases. The functions of these target genes mainly included plant hormone signal transduction, transcription regulation, macromolecular metabolism and auxin signaling. Nine highly expressed miRNAs (miR159, miR167, miR396, miR166, miR168, miR156, miR165, miR162 and miR394) were verified by qRT-PCR, and the results of Illumina high-throughput sequencing and qRT-PCR were consistent. Results from this study indicate that miRNAs remained stable in P. ginseng after high-temperature boiling. Additionally, Illumina high-throughput sequencing was superior in the acquisition of higher amount of small RNAs.

Aqueous and hydroalcoholic extracts of Black Maca (Lepidium meyenii) improve scopolamine-induced memory impairment in mice.

Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian hypocotyl growing exclusively between 4,000 and 4,500 m altitude in the central Peruvian Andes, particularly in Junin plateau. Previously, Black variety of Maca showed to be more beneficial than other varieties of Maca on learning and memory in ovariectomized mice on the water finding test. The present study aimed to test two different doses of aqueous (0.50 and 2.00 g/kg) and hydroalcoholic (0.25 and 1.00 g/kg) extracts of Black Maca administered for 35 days on memory impairment induced by scopolamine (1mg/kg body weight i.p.) in male mice. Memory and learning were evaluated using the water Morris maze and the step-down avoidance test. Brain acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities in brain were also determined. Both extracts of Black Maca significantly ameliorated the scopolamine-induced memory impairment as measured in both the water Morris maze and the step-down avoidance tests. Black Maca extracts inhibited AChE activity, whereas MAO activity was not affected. These results indicate that Black Maca improves scopolamine-induced memory deficits.

Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.

Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction.

Therapeutic Effects of Chinese Medicine Herb Pair, Huzhang and Guizhi, on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats Revealed by Anti-Inflammatory Assessments and NMR-Based Metabonomics.

The present study was undertaken to evaluate the therapeutic effects of Huzhang-Guizhi herb pair (HG), firstly included in Hu-Zhang Power documented in Taiping Shenghui Fang, on monosodium urate (MSU) crystals-induced gouty arthritis in rats. We found that pretreatment with HG in rats with gouty arthritis could significantly attenuate the ankle joint swelling, and this beneficial antigout effect might be mediated, at least in part, by inhibiting tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) production in synovial fluid as well as nuclear transcription factor-κB p65 (NF-κB p65) protein expression in synovial tissue. Moreover, metabonomic analysis demonstrated that 5 and 6 potential biomarkers associated with gouty arthritis in plasma and urine, respectively, which were mainly involved in energy metabolism, amino acid metabolism, and gut microbe metabolism, were identified. HG could reverse the pathological process of MSU-induced gouty arthritis through regulating the disturbed metabolic pathways. These results provided important mechanistic insights into the protective effects of HG against MSU-induced gouty arthritis in rats.

NMR-Based Metabonomic Studies on Stomach Heat and Cold Syndromes and Intervention Effects of the Corresponding Formulas.

Zuojin Wan (ZJW) and Lizhong Wan (LZW) have been widely used in the treatment of Stomach heat and cold syndrome (SH and SC), respectively. In this study, a proton nuclear magnetic resonance ((1)H NMR) based metabonomic approach was developed to profile SH and SC-related metabolic perturbations in rat serum and to investigate the intervention effects of ZJW and LZW on the corresponding SH and SC. Compared to the conventional macroscopic and histopathological examinations, the metabonomic approach could enable discrimination between SH and SC based on serum metabolic profiles. Meanwhile, 17 and 15 potential biomarkers associated with SH and SC, respectively, which were mainly involved in gastric dysfunction and mucosal lesions, gut microbiotal activity, transmethylation, glucose and lipid metabolism, and amino acid metabolism, were identified. Furthermore, taking the potential biomarkers as drug targets, it was revealed that administration of ZJW and LZW could exclusively reverse the pathological process of SH and SC, respectively, through partially regulating the disturbed metabolic pathways. This work showed biological basis related to SH and SC at metabolic level and offered a new paradigm for better understanding and explanation of "Fang Zheng Dui Ying" principle in traditional Chinese medicine from a systemic view.