Caffeic acid 3,4-dihydroxyphenethyl ester prevents colorectal cancer through inhibition of multiple cancer-promoting signal pathways in 1,2-Dimethylhydrazine/dextran sodium sulphate mouse model.

OBJECTIVE: To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) molecule, which can prevent colorectal cancer (CRC) in the 1,2-Dimethylhydrazine (DMH)/dextran sodium sulphate (DSS)-induced mouse model. METHODS: Institute of cancer research (ICR) male mice were injected with 20 mg/kg DMH for a week. After that, 2% DSS was administered in the drinking water for another 7 d. The CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their sacrifice. Histopathological examination was used for observing the CRC development at colonic mucosa. Immunohistochemistry (IHC), blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to CRC. The reversing targets searching method was applied with artificial intelligence (AI), computer-aided drug designing (CADD) and Ingenuity Pathway Analysis (IPA) techniques for predicting the potential targets and mechanism of CADPE highly related to CRC. RESULTS: The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early treatment. CADPE also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC development. Finally, our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) in two major cancer development pathways. CONCLUSIONS: CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR, ERK and mTOR activities in two highly related CRC developing pathways.

Advances in the treatment of Meige's syndrome with blepharospasm / 国际眼科杂志(Guoji Yanke Zazhi)

Meige's syndrome is a segmental craniocervical dystonia extrapyramidal disorder, which belongs to a type of adult attention deficit and hyperactivity disorder(ADHD). The cause is unknown and is commonly seen in middle-aged and elder women, and is often associated with depression, trauma, drugs, surgery and other risk factors. Blepharospasm is the earliest and most common clinical symptom of Meige's syndrome, although there is a possibility of spontaneous remission, the risk of blindness still exists. Clinically, treatment is often delayed and the prognosis is influenced due to insufficient understanding of Meige's syndrome. As the incidence of Meige syndrome increases, particularly blepharospasm in ophthalmology, a comprehensive understanding of Meige's syndrome is needed to improve the ability of ophthalmologists to treat the condition and to guide the appropriate use of clinical medication. In this paper, we review advances in the treatment of Meige's syndrome with blepharospasm and summarize the pros and cons of pharmacotherapy, surgery and traditional Chinese medicine, with a view to improving the diagnosis and treatment of this disease by ophthalmologists.

Clinical report on 5 cases of advanced malignancies with blood stasis and toxin treated by collateral disease theory.

BACKGROUND: "Collateral disease theory", as an important theory of traditional Chinese medicine, is often used in the clinical treatment of tumors, showing a remarkable effect, especially in advanced malignancies with blood stasis and toxin. METHODS: In this study, we analyzed 5 cases of advanced malignancies, and discussed the efficacy of collateral disease theory in advanced malignancies with blood stasis and toxin. The 5 cases were suffered from right lung squamous cell carcinoma, left lung squamous cell carcinoma, stage IV endometrial carcinoma, right submandibular lymphatic follicular lymphoma and right lower lung cancer, respectively. Combining with the pathogenesis of collateral disease in traditional Chinese medicine dialectically and taking insect medicine as an example, traditional Chinese medicine was prescribed. Furthermore, the application effect of "collateral disease theory" in malignancy with blood stasis and toxin was explored. RESULTS: After treated with traditional Chinese medicine, the tumor lesions in the 5 cases were reduced to varying degrees. CONCLUSION: The treatment based on "collateral disease theory" is effective for advanced malignancy with blood stasis and toxin, but this finding needs to be verified by prospective studies.

Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling.

OBJECTIVE: To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS: Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS: The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS: The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.

Neuromedin B receptor stimulation of Cav3.2 T-type Ca2+ channels in primary sensory neurons mediates peripheral pain hypersensitivity.

Background: Neuromedin B (Nmb) is implicated in the regulation of nociception of sensory neurons. However, the underlying cellular and molecular mechanisms remain unknown. Methods: Using patch clamp recording, western blot analysis, immunofluorescent labelling, enzyme-linked immunosorbent assays, adenovirus-mediated shRNA knockdown and animal behaviour tests, we studied the effects of Nmb on the sensory neuronal excitability and peripheral pain sensitivity mediated by Cav3.2 T-type channels. Results: Nmb reversibly and concentration-dependently increased T-type channel currents (IT) in small-sized trigeminal ganglion (TG) neurons through the activation of neuromedin B receptor (NmbR). This NmbR-mediated IT response was Gq protein-coupled, but independent of protein kinase C activity. Either intracellular application of the QEHA peptide or shRNA-mediated knockdown of Gß abolished the NmbR-induced IT response. Inhibition of protein kinase A (PKA) or AMP-activated protein kinase (AMPK) completely abolished the Nmb-induced IT response. Analysis of phospho-AMPK (p-AMPK) revealed that Nmb significantly activated AMPK, while AMPK inhibition prevented the Nmb-induced increase in PKA activity. In a heterologous expression system, activation of NmbR significantly enhanced the Cav3.2 channel currents, while the Cav3.1 and Cav3.3 channel currents remained unaffected. Nmb induced TG neuronal hyperexcitability and concomitantly induced mechanical and thermal hypersensitivity, both of which were attenuated by T-type channel blockade. Moreover, blockade of NmbR signalling prevented mechanical hypersensitivity in a mouse model of complete Freund's adjuvant-induced inflammatory pain, and this effect was attenuated by siRNA knockdown of Cav3.2. Conclusions: Our study reveals a novel mechanism by which NmbR stimulates Cav3.2 channels through a Gßγ-dependent AMPK/PKA pathway. In mouse models, this mechanism appears to drive the hyperexcitability of TG neurons and induce pain hypersensitivity.

[Retracted] In vitro antitumor activity of the ethyl acetate extract Potentilla chinensis in osteosarcoma cancer cells.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that several figures bore striking similarities to other papers that were published at around the same time written by different authors based in different research institutions. Fig. 3 (in colour) was essentially the same as a greyscale figure (Fig. 4) in a paper published in Oncology Reports, which has now been retracted [Wan G, Tao J­G, Wang G­D, Liu S­P, Zhao H­X and Liang Q­D: 3­ß­Εrythrodiol isolated from Conyza canadensis inhibits MKN­45 human gastric cancer cell proliferation by inducing apoptosis, cell cycle arrest, DNA fragmentation, ROS generation and reduces tumor weight and volume in mouse xenograft mode. Oncol Rep 35: 2328­2338, 2016]. Furthermore, Figs. 5 and 6 in the above paper appeared to share data with Figs. 7 and 11, respectively, in a paper published in Phytomedicine [Sui C­G, Meng F­D and Jiang Y­h: Antiproliferative activity of rosamultic acid is associated with induction of apoptosis, cell cycle arrest, inhibition of cell migration and caspase activation in human gastric cancer (SGC­7901) cells. Phyomedicine 22: 796­806, 2015]. After having conducted an independent investigation in the Editorial Office, the Editor of Molecular Medicine Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in Molecular Medicine Reports 14: 3634­3640, 2016; DOI: 10.3892/mmr.2016.5679].

Proteomic changes in the hippocampus and motor cortex in a rat model of cerebral palsy: Effects of topical treatment.

Cerebral palsy (CP) is a non-progressive motor-impairment disorder related to brain injury early in development. To gain new insights into the mechanisms of CP and the therapeutic efficacy of Baimai ointment, we used a high-throughput quantitative proteomic approach to evaluate proteomic changes in the hippocampus and motor cortex in a rat model of CP induced by lipopolysaccharide (LPS) combined with hypoxia/ischemia (H/I). More than 2000 proteins were identified in each brain region with high confidence. Quantitative analysis demonstrated profound disturbances in the proteomes of the hippocampus and motor cortex after LPS + H/I, in addition to the disruption of the motor system. In contrast, the topical application of Baimai ointment not only alleviated the motor deficit in the CP model rats, but also restored the proteomes in the brain cortex. Furthermore, astrocytes in the hippocampus were strongly activated in the Baimai-treated CP rat brains, associated with an increase in neurotrophic factors. Proteomic analysis demonstrated that the CP model induced neuroinflammatory responses in the brain which were reversed by the topical application of Baimai ointment. This study highlights the unexpected roles of hippocampus and motor cortex neurons in CP progress and treatment, thus providing potentially novel therapeutic targets for CP.

Increased antitumor efficacy of ginsenoside Rh2 via mixed micelles: in vivo and in vitro evaluation.

The aim of this work is to apply Solutol® HS15 and TPGS to prepare self-assembled micelles loading with ginsenoside Rh2 to increase the solubility of ginsenoside Rh2, hence, improving the antitumor efficacy. Ginsenoside Rh2-mixed micelles (Rh2-M) were prepared by thin film dispersion method. The optimal Rh2-M was characterized by particle size, morphology, and drug encapsulation efficiency. The enhancement of in vivo anti-tumor efficacy of Rh2-M was evaluated by nude mice bearing tumor model. The solubility of Rh2 in self-assembled micelles was increased approximately 150-folds compared to free Rh2. In vitro results demonstrated that the particle size of Rh2-M is 74.72 ± 2.63 nm(PDI = 0.147 ± 0.15), and the morphology of Rh2-M is spherical or spheroid, and the EE% and LE% are 95.27 ± 1.26% and 7.68 ± 1.34%, respectively. The results of in vitro cell uptake and in vivo imaging showed that Rh2-M could not only increase the cell uptake of drugs, but also transport drug to tumor sites, prolonging the retention time. In vitro cytotoxicity and in vivo antitumor results showed that the anti-tumor effect of Rh2 can be effectively improved by Rh2-M. Therefore, Solutol® HS15 and TPGS could be used to entrapping Rh2 into micelles, enhancing solubility and antitumor efficacy.

Taurine suppresses ROS-dependent autophagy via activating Akt/mTOR signaling pathway in calcium oxalate crystals-induced renal tubular epithelial cell injury.

Oxidative stress and autophagy are the key promoters of calcium oxalate (CaOx) nephrolithiasis. Taurine is an antioxidant that plays a protective role in the pathogenesis of kidney disease. Previous studies found that taurine suppressed cellular oxidative stress, and inhibited autophagy activation. However, the effect of taurine on CaOx kidney stone formation remains unknown. In the present work, we explored the regulatory effects of taurine on CaOx crystals-induced HK-2 cell injury. Results showed that pretreatment with taurine significantly enhanced the viability of HK-2 cells and ameliorated kidney tissue injury induced by CaOx crystals. Taurine also markedly reduced the levels of inflammatory cytokines, apoptosis, and CaOx crystals deposition. Furthermore, we observed that taurine supplementation alleviated CaOx crystals-induced autophagy. Mechanism studies showed that taurine reduced oxidative stress via increasing SOD activity, reducing MDA concentration, alleviating mitochondrial oxidative injury, and decreasing the production of intracellular ROS. Taurine treatment also effectively activated Akt/mTOR signaling pathway in CaOx crystals-induced HK-2 cells both in vitro and in vivo. In summary, the current study shows that taurine inhibits ROS-dependent autophagy via activating Akt/mTOR signaling pathway in CaOx crystals-induced HK-2 cell and kidney injury, suggesting that taurine may serve as an effective therapeutic agent for the treatment of CaOx nephrolithiasis.

Natural products action on pathogenic cues in autoimmunity: Efficacy in systemic lupus erythematosus and rheumatoid arthritis as compared to classical treatments.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by self-perpetuating inflammation and tissue/organ damage, resulting from the failure of lymphocyte auto-tolerance, cause morbidity and mortality worldwide. The current drugs or therapies including conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), as well as several biologic therapies such as B cell-targeted, T cell-targeted, cytokines-targeted and cytokines receptors-targeted therapy, cannot completely cure SLE and RA, and are always accompanied by unexpected side effects. Therefore, more studies have explored new methods for therapy and found that the herbal medicine as well as its natural products (NPs) exhibited promising therapeutic value through exerting effects of immunomodulation, anti-inflammation, anti-oxidation, and anti-apoptosis, etc. via regulating abnormal responses in kidney, innate and adaptive immune systems, intestine, synoviocytes, as well as bone system including chondrocytes, osteoclasts, joints and paw tissues. In the present review, we will elucidate the current mainstream drugs and therapies for SLE and RA, and summarize the efficacy and mechanisms of NPs in the treatment of SLE and RA based on available findings including in vitro and in vivo animal models, as well as clinical studies, and further analyze the existing challenges, in order to provide comprehensive evidence for improvement of SLE and RA therapy by NPs and to promote management of these two autoimmune diseases.

Multi-functional nanocomplex codelivery of Trp2 and R837 to activate melanoma-specific immunity.

Antigen-adjuvant combination could induce a protective and long-lasting anti-tumor immune response. However, exploiting system which could co-deliver melanoma antigen peptide Trp2 (Tyrosinase-related protein 2) and Toll-like-receptor-7 (TLR7) agonists imiquimod (R837) both are poor aqueous solubility is still challenging. Our new nanocomplex was explored for specific delivery of Trp2 and R837 into antigen-presenting cells (APCs). R837 was loaded into mannosylated-ß-cyclodextrin (Man-CD) to target dendritic cells (DCs) by binding mannose receptors (MR) on DCs. A fusion peptide (WT) was constructed by incorporating the amino acid region of TAT (cell-penetrating peptide) into Trp2 to improve the TAT-mediated intracellular efficiency. Negatively charged sodium alginate (SA), a biocompatible polymer, which can induce adjuvant responses by affecting the functions of DCs, was complexed with Man-CD/R837 and WT via physical adsorption. The optimized nanocomplex promoted the cellular uptake and showed remarkable efficacy to enhance the secreting of Th1-cytokines. This multi-functional nanocomplex system may allow effective targeting-codelivery of multi-hydrophobic drugs and be a promising subunit vaccine candidate as a potential prevention action of tumor.

Current status and dilemmas for early fluid resuscitation strategy in treating acute pancreatitis: a perspective from the integrated Chinese and Western medicine / 中华胰腺病杂志

Fluid resuscitation is an important support for the early treatment of acute pancreatitis. However, the timing, volume and type of fluid, the goal of fluid resuscitation and other related issues remain unanswered. A dilemma on under- and over-resuscitation is often encountered in clinical practice. This paper summarized the recent advances on early fluid resuscitation in acute pancreatitis and proposed an early fluid resuscitation strategy of " three stages and two steps" for acute pancreatitis from a perspective of the relationship and the corresponding changes between Qi and Xue based on the Qi-Xue-Jin-Ye theory of traditional Chinese medicine by integrating the Chinese and Western medicine thoughts, which could provide some insights into optimizing the current strategy.

Evaluation on the rationality of "Sandwich principle teaching mode" for internal medicine / 中华医学教育探索杂志

Objective:To evaluate the rationality of the "Sandwich Principle teaching mode" adopted in our teaching of internal medicine and verify the necessity of its "Intergroup intersecting discussion".Methods:33 students majoring in traditional Chinese medicine were divided into control group (taught by standard process of sandwich principle) and experiment group (taught by simplified process of sandwich principle). The Dundee Ready Education Environment Measure (DREEM) was used to evaluate students' feelings toward the two teaching modes.Results:The total score of DREEM in the control group was higher than that in the experiment group, with statistically significant difference; the total score in the academic perception subscale in the control group was higher than that in the experiment group, among which the scores of "I have faith in passing the exam this year" and other 2 items were better than that in the experiment group, with statistically significant difference ( P<0.05); there were no statistical difference in the total scores of other perception subscales between the two groups( P>0.05), but the scores of the 9 items including "the atmosphere is very harmonious in the clinical teaching process" in the control group were significantly better than those in the experiment group, with statistically significant difference( P<0.05). Conclusion:The teaching mode of Sandwich Principle can create a positive and effective learning environment for supporting students. "Intergroup intersecting discussion" can encourage students to actively participate in the teaching process, and help increase their academic confidence and sense of achievement in learning. It is also helpful to build a harmonious teacher-student relationship and create a relaxing and pleasant learning environment so that students can gain a better learning experience. Therefore, "Intergroup intersecting discussion" is indispensable in medical teaching.

Efficacy evaluation of Qingyan formulation in a smoking environment and screening of anti-inflammatory compounds.

Qingyan formulation (QF) is a common preparation that is often used to control inflammation in the haze environment. However, the efficacy and effective constituents of QF are still uncertain and difficult to identify. This paper aims to evaluate the efficacy by simulating a haze environment and determine its anti-inflammatory compounds by UPLC/Q-TOF-MS/MS combing with bioactivity screening. The therapeutic effect of QF in the simulated haze environment was confirmed from the aspects of lung histomorphology and inflammatory factor expression levels. QF showed strong anti-inflammatory activity with the minimum effective concentration reaching 1.5 g/kg. Potential anti-inflammatory components were screened by the NF-κB activity assay system and simultaneously identified based on mass spectral data. Then, the potential active compounds were verified by molecular biological methods, the minimum effective concentration can reach 0.1 mg/L. Six structural types of NF-κB inhibitors (phenolic acid, scopolamine, hydroxycinnamic acid, flavonoid, dihydroflavone and steroid) were identified. Further cytokine assays confirmed their potential anti-inflammatory effects of NF-κB inhibitors. This strategy clearly demonstrates that QF has a significant therapeutic effect on respiratory diseases caused by haze, so it is necessary to promote its commercialization and wider application.

UPLC-Q-TOF/MS-based metabolic profiling comparison of four major bioactive components in normal and CKD rat plasma, urine and feces following oral administration of Cornus officinalis Sieb and Rehmannia glutinosa Libosch herb couple extract.

Cornus officinalis-Rehmannia glutinosa herb couple is widely used herb medicine in clinical practice to treat chronic kidney disease (CKD). However, the in vivo integrated metabolism of its main bioactive components in CKD rats remains unknown. In this study, UPLC-Q-TOF/MS technique combined with Metabolynx™ software, was developed and successfully applied for analysis of metabolic profiles of the bioactive components of the herb couple in normal and CKD rat biological samples. Main parent components of the herb couple extract such as loganin, morroniside and catalpol were absorbed into the blood circulation of the normal and CKD rats. Another parent component acteoside was almost completely degraded. Seventeen metabolites involved in the in vivo metabolism processes were tentatively identified. These metabolites indicated that loganin was mainly metabolized to the demethylated product, and morroniside was firstly deglycosylated to the aglycone and the latter was subsequently demethylated and acetylated. Additionally, hydrogenation and deglycosylation were the principal metabolic reactions of catalpol; while O-glucuronide and O-sulphate conjugates were observed as major metabolites for methylated caffeic acid and hydroxytyrosol released from acteoside. Compared with the normal group, the CKD rat showed lower conversion capability. Few kinds and minor amounts of the metabolites appeared in the CKD rat samples. While considerable amounts of the parent compounds were detected in the CKD plasma. This will help maintain a high blood drug concentration which might be beneficial for the treatment of CKD. The proposed method could develop an integrated template approach to analyze screening and identification of the bioactive components in plasma, urine and feces after oral administration of herb medicines. Additionally, this investigation might provide helpful chemical information for further pharmacology and active mechanism research on herb medicines.

Melatonin-mediated inhibition of Cav3.2 T-type Ca2+ channels induces sensory neuronal hypoexcitability through the novel protein kinase C-eta isoform.

Recent studies implicate melatonin in the antinociceptive activity of sensory neurons. However, the underlying mechanisms are still largely unknown. Here, we identify a critical role of melatonin in functionally regulating Cav3.2 T-type Ca2+ channels (T-type channel) in trigeminal ganglion (TG) neurons. Melatonin inhibited T-type channels in small TG neurons via the melatonin receptor 2 (MT2 receptor) and a pertussis toxin-sensitive G-protein pathway. Immunoprecipitation analyses revealed that the intracellular subunit of the MT2 receptor coprecipitated with Gαo . Both shRNA-mediated knockdown of Gαo and intracellular application of QEHA peptide abolished the inhibitory effects of melatonin. Protein kinase C (PKC) antagonists abolished the melatonin-induced T-type channel response, whereas inhibition of conventional PKC isoforms elicited no effect. Furthermore, application of melatonin increased membrane abundance of PKC-eta (PKCη ) while antagonism of PKCη or shRNA targeting PKCη prevented the melatonin-mediated effects. In a heterologous expression system, activation of MT2 receptor strongly inhibited Cav3.2 T-type channel currents but had no effect on Cav3.1 and Cav3.3 current amplitudes. The selective Cav3.2 response was PKCη dependent and was accompanied by a negative shift in the steady-state inactivation curve. Furthermore, melatonin decreased the action potential firing rate of small TG neurons and attenuated the mechanical hypersensitivity in a mouse model of complete Freund's adjuvant-induced inflammatory pain. These actions were inhibited by T-type channel blockade. Together, our results demonstrated that melatonin inhibits Cav3.2 T-type channel activity through the MT2 receptor coupled to novel Gßγ -mediated PKCη signaling, subsequently decreasing the membrane excitability of TG neurons and pain hypersensitivity in mice.

Comparative metabolism of two major compounds in Fructus Corni extracts by gut microflora from normal and chronic nephropathy rats in vitro by UPLC-Q-TOF/MS.

Herbal medicines are widely used as therapeutic products in many countries. Fructus Corni, a traditional herb medicine, has been clinically used to cure chronic nephropathy for thousands of years. It could be converted by gut microflora in vivo to shape its pharmacological profiles. Thus, metabolic profiles of major active constituents in Fructus Corni extracts by gut microflora from rats in healthy and nephropathy state were firstly investigated in vitro by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) in this study. According to the features of protonated ions, five metabolites (M1, M2, M3, M5 and M6) were found and preliminarily authenticated. Intestinal bacteria were capable of converting N0 (loganin) to its aglycone M1 (loganetin). The latter was further hydrogenated to the corresponding M2 (hydrogenated loganetin) and subsequently to M3 (hydrogenated and demethylated loganetin) by demethylation; While M5 (demethylated morronisid aglycone) and M6 (dehydroxylated morronisid aglycone) were identified as the two metabolites of N4 (morronisid) through demethylation and dehydroxylation. Gut microflora from healthy and nephropathy rats could degrade loganin and morronisid to the above metabolites. However, healthy rat intestinal bacteria showed more powerful degradation and much more amounts of M1 and M6 were obtained in their samples. Additionally, this work demonstrated that UPLC-Q-TOF/MS approach connected with MetaboLynx™ analysis software was rapid and reliable for screening and authentication of natural product metabolites.

Advantages of Chinese Medicine for Patients with Acquired Immunodeficiency Syndrome in Rural Central China / 中国结合医学杂志

OBJECTIVE@#To analyze the effect of Chinese medicine (CM) on mortality and quality of life (QOL) of acquired immunodefificiency syndrome (AIDS) patients treated with combined antiretroviral therapy (cART).@*METHODS@#A random sample of AIDS patients enrolled in the National Chinese Medicine Treatment Trial Program (NCMTP) that met the inclusion criteria was included in this study. NCMTP patients were included as the CM+cART group, and those not in the NCMTP were included as the cART group. Survival from September 2004 to September 2012 was analyzed by retrospective cohort study. QOL was analyzed by cross-sectional study.@*RESULTS@#The retrospective cohort study included 528 AIDS patients, 322 in the CM+cART group and 206 in the cART group. After 8 years, the mortality in the CM+cART group was 3.3/100 person-years, which was lower than the cART group of 5.3/100 person-years (P<0.05). The hazard ratio (HR) for mortality in the cART group was 1.6 times that of the CM+cART group by Cox proportional hazard model analysis. After controlling for gender, age, marital status, education, and CD4 T-cell count, the HR was 1.9 times higher in the cART group compared with the CM+cART group (P<0.05). The cross-sectional study investigated 275 AIDS patients. The mean scores of all QOL domains except spirituality/personal beliefs were higher in the CM+cART group than in the cART group (P<0.05).@*CONCLUSIONS@#For AIDS patients, CM could help to prolong life, decrease mortality, and improve QOL. However, there were limitations in the study, so prospective studies should be carried out to confifirm our primary results.

Characterization and immunomodulatory activity of polysaccharides from the stems and leaves of Abelmoschus manihot and a sulfated derivative.

BACKGROUND: Abelmoschus manihot (Linn.) Medicus is a traditional herbal medicine whose flowers, stems and leaves exhibit widely pharmacological activities. However, only the flowers have long been used as medicine while the stems and leaves were mainly discarded and burned, which undoubtedly caused enormous waste of these resources and serious environment pollution. Many researches have indicated that bioactivities of polysaccharides were significantly improved after sulfation. The aim of this study was to investigate the characterization and immunomodulatory activity of polysaccharides from stems and leaves of A. manihot and a sulfated derivative. RESULTS: A mixed neutral polysaccharide (SLAMP-a) and two acidic polysaccharides (SLAMP-c and SLAMP-d) were obtained from stems and leaves of A. manihot by DEAE-cellulose chromatography. SLAMP-a was a water-insoluble mixture while its sulfated derivative (S-SLAMP-a3), prepared with aminosulfonic acid, was a homogeneous polysaccharide with excellent solubility. The average molecular weights of S-SLAMP-a3, SLAMP-c and SLAMP-d were 1044.2kDa, 477.8kDa and 264.2kDa respectively. SLAMP-a and its sulfate mainly contained glucose, and SLAMP-c and SLAMP-d were both composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro study indicated that S-SLAMP-a3, SLAMP-c and SLAMP-d exhibited significant immunomodulatory activity, while SLAMP-a showed little effects. CONCLUSION: SLAMP-c and SLAMP-d from A. manihot stems and leaves could be explored as immunomodulatory agents, which would provide a way to utilize these enormously discarded resources and avoid massive waste. Additionally, the neutral polysaccharide, SLAMP-a, could also be developed after sulfation, suggesting that these disused resources would be further used effectively.

Comparative pharmacokinetics of six major bioactive components in normal and type 2 diabetic rats after oral administration of Sanhuang Xiexin Decoction extracts by UPLC-TQ MS/MS.

A rapid, sensitive, and selective UPLC-TQ-MS/MS method was established and validated for the determination and pharmacokinetic investigation of rhein, coptisine, berberine, palmatine, baicalin and wogonoside from Sanhuang Xiexin Decoction (SXD) extracts. A Waters BEH C18 UPLC column was used with the mobile phases of Acetonitrile-0.1% formic acid-water. The lower limits of quantification (LLOQ) for rhein, coptisine, berberine, palmatine, baicalin and wogonoside were 24.16, 0.72, 0.68, 0.53, 18.07 and 28.56ng/mL, respectively. All calibration curves displayed good linearity (r2>0.995). The precision was evaluated by intra-day and inter-day assays and the RSD% were all within 9.12%, and the bias of the accuracies ranged from -7.50% to 8.03%. The recovery ranged from 74.83% to 94.32% and the matrix effects of six analytes were found to be between 90.17% and 103.10%. The stability study showed that compounds were stable during the experiment. Finally, the data showed that the pharmacokinetic (PK) profiles (especially AUC, Tmax and Cmax) of six analytes in diabetic rats were significantly diverse from that in normal group rats. The PK study under the pathological condition could provide more helpful information to guide the clinical usage of SXD to treat T2DM.