Toxicity mechanism of Rhododendri Mollis Flos: based on serum metabolomics and network toxicology / 中国中药杂志

This study aims to explore the toxicity mechanism of Rhododendri Mollis Flos(RMF) based on serum metabolomics and network toxicology. The toxic effect of RMF on normal rats was evaluated according to the symptoms, serum biochemical indexes, and histopathology. Serum metabolomics was combined with multivariate statistical analysis to search endogenous differential metabolites and related metabolic pathways. The toxic components, targets, and signaling pathways of RMF were screened by network toxicology technique, and the component-target-metabolite-metabolic pathway network was established with the help of serum metabolomics. The result suggested the neurotoxicity, hepatotoxicity, and cardiotoxicity of RMF. A total of 31 differential metabolites and 10 main metabolic pathways were identified by serum metabolomics, and 11 toxic components, 332 related target genes and 141 main signaling pathways were screened out by network toxicology. Further analysis yielded 7 key toxic components: grayanotoxin Ⅲ,grayanotoxinⅠ, rhodojaponin Ⅱ, rhodojaponin Ⅴ, rhodojaponin Ⅵ, rhodojaponin Ⅶ, and kalmanol, which acted on the following 12 key targets: androgen receptor(AR), albumin(ALB), estrogen receptor β(ESR2), sex-hormone binding globulin(SHBG), type 11 hydroxysteroid(17-beta) dehydrogenase(HSD17 B11), estrogen receptor α(ESR1), retinoic X receptor-gamma(RXRG), lactate dehydrogenase type C(LDHC), Aldo-keto reductase(AKR) 1 C family member 3(AKR1 C3), ATP binding cassette subfamily B member 1(ABCB1), UDP-glucuronosyltransferase 2 B7(UGT2 B7), and glutamate-ammonia ligase(GLUL). These targets interfered with the metabolism of gamma-aminobutyric acid, estriol, testosterone, retinoic acid, 2-oxobutyric acid, and affected 4 key metabolic pathways of alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism, steroid hormone biosynthesis, and retinol metabolism. RMF exerts toxic effect on multiple systems through multiple components, targets, and pathways. Through the analysis of key toxic components, target genes, metabolites, and metabolic pathways, this study unveiled the mechanism of potential neurotoxicity, cardiotoxicity, and hepatotoxicity of RMF, which is expected to provide a clue for the basic research on toxic Chinese medicinals.

Research on influence of environment factors to yield and quality traits of Perilla frutescen / 中国中药杂志

The research is aimed to study of the influence of environmental factors on the yield and quality traits, and find out the regularity of the growth and development of perilla. The main environmental factor data in six ecological area in Guizhou province were collected, and the correlation analysis with yield and quality traits of 15 perilla strains was conducted. The results showed that the cultivation environment has significant effects on the yield and quality traits of perilla. The effect of environment on main yield composed traits, contained grain number in top spike, effective panicle number per plant, plant height, top spike length, growth period, and thousand seed weight was degressive. In the different environmental factors, the latitude showed positive correlation with yield, growth period and effective panicle number per plant, and negative correlation with top spike length and grain number in top spike. Elevation showed negative correlation with the growth period of perilla. The perilla yield increased at first and then decreased with altitude rising, with the maximum in the 800 m altitude. The 600-900 m altitude is suitable area for perilla. Except for positive correlation with the plant height, and negative correlation with top spike length, the longitude showed in apparent impact on other traits. Sunshine duration, temperature and rainfall accumulation showed different effect on the different perilla strains. For yield composed traits, the sunshine duration was negatively correlation with the plant length. The accumulated temperature and mean temperature showed negative correlation with the main spike length, the rainfall showed negative correlation with the precipitation and growth period, plant height, ear number. The environmental impact on the oil compounds decreased with oleic acid, stearic acid, linoleic acid, -linolenic acid, palmitic acid and oil content. Correlation analysis showed that the significantly negative correlation between the oil content and palmitic acid and linoleic acid content, and the positive correlation between linolenic acid content, -linolenic acid content showed significant negative correlation with other fatty acids composition, and palmitic acid, stearic acid, oleic acid, linoleic acid showed significant positive correlation with each other. The influence of different environmental factors on the quality of perilla were as follows: the oil content was positively associated with elevation and sunshine duration. -Linolenic acid content showed negative correlation with longitude, latitude, accumulated temperature and mean temperature, but positive correlation with altitude, sunlight and rainfall capacity. The correlation between palmitic acid, stearic acid, oleic acid, linoleic acid and environmental factors showed contrast character of -linolenic acid. This study detailed discussed the influence of environmental factors on the quality of perilla, which provided the foundation of ecological planting technology and geoherbalism research of perilla.

Effects of Different Concentrations of Collagenous Peptide from Fish Scales on Osteoblast Proliferation and Osteoclast Resorption.

The incidence of osteoporosis has increased among the elderly population. Establishing a model of bone remodeling for screening new drugs is critical to identify safe and effective treatments for osteoporosis. In this study, we established a platform to investigate the therapeutic effects of collagenous peptides extracted from scales of two kinds of fish, namely, sparidae and chanos. These peptides were prepared using seven concentrations of collagenous peptide: 100, 80, 60, 40, 20, 10 and 1 mg/ml. Experimental results indicated that collagenous peptides promoted the proliferation of osteoblasts and inhibited the proliferation of mature osteoclasts; the effective concentration of collagenous peptide-sparidae was 10 mg/ml and that of collagenous peptide-chanos was 40 mg/ml. These findings demonstrate that, to a certain extent, collagenous peptides extracted from fish scales can be used to prevent osteoporosis to assist bone remodeling.

The Chinese medicine nutrient diet intervention prevent against the neurologic damage induce by EMF irradiation in rat hippocampus / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the neurologic damage in rat hippocampus after electromagnetic field (EMF) acute or chronic irradiation and research the protective effects of Chinese medicine diet (CMD) which comprised ferulic acid, ginsenoside, astragalus polysaccharide and rhodiola sachalinensis.</p><p><b>METHODS</b>Eighty rats were divided into ten groups (n = 8): normal diet with shame irradiation group (NS), normal diet with chronic irradiation group (NCI), three groups of normal diet with acute irradiation after 3 h, 24 h, 72 h (NAI), Chinese medicine diet with shame irradiation group (CS), Chinese medicine diet with chronic irradiation group (CCI), three groups of Chinese medicine diet with acute irradiation after 3 h, 24 h, 72 h (CAI). The chronic EMF irradiation were performed by electromagnetic wave at 15 W/cm2 for 20 min everyday for 8 weeks continuously. The acute EMF irradiation were performed by electromagnetic wave at 65 W/cm2 for 20 min after feeding with CMD for 8 weeks. The learning and memory were evaluated by Morris water maze before/after electromagnetic wave irradiation. The apoptotic cells in hippocampus was detected by Tunel staining. The peroxidation damage of EMF and the protective effect of CMD intervention were assayed by measuring superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and reactive oxygen species (ROS).</p><p><b>RESULTS</b>The acute and chronic EMF irradiation disturbed the ability of learning and memory significantly (P < 0.05), CMD intervention markedly antagonized this effect. The apoptotic cells in hippocampus increased evidently after EMF irradiation (P < 0.05), but CMD intervention reduced the apoptotic cells. The acute and chronic EMF irradiation induced the oxidative stress by down-regulating SOD activity, GSH-Px activity, ROS inhibiting and up-regulating the content of MDA obviously (P < 0.05), and CMD intervention reduced peroxidation damage significantly (P < 0.05).</p><p><b>CONCLUSION</b>The acute and chronic EMF irradiation could initiate neurologic damage in hippocampus. CMD intervention has protective effect on the impaired learning and memory, the neuron apoptosis, the peroxidation damage induced by EMF irradiation. CMD intervention plays a significant protective role in antagonizing neurologic damage in the later stage of acute irradiation and chronic irradiation.</p>

Changes in extratemporal integrity and cognition in temporal lobe epilepsy: a diffusion tensor imaging study.

BACKGROUND: Diffusion tensor imaging (DTI) is a sensitive technique for studying cerebral white matter. Only a few studies have examined the association between changes in extratemporal integrity and cognition in temporal lobe epilepsy (TLE), especially in Chinese patients. AIM: We used DTI to characterize microstructural changes and investigate their associations with cognition in patients with temporal lobe epilepsy. PATIENTS AND METHODS: We studied 27 adult patients with TLE and 21 healthy controls. A standardized neuropsychological evaluation and diffusion tensor imaging examination were conducted on each subject. Eight patients were excluded because T2-weighted magnetic resonance imaging (MRI) results showed visible lesions. Furthermore, we determined mean diffusivity (MD) and fractional anisotropy (FA) values in the different regions of interest - normal-appearing white matter (NAWM) in the frontal lobe white matter, the occipital lobe white matter, the corpus callosum, the internal capsules, the external capsules; and normal-appearing gray matter (NAGM) in the caudate nucleus head, the putamens and the thalami. These diffusion measurements were compared between the two groups, and we examined the correlations between DTI values and clinical characteristics. In addition, multiple linear regression analysis was used to study the association of DTI values with cognitive function. RESULTS: Compared with normal controls, TLE patients demonstrated decreased FA in NAGM of both thalami and NAWM of the posterior limb of the left internal capsule (P<.01). In patients with temporal lobe epilepsy, right thalamus FA showed a tendency to correlate with age at seizure onset (ß=0.47, P=.045), and left thalamus MD showed a tendency to correlate with the duration of epilepsy (ß=0.54 P=.038). Patients with temporal lobe epilepsy showed significantly poorer performance on nearly all tasks concerning category fluency and other executive functions (P<.01). In patients with TLE, there was a positive correlation between category fluency scores and FA in the white matter of the left frontal lobe (ß=0.429, P=.041) and the right occipital lobe (ß=0.613, P=.001). CONCLUSIONS: Our results suggested that the thalamus might be a potentially important extratemporal structure involved in temporal lobe epilepsy. Moreover, a longer duration of epilepsy or an earlier age at onset may result in more abnormalities in the thalamus. Patients with temporal lobe epilepsy showed significantly poorer performance on nearly all tasks concerning category fluency and other executive functions. Our results showed that frontal lobe white matter contributed to category fluency impairment in patients with TLE, but other areas might also contribute to these impairments.

Cross-reactivity of skin rashes with current antiepileptic drugs in Chinese population.

OBJECTIVE: Due to less experience with the cross-reactivity of antiepileptic drugs (AEDs) in Chinese population, we surveyed the rates of cross- reactivity of rash among commonly used AEDs in Chinese patients with epilepsy, particularly between the traditional and the new compounds. METHODS: We have retrospectively reviewed the medical records concerning all antiepileptic drug treatment in consecutive Chinese patients with epilepsy in our center. The incidence of AED-related rash was determined in 3793 outpatients, taking at least one of the AEDs-carbamazepine (CBZ), valproic acid (VPA), phenytoin (PHT), phenobarbital (PB), clonazepam (CZP), oxcarbazepine (OXC), lamotrigine (LTG), gabapentin (GBP), topiramate (TPM), levetiracetam (LEV) and traditional Chinese medicine (TCM). We have performed telephone interviews among all patients with AEDs-related rash. We described the clinical characteristics of the 18 patients with cross-reactivity involving the AEDs, and the cross- reactivity pattern for CBZ, PHT, OXC, and LTG. RESULTS: A total of 3.61% (137/3793) of patients experienced a skin rash to at least one AEDs, of these patients, 73 (53.28%) were female and 64 were males (46.72%). While 18 patients had a rash to two or more AEDs. Of patients who had a rash to CBZ and were also prescribed PHT (n = 17), 52.9% had a rash to PHT (abbreviated as CBZ → PHT: 52.9%); of patients who had a rash to PHT and were also prescribed CBZ (n = 13), rate of rash was 69.2% (i.e., PHT → CBZ: 69.2%). Other results: CBZ → LTG: 25% (n = 16); LTG → CBZ: 44.4% (n = 9); CBZ→ OXC: 40% (n = 10); OXC → CBZ: 66.7% (n = 6); LTG → PHT: 20% (n = 5); PHT → LTG: 16.7% (n = 6); OXC → LTG: 25% (n=4); LTG → OXC: 33.3% (n = 3); OXC → PHT: 25% (n = 4); PHT → OXC: 16.7% (n = 6). There was a highly significant mutual risk for cross- reactivity for CBZ and PHT, and OXC, and LTG (p<0.001), mutual risk reached statistical significance for LTG and CBZ (p = 0.01). CONCLUSION: Cross-reactivity rates between certain AEDs are high, especially when involving carbamazepine and phenytoin. There were also too few patients with rash to reach definitely conclusions about possible cross-reactivity. Larger numbers of patients would be needed to assess this and the mechanism. Caution should be exercised when prescribing certain AEDs (especially CBZ and PHT, but also OXC, and LTG).

Cycling and Tai Chi Chuan exercises exert greater immunomodulatory effect on surface antigen expression of human hepatitis B virus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Both athletes with intensive exercise and aged people may have weakened immunity against virus infection. This study aimed to evaluate whether people undergoing aerobic exercises including competitive cyclists with moderate training (CMT) and middle-aged people practicing Tai Chi Chuan (TCC) exercise have higher immunity against hepatitis B virus than age-matched sedentary controls including college students (CSC) and middle-aged people (MSC).</p><p><b>METHODS</b>Human peripheral blood mononuclear cells from competitive cyclists and sedentary controls were stimulated by phytohemagglutinin (PHA) to prepare conditioned medium (MNC-CM) for the assessment of inhibitory effects on hepatitis B surface antigen (HBsAg) expression in human hepatoma Hep3B cells.</p><p><b>RESULTS</b>The inhibitory effects on the relative HBsAg expression of CMT's and TCC's MNC-CM were greater than those of the controls. The CMT's MNC-CM prepared from 5 microg/ml PHA decreased HBsAg expression to 61.5%, whereas that of CSC remained at 83.8%. Similarly, this expression by treatment of TCC group' MNC-CM was 68.4% whereas that of MSC group was 84.3%. The levels of cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IFN-alpha and interleukin-1beta (IL-1beta) in the MNC-CM from the CMT and TCC groups were greater than those in the controls. Antibody neutralization of CMT's MNC-CM and addition of recombinant cytokines into CSC's MNC-CM indicated that IFN-gamma, TNF-alpha and IFN-alpha had synergistic effects against HBsAg expression. Similar blocking effect was noted in TCC versus MSC groups.</p><p><b>CONCLUSION</b>These results suggest that the immunomodulatory response to suppress HBsAg expression in CMT and TCC with moderate aerobic exercise is greater than that in age-matched sedentary controls.</p>

Treatment with phytoestrogen alpha-zearalanol might protect neurons of hippocampus in ovariectomized rats.

Although neuroprotective effects of estrogen on postmenopausal women have been recognized, an associated increased incidence of uterine and breast tumors has jeopardized the clinical use of estrogen. This study was designed to evaluate the neuroprotective effects of a novel phytoestrogen alpha-zearalanol (alpha-ZAL), on ovariectomized (OVX) rats. Adult Wistar rats were ovariectomized or sham-operated and treatment with equivalent doses of 17beta-estradiol or alpha-ZAL for 5 wk. Uteruses have been weighted and stained by hematoxylin and eosin for morphology analysis. The expression of synaptophysin and parvalbumin in hippocampus were evaluated by immunohistochemistry assays. Our experiments indicated that the synaptophysin and parvalbumin-positive areas were significantly decreased in the OVX group compared to the sham group, alpha-ZAL or 17beta-estradiol administration can reverse the effects. Although alpha-ZAL and 17beta-estradiol treatments reconciled uterus weight loss which was induced by ovariectomy, the effect of alpha-ZAL was less than 17beta-estradiol. This result suggests that alpha-ZAL may effectively abate neurons loss in the hippocampus while slightly promoting weight gain of the uterus.

Effect of sinomenine on adjuvant arthritis and its mechanisms / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the anti-inflammatory mechanism of sinomenine on inflammatory media in joint of adjuvant arthritis rats.</p><p><b>METHOD</b>Rats were randomly divided into the normal group and the model group, the prednisone group, the small, medium, large of sinomenine group (30, 60, 120 mg x kg(-1)). Except for the rats in the normal group, animals were modeled to adjuvant arthritiswith freund's complete adjuvant. The arthritis index (AI) and the swelling degree of paws were recorded, and the activity of IL-1, TNF and the levels of NO, PGE2 in joint fluids of secondary arthritis were determined.</p><p><b>RESULT</b>Compared with the normal group, the activity of IL-1, TNF and the levels of NO, PGE2 in joint fluids of secondary arthritis were increased significantly in the model group (P < 0.05). Compared with the model group, it was shown to exert a dramatic inhibitory effect on secondary reaction of freund's adjuvant arthritis of rats, and the activity of IL-1, TNF and the levels of NO, PGE2 in joint fluids of secondary arthritis were significantly decreased in the sinomenine group (P < 0.05).</p><p><b>CONCLUSION</b>Sinomenine has a remarkable treatment effect on RA. It is via NO to inhibit the activity of cytokines and decrease the level of inflammation mediators, which may be one of its curing RA mechanism.</p>