Yuanfu Lu

Zunyi Medical University, Tsun-i-ch’eng, Guizhou Sheng, China

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Publications (8)15.12 Total impact

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    ABSTRACT: Neurofibrillary tangles, one of the characteristic pathological features of Alzheimer's disease (AD), are composed of paired helical filaments mainly with hyperphosphorylated tau protein. Inhibition of the hyperphosphorylation of tau protein is an effective therapy for AD. The current study was designed to investigate the protective effects of alkaloids enriched extract from Dendrobium Nobile Lindl. (EDNLA), a Chinese medicinal herb, on hyperphosphorylation of tau protein in AD brain. Rats were administrated intragastrically with different doses of DNLA (20, 40mg/kg) every 8h for one day, followed by lipopolysaccharide (LPS, 100μg) injecting into the bilateral ventricle. Two hours later, the hippocampi of each group were collected to examine the hyperphosphorylated tau protein by western blotting. Additional rats were treated by EDNLA thrice daily for one week, to examine the effects on LPS-induced apoptosis in the brain. LPS injection significantly increased the expression of hyperphosphorylated tau protein at Ser396, Ser199-202, Ser404, Thr231, Thr205 sites and GSK-3β increased, LPS also induced apoptosis in the brain. EDNLA dramatically ameliorated these abnormal changes (P<0.05). The present study demonstrated that EDNLA attenuates LPS-induced hyperphosphorylation of tau protein in rat's hippocampus and protects against LPS-induced apoptosis in rat brain.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 11/2013; · 2.97 Impact Factor
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    ABSTRACT: BACKGROUND: Metallothionein (MT) is a small, cysteine-rich, metal-binding protein that plays an important role in protecting against toxicity of heavy metal and chemicals. This study was aimed to define diurnal and sex variation of MT in mice. METHODS: Adult mice were maintained in light- and temperature-controlled facilities for 2 weeks with light on at 8:00 and light off at 20:00. The blood, liver, and kidneys were collected every 4 h during the 24 h period. Total RNA was isolated, purified, and subjected to real-time RT-PCR analysis and MT protein was determined by western blot and the Cd/hemoglobin assay. RESULTS: The diurnal variations in mRNA levels of MT-1 and MT-2 in liver were dramatic, up to a 40-fold peak/trough ratio. MT mRNA levels in kidneys and blood also showed diurnal variation, up to 5-fold peak/trough ratio. The diurnal variation of MT mRNAs resembled the clock gene albumin site D-binding protein (Dbp), and was anti-phase to the clock gene Brain and Muscle ARNT-like Protein 1 (Bmal1) in liver and kidneys. The peaks of MT mRNA levels were higher in females than in males. Hepatic MT protein followed a similar pattern, with about a 3-fold difference. CONCLUSION: MT mRNA levels and protein showed diurnal- and sex-variation in liver, kidney, and blood of mice, which could impact the body defense against toxic stimuli.
    Journal of Circadian Rhythms 07/2012; 10(1):5.
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    ABSTRACT: Neuroinflammation is closely associated with the pathogenesis of neurological disorders. The hallmark of neuroinflammation is considered to be microglial activation. Therefore, inhibition of microglial activation might hold a promising therapy for neurological disorders. Resveratrol, a natural non-flavonoid polyphenol found in grapes and red wine, has been recognized as a bioactive agent with potential benefit for health. Several lines of evidence show that resveratrol could exert neuroprotection against ischemia, seizure, and neurodegenerative diseases. However, the mechanisms underlying its beneficial neuroprotective effects are poorly defined. Here, by using rat primary cortical neuron-glia cultures, results showed that resveratrol attenuated lipopolysaccharide (LPS)-induced cortical neurotoxicity. Further studies revealed that microglia were responsible for resveratrol-mediated neuroprotection. Resveratrol significantly inhibited LPS-induced microglial activation and subsequent production of multiple pro-inflammatory and cytotoxic factors such as tumor necrosis factor-α, nitric oxide, and interleukin-1β. Collectively, resveratrol produced neuroprotection against microglia-induced neurotoxicity. Thus, resveratrol might represent a potential benefit for the treatment of inflammation-related neurological disorders. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 05/2012; · 2.40 Impact Factor
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    ABSTRACT: This study was aimed to examine circadian variations of hepatic antioxidant components, including the Nrf2- pathway, the glutathione (GSH) system, antioxidant enzymes and metallothionein in mouse liver. Adult mice were housed in light- and temperature-controlled facilities for 2 weeks, and livers were collected every 4 h during the 24 h period. Total RNA was isolated, purified, and subjected to real-time RT-PCR analysis. Hepatic mRNA levels of Nrf2, Keap1, Nqo1 and Gclc were higher in the light-phase than the dark-phase, and were female-predominant. Hepatic GSH presented marked circadian fluctuations, along with glutathione S-transferases (GST-α1, GST-µ, GST-π) and glutathione peroxidase (GPx1). The expressions of GPx1, GST-µ and GST-π mRNA were also higher in females. Antioxidant enzymes Cu/Zn superoxide dismutase (Sod1), catalase (CAT), cyclooxygenase-2 (Cox-2) and heme oxygenase-1 (Ho-1) showed circadian rhythms, with higher expressions of Cox-2 and CAT in females. Metallothionein, a small non-enzymatic antioxidant protein, showed dramatic circadian variation in males, but higher expression in females. The circadian variations of the clock gene Brain and Muscle Arnt-like Protein-1(Bmal1), albumin site D-binding protein (Dbp), nuclear receptor Rev-Erbα (Nr1d1), period protein (Per1 and Per2) and cryptochrome 1(Cry1) were in agreement with the literature. Furthermore, acetaminophen hepatotoxicity is more severe when administered in the afternoon when hepatic GSH was lowest. Circadian variations and gender differences in transcript levels of antioxidant genes exist in mouse liver, which could affect body responses to oxidative stress at different times of the day.
    PLoS ONE 01/2012; 7(8):e44237. · 3.53 Impact Factor
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    ABSTRACT: Wan-Sheng-Hua-Feng-Dan (WSHFD) is a traditional Chinese medicine used for the treatment of neurological disorders. Cinnabar (HgS) and realgar (As(4)S(4)) are included in WSHFD. Are they remedies or poisons? To investigate the role of cinnabar and realgar in the protective effects of WSHFD on lipopolysaccharide (LPS)-induced neurotoxicity. Rat primary midbrain neuron-glia cultures were used to explore the effects of WSHFD on LPS-induced dopamine (DA) neurodegeneration. The experiment was randomly divided into control, LPS, LPS+removed (cinnabar and realgar in WSHFD were removed), LPS+reduced (cinnabar and realgar in WSHFD were reduced by 65%) and LPS+original (10% cinnabar and 10% realgar in WSHFD) groups. Dopaminergic neurotoxicity was assessed by [(3)H]DA uptake assay and the quantification of tyrosine hydroxylase (TH)-positive neurons. Microglial activation was evaluated using an anti-OX-42 antibody. The release of intracellular reactive oxygen species (ROS) was quantified via the DCFH-DA probe. The transcripts and production of pro-inflammatory factors were examined by real-time RT-PCR analysis and ELISA, respectively. WSHFD (original) significantly attenuated LPS-induced decrease of DA uptake capacity and TH-positive neuron number, inhibited microglial activation, decreased LPS-induced ROS production, ameliorated LPS-induced elevations of the mRNA expressions of TNFα, iNOS, IL-1β and COX-2 and the subsequent production of TNFα, NO, IL-1β and PGE(2) in neuron-glia cultures. However, WSHFD (removed) and (reduced) failed to protect against LPS-induced neurotoxicity. Cinnabar and realgar were active ingredients of WSHFD in producing protective effects against LPS-induced neurotoxicity.
    Journal of ethnopharmacology 12/2011; 139(3):822-8. · 2.32 Impact Factor
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    ABSTRACT: Realgar (90% of AS4S4) and cinnabar (96% of HgS) have been used in traditional Chinese medicines for thousands of years. Both arsenic and mercury are well-known for toxic effects and the safety of realgar-and cinnabar-containing traditional Chinese medicines is of concern. It is considered that any intentional use of known toxic metals in medicine is an unacceptable risk, while an opposing opinion presumes that realgar and cinnabar have clear pharmacological action with tolerable side effects. This review summarized the progress of toxicological study on realgar-and cinnbar-containing traditional Chinese medicines.
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 12/2011; 36(24):3402-5.
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    ABSTRACT: To determine the effects of Angong Niuhuang pill (AGNHW) on lipopolysaccharide (LPS)-induced neuroinflammation and further to investigate the role of realgar and cinnabar on AGNHW-mediated neuroprotection. Primary rat midbrain neuron-glia cultures were used as an in vitro model to examine the effects of AGNHW on LPS-induced dopamine (DA) neuronal damage. Cultures were divided randomly into five groups: control, LPS, LPS plus AGNHW, LPS plus realgar and LPS plus cinnabar. Dopaminergic neurotoxicity was measured by [3H] DA uptake assay. The production of intracellular reactive oxygen species (ROS) was quantified via the DCFH-DA probe. Real-time RT-PCR was applied to detect the mRNA expression of pro-inflammatory factors. Then the protein levels of these factors were determined by ELISA and western blot assay. Compared with the control group, LPS apparently decreased DA uptake capacity (P < 0.05); induced the production of intracellular ROS (P < 0.05); enhanced the mRNA expression of TNF-alpha, iNOS, IL-13 and COX-2 (P < 0.05) and the release of TNF-alpha, IL-1beta and PGE2 in the supernatant of cultures (P < 0.05); and also increased the level of iNOS protein (P < 0.05). Compared with the LPS group, AGNHW and realgar significantly inhibited LPS-induced reduction of DA uptake (P < 0.05); attenuated the production of intracellular ROS (P < 0.05) and the mRNA expression of TNF-alpha, iNOS, IL-1beta and COX-2 (P < 0.05) and the release of TNF-alpha, IL-1beta and PGE2 (P < 0.05) and the level of iNOS protein (P < 0.05). However, there was no significant difference between LPS group and LPS plus cinnabar group. AGNHW is effective in protecting against LPS-induced neuroinflammation, and realgar is one of active components for AGNHW to produce anti-inflammatory effects.
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 12/2010; 35(24):3333-8.
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    ABSTRACT: Mineral arsenicals have long been used in traditional medicines for various diseases, yet arsenic can be highly toxic and carcinogenic. Arsenic in traditional medicines typically comes from deliberate addition for therapeutic purposes, mainly in the form of mineral arsenicals, including orpiment (As2S3), realgar (As4S4), and arsenolite (contains arsenic trioxide, As2O3). Inorganic arsenic is now accepted in Western medicine as a first line chemotherapeutic agent against certain hematopoietic cancers. This perspective analyzes the pharmacology and toxicology of these arsenicals used in traditional medicines. Orpiment and realgar are less soluble and poorly absorbed from the gastrointestinal tract, whereas the bioavailability of arsenic trioxide is similar to inorganic arsenic salts such as sodium arsenite. Pharmacological studies show that arsenic trioxide and realgar are effective against certain malignancies. Orpiment and realgar are used externally for various skin diseases. Realgar is frequently included as an ingredient in oral traditional remedies for its antipyretic, anti-inflammatory, antiulcer, anti-convulsive, and anti-schistosomiasis actions, but the pharmacological basis for this inclusion still remains to be fully justified. Toxicological studies show that cardiovascular toxicity is the major concern for arsenic trioxide and that the gastrointestinal and dermal adverse effects may occur after prolonged use of mineral arsenicals. Little is known regarding the possible secondary cancers resulting from the long-term use of any of these arsenicals. Similar to the safety evaluation of seafood arsenicals, total arsenic content alone appears to be insufficient for mineral arsenical safety evaluation. Arsenic speciation, bioavailability, and toxicity/benefit should be considered in evaluation of mineral arsenical-containing traditional medicines.
    Journal of Pharmacology and Experimental Therapeutics 09/2008; 326(2):363-8. · 3.89 Impact Factor