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Biomedical subjects

Sabina Lim

Publications and source records attributed to Sabina Lim.

8 recordsLinked to original sources

Acupuncture increases neuropeptide Y expression in hippocampus of maternally-separated rats.

Maternal separation (MS) is a risk factor in the development of mood-related disorders such as depression. Human and animal studies support the involvement of neuropeptide Y (NPY) in the pathology of depression. To investigate the effect of acupuncture on depression-like behavior and examine changes in NPY expression associated with MS, we observed body weight and locomotor activity, and performed NPY immunohistochemistry in the hippocampus. MS for 7 days beginning on postnatal day 14 induced a significant decrease in body weight and locomotion, while acupuncture treatment at acupoint Shenmen (HT7) resulted in a significant increase in both. NPY-immunoreactive cells in area CA1 and the dentate gyrus were decreased in the MS group, but significantly increased in the acupuncture group. These findings suggest that acupuncture has an effect on the depression-like disorder caused by MS, possibly by modulating NPY expression in the hippocampus.

Acupuncture↗

Cytochrome P450 2C8 and CYP3A4/5 are involved in chloroquine metabolism in human liver microsomes.

Chloroquine has been used for many decades in the prophylaxis and treatment of malaria. It is metabolized in humans through the N-dealkylation pathway, to desethylchloroquine (DCQ) and bisdesethylchloroquine (BDCQ), by cytochrome P450 (CYP). However, until recently, no data are available on the metabolic pathway of chloroquine. Therefore, the metabolic pathway of chloroquine was evaluated using human liver microsomes and cDNA-expressed CYPs. Chloroquine is mainly metabolized to DCQ, and its Eadie-Hofstee plots were biphasic, indicating the involvement of multiple enzymes, with apparent Km and Vmax values of 0.21 mM and 1.02 nmol/min/mg protein 3.43 mM and 10.47 nmol/min/mg protein for high and low affinity components, respectively. Of the cDNA-expressing CYPs examined, CYP1A2, 2C8, 2C19, 2D6 and 3A4/5 exhibited significant DCQ formation. A study using chemical inhibitors showed only quercetin (a CYP2C8 inhibitor) and ketoconazole (a CYP3A4/5 inhibitor) inhibited the DCQ formation. In addition, the DCQ formation significantly correlated with the CYP3A4/5-catalyzed midazolam 1-hydroxylation (r = 0.868) and CYP2C8-catalyzed paclitaxel 6alpha-hydroxylation (r = 0.900). In conclusion, the results of the present study demonstrated that CYP2C8 and CYP3A4/5 are the major enzymes responsible for the chloroquine N-deethylation to DCQ in human liver microsomes.

Aryl Hydrocarbon Hydroxylases↗

Acupuncture prevents 6-hydroxydopamine-induced neuronal death in the nigrostriatal dopaminergic system in the rat Parkinson's disease model.

Parkinson's disease (PD) is a chronic neurodegenerative disorder, and it has been suggested that treatments promoting survival and functional recovery of affected dopaminergic neurons could have a significant and long-term therapeutic value. In the present study, we investigated the neuroprotective effects of acupuncture on the nigrostriatal system in rat unilaterally lesioned with 6-hydroxydopamine (6-OHDA, 4 microg/microl, intrastriatal injection) using tyrosine hydroxylase (TH) and receptor for brain-derived neurotrophic factor, trkB, immunohistochemistries. Two weeks after the lesions were made, rats presented with asymmetry in rotational behavior (118.3 +/- 17.5 turns/h) following injection with apomorphine, a dopamine receptor agonist (0.5 mg/kg, sc). In contrast, acupunctural treatment at acupoints GB34 and LI3 was shown to significantly reduce this motor deficit (14.6 +/- 13.4 turns/h). Analysis via TH immunohistochemistry revealed a substantial loss of cell bodies in the substantia nigra (SN) (45.7% loss) and their terminals in the dorsolateral striatum ipsilateral to the 6-OHDA-induced lesion. However, acupunctural treatment resulted in the enhanced survival of dopaminergic neurons in the SN (21.4% loss) and their terminals in the dorsolateral striatum. Acupuncture also increased the expression of trkB significantly (35.6% increase) in the ipsilateral SN. In conclusion, we observed that only acupuncturing without the use of any drug has the neuroprotective effects against neuronal death in the rat PD model and these protective properties of acupuncture could be mediated by trkB.

Acupuncture Therapy↗

Effect of Puerariae radix on c-Fos expression in hippocampus of alcohol-intoxicated juvenile rats.

Alcohol consumption is known to cause substantial neuronal loss in several regions of the brain. In Oriental medicine, medications based on Puerariae radix have been known to be of efficacy in the treatment of alcohol-related problems. In the present study, the effect of the aqueous extract of Puerariae radix on the expression of c-Fos, an immediate early gene whose expression is sometimes used as a marker for stimulus-induced changes in the metabolic activity of neurons, in the hippocampus of acutely alcohol-intoxicated juvenile rats was investigated via immunohistochemistry. In the first part of the experiment, Sprague-Dawley rats were divided into six groups: the control group, the alcohol-treated group, the alcohol- and 0.3 mg/kg Puerariae radix-treated group, the alcohol- and 3 mg/kg Puerariae radix-treated group, the alcohol- and 30 mg/kg Puerariae radix-treated group, and the alcohol- and 300 mg/kg Puerariae radix-treated group. In the second part of the experiment, animals were divided into four groups: the control group, the 30 mg/kg Puerariae radix-treated group, the alcohol-treated group, and the alcohol- and 30 mg/kg Puerariae radix-treated group. From the results, it was demonstrated that alcohol administration significantly decreases the number of Fos-positive cells in the various regions of the hippocampus, and Puerariae radix treatment inhibits the alcohol-induced suppression of the expression of Fos in the hippocampus in a dose-dependent manner. Puerariae radix exerted no significant effect on Fos expression in the hippocampus of normal rats. The results presented in this study suggest that Puerariae radix may alleviate alcohol-induced disruption of hippocampal functions.

Alcoholic Intoxication↗

Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299.

To investigate whether bee venom (BV) induces apoptosis, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, terminal deoxynucleotidyl transferase- mediated dUTP nick end-labeling assay, 4,6-diamidino-2-phenylindole staining, flow cytometric analysis, and DNA fragmentation assay were performed on NCI-H1299 lung cancer cells treated with BV. Through morphological and biochemical analyses, it was demonstrated that NCI-H1299 cells treated with BV exhibit several features of apoptosis. In addition, reverse transcription-polymerase chain reaction and prostaglandin E(2) (PGE(2)) immunoassay were performed to verify whether BV possesses an inhibitory effect on the expression of cyclooxygenase (COX) and PGE(2 )synthesis. Expression of COX-2 mRNA and synthesis of PGE(2) were inhibited by BV. These results suggest the possibility that BV may exert an anti-tumor effect on human lung cancer.

Apoptosis↗

Acupuncture enhances cell proliferation in dentate gyrus of maternally-separated rats.

Maternal separation in early life can increase vulnerability to neuropsychiatric disorders over the lifespan. To investigate the effect of acupuncture on cell proliferation in the dentate gyrus (DG), 5-bromo-2'-deoxyuridine (BrdU)-immunohistochemistry was performed in maternally-separated rat pups. Maternal separation, for 7 days from postnatal day 14, induced a significant decrease of BrdU-immunoreactive cells in DG, while acupuncture treatment at acupoint Shenmen (HT7), at the end of the transverse crease of the ulnar wrist, resulted in the significant increase in the number of BrdU-positive cells in DG. However, acupuncture at acupoint ST36, near the knee joint, produced no increase in the number of BrdU-positive cells. These findings indicate that acupuncture at acupoint HT7 appears to stimulate cell proliferation, and we suggested that acupuncture may be useful in the treatment of diseases related to maternal separation.

Acupuncture↗

Decrease of the electroacupuncture-induced analgesic effects in nuclear factor-kappa B1 knockout mice.

To investigate the involvement of nuclear factor kappa B1 (NF-kappaB1; p50/p105) in electroacupuncture (EA)-induced analgesia, 2 and 100 Hz EA stimulations were applied at acupoint ST36 (Zusanli) in NF-kappaB1 knockout mice. EA was performed for 30 min and tail-flick latencies (TFLs) were evaluated every 15 min for 1 h. Wild-type mice displayed a 63.3% increase in TFLs compared to baseline after 2 Hz EA, whereas NF-kappaB1+/- mice exhibited a 41.8% increase and NF-kappaB1-/- mice showed only a 3.9% increase of TFLs. The TFLs of 100 Hz EA showed similar trends: a 72.6% increase of TFLs in wild-type, a 38.6% increase in NF-kappaB1+/- and a 9.3% increase in NF-kappaB1-/- mice. The present findings suggest that NF-kappaB1 may play a crucial role in both low and high frequency EA-induced analgesic effects.

Analgesia↗

Antipyretic effects of acupuncture on the lipopolysaccharide-induced fever and expression of interleukin-6 and interleukin-1 beta mRNAs in the hypothalamus of rats.

We observed the changes of body temperature and the cytokine expressions in the hypothalamus of rats to investigate the effect and mechanism of antipyretic action of acupuncture. Lipopolysaccharide (LPS, i.p., 2.5 mg/kg) was injected into rats and manual acupuncture was performed on Shaofu (HT8), Zutonggu (BL66) or Xingjian (LR2), respectively. The results showed that fever induced by LPS-injection was recovered significantly by acupuncture on each acupoint. LPS increased hypothalamic mRNA levels of interleukin-6 and interleukin-1 beta which, on the contrary, were also reduced to normal levels by acupuncture stimulation on BL66. These results suggest that the acupuncture stimulation may be effective for reducing elevated body temperature induced by bacterial inflammation, and part of its action may be mediated through the suppression of hypothalamic production of pro-inflammatory cytokines.

Acupuncture Therapy↗