Seong Hun Choi

Acupuncture suppresses morphine self-administration through the GABA receptors

The neurobiological substrate for morphine self-administration in animals is believed to involve the dopamine system of the nucleus accumbens. Our previous study has shown that acupuncture at the acupoint Shenmen (HT7) reduced dopamine release in the nucleus accumbens and behavioral hyperactivity induced by systemic administration of morphine. Here we investigated the effect of acupuncture on morphine self-administration and potential roles of GABA receptors in the mechanisms behind acupuncture. Male Sprague-Dawley rats were trained to self-administer morphine (0.1 mg/kg per infusion) during daily 1-h session under fixed-ratio 1 schedule. Following the stable responding on morphine self-administration, acupuncture was applied to HT7 points bilaterally (1 min) prior to the testing session. Another groups of rats were given the GABA(B) receptor antagonist SCH 50911 (3.0 mg/kg, i.p.), the GABA(A) receptor antagonist bicuculline (1.0 mg/kg, i.p.) or saline 30 min prior to the acupuncture treatment. We have found that acupuncture at the acupoint HT7, but not at the control point Yangxi (LI5), significantly decreased morphine self-administration. Moreover, either SCH 50911 or bicuculline blocked the inhibitory effects of acupuncture on morphine self-administration. Taken together, the current results suggest that acupuncture at specific HT7 points regulates the reinforcing effects of morphine via regulation of GABA receptors.

Differential involvement of GABA system in mediating behavioral and neurochemical effect of acupuncture in ethanol-withdrawn rats.

In our previous study we demonstrated that acupuncture at Shenmen (HT7) points suppressed a decrease of accumbal dopamine (DA) release in ethanol-withdrawn rats. Furthermore, here we found that it inhibited behavioral withdrawal signs of ethanol. In an effort to better understand the mechanisms underlying this inhibition, the potential role of GABA receptor system in acupuncture was investigated. Male Sprague-Dawley rats were treated with 3g/kg/day of ethanol (20%, w/v) or saline by intraperitoneal injection for 21 days. Following 48 or 72h of ethanol withdrawal, acupuncture was applied at bilateral HT7 for 1min. The selective GABA(A) antagonist bicuculline and the selective GABA(B) antagonist SCH 50911 were injected intraperitoneally 20min before acupuncture, respectively. Importantly, suppressive effects of acupuncture on DA deficiency were completely abolished by SCH 50911, but not by bicuculline, whereas ameliorating effects of acupuncture on ethanol withdrawal syndrome were completely blocked either by SCH 50911 or bicuculline. These results suggest that acupuncture at specific acupoint HT7 may normalize the DA release in the mesolimbic system and attenuate withdrawal syndrome through the GABA(B) receptor system in ethanol-withdrawn rats.

Fermentation with Aquilariae Lignum enhances the anti-diabetic activity of green tea in type II diabetic db/db mouse.

The major components of tea may be significantly influenced according to the type of fermentation, and consequently the effects of different teas will differ. We examined whether green tea fermented with Aquilariae Lignum (fGT) shows a stronger anti-diabetic effect than unfermented green tea (GT) on mice with type 2 diabetes. To evaluate the anti-obesity effect of fGT, we assessed body weight, fecal excretion, serum leptin levels, exocrine pancreatic zymogen granule contents, and periovarian fat weight and adiponectin contents. Blood glucose levels, pancreatic weight, and numbers of pancreatic islet insulin- and glucagon-producing cells were determined to evaluate anti-hypoglycemic effects, while total cholesterol, triglyceride, and low- and high-density lipoprotein levels were determined to evaluate anti-hyperlipidemic effects. The antioxidant effect of fGT was detected by measuring malondialdehyde and glutathione contents and the activities of catalase and superoxide dismutase. fGT showed anti-obesity, anti-hypoglycemic, anti-hyperlipidemia, and antioxidant effects. Additionally, fGT exerted stronger anti-diabetic effects compared with GT. Collectively, these results suggested that fGT fermented with the appropriate amounts of Aquilariae Lignum (49:1) has a stronger effect compared with GT. Thus, fGT is a promising and potent new therapeutic agent for type 2 diabetes.

Effect of acupuncture on naloxone-precipitated withdrawal syndrome in morphine-experienced rats: The mediation of GABA receptors

Repeated morphine administration increases extracellular dopamine levels in the nucleus accumbens, which results in behavioral sensitization that can be suppressed by acupuncture at Shenmen (HT7) points. The present study was conducted to investigate the effects of acupuncture at HT7 on morphine withdrawal syndrome as well as to explore the role of GABA receptors in mediating the effects of HT7 acupuncture. We induced morphine withdrawal by injecting naloxone to rats that self-administer morphine and evaluated the effects of acupuncture and/or GABA receptor antagonists on their withdrawal symptoms. Acupuncture at HT7, but not at the control point LI5, significantly decreased symptoms of morphine withdrawal. HT7 inhibition of the withdrawal syndrome was blocked by pretreatment with either the GABA(A) receptor antagonist bicuculline or the GABA(B) antagonist SCH 50911. These findings suggest that the effects of acupuncture on suppression of morphine withdrawal syndrome are mediated, at least in part, through GABA receptors.

Inhibition of UVB-Induced Skin Damage by Exopolymers from Aureobasidium pullulans SM-2001 in Hairless Mice

Because antioxidants from natural sources may be an effective approach to the treatment and prevention of UV radiation‐induced skin damage, the effects of purified exopolymers from Aureobasidium pullulans SM‐2001 (‘E‐AP‐SM2001’) were evaluated in UVB‐induced hairless mice. E‐AP‐SM2001 consists of 1.7% β‐1,3/1,6‐glucan, fibrous polysaccharides and other organic materials, such as amino acids, and mono‐ and di‐unsaturated fatty acids (linoleic and linolenic acids) and shows anti‐osteoporotic and immunomodulatory effects, through antioxidant and anti‐inflammatory mechanisms. Hairless mice were treated topically with vehicle, E‐AP‐SM2001 stock and two and four times diluted solutions once per day for 15 weeks against UVB irradiation (three times per week at 0.18 J/cm2). The following parameters were evaluated in skin samples: myeloperoxidase (MPO) activity, cytokine levels [interleukin (IL)‐1β and IL‐10], endogenous antioxidant content (glutathione, GSH), malondialdehyde (MDA) levels, superoxide anion production; matrix metalloproteases (MMP‐1, ‐9 and ‐13), GSH reductase and Nox2 (gp91phox) mRNA levels, and immunoreactivity for nitrotyrosine (NT), 4‐hydroxynonenal (HNE), caspase‐3, and cleaved poly(ADP‐ribose) polymerase (PARP). Photoageing was induced by UVB irradiation through ROS‐mediated inflammation, which was related to the depletion of endogenous antioxidants, activation of MMPs and keratinocyte apoptosis. Topical treatment with all three doses of E‐AP‐SM2001 and 5 nm myricetin attenuated the UV‐induced depletion of GSH, activation of MMPs, production of IL‐1β, the decrease in IL‐10 and keratinocyte apoptosis. In this study, E‐AP‐SM2001 showed potent inhibitory effects against UVB‐induced skin photoageing. Thus, E‐AP‐SM2001 may be useful as a functional ingredient in cosmetics, especially as a protective agent against UVB‐induced skin photoageing.

Role for GABA agonists in the nucleus accumbens in regulating morphine self-administration

In the present study, functional roles of GABA receptors in the nucleus accumbens on morphine self-administration behavior were investigated. Male Sprague-Dawley rats were trained to press lever for morphine (0.1 mg/kg per infusion) during daily 1-h self-administration session. After establishing stable baseline responses, rats were given microinjections of the GABA(A) receptor agonist muscimol (0, 250 and 500 ng/microl, bilateral) or the GABA(B) receptor agonist baclofen (0, 100 and 250 ng/microl, bilateral) into the nucleus accumbens immediately before the morphine self-administration. Microinjection of muscimol (250 and 500 ng/microl) into the nucleus accumbens, but not baclofen, decreased morphine self-administration responses. These results suggest that activation of GABA(A) receptors, but not GABA(B) receptors, in the nucleus accumbens plays a critical role in modulating the reinforcing effects of morphine.

Dried Pomegranate Potentiates Anti-Osteoporotic and Anti-Obesity Activities of Red Clover Dry Extracts in Ovariectomized Rats

Red clover (RC) shows potential activity against menopausal symptoms and pomegranates have antioxidative and beneficial effects on postmenopausal symptoms; thus, we investigated whether the anti-climacteric activity of RC could be enhanced by the addition of dried pomegranate concentrate powder (PCP) extracts in ovariectomized (OVX) rats. Regarding the anti-osteoporotic effects, bone mineral density increased significantly in OVX induced rats treated with 60 and 120 mg/kg of an RC:PCP 2:1 mixture, respectively, compared with OVX control rats. Additionally, femoral, tibia, and L4 bone resorption was decreased in OVX induced control rats treated with the RC:PCP 2:1 mixture (60 and 120 mg/kg), respectively, compared with OVX control rats. Regarding anti-obesity effects, the OVX induced rats treated with 60 and 120 mg/kg of the RC:PCP 2:1 mixture showed a decrease in total fat pad thickness, the mean diameters of adipocytes and the body weights gain compared with OVX induced control rats. The estradiol and bone-specific alkaline phosphatase levels were significantly increased in OVX induced rats treated with the RC:PCP 2:1 mixture (120 mg/kg) compared with OVX induced control rats, also, the uterine atrophy was significantly inhibited in 60 and 120 mg/kg of the RC:PCP 2:1 mixture treatment compared with OVX control rats. In conclusion, our results indicate that PCP enhanced the anti-climacteric effects of RC in OVX rats. The RC:PCP 2:1 mixture used in this study may be a promising new potent and protective agent for relieving climacteric symptoms.

Polycan, a β-glucan from Aureobasidium pullulans SM-2001, mitigates ovariectomy-induced osteoporosis in rats

The present study aimed to investigate the protective effects of Polycan, a β-glucan from Aureobasidium pullulans SM-2001, in a rat model of ovariectomy-induced osteoporosis. Ovariectomized (OVX) rats were orally administered 31.25, 62.5 or 125 mg/kg/day Polycan for 126 days, and alterations in body weight, bone mineral content, bone mineral density, failure load, histological profiles and histomorphometric indices were analyzed. In particular, serum levels of osteocalcin, bone-specific alkaline phosphatase (bALP), calcium and phosphorus, and the urine deoxypyridinoline/creatinine ratio, were measured. Furthermore, the femur, tibia and lumbar vertebrae were harvested from all rats, and histomorphometrical analyses were conducted in order to assess the mass and structure of the bones, and the rates of bone resorption and formation. One group of rats was treated with alendronate, which served as the reference drug. The results of the present study suggested that Polycan treatment was able to inhibit ovariectomy-induced alterations in bone resorption and turnover in a dose-dependent manner. In addition, the serum expression levels of bALP and all histomorphometrical indices for bone formation were markedly increased in the Polycan-treated groups. These results indicated that Polycan was able to preserve bone mass and strength, and increase the rate of bone formation in OVX rats; thus suggesting that Polycan may be considered a potential effective anti-osteoporosis agent.

The Effects of Acupuncture Stimulation for Brain Activation and Alcohol Abstinence Self-Efficacy: Functional MRI Study

We attempted to investigate whether acupuncture stimulation at HT7 can have an effect on brain activation patterns and alcohol abstinence self-efficacy. Thirty-four right-handed healthy subjects were recruited for this study. They were randomly assigned into two groups: the HT7 (Shenmen) group and the LI5 (Yangxi) group. Acupuncture stimulation was performed using a block paradigm during fMRI scanning. Additionally, the Korean version of Alcohol Abstinence Self-Efficacy Scale (AASES) was used to determine the effect of acupuncture stimulation on self-efficacy to abstain from alcohol use. According to the result of fMRI group analysis, the activation induced by HT7 stimulation was found on the bilateral postcentral gyrus, inferior parietal lobule, inferior frontal gyrus, claustrum, insula, and anterior lobe of the cerebellum, as well as on the left posterior lobe of the cerebellum (p < 0.001, uncorrected). According to the AASES analysis, the interaction effect for gender and treatment was marginally significant (F(1, 30) = 4.152, p = 0.050). For female group, the simple main effect of treatment was significant (F(1, 11) = 8.040, p = 0.016), indicating that the mean change score was higher in the HT7 stimulation than in the LI5 stimulation. Therefore, our study has provided evidence to support that HT7 stimulation has a positive therapeutic effect on the alcohol-related diseases.

Therapeutic Effects of Blue Honeysuckle on Lesions of Hyperthyroidism in Rats

Hyperthyroidism is a hypermetabolic syndrome characterized by an overproduction of thyroid hormones, which enhances the hormone-induced oxidative stress responsible for some complications in the liver, heart and muscle. Blue honeysuckle (BH) is an edible berry, rich in polyphenols, especially flavonoids or anthocyanins, known as strong antioxidants. The chemo-protective activities of the berry have been connected to the improvement of symptoms in cancer, diabetes mellitus, tumor or cardiovascular diseases. Therefore, the therapeutic effects of BH were examined in hyperthyroidism rat model. The hyperthyroidism was induced by injection with levothyroxine (LT4), and the model was treated with distilled water (LT4 control), propylthiouracil (PTU) or BH at 3 dosages of 500, 250 and 125[Formula: see text]mg/kg. The treatment was performed once a day for 15 days. Compared to LT4 control, the oral administration of BH dose-dependently ameliorated the hyperthyroidism, reducing thyroid hormones and increasing thyroid stimulating hormones. These effects were accompanied by improvement of body weight loss and atrophy in the thyroid gland, liver and epididymal fat pads. BH treatments also reduced the levels of hepatic enzymes (AST and ALT), which suggests BH exerts protective effects on hepatocytes. BH might also be involved in the augmentation of the anti-oxidant activities, supported by increased endogenous antioxidant (glutathione). In addition, the histopathological analyses revealed the beneficial effects of BH on the atrophic changes and cellular injuries in the thyroid gland, liver and epididymal fat pads. The therapeutic potentials of BH were either similar or more effective than PTU. These results provide valuable information that will guide more detailed studies to use the BH as a complementary and alternative medicine.