Youngmin Bu

Chlorogenic acid ameliorates brain damage and edema by inhibiting matrix metalloproteinase-2 and 9 in a rat model of focal cerebral ischemia

Chlorogenic acid (CGA) has been reported to have various beneficial effects on the cardiovascular and central nervous systems. The purpose of the current study was to investigate whether CGA has protective effects against cerebral ischemia and whether these effects are due to modification of brain edema-related vascular factors. In a rat model of transient middle cerebral artery occlusion (MCAo, 2h of occlusion followed by 22 h of reperfusion), we measured infarct volume and performed behavioral test to evaluate the effects of CGA on brain damage and sensory-motor functional deficits. Brain water content and Evans blue extravasation were measured to evaluate brain edema and blood brain barrier (BBB) damage. Lipid peroxidation (LPO) and the expressions and activities of matrix metalloproteinase (MMP)-2 and MMP-9 were measured to investigate the mechanisms of action. Intraperitoneal injection of CGA (3, 10, and 30 mg/kg) at 0 h and 2h after MCAo dose-dependently reduced infarct volume and sensory-motor functional deficits. It also reduced brain water content and Evans blue extravasation. Mechanistically, CGA reduced LPO and MMPs expressions and activities. These results suggest that CGA reduces brain damage, BBB damage and brain edema by radical scavenging activity and the inhibitory effects on MMP-2 and MMP-9.

Telomerase induction in astrocytes of Sprague-Dawley rat after ischemic brain injury.

Telomerase, a reverse transcriptase, consists of an RNA template and protein polymerase. This ribonucleoprotein protects the linearized chromosomal end region and elongates the telomere during chromosomal replication. Telomerase is not expressed in adult somatic cells but it shows high activity in most cells during embryonic development. We report, by RT-PCR and immunohistochemical results, that the induction of telomerase protein catalytic subunit (TERT) in transient middle cerebral artery occlusion induced brain injury. TERT mRNA emerged 24 h after ischemia. We examined which brain cell expressed TERT in the penumbra region of injured brain. The expression of TERT began from 24 h and remained until 5 days after ischemia. We identified that TERT was co-localized with the astrocyte marker, GFAP, at 3 days after ischemia. This is strong evidence that TERT is induced in astrocytes when the brain is damaged by ischemia, and that this enzyme may play an important role in ischemic brain injury.

Antiplatelet effects of Spatholobus suberectus via inhibition of the glycoprotein IIb/IIIa receptor

ETHNOPHARMACOLOGICAL RELEVANCE The vine stem of Spatholobus suberectus is a widely used blood-activating and stasis-dispelling medicine for the treatment of diseases related to blood stasis syndrome in traditional medicine in Korea, Japan, and China. AIM OF THE STUDY To demonstrate the clinical effects of Spatholobus suberectus against blood stasis syndromes using in vitro and in vivo platelet aggregation studies and to investigate its exact mechanisms. MATERIALS AND METHODS We extracted vine stems of Spatholobus suberectus, using 95% EtOH (SSE) and investigated its antiplatelet activity on platelet aggregation induced by collagen and ADP in human platelet-rich plasma (PRP). For the mechanism study, a glycoprotein IIb/IIIa (GP IIb/IIIa) assay using flow cytometric analysis and a thromboxane A(2) (TXA(2)) assay were performed. In addition, we investigated the effects of SSE in a thromboembolic mouse model. RESULTS SSE significantly inhibited ADP- and collagen-induced platelet aggregation in human PRP concentration-dependently without affecting plasma clotting time. It also significantly inhibited fibrinogen binding to the GP IIb/IIIa receptor and partly inhibited the formation of TXA(2). In the in vivo study, oral administration of SSE dose-dependently suppressed the death of thromboembolism model mice induced by intravenous injection of collagen plus epinephrine. CONCLUSIONS SSE showed antiplatelet activity without anticoagulant effects mainly through the inhibition of fibrinogen binding to the GP IIb/IIIa receptor. Our current results support the clinical usage of SSE in the East Asian region treating atherothrombotic diseases and may represent a new natural source to develop antiplatelet agents.

Therapeutic effects of traditional herbal medicine on cerebral ischemia: A perspective of vascular protection

Although many agents for acute ischemic stroke treatment have been developed from extensive preclinical studies, most have failed in clinical trials. As a result, researchers are seeking other methods or agents based on previous studies. Among the various prospective approaches, vascular protection might be the key for development of therapeutic agents for stroke and for improvements in the efficacy and safety of conventional therapies. Traditional medicines in Asian countries are based on clinical experiences and literature accumulated over thousands of years. To date, many studies have used traditional herbal medicines to prove or develop new agents based on stroke treatments mentioned in traditional medicinal theory or other clinical data. In the current review, we describe the vascular factors related to ischemic brain damage and the herbal medicines that impact these factors, including Salviae Miltiorrhizae Radix, Notoginseng Radix, and Curcumae Rhizoma, based on scientific reports and traditional medical theory. Further, we point out the problems associated with herbal medicines in stroke research and propose better methodologies to address these problems.

Antioxidant Components as Potential Neuroprotective Agents in Sesame (Sesamum indicum L.)

Sesame (Sesamum indicum L.) is one of the most important oilseed crops, having seeds and its edible oil that are highly valued as a traditional food. Many studies have examined the health value of sesame seeds and oil. Among the bioactive components in sesame seeds, lignans and tocopherols have been identified as the major antioxidants responsible for the resistant oxidative deterioration of sesame seeds and oil. These same antioxidants have been reported to have protective effects against human disease such as neurodegenerative disease. This review summarizes the chemical properties of lignans including lipid-soluble lignans, lignan glucosides and tocopherols, and their bioactivities such as antioxidativity and neuroprotection. We also review the biosynthesis of lignan in sesame seeds and transformation of lignans during food processing in sesame oil. Sesame seeds and its antioxidants may be a potent natural agent with both therapeutic applications and use in preventing human illness such as neurodegenerative disease.

Neuroprotective Effect of Defatted Sesame Seeds Extract against in vitro and in vivo Ischemic Neuronal Damage

Sesame (Sesamum indicum L.) is an important oilseed crop that possesses a wide spectrum of pharmacological activities. Many studies have been conducted to investigate its health-promoting effects. Compared to other plant oils, sesame seed oil is highly stable to oxidation and has been demonstrated to have protective effects against ischemia-reperfusion injury in the rat brain. However; the effects of defatted sesame seeds extract (DSE) have not been studied yet. The purpose of this study was to evaluate the protective effect of DSE against ischemia models. For in vitro ischemia, oxygen-glucose deprivation followed by reoxygenation (OGD-R, 4 h OGD followed by 24 h reoxygenation) in HT22 cells was used to investigate the protective effects on cell death and the inhibitory effects on lipid peroxidation. For in vivo ischemia, the middle cerebral artery occlusion (MCAo, 2 h of MCAo followed by 22 h of reperfusion) rat model was used. Twenty-two h after occlusion the rats were assessed for neurobehavioral deficit and infarct volume. DSE (0.1-10 microg/mL) significantly reduced the cell death and inhibited lipid peroxidation induced by OGD-R. DSE (30, 100 and 300 mg/kg, p.o.) given twice at 0 h and 2 h after onset of ischemia reduced brain infarct volume dose-dependently and improved sensory-motor function. The therapeutic time window of DSE (300 mg/kg, p.o.) was 2 h after MCAo in rats. In conclusion, our results show that DSE may be effective in ischemia models by an antioxidative mechanism.

Prophylactic effects of Lonicera japonica extract on dextran sulphate sodium-induced colitis in a mouse model by the inhibition of the Th1/Th17 response

Inflammatory bowel diseases (IBD) are chronically relapsing inflammatory disorders of the intestine. Although some therapeutic agents, including steroids, are available for the treatment of IBD, these agents have limited use. Therefore, dietary supplements have emerged as possible interventions for IBD. Japanese honeysuckle flower, the flower of Lonicera japonica, is a well-known dietary supplement and has been used to prevent or treat various inflammatory diseases. In the present study, we investigated the effects of L. japonica on experimental murine colitis. Colitis was induced by 5 % dextran sulphate sodium (DSS) in Balb/c mice. The water extract of L. japonica (LJE) at doses of 20, 100 or 500 mg/kg was orally administered to mice twice per day for 7 d. Body weight, colon length and a histological damage score were assessed to determine the effects on colitis. Cytokine profiles were assessed to examine the effects on helper T (Th) cell-related immunological responses. In addition, CD4⁺CD25⁺Foxp3⁺T cells were analysed in vivo and in vitro for investigating the effects on regulatory T (Treg) cells. LJE showed dose-dependent inhibitory effects against colon shortening, weight loss and histological damage. LJE down-regulated IL-1β, TNF-α, interferon-γ, IL-6, IL-12 and IL-17. However, LJE did not show any significant effects on IL-10, IL-23, transforming growth factor-β1 and Treg cell populations. In conclusion, LJE showed protective effects against DSS-induced colitis via the Th1/Th17 pathway and not via Treg cell-related mechanisms.

Gender Differences in Risk Factors for Intracranial Cerebral Atherosclerosis Among Asymptomatic Subjects

BACKGROUND Gender is known to be one of the factors linked to differences in cardiovascular morbidity and mortality. However, little information is available regarding gender differences in the risk factors for intracranial cerebral atherosclerosis (ICAS). OBJECTIVE This study investigated the risk factors for ICAS separately by gender in an asymptomatic population. METHODS We collected data from a consecutive series of 935 subjects who had no history of stroke and who had undergone transcranial Doppler ultrasonography (TCD). For each subject, their medical history was documented and tests for biochemical markers were performed. Multiple logistic regression analyses were separately conducted to assess the risk factors associated with ICAS by gender. RESULTS The risk factors for asymptomatic ICAS were determined for every 10-year increase in age (odds ratio [OR] = 1.74, 95% confidence interval [CI] = 1.23-2.46), diabetes mellitus (DM) (OR = 3.45, 95% CI = 1.49-7.95), smoking (OR = 2.09, 95% CI = 1.01-4.32), and hypercholesterolemia (OR = 3.31, 95% CI = 1.15-9.50) for male subjects; risk factors female subjects included hypertension (OR = 2.10, 95% CI = 1.40-3.15) and DM (OR = 2.45, 95% CI = 1.11-5.44). An additional stratified analysis indicated that there was no significant risk factor for male subjects aged <50 years, whereas hypertension (OR = 2.90, 95% CI = 1.57-5.37) was the significant risk factor for female subjects aged <50 years. For male subjects aged ≥50 years, DM (OR = 6.00, 95% CI = 1.87-19.20), hypercholesterolemia (OR = 4.72, 95% CI = 1.05-21.19), and every 10-year increase in age (OR = 4.33, 95% CI = 2.02-9.28) were significant risk factors for asymptomatic ICAS, whereas DM (OR = 2.93, 95% CI = 1.14-7.48) was significant for female subjects aged ≥50 years. CONCLUSIONS The findings suggest that the risk factors for asymptomatic ICAS differ between sexes, indicating a possible role of sex hormones in the development of ICAS.

Key compound groups for the neuroprotective effect of roots of Polygonum cuspidatum on transient middle cerebral artery occlusion in Sprague-Dawley rats

Polygonum cuspidatum is a potent anti-oxidant herb that is well known for its various bioactivities. The current study investigates which compound group is most effective, to establish the key compound groups for quality assessment, especially in terms of neuroprotective effects. The roots of P. cuspidatum were extracted with 85% methanol and fractionated with hexane, ethyl acetate, n-butanol and water. Each fraction was applied to an in vitro radical scavenging assay, a lipid peroxidation assay in brain homogenates and an in vivo assay using a transient focal cerebra ischemia model induced by a middle cerebral artery occlusion in a Sprague-Dawley rat. The ethyl acetate fraction was the most effective fraction in both in vitro and in vivo assays, having the highest stilbene and anthraquinone contents. These results suggest that stilbenes and anthraquinones may be key compound groups for the quality assessment of the anti-oxidative and neuroprotective effects of P. cuspidatum.

Neuroprotection and Enhancement of Spatial Memory by Herbal Mixture HT008-1 in Rat Global Brain Ischemia Model

To investigate whether HT008-1, a prescription used in traditional Korean medicine to treat mental and physical weakness, has a neuroprotective effect on a rat model of global brain ischemia and an enhancing effect against memory deficit following ischemia. Global brain ischemia was induced for 10 min by using 4-vessel occlusion (4-VO). HT008-1 was orally administered at doses of 30, 100, and 300 mg/kg respectively twice at 0 and 90 min after ischemia. The effect on memory deficit was investigated by using a Y-maze neurobehavioral test 4 days after brain ischemia, and the effect on neuronal damage was measured 7 days after ischemia. The mechanism of action was studied immunohistochemically using an anti-CD11b (OX-42) antibody. The oral administration of HT008-1 at 100 and 300 mg/kg significantly reduced hippocampal neuronal cell death by 49% and 53%, respectively, compared with a vehicle-treated group, and also improved spatial memory function in the Y-maze test. Immunohistochemically, HT008-1 inhibited OX-42 expression in the hippocampus. The effects of HT008-1 were more pronounced than those of its individual herb components. The herbal mixture HT008-1 protects the most vulnerable CA1 pyramidal cells of the hippocampus and enhances spatial memory function against global brain ischemia; an anti-inflammatory effect may be one of the mechanisms of action.