• Journal of Ginseng Research
• /
• v.40 no.2
• /
• pp.196-202
• /
• 2016

Background: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10-100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with $CD11b^+$, $iNOS^+$/interleukin-12/tumor necrosis factor-${\alpha}$ labeling. For the in vitro study, GSRd ($10-100{\mu}g/mL$) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin-eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-${\alpha}$. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion: These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization.

• The Journal of Korean Medicine
• /
• v.24 no.2
• /
• pp.66-80
• /
• 2003

Objectives : Recently, herbal acupuncture has been developed in the Korea since the earlier 1960' applied to various diseases including the cerebrovascular accident. The main characteristics of herbal acupuncture are a combination the merit of acupuncture and herbal medicine. It was not well known the therapeutic effect and the mechanism of herbal acupuncture on transient forebrain ischemic injury, although it has been used frequently in clinics. Ramulus Uncariae Cum Uncis (釣鉤藤) has been claimed to possess sedative, anti-spasmodic actions, and treat childhood epilepsy in oriental medical preparation. Also, it has been stated that Ramulus Uncariae Cum Uncis was antioxidatvie effect and neuroprotection against glutamateinduced neuronal death. Methods : In this study, effects of Ramulus Uncariae Cum Uncis' herbal acupuncture on the $GV_{20}{\;}or{\;}LR_3$, named Baek-hue or Tae-chung, on neuroprotection after the transient forebrain ischemia were investigated in Sprague-Dawely rats. Expressions of cFos, FosB and BDNF protein in the hippocampus and cortex were observed at 2 hrs and 48 hrs after transient forebrain ischemia by immunohistochemistry and ELISA technique. Results : Expression of cFos protein was increased slightly in the hippocampus and cortex at 2 hrs after transient forebrain ischemia, but FosB protein was increased highly comparing to cFos protein. However, pretreatment with Ramulus Uncariae Cum Uncis' herbal acupuncture on $GV_{20}{\;}or{\;}LR_3$ significantly increased expression of cFos protein and significantly decreased expression of FosB protein compared to control group, respectively. These features were observed in the motor cortex and retrosplenial granular cortex as well as the hippocampus. Especially, cFos expression was more increased at the herbal acupuncture on $GV_{20}{\;}than{\;}LR_3$, but FosB expression was more decreased in $LR_3$ group than $GV_{20}$ group. Also, pretreatment with Ramulus Uncariae Cum Uncis' herbal acupuncture on $GV_{20}{\;}or{\;}LR_3$ significantly increased the expression of BDNF protein in the hippocampus ($254.88{\pm}12{\;}pg/ml{\;}in{\;}GV_{20}$ group, $245.93{\pm}44.4{\;}pg/ml{\;}in{\;}LR_3$ group) and the cortex ($85.81{\pm}3.45{\;}pg/ml{\;}in{\;}GV_{20}$ group, $111.51{\pm}15.79{\;}pg/ml{\;}in{\;}LR_3$, group) compared to the hippocampus ($134.07{\pm}2.96{\;}pg/ml$) and the cortex ($61.16{\pm}4.11{\;}pg/ml$) in control group at 48 hrs after transient forebrain ischemia. Conclusion : These results suggest that pretreatment with Ramulus Uncariae Cum Uncis' herbal acupuncture on $GV_{20}{\;}or{\;}LR_3$ has neuroprotective effect on transient forebrain ischemia and the herbal acupunture on $GV_{20}{\;}or{\;}LR_3$ may be related to antioxidative effect and calcium channel block of Ramulus Uncariae Cum Uncis. Also, it could be mentioned there is specificity of acupoints treating ischemic injury through the difference between the herbal acupuncture of $GV_{20}{\;}and{\;}LR_3$.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.3
• /
• pp.594-601
• /
• 2002

The current study was carried out to evaluate neuroprotective effects of Citri Pericarpium after transient global ischemia in gerbils. Male Mongolian gerbils weighing 60-80g were anesthetized with 2% isoflurane mixed with 30% oxygen and 70 % nitrogen. Bilateral common carotid arteries were occluded for 5 minute with microaneurysm dips. On 3 or 7 days after ischemic surgery, the gerbils were sacrificed. The brain were removed, embedded in paraffin and sectioned at 8㎛-thickness. Gerbils that received ischemic insult for 5 min showed extensive neuronal damage in the hippocampal CA1 region, and the number of viable neuronal cell was 51.0±2.5/mm, 32.2% of normal group at 7 days after ischemic surgery. In animals that underwent the extract of Citri Pericarpium treatment, the number of viable neuronal cell were significantly better preserved at 110.58±3.58/mm, 72.0% of normal group than those of ischemic group (P<0.01). In the immunohistochemistry of Bax and Bcl-2, the Citri Pericarpium treated group down-regulated the expression of Bax protein at 72hr after transient global ischemia. In contrast, Bcl-2 protein level was not changed. The appearance in TUNEL assay is similar to the pattern of Bax protein. The water extract of Citri Pericarpium significantly reduced the number of TUNEL-positive CA1 pyramidal neurons at 72hr. The results suggest that Citri Pericarpium has potential neuroprotective effects in the transient global ischemia and the increase in the ratio of Bcl-2 to Bax may contribute to the anti-apoptotic effect of Citri Pericarpium.

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.145.1-145.1
• /
• 2003

Several lines of recent evidences have shown that several pro-inflammatory genes or mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and cytokines (e.g., tumor necrosis factor $\alpha$ and interleukin-1$\beta$), are strongly expressed in the ischemic brain. Inflammation is now recognized as a significant contributing mechanism in cerebral ischemia because anti-inflammatory compounds or inhibitors of iNOS and cyclooxygenase-2 have been proven to reduce ischemic brain damage. (omitted)

• Biomolecules & Therapeutics
• /
• v.12 no.3
• /
• pp.138-144
• /
• 2004

Therapeutic effect of a Kampo medicine, Choto-san, in patients with vascular dementia was demonstrated by a double-blind and placebo-controlled clinical trial. To clarify the therapeutic efficacy of Choto-san, anti-ischemic effect in mice, hypotensive effect in spontaneously hypertensive rats (SHR), anti-oxidative effects in vitro, and N-methyl-D-aspartate (NMDA) receptor-blocking activity using Xenopus oocytes were studied. (1) Pretreatment with Choto-san (0.75-6.O g/kg, P.O.) or a component herb Chotoko (Uncaria genus: 75 - 600 mg/kg, P.O.) prevented ischemia-induced impairment of spatial learning behaviour in mice. Indole alkaloids- and phenolic fractions extracted from Chotoko also improved significantly the learning deficit. (2) Subchronic administration of Choto-san (0.5 g/kg, p.o.) caused a significant hypotensive effects in SHR. (3) Choto-san, Chotoko, and the phenolic constituent, (-) epicatechin, significantly protected the NG108-15 cell injury induced by $H_20_2$ exposure in vitro and also inhibited lipid peroxidation in the brain homogenate. (4) Indole alkaloids, rhynchophylline and isorhynchophylline (1-100 uM), reversibly reduced NMDA-induced current in the receptor-expressed Xenopus oocytes. These results suggest that anti-vascular dementia effects of Choto-san are mainly due to the effect of Chotoko. From these results, it is possible to make a novel dietary supplement through several extraction steps from Chotoko.

• The Korean Journal of Physiology and Pharmacology
• /
• v.5 no.4
• /
• pp.323-331
• /
• 2001

A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of rutin, a flavonoid having antiprostanoid, anti-inflammatory, antithrombotic, antioxidant effect, were investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state resulted in a fatal outcome within 120 min of reperfusion in many rats. Rutin was given as a bolus (1.28 mg/kg) 10 min prior to reperfusion. Administration of rutin significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p＜0.05). Rutin treatment also resulted in a significant attenuation in the increase in plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. These results suggest that rutin provides beneficial effects in part by preserving endothelial function and attenuating neutrophil accumulation in the ischemic reperfused splanchnic circulation.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.303.2-304
• /
• 2002

Wogonin. a flavonoid originated from the root of Scutellaria baicalensis Georgi. is known to exhibit potent anti-inflammatory effects and variable degrees of antioxidant and free radical scavenging effects depending on the experimental systems. In addition. wogonin has been reported to protect neurons from excitotoxic and oxidative injuries in primary cultured rat cortical cells. (omitted)

• The Korean Journal of Pharmacology
• /
• v.32 no.1
• /
• pp.31-37
• /
• 1996

The protective effect of 'ischemic preconditioning (IP)'on ischemia-reperfusion injury of heart has been reported in various animal species, but the mechanism is unclear. In an attempt to elucidate the mechanism of IP, we examined the effects of blockers against adenosine and protein kinase C in preconditioned heart of rat. The hearts perfused with oxygen-saturated Krebs-Henseleit solution by Langendorff method were exposed to 30 min global ischemia followed by 20 min reperfusion. IP was performed with three episodes of 5 min ischcmia and 5 min reperfusion just before ischemia-reperfusion. IP prevented the depression of contractile function and the myocardial contracture in the ischemic-reperfused heart and reduced the release of lactate dehydrogenase during the reperfusion period. Polymyxin B, chelerythrine and colchicine, PKC inhibitors, attenuated almost completely the anti-ischemic effect of IP, while adenosine receptor antagonists did not. These results indicate that PKC may be a crucial intracellular mediator in anti-ischemic action of IP in ischemic-reperfused rat heart, while adenosine may not be involved in the mechanism of IP.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.1
• /
• pp.25-30
• /
• 2006

This Study was designed to investigate the effects of Patholobi Caulis on the change of regional cerebral blood flow (rCBF) and blood Pressure (MABP) in normal and Cerebral ischemic rats. And, this Study was designed to investigate the inhibition of lactate dehydrogenase (LDH) activity in neuronal cells. The results were as follows : In normal rats, Patholobi Caulis significantly increased rCBF in a dose-dependent manner, and MABP was somewhat increased. In ischemia rats, rCBF was significantly and stably increased by Patholobi Caulis (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. Patholobi Caulis significantly inhibited LDH activity in neuronal cells. It was suggested that Patholobi Caulis had an anti-ischemic effect through the improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• International Journal of Stem Cells
• /
• v.16 no.2
• /
• pp.168-179
• /
• 2023

Background and Objectives: We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury. Methods and Results: Forty male Sprague-Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla. Conclusions: The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.