• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1459-1466
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• 2006

The water extract of Hwansodan has been traditionally used for treatment of ischemic brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of Hwansodan rescues cells from neurodegenerative disease. PC12 pheochromocytoma cells have been used extensively as a model for studying the cellular and molecular mechanisms of neuronal cell damages. Under deprivation of growth factor and ischemic injury, PC12 cells spontaneously undergoes apoptotic cell death. Serum and glucose deprivation markedly decreased the viability of PC12 cells, which was characterized with apparent apoptotic features such as membrane blebbing as well as fragmentation of genomic DNA and nuclei. However, the aqueous extract of Hwansodan significantly reduced serum and glucose deprivation-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Pretreatment of Hwansodan also ingibited the activation of caspase-3, in turn, degradation of ICAD/DFF45 was completely abolished in serum and glucose deprivated cells. Furthermore, pretreatment of Hwansodan obviously increased heme oxygenase 1 (HO-1) expression in PC12 cells. Taken together, the data suggest that the protective effects of Hwansodan against serum and glucose deprivation induced oxidative injuries may be achieved through the scavenging of reactive oxygene species accompanying with HO-1 induction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.2
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• pp.475-480
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• 2005

This study is designed to find out the effect of Corydalidis Tuber Carthami Flos Paeoniae Radix Rubra mixed water extract on adjuvant arthritis, and to check the stability for Corydalidis Tuber Carthami Flos Paeoniae Radix Rubra mixed water extract about the liver. At first, rats were devided into four groups; Normal(Non-treated group with FCA), Control(Group administrated saline everyday for 1 week after treatment of FCA), Sample A(group administrated Corydalidis Tuber Paeoniae Radix Rubra Carthami Flos mixed water extract $9mg/200{\sim}220g$ everyday 1 week after treatment of FCA) and Sample B(Group administrated Corydalidis Tuber Paeoniae Radix Rubra Carthami Flos mixed water extract $18mg/200{\sim}220g$ everyday 1 week after treatment of FCA). After then, separated searches were made on the change of edema rate, the number of WBC, the contented quantities of total protein, total bilirubin, GOT, GPT in the serum. Result : In the right planter edema, both of Sample groups showed a decrease with statistical significance in comparison with control group. In the WBC count, Sample B group showed a decrease with statistical significance in comparison with control group and also sample A group showed a decrease, but did not show statistical significance. In the serum total protein, both of samples did not show statistically significant decrease in comparison with the control group. In the serum total bilirubin, GOT and GPT, both of samples did not show any harmful change about the liver in comparison with the control group. According to the above results, it is concluded that Corydalidis Tuber Paeoniae Radix Rubra Carthami Flos mixed water extract had the therapeutic effect of anti-inflammation in adjuvant arthritis with no injury to liver.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.98-102
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• 2006

The present stuby was carried out to determine if Radix Glycyrrhizae extract exerts beneficial effect against the ischemia-induced acute renal failure in rabbits. Radix Glycyrrhizae was known to reinforce the function of the spleen and replenish Qi, remove heat and counteract toxicity, dispel phlegm and relieve cough, alleviate spasmodic pain, and to moderate drug actions. It's indications are weakness of the spleen and the stomach marked by lassitude and weakness; cardiac palpitation and shortness of breath; cough with much phlegm; spasmodic pain in the epigastrium, abdomen and limbs; carbuncles and sores. It is often used for reducing the toxic or drastic actions of other drugs. Rabbits were treated with Radix Glycyrrhizae extract via i.v., followed by renal ischemia/reperfusion. Fractional excretion of glucose and phosphate, lipid peroxidation and light microscopy were done to evaluate the beneficial effect of Radix Glycyrrhizae extract on ischemia/reperfusion induced acute renal failure. Renal ischemia/reperfusion caused increase of fractional excretion of glucose and phosphate increased in ischemia-induced animals, which was partially prevented by Radix Glycyrrhizae extract treatment. Ischemia/reperfusion increased lipid peroxidation, which was prevented by Radix Glycyrrhizae extract administration. And the beneficial effect of Radix Glycyrrhizae extract on ischemia/reperfusion induced kidney injury was shown through the light micrographic observation. These results indicate that lipid peroxidation plays a critical role in ischemia-induced acute renal failure. Radix Glycyrrhizae extract exerts the protective effect against acute renal failure induced by renal ischemia/reperfusion.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.483-491
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• 2019

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. ${\beta}$-Amyloid ($A{\beta}$) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in $A{\beta}$ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine $A_1$ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the $A{\beta}$ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of $A_1R$ is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.533-543
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• 2021

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.2
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• pp.158-162
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• 2019

This study is to show the clinical effect of additional CP Pharmacopuncture on hypoesthesia of lower limb which was occurred by laminectomy. The patients were treated using CP Pharmacopuncture, and other treatments including acupunture, moxibustion and herbal medication. The effect of treatment was measured by Numeric Rating Scale(NRS) and American Spinal Injury Association(ASIA) scale. After treatment, NRS was gradully reduced and ASIA scale's score was incresed. These results suggest that CP Pharmacopuncture might be a possible therapeutic option for hypoesthesia of lower limb which was occurred by laminectomy.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.21-28
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• 2019

Swertiamarin (STM) is an iridoid compound that is present in the Gentianaceae swertia genus. Here we investigated antiapoptotic effects of STM on carbon tetrachloride ($CCl_4$)-induced liver injury and its possible mechanisms. Adult male Sprague Dawley rats were randomly divided into a control group, an STM 200 mg/kg group, a $CCl_4$ group, a $CCl_4+STM$ 100 mg/kg group, and a $CCl_4+STM$ 200 mg/kg group. Rats in experimental groups were subcutaneously injected with 40% $CCl_4$ twice weekly for 8 weeks. STM (100 and 200 mg/kg per day) was orally given to experimental rats by gavage for 8 consecutive weeks. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins were evaluated by western blot analysis. The expression of $TGF-{\beta}1$, collagen I, collagen III, CTGF and fibronectin mRNA were estimated by qRT-PCR. The results showed that STM significantly reduced the number of TUNEL-positive cells compared with the $CCl_4$ group. The levels of Bax and cleaved caspase-3 proteins, and $TGF-{\beta}1$, collagen I, collagen III, CTGF, and fibronectin mRNA were significantly reduced by STM compared with the $CCl_4$ group. In addition, STM markedly abrogated the repression of Bcl-2 by $CCl_4$. STM also attenuated the activation of the PI3K/Akt pathway in the liver. These results suggested that STM ameliorated $CCl_4$-induced hepatocyte apoptosis in rats.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.593-601
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• 2021

Primary cilia on kidney tubular cells play crucial roles in maintaining structure and physiological function. Emerging evidence indicates that the absence of primary cilia, and their length, are associated with kidney diseases. The length of primary cilia in kidney tubular epithelial cells depends, at least in part, on oxidative stress and extracellular signal-regulated kinase 1/2 (ERK) activation. Hydrogen sulfide (H₂S) is involved in antioxidant systems and the ERK signaling pathway. Therefore, in this study, we investigated the role of H₂S in primary cilia elongation and the downstream pathway. In cultured Madin-Darby Canine Kidney cells, the length of primary cilia gradually increased up to 4 days after the cells were grown to confluent monolayers. In addition, the expression of H₂S-producing enzyme increased concomitantly with primary cilia length. Treatment with NaHS, an exogenous H₂S donor, accelerated the elongation of primary cilia whereas DL-propargylglycine (a cystathionine γ-lyase inhibitor) and hydroxylamine (a cystathionine-β-synthase inhibitor) delayed their elongation. NaHS treatment increased ERK activation and Sec10 and Arl13b protein expression, both of which are involved in cilia formation and elongation. Treatment with U0126, an ERK inhibitor, delayed elongation of primary cilia and blocked the effect of NaHS-mediated primary cilia elongation and Sec10 and Arl13b upregulation. Finally, we also found that H₂S accelerated primary cilia elongation after ischemic kidney injury. These results indicate that H₂S lengthens primary cilia through ERK activation and a consequent increase in Sec10 and Arl13b expression, suggesting that H₂S and its downstream targets could be novel molecular targets for regulating primary cilia.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.385-393
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• 2021

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in N-acetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.2
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• pp.131-137
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• 2021

Aging is the process spontaneously occurred in living organisms. Cardiac fibrosis is a pathophysiological process of cardiac aging. Mangiferin is a well-known C-glucoside xanthone in mango leaves with lots of beneficial properties. In this study, rat model of cardiac fibrosis was induced by injected with 150 mg/kg/d D-galactose for 8 weeks. The age-related cardiac decline was estimated by detecting the relative weight of heart, the serum levels of cardiac injury indicators and the expression of hypertrophic biomakers. Cardiac oxidative stress and local inflammation were measured by detecting the levels of malondialdehyde, enzymatic antioxidant status and proinflammatory cytokines. Cardiac fibrosis was evaluated by observing collagen deposition via masson and sirius red staining, as well as by examining the expression of extracellular matrix proteins via Western blot analysis. The cardiac activity of profibrotic TGF-β1/p38/MK2 signaling pathway was assessed by measuring the expression of TGF-β1 and the phosphorylation levels of p38 and MK2. It was observed that mangiferin ameliorated D-galactose-induced cardiac aging, attenuated cardiac oxidative stress, inflammation and fibrosis, as well as inhibited the activation of TGF-β1/p38/MK2 signaling pathway. These results showed that mangiferin could ameliorate cardiac fibrosis in D-galactose-induced aging rats possibly via inhibiting TGF-β/p38/MK2 signaling pathway.