• CELLMED
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• v.13 no.14
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• pp.15.1-15.15
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• 2023

Background and objective: A new formular CPC22 consists of Cynanchum wilfordii root, Pueraria thomsonii flower, and Citrus unshiu peel and has been developed to improve the postmenopausal symptoms. The research intended to evaluate whether CPC22 would regulate bone loss, hot flashes, and dysregulated lipid metabolism in ovariectomized (OVX) postmenopausal mice. Method: The OVX mice were orally administered with CPC22 daily for 7 weeks. Results: CPC22 regulated OVX-induced bon loss by enhancing serum osteoprotegerin, alkaline phosphatase, and osteocalcin levels and diminishing serum receptor-activator of the NF-κB ligand (RANKL), collagen type 1 cross-linked N-telopeptide, and tartrate-resistant acid phosphatase levels. As a result of CPC22 treatment, notable decreases in tail skin temperature and rectal temperature were observed, along with diminishment in hypothalamic RANKL and monoamine oxidase A levels and enhancement in hypothalamic serotonin (5-HT), norepinephrine, dopamine, 5-HT2A, and estrogen receptor-β levels. CPC22 enhanced levels of serum estrogen and diminished levels of serum follicle-stimulating hormone and luteinizing hormone. CPC22 regulated levels of serum lipid metabolites, including total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Furthermore, CPC22 diminished levels of serum blood urea nitrogen, creatine kinase, alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase and restored vaginal dryness without affecting uterus atrophy index and vagina weights. Conclusion: Therefore, these results indicated that CPC22 improves OVX-induced bone loss, hot flashes, and dysregulated lipid metabolism by compensating for estrogen deficiency without side effects, suggesting that CPC22 may be used for the prevention and treatment of post menopause.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.201-209
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• 1996

Restoration of the blood flow after a period of ischemia is accompanied by generation of toxic oxygen radicals. This phenomenon may account for the occurrence of reperfusion-mediated tissue injury in ischemic hearts. In in vitro studies, although oxygen radicals can be generated from a variety of sources, including xanthine oxidase system, activated leucocytes, mitochondria and others, the most important source and mechanism of oxygen radical production in the post-ischemic reperfused hearts is unclear. In the present study, we tested the hypothesis that the respiratory chain of mitochondria might be an important source of oxygen radicals which are responsible for the development of the reperfusion injury of ischemic hearts. Langendorff-perfused, isolated rat hearts were subjected to 30 min of global ischemia at $37^{\circ}C$, followed by reperfusion. Amytal, a reversible inhibitor of mitochondrial respiration, was employed to assess the mitochondrial contributions to the development of the reperfusion injury. Intact mitochonria were isolated from the control and the post-ischemic reperfused hearts. Mitochondrial oxygen radical generation was measured by chemiluminescence method and the oxidative tissue damage was estimated by measuring a lipid peroxidation product, malondialdehyde(MDA). To evaluate the extent of the reperfusion injury, post-ischemic functional recovery and lactate dehydrogenase(LDH) release were assessed and compared in Amytal-treated and -untreated hearts. Upon reperfusion of the ischemic hearts, MDA release into the coronary effluent was markedly increased. MDA content of mitochondria isolated from the post-ischemic reperfused hearts was increased to 152% of preischemic value, whereas minimal change was observed in extramitochondrial fraction. The generation of superoxide anion was increased about twice in mitochondria from the reperfused hearts than in those from the control hearts. Amytal inhibited the mitochondrial superoxide generation significantly and also suppressed MDA production in the reperfused hearts. Additionally, Amytal prevented the contractile dysfunction and the increased release of LDH observed in the reperfused hearts. In conclusion, these results indicate that the respiratory chain of mitochondria may be an important source of oxygen radical formation in post-ischemic reperfused hearts, and that oxygen radicals originating from the mitochondria may contribute to the development of myocardial reperfusion injury.

• Journal of Life Science
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• v.29 no.11
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• pp.1179-1191
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• 2019

Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.