Hye Lim Lee

A new cerebroside from the fruiting bodies of Hericium erinaceus and its applicability to cancer treatment.

A new cerebroside, cerebroside E (1) was isolated from the fruiting bodies of Hericium erinaceus (Hericiaceae). The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including extensive 2D NMR, HR-MS, and chemical reactions. Compound 1 was evaluated for its applicability to medicinal use in several human diseases using cell-based assays. As a result, compound 1 attenuated cisplatin-induced nephrotoxicity in LLC-PK1 cells and exhibited a significant inhibitory effect on angiogenesis in HUVECs. These results collectively reflect the beneficial effects of compound 1 in cancer treatment.

Protective effect of cirsimaritin against streptozotocin-induced apoptosis in pancreatic beta cells

Maintaining glucose homoeostasis is essential for the survival of cells. Despite the various health benefits of Korean thistle (Cirsium japonicum var. maackii), their effects on pancreatic β‐cell apoptosis in type 1 diabetes mellitus and the underlying mechanisms remain unclear, and experimentally investigated in this study.

Protective effect of ginsenoside Rh3 against anticancer drug-induced apoptosis in LLC-PK1 kidney cells

Background Ginsenosides are active components of Panax ginseng that exert various health benefits including kidney protection effect. The medicinal activity of ginsenosides can be enhanced by modulating their stereospecificity by heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the double bond at C-20(21) or C-20(22). Methods The present study investigated the kidney-protective effects of ginsenosides Rk2 and Rh3 against cisplatin, a platinum based anticancer drug, induced apoptotic damage in renal proximal LLC-PK1 cells. Results As a result, ginsenoside Rh3 shows a stronger protective effect than that shown by Rk2. Cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38, and cleaved caspase-3 decreased after cotreatment with ginsenoside Rh3. The increase in the percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment also significantly reduced after cotreatment with ginsenoside Rh3. Conclusion These results demonstrate that inhibition of the JNK and ERK mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of ginsenoside Rh3.

Wound healing effects of deoxyshikonin isolated from Jawoongo: In vitro and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE Jawoongo is a traditional drug ointment (with a traditional botanic formula) used for the treatment of burns and wounds in Korea. One of the components of Jawoongo is Lithospermi Radix (LR, the dried root of Lithospermum erythrorhizon Siebold & Zucc., also known as Zicao or Gromwell), which contains deoxyshikonin and its derivatives. OBJECTIVE The aim of the present study was to investigate the effects of deoxyshikonin on wound healing. MATERIALS AND METHODS The effects of LR extract and deoxyshikonin on tube formation and migration were measured in human umbilical vein vascular endothelial cells (HUVEC) and HaCaT cells, respectively. We evaluated protein expression of mitogen-activated protein kinase (MAPK) activation by Western blotting. The wound healing effects of deoxyshikonin was assessed in a mouse model of cutaneous wounds. RESULTS The results showed that deoxyshikonin enhanced tube formation in HUVEC and migration in HaCaT cells. From the western blot analysis, we found that deoxyshikonin stimulated the phosphorylation of p38 and extracellular signal-regulated kinase (ERK) in HaCaT cells. Moreover, 20µm deoxyshikonin-treated groups showed accelerated wound closure compared with the controls in a mouse model of cutaneous wounds. CONCLUSION In conclusion, the current data indicate that deoxyshikonin treatment elevated tube formation in HUVECs, and that deoxyshikonin-induced proliferation and migration in HaCaT cells were mediated by the activation of ERK and p38 MAPKs, respectively. Collectively, these data suggest that deoxyshikonin in Jawoongo must be an active compound for may be wound healing.

Assessment of the anti-metastatic properties of sanguiin H-6 in HUVECs and MDA-MB-231 human breast cancer cells

The anti-metastatic properties of sanguiin H-6 were examined in human umbilical vein vascular endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cells. In HUVECs, sanguiin H-6 inhibited the density of migrated cells compared to that observed after treatment with the vehicle. In addition, sanguiin H-6 at a concentration of 6.25μM significantly blocked tube formation. Treatment with up to 25μM sanguiin H-6 had no effect on MDA-MB-231 cells, whereas treatment with 200μM sanguiin H-6 decreased cell viability. Sanguiin H-6 significantly decreased the expression levels of vascular endothelial growth factor (VEGF), phosphorylated Akt, and extracellular signal-regulated kinase 1/2 (ERK1/2) in MDA-MB-231 cells. These findings suggest that sanguiin H-6 is potentially useful as an anti-metastatic agent.

Beneficial effects of Panax ginseng for the treatment and prevention of neurodegenerative diseases: past findings and future directions

In recent years, several therapeutic drugs have been rationally designed and synthesized based on the novel knowledge gained from investigating the actions of biologically active chemicals derived from foods, plants, and medicinal herbs. One of the major advantages of these naturalistic chemicals is their ability to interact with multiple targets in the body resulting in a combined beneficial effect. Ginseng is a perennial herb (Araliaceae family), a species within the genus Panax, and a highly valued and popular medicinal plant. Evidence for the medicinal and health benefits of Panax ginseng and its components in preventing neurodegeneration has increased significantly in the past decade. The beneficial effects of P. ginseng on neurodegenerative diseases have been attributed primarily to the antioxidative and immunomodulatory activities of its ginsenoside components. Mechanistic studies on the neuroprotective effects of ginsenosides revealed that they act not only as antioxidants but also as modulators of intracellular neuronal signaling and metabolism, cell survival/death genes, and mitochondrial function. The goal of the present paper is to provide a brief review of recent knowledge and developments concerning the beneficial effects as well as the mechanism of action of P. ginseng and its components in the treatment and prevention of neurodegenerative diseases.

Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Background Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results The reduction in LLC-PK1 cell viability by 60μM FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with 60μM FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by 60μM FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

Cytotoxic effect of sanguiin H-6 on MCF-7 and MDA-MB-231 human breast carcinoma cells

Sanguiin H-6 is a dimer of casuarictin linked by a bond between the gallic acid residue and one of the hexahydroxydiphenic acid units. It is an effective compound extracted from Rubus coreanus. It has an anticancer effect against several human cancer cells; however, its effect on breast cancer cells has not been clearly demonstrated. Thus, we aimed to investigate the anticancer effect and mechanism of action of sanguiin H-6 against two human breast carcinoma cell lines (MCF-7 and MDA-MB-231). We found that sanguiin H-6 significantly reduced cell viability in a concentration-dependent manner. It also increased the rates at which MCF-7 and MDA-MB-231 cells underwent apoptosis. Furthermore, sanguiin H-6 induced the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, which resulted in apoptosis. However, cleavage of caspase-9 was only detectable in MCF-7 cells. In addition, sanguiin H-6 increased the ratio of Bax to Bcl-2 in both MCF-7 and MDA-MB-231 cells. These findings suggest that sanguiin H-6 is a potent therapeutic agent against breast cancer cells. In addition, it exerts its anticancer effect in an estrogen-receptor-independent manner.

Preventive Effect and Safety of a Follicle Stimulating Hormone Inhibitory Formulation Containing a Mixture of Coicis Semen and Artemisia capillaris for Precocious Puberty: A Preliminary Experimental Study Using Female Rats

Background Precocious puberty is a common endocrine disease in children. Inappropriate activation of hypothalamic–pituitary–gonadal axis leads to the development of secondary sexual characteristics at an earlier age than normal children and causes short stature in adulthood. Objectives The aim of this study is to evaluate the preventive effects of a herbal formulation containing a mixture of Coicis Semen and Artemisia capillaris (hEIF extract) on precocious puberty. Methods The preventive effect of hEIF extract on precocious puberty in rats was evaluated by measuring blood component after 3 weeks of treatment via oral administration. Network pharmacological analyses were performed to predict the bioactive components of hEIF extract. Results In vivo studies showed that hEIF extract significantly reduced follicle stimulating hormone (FSH) levels. After treatment with 200 mg/kg of hEIF extract, the FSH level was 5.33 ± 1.10 ng/mL, whereas the FSH level in the vehicle group was 46.73 ± 0.80 ng/mL. Moreover, the use of hEIF extract did not stimulate body growth and bone accretion in rats. The network pharmacological analysis led to the identification of multiple targets of hEIF extract related to lipolysis and the female sex hormone-related pathways. Conclusion hEIF extract can be used as an FSH inhibitor for the treatment of precocious puberty.

A New Steroidal Saponin from the Tubers of Ophiopogon japonicus and Its Protective Effect Against Cisplatin-Induced Renal Cell Toxicity

A new furostanol saponin, ophiopogonin T, was isolated from the tubers of Ophiopogon japonicus. Its structure was established by extensive spectroscopic techniques including 1D (1H and 13C) and 2D nuclear magnetic resonance (NMR) experiments (correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC) and nuclear Overhauser effect spectroscopy (NOESY)), high-resolution electrospray ionization mass spectrometry (ESIMS), and chemical methods. Using cell-based assays, this compound was evaluated for its cytotoxic effect on cancer cell lines and its protective effect against anticancer drug-induced nephrotoxicity. Cisplatin-induced cytotoxicity in porcine kidney (LLC-PK1) cells was significantly reduced upon treatment with ophiopogonin T, without affecting human hepatoma (HepG2) cancer cell proliferation or tube formation in human umbilical vein endothelial cells (HUVECs). These results collectively reflect the beneficial effect of ophiopogonin T on the side effects of cisplatin.