• Herbal Formula Science
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• v.31 no.3
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• pp.183-191
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• 2023

Objective : UVB damages skin health by causing skin redness and intense inflammation, sunburn, and skin cancer. Paeoniae Radix Alba has been used to relieve gynecological symptoms, muscle spasms, and skin ailments. This study was conducted to confirm whether it has a protective effect against UVB photodamage. Methods : Ethanol extract of Paeoniae Radix Alba (PRA) was prepared by extracting 100 g Paeoniae Radix Alba in 1 L of ethanol for 48 h. Apoptosis was monitored by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and expression levels of apoptosis indicator proteins, and tyrosinase activity was measured with a colorimetric commercial kit. Results : In human keratinocyte HaCaT cells, PRA reduced UVB-induced cell death through apoptosis by inhibiting PARP cleavage and caspase-3 and -9. UVB-induced increase in cellular reactive oxygen species (ROS) was suppressed by PRA pretreatment. PRA also showed dose-dependent ABTS and DPPH radical scavenging activities. Furthermore, the inhibitory effect of tyrosinase activity by PRA was confirmed. Conclusion : These results demonstrated the protective role of PRA in UVB photodamage of human keratinocytes, mainly due to its antioxidant and antiapoptotic properties. We also suggest that PRA can be considered as an effective natural agent to prevent skin photodamage.

• Korean Journal of Veterinary Research
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• v.64 no.1
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• pp.2.1-2.8
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• 2024

This study was performed to assess the antiapoptotic effect of canine platelet-rich plasma (PRP) treated on the canine adipose-derived mesenchymal stem cells (cMSCs) under cold ischemic conditions. The effect of preventing apoptosis of cMSCs was evaluated in the apoptotic condition induced by cold ischemic injury in vitro. To determine the progression of apoptosis, the changes in cell nucleus were observed using 4',6-diamidino-2-phenylindole (DAPI) fluorescence staining. In addition, we examined the mitochondrial membrane potential (MMP) and caspase-3 activity. When the cold hypoxic injury was applied to cMSCs, the apoptotic change was observed by DAPI staining, mitochondrial staining for MMP, and caspase-3 assay. PRP significantly decreased the number of apoptotic cells. Nuclear shrinkage and fragmentation of apoptotic cells in control groups were observed by DAPI staining. The MMP was recovered by the treatment of PRP. In addition, when the luminescence intensity was measured for caspase-3 activity, the value was significantly higher in the PRP treated groups than the control groups. The results of this study showed that the PRP may have a beneficial effect on apoptosis induced by cold ischemic injury.

• Clinical and Experimental Pediatrics
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• v.58 no.2
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• pp.41-46
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• 2015

Growth hormone (GH) treatment has been increasingly widely used for children with GH deficiencies as the survival rate of pediatric patients with malignancies has increased. Both GH and insulin-like growth factor-I have mitogenic and antiapoptotic activity, prompting concern that GH treatment may be associated with tumor development. In this review, the authors examined the relationship between GH treatment and cancer risk in terms of de novo malignancy, recurrence, and secondary neoplasm. Although the results from numerous studies were not entirely consistent, this review of various clinical and epidemiological studies demonstrated that there is no clear evidence of a causal relationship between GH treatment and tumor development. Nonetheless, a small number of studies reported that childhood cancer survivors who receive GH treatment have a small increased risk of developing de novo cancer and secondary malignant neoplasm. Therefore, regular follow-ups and careful examination for development of cancer should be required in children who receive GH treatment. Continued surveillance for an extended period is essential for monitoring long-term safety.

• International Journal of Oral Biology
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• v.32 no.2
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• pp.51-57
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• 2007

Cyclosporin A (CsA) plays an important role in clinical medicine and basic biology as an immunosuppressant and a mitochondrial permeability blocker, respectively. It was reported that CsA has a protective role by preventing apoptosis and promoting the proliferation in severed neurons. However, the molecular mechanisms for CsA-induced neuronal cell proliferation are unclear. In this study, we examined the mechanisms underlying the CsA-induced proliferation of PC12 cells. CsA increased the viability of PC12 cells in a dose(over $0.1{\sim}10\;{\mu}M$)-and time-dependent manner. The level of ROS generation was decreased in the CsA-treated PC12 cells. Expression of Bcl-2, an antiapoptotic molecule that inhibits the release of cytochrome c from the mitochondria into the cytosol, was upregulated, whereas Bax, a proapototic molecule, was not changed in the CsA-treated PC12 cells. CsA downregulated the mRNA expression of VDAC 1 and VDAC 3, but VDAC 2 was not changed in the CsA-treated PC12 cells. The level of cytosolic cytochrome c released from the mitochondria and the caspase-3 activity were attenuated in the CsA-treated PC12 cells. These results suggest that the mitochondria-mediated apoptotic signal and Bcl-2 family may play an important role in CsA-induced proliferation in PC12 cells.

• Journal of Pharmacopuncture
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• v.17 no.2
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• pp.7-17
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• 2014

Objectives: Condurango is widely used in various systems of complementary and alternative medicines (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats, in vivo to validate its use as traditional medicine. Methods: Fifteen male and 15 female Sprague-Dawley (SD) rats were treated with 0.28 mg/kg of Sweet Bee Venom (SBV) (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate reactive oxygen species (ROS), which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer cell-death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusion: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.86-87
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• 2015

Objectives: Condurango is widely used in various systems of complementary and alternative medicine (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats in vivo to validate its use as a traditional medicine. Methods: After one month of scheduled BaP feeding (50 mg/kg body-weight), lung cancer developed after four months. BaP-intoxicated rats were then treated with Condurango (0.06 mL) twice daily starting at the end of the four months for an additional one, two and three months, respectively. Effects of Condurango were evaluated by analyzing lung histology, reactive oxygen species (ROS) and antioxidant biomarkers, DNA-fragmentation, RT-PCR (Reverese Transcriptase-Polymerase Chain Reaction), ELISA (Enzyme linked immunosorbent assay) and western blot of several apoptotic signalling markers and comparing the results against those obtained for controls. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate ROS, which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer-cell death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusions: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6369-6374
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• 2012

Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an $IC_{50}{\sim}28.8{\mu}M$. Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma.

• The Journal of Korean Medicine
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• v.30 no.4
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• pp.79-92
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• 2009

Objectives: The aim of the present study was to explore the neuroprotective effect and the possible mechanism of the PD-1 extracts on 1-methyl-4-phenyl-1,2,3,6-tetrahydrophridine (MPTP)-lesioned C57BL/6 mouse model of Parkinson's disease (PD). Methods: The mice were supplemented (or not) with 50 or 100 mg/kg/day of PD-1 for 2 weeks, after which MPTP was injected intraperitoneally. We observed that daily administration of PD-1 prevented MPTP-induced depletion of striatal DA, and maintained striatal and nigral tyrosine hydroxylase (TH) protein levels. Results: Our results demonstrated that mice treated with PD-1 prior to MPTP administration showed more abundant TH-immunopositive (TH-ir) fibers and neurons than mice given only MPTP, indicating that PD-1 protects dopaminergic striatal fibers and nigral neurons from MPTP insults. Possible neuroprotective effect of PD-1 was further studied by the detection of antiapoptotic protein (bcl-2) and proapoptotic protein (Bax). In this assay, MPTP elevated the Bax protein and decreased the bcl-2 protein, while these expressions were prevented by PD-1 pre-treatment. Conclusions: The present results suggest that PD-1 is able to protect dopaminergic neurons from MPTP-induced neuronal injury with anti-apoptotic activity being one of the possible mechanisms.

• Journal of Ginseng Research
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• v.36 no.1
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• pp.78-85
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• 2012

Endothelial progenitor cells (EPC) are a population of cells that circulate in the blood stream. They play a role in angiogenesis and, therefore, can be prognostic markers of vascular repair. Ginsenoside $Rg_3$ prevents endothelial cell apoptosis through the inhibition of the mitochondrial caspase pathway. It also affects estrogen activity, which reduces EPC senescence. Sun ginseng (SG), which is heat-processed ginseng, has a high content of ginsenosides. The purpose of this study was to investigate the protective effects of SG on senescence-associated apoptosis in EPCs. In order to isolate EPCs, mononuclear cells of human blood buffy coats were cultured and characterized by their uptake of acetylated low-density lipoprotein (acLDL) and their binding of Ulex europaeus agglutinin I (ulex-lectin). Flow cytometry with annexin-V staining was performed in order to assess early and late apoptosis. Senescence was determined by ${\beta}$-galactosidase (${\beta}$-gal) staining. Staining with 4'-6-Diamidino-2-phenylindole verified that most adherent cells (93${\pm}$2.7%) were acLDL-positive and ulex-lectin-positive. The percentage of ${\beta}$-gal-positive EPCs was decreased from 93.8${\pm}$2.0% to 62.5${\pm}$3.6% by SG treatment. A fluorescence-activated cell sorter (FACS) analysis showed that 4.9% of EPCs were late apoptotic in controls. Sun ginseng decreased the apoptotic cell population by 39% in the late stage of apoptosis from control baseline levels. In conclusion, these results show antisenescent and antiapoptotic effects of SG in human-derived EPCs, indicating that SG can enhance EPC-mediated repair mechanisms.

• Journal of Ginseng Research
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• v.37 no.4
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• pp.413-424
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• 2013

Korean Red Ginseng extract (KRGE) is a traditional herbal medicine utilized to prevent endothelium dysfunction in the cardiovascular system; however, its underlying mechanism has not been clearly elucidated. We here examined the pharmacological effect and molecular mechanism of KRGE on apoptosis of human umbilical vein endothelial cells (HUVECs) in a serum-deprived apoptosis model. KRGE protected HUVECs from serum-deprived apoptosis by inhibiting mitochondrial cytochrome c release and caspase-9/-3 activation. This protective effect was significantly higher than that of American ginseng extract. KRGE treatment increased antiapoptotic Bcl-2 and Bcl-$X_L$ protein expression and Akt-dependent Bad phosphorylation. Moreover, KRGE prevented serum deprivation-induced subcellular redistribution of these proteins between the mitochondrion and the cytosol, resulting in suppression of mitochondrial cytochrome c release. In addition, KRGE increased nitric oxide (NO) production via Akt-dependent activation of endothelial NO synthase (eNOS), as well as inhibited caspase-9/-3 activities. These increases were reversed by co-treatment of cells with inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) and pre-incubation of cell lysates in dithiothreitol, indicating KRGE induces NO-mediated caspase modification. Indeed, KRGE inhibited caspase-3 activity via S-nitrosylation. These findings suggest that KRGE prevents serum deprivation-induced HUVEC apoptosis via increased Bcl-2 and Bcl-$X_L$ protein expression, PI3K/Akt-dependent Bad phosphorylation, and eNOS/NO-mediated S-nitrosylation of caspases. The cytoprotective property of KRGE may be valuable for developing new pharmaceutical means that limit endothelial cell death induced during the pathogenesis of vascular diseases.