• Journal of Ginseng Research
• /
• v.43 no.2
• /
• pp.218-225
• /
• 2019

Background: Streptococcus pneumoniae, more than 90 serotypes of which exist, is recognized as an etiologic agent of pneumonia, meningitis, and sepsis associated with significant morbidity and mortality worldwide. Immunization with a pneumococcal pep27 mutant (${{\Delta}}pep27$) has been shown to confer comprehensive, long-term protection against even nontypeable strains. However, ${{\Delta}}pep27$ is effective as a vaccine only after at least three rounds of immunization. Therefore, treatments capable of enhancing the efficiency of ${{\Delta}}pep27$ immunization should be identified without delay. Panax ginseng Mayer has already been shown to have pharmacological and antioxidant effects. Here, the ability of Korean Red Ginseng (KRG) to enhance the efficacy of ${{\Delta}}pep27$ immunization was investigated. Methods: Mice were treated with KRG and immunized with ${{\Delta}}pep27$ before infection with the pathogenic S. pneumoniae strain D39. Total reactive oxygen species production was measured using lung homogenates, and inducible nitric oxide (NO) synthase and antiapoptotic protein expression was determined by immunoblotting. The phagocytic activity of peritoneal macrophages was also tested after KRG treatment. Results: Compared with the other treatments, KRG significantly increased survival rate after lethal challenge and resulted in faster bacterial clearance via increased phagocytosis. Moreover, KRG enhanced ${{\Delta}}pep27$ vaccine efficacy by inhibiting reactive oxygen species production, reducing extracellular signal-regulated kinase apoptosis signaling and inflammation. Conclusion: Taken together, our results suggest that KRG reduces the time required for immunization with the ${{\Delta}}pep27$ vaccine by enhancing its efficacy.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2019.10a
• /
• pp.67-67
• /
• 2019

Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of ${\alpha}$-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced $NF-{\kappa}B$ signaling activation through blocking $I{\kappa}B-{\alpha}$ degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

• Journal of Pharmacopuncture
• /
• v.24 no.2
• /
• pp.41-53
• /
• 2021

Objectives: Cesarean sections are one of the common surgical procedures around the world. Management of cesarean section side effects, including pain, hematoma, delayed wound healing, is of particular importance in maintaining maternal health and ability to care for the baby. The tendency to use complementary medicine strategies is on the rise because of the easy treatment with low side effects. The purpose of this study was to systematically review the efficacy and safety of clinical trials performed in Iran and worldwide on the effect of complementary medicine on pain relief and wound healing after cesarean section. Methods: PRISMA checklist was followed to prepare the report of this systematic review. The search process was carried out on databases on databases of Magiran, SID, Iran Medex, Scopus, Pub Med, Science direct, Medline and Cochrane library using keywords of cesarean, pain, wound healing, Herbal medicine, acupressure, massage, complementary medicine and their Persian equivalent and all possible combinations, from inception until February 2020. We used the Jadad scale to assess the quality of the searched articles. According to the Jadad scale, the articles with a score of at least 3 were included in the study. Results: Finally, 28 clinical trials (with a sample size of 3,245) scored at least 3 on the Jadad scale were included into the analysis. This article reviewed 13 articles on medicinal herbs, 4 articles on massage, 1 article on reflexology, 2 articles on acupressure. Conclusion: According to the present review, the use of medicinal herbs was the most common method of complementary medicine in pain relief and wound healing after cesarean section.

• Journal of Nutrition and Health
• /
• v.54 no.4
• /
• pp.342-354
• /
• 2021

Purpose: Obesity is a serious public health issue for the modern society and is considered a chronic health hazard. There are many surgical and pharmacological approaches to treat obesity. However, various potentially hazardous side effects remain the biggest challenge. Therefore, diets based on foods derived from natural products have gained increasing attention compared to anti-obesity drugs. Recently, research on edible insects as a food source has been a topic of considerable interest in the scientific communities. This study examined the anti-obesity effects of ingesting an edible insect by feeding a high-fat diet (HFD)-induced obese mouse models with a diet containing Tenebrio molitor larvae powder (TMLP). Methods: Six-week-old female C57BL/6J mice were divided into 4 groups according to treatment: 100% normal diet (ND), 100% HFD (HFD), HFD 99% + TMLP 1% (TMLP), and HFD 97% + TMLP 3% (TMLP 3%). TMLP was added to the HFD for 6 weeks for the latter two groups. Results: Compared to the HFD group, mice in the TMLP group showed weight loss, and micro-computed tomographic imaging revealed that the volume of the adipose tissue in the abdominal area also showed significant reduction. After an autopsy, the fat weight was found to be significantly reduced in the TMLP group compared to the HFD group. In addition, the degree of fat cell deposition in the liver tissue and the size of the adipocytes significantly decreased in the TMLP group. Reverse transcription polymerase chain reaction analysis for the mRNA expression of adipogenesis-related genes namely CCAAT-enhancer-binding proteins (C/EBP-β, C/EBP-δ), and fatty acid-binding protein 4 (FABP4) showed that the expression levels of these genes were significantly reduced in the TMLP group compared to the HFD group. Serum leptin level also decreased significantly in the TMLP group in the comparison with the HFD group. In addition, total cholesterol, triglyceride, and glucose levels in mouse serum also decreased in the TMLP group. Conclusion: Taken together, our results showed that TMLP effectively inhibited adipocyte growth and reduced body weight in obese mice.

• Journal of Ginseng Research
• /
• v.46 no.3
• /
• pp.387-395
• /
• 2022

Background: Fermentation may alter the bioavailability of certain compounds, which may affect their efficacy and pharmacological responses. This study investigated the antiplatelet effects of red ginseng extract (RGE) and fermented red ginseng extract (FRG). Methods: A rodent model was used to evaluate the antiplatelet and antithrombotic effects of the extracts. Rats were orally fed with human equivalent doses of the extracts for 1 week and examined for various signaling pathways using standard in vivo and ex vivo techniques. Light transmission aggregometry was performed, and calcium mobilization, dense granule secretion, integrin α_IIbβ₃-mediated signaling molecules, cyclic nucleotide signaling events, and various protein molecules were evaluated ex vivo in collagen-stimulated washed platelets. Furthermore, antithrombotic properties were evaluated using a standard acute pulmonary thromboembolism model, and the effects on hemostasis were investigated using rat and mice models. Results: Both RGE and FRG significantly inhibited platelet aggregation, calcium mobilization, and dense granule secretion along with integrin-mediated fibrinogen binding and fibrinogen adhesion. cAMP levels were found to be elevated in RGE-treated rat platelets. Ginseng extracts did not exert any effect on prothrombin time and activated partial thromboplastin time. RGE-treated mice showed significantly better survival under thrombosis than FRG-treated mice, with no effects on hemostasis, whereas FRG-treated mice exhibited a slight increment in bleeding time. Conclusion: Both extracts, especially RGE, are remarkable supplements to maintain cardiovascular health and are potential candidates for the treatment and prevention of platelet-related cardiovascular disorders.

• Biomolecules & Therapeutics
• /
• v.30 no.1
• /
• pp.72-79
• /
• 2022

Licochalcone H (LCH) is a phenolic compound synthetically derived from licochalcone C (LCC) that exerts anticancer activity. In this study, we investigated the anticancer activity of LCH in human skin cancer A375 and A431 cells. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assay was used to evaluate the antiproliferative activity of LCH. Cell cycle distribution and the induction of apoptosis were analyzed by flow cytometry. Western blotting assays were performed to detect the levels of proteins involved in cell cycle progression, apoptosis, and the JAK2/STAT3 signaling pathway. LCH inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay revealed that LCH induced apoptosis, and the LCH-induced apoptosis was accompanied by cell cycle arrest in the G1 phase. Western blot analysis showed that the phosphorylation of JAK2 and STAT3 was decreased by treatment with LCH. The inhibition of the JAK2/STAT3 signaling pathway by pharmacological inhibitors against JAK2/STAT3 (cryptotanshinone (CTS) and S3I-201) simulated the antiproliferative effect of LCH suggesting that LCH induced apoptosis by modulating JAK2/STAT3 signaling.

• Molecules and Cells
• /
• v.45 no.7
• /
• pp.454-464
• /
• 2022

DJ-1 is one of the causative genes of early-onset familial Parkinson's disease (PD). As a result, DJ-1 influences the pathogenesis of sporadic PD. DJ-1 has various physiological functions that converge to control the levels of intracellular reactive oxygen species (ROS). Based on genetic analyses that sought to investigate novel antioxidant DJ-1 downstream genes, pyruvate dehydrogenase (PDH) kinase (PDK) was demonstrated to increase survival rates and decrease dopaminergic (DA) neuron loss in DJ-1 mutant flies under oxidative stress. PDK phosphorylates and inhibits the PDH complex (PDC), subsequently downregulating glucose metabolism in the mitochondria, which is a major source of intracellular ROS. A loss-of-function mutation in PDK was not found to have a significant effect on fly development and reproduction, but severely ameliorated oxidative stress resistance. Thus, PDK plays a critical role in the protection against oxidative stress. Loss of PDH phosphatase (PDP), which dephosphorylates and activates PDH, was also shown to protect DJ-1 mutants from oxidative stress, ultimately supporting our findings. Further genetic analyses suggested that DJ-1 controls PDK expression through hypoxia-inducible factor 1 (HIF-1), a transcriptional regulator of the adaptive response to hypoxia and oxidative stress. Furthermore, CPI-613, an inhibitor of PDH, protected DJ-1 null flies from oxidative stress, suggesting that the genetic and pharmacological inhibition of PDH may be a novel treatment strategy for PD associated with DJ-1 dysfunction.

• BMB Reports
• /
• v.55 no.7
• /
• pp.354-359
• /
• 2022

MitoNEET, a mitochondrial outer membrane protein containing the Asn-Glu-Glu-Thr (NEET) sequence, controls the formation of intermitochondrial junctions and confers autophagy resistance. Moreover, mitoNEET as a mitochondrial substrate undergoes ubiquitination by activated Parkin during the initiation of mitophagy. Therefore, mitoNEET is linked to the regulation of autophagy and mitophagy. Mitophagy is the selective removal of the damaged or unnecessary mitochondria, which is crucial to sustaining mitochondrial quality control. In numerous human diseases, the accumulation of damaged mitochondria by impaired mitophagy has been observed. However, the therapeutic strategy targeting of mitoNEET as a mitophagy-enhancing mediator requires further research. Herein, we confirmed that mitophagy is indeed activated by mitoNEET inhibition. CCCP (carbonyl cyanide m-chlorophenyl hydrazone), which leads to mitochondrial depolarization, induces mitochondrial dysfunction and superoxide production. This, in turn, contributes to the induction of mitophagy; mitoNEET protein levels were initially increased before an increase in LC3-II protein following CCCP treatment. Pharmacological inhibition of mitoNEET using mitoNEET Ligand-1 (NL-1) promoted accumulation of Pink1 and Parkin, which are mitophagy-associated proteins, and activation of mitochondria-lysosome crosstalk, in comparison to CCCP alone. Inhibition of mitoNEET using NL-1, or mitoNEET shRNA transfected into RAW264.7 cells, abrogated CCCP-induced ROS and mitochondrial cell death; additionally, it activated the expression of PGC-1α and SOD2, regulators of oxidative metabolism. In particular, the increase in PGC-1α, which is a major regulator of mitochondrial biogenesis, promotes mitochondrial quality control. These results indicated that mitoNEET is a potential therapeutic target in numerous human diseases to enhance mitophagy and protect cells by maintaining a network of healthy mitochondria.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.35 no.3
• /
• pp.24-36
• /
• 2022

Objectives: Excessive melanin production leads to skin pigmentation, which causes various cosmetic and health problems. Citrus unshiu Markovich peel (CS) and Cimicifuga dahurica (CD) have long been widely used as a oriental medicinal plant because of their pharmacological properties including anti-ulcer, anti-oxidant, and anti-inflammatory properties. Methods: In this study, we investigated the inhibitory effects of CS, CD extracts or CS:CD=1:2 mixture on melanogenesis according to the various extraction methods. CS and CD extracted were prepared by ethanol extraction (EE), ultrasonification extraction (USE), Supercritical extraction (SCE), reflux extraction (RE), respectively. Results: DPPH radical scavenging and tyrosinase inhibitory activity of CD extracts or CS:CD=1:2 mixture were increased in dose-dependent manners. In addition, we evaluated the effect of CS, CD extracts or CS:CD=1:2 mixture on tyrosinase activity and melanogenesis in α-melanocyte stimulating hormone-induced B16-F10 melanoma cells. CS, CD extracts or CS:CD=1:2 mixture significantly inhibited tyrosinase activity and melanogenesis at 10-200 ㎍/mL. Conclusions: Therefore, our study suggests that CS and CD extracts have potential as a safe treatment for excessive pigmentation or as a natural ingredient in cosmetics.

• Journal of Veterinary Science
• /
• v.22 no.6
• /
• pp.92.1-92.12
• /
• 2021

Background: Naringin and its aglycone naringenin are citrus-derived flavonoids with several pharmacological effects. On the other hand, the mechanism for the anti-diabetic effects of naringenin and naringin are controversial and remain to be clarified further. Objective: This study examined the relationship between glucose uptake and AMP-activated protein kinase (AMPK) phosphorylation by naringenin and naringin in high glucose-treated HepG2 cells. Methods: Glucose uptake was measured using the 2-NBDG fluorescent D-glucose analog. The phosphorylation levels of AMPK and GSK3β (Glycogen synthase kinase 3 beta) were observed by Western blotting. Molecular docking analysis was performed to evaluate the binding affinity of naringenin and naringin to the γ-subunit of AMPK. Results: The treatment with naringenin and naringin stimulated glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Both flavonoids increased glucose uptake by promoting the phosphorylation of AMPK at Thr172 and increased the phosphorylation of GSK3β. Molecular docking analysis showed that both naringenin and naringin bind to the γ-subunit of AMPK with high binding affinities. In particular, naringin showed higher binding affinity than the true modulator, AMP with all three CBS domains (CBS1, 3, and 4) in the γ-subunit of AMPK. Therefore, both naringenin and naringin could be positive modulators of AMPK activation, which enhance glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Conclusions: The increased phosphorylation of AMPK at Thr172 by naringenin and naringin might enhance glucose uptake regardless of insulin stimulation in high glucose treated HepG2 cells.