• Natural Product Sciences
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• v.29 no.2
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• pp.104-112
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• 2023

COVID-19 caused a catastrophe in human health. People infected with COVID-19 also suffer from various clinical illnesses during and after the infection. The Boerhavia diffusa plant is well known for its antihypertensive activity. ACE-II inhibitors and calcium channel blockers are reported as mechanisms for the antihypertensive activity of B. diffusa phytoconstituents. Various studies have said ACE-II is the virus's binding site to attack host cells. COVID-19 treatment commonly employs a variety of synthetic antiviral and steroidal drugs. As a result, other clinical illnesses, such as hypertension and hyperglycemia, emerge as serious complications. Safe and effective drug delivery is a prime objective of the drug development process. COVID-19 is treated with various herbal treatments; however, they are not widely used due to their low potency. Many herbal plants and formulations are used to treat COVID-19 infection, in which B. diffusa is the most widely used plant. The current study relies on discovering active phytoconstituents with ACE-II inhibitory activity in the B. diffusa plant. As a result, it can be used as a treatment option for patients with COVID-19 and related diseases. Different phytoconstituents of the B. diffusa plant were selected from the reported literature. The activity of phytoconstituents against ACE-II proteins has been studied. Molecular docking and ligand-protein interaction computation tools are used in the in-silico experiment. Physicochemical, drug-likeness, water solubility, lipophilicity, and pharmacokinetic parameters are used to evaluate phytoconstituents. Liriodenine has the best drug-likeness, bioactivity, and binding score characteristics among the selected ligands. The in-silico study aims to find the therapeutic potential of B. diffusa phytoconstituents against ACE-II. Targeting ACE-II also shows an effect against SARS-CoV-2. It can serve as a rationale for designing a drug for patient infected with COVID-19 and associated diseases.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.735-742
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• 2023

Background: Gintonin is a new material of ginseng that acts through the ginseng-derived lysophosphatidic acid (LPA) receptor ligand. The gintonin-enriched fraction (GEF) inhibits amyloid plaque accumulation in the cortex and hippocampus, improves cognitive dysfunction by increasing acetylcholine levels, and promoted hippocampal neurogenesis in an animal model of Alzheimer's disease. We evaluated the effect of the GEF on the cognitive performance of subjects with subjective memory impairment (SMI). Methods: In this eight-week, randomized, assessor- and participant-blinded, placebo-controlled study, participants with SMI were assigned to three groups receiving placebo, GEF 300 mg/day or GEF 600 mg/day. The Korean versions of the Alzheimer's Disease Assessment Scale (K-ADAS), Mini-Mental State Examination (K-MMSE), and Stroop color-word test (K-SCWT) were also evaluated along with the safety profiles. Results: One hundred thirty-six participants completed the study. After eight weeks, we analyzed intergroup differences in primary or secondary outcome score changes. When we compared the GEF group with the placebo group, we observed significant improvements in the K-ADAS and K-SCWT scores. The GEF group did not show a significant improvement in K-MMSE and BDI scores compared to the placebo group. No adverse events were observed in the gintonin and placebo groups for eight weeks. Conclusion: The GEF is safe and effective in improving subjective cognitive impairment related to both the K-ADAS and K-SCWT in this study. However, further large-scale and randomized controlled studies are warranted to secure other cognitive function tests besides the K-ADAS and K-SCWT, and to confirm the findings of the current study.

• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.205-213
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• 2024

Hydroxychavicol, a primary active phenolic compound of betel leaves, previously inhibited bone loss in vivo by stimulating osteogenesis. However, the effect of hydroxychavicol on bone remodeling induced by osteoclasts is unknown. In this study, the anti-osteoclastogenic effects of hydroxychavicol and its mechanism were investigated in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclasts. Hydroxychavicol reduced the number of tartrate resistance acid phosphatase (TRAP)-positive multinucleated, F-actin ring formation and bone-resorbing activity of osteoclasts differentiated from RAW264.7 cells in a concentration-dependent manner. Furthermore, hydroxychavicol decreased the expression of osteoclast-specific genes, including cathepsin K, MMP-9, and dendritic cell-specific transmembrane protein (DC-STAMP). For mechanistic studies, hydroxychavicol suppressed RANKL-induced expression of major transcription factors, including the nuclear factor of activated T-cells 1 (NFATc1), c-Fos, and c-Jun. At the early stage of osteoclast differentiation, hydroxychavicol blocked the phosphorylation of NF-κB subunits (p65 and Iκβα). This blockade led to the decrease of nuclear translocation of p65 induced by RANKL. In addition, the anti-osteoclastogenic effect of hydroxychavicol was confirmed by the inhibition of TRAP-positive multinucleated differentiation from human peripheral mononuclear cells (PBMCs). In conclusion, hydroxychavicol inhibits osteoclastogenesis by abrogating RANKL-induced NFATc1 expression by suppressing the NF-κB signaling pathway in vitro.

• The Korea Journal of Herbology
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• v.39 no.3
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• pp.85-95
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• 2024

Objectives : We proposed the hypothesis that administering Trigonella foenum-graecum seed extract (TSE) could alleviate menopausal symptoms and osteoporosis resulting from estrogen deficiency. Methods : Ovariectomized (OVX) rats were administered TSE at doses of 300 or 600 mg/kg body weight for 8 weeks, followed by measurement of serum lipid profile and serum bone markers using ELISA kits. Additionally, analysis of related genes in the femur and uterus was performed using Western blot and real-time PCR. Additionally, micro-CT analysis was performed to investigate the protective effect of TSE against bone loss due to oophorectomy. Results : The administration of TSE led to significant reductions in triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and glucose levels in the serum of OVX rats. Furthermore, TSE increased estradiol levels in the serum and notably improved the levels of biochemical markers associated with bone metabolism. Additionally, TSE exerted significant regulatory effects on the mRNA levels of alkaline phosphatase (ALP) and receptor activator of nuclear factor kappa-B ligand (RANKL)-genes closely associated with bone metabolism in the femur. TSE also demonstrated pronounced effects on uterine tissue, with improvements observed in gene expression related to estrogen receptors. Conclusion : Our findings confirm the efficacy of TSE in ameliorating menopause symptoms by modulating elements associated with both bone and lipid metabolism in the serum, uterine tissue, and femur of OVX rats. The present findings suggest that TSE may offer potential therapeutic effects for symptoms related to menopause and osteoporosis in females.

• IMMUNE NETWORK
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• v.23 no.5
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• pp.37.1-37.11
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• 2023

Forkhead box P3-positive (Foxp3⁺)-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1-mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1-mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1-mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF-mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.5.1-5.15
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• 2020

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

• Journal of Life Science
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• v.18 no.7
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• pp.931-939
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• 2008

The purpose of this study was to determine the effect of energy supplement on responses of plasma insulin-like growth factor (IGF)-1 and IGF binding proteins (IGFBPs) to growth hormone-releasing peptide-2 (GHRP-2) administration in normal protein-fed wethers, and to observe the effect of GHRP-2 treatment on hepatic growth hormone (GH) receptor in well-fed wethers. Plasma IGF-1 and 39-42 kDa IGFBP-3 during the HENP (CP, crude protein 0.34 and TDN, total digestible nutrients 1.83 kg/day DM, dry matter intake) treatment period were higher than in the LENP (CP 0.32 kg and TDN 0.87 kg/day DM intake) period (P<0.05). The response of GH was stimulated by GHRP-2 ($12.5\;{\mu}g/kg$ body weight/day) administration during both of the feed treatment periods (P<0.05). The area under curve (AUC) increment and average concentration of GH (0-180 min) with GHRP-2 administration was higher during HENP treatment than LENP treatment (P<0.01). During the HENP treatment period from day 1 to day 7 of twice daily GHRP-2 treatment, the plasma IGF-1 increment was increased on days 2, 6 and 7 of GHRP-2 administration (P<0.05). On the basis of ligand blotting, the proportions of plasma 39-43 kDa IGFBP-3 during the HENP treatment period only showed a significant difference on days 6 and 7 with GHRP-2 administration. No significant difference in the specific binding of $^{125}I-labeled$ oGH to hepatic membranes was detected between the saline and GHRP-2 treatments of the HENP-fed wethers. These results suggest that the nutritional balance between energy and protein may affect the endogenous GH / IGF-1 axis as well as plasma IGFBP-3 levels.

• Journal of Life Science
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• v.16 no.2 s.75
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• pp.199-205
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• 2006

Peroxisome proliferator activated receptor (PPAR)-$\alpha$ of three PPAR subtypes ($-\alpha,\;-\beta/-\gamma,\;-\delta$), which are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors, plays a key role in lipoprotein and glucose homeostasis. A variation in the PPAR-a gene expression has been suggested to influence the development of metabolic syndrome through alterations in lipid concentrations. The aim of our study was to investigate the association between the PPAR-a and metabolic syndrome among South Korean. A total of 542 health screen examinees were enrolled in this study who were examined in Kosin University Gospel Hospital from December, 2004 to July, 2005. The height, weight, waist circumference, and systolic and diastolic blood pressure of the subjects were examined and fasting blood glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride were measured by-sampling in venous blood. The metabolic syndrome was defined as the presence of three or more of the following : waist circumference men ${\geq}90cm$, women ${\geq}80cm$, blood pressure ${\geq}130/85mmHg$, fasting glucose ${\geq}110mg/dL$, HDL cholesterol men <40 mg/dL, women <50 mg/dL, triglyceride ${\geq}150mg/dL$. The blood pressure, fasting glucose, HDL cholesterol, triglyceride were evaluated by using the criteria of NECP ATP III and waist circumference was assessed by using the criteria of WHO Asia-Western Pacific. And the author compared the frequency of the PPAR-$\alpha$ mutation of L162V ($C{\rightarrow}G$ variant in exon 5) in a sample of 542 subjects with and without the metabolic syndrome by polymerase chain reaction allele-specific oligonucleotide (PCR-ASO) method. One (0.2%) hetero-isotype among high risk of metabolic syndrome was identified. The values of waist circumference, body mass index and low density lipoprotein cholesterol of the mutant were 100 cm, 28.6 $kg/m^2$ and 120 mg/dL, respectively. Although the author failed to see significant association between the presence of the PPAR-$\alpha$ L162V polymorphism and metabolic syndrome, one PPAR-$\alpha$ L162V polymorphism in metabolic syndrome patients was found.

• Journal of Animal Science and Technology
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• v.46 no.4
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• pp.563-570
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• 2004

The insulin-like growth factor(IGF) system, consisting of IGFs-I and -II ligands and their receptors and six IGF-binding proteins(IGFBPs), plays an important role in survival, proliferation and differentiation of a variety of cell types. Lithium is a known modulator of survival and proliferation of many cell types in vitro. The present study was undertaken to investigate the relationship between LiCI-induced changes in cell survival and growth and the expression of the IGF system components in C6 rat glioma cell line which, besides IGF-I and its receptor, is known to express IGFBP-3 as its major IGF carrier. When C6 cells were cultured for 24h in the absence or presence of 2mM or 5mM LiCl in a 10% serwn-containing medium, the viability and the number of cells were not affected by added lithium. In 72-h culture, however, C6 cells clearly exhibited a dose-dependent response to added LiCl. The cells cultured for 72h in the presence of 0, 2mM and 5mM LiCl exhibited a typical mitotic, a growth-arrested and an apoptotic appearances, respectively. Moreover, the apoptotic cells were accompanied by reduced expression of IGF-I, IGF-I receptor and IGFBP-3 as examined by semi-quantitative reverse transcription-polymerase chain reaction. Interestingly, blockade of IGFBP-3 mRNA translation by addition of 101${\mu}M$ IGFBP-3 anti-sense oligodeoxyribonucleotide in serum-free, 24-h culture resulted in a decrease in the number of cells as well as relative abundance of the target mRNA. In summary, results suggest that the cytotoxic effect of lithium in C6 cell is likely to be mediated, in part, by suppression by this agent of the expression of the IGF system components. In this regard, IGFBP-3 may play at least a 'permissive' role in normal proliferation of this cell.

• Journal of Chest Surgery
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• v.30 no.9
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• pp.854-861
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• 1997

CYPRA 21-1 is known to be a cytokeratin 19 fragment, and it can be detected by using two specific monoclonal antibodies (KS 19-1 and BM 19-21) and can be clinically applied as a useful circulating tumor marker The epidermal growth factor receptor (EGF-R) expression was evaluated and characterized by its tyrosine protein kinase activity and by its ligand-stimulated autophosphorylation, a property shared with other peptide growth factor receptors. Autocrine or para'urine action was initiated by a growth factor, or by a transforming growth factor o, which had an extensive homology with EGP and which also stimulated tyrosine kinase activity on the EGF-R. The CYFRA 21-1 and the EGF-R levels in 30 patients with primary lung tumors were investigated. There were 24 patients with squamous cell carcinomas and 6 patients with adenocarcinomas. Specimen 5 mm3 in size were sampled at three different locations ; the main lesion, the boundary between the lesion and the unaffected tissue, and the unaffected tissue of the patients. The results were as follows 1. The CYPRA 21-1 concentration in the cancer boundary, the most malignant region,(348.6 : 89.9 ng/ml) was the lowest value. The CYFRA 21-1 concentration in unaffected tissue,(718.4$\pm$77.8 ng/ml) was higher than that in the main lesion. which had intact cellularity. 2. The EGF-R concentration in the main lesion was higher than that in the unaffected tissue, and the EGF-R concentration in a squamous cell cacinoma was higher than that in an adenocarcinoma. also, the EGF-R concentration in the cancer b undary was highest at stage 1, ll. The EGF-R concentration was higher in the main cancer lesion that in the unaffected tissue at stage 111, IV. 3. The CYFRA 21-1 was a cytoplasmic skeleton and the EGF-R was a cell-wall component; there was no correlation. In conclusion, CYFRA 21-1 was abundant in the cytoplasm but had a higher concentration in the unaffected tissue than in the main cancer lesion. The CYFRA 21-1 concentration of the tissue did not reflect the amount of cancer activity, the EGP-R was located in the cell membrane, the level of tissue that reflects cancer activity, so the main cancer lesion had a higher concentration than the unaffected tissue. CYFRA 21-1 is not a useful tumor maker at the tissue level. Because the EGF-R concentration re(looted the cancer activity, its a useful tumor marker for lung cancer.