• Natural Product Sciences
• /
• v.3 no.1
• /
• pp.59-70
• /
• 1997

A rat chemokine, cytokine-induced neutrophil chemoattractant-1 (CINC-1) has chemotactic and activating properties to neutrophils. Rat kidney epithelioid NRK-52E cells contained 4 ng/ml of ClNC-1 as a basal level and their CINC-1 production was significantly increased by stimulation with lipopolysaccharide (LPS) of E. coli. Maximal induction of ClNC-1 was 58 ng/ml when 3 ${\mu}g/ml$ of LPS was treated to the NRK-52E cells. Inhibitory effects on CINC-1 induction in LPS-stimulated NRK-52E cells by extracts prepared from herbal medicines and wild plants in Korea were analyzed. At the final concentration of 100 ${\mu}g/ml$ , 9 species out of 304 species of herbal extracts exhibited more than 50% of inhibition on the CINC-1 induction. The active extracts prepared from Artemisia argyi, Lythrum salicaria, Machilus thunbergii, Magnolia sieboldii, Nelumbo nucifera, Prunus persica, Rubus coreanus, Sanguisorba officinalis, and Tripterygium regelii have been sequentially fractionated to obtain methylene chloride, ethyl acetate, butanol, and aqueous layers. Among solvent fractions of the active herbal extracts, methylene chloride fractions of Artemisia argyi and Magnolia sieboldii exhibited the highest inhibitory effects on CINC-1 induction in LPS-stimulated NRK-52E cells.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.34 no.4
• /
• pp.170-176
• /
• 2020

Palmijihwang-tang is an herbal formula frequently used to treat many symptoms, such as lumbago, pollakiuria, cold hands and feet, nephritis, sterilitas virilis, and prostatic disorders. The aim of this study was to investigate the effects of Palmijihwang-tang on cisplatin-induced nephrotoxicity in rat kidney proximal tubular NRK-52E cells. NRK-52E cells were treated with Palmijihwang-tang in absence or presence of 30 µM cisplatin for 12 or 24 h. Palmijihwang-tang at concentrations of 50-800 ㎍/ml did not change the cell viability in NRK-52E cells, and showed no significant toxicity. Palmijihwang-tang at concentrations of 400 and 800 ㎍/ml significantly increased the cell viability and reduced apoptotic cells in NRK-52E cells exposed to cisplatin. Also, Palmijihwang-tang markedly inhibited cisplatin-induced caspase-3 activation, PARP cleavage, ROS production and p53 activation in NRK-52E cells. Furthermore, Palmijihwang-tang did not interfere with the antitumor activity of cisplatin in AGS and A549 cancer cells. Particularly, Palmijihwang-tang enhanced antitumor activity of cisplatin in A549 cells. Taken together, these results suggest that Palmijihwang-tang ameliorated cisplatin-induced nephrotoxicity through reduction of ROS production and p53 activation, and did not interrupt antitumor efficacy of cisplatin against cancer cells.

• Genomics & Informatics
• /
• v.8 no.1
• /
• pp.50-57
• /
• 2010

Mercuric chloride, a model nephrotoxicant was used to elucidate time- and dose- dependent global gene expression changes associated with proximal tubular toxicity. Rat kidney cell lines NRK-52E cells were exposed for 2, 6 and 12 hours and with 3 different doses of mercuric chloride. Cell viability assay showed that mercuric chloride had toxic effects on NRK-52E cells causing 20% cell death (IC20) at $40{\mu}M$ concentration. We set this IC20 as high dose concentration and 1/5 and 1/25 concentration of LC20 were used as mid and low concentration, respectively. Analyses of microarray data revealed that 738 genes were differentially expressed (more than two-fold change and p<0.05) by low concentration of mercuric chloride at least one time point in NRK-52E cells. 317 and 2,499 genes were differentially expressed at mid and high concentration of mercuric chloride, respectively. These deregulated genes showed a primary involvement with protein trafficking (CAV2, CANX, CORO1B), detoxification (GSTs) and immunity and defense (HMOX1, NQO1). Several of these genes were previously reported to be up-regulated in proximal tubule cells treated with nephrotoxicants and might be aid in promoting the predictive biomarkers for nephrotoxicity.

• Environmental Mutagens and Carcinogens
• /
• v.24 no.2
• /
• pp.85-90
• /
• 2004

Nickel(II) compounds are carcinogenic metals which induce genotoxicity and oxidative stress through the generation of reactive oxygen species. In search of new molecular pathways toward understanding the molecular mechanism of nickel(II)-induced carcinogensis, we performed mRNA differential display analysis using total RNA extracted from nickel(II) acetate-treated normal rat kidney cells (NRK-52E). Cells were exposed for 3 days to 160 and 240 uM nickel(II) concentrations. cDNAs corresponding to mRNAs for which expression levels were altered by nickel(II) were isolated, sequenced, and followed by a GenBank Blast homology search. Specificity of differential expression of cDNAs was determined by RT-PCR and Western blot analysis. Two of them (SH3BGRL3 and FHIT) were down-regulated and one (metallothionein) was up-regulated by nickel(II) treatment. The expression of these mRNAs were nickel(II) concentration-dependent. The levels of FHIT and metallothionein proteins were also consistent with the results for mRNAs. Overall, although the fundamental questions related to function of these genes in nickel(II)-mediated carcinogenicity are not answered, our study suggests that they can be interesting candidates for studies of molecular mechanisms of nickel(II) carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.7
• /
• pp.2763-2769
• /
• 2015

Background: Cancer is an unnatural type of tissue growth in which the cells exhibit unrestrained division, leading to a progressive increase in the number of dividing cells. It is now the second largest cause of death in the world. The present study concerned antioxidant, anticancer and anticholinesterase activities and protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in methanol extracts of flowers, fruits and seeds of Hypericum amblysepalum. Materials and Methods: Antioxidant properties including free radical scavenging activity and reducing power, and amounts of total phenolic compounds were evaluated using different tests. Protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in extracts were determined by HPLC. Cytotoxic effects were determined using the MTT test with human cervix cancer (HeLa) and rat kidney epithelium cell (NRK-52E) lines. Acetyl and butyrylcholinesterase inhibitory activities were measured by by Ellman method. Results: Total phenolic content of H. amblysepalum seeds was found to be higher than in fruit and flower extracts. DPPH free radical scavenging activity of the obtained extracts gave satisfactory results versus butylated hydroxyanisole and butylated hydroxytoluene as controls. Reducing power activity was linearly proportional to the studied concentration range: $10-500{\mu}g/mL\;LC_{50}$ values for H. amblysepalum seeds were 11.7 and 2.86 respectively for HeLa and NRK-52E cell lines. Butyryl-cholinesterase inhibitory activity was $76.9{\pm}0.41$ for seed extract and higher than with other extracts. Conclusions: The present results suggested that H. amblysepalum could be a potential candidate anti-cancer drug for the treatment of human cervical cancer, and good source of natural antioxidants.

• Archives of Pharmacal Research
• /
• v.29 no.12
• /
• pp.1164-1170
• /
• 2006

A triptolide-lysozyme (TP-LZM) conjugate was synthesized to achieve renal specific delivery and to reduce the side effects of triptolide. Triptolide was coupled to lysozyme through succinic via an ester bond with an average coupling degree of 1 mol triptolide per 1 mol lysozyme. The lysozyme can specifically accumulate in the proximal tubular cells of the kidney, making it a potential carrier for targeting drugs to the kidney. The structure of triptolide succinate (TPS) was confirmed by IR, $^{1}H-NMR$, MS and UV. The concentrations of triptolide in various samples were determined by reversed-phase high-performance liquid chromatography (HPLC). In this study, the physicochemical and stability profiles of TP-LZM under various conditions were investgated the stability and releasing profiles of triptolide-lysozyme (TP-LZM) under various conditions. In vitro release trails showed triptolide-lysozyme was relatively stable in plasma (less than 30% of free triptolide released) and could release triptolide quickly in lysosome (more than 80% of free triptolide released) at $37^{\circ}C$ for 24 h. In addition, the biological activities of the conjugate on normal rat kidney proximal tubular cells (NRK52E) were also tested. The conjugate can effectively reduce NO production in the medium of NRK52E induced by lipopolysaccharide (LPS) but with much lower toxicity. These studies suggest the possibility to promote curative effect and reduce its extra-renal toxicity of triptolide by TP-LZM conjugate.

• Journal of the Korean Society of Food Culture
• /
• v.37 no.6
• /
• pp.503-509
• /
• 2022

Methylglyoxal is a highly reactive precursor which forms advanced glycation end products (AGEs). AGEs and methylglyoxal are known to induce various diseases such as diabetes, vascular disorders, Diabetes Mellitus (DM), and neuronal disorders. Juglans regia L is an important food commonly used worldwide, having nutritious components, including phenolic compounds. Since ancient times, Juglans regia L have been differently applied by various countries for health and in diverse diseases, including arthritis, asthma, skin disorders, cancer, and diabetes mellitus. However, the effect of diabetes-induced renal damage against AGEs remains unclear. This study evaluates the anti-glycation and renal protective effects of ethanol extract of Juglans regia L against methylglyoxal-induced renal tubular epithelial cell death. Exposure to methylglyoxal resulted in reduced cell viability in NRK-52E cells, but co-treatment with Juglans regia L extracts significantly increased the cell viability. In addition, we examined the anti-glycation effect of Juglans regia L extracts. Compared to the positive control aminoguanidine and Alagebrium, treatment with Juglans regia L extracts significantly inhibited the formation of AGEs, collagen cross-linking, and breaking collagen cross-linking. Taken together, our results indicate that Juglans regia L is a potential therapeutic agent for regulating diabetic complications by exerting anti-glycation and renal protective activities.

• Biomolecules & Therapeutics
• /
• v.31 no.1
• /
• pp.97-107
• /
• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.