Renoprotective Effects of Hypoxylonol C and F Isolated from Hypoxylon truncatum against Cisplatin-Induced Cytotoxicity in LLC-PK1 Cells

Hwang, Buyng Su; Lee, Dahae; Choi, Pilsoon; Kim, Kyu Sun; Choi, Seon-Jun; Song, Bong Geun; Kim, Taejung; Song, Ji Hoon; Kang, Ki Sung; Ham, Jungyeob

doi:10.3390/ijms19040948

Cited by 9 publications

(4 citation statements)

References 27 publications

(44 reference statements)

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“…Treatment with hypoxylonols D and E, novel benzo[ j ]fluoranthene derivatives, isolated from Annulohypoxylon annulatum , inhibits proliferation of the human umbilical vein endothelial cell line (HUVEC) and human umbilical artery endothelial cell line (HUAEC) as the essential step in tumor angiogenesis [22]. In addition, it has been reported to protect against cisplatin-induced cytotoxicity in the porcine renal proximal tubule epithelial cell line (LLC-PK1) through anti-apoptosis by inhibiting p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) phosphorylation and caspase-3 cleavage [23].…”

Section: Introductionmentioning

confidence: 99%

Hypoxylonol F Isolated from Annulohypoxylon annulatum Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism

et al. 2019

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Insulin plays a key role in glucose homeostasis and is hence used to treat hyperglycemia, the main characteristic of diabetes mellitus. Annulohypoxylon annulatum is an inedible ball-shaped wood-rotting fungus, and hypoxylon F is one of the major compounds of A. annulatum. The aim of this study is to evaluate the effects of hypoxylonol F isolated from A. annulatum on insulin secretion in INS-1 pancreatic β-cells and demonstrate the molecular mechanisms involved. Glucose-stimulated insulin secretion (GSIS) values were evaluated using a rat insulin ELISA kit. Moreover, the expression of proteins related to pancreatic β-cell metabolism and insulin secretion was evaluated using Western blotting. Hypoxylonol F isolated from A. annulatum was found to significantly enhance glucose-stimulated insulin secretion without inducing cytotoxicity. Additionally, hypoxylonol F enhanced insulin receptor substrate-2 (IRS-2) levels and activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. Interestingly, it also modulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) and pancreatic and duodenal homeobox 1 (PDX-1). Our findings showed that A. annulatum and its bioactive compounds are capable of improving insulin secretion by pancreatic β-cells. This suggests that A. annulatum can be used as a therapeutic agent to treat diabetes.

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Section: Introductionmentioning

confidence: 99%

Hypoxylonol F Isolated from Annulohypoxylon annulatum Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism

et al. 2019

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“…Therefore, finding the adjuvant agents to reduce cisplatin nephrotoxicity is an important approach for cisplatin cancer therapeutic. Our previous studies had reported other agents from natural products which had potential in reducing cisplatin nephrotoxicity [38][39][40]. In this study, we focused on the renoprotective effect of shikimic acid isolated from A. absinthium on LLC-PK1 cells and mouse model.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies

Lee

Nguyen

Park

et al. 2020

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Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of Artemisia absinthium extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL A. absinthium extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the A. absinthium extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of A. absinthium extract and its mechanism of action against cisplatin-induced renal injury.

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“…The apoptotic cells were measured using a Tali Image-Based Cytometer (Invitrogen) [34]. In brief, cells were harvested after the treatment of 5 mM glutamate for 12 h. The cells were treated with annexin-binding buffer and labeled with AlexaFluor 488-conjugated annexin V for 20 min.…”

Section: Quantification Of Apoptotic Cellsmentioning

confidence: 99%

Neuroprotective Effects of Tetrahydrocurcumin against Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

et al. 2019

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In the central nervous system, glutamate is a major excitable neurotransmitter responsible for many cellular functions. However, excessive levels of glutamate induce neuronal cell death via oxidative stress during acute brain injuries as well as chronic neurodegenerative diseases. The present study was conducted to examine the effect of tetrahydrocurcumin (THC), a major secondary metabolite of curcumin, and its possible mechanism against glutamate-induced cell death. We prepared THC using curcumin isolated from Curcuma longa (turmeric) and demonstrated the protective effect of THC against glutamate-induced oxidative stress in HT22 cells. THC abrogated glutamate-induced HT22 cell death and showed a strong antioxidant effect. THC also significantly reduced intracellular calcium ion increased by glutamate. Additionally, THC significantly reduced the accumulation of intracellular oxidative stress induced by glutamate. Furthermore, THC significantly diminished apoptotic cell death indicated by annexin V-positive in HT22 cells. Western blot analysis indicated that the phosphorylation of mitogen-activated protein kinases including c-Jun N-terminal kinase, extracellular signal-related kinases 1/2, and p38 by glutamate was significantly diminished by treatment with THC. In conclusion, THC is a potent neuroprotectant against glutamate-induced neuronal cell death by inhibiting the accumulation of oxidative stress and phosphorylation of mitogen-activated protein kinases.Molecules 2020, 25, 144 2 of 10 neurodegenerative diseases [3,4]. Earlier studies showed that an excessive release of glutamate in the extracellular region provoked the accumulation of intracellular ROS by depletion of intracellular glutathione levels through blocking cysteine uptake [5]. The presence of an antioxidant, such as flavonoids or N-acetylcysteine, strongly prevented ROS-induced neuronal cell death [6,7].The use of natural antioxidants for scavenging free radicals and maintaining homeostasis contributes to alleviating neuronal dysfunction [8]. Typically, natural compounds are multiple-target molecules found mainly in microorganisms and plants and exhibit strong antioxidant activity [8,9]. Phenolic compounds from natural sources also exhibit various beneficial effects in cancer, inflammation, and neurodegenerative disorders [9]. This broad spectrum of biological or pharmacological activities has made phytochemicals suitable candidates for treating multifactorial diseases, such as neurodegenerative diseases [10,11]. However, there are also several concerns regarding their poor bioavailability, stability and safety, which must be resolved before effective therapeutics can be developed.Mitogen-activated protein kinases (MAPKs), known as a family of serine/threonine protein kinases, are well-identified biological molecules involved in glutamate-induced oxidative neuronal cell death. MAPKs are related to multiple cellular functions including differentiation, proliferation, cell survival, inflammation, and cell death [12]. The presence of excessive glutam...

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Renoprotective Effects of Hypoxylonol C and F Isolated from Hypoxylon truncatum against Cisplatin-Induced Cytotoxicity in LLC-PK1 Cells

Cited by 9 publications

References 27 publications

Hypoxylonol F Isolated from Annulohypoxylon annulatum Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism

Hypoxylonol F Isolated from Annulohypoxylon annulatum Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism

Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies

Neuroprotective Effects of Tetrahydrocurcumin against Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

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