Publications by authors named "Bangrong Cai"

9 Publications

  • Page 1 of 1

Cigarette smoke extract amplifies NADPH oxidase-dependent ROS production to inactivate PTEN by oxidation in BEAS-2B cells.

Food Chem Toxicol 2021 Apr 10;150:112050. Epub 2021 Feb 10.

Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, China. Electronic address:

Chronic obstructive pulmonary disease (COPD) is widely recognized as a global public health problem and the third leading cause of mortality worldwide by 2020. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a dual-specificity protein and lipid phosphatase that plays an important role in COPD. However, the redox regulation of PTEN in the development of COPD was poorly studied. Our results showed that cigarette smoke extract (CSE) could oxidize PTEN in a time-dependent manner in BEAS-2B cells, whereas PTEN oxidation exposed to CSE was delayed compared to that of HO Additionally, we found that ROS derived from DUOX1 and 2 of NADPH oxidases were mainly responsible for oxidative inactivation PTEN, also simultaneously led to Trx-1 inactivation by dimerization. Oxidative mechanism of PTEN exposed to CSE was mediated by forming a disulfide bond between Cysand Cys, similar to HO. Inactivation of PTEN resulted in the increased phosphorylation of Akt. In conclusion, CSE exposure could elevate the intracellular ROS mainly from DUOX1 and 2 to oxidize PTEN and Trx-1 resulting in Akt activation, eventually cause the occurrence of COPD, suggesting that PTEN is a potential target for new therapies in COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2021.112050DOI Listing
April 2021

Synthesis, anticancer activity and potential application of diosgenin modified cancer chemotherapeutic agent cytarabine.

Food Chem Toxicol 2021 Feb 18;148:111920. Epub 2020 Dec 18.

College of Pharmacy, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address:

Diosgenin (DG), a steroidal saponin, is mainly found in yam tubers. DG and its derivatives displayed significant pharmacological activities against inflammatory, hyperlipidemia, and various cancers. DG was selected to modify the cancer chemotherapeutic agent cytarabine (Ara-C) due to its anti-tumor activities as well as lipophilicity. After characterization, the biomembrane affinity and the kinetic thermal processes of the obtained DG-Ara-C conjugate were evaluated by differential scanning calorimetry (DSC). Thin hydration method with sonication was applied to prepare the DG-Ara-C liposomes without cholesterol since the DG moiety has the similar basic structure with cholesterol with more advantages. Dynamic Light Scattering (DLS) analysis and cytotoxic analysis were employed to characterize the DG-Ara-C liposomes and investigate their biological activities, respectively. The results indicated that DG changed the biomembrane affinity of Ara-C and successfully replaced the cholesterol during the liposome preparation. The DG-Ara-C liposomes have an average particle size of around 116 nm with a narrow size distribution and revealed better anti-cancer activity against leukemia cells and solid tumor cells than that of free DG or Ara-C. Therefore, it can be concluded that DG displayed the potential application as an anti-cancer drug carrier to improve the bio-activities, since DG counted for a critical component in modulating the biomembrane affinity, preparation of liposome, and release of hydrophilic Ara-C from lipid vesicles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2020.111920DOI Listing
February 2021

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances.

Oxid Med Cell Longev 2020 6;2020:3153082. Epub 2020 Mar 6.

Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, China.

Diosgenin (DG), a well-known steroidal sapogenin, is present abundantly in medicinal herbs such as , , , , and . DG is utilized as a major starting material for the production of steroidal drugs in the pharmaceutical industry. Due to its wide range of pharmacological activities and medicinal properties, it has been used in the treatment of cancers, hyperlipidemia, inflammation, and infections. Numerous studies have reported that DG is useful in the prevention and treatment of neurological diseases. Its therapeutic mechanisms are based on the mediation of different signaling pathways, and targeting these pathways might lead to the development of effective therapeutic agents for neurological diseases. The present review mainly summarizes recent progress using DG and its derivatives as therapeutic agents for multiple neurological disorders along with their various mechanisms in the central nervous system. In particular, those related to therapeutic efficacy for Parkinson's disease, Alzheimer's disease, brain injury, neuroinflammation, and ischemia are discussed. This review article also critically evaluates existing limitations associated with the solubility and bioavailability of DG and discusses imperatives for translational clinical research. It briefly recapitulates recent advances in structural modification and novel formulations to increase the therapeutic efficacy and brain levels of DG. In the present review, databases of PubMed, Web of Science, and Scopus were used for studies of DG and its derivatives in the treatment of central nervous system diseases published in English until December 10, 2019. Three independent researchers examined articles for eligibility. A total of 150 articles were screened from the above scientific literature databases. Finally, a total of 46 articles were extracted and included in this review. Keywords related to glioma, ischemia, memory, aging, cognitive impairment, Alzheimer, Parkinson, and neurodegenerative disorders were searched in the databases based on DG and its derivatives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/3153082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079249PMC
October 2020

Water-Soluble Arginyl-Diosgenin Analog Attenuates Hippocampal Neurogenesis Impairment Through Blocking Microglial Activation Underlying NF-κB and JNK MAPK Signaling in Adult Mice Challenged by LPS.

Mol Neurobiol 2019 Sep 11;56(9):6218-6238. Epub 2019 Feb 11.

Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, Department of Oral Physiology, School of Dentistry, Chonnam National University, 77 Yongbong-Ro, Buk-Gu, Gwangju, 61186, Republic of Korea.

Microglia-mediated neuroinflammatory responses are well known to inhibit neurogenesis in the dentate gyrus (DG) of the adult hippocampus, and growing evidence indicates that therapeutic intervention to suppress microglial activation could be an effective strategy for restoring the impaired neurogenesis and memory performance. In the present study, we investigated the effects of water-soluble arginyl-diosgenin analog (Arg-DG) on the adult hippocampal neurogenesis using a central LPS-induced inflammatory mice model, along with the fundamental mechanisms in vivo and in vitro using LPS-stimulated microglial BV2 cells. Arg-DG (0.6 mg/kg) attenuates LPS-impaired neurogenesis by ameliorating the proliferation and differentiation of neural stem cells (NSCs), and prolonging their survival. The impaired neurogenesis in the hippocampal DG triggered the cognitive function, and that treatment of Arg-DG led to the recovery of cognitive decline. Arg-DG also suppressed the production of LPS-induced pro-inflammatory cytokines in hippocampal DG by blocking microglial activation. In in vitro study, Arg-DG inhibited the production of nitric oxide (NO), nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression, and prostaglandin D2 production (PGD2), as well as the pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α). The anti-inflammatory effect of Arg-DG was regulated by NF-κB and MAPK JNK signaling both in vivo, and in LPS-stimulated microglial BV2 cells. Taken together, these results suggest that Arg-DG might have the potential to treat various neurodegenerative disorders resulting from microglia-mediated neuroinflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-019-1496-3DOI Listing
September 2019

A synthetic diosgenin primary amine derivative attenuates LPS-stimulated inflammation via inhibition of NF-κB and JNK MAPK signaling in microglial BV2 cells.

Int Immunopharmacol 2018 Aug 8;61:204-214. Epub 2018 Jun 8.

Dental Science Research Institute, Department of Oral Physiology, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea. Electronic address:

Diosgenin, a precursor of steroid hormones in plants, is known to exhibit diverse pharmacological activities including anti-inflammatory properties. In this study, (3β, 25R)‑spirost‑5‑en‑3‑oxyl (2‑((2((2‑aminoethyl)amino)ethyl)amino)ethyl) carbamate (DGP), a new synthetic diosgenin derivative incorporating primary amine was used to investigate its anti-inflammatory effects and underlying mechanisms of action in lipopolysaccharide (LPS)-stimulated microglial BV2 cells. Pretreatment with DGP resulted in significant inhibition of nitric oxide (NO) synthesis, and down-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated microglial BV2 cells. In addition, DGP decreased the production of reactive oxygen species (ROS) and pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α). The inhibitory effects of DGP on these inflammatory mediators in LPS-stimulated microglial BV2 cells were regulated by NF-κB signaling through blocking p65 nuclear translocation and NF-κB p65/DNA binding activity. DGP also blocked the phosphorylation of c-Jun amino-terminal kinase (JNK), but not p38 kinase or extracellular signal-regulated kinases (ERK). The NF-κB inhibitor JSH-23 and JNK-specific inhibitor SP600125 significantly decreased NO production and IL-6 release in LPS-stimulated BV2 cells, respectively. The overall results demonstrate that DGP has anti-inflammatory effects on LPS-stimulated BV2 cells via inhibition of NF-κB and JNK activation, suggesting that DGP is a potential prophylactic agent in various neurodegenerative disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2018.05.021DOI Listing
August 2018

Toll-like receptor 2 promotes neurogenesis from the dentate gyrus after photothrombotic cerebral ischemia in mice.

Korean J Physiol Pharmacol 2018 Mar 23;22(2):145-153. Epub 2018 Feb 23.

Dental Science Research Institute, Department of Oral Physiology, School of Dentistry, Chonnam National University, Gwangju 61186, Korea.

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4196/kjpp.2018.22.2.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840073PMC
March 2018

Synthesis and biological evaluation of arginyl-diosgenin conjugate as a potential bone tissue engineering agent.

Chem Biol Drug Des 2018 01 14;91(1):17-28. Epub 2017 Jul 14.

Research Institute of Drug Development, College of Pharmacy, Chonnam National University, Gwangju, Korea.

Water-soluble arginyl-diosgenin (Arg-DG) conjugate was designed, synthesized, and evaluated for a biological activity. The Arg-DG conjugate was characterized using FT-IR, H NMR, C NMR, and HPLC-MS analyses, followed by a biological activity evaluation. Compared with DG, the Arg-DG conjugate showed a decreased cytotoxicity against L929 cells and an increased antiproliferative activity against hepatocellular cells. The safety of the Arg-DG conjugate was confirmed using the highly sensitive Alamar Blue assay, which indicated that it increased the cellular metabolic activity at suitable concentrations. The Arg-DG conjugate promoted an endothelial tube formation as well. Furthermore, the Arg-DG conjugate improved the bone morphogenetic protein 2 (BMP2)-induced osteoblastic differentiation with synergistic effects on alkaline phosphatase (ALP) activity and mineralization. These results suggest that the Arg-DG conjugate developed in this study has great potentials for biomedical applications such as bone tissue engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cbdd.13050DOI Listing
January 2018

Design, synthesis and evaluation of 5-substituted 1-H-tetrazoles as potent anticonvulsant agents.

Arch Pharm Res 2017 Apr 31;40(4):435-443. Epub 2016 Dec 31.

Department of Medicinal Chemistry, College of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang, 330004, China.

A series of 5-substituted 1-H-tetrazoles were designed and synthesized as potent anticonvulsant agents. Their preliminary anticonvulsant activities were evaluated using maximal electroshock and subcutaneous pentylenetetrazole (scPTZ) seizure tests. Neurotoxicity was determined using rotarod test. The results indicated that the compound 2j in scPTZ model exhibited the ED values of 83.3 mg/kg, superior to the standard drug ethosuximide with the maximum activity. In addition, compound 2k showed the most potent activity in MES model with ED value of 9.6 mg/kg and TD value of 189.5 mg/kg after intraperitoneal injection in mice, and displayed a high protective index (TD/ED) of 19.7 compared to reference antiepileptic drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12272-016-0881-yDOI Listing
April 2017

Design, synthesis of methotrexate-diosgenin conjugates and biological evaluation of their effect on methotrexate transport-resistant cells.

Steroids 2016 12 19;116:45-51. Epub 2016 Oct 19.

Research Institute of Drug Development, College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address:

A series of methotrexate-diosgenin conjugates was designed and synthesized to enhance the passive internalization of methotrexate (MTX) into transport-resistant cells. The inhibitory effects of these conjugates on dihydrofolate reductase (DHFR), and their anti-proliferation behaviors against a transport-resistant breast cancer cell line, MDA-MB-231, were investigated. All of the synthesized conjugates retained an ability to inhibit DHFR after the diosgenin substitution. The MTX conjugates were much more potent against methotrexate-resistant MDA-MB-231 cells than MTX. Conjugate 18, containing a disulfide bond, exhibited the most potent anti-proliferative and DHFR inhibitory effects (IC=4.1μM and 17.21nM, respectively). Anti-proliferative activity was higher in the conjugate with a longer space linker (conjugate 21) than those with shorter linkers (conjugates 19 and 20). These results suggest that diosgenin conjugation of MTX may be an effective way to overcome its transport resistance in cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.steroids.2016.10.006DOI Listing
December 2016