Comparison of Anti-Inflammatory and Antinociceptive Effects of the Extracts from Mixed Agrimonia pilosa Ledeb and Salvia miltiorrhiza Bunge and of Perna canaliculus In Vivo and In Vitro

Jing Hui Feng,Seung Hwan Hwang,Youn Gil Kwak,Min-Jung Kim,Jeong Hun Jo,Soon Sung Lim,Hong Won Suh 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Agrimonia pilosa Ledeb, as a traditional medicine, has been reported to be widely used on anti-inflammatory activity in many studies, as well as Salvia miltiorrhiza Bunge. Previously, we have reported that the mixture extract (ME) from Agrimonia pilosa Ledeb (AP) and Salvia miltiorrhiza Bunge (SM) could produce an antinociceptive effect in the gout arthritis model. Also, the Perna canaliculus extracts (PCE) has well-known anti-inflammatory and anti-arthritis effects. Then, in the present study, we aimed to investigate the potential anti-inflammatory and antinociceptive effects of the ME by using in vitro and in vivo models. At the same time, we project to compare with the PCE, which as a positive control. Results showed that both the once or continuously one-week treatment of the ME or the PCE reduced the pain threshold in a dose-dependent manner in the mono-iodoacetate (MIA)-induced arthritis model. However, we found that at the same dose of the ME and PCE, ME showed more and earlier effectiveness than the PCE. Both the ME and PCE also suppressed the plasma TNF-α, IL-6, and CRP expression in the MIA-induced arthritis model. Additionally, the release of nitric oxide (NO) and IL-6 were inhibited by the ME and the PCE in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Moreover, TNF-α and MAPKs proteins expression were down-regulated by the ME and the PCE in LPS-stimulated RAW 264.7 cells. Furthermore, in the other in vivo assay, the change of ear weight in croton oil-induced ear edema model in mice was significantly reduced by treatment with the ME or the PCE at equally efficacy. Therefore, we suggest that the ME from AP and SM possesses anti-inflammatory and antinociceptive effects which indicate AP and SM could be a potential candidate for arthritis or ear edema treatment.

The mixture of Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge. extract produces analgesic and anti-inflammatory effects in a collagen-induced arthritis mouse model

Jing-Hui Feng,정전섭,황승환,이수경,이상윤,곽연길,김두호,송추연,김민정,서홍원,김성찬,임순성 한국통합생물학회 2022 Animal cells and systems Vol.26 No.4

Pain and inflammation typically manifest in patients with arthritis. It is now widely known that Agrimonia pilosa Ledeb (AP) and Salvia miltiorrhiza Bunge (SM) exert anti-inflammatory and antinociceptive effects. We have previously reported that the mixture extract (ME) from AP and SM produces antinociceptive and anti-inflammatory effects in gout arthritis and monoiodoacetate (MIA)-induced arthritis models. In the present study, we assessed the antinociceptive and anti-inflammatory effects on the collagen-induced arthritis (CIA) model. The antinociceptive effects in mice were measured using the von Frey test. ME administered once or for one week (once per day) once, and one-week reduced the pain in a dose-dependent manner (from 50 to 100 mg/kg) in the CIA-induced osteoarthritis (OA) model. ME treatment also reduced tumor necrosis factor (TNF)-α and C-reactive protein (CRP) levels in plasma and ankle tissues. Furthermore, COX-1, COX-2, NF-κB, TNF-α, and IL-6 expressions were attenuated after ME treatment. In most experiments, the antinociceptive and anti-inflammatory effects induced by ME treatment were almost equal to or slightly better than those induced by Perna canaliculus (PC) treatment, which was used as a positive control. Our results suggest that ME possesses antinociceptive and anti-inflammatory effects, indicating its potential as a therapeutic agent for arthritis treatment.

The changes of nociception and the signal molecules expression in the dorsal root ganglia and the spinal cord after cold water swimming stress in mice

Feng, Jing-Hui,Sim, Su-Min,Park, Jung-Seok,Hong, Jae-Seung,Suh, Hong-Won The Korean Society of Pharmacology 2021 The Korean Journal of Physiology & Pharmacology Vol.25 No.3

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4℃) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice. Here, we show that 3 min of CWSS was sufficient to produce antinociception in tail-flick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS. CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

The Molecular Signatures of Acute-immobilization-induced Antinociception and Chronic-immobilization-induced Antinociceptive Tolerance

Jing-Hui Feng,Hee-Jung Lee,서홍원 한국뇌신경과학회 2019 Experimental Neurobiology Vol.28 No.6

In the present study, the productions of antinociception induced by acute and chronic immobilization stress were compared in several animal pain models. In the acute immobilization stress model (up to 1 hr immobilization), the antinociception was produced in writhing, tail-flick, and formalin-induced pain models. In chronic immobilization stress experiment, the mouse was enforced into immobilization for 1 hr/day for 3, 7, or 14 days, then analgesic tests were performed. The antinociceptive effect was gradually reduced after 3, 7 and 14 days of immobilization stress. To delineate the molecular mechanism involved in the antinociceptive tolerance development in the chronic stress model, the expressions of some signal molecules in dorsal root ganglia (DRG), spinal cord, hippocampus, and the hypothalamus were observed in acute and chronic immobilization models. The COX-2 in DRG, p-JNK, p-AMPKα1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKα1 in the hypothalamus were elevated in acute immobilization stress, but were reduced gradually after 3, 7 and 14 days of immobilization stress. Our results suggest that the chronic immobilization stress causes development of tolerance to the antinociception induced by acute immobilization stress. In addition, the COX-2 in DRG, p-JNK, p-AMPKα1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKα1 in the hypothalamus may play important roles in the regulation of antinociception induced by acute immobilization stress and the tolerance development induced by chronic immobilization stress.

Modulation of corticosterone and changes of signal molecules in the HPA axis after cold water swimming stress

Feng Jing-Hui,심수민,박정석,홍재승,서홍원 한국통합생물학회 2021 Animal cells and systems Vol.25 No.1

In the present study, we examined the effect of cold-water swimming stress (CWSS) on plasma corticosterone levels. Mice were exposed to stress in 4°C for 3 mins. Plasma corticosterone (CORT) level was measured at 0, 15, and 30 min after stress stimulation. The plasma CORT level was gradually increased up to 30 min. Then we further examined the changes of several signaling molecules expression levels, such as p-ERK, p-JNK, p-P38, p-AMPKα1, p-AMPKα2, and p-mTOR, in the HPA axis. We observed that those signaling molecules were altered after stress in the HPA axis. p-ERK, p-JNK, p-P38, and p-mTOR proteins expression were reduced by CWSS in the HPA axis. However, the phosphorylation of AMPKα1 and AMPKα2 were activated after CWSS in the HPA axis. Our results suggest that the upregulation of plasma CORT level induced by CWSS may be modulated by the those signaling molecules.

Construction of Novel Bifunctional Chimeric Proteins Possessing Antitumor and Thrombolytic Activities

( Hui Jing ),( You Jin Dai ),( Yuan Yuan Bian ),( Hui Li ),( Xiao Jin Cui ),( Xiao Jie Yu ),( Song You ),( Feng Qing Hu ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.7

Based on their respective antitumor and thrombolytic activities, the superantigen staphylococcal enterotoxin C2 (SEC2) and staphylokinase (Sak) were chosen for the construction of the novel chimeric proteins Sak-linker- SEC2 and SEC2-linker-Sak using a linker composed of nine Ala residues. Both chimeric proteins possessed nearly the same PBMC proliferation stimulating activity and antitumor activity as SEC2 and thrombolytic activity as Sak. Neither the SEC2 or Sak component of each chimeric protein affected the activity of the other component. The results presented in this study provide a possible strategy to prevent and cure tumor thrombus.

Mitochondrial citrate accumulation drives alveolar epithelial cell necroptosis in lipopolysaccharide-induced acute lung injury

Yang Hui-Hui,Jiang Hui-Ling,Tao Jia-Hao,Zhang Chen-Yu,Xiong Jian-Bing,Yang Jin-Tong,Liu Yu-Biao,Zhong Wen-Jing,Guan Xin-Xin,Duan Jia-Xi,Zhang Yan-Feng,Liu Shao-Kun,Jiang Jian-Xin,Zhou Yong,Guan Cha-Xi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.

Crocetin Induces Cytotoxicity in Colon Cancer Cells Via p53-independent Mechanisms

Li, Cai-Yan,Huang, Wen-Feng,Wang, Qun-Li,Wang, Fan,Cai, E.,Hu, Bing,Du, Jia-Cheng,Wang, Jing,Chen, Rong,Cai, Xiao-Jing,Feng, Jing,Li, Hui-Hui Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Objective: Crocin has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of crocin against human colon cancer cells in vitro. Methods: Cell proliferation was examined using MTT assay and the cell cycle distribution fractions were analyzed using fow cytometric analysis after propidium iodide staining. Apoptosis was detected using theTUNEL Apoptosis Detection Kit with laser scanning confocal microscope. DNA damage was assessed using the alkaline single-cell gel electrophoresis assay, while expression levels of p53, cdk2, cyclinA and P21 were examined by Western blot analysis. Results: Treatment of SW480 cells with crocetin (0.2, 0.4, 0.8 mmol/L) for 48 h signifcantly inhibited their proliferation in a concentration-dependent manner. Crocetin (0.8 mmol/L) signifcantly induced cell cycle arrest through p53-independent mechanisms accompanied by P21 induction. Crocetin (0.8 mmol/L) caused cytotoxicity in the SW480 cells by enhancing apoptosis and decreasing DNA repair capacity in a time-dependent manner. Conclusions: This report provides evidence that crocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug.

Prevalence, Risk Factors, and Psychological Effects of Primary Nocturnal Enuresis in Chinese Young Adults

Hui Jie Hu,Zhen Wei Zhang,Yu Liang,Yan Yan Luo,Qi Feng Dou,Cui Ping Song,Hui Min Zhang,Ying Zhao,Guang Run Tian,Ke Zhang,Qiu Fang Mao,Jing Gui Song,Soren Rittig,Jian Guo Wen 대한배뇨장애요실금학회 2021 International Neurourology Journal Vol.25 No.1

Purpose: This study aimed to investigate the prevalence, risk factors, and effects of primary nocturnal enuresis (PNE) on physical and mental health in young adults in mainland China. Methods: An anonymous questionnaire was used to collect information including the sociodemographic characteristics, history of PNE, family history, daytime voiding symptoms, Pittsburgh Sleep Quality Index (PSQI) scores, Self-Esteem Scale (SES), and Self-Rating Depression Scale (SDS). A total of 22,500 university students from 23 provinces and 368 cities in mainland China were included. Results: In total, 21,082 questionnaires were collected, and 20,345 of them qualified for statistical analysis. The PNE prevalence was 1.17%, and the distribution of monosymptomatic nocturnal enuresis (MNE) and nonmonosymptomatic nocturnal enuresis (NMNE) was 66.1% and 33.9%, respectively. In total, 28% of respondents with PNE reported bedwetting daily, 31.6% between 1 and 7 times weekly, and 40.4% between 1 and 4 times monthly; 80% of PNE cases had no history of treatment. The prevalence of PNE in patients with a family history, frequency, urgency, urinary incontinence, and recurrent urinary tract infections was significantly higher than in those without these conditions (P<0.001). PNE was significantly correlated with the PSQI total score (sleep quality) (P=0.011). The SES score was lower and the SDS was higher (P<0.001) in the PNE group than in those without PNE. Conclusions: In mainland China, the PNE prevalence among young adults was found to be high, and PNE had significant effects on physical and mental health. Risk factors included a family history, daytime voiding symptoms, and lack of treatment.

Bone Formation in Ectopic and Osteogenic Tissue Induced by a Novel BMP-2-related Peptide Combined with Rat Tail Collagen

Jing-Feng Li,Zhen-Yu Lin,Qi-Xin Zheng,Xiao-Dong Guo,Shu-Hua Yang,Hong-Wei Lu,Sheng-Hui Lan 한국생물공학회 2010 Biotechnology and Bioprocess Engineering Vol.15 No.5

Bone morphogenetic proteins (BMPs) play an important role in regulating osteoblast differentiation and subsequent bone formation, mainly evidenced by the induced osteogenic ability of BMP-2 from BMPs. However, BMP-2 alone does not induce the expected efficacy due to its short retention in vivo. In this study, a novel BMP-2-related peptide (designated P24) derived from the “knuckle epitope”of BMP-2 was coupled covalently to type I collagen derived from rat tail and observed under scanning electron microscopy (SEM) in low vacuum mode. The BMP-2-related peptide/collagen composite was implanted in vivo into the pocket of the quadriceps musculature of Sprague-Dawley (SD) rats and then harvested 3 or 6 weeks after surgery. It was found that lyophilized collagen retained a porous network structure with an average inner-diameter of 90 ~ 160 μm. Based on radiographic evaluation and histological examination, BMP-2-related peptide/collagen induced significant ectopic bone formation compared to that of rat tail collagen alone as a control. Our results indicate collagen served as a good carrier for newly synthesized BMP-2-related peptide and that the BMP-2-related peptide/collagen composite was an effective substitute in bone tissue engineering.