• Biomolecules & Therapeutics
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• 제28권5호
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• pp.414-422
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• 2020

Fangchinoline (FAN) is a bisbenzylisoquinoline alkaloid that is widely known for its anti-tumor properties. The goal of this study is to examine the effects of FAN on arthritis and the possible pathways it acts on. Human fibroblast-like synovial cells (FLS), carrageenan/kaolin arthritis rat model (C/K), and collagen-induced arthritis (CIA) mice model were used to establish the efficiency of FAN in arthritis. Human FLS cells were treated with FAN (1, 2.5, 5, 10 µM) 1 h before IL-1β (10 ng/mL) stimulation. Cell viability, reactive oxygen species measurement, and western blot analysis of inflammatory mediators and the MAPK and NF-κB pathways were performed. In the animal models, after induction of arthritis, the rodents were given 10 and 30 mg/kg of FAN orally 1 h before conducting behavioral experiments such as weight distribution ratio, knee thickness measurement, squeaking score, body weight measurement, paw volume measurement, and arthritis index measurement. Rodent knee joints were also analyzed histologically through H&E staining and safranin staining. FAN decreased the production of inflammatory cytokines and ROS in human FLS cells as well as the phosphorylation of the MAPK pathway and NF-κB pathway in human FLS cells. The behavioral parameters in the C/K rat model and CIA mouse model and inflammatory signs in the histological analysis were found to be ameliorated in FAN-treated groups. Cartilage degradation in CIA mice knee joints were shown to have been suppressed by FAN. These findings suggest that fangchinoline has the potential to be a therapeutic source for the treatment of rheumatoid arthritis.

• The Korean Journal of Pain
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• 제32권2호
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• pp.87-96
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• 2019

Background: This study was performed in order to examine the effect of intrathecal sec-O-glucosylhamaudol (SOG), an extract from the root of the Peucedanum japonicum Thunb., on incisional pain in a rat model. Methods: The intrathecal catheter was inserted in male Sprague-Dawley rats (n = 55). The postoperative pain model was made and paw withdrawal thresholds (PWTs) were evaluated. Rats were randomly treated with a vehicle (70% dimethyl sulfoxide) and SOG ($10{\mu}g$, $30{\mu}g$, $100{\mu}g$, and $300{\mu}g$) intrathecally, and PWT was observed for four hours. Dose-responsiveness and ED50 values were calculated. Naloxone was administered 10 min prior to treatment of SOG $300{\mu}g$ in order to assess the involvement of SOG with an opioid receptor. The protein levels of the ${\delta}$-opioid receptor, ${\kappa}$-opioid receptor, and ${\mu}$-opioid receptor (MOR) were analyzed by Western blotting of the spinal cord. Results: Intrathecal SOG significantly increased PWT in a dose-dependent manner. Maximum effects were achieved at a dose of $300{\mu}g$ at 60 min after SOG administration, and the maximal possible effect was 85.35% at that time. The medial effective dose of intrathecal SOG was $191.3{\mu}g$ (95% confidence interval, 102.3-357.8). The antinociceptive effects of SOG ($300{\mu}g$) were significantly reverted until 60 min by naloxone. The protein levels of MOR were decreased by administration of SOG. Conclusions: Intrathecal SOG showed a significant antinociceptive effect on the postoperative pain model and reverted by naloxone. The expression of MOR were changed by SOG. The effects of SOG seem to involve the MOR.

• 생명과학회지
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• 제14권3호
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• pp.385-390
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• 2004

키토산은 자연에 풍부하게 존재하는 다당의 중합체로 식품이나 약제의 성분으로 활용성이 있어 많은 연구가 이루어져 왔다. 본 연구에서는 키토산 투여와 저칼슘사료 급이가 랫드에서 골절의 치유과정에 미치는 영향을 실험하였다. 좌측 대퇴골을 골절시킨 후 핀을 골내에 삽입하여 고정하였다. 이후 랫드에 일반사료 또는 저칼슘사료를 급이하고 키토산을 0, 50, 100, 150 mg/kg 용량으로 10주간 주 5회 경구투여 하였다. 실험종료 시에 골절시킨 대퇴골의 X-ray 촬영과 물리적 측정을 실시하였다. X-ray필름 관찰에서는 골절을 유발한 모든 대퇴골에서 골절치유의 과정과 가골이 형성되었다. 물리적인 골강도 측정에서는 저칼슘사료를 급이한 랫드에서 일반사료를 급이한 랫드에 비해 최대하중과 강도의 감소를 나타내었다. 키토산을 투여한 랫드와 부형제를 투여한 랫드에서의 대퇴골의 최대하중과 강도의 차이는 없었다 또한 키토산 투여 및 저칼슘사료 급이는 최대하중과 강도에 대한 골절유발 대퇴골/비유발 대퇴골의 비율에는 영향을 미치지 않았다. 이 같은 결과로 보아 키토산은 골절의 치유과정과 제의 물리적 강도에 영향을 미치지 않는 것으로 사료된다. 또한 저칼슘사료 급이는 뼈의 물리적 강도를 감소시키는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제9권1호
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• pp.45-53
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• 2005

The present study was designed to examine the effect of d-amphetamine on CA release from the isolated perfused model of the rat adrenal gland, and to establish its mechanism of action. Damphetamine $(10{\sim}100{\mu}M$), when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced the CA secretory responses evoked by ACh ($5.32{\times}10^{-3}$ M), excess $K^+$ ($5.6{\times}10^{-2}$ M, a membrane depolarizer), DMPP ($10^{-4}$ M, a selective neuronal nicotinic $N_n-receptor$ agonist) and McN-A-343 ($10^{-4}$ M, a selective $M_1-muscarinic$ agonist) only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, d-amphetamine ($30{\mu}M$) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type $Ca^{2+}$ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}$ ATPase only for the first period (4 min). However, in the presence of high concentration ($500{\mu}M$), d-amphetamine rather inhibited the CA secretory responses evoked by the above all of secretagogues. Collectively, these experimental results suggest that d-amphetamine at low concentrations enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization, but at high concentration it rather inhibits them. It seems that d-amphetamine has dual effects as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that these actions of d-amphetamine are probably relevant to the $Ca^{2+}$ mobilization through the dihydropyridine L-type $Ca^{2+}$ cha$N_n$els located on the rat adrenomedullary chromaffin cell membrane and the release of $Ca^{2+}$ from the cytoplasmic store.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8377-8382
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• 2014

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

• 동의생리병리학회지
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• 제22권4호
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• pp.835-840
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• 2008

Acupuncture has long been contended to be effective in an ischemic stroke. A real-time monitoring of glutamate, an excitotoxin in the process of ischemic neuronal damage, in the striatum is tried in a rat model of global ischemia. Global ischemia was induced by the 11 vessel occlusion method for 10 minutes, during which acupuncture stimulation on GB34 and GB39 points was executed. Glutamate release in the rat striatum was monitored 256 times per second using real-time amperometric biosensor. Real time measurement data of 10 minutes prior to the induction of ischemia served as baseline data. Data acquisition continued for 30 minutes after the initiation of reperfusion. Peak concentration of glutamate release along with incidentally measured EEG and cerebral blood flow was compared between cases with and without acupuncture stimulation. Peak concentration of glutamate lowered when acupuncture stimulation was executed. A real time monitoring system of 11 vessel-occlusion induced global ischemia model was successfully established. The effect by acupuncture on acute global ischemia was successfully observed in this real-time monitoring setting, which may be one of the neuroprotective mechanism of acupuncture.

• 대한한의학회지
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• 제34권2호
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• pp.20-28
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• 2013

Objectives: This study examined the effects of 8 types of herbal prescriptions prescribed to alleviate dementia symptoms in a rat model of arterial thrombosis induced by ferric chloride ($FeCl_3$). Methods: Thirty minutes before 35% $FeCl_3$ treatment, SD rats were intraperitoneally injected with the 8 types of herbal prescriptions, respectively. We tested the effects of the herbal prescriptions on time to occlusion (TTO) in an arterial thrombosis model using a laser Doppler flow meter. In addition, thrombus weight (TW) and collagen fiber damages were evaluated in the same condition. Results: Herbal prescriptions showed the following rank-order based on their TTO: Chong-myung-tang (CMT) > modified Jangwonhan 02 (LMK02) > Toki-shakuyaku-san (TSS) ${\geq}$ Oren-gedoku-to (OGT) ${\geq}$ Yokukansan (YKS). In particular, CMT (100 mg/kg, i.p.) and LMK02 (100 mg/kg, i.p.) delayed the TTO the most ($14.83{\pm}0.98$ and $13.67{\pm}1.03$ min, respectively) compared with the vehicle group ($7.95{\pm}0.78$ min, P<0.001). In addition, CMT, LMK02, and OGT treatment ($0.63{\pm}0.01$, $0.66{\pm}0.02$ and $0.67{\pm}0.01$ mg/mm, respectively) significantly reduced thrombus weight compared with the vehicle treatment ($0.78{\pm}0.03$, P<0.001) and also alleviated collagen fiber damage (CMT; $28.40{\pm}2.22$%, LMK02; $30.79 {\pm} 4.07$%, OGT; $26.20{\pm}1.48$%) in the vessels injured by $FeCl_3$. Therefore, CMT and LMK02 showed the greatest preventive activity in rat model of arterial thrombosis induced by $FeCl_3$. Conclusions: These results provide experimental evidence for traditional use of herbal prescriptions, suggesting that CMT and LMK02 extracts could be used to prevent vascular injury and thrombosis in the early stages of dementia.

• 한국식품위생안전성학회지
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• 제6권1호
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• pp.13-26
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• 1991

간의 부분적 절제수술을 하지 않고 새로운 발암성 검색법을 찾고자, 화학물질에 민감한 신생암첫 Sprague-Dawley 랫드를 이용하여 diethylnitrosamine(DENA)으로 암을 유발시킨 후, 제1군에는 강력한 촉진제로서 2-acetylaminofluorene(2-AAF)을 사료하여 0.01%가 되게 섞어 투여하였고, 제2군은 약한 촉진제인 phenobarbital을 암수에 0.05% 농도로 녹여 토여하였으며, 제 3군은 대조군으로 DENA만을 1회 투여하였다. 그리고 발암성 평가는 glutathione S-transeferase placental form을 사용하여 검색하였다. 그 결과 체중에 대한 간의 무게비는 이유후 4주째 (7주)에 제2군이 제3군인 대조군에 비해 유의성 있게 (p<0.01)높았으며, 이유후 8주째(11주)에는 제1군과 제 2군이 대조군에 비해 각각 유의성 있게 (p<0.01, p<0.001)높았다. 그리고 이유후 4주(7주)째에 GST-P 양성병변을 이용한 전암병변의 면적을 비교해본바 제 1군과 제2군이 각각 유의성있게 (p<0.01, p<0.05)높게 나타났다. 이상의 결과에서 신생 랫드를 이용한 발암성 실험은 간의 부분적 절제수술을 하지 않고도 화학물질의 발암성을 좀더 이른 시기에 검색할 수 있음을 알 수 있었다. 그러므로 신생동물을 이용한 발암성 실험은 많은 화학물질들의 발암성을 검색하는데 매우 유용한 방법으로 사료된다.

• Korean Journal of Acupuncture
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• 제21권3호
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• pp.59-76
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• 2004

Objectives : The usage of acupuncture has gained popularity for certain chronic pain conditions. However, the efficacy of acupuncture in various diseases has not been fully established and the underlying mechanism is not clearly understood. In the present study, the effect of electroacupuncture (EA) applied to yangno$(SI_6)$ on the neuropathic pain was examined. Methods : A common source of persistent pain in human is a neuropathic pain. Neuropathic pain was induced by tight ligation of L5 spinal nerve. When rats developed pain behaviors, EA was applied for 30 min. under enflurane anesthesia with repeated train stimuli at the intensity of 10X of muscle twitch threshold. The foot withdraw latency of the hind limb was measured for an indicator of pain level after each manipulation. Results : EA increased the mechanical threshold of the foot in the rat model of neuropathic pain significantly for the duration of 1 hr. suggesting a partial alleviation of pain. EA applied to SI6 point produced a significant improvement of mechanical sensitivity of the foot lasting for at least 1 h. However, $ST_{36}$ point did not produce any significant increase of mechanical sensitivity. The improvement of mechanical threshold was interpreted as an analgesic effect. The analgesic effort was specific to the acupuncture point since the analgesic effect on the neuropathic pain model could not be mimicked by EA applied to a point, $ST_{36}$. In addition, this analgesic effect of EA is mediated by a adrenergic mechanism of descending control of spinal cord from the brain. Conclusions : The data suggest that EA produces a potent analgesic effect on the neuropathic pain model in the rat; and 2) that EA-induced analgesia is mediated by a adrenergic mechanism of descending control in a point specific manner.

• Korean Journal of Acupuncture
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• 제22권3호
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• pp.83-104
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• 2005

Objectives : DaeBangPungTang(DBPT) is one of the prescriptions used for the treatment of knee arthritis in oriental medicine. The present study aimed to examine the analgesic effect of DBPT on a rat model of carrageenan-induced arthritis, and the relations between DBPT-induced analgesia and endogenous nitric oxide(NO) and inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and c-Fos protein expression in the spinal cord. Methods : Carrageenan-induced arthritis rat model was used to test the effect of DBPT as a chronic pain model. After the induction of arthritis, rats subsequently showed a reduced stepping force of the affected limb for at least tile next 4 days. The reduced stepping force of the limb was presumably due to a painful knee, since oral infection of indomethacin produced temporary improvement of weight bearing. DBPT dissolved in normal saline was minted several acupoints. After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 12 hours. Results : DBPT produced significant improvement of stepping force of the hindlimb affected by the arthritis lasting at least 9 hours. The magnitude of this improvement was equivalent to that obtained after an oral injection of 3mg/kg of indomethacin and this improvement of stepping force was interpreted as an analgesic effect. DBPT produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner. Both NO production and iNOS, COX-2 protein expression increased by arthritis were suppressed by DBPT. DBPT on combination with electroacupuncture (EA) produced more powerful and longer lasting improvement of stepping force of the hindlimb affected by the arthritis than either DBPT or EA did. Conclusion : The present study suggest that DBPT produces a potent analgesic effect on the chronic hee arthritis pain model in the rat and that DBPT-induced analgesia modulate endogenous NO through the suppression of iNOS/COX-2 protein expression.