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Gang Jiang, Weidong Zhang, Minlian Peng, Wenguang Yan
To explore the clinical efficacy and safety of lumbrokinase in the treatment of acute and moderate risk pulmonary thromboembolism.
 Methods: The clinical data of 60 patients with acute and moderate risk pulmonary thromboembolism, who were collected from January 2010 to October 2015 in Hunan Provincial People's Hospital, were retrospectively analyzed. According to the different treatments, 60 patients were randomly divided into a lumbrokinase group (lumbrokinase in combination with low molecular heparin and sequential warfarin, n=30) and a control group (low molecular heparin and sequential warfarin, n=30)...
October 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Alexia Dickey, Nan Wang, Edwin Cooper, Lauren Tull, Drew Breedlove, Hugh Mason, Dehu Liu, Kevin Yueju Wang
Lumbrokinases, a group of fibrinolytic enzymes extracted from earthworm, have been widely used to prevent and treat various cardiovascular diseases. They specifically target fibrin to effectively degrade thrombi without major side effects. Plant expression systems are becoming potential alternative expression platforms for producing pharmaceutical proteins. In this work, a lumbrokinase (PI239) was produced from a plant system. Both wild-type (WT) and plant codon-optimized (OP) PI239 gene sequences were synthesized and cloned into a geminivirus-based single-vector DNA replicon system...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Shin-Ichi Akazawa, Haruka Tokuyama, Shunsuke Sato, Toshinori Watanabe, Yosuke Shida, Wataru Ogasawara
Earthworms contain several digestive and therapeutic enzymes that are beneficial to our health and useful for biomass utilization. Specifically, earthworms contain potent fibrinolytic enzymes called lumbrokinases, which are highly stable even at room temperature and remain active in dried earthworm powder. However, the high-temperature sterilization method leads to the inactivation of enzymes. Therefore, we investigated the effect of high-pressure treatment (HPT) (from 0.1 MPa to 500 MPa at 25°C and 50°C) on the enzymatic activity of lumbrokinase (LK), α-amylase (AMY), endoglucanase (EG), β-glucosidase (BGL), and lipase (LP) of the earthworm Eisenia fetida, Waki strain, and its sterilization ability in producing dietary supplement...
February 2018: Journal of Bioscience and Bioengineering
Mingji Jin, Guangming Jin, Wei Huang, Zhonggao Gao
The present study aimed to prepare injectable Lumbrokinase (LK) with long circulation time in addition to enhanced anti-thrombotic efficacy. Following preparation, the pharmacokinetic and anti‑thrombotic effect of the drug in a rat carotid artery thrombosis model was evaluated. The drug was prepared by conjugation of LK with mPEG‑SC20000 as previously reported. The pharmacokinetics of the mPEG‑SC20000‑LK were then examined and the anti‑thrombotic activity in an artery‑vein bypass thrombosis rat model was evaluated...
October 2017: Molecular Medicine Reports
Yang Pan, Xiaoting Ren, Shuang Wang, Xin Li, Xianglin Luo, Zongning Yin
To alleviate the hemorrhagic side effect of thrombolysis therapy, a thrombus targeted drug delivery system based on the specific affinity of Annexin V to phosphatidylserine exposed on the membrane surface of activated platelet was developed. The amphiphilic and biodegradable biomaterial, polycaprolactone-block-poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-hydroxyethyl methacrylate) (PCL-b-PDMAEMA-b-PHEMA (PCDH)) triblock polymer, was synthesized via ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) to use as the nanocarriers of thrombolytic drug...
March 13, 2017: Biomacromolecules
Mahendra Kumar Verma, K K Pulicherla
In this research, a serine protease was isolated and purified from Indian earthworm Pheretima posthumous by fractionation with ammonium sulfate followed by ion exchange and size exclusion chromatography. The molecular weight of purified protease was determined 29.5kDa by Maldi-TOF/MS. The enzyme exhibited a maximum proteolytic activity of 1.2U/ml with specific activity of 17.65U/mg at pH 8 and temperature 40°C. 2D electrophoresis study illustrated purity of enzyme, purified as a single peptide and isoelectric point (pI) 4...
February 2017: International Journal of Biological Macromolecules
Florensia Nailufar, Raymond R Tjandrawinata, Maggy T Suhartono
Objective. To evaluate thrombus degrading effect of a fibrinolytic enzyme from food origin Stenotrophomonas sp. of Indonesia. Methods. Prior to animal study, the enzyme safety was tested using cell culture. The effect on expression of tissue plasminogen activator was also analysed in the cell culture. For in vivo studies, 25 Wistar rats were used: normal control, negative control, treatment groups with crude and semipurified enzyme given orally at 25 mg/kg, and positive control group which received Lumbrokinase at 25 mg/kg...
2016: Advances in Pharmacological Sciences
Yi-Hsin Wang, Ke-Min Chen, Ping-Sung Chiu, Shih-Chan Lai, Hsing-Hui Su, Ming-Shiou Jan, Chia-Wei Lin, Dah-Yuu Lu, Yuan-Tsung Fu, Jiuan-Miaw Liao, Jinghua Tsai Chang, Shiang-Suo Huang
Lumbrokinase, a novel antithrombotic agent, purified from the earthworm Lumbricus rubellus, has been clinically used to treat stroke and cardiovascular diseases. However, inflammatory responses associated with the cardioprotective effect of lumbrokinase remain unknown. In this study, the signaling pathways involved in lumbrokinase-inhibited expressions of inflammation mediators were investigated in rats subjected to myocardial ischemia-reperfusion (I-R) injury. The left main coronary artery of anesthetized rats was subjected to 1h occlusion and 3h reperfusion...
October 2016: Journal of Molecular and Cellular Cardiology
R R Tjandrawinata, D A Yunaidi, L W Susanto
BACKGROUND: This study was aimed to evaluate the safety and tolerability of Lumbrokinase DLBS1033 in healthy adult subjects. METHODS: This was a 2-arm, randomized, double-blind, placebo-controlled, cross-over study over 14 days of treatment with DLBS1033 490 mg 3 times daily. Eligible subjects were enrolled at Period 1 and allocated to receive either test drug or placebo, and underwent a clinical assessment including vital signs, electrocardiography, laboratory examination (hemostasis parameters, routine hematology, liver and renal function), the presence of hemorrhagic symptoms and allergic reactions...
June 2016: Drug Research
Hung-En Liao, Chao-Hung Lai, Tsung-Jung Ho, Yu-Lan Yeh, Gwo-Ping Jong, Wu-Hsien Kuo, Li-Chin Chung, Pei-ying Pai, Su-Ying Wen, Chih-Yang Huang
Exposure to second-hand tobacco smoke (SHS) has been epidemiologically linked to heart disease among non-smokers. However, the molecular mechanism behind SHS-induced cardiac disease is not well known. This study found that SD rats exposed to cigarette smoke at a dose of 10 cigarettes for 30 min twice a day for 1 month had a reduced left ventricle-to-tibia length ratio (mg/mm), increased cardiomyocyte apoptosis by TUNEL assay and a wider interstitial space by H&E staining. However, lumbrokinase and dilong both reversed the effects of SHS...
June 30, 2015: Chinese Journal of Physiology
Yuan-Tsung Fu, Shi-Yuan Sheu, Yueh-Sheng Chen, Kuo-Yu Chen, Chun-Hsu Yao
Bone cell activities are very important in bone remodeling. This study investigates the effects of lumbrokinase on bone cell activities in cultures. Moreover, a biodegradable composite (GGT) containing genipin-crosslinked gelatin and β-tricalcium phosphate was prepared to carry lumbrokinase (GGTLK). Rat calvarial bone defects were filled with GGT and GGTLK composites. Bone healing was monitored in vivo by bioluminescence imaging and micro-CT. Lumbrokinase was found to have a dose-dependent effect on bone cell activities...
September 2015: Bone
Han-Chung Lee, Yuan-Man Hsu, Chin-Chuan Tsai, Cherng-Jyh Ke, Chun-Hsu Yao, Yueh-Sheng Chen
We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances...
2015: American Journal of Chinese Medicine
Nora L El-Tantawy
By definition, parasites cause harm to their hosts. But, considerable evidence from ancient traditional medicine has supported the theory of using parasites and their products in treating many diseases. Maggots have been used successfully to treat chronic, long-standing, infected wounds which failed to respond to conventional treatment by many beneficial effects on the wound including debridement, disinfection, and healing enhancement. Maggots are also applied in forensic medicine to estimate time between the death and discovery of a corpse and in entomotoxicology involving the potential use of insects as alternative samples for detecting drugs and toxins in death investigations...
February 2015: Parasitology Research
Chien-Kuo Han, Wei-Wen Kuo, Chia-Yao Shen, Tung-Sheng Chen, Peiying Pai, Chang-Hai Tsai, Feng-Yueh Lo, Da-Tong Ju, Chih-Yang Huang
Infusion of high-KCl cardioplegic solution (High-KCS) is the most common method used to induce asystole before cardiac surgery. However, our previous study showed the High-KCS can cause the apoptosis of cardiomyocytes in patients who were administered High-KCS prior to undergoing coronary artery bypass graft (CABG) to treat coronary artery disease (CAD). Therefore, it is urgent today to find a complementary medicine to reduce this damage. Dilong (earthworm) has been used as a traditional medicine in China for several thousand years, and extract from the dilong has been empirically used in Asia for the treatment of vascular disorders...
2014: American Journal of Chinese Medicine
Raymond R Tjandrawinata, Jessica Trisina, Puji Rahayu, Lorentius Agung Prasetya, Aang Hanafiah, Heni Rachmawati
DLBS1033 is a bioactive protein fraction isolated from Lumbricus rubellus that tends to be unstable when exposed to the gastrointestinal environment. Accordingly, appropriate pharmaceutical development is needed to maximize absorption of the protein fraction in the gastrointestinal tract. In vitro, ex vivo, and in vivo stability assays were performed to study the stability of the bioactive protein fraction in gastric conditions. The bioactive protein fraction DLBS1033 was found to be unstable at low pH and in gastric fluid...
2014: Drug Design, Development and Therapy
Chunfeng Guan, Jing Ji, Chao Jin, Gang Wang, Xiaozhou Li, Wenzhu Guan
Lumbrokinase (LK) is a group of serine proteases with strong fibrinolytic and thrombolytic activities and is useful for treating diseases caused by thrombus. Cholera toxin B subunit (CTB) has been widely used to facilitate antigen delivery by serving as an effective mucosal carrier molecule for the induction of oral tolerance. We investigate here the application of CTB as a transmucosal carrier in enhancing its fusion protein-LKs effect to protect rats against thrombosis. Thus, in this study, CTB-LK fusion gene separated by a furin cleavage site was expressed in seeds of Helianthus annuus L...
September 2014: Biotechnology Progress
Chao-Hung Lai, Chien-Kuo Han, Marthandam Asokan Shibu, Pei Ying Pai, Tsung-Jung Ho, Cecilia Hsuan Day, Fuu-Jen Tsai, Chang-Hai Tsai, Chun-Hsu Yao, Chih-Yang Huang
Exposure to tobacco smoke has epidemiologically been linked to the occurrence of cardiovascular disease among nonsmokers but the associated molecular events are not well elucidated yet. When Sprague Dawley rats were exposed to second-hand tobacco cigarette smoke twice a day for a 30 days period at an exposure rate of 10 cigarettes/30 min, they showed adverse effects including reduced left ventricle weight, increased cardiac damages, deteriorated cardiac features, and cardiac fibrosis. Exposure to second-hand smoking (SHS) increased the molecular markers of cardiac fibrosis such as urokinase plasminogen activator and matrix metallopeptidases...
September 2015: Environmental Toxicology
Kevin Yueju Wang, Lauren Tull, Edwin Cooper, Nan Wang, Dehu Liu
Earthworms have been used as a traditional medicine in China, Japan, and other Far East countries for thousands of years. Oral administration of dry earthworm powder is considered as a potent and effective supplement for supporting healthy blood circulation. Lumbrokinases are a group of enzymes that were isolated and purified from different species of earthworms. These enzymes are recognized as fibrinolytic agents that can be used to treat various conditions associated with thrombosis. Many lumbrokinase (LK) genes have been cloned and characterized...
2013: Evidence-based Complementary and Alternative Medicine: ECAM
Yong-Jun Cao, Xia Zhang, Wan-Hua Wang, Wan-Qing Zhai, Ju-Fen Qian, Jian-Sheng Wang, Jun Chen, Nian-Xing You, Zhong Zhao, Qiu-Yi Wu, Yuan Xu, Lei Yuan, Rui-Xia Li, Chun-Feng Liu
BACKGROUND: Elevated fibrinogen (Fg) level is a known risk factor for ischemic stroke. There are few clinical trials on oral fibrinogen-depleting therapies for secondary ischemic stroke prevention. We aimed to assess the effects of one-year therapy with oral lumbrokinase enteric-coated capsules on secondary ischemic stroke prevention. METHODS: This is a multicenter, randomized, parallel group and controlled study that began treatment in hospitalized patients with ischemic stroke and continued for 12 months...
November 2013: Chinese Medical Journal
Chih-Yang Huang, Wei-Wen Kuo, Hung-En Liao, Yueh-Min Lin, Chia-Hua Kuo, Fuu-Jen Tsai, Chang-Hai Tsai, Jia-Long Chen, Jing-Ying Lin
Recent studies have found that cigarette smoke is epidemiologically linked to an increased risk for impaired cognitive development in adolescents. This study evaluated the influence of side stream smoke (SSS) exposure on hippocampal apoptosis and of the lumbrokinase (LK) effects on SSS induced apoptosis in young hamster hippocampus. Twenty male hamsters at six weeks of age were randomly divided into control group, SSS group (exposed to tobacco cigarettes smoke at doses of 10 cigarettes for 30 min twice a day for 1 month), and SSS hamsters with LK treatment (1...
May 20, 2013: Chemical Research in Toxicology
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