Study progress in therapeutic effects of traditional Chinese medicine monomer in severe acute pancreatitis

Study progress in therapeutic effects of traditional Chinese medicine monomer in severe acute pancreatitis 1 first-author †E-mail:zxp99688@vip.163.com †E-mail:zxp99688@vip.163.com zxp99688@vip.163.com 2 3 Department of General Surgery, Hangzhou First People’s Hospital, Hangzhou 310006, China Department of General Surgery, Hangzhou First People’s Hospital, Hangzhou 310006, China Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China Department of Acupuncture and Massage, Zhejiang College of Traditional Chinese Medicine, Hangzhou 310053, China Department of Acupuncture and Massage, Zhejiang College of Traditional Chinese Medicine, Hangzhou 310053, China Severe acute pancreatitis (SAP) is a common acute abdomen clinical problem characterized by high mortality, multiple complications, complicated pathogenesis and difficult treatment. Recent studies found traditional Chinese medicine (TCM) monomers have markedly good effect for treating SAP. Many TCM monomers can inhibit pancreatin, resist inflammation, improve microcirculation and immunoloregulation, etc. to block the pathological progress of SAP in multiple ways, reduce complications and lower mortality with rapid effects. It is significant for enhancing SAP treatment to deeply understand the current situation in TCM monomers for treating SAP and take precious references therein. This article summarizes the treating effects and mechanisms of TCM monomers for SAP in recent years. Severe acute pancreatitis Treatment Traditional Chinese medicine (TCM) monomer INTRODUCTION 1 Severe acute pancreatitis (SAP) is one of the three main acute abdominal problems always accompanied by multiple-system and multiple-organ impaired function or failure. Its onset and development are characterized by rapid changes, complicated illness state and difficult treatment. With the continuous development of the traditional Chinese medicine industry in recent years, it is proved that traditional Chinese medicine (TCM) monomers monomers have a marked effect for treating SAP with unique advantages. Therefore this article has summarized the TCM monomers with marked therapeutic effects on SAP in recent years and demonstrated their treating effects and mechanisms. EXPERIMENTAL STUDY PROGRESS 1 Emodin 2 Emodin, an anthraquinone derivative extracted from rhubarb ( Rheum palmatum L., Rheum tanguticum Maxim. ex Balf or Rheum officinale Baill ) and free anthraquinone aglucone can lead to catharsis, serve as cholagogue, protect liver, resist infection, promote secretion of pancreatic fluid and pancreatin, etc. TGFβ1 mRNA expression was tested on rat acute pancreatitis models induced by intraperitoneal infusion of caerulein, treated or untreated by emodin (Lou et al., 2001 2001 ). TGFβ1 mRNA expression was strongly detected at 6 h after treatment and reaching the peak at 48 h (move forward compared to the untreated group). The DNA synthesis and total protein content in pancreatic tissue also increased significantly in the emodin treated group, which indicated the mechanism of emodin in treating acute pancreatitis might be by way of enhancing cytokine TGFβ1 gene expression, regulating cell growth and differentiation, stimulating the formation of extracellular matrix components, increasing DNA synthesis and protein content, and taking part in pancreatic repairing and remodeling. The expression of Bax mRNA was detected to increase significantly in SAP rats treated by emodin compared with the untreated ones, which indicated the therapeutic efficacy of emodin in the treatment of acute pancreatitis may be attributed to its action of modulating apoptosis-related genes (Pan et al., 2002 2002 ). Wu et al.( 1997 1997 ) found emodin could markedly improve pancreatic ischemia in early stage of SAP, which may be due to inhibiting abnormal metabolism of gadoleic acid. Emodin can improve microcirculation and enhance cell protection, which is beneficial to SAP treatment. So, as a common medicine in treating SAP, emodin mainly can lead to catharsis, promote secretion of bilirubin and bile acid, relieve sphincter of Oddi spasm, eliminate oxygen free radicals, lower endotoxin level of plasma, effectively inhibit the abnormal metabolism of vasoactive substances such as gadoleic acid to improve microcirculation; It also can promote secretion of pancreatic fluid, interfere with function of apoptotic gene, induce acinar cell apoptosis of pancreas and thus avoid or reduce the release of pancreatin and inflammatory mediators to block pathogenic process (Gao and Chen, 1990 1990 ). Tripterygium glycosides 2 Tripterygium glycosides (TII), a glucoside preparation extracted from the root of Tripterygium wilfordii Hook. F, is a non-steroidal immunosuppressor. Its main component is diterpene lactone with relatively strong anti-inflammatory and immunosuppressive activities (Men, 1994 1994 ). NF-κB is a transcription factor playing an important role in a series of immunological and inflammatory reactional genetic transcription. It has obvious inhibiting effect on T cell proliferation and the activity of mediators of inflammation, including IL-1, IL-6, IL-8 and TNFα and thus blocks the “waterfall” cascade effect of inflammatory mediators. SAP models induced by retrograde injection of 5% sodium taurocholate to the pancreatic duct were treated by intraperitoneal injection of TII (Zhang et al., 2005 2005 ). Serum amylase, endotoxin level of plasma, IL-1, TNFα and NF-κB activity were significantly decreased and life span extended in the treated group compared with the untreated one. Suspension of TII powder was injected into 30 SAP rats intraperitoneally, 50 mg/(kg·d), 3 d or ended the administration upon death of animals (Jin et al., 2000 2000 ). After treatment, amylase, endotoxin, TNF-α and IL-1 indexes dropped markedly, pancreas pathological grading by optical microscope dropped obviously, cell injury was reduced under electron microscope. The mechanism of TII treating SAP might be through inhibiting NF-κB activity, decreasing inflammatory mediator levels and reducing the pathological damage of the pancreas. Ginkolide B 2 Ginkolide B which is the main active ingredient of extract from Ginkgo Biloba, EGb of Ginkgo family, is a terpene compound and natural platelet activating factor (PAF) antagonist with strong activity (Pietri et al., 1997 1997 ). Flavone glycosides (24%) and lactone (6%) are two effective constituent of Ginkolide B. Flavone glycosides plays an important role in eliminating excessive oxygen free radicals in body, inhibiting the lipid peroxidation of cell membrane, enhancing the superoxide dismutase (SOD) activity of red cells and thus protecting cell membrane, preventing serious body injuries from free radicals. Lactone acts as a PAF antagonist and improves blood rheology, modulates neurotransmitter release, increases oxygen and glucose supply of ischemic tissues and lowers blood viscosity. Two randomized, double-blind, placebo-controlled trials (Schneider et al., 2005 2005 ; Horsch and Walther, 2004 2004 ) proved that EGb could improve cognitive performance of patients with Alzheimer’s disease and the outcome of patients with peripheral arterial occlusive disease. Zeybek et al.( 2003 2003 ) found prophylactic application of EGb caused significant decrease in serum amylase and lipase levels compared with the control group. Yamaguchi et al.( 1999 1999 ) treated rats with EGb after inducing SAP by caerulin. Edema, leucocytes, amylase, pancreas weight and PAF concentration all changed markedly, while lucigenin, luminol, NO marks declined markedly. Treatment of SAP rats with EGb significantly reduced both frequency of bacterial translocation and intestinal mucosal cells apoptosis compared with the control group, which suggest EGb has protective effect on cell membrane, prevents serious body injuries from free radicals, improves microcirculation of pancreas and intestines and lowers endotoxin level (Zhang et al., 2004 2004 ). Sanchinoside 2 Sanchinoside extracted from Panax notoginseng (Fam. Araliaceae) is dammarane type triterpene saponin, mainly includes 9 kinds of monomers such as panaxoside Rb1, Rb2, Rc, Rd and Rg1. The hydrolysates of sanchinoside are panoxadiol (PDS) and panoxatriol (PTS). It can dilate blood vessel, improve microcirculation, protect anti-oxidation capacity of tissue, inhibit lipid peroxidation, reduce Ca 2+ inflow, and affect generation of free radicals (Guan et al., 1990 1990 ). Xiong et al.( 2004 2004 ) found sanchinoside could reduce the nitric oxide levels in plasma and pancreas in rats with acute necrotizing pancreatitis (ANP) (2~12 h after induction). Sanchinoside can inhibit the release of pancreatic amylase, inflammatory factor, cytokine and activate macrophage and T cells. SAP rats were treated by sanchinoside (20 mg/100 g) and somatostatin (1 μg/100 g) and put to death respectively after 2 h and 4 h. The pathological injury of pancreas tissue was markedly reduced, serum amylase, TXB2 and TNF-α level dropped markedly especially during early stage of function (Ge et al., 2002 2002 ). Especially, sanchinoside showed more inhibitive efficacy on TXB2 and TNF-α compared with somatostatin group. Taxol 2 Taxol, an extract from bark of torreya (Taxaceae) and diterpene compound has potent anti-cancer effect. It can induce apoptosis of pancreatic acinar cell and can be used to treat cancer by adjusting the contents of apoptosis-associated protein Bcl-2, Bax, Fas, FasL and p53. It can raise Bax level to promote acinar cell apoptosis, markedly elevate the expression of p53 protein which had declined during SAP, increase the expression of FasL mRNA and promote acinar cell apoptosis by increasing the Fas expression of acinar cell. The apoptosis promoting effect of taxol depends on dosage. There is a marked positive correlation between dose of taxol and pancreatic acinar cell apoptosis index within a relative small dose range. Which indicates in small doses, taxol tends to induce pancreatic acinar cell apoptosis and thus relieve the severity of the pancreatitis. But there is a marked negative correlation between dose of taxol and pancreatic histological changes within a relative high dose range, and increase of dose makes the signal channel of cell necrosis dominant and aggravates pancreatitis. Various taxol doses were given to the rats of SAP by intraperitoneal infusion, and checked the cell apoptosis index after 24 h (Chao and Qi, 2003 2003 ). The result showed 5 mg/kg dose resulted in the most marked effect and minimum necrosis of the acinus. The treating effect declines with the increase or decrease of the dosage. Resveratrol 2 Resveratrol, an extract from dried giant knotweed rhizome (polygonaceae) and hydroxyl diphenyl ethylene extensively distributed in the vegetable kingdom can resist inflammation, oxidation, platelet aggregation, etc. Resveratrol can inhibit the generation, activation and release of inflammatory mediators: it can reduce the generation of NO, IL-1, IL-6, TNF, etc. during inflammatory process by inhibiting the NF-κB activation of macrophage, lymphocyte, etc., block NF-κB activation induced by TNF, and inhibit mitogen caused protein kinase activation induced by TNF. After 90 rats were randomly divided into 5 groups, including blank control group and treatment groups, determinations were conducted respectively at 3, 6, 12 h and the result showed resveratrol can inhibit the serum IL-6 and TNF level of SAP rat model at dosage of 10 mg/kg, and reduce the generation of inflammatory mediators of acute pancreatitis and mortality (Huang et al., 2005 2005 ). Rutoside 2 Rutoside (Ru), the main extract and flavonol from bud of Chinese scholar tree (Leguminosae) can resist inflammation, reduce capillary fragility and resist oxidation. In AP (acute pancreatitis) pancreatic tissues, the expression of inducible nitric oxide synthase (iNOS) increases. In inflammatory reactions, the activity of iNOS and NO level increase abnormally leading to systemic hemodynamic disturbance and lipid peroxidation injury. Rats were randomly divided into 5 groups, including control group, model group and three Ru treatment groups with different doses (Tian et al., 2006 2006 ). Ru was injected subcutaneously at posterior limb and determined after 24 h. The serum amylase (AMS) of rats in treatment group dropped markedly and edema in pancreatic tissues was markedly alleviated. It effectively lowers elevated serum NO level, enhances SOD (superoxide dismutase) activity and reduces MDA (malondialdehyde) generation. Ru can also effectively inhibit the activity of type II phosphatidase A 2 (II PLA 2 ). Ru (60, 120 mg/kg) increases serum Ca 2+ concentrations after the induction of AP at 6 and 12 h and decreases Ca 2+ concentrations of pancreas tissue and significantly raises PLA 2 levels after the induction of AP at 24 h. The study indicated that the mechanisms of protective effect of Ru on the experimental AP might block the translocation of calcium from extracellular to intracellular compartments and attenuate the injury of Ca 2+ overload in acinus. And possibly, the antagonistic effect is also related to the inhibition on PLA 2 activation. CLINICAL TREATMENT PROGRESS 1 Anisodamine 2 Anisodamine also named 654-2 is alkaloid extracted from Anisodus Tonguticus. As acetylcholine receptor antagonist, anisodamine can block M and α receptor, improve metabolism of arachidonic acid, relieve vascular smooth muscle spasm, lower vascular resistance, modulate calcium homeostasis, block Ca 2+ inflow, effectively stop cell calcium overload in ischemia reperfusion injury, increase energy and oxygen supply of tissue, protect cells at cell level, enhance their tolerance to ischemia and hypoxidosis, stabilize lysosome membrane of gland cells, and thus block the activation and occurrence of pancreatin, evolution of self digestion in early stage, inhibit pancreas gland secretion and let pancreas glands with pathological changes rest and recover (Yu and Tan, 1992 1992 ). In addition, it also can resist oxygen free radicals and endotoxin at cell membrane level, etc. (Tang, 1986 1986 ). Ma et al.( 2003 2003 ) randomly divided 60 cases of hospitalized SAP patients into two groups, and the treatment group was given anisodamine 40~100 mg, intravenously continuously each day and yielded distinct treatment effects. Finally, there was marked statistical difference between the two groups in average abdominal pain relieved days, days of hospital stay and hospital charge as well as mortality. Tetramethylpyrazine 2 Tetramethylpyrazine (TMP), an amide alkaloid monomer with typical feature of “calcium channel blocker” isolated from the rhizome of Ligusticum walliichi can potently dilate blood vessel, improve microcirculation, lower blood viscosity, improve blood rheology, and increase blood flow in microcirculation of viscera. It can indirectly dilate blood vessel by inhibiting TXA 2 synthesis, promoting generation of PGI 2 , modulating TXA 2 /PGI 2 imbalance, and increasing stability of lysosome membrane. TMP can raise surface charge of red cell and platelet, lower platelet aggregation, enhance transforming capacity of red cell, relieve high coagulative state, lower blood viscosity, and thus improve blood rheology, change blood flow during blood stagnancy, accelerate blood flow, maintain openness of capillary vessel, increase total blood flow, prevent thrombosis and enhance hemolysis. In addition, it can also eliminate oxygen free radicals (Qian et al., 1993 1993 ) to resist oxidation. Ninty-five cases of SAP patients were randomly divided into 2 groups, the 50 cases of the treatment group were given TMP injection 100 ml, intravenously, once daily and after 5 d of treatment 31 cases were cured, 14 cases effective, 5 cases ineffective, total effective rate 90.0%, and there was no marked difference between treatment group and control group (Chang et al., 2003 2003 ). Tetrandrine 2 Tetrandrine (Tet), a bisbenylisoquinoline alkaloid isolated from the dried root of Stephenia tetrandra S Moore, is a calcium antagonist, now also used as PAF antagonist. PAF plays an important role in the occurrence and progress of acute pancreatitis and its complications. The mechanism of Tet for treating SAP might be: reduce PAF release by inhibiting Ca 2+ inflow or inner calcium outflow (Zhang, 1993 1993 ), inhibit PLA 2 , reduce PAF release and can reduce the activation of PLA by PAF (He, 1995 1995 ). Tet can reduce peroxidation injury by inhibiting pancreatin activation, inhibit the calcium overload of pancreatic acinar cell, stop NF-κB activation and alleviate pancreatic inflammatory reaction by its calcium antagonist function. Twenty-six cases of SAP patients were randomly divided into 2 groups, the treatment group took Tet tablets or dissolved physiological saline orally, tube clamp 0.5 h, 2 tablets each time, thrice daily and one week for a treatment period (Jiang et al., 2000 2000 ). After treatment, 12 cases in treatment group were cured, 1 dead, recovery rate 92.3%, which indicates better treatment effect than that of the control group. The main complication occurrence rate and mortality were all obviously lower than those of the control group. Breviscapine 2 Breviscapine (Bre) also named scutellarein is ethanol extract water solution of the herb Erigeron breviscapus (ASTERACEAE). Its main ingredients are total flavone, Bre A and B. Bre can improve blood circulation, lower vascular resistance, inhibit intravascular coagulation and promote fibrolysis. Therefore, it can improve pancreatic microcirculation, lower blood viscosity, improve local blood supply of pancreas, correct ischemia and prevent necrosis. The total flavone can potently improve microcirculation, activate blood and eliminate stagnancy. It can relax blood vessel smooth muscle, dilate arteriole, especially sphincter before and behind capillary vessel (Xu, 2001 2001 ). Bre B can lower red cell accumulation, inhibit platelet aggregation and raise TXB 2 , TXB 2 /6-keto-PGF 1 α ratio, and also restore 6-keto-PGF 1 α level after ischemia, inhibit intravascular coagulation, promote fibrinolysis and thus lower blood viscosity (Chen, 1998 1998 ). In addition, Bre can enhance macrophage capacity and immune system, eliminate harmful oxygen free radicals, prevent and treat serious pathological and physiological reactions induced by calcium overload, and prevent neuron injury due to ischemia reperfusion. Sixty cases of acute pancreatitis patients were randomly divided into 2 groups (4 cases of SAP in treatment group, 5 in control group) (Yu et al., 2000 2000 ). The treatment group was given Bre injection, and after completion of treatment period, 28 cases were cured, 2 cases were effective, total effective rate 100%, average days for cure 6.28 d, and all indexes for sign disappearance were better than those of the control group. Sodium β-aescin 2 Sodium β-aescin, an extract from Aesculus hippocastanum (Hippocastanaceae), mainly plays roles in anti-effusion by influencing the metabolism of prostaglandin and increasing PGF 2 α secretion and in anti-inflammation by increasing the secretion of cortisol compound. It can dilate arteriole, slowly and persistently contract veinule, improve the blood stagnancy of pancreatic microcirculation, accelerate microcirculation, eliminate inflammatory mediators and promote lymphatic return in order to reduce the inflammatory effusion of pancreas and eliminate pancreatic edema. It also can stabilize unit membrane, further reduce the injury of lysosome and mitochondria, restore the motor function of intestine, reduce intestinal bacterial translocation and eliminate intestinal infection. Fifty cases of acute pancreatitis patients were randomly divided into 2 groups (17 male patients and 33 female patients, age from 25 to 80, average age 42.5). The 24 patients in control group were only given conventional therapy while the 26 patients in treatment group were given sodium β-aescin plus conventional therapy. The result shows that after being treated by sodium β-aescin, the time required by acute pancreatitis patients to dispel abdominal pain, abdominal tenderness, restore normal intestinal functions and hemodiastase was markedly shorter than that of the control group ( P < 0.01) (Fu et al., 2003 2003 ). CONCLUSION 1 The conservative treatment of SAP by TCM monomers is quite significant. Markedly different from Western medicine such as somatostatin, TCM monomers not only act on pancreas, stomach and intestines, but also have marked treatment effects on other viscera injuries due to systemic inflammatory response accompanying pancreatitis and block pathological progress of SAP in a way. Its functions are more extensive than those of somatostatin and mutually supplementary. Therefore, the application of TCM monomers for treating SAP has significant clinical value and broad development prospect. We believe by further experimental study and clinical application that TCM monomer can become a promising preparation for clinical treatment of SAP. References DM Chang , YJ Gu , XC Zhang . The observation of therapeutic effect of Ligustrazine injection on treating 50 case of patients with acute pancreatitis . Acad Periodical Changchun Coll Tradit Chin Med , 2003 . 19 ( 1 ): 40 - 41 . (in Chinese) . The observation of therapeutic effect of Ligustrazine injection on treating 50 case of patients with acute pancreatitis HW Chao , QH Qi . The study of taxol to induce apoptosis of pancreatic acinar cell and relieve severity of acute pancreatitis . Chin J Gen Surg , 2003 . 18 ( 5 ): 307 - 308 . (in Chinese) . The study of taxol to induce apoptosis of pancreatic acinar cell and relieve severity of acute pancreatitis XQ Chen . New Pharmacology , 1998 . : Beijing Publishing Company of People Public Health , 276 (in Chinese) . New Pharmacology X Fu , XF Yang , H Zhen , XD Zhou . The observation of curative effects on sodium β-aescin treating 26 cases of acute pancreatitis . J Nanhua Univ , 2003 . 31 ( 4 ): 479 - 480 . (in Chinese) . The observation of curative effects on sodium β-aescin treating 26 cases of acute pancreatitis XS Gao , FX Chen . To use Rhubarb properly on behalf of mankind healthy . J Integr Tradit Western Med , 1990 . 10 ( 12 ): 754 (in Chinese) . To use Rhubarb properly on behalf of mankind healthy Z Ge , DS Zhang , YL Hu , Y Wang . Experimental study on therapeutic effect of pngs and somatostatin for severe acute pancreatitis model in rats . China J Mod Med , 2002 . 12 ( 14 ): 17 - 19 . (in Chinese) . Experimental study on therapeutic effect of pngs and somatostatin for severe acute pancreatitis model in rats YY Guan , KM Chen , JJ Sun . The effection of Sanchinoside to α receptor of vascular smooth muscle in extending pulse and inflow of Ca++ . Chin Pharmacol Bull , 1990 . 6 ( 4 ): 229 - 231 . (in Chinese) . The effection of Sanchinoside to α receptor of vascular smooth muscle in extending pulse and inflow of Ca++ MH He . Investagate the effect of phospholipase A 2 in leucocyte and its mechanism of tetrandrine . Chin Pharmacol Bull , 1995 . 11 ( 1 ): 53 (in Chinese) . Investagate the effect of phospholipase A2 in leucocyte and its mechanism of tetrandrine S Horsch , C Walther . Ginkgo biloba special extract EGb 761 in the treatment of peripheral arterial occlusive disease (PAOD)—a review based on randomized, controlled studies . Int J Clin Pharmacol Ther , 2004 . 42 ( 2 ): 63 - 72 . 15180165 . Ginkgo biloba special extract EGb 761 in the treatment of peripheral arterial occlusive disease (PAOD)—a review based on randomized, controlled studies JY Huang , QY Ma , Q Sun , XM Liu , J Xu . Experimental study of resveratrol on severe acute pancreatitis . J Xi’an Jiaotong Univ , 2005 . 26 ( 2 ): 163 - 165 . (in Chinese) . Experimental study of resveratrol on severe acute pancreatitis ZH Jiang , JB Yu , J Yu . Tetrandrine treat acute hemorrhagic necrotizing pancreatitis . J Tradit Chin Med Univ Hunan , 2000 . 20 ( 1 ): 47 - 48 . (in Chinese) . Tetrandrine treat acute hemorrhagic necrotizing pancreatitis C Jin , QX Ni , QH Zhang , Y Xiang , N Zhang , YL Zhang . An experimental study on the immunoregulatory effect of an extract of Tripterygium Wilfordii Hook F in rats with acute necrotizing pancreatitis . Chin J Gen Surg , 2000 . 15 ( 5 ): 283 - 285 . (in Chinese) . An experimental study on the immunoregulatory effect of an extract of Tripterygium Wilfordii Hook F in rats with acute necrotizing pancreatitis KX Lou , ZH Gong , YZ Yuan , SP Tu , YZ Zhai , JY Xu . Study on effect of emodin on TGF beta 1 expression in pancreatic tissue of rats suffering from acute pancreatitis . Chin J Integr Tradit Western Med , 2001 . 21 ( 6 ): 433 - 436 . (in Chinese) . Study on effect of emodin on TGF beta 1 expression in pancreatic tissue of rats suffering from acute pancreatitis XG Ma , CC Wang , JC Zhu . Continuous intravenous instillation of anisodamine as a treatment for severe acute pancreatitis: a controlled study of 60 cases . Chin J Pancreatol , 2003 . 3 ( 3 ): 167 - 169 . (in Chinese) . Continuous intravenous instillation of anisodamine as a treatment for severe acute pancreatitis: a controlled study of 60 cases FC Men . Study progress of Tripterygium Wilfordii and its monomer in antifertility and immunosuppressive action . J Chin Tradit Herbal Drugs , 1994 . 25 ( 11 ): 607 (in Chinese) . Study progress of Tripterygium Wilfordii and its monomer in antifertility and immunosuppressive action L Pan , YZ Yuan , YP Zhang , MM Qiao , ZK Zhai . Mechanisms of emodin in apoptosis of pancreatic cells in acute pancreatitis in rats . Clin J Pancreatol , 2002 . 12 ( 2 ): 214 - 217 . (in Chinese) . Mechanisms of emodin in apoptosis of pancreatic cells in acute pancreatitis in rats S Pietri , E Maurelli , K Drieu , M Culcasi . Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761) . J Mol Cell Cardiol , 1997 . 29 ( 2 ): 733 - 742 . 9140830 DOI: 10.1006/jmcc.1996.0316 http://doi.org/10.1006/jmcc.1996.0316 . Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761) YH Qian , SZ Gao , Z Yao . The effection on oxygen free radical of danshen, allopurinol and tetramethyl-pyrazine in extracorporeal circulation . Chin J Thorac Cardiovasc Surg , 1993 . 9 ( 3 ): 224 - 226 . (in Chinese) . The effection on oxygen free radical of danshen, allopurinol and tetramethyl-pyrazine in extracorporeal circulation LS Schneider , ST DeKosky , MR Farlow , PN Tariot , R Hoerr , M Kieser . A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer’s type . Curr Alzheimer Res , 2005 . 2 ( 5 ): 541 - 551 . 16375657 DOI: 10.2174/156720505774932287 http://doi.org/10.2174/156720505774932287 . A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer’s type C Tang . Effect of endotoxin on lipid peroxidation in liposomes and the salutary effects of anisodamine and α-tocophero . Circ Shock , 1986 . 18 ( 3 ): 354 - 359 . (in Chinese) . Effect of endotoxin on lipid peroxidation in liposomes and the salutary effects of anisodamine and α-tocophero J Tian , SG Song , YL Wang , ZW Chen , WZ Zhao . Effect of rutoside on phospholipase A 2 and Ca 2+ in murine acute pancreatitis . Anhui Med Pharm J , 2006 . 10 ( 2 ): 88 - 90 . (in Chinese) . Effect of rutoside on phospholipase A2 and Ca2+ in murine acute pancreatitis JX Wu , JY Xu , YZ Yuan . Effect of emodin and stilamin on pancreatic ischemiain acute hemorrhagic necrotizing pancreatitis and its mechanism . Chin Crit Care Med , 1997 . 9 ( 7 ): 405 - 408 . (in Chinese) . Effect of emodin and stilamin on pancreatic ischemiain acute hemorrhagic necrotizing pancreatitis and its mechanism JW Xiong , WL Shen , GZ Chen , J Wen , SJ Liu . Changes of nitric oxide in acute necrotizing pancreatitis and therapeutic action of sanqizongdai . Chin J Surg Integr Tradit Western Med , 2004 . 10 ( 3 ): 192 - 194 . (in Chinese) . Changes of nitric oxide in acute necrotizing pancreatitis and therapeutic action of sanqizongdai JH Xu . Scutellarin injections of Yunan treat 67 cases of patients with cerbral infaction . Chin J Integr Tradit Western Med , 2001 . 21 ( 3 ): 228 (in Chinese) . Scutellarin injections of Yunan treat 67 cases of patients with cerbral infaction Y Yamaguchi , F Matsumura , J Liang , K Okabe , T Matsuda , H Ohshiro , K Ishihara , E Akizuki , S Yamada , M Ogawa . Platelet-activating factor antagonist (TCV-309) attenuates the priming effects of bronchoalveolar macrophages in cerulein-induced pancreatitis rats . Pancreas , 1999 . 18 ( 4 ): 355 - 363 . 10231840 DOI: 10.1097/00006676-199905000-00005 http://doi.org/10.1097/00006676-199905000-00005 . Platelet-activating factor antagonist (TCV-309) attenuates the priming effects of bronchoalveolar macrophages in cerulein-induced pancreatitis rats BR Yu , YH Tan . The cytoprotection and calcium rivalry of Anisodamine . Chin Pharmacol Bull , 1992 . 8 257 - 261 . (in Chinese) . The cytoprotection and calcium rivalry of Anisodamine DS Yu , JP Fen , HF Li . Scutellarin treat 30 case of patients with acute pancreatitis . World Chin J Digestol , 2000 . 8 ( 8 ): 112 (in Chinese) . Scutellarin treat 30 case of patients with acute pancreatitis N Zeybek , S Gorgulu , G Yagci , M Serdar . The effects of Gingko biloba extract (EGb 761) on experimental acute pancreatitis . J Surg Res , 2003 . 115 ( 2 ): 286 - 293 . 14697296 DOI: 10.1016/S0022-4804(03)00190-2 http://doi.org/10.1016/S0022-4804(03)00190-2 . The effects of Gingko biloba extract (EGb 761) on experimental acute pancreatitis M Zhang . The vulnerating effect of PAF in rabbits with inhalation injury by smog and prevention and therapeutic effect of tetrandrine . Chin J Exp Surg , 1993 . 10 ( 4 ): 156 (in Chinese) . The vulnerating effect of PAF in rabbits with inhalation injury by smog and prevention and therapeutic effect of tetrandrine JP Zhang , JL Xu , LF Xu , P Zhang . Effects of EGb on intestinal mucosal barrier function in acute severe pancreatitis of rats . Jiangsu Med , 2004 . 30 18 - 20 . (in Chinese) . Effects of EGb on intestinal mucosal barrier function in acute severe pancreatitis of rats SJ Zhang , WL Zhai , YF Zhao , CJ Zhu , YZ Deng . Triptolide treatment of severe acute pancreatitis in rats . World Chin J Digestol , 2005 . 13 ( 8 ): 997 - 1001 . (in Chinese) . Triptolide treatment of severe acute pancreatitis in rats 10.1631/jzus.2007.B0147 Project supported by the Adminisitration of Traditional Chinese Medicine of Zhejiang Province (Nos. 2003C130 and 2004C142), the Medical Science and Technology of Health Department of Zhejiang Province (No. 2003B134), the Technology and Development of Technological Bureau of Hangzhou (No. 2003123B19), China 2006-06-13 2006-11-28 2022-01-05 Copyright © 2007, Journal of Zhejiang University Science 2007 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 02 08