Current Medicinal Chemistry (v.18, #23)
Editorial [Hot topic: Myocardial Damage: Not the Only Cause of Cardiac Troponin Release? (Guest Editor: Rob Shave)] by Rob Shave (3441-3441).
Following their introduction in the late 1980's cardiac troponins (cTn) have become a cornerstone within the diagnosis and managementof acute coronary syndrome (ACS) . Since the initial introduction of cTn assays many manufacturers have improved the sensitivity oftheir assays, which in turn has lead to a reduction in the recognized clinical cut-offs for ACS. The ongoing development of high sensitiveassays in an attempt to further improve the analytical performance provides significant challenge within the clinical/laboratory setting. Thefirst paper in this special edition by Gaze  provides insight into some of the issues associated with the assessment and interpretation of cTndata in relation to both currently available assays, and also future potential developments.Although cTn release has become synonymous with cardiac damage it is important to note that not all release of cTn is related to acutemyocardial infarction (AMI). Indeed, a number of other secondary-ischemic and non-ischemic conditions have been identified that also resultin cTn release, all of which are associated with poor patient prognosis . Exercise, and specifically prolonged exercise is presently the onlyknown stimulus for cTn release that does not appear to be related to poor outcome. In order to demonstrate and to characterize the variousexercise stimuli that result in cTn release Williams et al.  and Nie et al.  present original data from two very different exercise studies.These studies show that exercise cTn release is not only restricted to highly trained endurance athletes following ultra-endurance exercise, butcan also occur in adolescents completing moderate duration exercise. These data build on previous work demonstrating cTn release followingas little as 30 minutes of exercise .The fact that relatively short duration activity elicits a post-exercise release of cTn, coupled with the manufacturers drive to increase assaysensitivity means that there is increasing potential for a significant elevation in the false-positive diagnosis of ACS. The risk of falsepositivesis increased further as it is well known that exercise is a potent trigger for ACS , accordingly a real threat exists for clinical confusionif hospital admission is preceded by strenuous exercise . Using a case-study approach in the last paper of this special edition, Eijsvogelset al.  highlight a number of real-life situations that may result in clinical dilemma and offer practical advice on how patients presentingwith elevations in cTn following a bout of exercise may be clinically managed.
The Perils, Pitfalls and Opportunities of Using High Sensitivity Cardiac Troponin by D.C. Gaze (3442-3445).
Cardiac troponins (cTn) are considered to be the ‘gold standard’ biomarker for the diagnosis of acute coronary syndrome(ACS); a pathological spectrum which includes cardiac ischemia, angina, myocardial infarction and ultimately cardiac failure. The growingevidence base for the diagnostic and prognostic use of cTn in ACS has resulted in a universal redefinition of acute myocardial infarction(AMI). Recently a number of immunoassays with claims of superior sensitivity have been produced. The analytical and clinical performanceof these assays require appropriate evaluation. Sensitive assays can be used for diagnosis in the first few hours after anischemic episode. Early elevations in cTn are prognostic. A single time point for cTn testing may be useful for rule out, however such astrategy does not detect the rising and falling pattern required for diagnosis as suggested in the universal definition of AMI. The newerassays demonstrate low level cTn positivity in apparently healthy people. In addition, the sensitive assays detect more cTn positive patientswho do not have a final diagnosis of ACS. It is unknown if such mild elevations in cTn detected by sensitive assays are of clinicalconcern. What is certain is that AMI remains a clinical not a biochemical diagnosis and interpretation of cTn concentrations should bemade according to the clinical context. This review highlights the development of the sensitive assays, documents their analytical andclinical performance and reviews the usefulness of cTn elevation in non-ACS conditions.
A Unique Case Series of Novel Biomarkers of Cardiac Damage in Cyclists Completing the 4800 km Race Across America (RAAM) by K. Williams, K. George, A. Hulton, R. Godfrey, I. Lahart, M.G. Wilson, S. Charlesworth, D. Warburton, D. Gaze, G. Whyte (3446-3451).
Prolonged strenuous exercise is associated with the appearance of biomarkers of cardiac cell damage and a decline in cardiacfunction during recovery. Few studies have assessed repeated bouts of prolonged exercise and whether this results in further biomarkeraccumulation and greater dysfunction. Further, it may be useful to describe the changes in a range of biomarkers that may provide additionalinsight into the clinical significance of cardiac biomarker release. Four highly trained cyclists completed the 4800 km Race AcrossAmerica (RAAM) in 7 days. Venous blood samples and echocardiograms were taken prior to, every 24 hours during and immediately afterthe RAAM. Venous blood was analysed for cardiac troponin I (cTnI), creatine kinase MB (CK-MB), fatty acid binding protein (HFABP),glycogen phosphorylase BB (GPBB) and N-Terminal Brain Natriuretic Peptide (NTproBNP). Echocardiograms allowed analysisof septal, left ventricular free wall and right ventricular free wall tissue velocities during systole and diastole. Before the RAAM cTnIlevels were below the assay detection level (0.02 ng.ml-1). In three riders cTnI peaked on day one (0.03 ng.ml-1) and returned below detectionlevels post race. In the 4th rider cTnI peaked on day 5 (0.08 ng.ml-1) and was still elevated post-race. Both CK-MB and H-FABPwere increased during the RAAM in all 4 cyclists. In three riders H-FABP peaked on day one (3.49 to 5.09 ng.ml-1) and declined over therest of the RAAM. In the final rider H-FABP peaked on day two (5.90 ng.ml-1) and then dropped back to baseline by the post-RAAM assessment.Interestingly, changes in H-FABP mirrored, temporally, changes in CK-MB in places and this may reflect an association withskeletal muscle damage. Data for GPBB value to (2.9 - 149.6 ng.ml-1) and NTproBNP value to (27.3 - 310.0 ng.L-1) were variable butagain was elevated in all riders during the course of the RAAM. Changes in ventricular wall tissue velocities were minor and not cumulative.Peak atrial diastolic tissue velocity in the left ventricular free wall increased (P ‹ 0.05) from 11 to 18 cm.s-1 over the last two racedays but this did not significantly impact the ratio of early to late diastolic wall motion. Cardiac biomarkers were elevated during thecompletion of the RAAM in all 4 cyclist but changes were not cumulative which suggest that the hearts of the cyclists coped well withthe extreme cardiac work demanded by this ultra-endurance exercise challenge.
The Influence of a Half-Marathon Race Upon Cardiac Troponin T Release in Adolescent Runners by J. Nie, K.P. George, T.K. Tong, D. Gaze, Y. Tian, H. Lin, Q. Shi (3452-3456).
Objectives: Post-exercise cardiac troponin T (cTnT) release has been widely reported in adult athletes but limited data is availablefor adolescents. The aim of this study was to determine the incidence and magnitude of cTnT appearance in a large group of adolescentrunners, and to determine any association between cTnT release and personal characteristics of adolescents.Methods: We recruited 63 adolescent runners (mean±SD: age 16.4±1.5 years; 10 females) who all completed a simulated half-marathonrace (an all-out 21-km run) during routine training. Personal data collected included age, training history, 21-km run performance as wellas pre-post exercise serum cTnT levels. Serum cTnT was assayed using a 3rd generation assay.Results: At pre-exercise, cTnT concentrations were below the 0.01 μg/L cTnT detection limit of assay in 58/63 runners. The post-exercisecTnT level (range: <0.01-1.36 μg/L) was significantly (p<0.001) greater than that of the pre-exercise (range: <0.01-0.02 μg/L). After theexercise, 57 (90%) and 44 (70%) subjects had cTnT concentrations above the detection: 0.01, and clinical thresholds: 0.05 μg/L, respectively.Post-exercise cTnT was inversely correlated with training years (r=-0.25, p<0.05) and age (r=-0.31, p<0.05). Compared with runnerswho had trained for ..3 years, runners with less training experience demonstrated increased post-race cTnT levels (p<0.01).Conclusion: cTnT increases are virtually universal among adolescent runners following a 21-km run during routine training and can reachlevels typically diagnostic for acute myocardial infarction potentially initiating diagnostic dilemmas. Adolescents with less training experiencehad higher post-exercise cTnT.
Exercise-Induced Cardiac Troponin Release: Real-Life Clinical Confusion by T.M.H. Eijsvogels, R. Shave, A. van Dijk, M.T.E. Hopman, D.H.J. Thijssen (3457-3461).
Exercise training represents a successful and powerful strategy to prevent future cardiovascular disease. Paradoxically, performanceof exercise is also associated with an increased risk of acute cardiac events. Accordingly, patients may present to hospital withcardiac symptoms following a bout of unaccustomed physical effort (e.g. exercise). Current guidelines for the identification of an acutemyocardial infarction (AMI) importantly depend on the presence of cardiac troponin as a highly sensitive marker of cardiac damage.However, a number of studies have reported elevated cardiac troponin levels in asymptomatic, healthy subjects after endurance exercise(such as a marathon, prolonged cycling or prolonged walking). These observations indicate that elevated cardiac troponin levels can bethe result of cardiac ischemia, and subsequent necrosis, but also may be related to strenuous exercise. In this paper, we present three differentclinical cases of post-exercise elevations in cardiac troponins, each with a distinct clinical presentation. These case studies emphasizethat a detailed assessment of all symptoms and a thorough patient-history are prerequisite for accurate interpretation of a positivecardiac troponin test following exercise.
Malignant Hypercalcemia by U. Bass, M. Maruzzo, A. Roma, V. Camozzi, G. Luisetto, F. Lumachi (3462-3467).
Malignancy-associated hypercalcemia (MAH) is one of the clinical emergencies in medical oncology, arising early or, moreoften, during the late phases of disease. Prevalence cannot be estimated accurately because previous figures of 5-30% of all cancer patientshave progressively reduced thanks to the widespread use of bisphosphonates for the prevention of skeletal events. The classic distinctionof humoral vs. osteolytic hypercalcemia is still relevant from an etiological point of view, but should not be considered as a rigidalternative since both mechanisms may be active in the same patients and the activation of the RANKL pathway is a common pathogeneticmechanism. Parathyroid hormone-related protein mimics the effects of PTH on the bone and kidney (tubular calcium resorption)and may represent an attractive druggable target, but additional agents (cytokines or other mediators) as well as ectopic production of1,25(OH)2D3 may give an important contribution to humoral hypercalcemia. Conversely, bone invasion by cancer cells determines massivebone reabsorption due to the release of proteolytic enzymes and pro-osteolytic agents with paracrine activity on adjacent bone andstromal cells. When cancer patients develop headache, confusion, de-hydration and tremors hypercalcemia should be suspected althoughslow rise of calcium levels may produce more indolent symptoms. Bisphosphonates (with or without hydration and diuretics) may efficientlycontrol MAH but only if an active treatment for the underlying cancer is promptly started. The anti-RANKL monoclonal antibodydenosumab represents a novel agent able to revert the vicious cycle of bone metastases and data from phase III studies are currentlyshowing promising activity in reverting bone resorption with manageable toxicity.
Treating Benign Prostatic Hyperplasia with Botulinum Neurotoxin by G. Brisinda, S. Vanella, G. Marniga, A. Crocco, G. Maria (3468-3475).
Botulinum toxin (BoNT) has been increasingly used in the interventional treatment of several disorders; the use of this agenthas extended to a plethora of conditions including focal dystonia, spasticity, inappropriate contraction in most gastrointestinal sphincters,eye movement disorders, hyperhidrosis, genitourinary disorders and aesthetically undesirable hyperfunctional facial lines. In addition,BoNT is being investigated for the control of pain, and for the management of tension or migraine headaches and myofascial pain syndrome.Benign prostatic hyperplasia (BPH) is a common condition in ageing men; the goal of therapy is to reduce the lower urinary tractsymptoms (LUTS) associated with BPH and to improve the quality of life. However, medical treatment, including drugs that relax smoothmuscle within the prostate and drugs that shrink the gland are not totally effective or without complications. The standard surgicaltreatment for BPH is progressively changing to minimally invasive therapies, but none of them has provided clear results. The use ofBoNT-A to inhibit the autonomic efferent effects on prostate growth and contraction, and inhibit the abnormal afferent effects on prostatesensation, might be an alternative treatment for BPH. BoNT injections have several advantages over drugs and surgical therapies in themanagement of intractable or chronic disease; systemic pharmacologic effects are rare, permanent destruction of tissue does not occur,and graded degrees of relaxation may be achieved by varying the dose injected. In this paper, clinical experience over the last years withBoNT in BPH impaired patients will be illustrated.
Imaging Studies in Hypercalcemia by D. Cecchin, R. Motta, P. Zucchetta, F. Bui, S.M.M. Basso, F. Lumachi (3485-3493).
Hypercalcemia is a relatively common clinical problem, mainly (>90%) related to primary hyperparathyroidism (HPT) andmalignancies. The anatomical and functional imaging techniques available for locating enlarged parathyroid glands include ultrasound(US), computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine imaging techniques. The most commonlyemployed are US and parathyroid scintigraphy, while CT, MRI, positron emission tomography (PET)/CT, and selective venous samplingare generally used in patients with persistent or recurrent HPT, or when findings of non-invasive studies are negative or conflicting. Thereported accuracy is 57-93%, 54-93%, and up to 95% for US, 99mTc-sestamibi scintigraphy, and the two modalities combined, respectively.A multimodality approach (x-ray, whole-body scintigraphy, CT, MRI, and PET) is usually recommended for whole body assessmentin cases of cancer-induced hypercalcemia (CIH). Imaging studies should evaluate each organ (i.e. breast, kidney, prostate, parathyroid)potentially involved in the pathogenesis of hypercalcemia in patients with CIH. In cases of skeletal metastases, when findings onplain x-ray or bone scans are uncertain, any unexplained region of abnormal uptake should be examined by MRI and/or 18F-fluoro-2-deoxyglucose (FDG)-PET/CT, which has proved more accurate than classical bone scintigraphy, especially for dealing with hematologicmalignancies. A number of radionuclide tracers, other than 18F-FDG, are available for use in selected cases to locate specific tumors (i.e.68Ga for neuroendocrine tumors). This is a review of recently published information on the imaging techniques currently available for patientswith hypercalcemia.
COXIBs, CINODs and H2S-Releasing NSAIDs: Current Perspectives in the Development of Safer Non Steroidal Anti-Inflammatory Drugs by S. Fiorucci, E. Distrutti (3494-3505).
Traditional nonsteroidal anti-inflammatory drugs, tNSAIDs, are effective medication for prevention of ischemic events andtreatment of pain, fever and inflammation. However their use associates with a significant risk to develop gastrointestinal and cardiovascularcomplications. Low doses of acetyl salicylic acid (ASA) and effective doses of tNSAIDs associate with a 2-6 fold increase in therisk of gastrointestinal bleeding. ASA and tNSAIDs inhibit cyclooxygenases (COXs). The COX exists at least in two isoforms, COX-1and COX-2. Selective inhibitors of COX-2, the coxibs, spares the gastrointestinal tract while exert anti-inflammatory and analgesic effects.However, coxibs increase the risk of thrombo-embolic events. Nitric oxide (NO) and hydrogen sulfide (H2S), are potent vasodilatoryagents that maintain mucosal integrity in the gastrointestinal tract. Hybrid molecules generated by coupling a NO or H2S releasingmoiety to ASA or tNSAIDs has resulted into new classes of NSAIDs. These agents, the NO-releasing NSAIDs, or CINOD, and the H2SreleasingNSAIDs are currently investigated as a potential alternative to tNSAIDs and coxibs. Naproxcinod has been the first, and so farthe only, CINOD investigated in clinical trials. These studies have shown a slightly improvement in gastrointestinal tolerability in comparisonto naproxen in surrogate endpoints (number of gastric and duodenal ulcers) and a significant reduction in the risk of destabilizationof blood pressure control in patients with osteoarthosis taking anti-hypertensive medications in comparison to either naproxen androfecoxib. The lack of outcome studies, however, has precluded the approval of naproxcinod by the Food and Drug Administration leadingto a voluntary withdrawn of an application to the EMEA in May 2011. NSAIDs that releases H2S as a mechanism supporting an intrinsicgastrointestinal and cardiovascular safety are being investigated in preclinical models. Either naproxen and diclofenac hybridshave been reported to cause less gastrointestinal injury than parent NSAIDs. These novel chemical entities exert a variety of beneficialeffects in rodent models of cardiovascular and metabolic disorders through a mechanism that might involve the release of H2S and/or byexerting anti-oxidant effects. The beneficial role these mechanisms in clinical settings await a proof-of-concept study.
Local Renin-Angiotensin II Systems, Angiotensin-Converting Enzyme and its Homologue ACE2: Their Potential Role in the Pathogenesis of Chronic Obstructive Pulmonary Diseases, Pulmonary Hypertension and Acute Respiratory Distress Syndrome by A. Kaparianos, E. Argyropoulou (3506-3515).
Renin-angiotensin II-aldosterone axis has long been known as a regulator of blood pressure and fluid homeostasis. Yet, localrenin-angiotensin II systems have been discovered and novel actions of angiotensin II (AngII) have emerged among which its ability toact as a immunomodulator and profibrotic molecule. The enzyme responsible for its synthesis, Angiotensin-converting-enzyme (ACE), ispresent in high concentrations in lung tissue. In the present paper, we review data from studies of the past decade that implicate AngIIand functional polymorphisms of the ACE gene that increase ACE activity with increased susceptibility for asthma and chronic obstructivepulmonary disease (COPD) and for pulmonary hypertension. Moreover, drugs that inhibit the synthesis of AngII (ACE inhibitors) orthat antagonize its actions on its receptors (Angiotensin II receptor blockers -ARBs) have been shown to provide beneficial effects. Anotherrecent discovery reviewed is the presence of a homologue of ACE, ACE2, which cleaves a single amino acid from AngII and formsa heptapeptide with vasodilatory actions, Ang 1-7. The balance between ACE and ACE2 is crucial for controlling AngII levels. ACE andACE2 also appear to modify the severity of Acute Respiratory Distress Syndrome (ARDS), with ACE2 playing a protective role. Finally,mention is made to the recent discovery of ACE2 as a receptor for the SARS Corona Virus.
Quantum Dot-Based Nanocomposites for Biomedical Applications by Z.S. Lu, C.M. Li (3516-3528).
Quantum dot (QD) has been extensively investigated as a nanoprobe to replace conventional organic dyes due to its unique opticalproperties. However, nanotoxicity of QD greatly hampers its biomedical applications, particularly in in vivo imaging. It is critical tofunctionalize QD and/or composite QD with other functional materials for biocompatibility, multifunction and expanded applications. Inthis review, advances of QD-based nanocomposites are addressed with emphasis of their synthesis, fundamental understanding and applicationsin biosensor, multimodal imaging, drug delivery, diagnostics and cancer therapy. Some specific QD-based bionanosystems andfuture development directions are also discussed.
Calcium Metabolism & Hypercalcemia in Adults by F. Lumachi, R. Motta, D. Cecchin, S. Ave, V. Camozzi, S.M.M. Basso, G. Luisetto (3529-3536).
Calcium is essential for many metabolic process, including nerve function, muscle contraction, and blood clotting. The metabolicpathways that contribute to maintain serum calcium levels are bone remodeling processes, intestinal absorption and secretion, andrenal handling, but hypercalcemia occurs when at least 2 of these 3 metabolic pathways are altered. Calcium metabolism mainly dependson the activity of parathyroid hormone (PTH). Its secretion is strictly controlled by the ionized serum calcium levels through a negativefeed-back, which is achieved by the activation of calcium-sensing receptors (CaSRs) mainly expressed on the surface of the parathyroidcells. The PTH receptor in bone and kidney is now referred as PTHR1. The balance of PTH, calcitonin, and vitamin D has long been consideredthe main regulator of calcium metabolism, but the function of other actors, such as fibroblast growth factor-23 (FGF-23), Klotho,and TPRV5 should be considered. Primary hyperparathyroidism and malignancy are the most common causes of hypercalcemia, accountingfor more than 90% of cases. Uncontrolled hypercalcemia may cause renal impairment, both temporary (alteration of renal tubularfunction) and progressive (relapsing nephrolithiasis), leading to a progressive loss of renal function, as well as severe bone diseases, andheart damages. Advances in the understanding of all actors of calcium homeostasis will be crucial, having several practical consequencesin the treatment and prevention of hypercalcemia. This would allow to move from a support therapy, sometimes ineffective, to a specificand addressed therapy, especially in patients with chronic hypercalcemic conditions unsuitable for surgery.
High-Affinity Ligands of Siglec Receptors and their Therapeutic Potentials by S. Magesh, H. Ando, T. Tsubata, H. Ishida, M. Kiso (3537-3550).
Sialic acids are one of the important constituents of glycoconjugates in the deuterostome lineage of animals and microorganisms.Siglecs (Sialic acid-binding immunoglobulin like lectins) are a family of cell-surface receptor proteins that recognize sialylatedglycoconjugates as ligands. To date, 15 Siglecs have been described in humans and are mainly known as regulators of the immunesystem. Several of the Siglecs are emerging as potential targets for the treatment of some inflammatory, autoimmune, allergic, neurodegenerativeand infectious diseases. In addition to antibody mediated therapy, high-affinity ligand-based probes of Siglec receptors wouldrepresent invaluable tools to effectively address therapeutic opportunities of Sialic acid-mediated Siglec recognition. This review discussessome aspects of structure and function of Siglec receptors, and concisely summarizes up-to-date progress on the identification ofsialic acid based high-affinity ligands of certain well explored Siglec receptors.
From the Sea to Anticancer Therapy by P. Russo, C. Nastrucci, A. Cesario (3551-3562).
Discovery, isolation, characterisation and pre-clinical and clinical trials of plant- or animal-derived drugs displaying pharmacological activities continue to develop and enlarge. Cancer chemotherapy is one of the most promising areas for these drugs. Since a very long time, nature has been an attractive source of potential medicinal agents for human use. The deep sea is becoming a novel and potently appealing source for new drugs, as well as shallow waters. This interest is mainly related to the terrific chemical diversity found in the vast number of plants and animal species, as well as in the microbial world. During the evolution, a rich source of biologically active compounds is developed in the depths of the sea, often reflecting ecological adaptation. Most of them (toxins) are developed to allow survival and flourishing acting against predators and parasites. Recent progress in Scuba diving, hitech/biotechnological and procedural advances in structure clarification, organic synthesis and biological assay determined the characterisation and preclinical/clinical evaluation of novel anticancer drugs. The aim of this review is to provide a description of their discovery, mode of action and clinical application.
Multifaceted Role of Neuropilins in Cancer by S. Rizzolio, L. Tamagnone (3563-3575).
Neuropilins comprise two homologous widely-expressed single-pass plasma membrane receptors (Nrp1 and Nrp2), originally identified for binding secreted Semaphorins and Vascular Endothelial Growth Factors (in association with Plexins and VEGF-Receptors). Semaphorins have been implicated with opposite functions in cancer: either as putative tumor suppressors and anti-angiogenic factors, or mediating tumour angiogenesis, invasion and metastasis. Moreover, due to their implication in VEGF signaling, neuropilins regulate vascular development and tumor angiogenesis.Recent evidence further suggests a role of neuropilins in cancer progression due to their interaction with receptor tyrosine kinases, adhesion molecules, and integrins. Furthermore, neuropilins have been implicated in response to additional growth factors, such as Hepatocyte Growth Factor, Fibroblast Growth Factor, Transforming Growth Factor beta, Galectin, etc. Altogether, these data seem to qualify neuropilins as signaling platforms on the cell surface, potentially capable of regulating cancer cells, as well as cells of the tumor microenvironment.Intriguingly, clinical-pathological data often indicate a correlation between increased expression of neuropilins and advanced stage tumors with poor prognosis. In this article, we will review the current experimental evidence about the functional role of neuropilins in cancer and the underlying molecular mechanisms.
A Review on Steroidal 5α-Reductase Inhibitors for Treatment of Benign Prostatic Hyperplasia by J. Sun, H. Xiang, L.-L. Yang, J.-B. Chen (3576-3589).
Benign prostatic hyperplasia (BPH) is a kind of common noncancerous prostate gland enlargement with growing tendency inrecent years. 5α-reductase is the key enzyme responsible for dihydrotestosterone biosynthesis and has been considered as an importanttarget for designing inhibitors as potent therapeutic agents for BPH. Finasteride, the first steroidal 5α-reductase inhibitor, has been marketedworldwide as a drug for BPH. During these years, many other novel types of 5α-reductase inhibitors are being studied. This reviewsummarizes recent advancement in steroidal 5α-reductase inhibitors.
How Would Composite Traditional Chinese Medicine Protect the Brain - An Example of the Composite Formula Pien Tze Huang by L. Zhang, W.P. Lam, L. Lu, Y.-X.J. Wang, Y.W. Wong, L.H. Lam, H.C. Tang, M.S. Wai, Y.T. Mak, M. Wang, D.T. Yew (3590-3594).
Chinese medicine has a long history of several thousand years. The main form of Traditional Chinese Medicine (TCM) iscomposite, i.e. a mixture of up to 10 medicinal products. Thus a composite prescription of 4-5 kinds of Chinese medicinal products maycontain several hundred kinds of chemical composition. The active ingredients and clinical efficacy of which are difficult to characterize.We aim to review the Chinese literature of TCMs with neuroprotective effects. We illustrate with our study on Pien Tze Huang (PZH) theuse of in vivo tests in the study of composite TCM. Our results show evidence that PZH might have neuropreventive effects in rats.