Medicine Formula Research Articles

Preliminary study on pharmacodynamic evaluation method of Houpo formula particles

To discuss the feasibility of the pharmacodynamic evaluation method for traditional Chinese medicine (TCM) formula particles, with traditional decoction for reference and the intervention of Magnoliae Officinalis Cortex in rats with ulcerative colitis (UC). First of all, the similarity of traditional Magnoliae Officinalis Cortex decoction and formula particles of different manufacturers was defined by using the IR fingerprint. The UC rat model was established and given Houpo formula particles of different doses and manufacturers, with the decoction for reference, in order to observe disease activity index (DAI), colon mucosa damage index (CMDI), pathologic changes, nitric oxide (NO), endothdin (ET), substance P, vasoactive intestinal peptide (VIP). Their intervention effects on UC rats were compared to study the difference between Sanjiu and Tianjiang Houpo formula particles, in order to demonstrate the feasibility of the pharmacodynamic evaluation method for Houpo formula particles. According to the results, Houpo formula particles showed similar pharmacodynamic actions with the traditional decoction. The pharmacodynamic comparison of Houpo formula particles of different manufacturers showed no statistical significance. The experiment showed that on the basis of the TCM compounds, a prescription dismantlement study was conducted to define target points of various drugs. The traditional decoction was selected for reference in the comparison of corresponding formula particles for their pharmacodynamic equivalence. This method could avoid controversies about single or combined boiling of formula particles, and give objective comments on the pharmacodynamic effect of the formula particles. The method is proved to be feasible.

An MDL approach to efficiently discover communities in bipartite network

An minimum description length (MDL) criterion is proposed to choose a good partition for a bipartite network. A heuristic algorithm based on combination theory is presented to approach the optimal partition. As the heuristic algorithm automatically searches for the number of partitions, no user intervention is required. Finally, experiments are conducted on various datasets, and the results show that our method generates higher quality results than the state-of-art methods, cross-association and bipartite, recursively induced modules. Experiment results also show the good scalability of the proposed algorithm. The method is applied to traditional Chinese medicine (TCM) formula and Chinese herbal network whose community structure is not well known, and found that it detects significant and it is informative community division.

Intervention effects of QRZSLXF, a Chinese medicinal herb recipe, on the DOR-β-arrestin1-Bcl2 signal transduction pathway in a rat model of ulcerative colitis

Ethnopharmacological relevanceQingre Zaoshi Liangxue Fang (QRZSLXF) is a Chinese medicinal herb recipe that is commonly prescribed for the treatment of ulcerative colitis. It includes 5 quality assured herbs: Sophora flavescens Aiton., Baphicacanthus cusia (Nees) Bremek., Bletilla striata Rchb.f., Glycyrrhiza uralensis Fisch. and Coptis chinensis Franch. The main phytochemical ingredient of QRZSLXF includes ammothamnine, sophocarpidine, liquiritin, berberine and indirubin. QRZSLXF has been clinically proven for use in the treatment of ulcerative colitis for over twenty years. In the past ten years, research has confirmed the therapeutic effect of QRZSLXF in ulcerative colitis and partially revealed its mechanism of action. Here, we further reveal the therapeutic mechanism of QRZSLXF in ulcerative colitis. To investigate the role of the DOR-β-arrestin1-Bcl-2 signal transduction pathway in ulcerative colitis and to determine the effects of QRZSLXF on this signal transduction pathway. Materials and methodsEighty-four Sprague-Dawley rats were randomly divided into six groups: normal control group, model group, mesalazine group, and QRZSLXF high-dose, medium-dose group and low-dose groups (n=14). Experimental colitis was induced by trinitrobenzenesulfonic acid (TNBS) in each group, except the normal control group. After modeling, bloody stool, mental state and diarrhea were observed and recorded. Two rats were randomly selected from the model groups adfnd sacrificed on day 3 to observe pathological changes in the colon tissue by microscopy. The rats in the QRZSLXF-treated groups received intramuscular injections of different concentrations of QRZSLXF for 15 days. The rats in the mesalazine group were treated with mesalazine solution (0.5g/kg/day) by gastric lavage for 15 days. The rats in the normal control group and the model group were treated with 3mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24h, the remaining rats were sacrificed and their colon tissues were used to detect the mRNA and protein expressions of DOR, β-arrestin1 and Bcl-2 by Real-time PCR and immunohistochemistry, respectively. Histological changes in the colon tissues were also examined. Results and conclusionsThe expressions of DOR, β-arrestin1 and Bcl-2 were significantly different among the four groups. The expressions of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group compared with the other groups (P<0.05). In contrast to the model group, the expressions of DOR, β-arrestin1 and Bcl-2 were significantly decreased in the mesalazine group and the groups that received different doses of QRZSLXF (P<0.05), and there were no statistically significant differences among the mesalazine and QRZSLXF-treated groups (P>0.05). This study indicates that the DOR-beta-arrestin1-Bcl-2 signal transduction pathway may participate in the pathologic course of ulcerative colitis. Moreover, QRZSLXF could attenuate ulcerative colitis by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway.

ZiBuPiYin Recipe Protects db/db Mice from Diabetes-Associated Cognitive Decline through Improving Multiple Pathological Changes

Multiple organ systems, including the brain, which undergoes changes that may increase the risk of cognitive decline, are adversely affected by diabetes mellitus (DM). Here, we demonstrate that type 2 diabetes mellitus (T2DM) db/db mice exhibited hippocampus-dependent memory impairment, which might associate with a reduction in dendritic spine density in the pyramidal neurons of brain, Aβ1-42 deposition in the prefrontal cortex (PFC) and hippocampus, and a decreased expression of neurostructural proteins including microtubule-associated protein (MAP2), a marker of dendrites, and postsynaptic density 95 (PSD95), a marker of excitatory synapses. To investigate the effects of the ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine recipe, on diabetes-related cognitive decline (DACD), db/db mice received daily administration of ZBPYR over an experimental period of 6 weeks. We then confirmed that ZBPYR rescued learning and memory performance impairments, reversed dendritic spine loss, reduced Aβ1-42 deposition and restored the expression levels of MAP2 and PSD95. The present study also revealed that ZBPYR strengthened brain leptin and insulin signaling and inhibited GSK3β overactivity, which may be the potential mechanism or underlying targets of ZBPYR. These findings conclude that ZBPYR prevents DACD, most likely by improving dendritic spine density and attenuating brain leptin and insulin signaling pathway injury. Our findings provide further evidence for the effects of ZBPYR on DACD.

Bioactives and traditional herbal medicine for the treatment of cardiovascular/cerebrovascular diseases.

Cardiovascular diseases (CVDs) are still the principal cause of death worldwide. Weakened endothelial function followed by inflammation of the vessel wall hints at atherosclerotic lesion formation that causes myocardial infarction and stroke. Heart failure can arise as consequence of large myocardial infarctions. In its more severe stages, heart failure patients have a life anticipation that is parallel to destructive cancers. Accordingly, the increase in risk factor load by metabolic diseases and age augments the incidence for vascular and cardiac diseases and provides a challenge for developing efficient treatments. There is widespread proof to show that drug treatment of conventional risk factors is effective in reducing cardiovascular events. More effective treatment of CVD with various classes of antihypertensive drugs has been associated with greater benefits, but some recent studies suggest we may be reaching the optimal level of treated blood pressure in some patient groups. Apart from the treatment of cardiovascular risk factors with pharmacological agents and the use of antithrombotic drugs, there is growing awareness of the role of dietary factors and herbal medicines in the prevention of CVD and the possibility of their use in treatment. Investigators from different places of the world like China, Taiwan, Bangladesh, Pakistan, and so forth contributed to this special issue by presenting tremendous papers. These papers deliver an analysis in this field and create innovative contributions concerning the mechanism of action of bioactives and traditional herbal medicine for the treatment of cardiovascular/cerebrovascular diseases. Some interesting papers in this special issue address the cardioprotective effects of Chinese herbal medicine and natural compounds. For instance, a paper summarized the synergetic cardioprotective potential of herbal combination of four plants, namely, Terminalia arjuna, Cactus grandiflorous, Crataegus oxyacantha, and Piper nigrum through curative and preventive mode of treatment analysis and this paper reported preadministration and postadministration of herbal mixture restore the levels of biomarker of cardiotoxicity, which includes cardiac marker enzymes, lipids profile, and antioxidant enzymes. Similarly, another paper in this issue reports the cardioprotective effects of Sundarban honey on cardiac troponin I, cardiac marker enzymes, the lipid profile, lipid peroxidation products, and histoarchitecture of the myocardium against isoproterenol-induced myocardial infarction in Wistar rats. Pinggan Qianyang recipe (PQR), a Chinese medicine recipe, has long been used for calming the liver. It has also been used to treat essential hypertension with satisfactory results. Consistent with this concern, this special issue published a paper that reports PQR exerts its antihypertensive effect through deterioration of the vascular remodeling process. The mechanism might be associated with regulating differentially expressed miRNAs in aorta tissue. Despite the fact that there are major developments in treating ischemic stroke over the last decade, stroke is still a serious concern for which effective drug therapy is not yet available. In the search for neuroprotective agents from natural sources, a number of plant extracts and several natural products were isolated and reported to provide neuroprotection against ischemic stroke. A few papers in this special issue report the neuroprotective effects of Chinese herbal medicine and natural compounds. For instance, Antrodia camphorata (A. camphorata), a fungus generally used in Chinese folk medicine for the treatment of viral hepatitis and cancer, has shown neuroprotective effects in embolic rats. This effect may correlate with the downregulation of the iNOS, HO-1, Bax, and activated caspase-3 and the inhibition of OH° signals. Another study shows alpha-lipoic acid attenuates middle cerebral artery occlusion-induced cerebral ischemia and reperfusion injury via insulin receptor-dependent and PI3K/Akt-dependent inhibition of NADPH oxidase. Moreover, an interesting study in this special issue established the effects of tetramethylpyrazine (TMP) on functional recovery and neuronal dendritic plasticity after experimental stroke. In this study, the authors have shown that enhanced dendritic plasticity contributes to TMP-elicited functional recovery after ischemic stroke. Hinokitiol is a naturally occurring compound isolated from the wood of Chamaecyparis taiwanensis. It is involved in multiple biological activities, including antimicrobial and antitumorigenic activities. Although hinokitiol has been reported to inhibit inflammation, its immunological regulation in lymphocytes remains inadequate. With this context, a well-designed study reported that hinokitiol downregulated cyclin D3, E2F1, and Cdk4 expression and upregulated p21 expression in concanavalin A- (ConA-) stimulated T lymphocytes. It further demonstrated that hinokitiol upregulates p21 expression and attenuates IFN-γ secretion in T lymphocytes from the spleens of mice, thereby arresting the cell cycle in the G0/G1 phase. These authors concluded that hinokitiol provides benefits in treating patients with autoimmune diseases. We expect that this special issue grants inventive awareness to increase the therapeutic value of herbal and/or Chinese medicines for treatment or prevention of cardiovascular and ischemia-reperfusion injury-related disorders. Joen-Rong Sheu Pitchairaj Geraldine Mao-Hsiung Yen

LC-MS/MS determination and pharmacokinetics study of puerarin and daidzein in rat plasma after oral administration of Gegenqinlian decoction and Radix Puerariae extract.

Background:Gegenqinlian decoction (GQD) is a famous traditional medicine recipe. It is composed of four herbs including Radix Puerariae (GG), Radix Scutellariae (HQ), Rhizoma Coptidis (HL) and Radix Glycyrrhizae (GC), which is widely used for treating gastro-intestinal disorders in the clinical practice of Traditional Chinese medicine (TCM). The aim of this study was to compare the pharmacokinetics of puerarin and daidzein in rats following oral administration of Gegenqinlian Decoction and Radix Puerariae extract. Thus, a sensitive and selective liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of puerarin and daidzein in rat plasma following oral administration of Gegenqinlian Decoction and Radix Puerariae extract.Materials and Methods:Chromatographic separation was performed on a Shiseido CAPCELL PAK C18 analytical column (100 mm × 2.0 mm i.d., 5 μm) by linear gradient elution, with water (0.1% formic acid)-acetonitrile (0.1% formic acid) as mobile phase. Detection was carried out by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode.Results:The calibration curves were linear over a range of 7.80-1560 ng/mL for puerarin and 6.30-1260 ng/mL for daidzein. The intra- and inter-day precision values were less than 13.6% and their average recoveries was in the range of 77.8% and 88.6% for puerarin and was between 76.3 and 86.8% for daidzein, respectively.Conclusion:The validated method was applied to the comparative pharmacokinetic studies of puerarin and daidzein after oral administration of Gegenqinlian Decoction and Radix Puerariae extract. The pharmacokinetic parameters showed that puerarin and daidzein from Gegenqinlian Decoction were absorbed more effectively with slower elimination in rat plasma than that from Radix Puerariae extract. These results revealed that as far as the Radix Puerariae extract was concerned, it is very valuable to be used as a clinical directions of Gegenqinlian Decoction.

Identification and Comparison of Anti-Inflammatory Ingredients from Different Organs of Lotus Nelumbo by UPLC/Q-TOF and PCA Coupled with a NF-κB Reporter Gene Assay

Lotus nelumbo (LN) (Nelumbo nucifera Gaertn.) is an aquatic crop that is widely distributed throughout Asia and India, and various parts of this plant are edible and medicinal. It is noteworthy that different organs of this plant are used in traditional herbal medicine or folk recipes to cure different diseases and to relieve their corresponding symptoms. The compounds that are contained in each organ, which are named based on their chemical compositions, have led to their respective usages. In this work, a strategy was used to identify the difference ingredients and screen for Nuclear-factor-kappaB (NF-κB) inhibitors with anti-inflammatory ability in LN. Seventeen main difference ingredients were compared and identified from 64 samples of 4 different organs by ultra-performance liquid chromatography that was coupled with quadrupole/time of flight mass spectrometry (UPLC/Q-TOF-MS) with principal component analysis (PCA). A luciferase reporter assay system combined with the UPLC/Q-TOF-MS information was applied to screen biologically active substances. Ten NF-κB inhibitors from Lotus plumule (LP) extracts, most of which were isoquinoline alkaloids or flavone C-glycosides, were screened. Heat map results showed that eight of these compounds were abundant in the LP. In conclusion, the LP extracts were considered to have the best anti-inflammatory ability of the four LN organs, and the chemical material basis (CMB) of this biological activity was successfully validated by multivariate statistical analysis and biological research methods.

Studies on neutralizing effect of Ophiorrhiza mungos root extract against Daboia russelii venom

Ethnopharmacological relevanceThe folklore or traditional therapy in southern India widely utilizes a plethora of local herbs to treat the patients challenged with snake venom. Despite the widespread implementation of antisera therapy, the local population of the country still relies on this century's old medicinal formulas mainly due to the cost effectiveness, lesser side effects and also its cultural acceptability. The present study aims to validate the neutralizing ability of one such traditionally acclaimed antidote Ophiorrhiza mungos root extract against Russell's viper (Daboia russelii) venom in the early developing chick embryos. Materials and methodsThe disc impregnated with venom, root extract or the combination of both was placed on the yolk sac membrane preferably over the anterior blood vessel of 6th day chick embryo. The neutralization/inhibition of venom-induced lethality or hemorrhage was achieved by incubating venom and extract before being applied to the embryo. The membrane stabilizing properties of root extract was estimated by HRBC lysis method. The preliminary phytochemical analysis was done to assess the phyto constituents in the root extract. ResultsThe LD50 of Russell's viper venom in 6th day chick embryo was found to be 3μg/μl. The neutralising effect of root extract was achieved by pre-incubating venom with various concentrations of extract and at the concentration of 10μg/μl, 100% recovery of embryos was observed after 6h of incubation. Higher concentration of root extract showed remarkable results by completely abolishing traces of hemorrhagic lesions induced by viper venom. ConclusionsThe above observations confirmed that the root extract of Ophiorrhiza mungos possess potent anti snake venom neutralizing compounds, which inhibit the activity of viper venom. The chick embryo, a new insensate model used in the present study is significant in venom research as it reduces the ruthless suffering of higher mammalian experimental models.

Expert system for skin problem consultation in Thai traditional medicine.

This paper aimed to demonstrate the research and development of a rule-based expert system for skin problem consulting in the areas of acne, melasma, freckle, wrinkle, and uneven skin tone, with recommended treatments from Thai traditional medicine knowledge. The tool selected for developing the expert system is a software program written in the PHP language. MySQL database is used to work together with PHP for building database of the expert system. The system is web-based and can be reached from anywhere with Internet access. The developed expert system gave recommendations on the skin problem treatment with Thai herbal recipes and Thai herbal cosmetics based on 416 rules derived from primary and secondary sources. The system had been tested by 50 users consisting of dermatologists, Thai traditional medicine doctors, and general users. The developed system was considered good for learning and consultation. The present work showed how such a scattered body of traditional knowledge as Thai traditional medicine and herbal recipes could be collected, organised and made accessible to users and interested parties. The expert system developed herein should contribute in a meaningful way towards preserving the knowledge and helping promote the use of Thai traditional medicine as a practical alternative medicine for the treatment of illnesses.

Component analysis of Chinese medicine and advances in fuming-washing therapy for knee osteoarthritis via unsupervised data mining methods

ObjectiveTo analyze the component law of Chinese medicines in fuming-washing therapy for knee osteoarthritis (KOA), and develop new fuming-washing prescriptions for KOA through unsupervised data mining methods. MethodsChinese medicine recipes for fuming-washing therapy for KOA were collected and recorded in a database. The correlation coefficient among herbs, core combinations of herbs, and new prescriptions were analyzed using modified mutual information, complex system entropy cluster, and unsupervised hierarchical clustering, respectively. ResultsBased on analysis of 345 Chinese medicine recipes for fuming-washing therapy, 68 herbs occurred frequently, 33 herb pairs occurred frequently, and 12 core combinations were found. Five new fuming-washing recipes for KOA were developed. ConclusionChinese medicines for fuming-washing therapy of KOA mainly consist of wind-dampness-dispelling and cold-dispersing herbs, blood-activating and stasis-resolving herbs, and wind-dampness-dispelling and heat-clearing herbs. The treatment of fuming-washing therapy for KOA also includes dispelling wind-dampness and dispersing cold, activating blood and resolving stasis, and dispelling wind-dampness and clearing heat. Zhenzhutougucao (Herba Speranskiae Tuberculatae), Honghua (Flos Carthami), Niuxi (Radix Achyranthis Bidentatae), Shenjincao (Herba Lycopodii Japonici), Weilingxian (Radix et Rhizoma Clematidis Chinensis), Chuanwu (Radix Aconiti), Haitongpi (Cortex Erythrinae Variegatae), Ruxiang (Olibanum), Danggui (Radix Angelicae Sinensis), Caowu (Radix Aconiti Kusnezoffii), Moyao (Myrrha), and Aiye (Folium Artemisiae Argyi) are the main herbs used in the fuming-washing treatment for KOA.

Sample Description of Diabetic Rats Treated with the Drug Pair of Astragalus and Chinese Yam by Using Multivariated Data Mapping Methods of R

The drug pair ofAstragalusandChinese yamis an effective Traditional Chinese Medicine (TCM) formula treating diabetes, but its mechanism of action is not explicit. In order to reveal its antidiabetic mechanism, we carried out metabonomics study on diabetic rats treated with drug pair ofAstragalusandChinese yam. Data obtained by using UPLC-Q-TOF/MS method were classified into five groups (normal control group, Model Group,AstragalusGroup,Chinese yamGroup and the drug pair ofAstragalusandChinese yamGroup). R software was used for Principal Component Analysis (PCA), Sammon mapping, Kruskal-Wallis mapping (isoMDS) and Independent Component Analysis (ICA). The exported LC/MS data were processed by R. PCA, isoMDS and ICA function were used to perform preliminary metabonomics analysis of diabetic rata treated with drug pair ofAstragalusandChinese yam. These results indicated the capacity of multivariate data mapping methods in metabonomics data.

Skin UV-protective effect of Microsorum grossum extract on human dermal fibroblast

Microsorum grosum (Polypodiaceae family), locally called ”metuapua'a”, are two of the most frequently fern species used in Polynesian traditional medicine. Fronds or rizhomes of this species are common ingredient of popular medicine recipes to cure various ailments. M. grosum frond and rizhome extracts contains phytoecdysteroids as main bioactive components such as ecdysone analogues, known to have many interesting biological activities and so considered as adaptogenic compounds. Skin UV-protective effect and mode of action of M. grosum extract was investigated using three ways: a transcriptomic study with c-DNA array for gene expression modulation, a stress induced premature senescence (SIPS) test on human dermal fibroblasts and cellular response experiment by activation of protein p53. The total extract of M. grosum up-regulates both heme oxygenase 1 and ferritin in human fibroblasts of the m-RNAs, enzymes which protect cells from oxidative stress (through the liberation of biliverdin, itself quickly converted into the antioxidant bilirubin) and which exerts several activities like the photoimmunoprotection of skin by UVA through the liberation of CO. The present work also report that premature senescence of human skin induced by repeated UV irradiations can be prevented by an ecdysteroid fraction of M. grosum. The activation of the protein p53 by ecdysone content of M. grosum is also indicative of a protective effect provided by cellular response including damage DNA repair processes. It seems therefore that extracts of M. grosum could protect skin against oxidative stresses and they could be used to formulate innovative cosmetic products.

Potent antihypertensive activity of Thai-Lanna medicinal plants and recipes from “MANOSROI III” database

Context: Traditional medicines have long been used by Thai practitioners for the treatment of many diseases including hypertension. The antihypertensive recipes and plants were searched and selected by a computer program from Thai/Lanna medicinal plant recipe database “MANOSROI III” using hypertensive symptoms as keywords.Objectives: To evaluate the antihypertensive potential of 30 recipes and 10 Thai-Lanna medicinal plants selected from “MANOSROI III” database using l-NAME induced hypertensive rat model.Materials and methods: Extracts from the selected recipes and plants were prepared according to the traditional indications. Antihypertensive activities including the decrease of the mean arterial blood pressure (MABP) and heart rate (HR) of the extracts as well as duration of action were investigated by intra-arterial assessment technique. All extracts were screened for phytochemicals including anthraquinone, glycoside, xanthone, tannin, carotenoid, flavones and alkaloids using standard methods.Results and conclusions: All 12 of the 30 selected recipes (40%) demonstrated antihypertensive activity with the maximum decrease of MABP at 27.17 ± 3.17% that was 2.41-fold of prazosin hydrochloride. Most recipes exhibiting antihypertensive activity contained plants in the families of Zingiberaceae and Piperaceae. The top five antihypertensive recipes showed the presence of glycosides, xanthones and alkaloids. Ten single plants from these recipes were extracted and evaluated for antihypertensive activity. The cassumunar ginger extract exhibited the maximum decrease of MABP at 39.83 ± 3.92%, which was 3.54-times that of prazosin hydrochloride. This study demonstrated the potent antihypertensive activity of Thai medicinal plants and recipes that can be further developed as antihypertensive agents.

Potent anti-cervical cancer activity: Synergistic effects of Thai medicinal plants in recipe N040 selected from the MANOSROI III database

Ethnopharmacological relevancesOne of the prestigious Thai/Lanna folklore wisdoms is the medicinal plant recipes. Thai/Lanna medicinal plant recipe database MANOSROI III has been developed by Prof. Dr. Jiradej Manosroi. It consists of over 200,000 recipes covering all diseases including cancer. Aim of this studyTo investigate the in vitro and in vivo anti-cervical cancer activity and the active constituents of the Thai medicinal plant recipe N040 selected from the MANOSROI III database. Materials and methodsThe extracts of recipe N040 and single medicinal plants in the recipe were prepared by hot water and methanol extraction, respectively. The n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH) and water fractions of Caesalpinia sappan, the plant which showed the highest anti-proliferative activity were prepared by liquid–liquid partition extraction. The fraction which showed the highest anti-proliferative activity was further isolated for active constituents. Anti-proliferative activity of recipe N040, methanolic extracts, fractions of Caesalpinia sappan and brazilin, an active constituent on HeLa cell were investigated using sulforhodamine B (SRB) assay. Anti-oxidative activities including free radical scavenging and metal ion-chelating activities, as well as the phenolic and flavonoid contents of these fractions were also determined. The in vivo anti-cancer activity of recipe N040 on HeLa cell xenograft and the subchronic toxicity were performed in nude mice and rats, respectively. Results and conclusionsN040 showed the potent in vitro anti-proliferative activity on HeLa cell with the IC50 value of 0.11µg/ml. Phytochemicals detected in the plants were steroids/triterpenoids, tannins, flavonoids, saponins and alkaloids. For the single plant, methanolic extract of Caesalpinia sappan gave the highest anti-proliferative activity with the IC50 of 33.46µg/ml. EtOAc fraction of Caesalpinia sappan showed the highest anti-proliferative and free radical scavenging activities with the IC50 and SC50 of 17.81 and 21.95µg/ml which were 1.88 and 0.83 folds of its methanolic extract and ascorbic acid, respectively. Poor metal chelating activity (MC50>500µg/ml) was observed in methanolic extract and all fractions. The highest phenolic and flavonoid contents were observed in the methanolic extract. Brazilin, the known compound isolated from the EtOAc fraction exhibited potent anti-proliferative activity with the IC50 of 0.28µg/ml which was higher than its methanolic extract and EtOAc fraction of 119.50 and 63.61 folds, respectively, but only 0.39 fold of the recipe extract N040. The tumor size of the HeLa cell xenograft nude mice treated with the recipe N040 at the dose of 44.50mg/kg body weight per day was significantly smaller (p<0.05) than that of the control with the relative tumor weight inhibition of 57.23% which was 0.65 fold of cisplatin. In the subchronic toxicity study, N040 given orally at the dose of 1000mg/kg body weight per day for 90 days showed no alteration in body weight gain, hematology [except the increase mean corpuscular hemoglobin (MCH) in the treated male rats] and clinical blood chemistry (except the increase blood glucose in the treated male rats) both in female and male rats. Only minor lesions of the organs including lung, liver, kidney and small intestine were observed in both sexes. This study has demonstrated the synergistic effect of the plants composed in the recipe which resulted in the potent anti-cancer activity and confirmed the traditionally use of the recipe N040. In addition, this study has also suggested the compound brazilin isolated from Caesalpinia sappan for its high potential to be further investigated as a novel anti-cervical cancer drug.

The use of sugar in the pharmacy manual of Cohen al-‘Aṭṭar, a Jewish doctor in 13th century Cairo

In the absence of a pharmaceutical guide for the usage of apothecaries and merchants of drugs and drinks, which took into account the evolution of pharmacy and the development of pharmaceutical products, Cohen al-‘Aṭṭar wrote a new manual in which he reminded us not only of the writings of his predecessors, but also the point of view of his contemporaries, notably his proper experiences he carried out in his shop in Cairo to make pharmaceutical products and the means to preserve them. This pharmaceutical manual, the richest in medicine formulas, also stands out on account of the extensive use of sugar in the making of recipes. Given the fact that this product was available in large quantities in Egypt and Syria during the second half of the 13th century, it gradually substituted honey to become the principal ingredient in the making of drugs and drinks. Thus, sugar broke through the food world to become the privilege of the royal class, who turned it into one of the essential elements for their festivities.

Comparative Pharmacokinetic Study of Chlorogenic Acid after Oral Administration of Lonicerae Japonicae Flos and Shuang‐Huang‐Lian in Normal and Febrile Rats

Shuang-Huang-Lian (SHL), a famous traditional Chinese medicine recipe containing Lonicerae Japonicae Flos (LJF), Forsythiae Fructus, and Scutellariae Radix, is clinically used for the treatment of fever and acute upper respiratory tract infection. In this research, a comparative study was conducted to compare the pharmacokinetic difference of chlorogenic acid (ChA) after oral administration of LJF and SHL to normal and febrile rats with approximately the same dose of 60 mg/kg, and the antipyrexia effect of LJF and SHL on rectal temperature changes induced by Baker's yeast was investigated. The results indicated that AUC(0-t) and plasma concentrations of ChA in the febrile rats were significantly higher than normal rats whether in the extract of LJF or SHL. In addition, SHL increased the values of AUC of ChA in both febrile and normal rats compared with LJF alone (p < 0.05), and SHL showed better antipyrexia effect than LJF. These results indicate that fever could play an important role in pharmacokinetic process of ChA. Meanwhile, the combined formula SHL exhibits higher bioavailability of ChA and superior antipyrexia effect than the single herb.

Expression Profiling and Proteomic Analysis of JIN Chinese Herbal Formula in Lung Carcinoma H460 Xenografts

Many traditional Chinese medicine (TCM) formulae have been used in cancer therapy. The JIN formula is an ancient herbal formula recorded in the classic TCM book Jin Kui Yao Lue (Golden Chamber). The JIN formula significantly delayed the growth of subcutaneous human H460 xenografted tumors in vivo compared with the growth of mock controls. Gene array analysis of signal transduction in cancer showed that the JIN formula acted on multiple targets such as the mitogen-activated protein kinase, hedgehog, and Wnt signaling pathways. The coformula treatment of JIN and diamminedichloroplatinum (DDP) affected the stress/heat shock pathway. Proteomic analysis showed 36 and 84 differentially expressed proteins between the mock and DDP groups and between the mock and JIN groups, respectively. GoMiner analysis revealed that the differentially expressed proteins between the JIN and mock groups were enriched during cellular metabolic processes, and so forth. The ones between the DDP and mock groups were enriched during protein-DNA complex assembly, and so forth. Most downregulated proteins in the JIN group were heat shock proteins (HSPs) such as HSP90AA1 and HSPA1B, which could be used as markers to monitor responses to the JIN formula therapy. The mechanism of action of the JIN formula on HSP proteins warrants further investigation.

Study on Incompatibility of Traditional Chinese Medicine: Evidence from Formula Network, Chemical Space, and Metabolism Room

A traditional Chinese medicine (TCM) formula network including 362 TCM formulas was built by using complex network methodologies. The properties of this network were analyzed including network diameter, average distance, clustering coefficient, and average degree. Meanwhile, we built a TCM chemical space and a TCM metabolism room under the theory of chemical space. The properties of chemical space and metabolism room were calculated and analyzed. The properties of the medicine pairs in “eighteen antagonisms and nineteen mutual inhibitors,” an ancient rule for TCM incompatibility, were studied based on the TCM formula network, chemical space, and metabolism room. The results showed that the properties of these incompatible medicine pairs are different from those of the other TCM based on the analysis of the TCM formula network, chemical space, and metabolism room. The lines of evidence derived from our work demonstrated that the ancient rule of TCM incompatibility, “eighteen antagonisms and nineteen mutual inhibitors,” is probably scientifically based.

Effect of kidney-reinforcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone marrow mesenchymal stem cells from chronic aplastic anemia patients

ObjectiveTo explore the effect of kidney-reinforcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone marrow mesenchymal stem cells (MSCs) from patients with chronic aplastic anemia (CAA). MethodsWe used three Traditional Chinese Medicine recipes, namely a kidney-reinforcing recipe (KRR), blood-activating and stasis-removing recipe (BASRR), and kidney-reinforcing, blood-activating and stasis-removing recipe (KRBASRR), and a normal saline control to prepare herbal medicine serum in Sprague Dawley rats. Thirty CAA patients were enrolled in the experimental group, including 17 kidney-Yang deficient patients and 13 kidney-Yin deficient patients. Ten healthy individuals were included in the control group. MSCs were isolated from bone marrow samples, and the cell density was observed to measure their proliferation ability by microscopy on days 2, 7, and 14 after isolation. In addition, the expression of adhesion molecules of bone marrow MSCs (CD106, CD49d, CD31 and CD44) were detected by flow cytometry after 48 h of treatment with the four different herbal medicine serums. ResultsThe proliferation of MSCs from kidney-Yang deficient and kidney-Yin deficient patients was weaker than that of MSCs from the control group. The expression of all adhesion molecules of bone marrow MSCs from CAA patients was obviously lower than that in the control group (P<0.01). The expression of CD49d and CD31 in MSCs from patients with a kidney-Yin deficiency was lower than in those with a kidney-yang deficiency (P<0.05 and P<0.01, respectively). For kidney-Yang deficient patients, CD31 expression in the KRBASRR group was significantly higher than that in the BASRR group (P<0.01), while CD44 in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P<0.01). For kidney-Yin deficient patients, CD106 and CD49d expression in the KRBASRR group was obviously higher than that in the KRR group (P<0.05), while CD31 and CD44 expression in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P<0.05 and P<0.01, respectively). ConclusionThe bone marrow microenvironment in CAA patients is abnormal. The effect of KRBASRR may be better than that of KRR and BASRR for kidney-Yang deficient and kidney-Yin deficient patients by improving the expression levels of MSC adhesion molecules.

Down-regulation of CatSper1 channel in epididymal spermatozoa contributes to the pathogenesis of asthenozoospermia, whereas up-regulation of the channel by Sheng-Jing-San treatment improves the sperm motility of asthenozoospermia in rats

To determine the expression of CatSper1 channel in epididymal spermatozoa in a rat model of asthenozoospermia, induced by cyclophosphamide (CP), and further examine the effects of soluble granules of Sheng-Jing-San (SJS), a traditional Chinese medicine recipe, on CatSper1 expression and sperm motility in the CP-induced asthenozoospermic rats. Placebo-controlled, randomized trial. Neuroscience Research Institute, Peking University, China. Sexually mature male Sprague-Dawley rats (n = 60). In the CP group, CP at the dose of 35 mg/kg intraperitoneally injected into rats once a day for 7 days; in the normal saline (NS) group, 0.9% saline solution was injected as control. Sperm motility and count were evaluated by computer-assisted sperm assay (CASA); protein and mRNA expression of CatSper1 channel in epididymal spermatozoa was determined by Western blotting and quantitative real-time RT-PCR, respectively. The rats were randomly divided into five groups with 12 rats in each group: CP, normal saline (NS), CP + SJS, CP + NS, and treatment naïve. In the CP + SJS group, after the last injection of CP, SJS at a dose of 30 mg/kg was intragastrically administrated to rats once a day for 14 days; in CP + NS group, saline solution instead of SJS was administrated as control. In the treatment naïve group, rats were normally fed for 21 days as controls. We found a statistically significant reduction of the CatSper1 channel, which is associated with an impairment of sperm motility in the epididymal spermatozoa of CP-induced asthenozoospermic rats. Soluble granules of SJS could dramatically restore the CP-induced down-regulation of CatSper1 in epididymal spermatozoa, which greatly improved the sperm motility in the asthenozoospermic rats. Down-regulation of the CatSper1 channel in epididymal spermatozoa likely contributes to the pathogenesis of asthenozoospermia, whereas up-regulation of the channel by SJS improves sperm motility and thus can be used as an effective therapeutic strategy for the treatment of male infertility diagnosed with asthenozoospermia.