Showing papers in "Planta Medica in 2010"

Goji (Lycium barbarum and L. chinense): Phytochemistry, pharmacology and safety in the perspective of traditional uses and recent popularity.

Abstract: Since the beginning of this century, Goji berries and juice are being sold as health food products in western countries and praised in advertisements and in the media for well-being and as an anti-aging remedy. The popularity of Goji products has rapidly grown over the last years thanks to efficient marketing strategies. Goji is a relatively new name given to Lycium barbarum and L. chinense, two close species with a long tradition of use as medicinal and food plants in East Asia, in particular in China. While only L. barbarum is officinal, the fruit (fructus Lycii) and the root bark (cortex Lycii radicis) of both species are used in the folk medicine. We review here the constituents, pharmacology, safety, and uses of L. barbarum and L. chinense with consideration to the different parts of the plant. Investigations of the fruit have focused on proteoglycans, known as " Lycium barbarum polysaccharides", which showed antioxidative properties and some interesting pharmacological activities in the context of age related diseases such as atherosclerosis and diabetes. As to the root bark, several compounds have demonstrated a hepatoprotective action as well as inhibitory effects on the rennin/angiotensin system which may support the traditional use for the treatment of hypertension. While there are no signs of toxicity of this plant, two cases of possible interaction with warfarin point to a potential risk of drug interaction. In view of the available pharmacological data and the long tradition of use in the traditional Chinese medicine, L. barbarum and L. chinense certainly deserve further investigation. However, clinical evidences and rigorous procedures for quality control are indispensable before any recommendation of use can be made for Goji products.

Potential of Cameroonian plants and derived products against microbial infections: a review.

Abstract: In Cameroon, infectious diseases are amongst the most commonly notified diseases and largest cause of mortality. Many plants are used locally in traditional medicine for their treatment. The aim of the present review is to summarize currently available evidence and knowledge concerning Cameroonian plants used to treat bacterial and fungal infections, and the efficacy of plant-derived extracts and compounds. The traditional uses of plants in the treatment of infectious diseases have been collected and tabulated. The antimicrobial activity of the extracts and the chemical constituents of most of these plants are summarized in this report. Plants used traditionally in Cameroonian medicine, with laboratory work on any part or products, have been documented. Numerous extracts and compounds have been tested for antimycobacterial, antibacterial and antifungal efficacy and some of them were significantly active. Most of the bioactive compounds isolated were phenolics and alkaloids. In conclusion, many plant species are used in traditional medicine in Cameroon to treat infectious diseases, and several interesting openings have originated for further inquiry following IN VITRO antimicrobial activity evaluation. However, much work is still to be done to standardize methods and cut-off points for describing the antimicrobial activity, and on the study of the mechanisms of action.

The role of traditional Chinese herbal medicines in cancer therapy--from TCM theory to mechanistic insights.

Abstract: Traditional Chinese medicine-based herbal medicines have gained increasing acceptance worldwide in recent years and are being pursued by pharmaceutical companies as rich resources for drug discovery. For many years, traditional Chinese medicines (TCM) have been applied for the treatment of cancers in China and beyond. Herbal medicines are generally low in cost, plentiful, and show very little toxicity or side effects in clinical practice. However, despite the vast interest and ever-increasing demand, the absence of strong evidence-based research and the lack of standardization of the herbal products are the main obstacles toward the globalization of TCM. In recent years, TCM research has greatly accelerated with the advancement of analytical technologies and methodologies. This review of TCM specifically used in the treatment of cancer is divided into two parts. Part one provides an overview of the philosophy, approaches and progress in TCM-based cancer therapy. Part two summarizes the current understanding of how TCM-derived compounds function as anticancer drugs.

Metabolomics: towards understanding traditional Chinese medicine.

Abstract: Metabolomics represent a global understanding of metabolite complement of integrated living systems and dynamic responses to the changes of both endogenous and exogenous factors and has many potential applications and advantages for the research of complex systems. As a systemic approach, metabolomics adopts a "top-down" strategy to reflect the function of organisms from the end products of the metabolic network and to understand metabolic changes of a complete system caused by interventions in a holistic context. This property agrees with the holistic thinking of Traditional Chinese Medicine (TCM), a complex medical science, suggesting that metabolomics has the potential to impact our understanding of the theory behind the evidence-based Chinese medicine. Consequently, the development of robust metabolomic platforms will greatly facilitate, for example, the understanding of the action mechanisms of TCM formulae and the analysis of Chinese herbal (CHM) and mineral medicine, acupuncture, and Chinese medicine syndromes. This review summarizes some of the applications of metabolomics in special TCM issues with an emphasis on metabolic biomarker discovery.

Modulation of Apoptosis by Natural Products for Cancer Therapy

Abstract: Natural products can exhibit many beneficial effects on human health. As far as cancer is concerned, naturally occurring compounds have been reported to prevent tumorigenesis and also to suppress the growth of established tumors. As cancer cells have evolved multiple mechanisms to resist the induction of programmed cell death (apoptosis), the modulation of apoptosis signaling pathways by natural compounds has been demonstrated to constitute a key event in these antitumor activities. This review presents some examples of how apoptosis pathways are targeted by selected naturally occurring agents and how these events can be exploited for cancer therapy.

Targeting inflammatory pathways by flavonoids for prevention and treatment of cancer

Abstract: Observational studies have suggested that life- style risk factors such as tobacco, alcohol, high- fat diet, radiation, and infections can cause cancer and that a diet consisting of fruits and vegetables can prevent cancer. Evidence from our laboratory and others suggests that agents either causing or preventing cancer are linked through the regula- tion of inflammatory pathways. Genes regulated by the transcription factor NF-κB have been shown to mediate inflammation, cellular trans- formation, tumor cell survival, proliferation, inva- sion, angiogenesis, and metastasis. Whereas vari- ous lifestyle risk factors have been found to acti- vate NF-κB and NF-κB-regulated gene products, flavonoids derived from fruits and vegetables have been found to suppress this pathway. The present review describes various flavones, flava- nones, flavonols, isoflavones, anthocyanins, and chalcones derived from fruits, vegetables, le- gumes, spices, and nuts that can suppress the proinflammatory cell signaling pathways and thus can prevent and even treat the cancer. " cancer l " inflammation l " flavonoids

A Unique Issue in the Standardization of Chinese Materia Medica: Processing

Abstract: Processing of Chinese Materia Medica (CMM) is a pharmaceutical technique to fulfill the different requirements of therapy, dispensing and making preparations according to traditional Chinese medicine theory. The aims of processing are to enhance the efficacy and/or reduce the toxicity of crude drugs. Those processed products are named as decoction pieces, which are used in clinics. Therefore, there is a close relationship between processing, safety, and efficacy of Chinese medicines. Some toxicity or side effects are caused by improper processing methods and some are due to improper combination of herbal mixtures. Standardization of processing methods for Chinese herbs is as important as authentication to maintain their quality and ensure their safe use. The objective of this paper is to review the literature covering the current situation and problems of CMM processing as well as recent progress in research in this area. A summary of the most urgent work needed is proposed.

Toxicological risks of Chinese herbs.

Abstract: As traditional Chinese medicine (TCM) has become more popular there have been increasing concerns about safety and potential toxicity of the Chinese materia medica (CMM) comprising plants, animal parts and minerals. The potential toxicity of many CMM is well recognised in TCM and to reduce risks use of some herbs is restricted whilst specific processing methods have been developed to modify the activities/toxicity of others. However adverse reactions have been reported, many of these are due misuse or abuse of Chinese medicine. The main problem remains products adulterated with pharmaceuticals for weight loss or erectile dysfunction. But some herbs have narrow therapeutic ranges (e.g., Aconitum species) so toxic effects are frequently reported. Toxic effects from chronic or cumulative dosing are difficult to detect in the traditional setting and recent reports have demonstrated the health problems from Aristolochia species. Despite safety concerns, Chinese medicine appears to be relatively safe with comparatively few reports of adverse reactions compared with overall drug reports. The wealth of information in the Chinese literature needs to be more widely available. As TCM is widely used by patients, improved pharmacovigilance and pharmacoepidemiology can contribute valuable safety information, relevant to clinical use.

Anti-inflammatory plant natural products for cancer therapy.

Abstract: !Much of the current research in cancer therapeutics is aimed at developing drugs or vaccines to target key molecules for combating tumor cell growth, metastasis, proliferation, or changes in the associated stromal microenvironment. Studies on a wide spectrum of plant secondary metabolites extractable as natural products from fruits, vegetables, teas, spices, and traditional medicinal herbs show that these plant natural products can act as potent anti-inflammatory, antioxidant or anticancer agents. The recent advances in genomics and metabolomics have enabled biologists to better investigate the potential use of immunomodulatory natural products for treatment or control of various cancerous diseases. The cancer preventive or protective activities of the various immunomodulatory natural products lie in their effects on cellular defenses including detoxifying and antioxidant enzyme systems, and the induction of anti-inflammatory and antitumor or antimetastasis responses, often by targeting specific key transcription factors like nuclear factor kappa B (NF-κB), activator protein (AP-1), signal transducers and activators of transcription (STAT) and others. This review presents recent findings and hypotheses on the molecular mechanisms through which various inflammatory activities are linked to tumorigenic processes and the specific immunomodulatory natural products that may suppress inflammation and the associated tumor progression and metastasis both in vitro and in vivo. In addition to tumor cells per se ,t he various associated roles of myeloid-derived suppressor cells, stromal fibroblasts, myofibroblasts, and inflammatory immune cells, and the possible effects of phytomedicines on these cells in the tumor microenvironment will be discussed. Abbreviations ! AKT: v-akt murine thymoma viral oncogene homolog

New Aspects of DNA-based Authentication of Chinese Medicinal Plants by Molecular Biological Techniques

Abstract: DNA technology provides a powerful tool to complement chemical analyses for authentication of Chinese medicinal plants and to ensure that herbal materials are not contaminated with ineffective or potentially harmful substitutes or adulterants. In the last two decades molecular biotechnology has provided sophisticated molecular techniques for authentication of botanical materials at the DNA level. This review provides an account of the most commonly used DNA-based technologies (RAPD, RFLP, ARMS, CAPS, AFLP, DAF, ISSR, SSR, sequencing, hybridization and microarrays) including suitable examples of Chinese medical plants. A critical evaluation of all methods is presented concerning sensitivity, reliability, reproducibility, and running costs. Recent achievements in the field of DNA barcoding and DNA chip technology that offer great potentials for screening of DNA and emerging new developments for future identification of species are briefly outlined.

Rhein improves renal lesion and ameliorates dyslipidemia in db/db mice with diabetic nephropathy.

Abstract: Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is purified from rhubarb (Rheum officinale), a widely used traditional Chinese herb. In our previous studies, rhein was shown to be effective in ameliorating diabetic renal pathological changes and attenuating hyperlipidemia. Statins have also been proven to ameliorate renal pathological changes associated with diabetic nephropathy (DN) through lipid-dependent and -independent mechanisms. We here study the protective and regulatory effects of rhein on renal injury and dyslipidemia in db/db mice with DN, using simvastatin as the control, and provide information on the mechanisms by which rhein protects against renal damage from DN. The results indicated that urinary albumin excretion (UAE) was reduced after 8 weeks of treatment in the rhein group, and 12 weeks in the simvastatin group. The morphometric analysis revealed that levels of extracellular matrix (ECM) significantly decreased in the rhein group after the full treatment course, but not in the simvastatin group. The more powerful effects of rhein on decreasing transforming growth factor-beta1 (TGF-beta1) and fibronectin immunohistochemistry expression in renal tissue were also observed. And the plasma levels of cholesterol (Chol), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and ApoE all decreased in both the rhein and the simvastatin groups. Together, our data suggested that both rhein and simvastatin regulate dyslipidemia. The powerful effect of rhein in renal protection is due to its widespread effects. Rhein is a new drug that can decrease lipid levels and protect against DN progression in a different fashion with simvastatin.

Plectranthus barbatus: a review of phytochemistry, ethnobotanical uses and pharmacology - Part 1.

Abstract: Plectranthus barbatus Andr. is one of the most important species of the genus Plectranthus L' Herit. (Lamiaceae), with a wide variety of traditional medicinal uses in Hindu and Ayurvedic traditional medicine as well as in the folk medicine of Brazil, tropical Africa and China. The plant has therefore been an attractive target for intensive chemical and pharmacological studies up to now. This review presents data about the phytochemistry, ethnobotanical uses and pharmacology of Plectranthus barbatus as well as the pharmacology of its constituents. In addition to essential oil, abietane diterpenoids and 8,13-epoxy-labd-14-en-11-one diterpenoids are the main constituents found in Plectranthus barbatus. The major ethnobotanical uses are for intestinal disturbance and liver fatigue, respiratory disorders, heart diseases and certain nervous system disorders. Forskolin as one of the major constituents with its unique adenylyl cyclase activation that underlies the wide range of pharmacological properties could explain the different traditional uses of Plectranthus barbatus. Forskolin is involved in a number of patented pharmaceutical preparations used as over-the-counter drugs for the treatment of several ailments. However, the water-insoluble nature of forskolin limits its clinical usefulness. Forskolin thus served as a prototype for the development of 6-(3-dimethylaminopropionyl)forskolin hydrochloride (NKH477) as a potent water-soluble forskolin derivative that finds use in the therapy for a number of diseases especially of the cardiovascular system.

Application of mid-infrared spectroscopy in the quality control of traditional Chinese medicines.

Abstract: Chinese herbal medicines are often referred to as Chinese materia medica (CMM). Composite formulae containing mixtures of CMM are prescribed for treatment and prevention of diseases in the practice of traditional Chinese medicine (TCM). Some of the well-known CMM formulae (Fufang in Chinese) are manufactured and marketed as proprietary Chinese medicines (PCM). Quality assessment and assurance of these products are difficult; they are a challenging task. Mid-infrared spectroscopy, a classic molecular structure analysis method, has been innovatively applied in the quality control of TCM, and has gained significant impact and advancement in analytical fields. Infrared fingerprinting features appear particularly suitable for the identification of multicomponent matrices in samples whose chemical integrity has not been altered or destroyed because no extraction procedure is needed. This review summarizes and gives an overall view on the application of mid-infrared and two-dimensional correlation infrared (2D-IR) spectroscopy as well as chemometric techniques in the identification of CMM, investigation of TCM processing procedures, and analysis of herb extracts and preparations.

Microtubule-Binding Natural Products for Cancer Therapy

Abstract: Natural products, especially microtubule-binding natural products, play important roles in the war against cancer. From the clinical use of vinblastine in 1961, paclitaxel in 1992, to ixabepilone in 2007, microtubule-binding natural products have continually contributed to the development of cancer therapy. The present review summarizes the development of representative microtubule-binding natural products including agents binding to the colchicine-binding site, the Vinca alkaloid-binding site, the taxane-binding site and other binding sites. Future directions for the development of new anticancer microtubule-binding natural products are discussed. Finding new formulations, new targets and new sources of microtubule-binding natural products may enable more members of this kind of agent to be introduced into the clinic for cancer therapy.

Historic Perspectives on Annonaceous Acetogenins from the Chemical Bench to Preclinical Trials

Abstract: Studies on the Annonaceous acetogenins began after the first cytotoxic acetogenin, uvaricin, was isolated in 1982. This attractive finding made many medicinal and natural product chemists direct their efforts on the isolation and identification of these classes of compounds. As more Annonaceous acetogenins were isolated, more information about them was uncovered. From their structural identification to the total synthesis of natural product analogues and from cell-based screening and molecular-based targeting to animal testing, the mechanisms of action of the Annonaceous acetogenins became clearer. The purpose of this review is to give an account of recent studies on this class of compounds and their analogues, which will aid us not only in clarifying how the Annonaceous acetogenins act but also in establishing principles for the further development of this class of compounds.

Plasma Levels and Distribution of Flavonoids in Rat Brain after Single and Repeated Doses of Standardized Ginkgo biloba Extract EGb 761

Abstract: It is undisputed that terpene lactones and flavonoid glycosides of Ginkgo biloba are responsible for most of the extracts (e.g., EGb 761®) pharmacological actions. This investigation focused on the pharmacokinetic and the ability of the flavonoid constituents to cross the blood-brain barrier in rats, after single (600 mg/kg) or repeated (8 days, 100, or 600 mg/kg) oral administration of EGb 761®, and their distribution in different areas of the brain. For this purpose, we developed an HPLC-fluorescence method for the determination of the Ginkgo flavonoid metabolites (quercetin, kaempferol, and isorhamnetin derivatives) in the brain and plasma. A single dose of 600 mg/kg EGb 761® resulted in maximum plasma concentrations of 176, 341, and 183 ng/mL for quercetin, kaempferol, and isorhamnetin/tamarixetin, respectively and in maximum brain concentrations of 291 ng/g protein for kaempferol and 161 ng/g protein for isorhamnetin/tamarixetin. In comparison, the repeated administration of the same dose for 8 days led to an approximate 4.5-fold increase in the plasma concentration for quercetin, 11.5-fold increase for kaempferol, and 10-fold increase for isorhamnetin/tamarixetin. In the brain, an approximate 2-fold increase was observed for kaempferol and isorhamnetin/tamarixetin. About 90% of the determined flavonoids were distributed in the hippocampus, frontal cortex, striatum, and cerebellum, which together represent only 38% of the whole brain.

Cellular mechanisms of the anticancer effects of the lichen compound usnic acid.

Abstract: The lichen compound usnic acid is used for its antimicrobial activities in cosmetic products and is also a component of slimming agents. Its effect against cancer cells was first noted over 30 years ago. In this study possible mechanisms of this effect were investigated using two human cell lines, the breast cancer cell line T-47D and the pancreatic cancer cell line Capan-2. Pure (+)-usnic acid from CLADONIA ARBUSCULA and (-)-usnic acid from ALECTORIA OCHROLEUCA were shown to be equally effective inhibitors of DNA synthesis, with IC (50) 4.2 microg/mL and 4.0 microg/mL for (+) and (-)-usnic acid against T-47D, and 5.3 microg/mL and 5.0 microg/mL against Capan-2, respectively. Flow cytometric analysis confirmed the inhibited entry into the S-phase and showed reduction in cell size. Classical apoptosis, as assessed by TUNEL staining, was not observed. Necrosis, measured by LDH release, was seen only in Capan-2 after exposure for 48 hours. Staining with the mitochondrial dye JC-1 demonstrated dose-dependent loss of mitochondrial membrane potential following treatment with usnic acid in both cell lines. In conclusion, usnic acid had a marked inhibitory effect on growth and proliferation of two different human cancer cell lines and led to loss of mitochondrial membrane potential. Cell survival was little affected; late necrosis was seen in one of the cell lines. No difference was noted between the two enantiomers.

Hovenia dulcis--an Asian traditional herb.

Abstract: Hovenia dulcis Thunb., known as Japanese raisin tree, is commonly found in East Asia. It has a long history as a food supplement and traditional medicine in Japan, China and Korea, but is little known and used in Western countries so far. This minireview summarizes traditional uses and current knowledge on the pharmacology and phytochemistry of H. duclcis and covers, in particular, literature from specialized Asian journals that are not readily accessible. Extracts from H. dulcis accelerate detoxification of ethanol, and possess hepatoprotective, antioxidative, antimicrobial and antidiabetic properties. Although the underlying molecular mechanisms are not fully understood, free radical scavenging and enhancement of ethanol catabolism have been reported.

Clinical Studies with Traditional Chinese Medicine in the Past Decade and Future Research and Development

Abstract: Traditional Chinese medicine (TCM) is currently considered a complementary or alternative medical system in most Western countries and has been increasingly accepted worldwide. More and more clinical trials on TCM have been conducted internationally, and scientists worldwide are becoming increasingly interested in the evaluation of clinical efficacy of TCM based on clinical trials. This paper reviews the situation of clinical trials on TCM in the past decade, including systematic reviews about clinical trials either focusing on the treatment of disease with TCM approaches or focusing on one herbal product, conduction of clinical trials on TCM either with randomization and controlled methods or general observation. Some general issues on the conduct of clinical trials on TCM, such as randomization, control, quality of life (QOL), patient reported outcomes (PROs) and biomarkers, quality control, safety evaluation and case studies, are discussed, and accordingly some suggestions are proposed.

Antinociceptive activity of the essential oil of Zingiber zerumbet.

Abstract: In the present study, the rhizome essential oil from Zingiber zerumbet (Zingiberaceae) was evaluated for antinociceptive activity using chemical and thermal models of nociception, namely, the acetic acid-induced abdominal writhing test, the hot-plate test and the formalin-induced paw licking test. It was demonstrated that intraperitoneal administration of the essential oil of Z. zerumbet (EOZZ) at the doses of 30, 100 and 300 mg/kg produced significant dose-dependent inhibition of acetic acid-induced abdominal writhing, comparable to that of obtained with acetylsalicylic acid (100 mg/kg). At the same doses, the EOZZ produced significant dose-dependent increases in the latency time in the hot-plate test with respect to controls, and in the formalin-induced paw licking test, the EOZZ also significantly reduced the painful stimulus in both neurogenic and inflammatory phase of the test. In addition, the antinociceptive effect of the EOZZ in the formalin-induced paw licking test as well as hot-plate test was reversed by the nonselective opioid receptor antagonist, naloxone suggesting that the opioid system was involved in its analgesic mechanism of action. On the basis of these data, we concluded that the EOZZ possessed both central and peripheral antinociceptive activities which justifying its popular folkloric use to relieve some pain conditions.

Anti-inflammatory activity of myricetin isolated from Myrica rubra Sieb. et Zucc. leaves.

Abstract: MYRICA RUBRA Sieb. et Zucc. leaves are commonly used in folk medicine to treat inflammatory disorders in China. Present studies on the anti-inflammatory effect of myricetin from MYRICA RUBRA Sieb. et Zucc. leaves was evaluated with various IN VIVO models of both acute and chronic inflammations such as xylene-induced ear edema, acetic acid-induced vascular permeability, carrageenan-induced paw edema, leukocyte migration assay, and cotton pellet granuloma models. Myricetin showed a significant inhibition on ear edema and hind paw edema caused by xylene and carrageenan, respectively. Furthermore, it also inhibited the increase in capillary permeability induced by the production of acetic acid in the human body. Myricetin significantly decreased the serum levels of MDA and, in turn, increased the serum levels of SOD in the carrageenan-induced paw edema model. Concurrently, myricetin also significantly decreased leukocyte count. During chronic inflammation, myricetin inhibited the formation of granuloma tissue. These results, collectively, demonstrate that myricetin possesses a potent anti-inflammatory function on acute and chronic inflammation. Its anti-inflammatory mechanisms are probably associated with the inhibition of antioxidant activity. These results also support the claims of traditional Chinese medicine practitioners about the use of MYRICA RUBRA Sieb. et Zucc. leaves in the treatment of inflammatory diseases.

The bioactive metabolites of the mangrove endophytic fungus Talaromyces sp. ZH-154 isolated from Kandelia candel (L.) Druce.

Abstract: Bioactivity-directed fractionation of the extract of the mangrove endophytic fungus Talaromyces sp. ZH-154, which was isolated from the stem bark of Kandelia candel (L.) Druce, Rhizophoraceae, afforded two new metabolites, 7-epiaustdiol ( 1) and 8-O-methylepiaustdiol ( 2), together with the known compounds, stemphyperylenol ( 3), skyrin ( 4), secalonic acid A ( 5), emodin ( 6), and norlichexanthone ( 7). Their structures were elucidated on the basis of spectroscopic evidences including CD, MS, and 1D, 2D NMR techniques. The absolute configuration of 1 was unequivocally determined by single-crystal X-ray diffraction. All isolated compounds were evaluated for their antimicrobial and in vitro cytotoxic activities.

Toxicity assessment of nine types of decoction pieces from the daughter root of Aconitum carmichaeli (Fuzi) based on the chemical analysis of their diester diterpenoid alkaloids.

Abstract: Various processed types of FUZI (the daughter roots of the highly toxic plant Aconitum carmichaeli Debx, FZ) decoction pieces (the herbal materials processed according to the specifications of Chinese medicine manuals; " YINPIAN" in Chinese transliteration) are widely used in traditional medicine to treat various diseases, but their toxicities are not known. Nine types of FZ decoction pieces, including one raw slice and eight processed forms, were therefore prepared, each in 7 to 10 batches, to assess for their toxicity. Altogether 84 FZ samples were quantified on the amount of highly toxic diester diterpenoid alkaloids, i.e., aconitine, mesaconitine and hypaconitine by a newly developed HPLC method with HPLC-DAD and LC-MS techniques. The comparison of the processed FZ to raw slices of the root showed that the amount of each analyte in the processed FZ was drastically decreased. The sum of the three toxic compounds in the 8 types of processed FZ was only 3.91-34.80 % of this value in the FZ raw slice. This implies that the toxicity of processed FZ was decreased significantly. The amounts of toxic components in the 8 types of processed FZ varied significantly, often by a power of ten, indicating that the dosage of these herbs, when prescribed for clinical uses, should be cautiously set in order to avoid poisoning incidents.

Anti-inflammatory effects of madecassic acid via the suppression of NF-κB pathway in LPS-induced RAW 264.7 macrophage cells.

Abstract: We have investigated the anti-inflammatory effects of madecassic acid and madecassoside isolated from Centella asiatica (Umbelliferae) on lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. Both madecassic acid and madecassoside inhibited the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and IL-6. However, madecassic acid more potently suppressed these inflammatory mediators than did madecassoside. Consistent with these observations, madecassic acid inhibited the LPS-induced expression of iNOS and COX-2 at the protein level and of iNOS, COX-2, TNF-alpha, IL-1beta, and IL-6 at the mRNA level in RAW 264.7 macrophage cells, as determined by Western blotting and RT-PCR, respectively. Furthermore, madecassic acid suppressed the LPS-induced activation of nuclear factor-kappaB (NF-kappaB), and this was associated with the abrogation of inhibitory kappa B-alpha (IkappaB-alpha) degradation and with the subsequent blocking of p65 protein translocation to the nucleus. These results suggest that the anti-inflammatory properties of madecassic acid are caused by iNOS, COX-2, TNF-alpha, IL-1beta, and IL-6 inhibition via the downregulation of NF-kappaB activation in RAW 264.7 macrophage cells.

Xanthohumol and related prenylated flavonoids inhibit inflammatory cytokine production in LPS-activated THP-1 monocytes: structure-activity relationships and in silico binding to myeloid differentiation protein-2 (MD-2).

Abstract: Xanthohumol (XN) is a prenylated chalcone-type flavonoid found in hops and beer. Our objective of this study was to determine the anti-inflammatory activities of XN, isoxanthohumol (IX), and 15 related prenylated chalcones and flavanones, as well as their structure-activity relationships. The anti-inflammatory activities of the flavonoids were measured by their ability to inhibit lipopolysaccharide (LPS)-induced cytokine production in human monocytic THP-1 cells. The position, number, and length of the prenyl groups had a marked influence on the inhibitory activity of the prenylfavonoids towards MCP-1 and IL-6 production. The α,β-unsaturated carbonyl moiety present in chalcones such as XN was not an absolute requirement for inhibitory activity, as the saturated XN derivative, tetrahydroxanthohumol (TX), showed inhibitory activity comparable to XN. With the aim to determine the mechanism of the observed anti-inflammatory effects, cellular protein levels of Toll-like receptor 4 (TLR4) were measured by Western blot 24 h following coexposure of THP-1 cells to LPS and either XN, TX, or IX. Only XN reduced the cellular TLR4 protein content. Therefore, an additional hypothesis was developed for an anti-inflammatory mechanism that involves the TLR4 coreceptor myeloid differentiation protein-2 (MD-2), which provides the actual binding site for LPS. Molecular docking studies showed that the complementarity of prenylated flavonoids with the hydrophobic MD-2 pocket (indicating goodness of fit) directly predicted their relative ability to inhibit MCP-1 and IL-6 production. In conclusion, prenylated flavonoids may suppress LPS-induced TLR4 activation at least partly by interfering with LPS binding to the TLR4 coreceptor MD-2, and XN (but not other prenylflavonoids) exerts an additional anti-inflammatory effect by downregulating the cellular TLR4 protein content.

Plectranthus barbatus: a review of phytochemistry, ethnobotanical uses and pharmacology - part 2.

Abstract: Plectranthus barbatus andr. is one of the most important species of the genus Plectranthus L' Herit. (Lamiaceae), with a wide variety of traditional medicinal uses in Hindu and Ayurvedic traditional medicine as well as in the folk medicine of Brazil, tropical Africa and China. The plant has therefore been an attractive target for intensive chemical and pharmacological studies up to now. This review presents data about the phytochemistry, ethnobotanical uses and pharmacology of Plectranthus barbatus as well as the pharmacology of its constituents. In addition to essential oil, abietane diterpenoids and 8,13-epoxy-labd-14-en-11-one diterpenoids are the main constituents found in Plectranthus barbatus. The major ethnobotanical uses are for intestinal disturbance and liver fatigue, respiratory disorders, heart diseases and certain nervous system disorders. Forskolin as one of the major constituents with its unique adenylyl cyclase activation that underlies the wide range of pharmacological properties could explain the different traditional uses of Plectranthus barbatus. Forskolin is involved in a number of patented pharmaceutical preparations used as over-the-counter drugs for the treatment of several ailments. However, the water-insoluble nature of forskolin limits its clinical usefulness. Forskolin thus served as a prototype for the development of 6-(3-dimethylaminopropionyl)forskolin hydrochloride (NKH477) as a potent water-soluble forskolin derivative that finds use in the therapy for a number of diseases especially of the cardiovascular system.

Systems biology-based diagnostic principles as pillars of the bridge between Chinese and Western medicine

Abstract: Innovative systems approaches to develop medicine and health care are emerging from the integration of Chinese and Western medicine strategies, philosophies and practices. The two medical systems are highly complementary as the reductionist aspects of Western medicine are favourable in acute disease situations and the holistic aspects of Chinese medicine offer more opportunities in chronic conditions and for prevention. In this article we argue that diagnosis plays a key role in building the bridge between Chinese and Western medicine. Recent advances in the study of health, healing, placebo effects and patient-physician interactions will be discussed pointing out the development of a system-based diagnosis. Especially, a system biology-based diagnosis can be used to capture phenotype information, leading towards a scientific basis for a more refined patient characterization, new diagnostic tools and personalized heath strategies. Subtyping of rheumatoid arthritis patients based on Chinese diagnostic principles is discussed as an example. New insights from this process of integrating Western and Chinese medicine will pave the way for a patient-centred health care ecosystem.

The Effect of Thymoquinone, the Main Constituent of Nigella sativa on Tracheal Responsiveness and White Blood Cell Count in Lung Lavage of Sensitized Guinea Pigs

Abstract: In previous studies, the relaxant, anticholinergic (functional antagonism) and antihistaminic, effects of Nigella sativa have been demonstrated on guinea pig tracheal chains. In the present study, the prophylactic effect of thymoquinone (one of the constituents of Nigella sativa) on tracheal responsiveness and white blood cell (WBC) count in lung lavage of sensitized guinea pigs was examined. Four groups of sensitized guinea pigs to ovalbumin (OA) were given drinking water alone (group S), drinking water containing low or high concentrations of thymoquinone (S + LTQ and S + HTQ groups) or inhaled fluticasone propionate (FP 250 microg) twice a day (positive control group) (n = 7, for all groups). Tracheal responses of control and four groups of sensitized animals to methacholine at an effective concentration causing 50 % of maximum response (EC(50) M) were measured. Tracheal responses to 0.1 % OA, relative to contraction induced by 10 microM methacholine were also examined. Total WBC and its differential count in lung lavage were also measured. The tracheal responsiveness to methacholine, OA and WBC of S guinea pigs was significantly higher than those of controls (p < 0.001 for all cases). Tracheal responsiveness in S + LTQ, S + HTQ, and FP groups to both methacholine (p < 0.05 to p < 0.001) and OA (p < 0.001 for all cases) was significantly decreased compared to that of the S group. Total WBC was also decreased in all experimental groups compared to that of the S group (p < 0.001 for all groups). There was an increase in eosinophils and a decrease in neutrophils, lymphocytes and monocytes in the S animals compared to the controls (p < 0.001 for all cases). Treatment with both concentrations of thymoquinone and FP variably improved differential WBC count changes compared to the S animals (nonsignificant to p < 0.001). The improvement in tracheal responsiveness, total WBC, eosinophils and lymphocytes changes in the S animals treated with both concentrations of TQ were significantly greater than those of FP (p < 0.05 to p < 0.001). These results showed a preventive effect of thymoquinone, one constituent of N. sativa, on tracheal responsiveness and inflammatory cells of lung lavage of sensitized guinea pigs which was comparable or even greater than that of the inhaled steroid.

Raspberry ketone increases both lipolysis and fatty acid oxidation in 3T3-L1 adipocytes.

Abstract: Raspberry ketone (RK) is a natural phenolic compound of the red raspberry. The dietary administration of RK to male mice has been reported to prevent high-fat diet-induced elevation in body weight and to increase lipolysis in white adipocytes. To elucidate a possible mechanism for the antiobesity action of RK, its effects on the expression and the secretion of adiponectin, lipolysis, and fatty acid oxidation in 3T3-L1 were investigated. Treatment with 10 μM of RK increased lipolysis significantly in differentiated 3T3-L1 cells. An immunoassay showed that RK increased both the expression and the secretion of adiponectin, an adipocytokine mainly expressed and secreted by adipose tissue. In addition, treatment with 10 μM of RK increased the fatty acid oxidation and suppressed lipid accumulation in 3T3-L1 adipocytes. These findings suggest that RK holds great promise as an herbal medicine since its biological activities alter the lipid metabolism in 3T3-L1 adipocytes.

The Effects of the Diterpenes Isolated from the Brazilian Brown Algae Dictyota pfaffii and Dictyota menstrualis against the Herpes Simplex Type-1 Replicative Cycle

Abstract: We describe in this paper that the diterpenes 8,10,18-trihydroxy-2,6-dolabelladiene ( 1) and (6 R)-6-hydroxydichotoma-4,14-diene-1,17-dial ( 2), isolated from the marine algae DICTYOTA PFAFFII and D. MENSTRUALIS, respectively, inhibited HSV-1 infection in Vero cells. We initially observed that compounds 1 and 2 inhibited HSV-1 replication in a dose-dependent manner, resulting in EC (50) values of 5.10 and 5.90 microM, respectively, for a multiplicity of infection (MOI) of 5. Moreover, the concentration required to inhibit HSV-1 replication was not cytotoxic, resulting in good selective index (SI) values. Next, we found that compound 1 sustained its anti-herpetic activity even when added to HSV-1-infected cells at 6 h after infection, while compound 2 sustained its activity for up to 3 h after infection, suggesting that these compounds inhibit initial events during HSV-1 replication. We also observed that both compounds were incapable of impairing HSV-1 adsorption and penetration. In addition, the tested molecules could decrease the contents of some HSV-1 early proteins, such as UL-8, RL-1, UL-12, UL-30 and UL-9. Our results suggest that the structures of compounds 1 and 2, Brazilian brown algae diterpenes, might be promising for future antiviral design.