Antimalarial Activity of Cryptolepine and Isocryptolepine,Alkaloids Isolated from Cryptolepis sanguinolenta

Cryptolepis sanguinolenta extracts are currently used by African herbalists to cure malaria but the compounds involved in its antimalarial activity have not been identified. Two alkaloids, cryptolepine and isocryptolepine, have been isolated from the roots of C. sanguinolenta and their antimalarial activity evaluated. Both alkaloids possess intrinsic inhibitory activity against the human malaria parasite, Plasmodium falciparum in vitro , whatever the chloroquine-resistance status of the strains used. Cryptolepine was slightly more efficient for parasite killing with an IC₅₀ in the range of 0.2 to 0.6 μMSC compared with an IC₅₀ of about 0.8 μMSC for isocryptolepine. The antimalarial activity of cryptolepine was confirmed in vivo on the rodent malarial parasites Plasmodium vinckei petteri and Plasmodium berghei ANKA.     

Antimalarial Activity of Cryptolepine and Some Other Anhydronium Bases

Eight naturally occurring anhydronium bases and the synthetic quaternary compound N b -methylharmalane were tested against Plasmodium falciparum (strain K1) in vitro . Cryptolepine was found to have similar activity to that of chloroquine but alstonine, 5,6-dihydroflavopereirine, matadine, N b -methylharmalane, melinonine F, normelinonine F, strychnoxanthine and serpentine were found to have little activity. Cryptolepine, given orally to mice infected with Plasmodium berghei berghei was found to have moderate antimalarial activity; parasitaemia was suppressed by 80% at 50 mg/kg/day.     

In vitro and in vivo antimalarial activity of cryptolepine,a plant-derived indoloquinoline

Cryptolepine is an indoloquinoline, high yields of which may be extracted from the roots of the West African shrub Cryptolepis sanguinolenta. The use of this plant as a traditional treatment for malaria is widespread in Ghana and is reported to be clinically effective. We have tested cryptolepine for in vitro antiplasmodial activity against the multidrug resistant (K1) strain of Plasmodium falciparum and found it to be highly active with an IC₅₀ value of 0.031±0.0085 (SE) μg/mL, equivalent to 0.134±0.037 μM (n = 3). In a 4-day suppression test there was, however, no significant reduction in parasitaemia in P. berghei-infected mice treated subcutaneously with cryptolepine (7–113 mg/kg/d×4), when compared with untreated controls. Like 9-aminoacridine, this compound appears to intercalate with DNA and this may explain the high degree of antimalarial activity demonstrated in vitro.     

Cryptolepine,isolated from Sida acuta,sensitizes human gastric adenocarcinoma cells to TRAIL‐induced apoptosis

Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2–3). Compound 1 showed strong activity in overcoming TRAIL‐resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm . Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL‐induced apoptosis at the aforementioned concentrations. Copyright © 2010 John Wiley & Sons, Ltd.     

Homopseudopteroxazole,a new antimycobacterial diterpene alkaloid from Pseudopterogorgia elisabethae

In the course of our study to find novel antimycobacterial secondary metabolites from Caribbean gorgonian octocorals, we have isolated a new diterpene alkaloid, namely, homopseudopteroxazole (1), as a minor constituent of the hexane extract from the sea plume Pseudopterogorgia elisabethae. Its structure was deduced by interpretation of combined spectroscopic data, including extensive 1D and 2D NMR measurements, and NMR spectral comparisons with known amphilectane models. Biological screening studies indicate that homopseudopteroxazole (1) is a strong growth inhibitor of Mycobacterium tuberculosis H(37)Rv.     

The antimycobacterial components of hops (Humulus lupulus) and their dereplication

Bioassay-guided fractionation of a hexane extract of strobile hops (Humulus lupulus) was undertaken to isolate and characterize the antimycobacterial constituents using the fast-growing mycobacterial species Mycobacterium fortuitum. Activity was associated with a low polarity fraction and 1H NMR spectra indicated the presence of a fatty acid mixture with unsaturated components. GC-MS of the derivatives indicated the presence of palmitic, stearic and oleic acids with small quantities of lignoceric, arachidic, behenic and linoleic acids. These compounds were assessed against M. fortuitum and all saturated fatty acids were inactive at concentrations greater than 256 microg/ml, whereas the unsaturated fats oleic and linoleic acids displayed minimum inhibitory concentrations of between 4 and 16 microg/ml against the fast-growing species tested. The widespread occurrence of these components could render screening for antimycobacterials from natural sources highly problematic without adequate dereplication. We propose that GC-MS of derivatised components of lipophilic extracts be a first step before any antimycobacterial bioassay-guided study, as this technique is the method of choice for dereplication of fatty acids.     

东北鹤虱中一个具有抗菌活性的新喹酮类生物碱

目的 对东北鹤虱的化学成分进行分离和结构鉴定并进行抗菌活性测定。方法 通过硅胶柱色谱、凝胶柱色谱等分离方法从东北鹤虱的BuOH提取物中分离得到一个新喹酮类化合物，以有机波谱方法(^1H-NMR、^13C-NMR、2D-NMR、HR-MS，UV和IR等)进行结构鉴定，并以纸片琼脂扩散法进行抗菌活性测定。结果 从东北鹤虱中分离出一个新喹酮类生物碱，鉴定为8-甲氧基-4-喹酮-2-羧酸，并对铜绿假单胞菌、肠致病性大肠埃希菌、肺炎克雷伯菌及表皮葡萄球菌具有抗菌活性。结论 该化合物为一新化合物，并具有抗菌活性。     

Honeydew honey as a potent antibacterial agent in eradication of multi-drug resistant Stenotrophomonas maltophilia isolates from cancer patients

Multi-drug resistance in nosocomial pathogens is a continually evolving and alarming problem in health care units. Since ancient times, honey has been used successfully for the treatment of a broad spectrum of infections with no risk of resistance development. This study investigated the antibacterial activity of two natural honeys, namely honeydew and manuka, against 20 nosocomial multi-drug resistant Stenotrophomonas maltophilia (S. maltophilia) isolates from cancer patients. An antibiotic susceptibility test was carried out using the disk diffusion method with 20 antibiotic disks. The antibacterial activity of honey was determined using a broth dilution method. The concentration of honey used in the study was within the range of 3.75% to 25% (w/v). All 20 clinical isolates were multi-drug resistant against 11 to 19 antibiotics. The MICs for honeydew honey ranged from 6.25% to 17.5%, while those for active manuka honey ranged from 7.5% to 22.5%. Honeydew honey had lower MICs than manuka honey against 16 of the tested isolates. This study showed that Slovak honeydew honey has exceptional antibacterial activity against multi-drug resistant S. maltophilia isolates and was more efficient than manuka honey (UMF 15+). Honeydew honey with strong antibacterial activity could be used as a potential agent to eradicate multi-drug resistant clinical isolates.     

A new class of alkaloids from a dendrobatid poison frog: a structure for alkaloid 251F.

Alkaloids of a new class are present in skin extracts of the dendrobatid poison frog, Minyobates bombetes, of Colombia. The structure of the major alkaloid of this class, 251F, has been determined as a trimethylcyclopenta[b]quinolizidinemethanol 1 by nmr, gc-Ft-ir, and ms studies including ms-ms. At least nine congeners of 251F were detected in these extracts.     

A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with potent antimalarial activity against a multidrug resistant Plasmodium falciparum strain

Ethnopharmacological relevance

The aerial components of Meconopsis simplicifolia (D. Don) Walpers are indicated in Bhutanese traditional medicine for treating malaria, coughs and colds, and the infections of the liver, lung and blood. This study is to validate the ethnopharmacological uses of this plant and also identify potent antimalarial drug leads through bioassays of its crude extracts and phytochemical constituents.

Materials and methods

Meconopsis simplicifolia (D. Don) Walpers was collected from Bhutan and its crude MeOH extract was subjected to acid-base fractionation. Through repeated extractions, separations and spectroscopic analysis, the alkaloids obtained were identified and tested for their antimalarial and cytotoxicity activities.

Results

Phytochemical studies resulted in the isolation of one new protoberberine type alkaloid which we named as simplicifolianine and five known alkaloids: protopine, norsanguinarine, dihydrosanguinarine, 6-methoxydihydrosanguinarine and oxysanguinarine. Among the five of the alkaloids tested, simplicifolianine showed the most potent antiplasmodial activities against the Plasmodium falciparum strains, TM4/8.2 (chloroquine–antifolate sensitive strain) and K1CB1 (multidrug resistant strain) with IC₅₀ values of 0.78 μg/mL and 1.29 μg/mL, respectively. The compounds tested did not show any significant cytotoxicity activities against human oral carcinoma KB cells and normal Vero cells of African kidney epithelial cells.

Conclusions

This study validated the traditional uses of the plant for the treatment of malaria and identified a new alkaloid, simplicifolianine as a potential antimalarial drug lead.     

Haploscleridamine, a novel tryptamine-derived alkaloid from a sponge of the order haplosclerida: an inhibitor of cathepsin K

As part of a search for novel inhibitors of cathepsin K, the MeOH extract of a Micronesian sponge of the order Haplosclerida was shown to be active. Bioassay-guided fractionation of the extract yielded halitoxins, tryptamine, and a novel tryptamine-derived alkaloid, haploscleridamine (1). The tetrahydro-beta-carboline structure of haploscleridamine (1) was elucidated through spectral techniques. Haploscleridamine (1) was found to be an inhibitor of cathepsin K with an IC(50) of 26 microM.     

Isolation of a Novel Antibacterial Phenyl Thioketone from the Seagrass,Cymodocea serrulata

A total of 40 extract types of varying polarities from commonly occurring seagrasses were tested for their antibacterial efficiency against 14 clinically isolated human pathogens using agar well diffusion technique. The extracts from acetone of Cymodocea serrulata expressed moderate broad span of activity against a range of gram‐positive and gram‐negative isolates that were at least resistant to five of the commercially available antibiotics at a minimal concentration of 10 µg. The active extracts of C. serrulata that showed maximal inhibitions were purified using column chromatography that afforded six compounds (a–f). Compound f elicited pronounced inhibitions against Escherichia coli with minimal inhibitory concentration values of 1–3 µg concentration using micro‐dilution method. The active compound was identified as phenyl thioketone using various spectral analyses. This is the first investigation that reveals thioketone functionality from this seagrass species possessing antibacterial actions. This study indicates that there are thiocarbonyl groups from marine floral sources too, which could be possibly used for therapeutic purposes. Copyright © 2015 John Wiley & Sons, Ltd.     

姜黄属中药活血化瘀功效关联物质研究进展

姜黄、莪术、片姜黄和郁金均属于姜黄属中药,是临床常用活血化瘀代表药,多用于治疗瘀血阻滞引起的闭经痛经,胸痹心痛,风湿痹痛等.现代研究表明,姜黄属中药中的标识性成分姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素、莪术二酮、吉马酮、莪术醇及β-榄香烯等均具有改善血液流变性、抗血小板聚集、抗血栓、抗炎、抗肿瘤、抗纤维化等活血化瘀作...     

广藿香内生真菌索氏平脐蠕孢中1个新旋孢腔菌醌类化合物及其生物活性

目的研究分离自广藿香内生真菌索氏平脐蠕孢Bipolaris sorokiniana A606的活性次级代谢产物的化学结构及其活性。方法运用正相硅胶、C18反相硅胶、Sephadex LH-20凝胶和HPLC等色谱技术对菌株B.sorokiniana A606发酵液的醋酸乙酯萃取物进行分离纯化,并通过各种谱学分析方法进行结构鉴定;采用SRB染色法和滤纸片法分别测定化合物的细胞毒和抗菌活性。结果从B.sorokiniana A606发酵液的醋酸乙酯萃取物中分离得到2个化合物,分别鉴定为(3S*,4a S*,6a S*,12b S*)-3-(2-羟基-2-丙烷基)-6a,12b-二甲基-9-[(2R*,4R*)-2-(4-甲基-3-己酮基)]-1,2,3,4a,5,6-六氢吡喃并[3,2-a]氧杂蒽-8,11-二酮(1)和precochlioquinol D(2)。结论化合物1为新化合物,命名为11-羟基-12,13-去氢旋孢腔菌醌B。化合物2为首次从该属真菌中分离得到。其中化合物1具有细胞毒和抗菌活性。     

Diabetic kidney disease treated with a modified Shenzhuo formula derived from Traditional Chinese Medicine: a case report

INTRODUCTION: Diabetic kidney disease(DKD) is one of the most common microvascular complications of diabetes mellitus and is the leading cause of end-stage renal disease. DKD seriously affects the quality of life of patients and brings heavy economic burden to the country. At present, the pathogenesis of DKD is not entirely clear, and clinical treatment is mainly to control blood glucose and lower blood pressure and urine protein. However,the clinical effect is not satisfactory.CASE PRESENTATION: A female patient, aged 72 years, first visited our hospital endocrinology clinic,and was diagnosed with DKD. She suffered from fatigue, cold sensation in the lower extremities, convulsion of the lower limbs and frequent urination at night. She had a dark purple tongue with white and yellow fur and sublingual varices. Accessory examinations showed that her fasting blood glucose was 5.7 mmol/L, serum creatinine 159 μmol/L,blood urea nitrogen 13.6 μmol/L, blood uric acid493 μmol/L, and blood pressure 138/65 mm Hg.The patient received Traditional Chinese Medicine treatment of the modified Shenzhuo formula[Huangqi(Radix Astragali Mongolici), Dahuang(Radix Et Rhizoma Rhei Palmati), Shuizhi(Hirudo) and Danshen(Radix Salviae Miltiorrhizae)] for 7 years and achieved good results.CONCLUSION: This case provides a specific treatment plan and an effective reference for clinical application of Traditional Chinese Medicine for treating DKD. This may be an alternative treatment for DKD.     

Palbinone,a novel terpenoid from Paeonia albiflora: A potent inhibitory activity on human monocyte interleukin-1β

Palbinone, a novel terpenoid from the roots of Paeonia albiflora, has a very strong inhibitory activity on the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) linked 3α-hydroxysteroid dehydrogenase (3α-HSD) of rat liver cytosol and showed a significant inhibitory activity on human monocyte interleukin-1β, a polypeptide which is though to play an important role in inflammation. In contrast the enzymes cyclooxygenase (CO), thromboxane A synthase (TX) and 5-lipoxygenase (LO) were not significantly inhibited by palbinone when it was compared with tenokisicum, indomethacin, imidazole and 2, 3, 5-trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1, 4-benzoquinone (AA-861) as positive controls under similar experimental conditions. The activity of palbinone was highly selective since it inhibited strongly only human monocyte interleukin-1β and did not show any significant activity on CO, TX and LO.     

Paeoniflorin, a potent natural compound, protects PC12 cells from MPP and acidic damage via autophagic pathway

Ethnopharmacological relevance

Paeoniflorin (PF) is the principal bioactive component of Radix Paeoniae alba, which is widely used in Traditional Chinese Medicine for the treatment of neurodegenerative disorders such as Parkinson's disease (PD).

Aim of the study

To evaluate the neuroprotective effects of PF on MPP⁺- or acid- (pH 5.0) induced injury in cultured PC12 cells and to investigate the activity of autophagy-lysosome pathway (ALP). Amiloride (Ami), a non-selective blocker of acid-sensing ion channels (ASICs), as a positive control drug, since it is neuroprotective in rodent models of PD.

Materials and methods

The cell viability was analyzed with MTT assay. The cell injury was assessed by lactate dehydrogenase (LDH) assay. Flow cytometry and Western blot analysis were used to study the apoptotic, calcium influx and autophagic mechanisms.

Results

Ami (100 μM) and PF (50 μM) both protected PC12 cells against MPP⁺- or acid-induced injury as assessed by MTT assay, lactate dehydrogenase release, and apoptosis rate. The concentrations of cytosolic free Ca²⁺ were raised after exposure to MPP⁺ or acidosis, while Ami and PF both reduced the influx of Ca²⁺. More importantly, we found that the mechanisms of neuroprotective effects of Ami and PF were closely associated with the upregulation of LC3-II protein, which is specifically associated with autophagic vacuole membranes. Furthermore, application of MPP⁺ or acid induced the overexpression of LAMP2a, which is directly correlated with the activity of the chaperone-mediated autophagy pathway. However, Ami and PF inhibited the overexpression of LAMP2a.

Conclusions

Our data provide the first experimental evidence that PF modulates autophagy in models of neuron injury, as well as providing the first indication of a relationship between ASICs and ALP.     

Herbal modulation of drug bioavailability: enhancement of rifampicin levels in plasma by herbal products and a flavonoid glycoside derived from Cuminum cyminum

The bioavailability of rifampicin (RIF) in a fixed dose combination (FDC) used for the treatment of tuberculosis remains an area of clinical concern and several pharmaceutical alternatives are being explored to overcome this problem. The present study presents a pharmacological approach in which the bioavailability of a drug may be modulated by utilizing the herb-drug synergism. The pharmacokinetic interaction of some herbal products and a pure molecule isolated from Cuminum cyminum with RIF is shown in this paper. An aqueous extract derived from cumin seeds produced a significant enhancement of RIF levels in rat plasma. This activity was found to be due to a flavonoid glycoside, 3',5-dihydroxyflavone 7-O-beta-D-galacturonide 4'-O-beta-D-glucopyranoside (CC-I). CC-I enhanced the Cmax by 35% and AUC by 53% of RIF. The altered bioavailability profile of RIF could be attributed to a permeation enhancing effect of this glycoside.     

A water soluble extract from Uncaria tomentosa (Cat's Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin

Cat's Claw (Uncaria tomentosa) water extracts, essentially free of oxindole alkaloids, have been shown to possess a broad spectrum of biological activity including DNA repair enhancement and antiinflammatory properties. These two biological mechanisms are key molecular targets to develop treatments that protect skin exposed to ultraviolet light from the sun. Because C-Med-100, a Cat's Claw water extract, is the only documented natural source of components that can up-regulate simultaneously both DNA repair and antiinflammation, its ability to modulate DNA repair in human skin organ cultures was undertaken. For this purpose skin cultures were treated with or without 5 mg/mL C-Med-100, irradiated with 0-100 mJ/cm2 UVB, and microscopically analysed for necrosis as well as the level of pyrimidine dimers using immunofluorescent TT-dimer antibody staining. The data clearly demonstrated that co-incubation with C-Med-100 reduced skin cell death from UV exposure, and this protection was accounted for by a concomitant increase in DNA repair. Based on these results, it was concluded that C-Med-100 was a natural plant extract worthy of further consideration as a sunscreen product.     

Musclide-A1: A novel Ca2+-dependent protein kinase activator derived from musk and its cardiotonic potentiating action in guinea-pig cardiac muscles

Musclide-A1 (6-methyl-2, 5-heptanediol 5-(hydrogen sulfate)) was isolated from musk, a dried secretion from the preputial follicle of musk deer, Moschus moschiferus Linn. Musclide (100 μg/mL), a water-soluble extract, and musclide-A1 (30 μg/mL) potentiated β-adrenergic cardiotonic action in guinea-pig papillary muscles. Musclide-A1 at 130 μM or 1,2-dioctanoylglycerol at 200 μM potentiated the positive inotropic action induced by the maximal concentration of isoproterenol (258 nM). The potentiation was suppressed by 3 nM staurosporine or 1 μM H-7, an inhibitor of Ca²⁺-dependent protein kinase. Musclide-A1 at 4 and 8 μM activated protein kinase C and other Ca²⁺-dependent protein kinase in ventricular muscles of guinea-pig. The activation of Ca²⁺-dependent protein kinase was completely suppressed by 3 nM saturosporine. The activity of musclide-A1 (4 μM) was comparable to that of 1,2-dioctanoylglycerol (4 μM, the optimum concentration to stimulate protein kinase C), and were inhibited completely by 30 nM staurosporine. These results indicate that one mechanism of cardiotonic potentiation induced by musk, may be in part due to the activation of protein kinase C and other Ca²⁺-dependent protein kinases.