Antidiabetic and antioxidant properties of Boswellia sacra oleo-gum in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes is a metabolic disorder requiring the administration of insulin or other oral hypoglycemic medicines. Although metformin is a popular prescription for type 2 diabetes, long-term use of chemotherapy-based diabetes medications can be hazardous. As a result, novel plant medicines with a high concentration of bioactive molecules, no harmful side effects, and potent pharmacological effects must be found. Edible Boswellia sacra (B. sacra) Flueck oleo-gum resin is widely utilized to treat many clinical diseases in traditional Arab, Chinese, African, and Ayurvedic medicine. OBJECTIVE: The goal of this study was to examine the possible therapeutic benefits of several B. sacra oleo-gum resin extracts on rat streptozotocin (STZ)-induced hyperglycemia (Type II). MATERIALS AND METHODS: For 29 days, hyperglycemic rats are given either metformin (the reference drug; 250 mg/kg body weight per day) or several B. sacra extracts (ethanol, methanol, hydrodistilled, ethyl acetate, and acetone extracts) at doses of 200 or 400 mg/kg/day. Blood glucose levels and body weights were measured before the initiation and at 7, 11, 16, 22, and 29 days after oral treatment. Furthermore, an oral glucose tolerance test (OGTT) was carried out. At the end of the study, the rats were euthanized, and blood samples were obtained to evaluate cytokines (interleukin (IL-)2 and IL-8), reduced glutathione (GSH), superoxide dismutase (SOD), and serum insulin levels. The pancreas and liver tissues were rapidly excised, washed, fixed, and kept in a 10% formalin buffer for histological examination. RESULTS: B. sacra's ethanolic extract had the greatest concentration of total pentacyclic triterpenic acid (PTA) (391.52 mg/g) in comparison to the other extracts. The lower dose of B. sacra ethanol extract, 200 mg/kg/day, reduces blood glucose levels more efficiently than the higher dose of 400 mg/kg/day. In a 180-min OGTT, diabetic rats given ethanol extract (200 mg/kg) performed no better than control rats and even outperformed those given the reference medication metformin. Additionally, ethanol extract (200 mg/kg)- or metformin-treated diabetic rats gained weight. This was associated with a significant (p < 0.05) decrease in serum levels of IL-2 and IL-8, a reduction in oxidative stress as evidenced by a significant (p < 0.05) increase in SOD and GSH compared to the untreated diabetic group, and a significant (p < 0.05) increase in serum insulin levels compared to normal plasma rat levels. These discoveries, which were eventually confirmed by histochemical assays, indicated that the ethanol extract of B. sacra greatly enhanced the cellular architecture of pancreatic and liver cells. CONCLUSION: The present investigation indicates that the ethanol extract of B. sacra oleo-gum resin, which contains a high proportion of acetyl-ß-boswellic acid (ß-ABA) and acetyl-11-keto-ß-boswellic acid (AKBA), possesses antihyperglycemic, anti-inflammatory, and anti-oxidant properties for the first time to our knowledge. Additionally, it restores hepatic cells in STZ-induced diabetic rats and protects the pancreas against oxidative damage. Thus, the current study's results give a scientific rationale for the use of B. sacra in the medical management of diabetes and associated complications. More investigation into the metabolic profiles of these extracts must be conducted to establish the precise mechanism of action of the ethanol extract.

Therapeutic potential of boswellic acids: an update patent review (2016-2023).

INTRODUCTION: Boswellic acids (BAs) are a group of pentacyclic triterpenoids of the ursane and oleanane type. They have shown very interesting biological properties that have led to the development of a number of synthesis protocols. Both natural BAs and their synthetic derivatives may be useful in the treatment of a variety of cancers, viral infections and inflammatory diseases. AREAS COVERED: This review covers patents relating to the therapeutic activities of natural BAs and their synthetic derivatives. The latest patented studies of boswellic acids (are summarized by using the keywords 'boswellic acid,' in SciFinder, PubMed, and Google Patents and databases in the year from 2016 to 2023. EXPERT OPINION: Boswellic acids have shown potent antiviral, anticancer and anti-inflammatory potential. Few BAs analogues have been prepared by modification at the C24-CO2H functional groups. In particular, the C-24 amide and amino analogues have shown enhanced anticancer effects compared to the parent AKBA. In addition, BAs have the ability to form conjugates with other antiviral, anti-inflammatory and anticancer drugs that synergistically enhance their biological efficacy. In addition, this conjugation strategy will increase the solubility and bioavailability of BAs, which is one of the most important issues in the development of BAs.

Transgenerational hormesis in healthy aging and antiaging medicine from bench to clinics: Role of food components.

Neurodegenerative diseases have multifactorial pathogenesis, mainly involving neuroinflammatory processes. Finding drugs able to treat these diseases, expecially because for most of these diseases there are no effective drugs, and the current drugs cause undesired side effects, represent a crucial point. Most in vivo and in vitro studies have been concentrated on various aspects related to neurons (e.g. neuroprotection), however, there has not been focus on the prevention of early stages involving glial cell activation and neuroinflammation. Recently, it has been demonstrated that nutritional phytochemicals including polyphenols, the main active constituents of the Mediterranean diet, maintain redox balance and neuroprotection through the activation of hormetic vitagene pathway. Recent lipidomics data from our laboratory indicate mushrooms as strong nutritional neuronutrients with strongly activity against neuroinflammation in Meniere' diseaseas, a model of cochleovestibular neural degeneration, as well as in animal model of traumatic brain injury, or rotenone induced parkinson's disease. Moreover, Hidrox®, an aqueous extract of olive containing hydroxytyrosol, and Boswellia, acting as Nrf2 activators, promote resilience by enhancing the redox potential, and thus, regulate through hormetic mechanisms, cellular stress response mechanisms., Thus, modulation of cellular stress pathways, in particular vitagenes system, may be an innovative approach for therapeutic intervention in neurodegenerative disorders.

Molecular Modes of Action of an Aqueous Nerium oleander Extract in Cancer Cells In Vitro and In Vivo.

Cancer drug resistance remains a major obstacle in clinical oncology. As most anticancer drugs are of natural origin, we investigated the anticancer potential of a standardized cold-water leaf extract from Nerium oleander L., termed Breastin. The phytochemical characterization by nuclear magnetic resonance spectroscopy (NMR) and low- and high-resolution mass spectrometry revealed several monoglycosidic cardenolides as major constituents (adynerin, neritaloside, odoroside A, odoroside H, oleandrin, and vanderoside). Breastin inhibited the growth of 14 cell lines from hematopoietic tumors and 5 of 6 carcinomas. Remarkably, the cellular responsiveness of odoroside H and neritaloside was not correlated with all other classical drug resistance mechanisms, i.e., ATP-binding cassette transporters (ABCB1, ABCB5, ABCC1, ABCG2), oncogenes (EGFR, RAS), tumor suppressors (TP53, WT1), and others (GSTP1, HSP90, proliferation rate), in 59 tumor cell lines of the National Cancer Institute (NCI, USA), indicating that Breastin may indeed bypass drug resistance. COMPARE analyses with 153 anticancer agents in 74 tumor cell lines of the Oncotest panel revealed frequent correlations of Breastin with mitosis-inhibiting drugs. Using tubulin-GFP-transfected U2OS cells and confocal microscopy, it was found that the microtubule-disturbing effect of Breastin was comparable to that of the tubulin-depolymerizing drug paclitaxel. This result was verified by a tubulin polymerization assay in vitro and molecular docking in silico. Proteome profiling of 3171 proteins in the NCI panel revealed protein subsets whose expression significantly correlated with cellular responsiveness to odoroside H and neritaloside, indicating that protein expression profiles can be identified to predict the sensitivity or resistance of tumor cells to Breastin constituents. Breastin moderately inhibited breast cancer xenograft tumors in vivo. Remarkably, in contrast to what was observed with paclitaxel monotherapy, the combination of paclitaxel and Breastin prevented tumor relapse, indicating Breastin's potential for drug combination regimens.

Frankincense diterpenes as a bio-source for drug discovery.

INTRODUCTION: Frankincense (Boswellia sp.) gum resins have been employed as an incense in cultural and religious ceremonies for many years. Frankincense resin has over the years been employed to treat depression, inflammation, and cancer in traditional medicines. AREAS COVERED: This inclusive review focuses on the significance of frankincense diterpenoids, and in particular, incensole derivatives for establishment future treatments of depression, neurological disorders, and cancer. The authors survey the available literature and furnish an overview of future perspectives of these intriguing molecules. EXPERT OPINION: Numerous diterpenoids including cembrane, prenylaromadendrane, and the verticillane-type have been isolated from various Boswellia resins. Cembrane-type diterpenoids occupy a crucial position in pharmaceutical chemistry and related industries because of their intriguing biological and encouraging pharmacological potentials. Several cembranes have been reported to possess anti-Alzheimer, anti-inflammatory, hepatoprotective, and antimalarial effects along with a good possibility to treat anxiety and depression. Although some slight drawbacks of these compounds have been noted, including the selectivity of these diterpenoids, there is a great need to address these in future research endeavors. Moreover, it is vitally important for medicinal chemists to prepare libraries of incensole-heterocyclic analogs as well as hybrid compounds between incensole or its acetate and anti-depressant or anti-inflammatory drugs.

Chemical Composition, Antibacterial Activity, and Antibiotic Potentiation of Boswellia sacra Flueck. Oleoresin Extracts from the Dhofar Region of Oman.

The emergence of MDR bacterial pathogens has directed antibiotic discovery research towards alternative therapies and traditional medicines. Boswellia sacra oleoresin (frankincense) was used to treat bacterial infections in traditional Arabian and Asian healing systems for at least 1000 years. Despite this, B. sacra extracts have not been rigorously tested for inhibitory activity against gastrointestinal pathogens or bacterial triggers of autoimmune diseases. Solvent extracts were prepared from Boswellia sacra oleoresins obtained from three regions near Salalah, Oman. MIC values were quantified against gastrointestinal pathogens and bacterial triggers of selected autoimmune diseases by disc diffusion and broth dilution methods. The antibacterial activity was also evaluated in combination with conventional antibiotics, and the class of interaction was determined by ΣFIC analysis. Isobolograms were used to determine the optimal ratios for synergistic combinations. Toxicity was evaluated by ALA and HDF cell viability bioassays. The phytochemical composition of the volatile components of all extracts was identified by nontargeted GC-MS headspace analysis. All methanolic extracts inhibited the growth of all of the bacteria tested, although the extracts prepared using Najdi oleoresin were generally more potent than the Sahli and Houjari extracts. Combinations of the methanolic B. sacra extracts and conventional antibiotics were significantly more effective in inhibiting the growth of several bacterial pathogens. In total, there were 38 synergistic and 166 additive combinations. Approximately half of the synergistic combinations contained tetracycline. All B. sacra extracts were nontoxic in the ALA and HDF cell viability assays. Nonbiased GC-MS headspace analysis of the methanolic extracts putatively identified a high diversity of monoterpenoids, with particularly high abundances of α-pinene. The antibacterial activity and lack of toxicity of the B. sacra extracts indicate their potential in the treatment and prevention of gastrointestinal and autoimmune diseases. Furthermore, the extracts potentiated the activity of several conventional antibiotics, indicating that they may contain resistance-modifying compounds.

Anti-Inflammatory Effects of a Polyphenol, Catechin-7,4'-O-Digallate, from Woodfordia uniflora by Regulating NF-κB Signaling Pathway in Mouse Macrophages.

Inflammation is a defense mechanism that protects the body from infections. However, chronic inflammation causes damage to body tissues. Thus, controlling inflammation and investigating anti-inflammatory mechanisms are keys to preventing and treating inflammatory diseases, such as sepsis and rheumatoid arthritis. In continuation with our work related to the discovery of bioactive natural products, a polyphenol, catechin-7,4'-O-digallate (CDG), was isolated from Woodfordia uniflora, which has been used as a sedative and remedy for skin infections in the Dhofar region of Oman. Thus far, no study has reported the anti-inflammatory compounds derived from W. uniflora and the mechanisms underlying their action. To investigate the effects of CDG on the regulation of inflammation, we measured the reduction in nitric oxide (NO) production following CDG treatment in immortalized mouse Kupffer cells (ImKCs). CDG treatment inhibited NO production through the downregulation of inducible nitric oxide synthase expression in lipopolysaccharide (LPS)-stimulated ImKCs. The anti-inflammatory effects of CDG were mediated via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, an important inflammatory-response-associated signaling pathway. Moreover, CDG treatment has regulated the expression of pro-inflammatory cytokines, such as IL-6 and IL-1ß. These results suggested the anti-inflammatory action of CDG in LPS-stimulated ImKCs.

Boswellic acids: privileged structures to develop lead compounds for anticancer drug discovery.

Introduction: Cancer has been identified to be the second major cause of death internationally as exemplified by ca. 9.6 million deaths in 2018 along with ca. 18 million new patients in 2018 that have been recorded. Natural boswellic acids (BAs) and their source, frankincense, have been reported to possess in vitro and in vivo anticancer effects toward various cancer cells.Areas covered: This comprehensive review focuses on the importance of boswellic acids (BAs) for the establishment of future treatments of cancer. Moreover, potent semisynthetic derivatives of BAs have been described along with their mode of action. In addition, important structural features of the semisynthetic BAs required for cytotoxic effects are also discussed.Expert opinion: Numerous semisynthetic BAs illustrate excellent cytotoxic effects. Of note, compounds bearing cyanoenone moieties in ring A, endoperoxides and hybrids display increased and more potent cytotoxic effects compared with other semisynthetic BAs. Moreover, BAs have the potential to conjugate or couple with other anticancer compounds to synergistically increase their combined anticancer effects. In addition, to get derived BAs to become lead anticancer compounds, future research should focus on the preparation of ring A cyanoenones, endoperoxides, and C-24 amide analogs.

Correction: Frankincense essential oil suppresses melanoma cancer through down regulation of Bcl-2/Bax cascade signaling and ameliorates heptotoxicity via phase I and II drug metabolizing enzymes.

[This corrects the article DOI: 10.18632/oncotarget.26930.].

Comparative Investigation of Frankincense Nutraceuticals: Correlation of Boswellic and Lupeolic Acid Contents with Cytokine Release Inhibition and Toxicity against Triple-Negative Breast Cancer Cells.

For centuries, frankincense extracts have been commonly used in traditional medicine, and more recently, in complementary medicine. Therefore, frankincense constituents such as boswellic and lupeolic acids are of considerable therapeutic interest. Sixteen frankincense nutraceuticals were characterized by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), revealing major differences in boswellic and lupeolic acid compositions and total contents, which varied from 0.4% to 35.7%. Frankincense nutraceuticals significantly inhibited the release of proinflammatory cytokines, such as TNF-α, IL-6, and IL-8, by LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood. Moreover, boswellic and lupeolic acid contents correlated with TNF-α, IL-1ß, IL-6, IL-8, and IL-10 inhibition. The nutraceuticals also exhibited toxicity against the human triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-453, and CAL-51 in vitro. Nutraceuticals with total contents of boswellic and lupeolic acids >30% were the most active ones against MDA-MB-231 with a half maximal inhibitory concentration (IC50) ≤ 7.0 µg/mL. Moreover, a frankincense nutraceutical inhibited tumor growth and induced apoptosis in vivo in breast cancer xenografts grown on the chick chorioallantoic membrane (CAM). Among eight different boswellic and lupeolic acids tested, ß-ABA exhibited the highest cytotoxicity against MDA-MB-231 with an IC50 = 5.9 µM, inhibited growth of cancer xenografts in vivo, and released proinflammatory cytokines. Its content in nutraceuticals correlated strongly with TNF-, IL-6, and IL-8 release inhibition.

Frankincense essential oil suppresses melanoma cancer through down regulation of Bcl-2/Bax cascade signaling and ameliorates heptotoxicity via phase I and II drug metabolizing enzymes.

Melanoma is a deadly form of malignancy and according to the World Health Organization 132,000 new cases of melanoma are diagnosed worldwide each year. Surgical resection and chemo/drug treatments opted for early and late stage of melanoma respectively, however detrimental post surgical and chemotherapy consequences are inevitable. Noticeably melanoma drug treatments are associated with liver injuries such as hepatitis and cholestasis which are very common. Alleviation of these clinical manifestations with better treatment options would enhance prognosis status and patients survival. Natural products which induce cytotoxicity with minimum side effects are of interest to achieve high therapeutic efficiency. In this study we investigated anti-melanoma and hepatoprotective activities of frankincense essential oil (FEO) in both in vitro and in vivo models. Pretreatment with FEO induce a significant (p < 0.05) dose-dependent reduction in the cell viability of mouse (B16-F10) and human melanoma (FM94) but not in the normal human epithelial melanocytes (HNEM). Immunoblot analysis showed that FEO induces down regulation of Bcl-2 and up regulation of BAX in B16-F10 cells whereas in FM94 cells FEO induced dose-dependent cleavage of caspase 3, caspase 9 and PARP. Furthermore, FEO (10 µg/ml) treatment down regulated MCL1 in a time-dependent manner in FM94 cells. In vivo toxicity analysis reveals that weekly single dose of FEO (1200 mg/kg body weight) did not elicit detrimental effect on body weight during four weeks of experimental period. Histology of tissue sections also indicated that there were no observable histopathologic differences in the brain, heart, liver, and kidney compare to control groups. FEO (300 and 600 mg/kg body weight) treatments significantly reduced the tumor burden in C57BL/6 mice melanoma model. Acetaminophen (750 mg/kg body weight) was used to induce hepatic injury in Swiss albino mice. Pre treatment with FEO (250 and 500 mg/kg body weight) for seven days retained hematology (complete blood count), biochemical parameters (AST, ALT, ALK, total bilirubin, total protein, glucose, albumin/globulin ratio, cholesterol and triglyceride), and the level of phase I and II drug metabolizing enzymes (cytochrome P450, cytochromeb5, glutathione-S-transferase) which were obstructed by the administration of acetaminophen. Further liver histology showed that FEO treatments reversed the damages (central vein dilation, hemorrhage, and nuclei condensation) caused by acetaminophen. In conclusion, FEO elicited marked anti-melanoma in both in vitro and in vivo with a significant heptoprotection.

Comparative Analysis of Pentacyclic Triterpenic Acid Compositions in Oleogum Resins of Different Boswellia Species and Their In Vitro Cytotoxicity against Treatment-Resistant Human Breast Cancer Cells.

Pentacyclic triterpenic acids from oleogum resins of Boswellia species are of considerable therapeutic interest. Yet, their pharmaceutical development is hampered by uncertainties regarding botanical identification and the complexity of triterpenic acid mixtures. Here, a highly sensitive, selective, and accurate method for the simultaneous quantification of eight boswellic and lupeolic acids by high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) was developed. The method was applied to the comparative analysis of 41 oleogum resins of the species B. sacra, B. dalzielli, B. papyrifera, B. serrata, B. carterii, B. neglecta, B. rivae, B. frereana, and B. occulta. Multivariate statistical analysis of the data revealed differences in the triterpenic acid composition that could be assigned to distinct Boswellia species and to their geographic growth location. Extracts of the oleogum resins exhibited cytotoxicity against the human, treatment-resistant, metastatic breast cancer cell line MDA-MB-231. Extracts from B. sacra were the most potent ones with an average IC50 of 8.3 ± 0.6 µg/mL. The oleogum resin of the B. sacra was further fractionated to enrich different groups of substances. The cytotoxic efficacy against the cancer cells correlates positively with the contents of pentacyclic triterpenic acids in Boswellia extracts.

Induction of HT-29 Colon Cancer Cells Apoptosis by Pyrogallol with Growth Inhibiting Efficacy Against Drug-Resistant Helicobacter pylori.

BACKGROUND: Colon cancer is the most aggressive form of cancers, that causes 0.5 million deaths per year around the globe. Targeting colon cancer by conventional therapeutic options elicits toxicity. Traditional medicines take a lead to alleviate the existing clinical challenges. OBJECTIVE: To investigate antibacterial activity against Helicobacter Pylori and in vitro anti-colon cancer activity by Acacia nilotica extract (ACE) and its active constituent pyrogallol. METHODS: Pyrogallol isolated from A. nilotica by column chromatography and HPLC and structure was elucidated by spectral analysis. Antibacterial activity was done by flow cytometry. Cytotoxicity was measured by MTT assay. Apoptotic morphology and nuclear fragmentation were assessed with AO/ethidium bromide and DAPI staining. DNA fragmentation was done by electrophoresis. Western blot used to analyze the molecular mechanism of apoptosis. Cell cycle arrest was determined using flow cytometry of propidium iodide stained cells. Cell migration was determined by wound healing assay. RESULTS: ACE (20 µg/ml) and pyrogallol (10 µg/ml) treatment reduced the survival of H.pylori at 61% and 62%, respectively. MTT results show that HT-29 cells are more sensitive to pyrogallol with an IC50 value of 35µg/ml compared to ACE. Pyrogallol treated HT-29 cells reached dead state i.e. late apoptotic state with severe nuclear fragmentation. Pyrogallol elicits dose dependent DNA fragmentation in HT-29 cells. Pyrogallol induced apoptosis by simultaneous down-regulation of Bcl-2 and up-regulation of BAX and cytochrome c. Pyrogallol arrested HT-29 cells in S and G2/M phase of cell cycle. Further pyrogallol exhibited marked antimetastatic potential by inhibiting the migration of HT-29 cells dose dependently. CONCLUSION: Both ACE and pyrogallol repressed the growth of H.pylori and as significant anti-colon cancer agent.

Dietary Crocin Reverses Melanoma Metastasis.

Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models. However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melanoma metastatic model was developed by tail vein injection of B16F-10 cells in to C57BL/6 mice. Metastatic mice treated with two different doses of crocin (250 and 500 µg/kg of bodyweight) for 10 days and parameters such as lung metastasis inhibition, mean survival time, lung hydroxyproline, uronic acid and hexosamine levels were analyzed after 21 days of treatment. Then blood was collected and serum gamma glutamyl transpeptidase (g-GGT), sialic acid, tumor necrosis factor alpha (TNF-a), interleukin 10 (IL-10), IL-6, IL-2, and TIMP-1 levels were measured. Further, a lung histological examination was done in crocin treated metastatic mice. Subsequently hallmark metastatic parameters such as matrix metalloproteases (MMPs), extracellular regulated kinase 2 (ERK2), vascular endothelial growth factor (VEGF), and K-ras gene expression were investigated in the lungs of crocin treated metastatic mice. Further, in-vitro adhesion, invasion and migration of B16F-10 cells were examined after 24 h of crocin (5 and 10 µg/mL) treatment. Administration of crocin to tumor bearing C57BL/6 mice reduced the lung metastasis by 85%. Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid andg-GGT in metastatic control were found to be significantly reduced in crocin treated mice. Crocin also inhibited expression of MMP-2, MMP-9, ERK-2, K-ras, and VEGF. Crocin reduced the ability of B16F-10 cells invasion (p<0.05), migration (p<0.05) and adhesion by upregulating E-cadherin expression. In conclusion, crocin elicited marked anti-metastatic potential by regulating the metastasis induced biomarkers.

Characterization of the anticancer properties of monoglycosidic cardenolides isolated from Nerium oleander and Streptocaulon tomentosum.

AIM OF THE STUDY: For identification of the active constituents we investigated the anticancer activity of cardenolides from Streptocaulon tomentosum Wight & Arn. (Asclepiadaceae) and from Nerium oleander L. (Apocynaceae) which are both used against cancer in the traditional medicine in their region of origin. MATERIAL, METHODS AND RESULTS: The antiproliferative activity of cardenolides isolated from roots of Streptocaulon tomentosum (IC(50)<1-15.3 µM after 2 days in MCF7) and of cardenolide containing fractions from the cold aqueous extract of Nerium oleander leaves ("Breastin", mean IC(50) 0.85 µg/ml in a panel of 36 human tumor cell lines), their influence on the cellular viability and on the cell cycle (block at the G2/M-phase or at the S-phase in tumor cells, respectively) were determined using different cell lines. The murine cell line L929 and normal non-tumor cells were not affected. Bioactivity guided fractionation of Breastin resulted in the isolation of the monoglycosidic cardenolides oleandrine, oleandrigeninsarmentoside, neritaloside, odoroside H, and odoroside A (IC(50)-values between 0.010 and 0.071 µg/ml). CONCLUSIONS: The observed anticancer activities of extracts and isolated cardenolides are in agreement with the ethnomedicinal use of Streptocaulon tomentosum and Nerium oleander. The most active anticancer compounds from both species are monoglycosidic cardenolides possessing the 3ß,14ß-dihydroxy-5ß-card-20(22)-enolide structure with or without an acetoxy group at C-16. The results indicate that the cytotoxic effects are induced by the inhibition of the plasma membrane bound Na(+)/K(+)-ATPase.

Synthesis, crystal structure and initial biological evaluation of the new enantiomerically pure chiral palladium(II) complex trans-bis[endo-(1R)-1,7,7-trimethylbicyclo[2.2.1]-heptan-2-amino]palladium(II)dichloride.

The palladium(II) complex trans-bis[(R)-(+)-bornylamino]palladium(II) dichloride was synthesised and characterised. The solid state structure of the complex was determined by X-ray structure analysis. The compound crystallises in the monoclinic space group P2(1) with a=12.383(2), b=23.689(5), c=12.769(3) A, beta=93.25(3) degrees, and V=3739.6(13) A(3). The complex was tested for its cytotoxicity against L(929), K(562) and HeLa cell lines using the MTT assay technique. It is also tested for its anticomplementary activity using a test that detects complement proteins inhibition. These activities were compared with those of the reference standards, cisplatin, carboplatin and oxaliplatin. The significance of these results is given and discussed.