An Update on Pharmacological and Phytochemical Aspects of Costus pictus D. Don - A Promising Anti-diabetic Plant.

BACKGROUND: The genus Costus is the largest genus in the family Costaceae and encompasses about 150 known species. Among these, Costus pictus D. Don (Synonym: Costus mexicanus) is a traditional medicinal herb used to treat diabetes and other ailments. Currently, available treatment options in modern medicine have several adverse effects. Herbal medicines are gaining importance as they are cost-effective and display improved therapeutic effects with fewer side effects. Scientists have been seeking therapeutic compounds in plants, and various in vitro and in vivo studies report Costus pictus D. Don as a potential source in treating various diseases. Phytochemicals with various pharmacological properties of Costus pictus D. Don, viz. anti-cancer, anti-oxidant, diuretic, analgesic, and anti-microbial have been worked out and reported in the literature. OBJECTIVE: The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research. METHODS: This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, Sci-Finder, other online journals and books for detailed analysis. RESULTS: Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare. CONCLUSION: This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.

Monoterpenoids: An upcoming class of therapeutic agents for modulating cancer metastasis.

Monoterpenoids, a sub-class of terpenoids, are secondary metabolites frequently extracted from the essential oils of aromatic plants. Their antitumor properties including antiproliferative, apoptotic, antiangiogenic, and antimetastatic effects along with other biological activities have been the subject of extensive study due to their diverse characteristics. In recent years, numerous investigations have been conducted to understand its potential anticancer impacts, specifically focusing on antiproliferative and apoptotic mechanisms. Metastasis, a malignancy hallmark, can exert either protective or destructive influences on tumor cells. Despite this, the potential antimetastatic and antiangiogenic attributes of monoterpenoids need further exploration. This review focuses on specific monoterpenoids, examining their effects on metastasis and relevant signaling pathways. The monoterpenoids exhibit a high level of complexity as natural products that regulate metastatic proteins through various signaling pathways, including phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin, mitogen-activated protein kinase/extracellular signal-regulated kinase/jun N-terminal kinase, nuclear factor kappa B, vascular endothelial growth factor, and epithelial mesenchymal transition process. Additionally, this review delves into the biosynthesis and classification of monoterpenoids, their potential antitumor impacts on cell lines, the plant sources of monoterpenoids, and the current status of limited clinical trials investigating their efficacy against cancer. Moreover, monoterpenoids depict promising potential in preventing cancer metastasis, however, inadequate clinical trials limit their drug usage. State-of-the-art techniques and technologies are being employed to overcome the challenges of utilizing monoterpenoids as an anticancer agent.

Escin enhanced the efficacy of sorafenib by autophagy-mediated apoptosis in lung cancer cells.

Combining anti-cancer drugs has been exploited as promising treatment strategy to target lung cancer. Synergistic chemotherapies increase anti-cancer effect and reduce effective drug doses and side effects. In this study, therapeutic potential of escin in combination with sorafenib has been explored. 3-(4,5-Dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide assay was used to calculate IC50 values. The synergy was evaluated using Chou-Talaly algorithm. Cellular reactive oxygen species, mitochondrial membrane potential, annexin V, and cell-cycle studies were done by flow-cytometer, and autophagy biomarkers expression were determined using western blotting. Moreover, autophagy was knocked down using ATG5 siRNA to confirm its role, diethylnitrosamine-induced lung cancer model was used to check the synergy of sorafenib/escin. Escin significantly reduced the IC50 of sorafenib in A549 and NCIH460 cells. The combination of sorafenib/escin produced a 2.95 and 5.45 dose reduction index for sorafenib in A549 and NCI-H460 cells. The combination of over-expressed p62 and LC3-II reflects autophagy block-mediated late apoptosis. This phenomenon was reconfirmed by ATG5 knockdown. This combination also selectively targeted G0/G1 phase of cancer cells. In in vivo study, the combination reduced tumour load and lower elevated serum biochemical parameters. The combination of sorafenib/escin synergistically inhibits autophagy to induce late apoptosis in lung cancer cells' G0/G1 phase.

Promising Essential Oils/Plant Extracts in the Prevention and Treatment of Dandruff Pathogenesis.

BACKGROUND: Dandruff is a scalp disorder affecting the male populace predominantly. Topical agents and synthetic drugs used for dandruff treatment have specific side effects including burning at the application site, depression, dizziness, headache, itching or skin rash, nausea, stomach pain, vision change, vomiting, discoloration of hair, dryness or oiliness of the scalp and increased loss of hair. Thus, essential oils and extracts from plants could be valuable in the treatment and prevention of dandruff. AIMS & OBJECTIVES: This review aims to highlight current findings in dandruff occurrence, its etiology, promising plant essential oils/extracts, and novel treatment strategies. The main emphasis has been given on the anti-dandruff effect of essential oils and plant extracts to disrupt microbial growth. The proposed mechanism(s) of action, novel approaches used to perk up its biopharmaceutical properties, and topical application have been discussed. RESULTS: The literature survey was done, and bibliographic sources and research papers were retrieved from different search engines and databases, including SciFinder, PubMed, NCBI, Scopus, and Google Scholar. The selection of papers was accomplished based on exclusion and inclusion criteria. The scalp of diverse populations revealed an association of dandruff with microbial symbiosis, including Staphylococcus, Propionibacterium, Malassezia, and Candida as the pathogens responsible for the cause of dandruff. Topical antifungals are considered the first line of treatment for dandruff including azoles, with clotrimazole (1%), ketoconazole (2%), and miconazole (2%). Other commonly used therapies integrate benzoyl peroxide, coal tar, glycerin, zinc pyrithione, lithium succinate/gluconate, salicylic acid, selenium disulfide/sulfide, sodium sulfacetamide, etc. However, these medicaments and chemicals are known to cause specific side effects. Alternative therapies, including tea tree oil, thyme, Aloe vera, Mentha have been reported to demonstrate anti-dandruff activity by disrupting the microbial growth associated with dandruff formation. CONCLUSION: Overall, this review explains the occurrence of dandruff, its pathogenesis, and the potential applicability of promising plant essential oils/extracts and their novel treatment strategies. Further studies based on pre-clinical and clinical research are essential before making any conclusion about its efficacy in humans.

Dietary flavonoid narirutin as a prospective antagonist of oncogenic pri/pre-microRNAs.

MicroRNAs (miRNAs) are involved in cancer progression via translational degradation in a sequence-specific manner of the 3'-untranslated region (3'UTR) of messenger RNA (mRNA). The involvement of miRNA in the biological progression of various cancer types is considered to be a potential target. Primary miRNA (pri-miRNA) and precursor-miRNA (pre-miRNA) synthesize the miRNA by dicer-catalyzed processes thus targeting pri/pre-miRNA by phytochemicals is amongst the appropriate approaches for anticancer therapies. Flavonoids category of phytochemicals is well-known for its chemotherapeutic and chemopreventive potential against multiple cancer types. However, the molecular interactions of flavonoids with miRNAs are not reported so far. Thus, this study aims to identify the promising flavonoids as the antagonist of miRNAs (pre-miR21, pri-miR-208a, pri-miR-378a, pri-miR320b, pri-miR-300, pri-miR-19b, and pre-miR-20b) using molecular docking simulations studies. Among the tested flavonoids, narirutin showed highest binding energy (-11.7 kcal/mol) against pri-miR19b followed by pri-miR-378a (-11.4 kcal/mol) > pri-miR320b (-11.2 kcal/mol) = pri-miR-300 (-11.2 kcal/mol) > pri-miR-208a (-9.0 kcal/mol) > pre-miR-20b (- 8.3 kcal/mol). The molecular dynamic simulation experiment confirmed that narirutin destabilizes the tertiary structure of pri-miRNA in comparison to apo-RNA. The finding indicates that narirutin binding with pre-miRNA causes disruption of pri-RNA structure that creates a loss of DICER-pre-miRNA interactions by hindering the pre-miRNA synthesis, thereby affecting miRNA processing. Further pharmacokinetics and toxicity prediction revealed that it is non-carcinogenic, non-mutagenic, and does not inhibit the CYPs activity. Thus, narirutin could be a possible antagonist of oncogenic miRNAs, therefore could be useful for miRNA-targeted cancer prevention and treatment.

Geraniol exerts its antiproliferative action by modulating molecular targets in lung and skin carcinoma cells.

Geraniol, an acyclic monoterpene present in several plant species' essential oils, is utilized as a food additive. It possesses potent antiproliferative and antitumor effects ascribed to its antiinflammatory, and antioxidant properties. The study aimed to understand geraniol's mechanism in human lung and skin cancer cells by employing molecular and cell target-based assays. SRB, NRU, MTT assays, qRT-PCR, molecular docking, and EAC model were used. Geraniol inhibits the proliferation of PC-3, A431, and A549 cells (~50%) and suppresses the activity of ornithine decarboxylase (15.42 ± 0.61 µM) and hyaluronidase (57.61 ± 8.53 µM) in A549 cells; LOX-5 (25.44 ± 3.50 µM) and hyaluronidase (90.71 ± 2.38 µM) in A431 cells. The qRT-expression analysis of the targeted gene depicts non-significant change at the transcriptional level of LOX-5 in A431 cells. A robust binding interaction of geraniol with molecular targets was observed in the molecular docking studies. In Ehrlich Ascites Carcinoma model, geraniol inhibit tumor growth by 50.08% at 75 mg/kg bw and was found to be safe up to 1,000 mg/kg bw in a toxicity study. Geraniol has two prenyl units allied head-to-tail and functionalized with one hydroxyl group at its tail end could be responsible for the antiproliferative activity. These observations provide evidence for geraniol to be used as a new prototype to develop a novel anticancer agent.

Antiproliferative Activity of Cissus quadrangularis L. Extract Against Human Cervical Cancer Cells: In Vitro and In Silico Analysis.

BACKGROUND: Cervical cancer is the second leading cause of cancer in women, which necessitates safe and potential therapeutic agents. OBJECTIVE: This study was designed to investigate the antiproliferative effect of ethanolic extract of Cissus quadrangularis L. (CQ) against human cervical adenocarcinoma HeLa cell line and in silico analysis of selected active agents against apoptosis executioner enzyme caspase-3. METHODS: Cell viability was analyzed in HeLa cells at different concentrations (25-300 µg/ml) of CQ extract. Reactive oxygen species (ROS) generation, cellular apoptosis, cell cycle analysis and caspases-3 activation were evaluated. In silico, structure-based virtual screening analysis was carried out using AutoDock Vina and iGEMDOCK. RESULTS: Cell viability of HeLa cells was reduced significantly (p < 0.05) in a dose-dependent manner, however, CQ extract showed non-toxic to normal kidney epithelial NRK-52E cells. CQ extract induced the intracellular ROS level, nuclear condensation and reduced the mitochondrial membrane potential (MMP) with the induction of annexin V-FITC positive cells. CQ extract arrested cells in G0/G1 and G2/M checkpoints and activated caspase-3 activity significantly in HeLa cells. The molecular docking study showed a strong binding affinity of CQ phytocomponents against the caspase-3 (PDB ID: 1GFW) protein of human apoptosis. PASS analyses of selected active components using Lipinski's Rule of five showed promising results. Further, drug-likeness and toxicity assessment using OSIRIS Data Warrior V5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. CONCLUSION: This study suggested that active constituents in CQ extract can be considered as potential chemotherapeutic candidates in the management of cervical cancer.

Diversity of Essential Oil-Secretory Cells and Oil Composition in Flowers and Buds of Magnolia sirindhorniae and Its Biological Activities.

Magnolia sirindhorniae Noot. & Chalermglin produces fragrant flowers. The volatile oil secretary cells, quantity and quality as well as antioxidant and antimicrobial activities of the oils extracted from buds and flowers, have been investigated. The distribution of essential oil secretory cell in bud and flower revealed that the density and size of the oil cells were significantly higher in flowers compared to buds. In different floral parts, carpel has a higher oil cell density followed by gynophore and tepal. The histochemical analysis revealed the essential oil is synthesized in oil secretory cells. The volatile oil yield was 0.25 % in the buds and 0.50 % in flowers. GC/FID and GC/MS analysis identified 33 compounds contributing 83.2-83.5 % of the total essential oil composition. Linalool is the main constituent contributing 58.9 % and 51.0 % in the buds and flowers oils, respectively. The essential oil extracted from the flowers showed higher antimicrobial efficacy against Klebsiella pneumoniae and Staphylococcus aureus. Similarly, the essential oil isolated from the flowers depicts higher free radical scavenging, and antioxidant activity compared to buds' oil.

Purpurin: A natural anthraquinone with multifaceted pharmacological activities.

Purpurin is a naturally occurring anthraquinone isolated from the roots of Rubia cordifolia. Historically, it has been used as a red dye. However, its photosensitizing property and biological effects have deciphered its novel application. Purpurin shows antigenotoxic, anticancer, neuromodulatory, and antimicrobial potential associated with antioxidant action in in vivo and in vitro experiments. A robust antioxidant nature of purpurin is responsible for the majority of its pharmacological effects. It produces anti-inflammatory activity by reducing oxidative stress, which is a fundamental property to target diseases involving endoplasmic reticulum and mitochondrial stress. It can cross the blood-brain barrier and produce neuroprotective effects, including antidepressant and anti-Alzheimer action. It shows antimutagenic property via inhibiting essential CYP-450 enzymes. Interestingly, it gets photosensitized by UV-light and produces target-specific ROS-dependent apoptosis in cancer cells. Therefore, it owns cell killing and cell survival potential subject to the influence of external conditions. Hitherto, limited research studies are performed with purpurin to understand its therapeutic potential. Hence, this review describes and discusses different in vivo, in vitro, and in silico studies performed using purpurin. It also covers physicochemical, pharmacokinetics, and toxicology aspects of purpurin. Moreover, in the end, the prospect of purpurin in the management of cancer has also been proposed.

Emerging role of phytochemicals in targeting predictive, prognostic, and diagnostic biomarkers of lung cancer.

Lung-cancer is the foremost cause of cancer in humans worldwide, of which 80-85% cases are composed of non-small cell lung carcinoma. All treatment decisions depend on the pattern of biomarkers selection to enhance the response to the targeted therapies. Although advanced treatments are available for lung-cancer, the disease treatment remains not adequate. There are several synthetic chemotherapeutic agents available for the treatment of lung cancer. However, due to their toxic effect, survival rate is still 15-18%. Besides, medicinal plants are a huge reservoir of natural products that provide protective effects against lung cancer. Likewise, successful studies of potential phytochemicals in targeting lung-cancer biomarkers have created a novel paradigm for the discovery of potent drugs against lung-cancer. Hence, to defeat severe toxicity and resistance towards the synthetic drugs, detailed studies are required regarding the available phytochemicals and targets responsible for the treatment of lung-cancer. The present review provides a comprehensive information about the lung-cancer biomarkers under the classification of predictive, prognostic, and diagnostic type. Moreover, it discusses and enlists the phytochemicals with mode of action against different biomarkers, effective doses in in vitro, in vivo, and clinical studies, the limitations associated with usage of phytochemicals as a drug to prevent/cure lung-cancer and the latest techniques employed to overcome such issues.

Brevifoliol ester induces apoptosis in prostate cancer cells by activation of caspase pathway.

Prostate cancer is fourth most abundant cancer type around the globe. Brevifoliol, a rearranged taxoid from Taxus walllichiana needles has been derivatized as C5 esters using Steglich esterification reaction. Seventeen diverse analogues were evaluated against a panel of human cancer cell lines by MTT assay. Among these, two of the semi-synthetic analogues, that is, 13 and 16 exhibited potent cytotoxicity, selectively against PC-3, prostate cancer cell lines. In cell cycle analysis, analogue 13 induced S and G2/M phase arrest and induced apoptosis by activating caspase-3. Compound 13 showed moderate efficacy in in-vivo Ehrlich ascites carcinoma in Swiss albino mice. Further, compound 13 was found to be safe in Swiss albino mice up to 1,000 mg/kg dose in acute oral toxicity. Brevifoliol ester 13 may further be optimized for better efficacy.

Application of the combinatorial approaches of medicinal and aromatic plants with nanotechnology and its impacts on healthcare.

BACKGROUND: Medicinal and aromatic plants are natural raw materials. Since ancient times these herbal materials are being commonly used as herbal drugs, food products, and cosmetics. The phytomolecules isolated from the medicinal and aromatic plants (MAPs) are in high demand specifically in drug industries. However, these phytomolecules have certain limitations of low absorption, high toxicity, and other side effects, bioavailability and efficacy. These limitations may be overcome by using nanotechnological tools. The plant extract or essential oil of MAPs are also useful in the synthesis of nanoparticles. In future this combinatorial application of MAPs and nanotechnology would be advantageous in the healthcare area. METHODS: Literature search was performed using databases like Pubmed, Scopus and Google Scholar with the keywords "nanoparticles," "phytomolecules," "medicinal and aromatic plants" and "green synthesis of nanoparticles" in the text. RESULT: Phytomolecules of medicinal and aromatic plants like curcumin, camptothecin, thymol, and eugenol have certain limitations of bioavailability, efficacy, and solubility. It limits its biological activity and therefore application in the biomedical area. The increment in the biological activity and sustained delivery was observed after the encapsulation of these potent phytomolecules encapsulated in the nanocarriers. Besides, MAPs and/or their molecules/oils mediate the synthesis of metal nanocarriers with less toxicity. CONCLUSION: This review highlights the impact of the combination of the MAPs with the nanotechnology along with the challenges. It would be an effective technique for the efficient delivery of different phytomolecules and also in the synthesis of novel nano-materials, which escalates the opportunity of exploration of potential molecules of MAPs. Graphical abstract Graphical representation of the combinatorial approach of MAPs and nanotechnology.

A relative assessment of essential oil of Chrysopogon zizanioides and Matricaria chamomilla along with calcium hydroxide and chlorhexidine gel against Enterococcus faecalis in ex vivo root canal models.

OBJECTIVE: The objective of this study was to evaluate the antibacterial efficacy of two doses of vetiver and chamomile essential oils compared with chlorhexidine and calcium hydroxide against Enterococcus faecalis. MATERIALS AND METHODS: The growth inhibition and minimum inhibitory concentration of all tested materials were determined ex vivo following agar diffusion and broth dilution assay procedure. Human maxillary anterior teeth were prepared with protaper rotary files, followed by incubation with standard broth of E. faecalis. A total of 140 teeth were included in the study. These teeth are randomized and equally divided into seven groups and were treated with low (1.25 µl) and high doses (2.5 µl) of essential oils of vetiver and chamomile and calcium hydroxide (0.1/1.0 mL), 2% chlorhexidine (2.5 µl). Microbial sampling of six teeth from each group was done with paper points and Gates-Glidden burs at 1, 7, and 14 days and colony-forming unit (CFU)/mL was determined. RESULTS: There was a significant reduction in mean ± standard deviation of CFU (log10) in vetiver oil high dose (3.32 ± 0.036) and chlorhexidine (3.34 ± 0.030), followed by calcium hydroxide (3.46 ± 0.015) and chamomile oil high dose (3.48 ± 0.20) on day 1. On 7th day, a significant reduction was seen in chlorhexidine (2.74 ± 0.212), chamomile oil (2.81 ± 0.035, low dose and 2.97 ± 0.119, high dose), followed by calcium hydroxide (3.25 ± 0.028). However, on 14th day, it was 2.32 ± 0.088 for chlorhexidine, 2.91 ± 0.029 for chamomile oil high dose, 3.15 ± 0.010 for vetiver oil high dose, and 3.09 ± 0.068 for calcium hydroxide. CONCLUSION: The study showed a good effectiveness of chamomile oils in root canal infection of E. faecalis at different time intervals compared to chlorhexidine and calcium hydroxide vetiver oil did not sustain their activity for a longer duration.

Rutin protects t­butyl hydroperoxide-induced oxidative impairment via modulating the Nrf2 and iNOS activity.

BACKGROUND: Rutin (quercetin-3-O-rutinoside), a flavonoid, is predominantly found in the buckwheat, cranberries, mulberry and citrus fruits. It is used as a restorative in the preparation of herbal medicine, multivitamin and known to reduce the fate of heart attack. HYPOTHESIS: We aimed to elucidate whether rutin attenuates oxidative stress and its possible mechanism of action in ameliorating the deleterious effect of t-BHP. We also provide evidence that rutin protects the antioxidant status of erythrocytes and liver via Nrf2 and iNOS pathway from oxidative stress. STUDY DESIGN/METHOD: Human erythrocytes and mice liver were used for the evaluation of rutin's effect against t-BHP induced oxidative stress. The non-enzymatic (GSH, MDA, -CO, -SH) and enzymatic stress markers (SOD, CAT, GPx, GR and GST) were estimated by the colorimetric method. The level of Nrf2, iNOS, liver marker enzymes, triglycerides, cholesterol, HDL-cholesterol, albumin, BUN was measured using ELISA kits. Reactive oxygen species (ROS) was quantified using flow cytometry and fluorometry. RT-PCR was used for the quantification of Nrf2 and iNOS expression levels in the liver tissue of mice. In silico studies were done through receptor-ligand binding interaction. RESULTS: Pre-treatment with the rutin ameliorated the toxic effect of t-BHP by modulating the basal level of GSH, -SH, MDA and -CO significantly (p < 0.01) with respect to untreated control. Rutin also protected the erythrocytes against the t-BHP-induced oxidative stress as evidenced by augmented activity of antioxidant enzymes (CAT, SOD, GPX, GR and GST). Furthermore, at the highest tested concentration (16.3 µM), it protected the morphology of the erythrocytes by decreasing the ROS level (p < 0.01). In addition, the lower MEF values of rutin (0.520 ±â€¯0.005) alone or along with t-BHP (0.630 ±â€¯0.021) indicated its non-toxic and protective behavior. The qPCR analyses revealed that t-BHP potently up-regulates the iNOS and down regulate the Nrf2 expression which was ameliorated with rutin treatment in a dose-dependent manner like silymarin. CONCLUSION: Our findings demonstrate that rutin potentiates its beneficial aspect by displaying a profound role in iNOS-Nrf2 signaling pathway. Accordingly, it may be concluded that the dietary factors wherein rutin is an ingredient could be helpful in the maintenance of the intracellular redox-homeostasis and thus may be effective against oxidative stress related secondary complications.

Isolation and antiproliferative activity of triterpenoids and fatty acids from the leaves and stem of Turraea vogelii Hook. f. ex benth.

Chloroform extract from the leaves of Turraea vogelii Hook f. ex Benth demonstrated cytotoxic activity against a chronic myelogenous leukemia cell, K-562 with IC50 of 14.27 µg/mL, while chloroform, ethyl acetate and methanol extracts from the stem of the plant inhibited K-562 cells growth with IC50 of 19.50, 24.10 and 85.40 µg/mL respectively. Bioactive chloroform extract of Turraea vogelii leaves affords two triterpenoids: oleana-12,15,20-trien-3ß-ol (1), and oleana-11,13-dien-3ß,16α,28-triol (2), with six fatty esters, ethyl hexaeicos-5-enoate (3), 3-hydroxy-1,2,3-propanetriyltris(tetadecanoate) (4), 1,2,3-propanetriyl(7Z,7'Z,7''Z)tris(-7-hexadecenoate) (5), 1,2,3-propanetriyl(5Z,5'Z,5''Z)tris(-5-hexadecenoate) (6), 1,2,3-propanetriyltris(octadecanoate) (7), and 2ß-hydroxymethyl tetraeicosanoate (8). Tetradecane (9), four fatty acids: hexadecanoic acid (10), tetradecanoic acid (11), (Z)-9-eicosenoic acid (12), and ethyl tetradec-7-enoate (13) were isolated from chloroform extract of Turraea vogelii stem. 1,2,3-propanetriyltris(heptadecanoate) (14), (Z)-9-octadecenoic acid (15) and (Z)-7-tetradecenoic acid (16) were isolated from ethyl acetate extract while (Z)-5-pentadecenoic acid (17) was obtained from methanol extract of the plant stem. Compounds 1, 2, 5, 6, 11, 12, 15, 16 and 17 exhibited pronounced antiproliferative activity against K-562 cell lines.

Isolation and antiproliferative activity of chemical constituents from Asystasia buettneri Lindau.

N-hexane and methanol extracts of Asystasia buettneri Lindau aerial parts exhibited antiproliferative activity on leukaemia blood carcinoma, K-562. Hexadecane (1), 1,3-propan-2-ol (9Z,12'Z,15″Z)-bis(doeicos-9,12,15-trienoate) (2), hydrocarbon, 2,3,3,10,23-pentamethyl tetraeicos-10,13,16-trien-1-ol (3), hexadecanoic acid (4) and taraxerol (5) were isolated from n-hexane extract; stigmasterol (6) and (Z)-9-octadecenoic acid (7) were isolated from ethyl acetate extract; while unsaturated hydrocarbons, octadecene (8), 8-methyl tetradec-6-ene (9) and 19-methyl eicos-1-ene (10), fatty acids, (Z)-5-hexadecenoic acid (11), 11,22-dimethyl ethyltrieicos-11-enoate (12) and taraxasterol (13) were isolated from methanol extract of the plant. Compounds 4, 5, 7, 11, 12 and 13 exhibited antiproliferative activity against K-562, while compounds 5, 6, 7 and 9 revealed antiproliferative activity by inhibiting hepatic liver (WRL68) cell lines.

Investigation of molecular mechanism of recognition between citral and MARK4: A newer therapeutic approach to attenuate cancer cell progression.

Microtubule affinity regulating kinase 4 (MARK4) is a member of AMP-activated protein kinase, found to be involved in apoptosis, inflammation and many other regulatory pathways. Since, its aberrant expression is directly associated with the cell cycle and thus cancer. Therefore, MARK4 is being considered as a potential drug target for cancer therapy. Here, we investigated the mechanism of inhibition of MARK4 activity by citral. Docking studies suggested that citral effectively binds to the active site cavity, and complex is stabilized by several interactions. We further performed molecular dynamics simulation of MARK4-citral complex under explicit water condition for 100ns and observed that binding of citral to MARK4 was quite stable. Fluorescence binding studies suggested that citral strongly binds to MARK4 and thereby inhibits its enzyme activity which was measured by the kinase inhibition assay. We further performed MTT assay and observed that citral inhibits proliferation of breast cancer cell line MCF-7. This work provides a newer insight into the use of citral as novel cancer therapeutics through the MARK4 inhibition. Results may be employed to design novel therapeutic molecule using citral as a scaffold for MARK4 inhibition to fight related diseases.

Fraxetin and ethyl acetate extract from Lawsonia inermis L. ameliorate oxidative stress in P. berghei infected mice by augmenting antioxidant defence system.

BACKGROUND: Lawsonia inermis L. is a well-documented plant for cosmetic as well as medicinal properties. It is used by local communities in India and Nigeria for the treatment of many parasitic diseases, including malaria. HYPOTHESIS/PURPOSE: Earlier studies on the plant's antiplasmodial activity were not assigned to any phytochemical with no quality assurance data. In this report, a recent chemically characterized extract and it's major constituent were investigated for in vitro antiplasmodial activity on chloroquine sensitive NF-54 strain. Furtherly, the potent extract and this constituent were assessed in vivo in Plasmodium berghei infected mice. The bioactive phytochemical and enriched extract were also monitored against various oxidative stress parameters. STUDY DESIGN/METHOD: The extract characterization was done by the quantitative analysis of eight phytochemicals using gradient reverse phase HPLC method. In vitro antiplasmodial activity was evaluated on chloroquine sensitive NF-54 strain by the determination of pfLDH activity. In vivo activity of the most potent extract and constituent were evaluated in P. berghei infected mice upon oral administration. The estimation of oxidative stress was done by monitoring various enzymatic and non-enzymatic parameters. RESULTS: The ethyl acetate extract of leaves (IC50 9.00 ±â€¯0.68 µg/ml) and fraxetin (IC50 19.21 ±â€¯1.04 µM) were the most effective in in vitro assays therefore selected for in vivo tests. The administration of the ethyl acetate extract of leaves and fraxetin to the infected mice resulted in significant (p < .05) suppression of parasitaemia as evidenced by a 70.44 ±â€¯2.58% to 78.77 ±â€¯3.43% reduction compared to non-infected group. In addition, a two-fold increase in mean survival time, a significant (p < .05) reduction in lipid peroxidation and an elevation in glutathione, catalase and superoxide dismutase were also observed in treated mice. The post-infection treatment also led to an augmentation of endogenous antioxidant enzymes (GST, GR, GPx) with respect to the infected control. A significant (p < .05) elevation in serum Nrf2-antioxidant response element level responsible for the activation of endogenous enzymes was also observed. CONCLUSION: It was evident from the experiments that ethyl acetate extract of L. inermis and fraxetin were able to suppress the oxidative damage by augmenting endogenous antioxidant system and thus ameliorated the plasmodium infection in mice.

Differential rubisco content and photosynthetic efficiency of rol gene integrated Vinca minor transgenic plant: Correlating factors associated with morpho-anatomical changes, gene expression and alkaloid productivity.

Transgenic plants obtained from a hairy root line (PVG) of Vinca minor were characterized in relation to terpenoid indole alkaloids (TIAs) pathway gene expression and vincamine production. The hairy roots formed callus with green nodular protuberances when transferred onto agar-gelled MS medium containing 3.0mg/l zeatin. These meristematic zones developed into shoot buds on medium with 1.0mg/l 2, 4-dichlorophenoxyacetic acid and 40mg/l ascorbic acid. These shoot buds subsequently formed rooted plants when shifted onto a hormone-free MS medium with 6% sucrose. Transgenic nature of the plants was confirmed by the presence of rol genes of the Ri plasmid in them. The transgenic plants (TP) had elongated internodes and a highly proliferating root system. During glass house cultivation TP consistently exhibited slower growth rate, low chlorophyll content (1.02±0.08mg/gm fr. wt.), reduced carbon exchange rate (2.67±0.16µmolm-2s-1), less transpiration rate (2.30±0.20mmolm-2 s-1) and poor stomatal conductance (2.21±0.04mmolm-2 s-1) when compared with non-transgenic population. The activity of rubisco enzyme in the leaves of TP was nearly two folds less in comparison to non-transgenic controls (1.80milliunitsml-1mgprotein-1 against 3.61milliunits ml-1mgprotein-1, respectively). Anatomically, the TP had a distinct tetarch arrangement of vascular bundles in their stem and roots against a typical ployarched pattern in the non-transgenic plants. Significantly, the transgenic plants accumulated 35% higher amount of total TIAs (3.10±0.21% dry wt.) along with a 0.03% dry wt. content of its vasodilatory and nootropic alkaloid vincamine in their leaves. Higher productivity of alkaloids in TP was corroborated with more than four (RQ=4.60±0.30) and five (RQ=5.20±0.70) times over-expression of TIAs pathway genes tryptophan decarboxylase (TDC) and strictosidine synthase (STR) that are responsible for pushing the metabolic flux towards TIAs synthesis in this medicinal herb.

Elucidation of Dietary Polyphenolics as Potential Inhibitor of Microtubule Affinity Regulating Kinase 4: In silico and In vitro Studies.

Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase belonging to AMPK-like family, has recently become an important drug target against cancer and neurodegenerative disorders. In this study, we have evaluated different natural dietary polyphenolics including rutin, quercetin, ferulic acid, hesperidin, gallic acid and vanillin as MARK4 inhibitors. All compounds are primarily binds to the active site cavity of MARK4. In silico observations were further complemented by the fluorescence-binding studies and isothermal titration calorimetry (ITC) measurements. We found that rutin and vanillin bind to MARK4 with a reasonably high affinity. ATPase and tau-phosphorylation assay further suggesting that rutin and vanillin inhibit the enzyme activity of MARK4 to a great extent. Cell proliferation, ROS quantification and Annexin-V staining studies are clearly providing sufficient evidences for the apoptotic potential of rutin and vanillin. In conclusion, rutin and vanillin may be considered as potential inhibitors for MARK4 and further exploited to design novel therapeutic molecules against MARK4 associated diseases.