Rehlingen, Germany
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Ramachandran C.,Nicklaus Childrens Hospital | Ramachandran C.,Dharma Biomedical LLC | Portalatin G.M.,Dharma Biomedical LLC | Prado A.M.,Dharma Biomedical LLC | And 4 more authors.
Journal of Evidence-Based Complementary and Alternative Medicine | Year: 2017

Glioblastoma multiforme (GBM) is one the most aggressive and lethal human neoplasms with poor prognosis and very limited positive treatment options. The antitumor effect of supercritical CO2 extract of mango ginger (Curcuma amada Roxb) (CA) with and without irinotecan (IR) was analyzed in U-87MG human glioblastoma multiforme (GBM) cells in vitro and in nude mice xenografts. CA is highly cytotoxic to GBM cells and is synergistic with IR as indicated by the combination index values of <1 in the CompuSyn analysis. CA inhibits tumor growth rate in GBM xenografts, the inhibition rate being higher than in IR treated group. GBM xenograft mice treated with IR + CA combination showed almost complete inhibition of tumor growth rate. Gene expression analysis of xenograft tumors indicated that IR + CA treatment significantly downregulated anti-apoptotic (Bcl-2 and mutant p53), inflammation-associated (COX-2) and cell division–associated (CCNB2) genes and upregulated pro-apoptotic genes (p21 and caspase-3). These results confirmed the therapeutic efficiency of IR + CA combination against GBM and the need for further clinical investigations. © 2016, © The Author(s) 2016.


Ramachandran C.,Miami Childrens Hospital | Ramachandran C.,Dharma Biomedical LLC | Lollett I.V.,Dharma Biomedical LLC | Escalon E.,Miami Childrens Hospital | And 3 more authors.
Journal of Evidence-Based Complementary and Alternative Medicine | Year: 2015

Mango ginger (Curcuma amada Roxb.) is among the less-investigated species of Curcuma for anticancer properties. We have investigated the anticancer potential and the mechanism of action of a supercritical CO2 extract of mango ginger (CA) in the U-87MG human glioblastoma cell line. CA demonstrated higher cytotoxicity than temozolomide, etoposide, curcumin, and turmeric force with IC50, IC75, and IC90 values of 4.92 μg/mL, 12.87 μg/mL, and 21.30 μg/mL, respectively. Inhibitory concentration values of CA for normal embryonic mouse hypothalamus cell line (mHypoE-N1) is significantly higher than glioblastoma cell line, indicating the specificity of CA against brain tumor cells. CompuSyn analysis indicates that CA acts synergistically with temozolomide and etoposide for the cytotoxicity with combination index values of <1. CA treatment also induces apoptosis in glioblastoma cells in a dose-dependent manner and downregulates genes associated with apoptosis, cell proliferation, telomerase activity, oncogenesis, and drug resistance in glioblastoma cells. © The Author(s) 2014.


Ramachandran C.,Dharma Biomedical LLC | Nair S.M.,Dharma Biomedical LLC | Quirrin K.-W.,Flavex Naturextrakte GmbH | Melnick S.J.,Dharma Biomedical LLC
Journal of Evidence-Based Complementary and Alternative Medicine | Year: 2013

The hypolipidemic effects of the poorly soluble ayurvedic resin guggul, especially the molecular targets and mechanism, have not been well investigated to date. In the present study, we have formulated a liquid product, GU-MCT810, composed of a proprietary Commiphora mukul gum resin extract and medium-chain triglyceride and investigated its hypolipidemic effects in vitro. Treatment of HepG2 cells significantly reduced low-density lipoprotein cholesterol and increased the high-density lipoprotein/low-density lipoprotein ratio. GU-MCT810 showed direct inhibition of HMG-CoA reductase activity in a dose-dependent manner and compared very well with the inhibitory effect of statins like Pravastatin and Mevastatin. The adipocyte differentiation was also inhibited by GU-MCT810 treatment. GU-MCT810 increased the AMPKα phosphorylation and AMPK kinase activity and inhibited the phosphorylated form of mTOR expression, indicating the molecular targets affected by the nutraceutical compound. The preparation also highly upregulated the expression of LXR and PPARα genes and moderately upregulated BABP and SHP genes. © The Author(s) 2013.


Ramachandran C.,Miami Childrens Hospital | Ramachandran C.,Dharma Biomedical LLC | Quirin K.-W.,Flavex Naturextrakte GmbH | Escalon E.A.,Miami Childrens Hospital | And 3 more authors.
Phytotherapy Research | Year: 2015

Synergistic effect of supercritical CO2 extracts of Curcuma species with conventional chemotherapeutic drugs was investigated in human alveolar (SJRH30) and embryonal (RD) rhabdomyosarcoma cell lines. The Curcuma amada (mango ginger) (CA) extract showed the highest levels of cytotoxicity with inhibitory concentration IC50 values of 7.133 μg/ml and 7.501 μg/ml for SJRH30 and RD cell lines, respectively, as compared with Curcuma longa (turmeric) and Curcuma xanthorrhiza (Javanese turmeric) extracts. CA showed synergistic cytotoxic effects with vinblastine (VBL) and cyclophosphamide (CP) as indicated by the combination index values of <1 for VBL + CA, CP + CA, and VBL + CP + CA combinations in both embryonal and alveolar rhabdomyosarcomas. When lower doses of CA (0.1-0.2 μg/ml) were combined with cancer drugs like CP and VBL, caspase-3 activity increased significantly compared with individual agents and correlated with the percentage of apoptotic cells. CA in combination with VBL and CP induced a higher percentage of apoptosis than single agents in both cell lines. CA also modulated the expression of genes associated with intrinsic pathway of apoptosis (Bcl-2, Bax, Bak, and p53) and also inhibited the expression of genes associated with inflammation such as COX-2 and NF-κB. Xenograft studies with SJRH30 tumors in nude mice showed that CA treatment inhibited tumor growth rate with and without VBL and increased the survival rate significantly. These results suggest that CA can be evaluated further as an adjuvant with cancer drugs for the treatment of rhabdomyosarcoma patients. © 2015 John Wiley & Sons, Ltd.


Pudel F.,Pilot Pflanzenoltechnologie Magdeburg E.V. | Habicht V.,Pilot Pflanzenoltechnologie Magdeburg E.V. | Piofczyk T.,Pilot Pflanzenoltechnologie Magdeburg E.V. | Matthaus B.,Max Rubner Institute | And 2 more authors.
OCL - Oilseeds and fats, crops and lipids | Year: 2014

Canolol (2,6-dimethoxy-4-vinylphenol, 4-vinylsyringol), which is formed by thermally initiated CO2splitting off from sinapic acid, possesses a high antioxidant potential. Furthermore different positive physiological properties are described. Due to rapeseed's high content of phenolic acids, particularly sinapic acid, it is obvious to produce canolol as by-product of rapeseed processing. Roasting of rapeseed meal or cake in a fluidized bed followed by extraction with supercritical carbon dioxide of the formed canolol represents a production procedure which not impairs the commercial oil mill process. This article summarizes results from the roasting process with rapeseed meal and cake in fluidized bed equipments of different design and size showing that it is a suitable technique to transform sinapic acid into canolol. The achieved canolol contents are at 500 mg/kg in minimum, if the material is rapidly cooled-down after reaching the optimal temperature of 165 °C. Further roasting leads to a fast reduction of the canolol content. In addition it could be observed, that the sinapic acid content is not decreasing in the same amount as the canolol content increases. Sinapic acid seems to be "reproduced" during roasting. The reaction mechanisms of the described phenomena are not known. © 2014 F. Pudel et al., published by EDP Sciences.


Ramachandran C.,Dharma Biomedical LLC | Ramachandran C.,Miami Childrens Hospital | Quirin K.-W.,Flavex Naturextrakte GmbH | Escalon E.,Miami Childrens Hospital | And 2 more authors.
Journal of Evidence-Based Complementary and Alternative Medicine | Year: 2014

Ethnobotanical evidence suggests that herbs such as brahmi (Bacopa monnieri) and rosemary (Rosmarinus officinalis) may possess antioxidant and neuroprotective properties. We compared the antioxidant and neuroprotective effects of supercritical extract of Bacopa monnieri and rosemary antioxidant extract obtained from Rosmarinus officinalis as well as their combination to examine the effects on human glial (U-87 MG) and embryonic mouse hypothalamus cells. Bacopa monnieri extract, rosemary antioxidant extract, and their combination (1:1) are not cytotoxic in both glial and embryonic mouse hypothalamus cell lines up to 200 μg/mL concentration. The combination of extracts of Bacopa monnieri + rosemary antioxidant has better antioxidant potential and antilipid peroxidation activity than either agent alone. Although the extract of Bacopa monnieri + rosemary antioxidant showed almost similar inhibition of phospho tau expression as Bacopa monnieri or rosemary antioxidant extract alone, the combination has better inhibitory effect on amyloid precursor protein synthesis and higher brain-derived neurotrophic factor production in hypothalamus cells than single agents. These results suggest that the extract of Bacopa monnieri + rosemary antioxidant is more neuroprotective than Bacopa monnieri or rosemary antioxidant extract. © The Author(s) 2014.


Tarvainen M.,University of Turku | Nuora A.,University of Turku | Quirin K.-W.,Flavex Naturextrakte GmbH | Kallio H.,University of Turku | Yang B.,University of Turku
Food Chemistry | Year: 2014

Increasing concern of consumers on the safety of synthetic food additives has created high interest in natural preservatives in food industry. Plant extracts produced by supercritical CO2 technology from rosemary (R), oregano (O) and an antimicrobial blend (AB) consisting of seven different plants were studied for their effects on lipid oxidation in Atlantic salmon (Salmo salar). Fish pieces were marinated with rapeseed oil containing 0, 1, 2 or 4 g of plant extracts/kg of fish. After cooking the pieces were stored in refrigerator for 26 days. Peroxide values (PVs) were determined and oxidised triacylglycerols (TAGs) measured by UHPLC-ESI/MS at 0, 7, 14 and 26 days of storage. During the first two weeks of storage, AB delayed oxidation by at least one week compared to control samples as shown by PVs (<10 meq. O2) and by the oxidised TAGs. Oregano and rosemary showed also some antioxidative potential. © 2014 Elsevier Ltd.


Patent
Dharma Biomedical Llc and Flavex Naturextrakte Gmbh | Date: 2016-01-31

The invention concerns carbon dioxide extracts of Curcuma amada (mango ginger), including supercritical carbon dioxide extracts of C. amada; methods for their production; compositions comprising the extracts; methods for treating or delaying the onset of conditions such as cell proliferation disorder (e.g., cancer), inflammation, infection, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, platelet hyper-aggregation, immune disorder such as autoimmune disorder, or neurodegenerative condition; and methods for inhibiting expression of Bcl-2, Bak, and p53 genes; inhibiting expression of the COX-2 and NF-kB genes, inhibiting production of phosphorylated target of rapamycin (TOR), modulating AMP-activated protein kinase (AMPK), inhibiting protein kinase B (AKT) signaling, modulating the Ras/Raf/MEK/ERK signaling pathway, and modulating the Ras/PI3K/PTEN/Akt/mTOR signaling pathway. Another aspect of the invention concerns a method for inhibiting contamination, comprising applying the extract or composition of the invention to a surface. Another aspect of the invention concerns a method for promoting longevity of a cell in vitro or in vivo, comprising contacting a target cell in vitro or in vivo with an effective amount of the extract or composition of the invention. Another aspect of the invention concerns a method for promoting longevity of a subject, comprising administering an effective amount of the extract or composition of the invention. Another aspect of the invention concerns a method for inhibiting the metabolism of a cancer cell, comprising contacting the target cancer cell in vitro or in vivo with an effective amount of the extract or composition of the invention. Another aspect of the invention concerns a kit including the extract or composition; a container containing the extract or composition; and packaging material.


Patent
Dharma Biomedical Llc and Flavex Naturextrakte Gmbh | Date: 2013-01-11

The subject invention pertains to supercritical carbon dioxide extracts of Commiphora mukul resin (guggul), which can be modified or not modified by some ethanol addition; methods for their production; and methods of use, such as inhibiting HMG-CoA reductase, inhibiting transformation of pre-adipocytes to adipocytes, inhibiting triglyceride storage, promoting insulin sensitivity in adipocytes, treatment of disorders (for example, hypercholesterolemia, hyperlipidemia, hyperglycemia, obesity, metabolic syndrome, cardiovascular disease, atherosclerotic heart disease, autoimmune disorder, insulin resistance, leptin resistance, arthritis, cell proliferation disorder, such as cancer and atherosclerosis; damaged skin, sores, cuts, rashes, bruises, dryness, burns, sunburn, radiation burn, and infection), and regulating or suppressing appetite.


CO

PubMed | University of Turku and Flavex Naturextrakte GmbH
Type: Journal Article | Journal: Journal of agricultural and food chemistry | Year: 2016

Cholesterol oxidation products (COPs) in foods may pose risks for human health. Suitable antioxidants can reduce the formation of COPs in industrial products. Consumer awareness of food additives has brought a need for more natural alternatives. This is the first study on the effects of supercritical CO

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