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

The subject invention pertains to supercritical carbon dioxide extracts of

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 | 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 | Quirin K.-W.,Flavex Naturextrakte GmbH | Resek A.,Dharma Biomedical LLC | Melnick S.J.,Dharma Biomedical LLC
International Journal of Cosmetic Science | Year: 2012

Synopsis Coenzyme Q10 (CoQ10) is a major ingredient in skin care products because of its anti-wrinkle effects, although it has some side effects especially at higher amounts. In this study, we compare the anti-wrinkle related properties of CoQ10 and a proprietary Commiphora mukul gum resin (guggul) and triheptanoin preparation (GU-TC7). GU-TC7 is prepared with a supercritical CO 2-co-solvent extraction with ethanol, standardized to 2% guggulsterones and triheptanoin, a triglyceride composed of three 7-carbon fatty acids. Treatment of CCL-110 skin fibroblasts with GU-TC7 demonstrates a mild proliferative effect compared to CoQ10 and increased type I collagen synthesis. Additionally, GU-TC7 inhibited matrix metalloproteinase-1 (MMP-1) expression in a dose-dependent manner at 20-100 μg mL -1 and inhibited human elastase expression by more than 50% as compared to no elastase inhibition with CoQ10 treatment. These results suggest that GU-TC7 possesses properties that are applicable to the treatment of wrinkles and may be considered for its further evaluation in skin care products. © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

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.

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