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Jagan M R Patlolla

Bio: Jagan M R Patlolla is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Apoptosis & Celecoxib. The author has an hindex of 2, co-authored 2 publications receiving 355 citations.

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Journal Article
TL;DR: Results from the in vitro experiments indicated that diosgenin inhibits cell growth and induces apoptosis in the HT-29 human colon cancer cell line in a dose-dependent manner and seems to have potential as a novel colon cancer preventive agent.
Abstract: Trigonella foenum graecum (fenugreek) is traditionally used to treat disorders such as diabetes, high cholesterol, wounds, inflammation, and gastrointestinal ailments. Recent studies suggest that fenugreek and its active constituents may possess anticarcinogenic potential. We evaluated the preventive efficacy of dietary fenugreek seed and its major steroidal saponin constituent, diosgenin, on azoxymethane-induced rat colon carcinogenesis during initiation and promotion stages. Preneoplastic colonic lesions or aberrant crypt foci (ACF) were chosen as end points. In addition, we assessed the mechanism of tumor growth inhibition of diosgenin in HT-29 human colon cancer cells. To evaluate the effect of the test agent during the initiation and postinitiation stages, 7-week-old male F344 rats were fed experimental diets containing 0% or 1% fenugreek seed powder (FSP) or 0.05% or 0.1% diosgenin for 1 week and were injected with azoxymethane (15 mg/kg body weight). Effects during the promotional stage were studied by feeding 1% FSP or 0.1% diosgenin 4 weeks after the azoxymethane injections. Rats were sacrificed 8 weeks after azoxymethane injection, and their colons were evaluated for ACF. We found that, by comparison with control, continuous feeding of 1% FSP and 0.05% and 0.1% diosgenin suppressed total colonic ACF up to 32%, 24%, and 42%, respectively (P < or = 0.001 to 0.0001). Dietary FSP at 1% and diosgenin at 0.1% fed only during the promotional stage also inhibited total ACF up to 33% (P < or = 0.001) and 39% (P < or = 0.0001), respectively. Importantly, continuous feeding of 1% FSP or 0.05% or 0.1% diosgenin reduced the number of multicrypt foci by 38%, 20%, and 36% by comparison with the control assay (P < or = 0.001). In addition, 1% FSP or 0.1% diosgenin fed during the promotional stage caused a significant reduction (P < or = 0.001) of multicrypt foci compared with control. Dietary diosgenin at 0.1% and 0.05% inhibited total colonic ACF and multicrypt foci formation in a dose-dependent manner. Results from the in vitro experiments indicated that diosgenin inhibits cell growth and induces apoptosis in the HT-29 human colon cancer cell line in a dose-dependent manner. Furthermore, diosgenin induced apoptosis in HT-29 cells at least in part by inhibition of bcl-2 and by induction of caspase-3 protein expression. On the basis of these findings, the fenugreek constituent diosgenin seems to have potential as a novel colon cancer preventive agent.

301 citations

Journal Article
TL;DR: It is found that treatment with celecoxib or DHA individually induces apoptosis and inhibits cell proliferation only at high concentrations in HCA-7 cell lines, which provides the basis for the development of combinations of low-dose regimens of a COX-2 inhibitor and omega-3 PUFAs such as DHA for the prevention and treatment of colon cancer.
Abstract: To develop efficient synergistic or additive combinations of chemopreventive and nutritional agents to reduce the risk of colon cancer, experiments were designed to test the application of a selective cyclooxygenase-2 (COX-2) inhibitor together with dietary ω-3 polyunsaturated fatty acids (PUFAs), such as decosahexaenoic acid (DHA). Thus, individual application of celecoxib, a COX-2 inhibitor, DHA, a ω-3 PUFA, and combinations of both were tested for their effectiveness using cell proliferation, apoptosis, and COX-2 expression as markers in the human colon cancer HCA-7 cell line. HCA-7 cells exposed to various subtoxic doses of celecoxib, DHA, or combinations of both were analyzed for inhibition of cell proliferation by trypan blue exclusion and proliferating cell nuclear antigen methods, induction of apoptosis by 4′,6-diamidino-2-phenylindole method, and COX-2 by reverse transcription-PCR and Western blot analysis. In addition, we examined the inhibitory potential of celecoxib and DHA on 14C-arachidonic acid metabolism mediated by COX-2 in the HCA-7 cell line. We found that treatment with celecoxib (50–150 μm) or DHA (150–225 μm) individually induces apoptosis and inhibits cell proliferation only at high concentrations in HCA-7 cell lines. A synergistic effect was observed on induction of apoptosis and inhibition of proliferation when cells were exposed to low doses of celecoxib (50–100 μm) together with DHA (75 μm). At high concentrations, celecoxib and DHA blocked the increase in COX-2 protein and mRNA expression in HCA-7 cells. Importantly, the inhibition of COX-2 expression was more pronounced in cells treated with low-dose combinations than with individual agents at high concentrations. In addition, celecoxib and DHA at low-dose levels inhibited 14C-arachidonic acid metabolism (50–85%, P < 0.0001) leading to very low levels of type 2 series prostaglandin formation. These findings provide the basis for the development of combinations of low-dose regimens of a COX-2 inhibitor and ω-3 PUFAs such as DHA for the prevention and treatment of colon cancer. We are currently testing this concept in preclinical models.

76 citations


Cited by
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Journal ArticleDOI
TL;DR: This review provides an update on the sources, properties, and applications of saponins with special focus on their extraction and purification, and is the recent literature on the effect of processing on saponin structure/properties and the extraction and Purification of sapogenins.
Abstract: Saponins are a diverse group of compounds widely distributed in the plant kingdom, which are characterized by their structure containing a triterpene or steroid aglycone and one or more sugar chains. Consumer demand for natural products coupled with their physicochemical (surfactant) properties and mounting evidence on their biological activity (such as anticancer and anticholesterol activity) has led to the emergence of saponins as commercially significant compounds with expanding applications in food, cosmetics, and pharmaceutical sectors. The realization of their full commercial potential requires development of new processes/processing strategies to address the processing challenges posed by their complex nature. This review provides an update on the sources, properties, and applications of saponins with special focus on their extraction and purification. Also reviewed is the recent literature on the effect of processing on saponin structure/properties and the extraction and purification of sapogenins.

778 citations

Journal ArticleDOI
TL;DR: This article reviews many such structures and their related chemistry along with the recent advances in understanding mechanism of action and structure-function relationships of saponins at the molecular and cellular levels.

377 citations

Journal ArticleDOI
TL;DR: The results validate the traditional use of this plant and zerumbone has been demonstrated to be a potent anti-inflammatory and analgesic agent.
Abstract: Moringa oleifera grown and used in many countries around the world is a multi-purpose tree with medicinal, nutritional and socio-economic values. In Senegal and Benin, M. oleifera leaves are dispensed as powder at health facilities to treat moderate malnutrition in children. It established the medicinal uses of M. oleiferaleaves by local communities in Uganda and identified phytochemicals present inM. oleifera leaves extracts. It used quantitative and experimental methods that established the uses, and identified phytochemicals in M. oleifera leaves. Employed serial extractions, using ether, ethanol and water as solvents. The phytochemicals were qualitatively identified using standard chemicals and standard outcomes. Twenty-four medicinal uses of M. oleifera leaves were established. Phytochemicals present included: tannins, steroids and triterponoids, flavonoids, saponins, anthraquinones, alkaloids and reducing sugars. The local communities in Uganda use M. oleifera leaves to treat common ailments. Presence of phytochemicals in the extracts, indicate possible preventive and curative property of M. oleifera leaves. There is need to standardize M. oleifera leaves use for nutrition and herbal medicine. Key words: Phytochemicals, medicinal plant extracts, herbal medicine, Uganda.

368 citations

Journal ArticleDOI
TL;DR: Ayurveda, a science of long life, almost 6,000 years old, can serve as a "goldmine" for novel anti-inflammatory agents used for centuries to treat chronic diseases, and description of various Ayurvedic plants currently used for treatment, their active chemical components, and the inflammatory pathways that they inhibit are provided.
Abstract: Inflammation, although first characterized by Cornelius Celsus, a physician in first Century Rome, it was Rudolf Virchow, a German physician in nineteenth century who suggested a link between inflammation and cancer, cardiovascular diseases, diabetes, pulmonary diseases, neurological diseases and other chronic diseases. Extensive research within last three decades has confirmed these observations and identified the molecular basis for most chronic diseases and for the associated inflammation. The transcription factor, Nuclear Factor-kappaB (NF-kappaB) that controls over 500 different gene products, has emerged as major mediator of inflammation. Thus agents that can inhibit NF-kappaB and diminish chronic inflammation have potential to prevent or delay the onset of the chronic diseases and further even treat them. In an attempt to identify novel anti-inflammatory agents which are safe and effective, in contrast to high throughput screen, we have turned to "reverse pharmacology" or "bed to benchside" approach. We found that Ayurveda, a science of long life, almost 6,000 years old, can serve as a "goldmine" for novel anti-inflammatory agents used for centuries to treat chronic diseases. The current review is an attempt to provide description of various Ayurvedic plants currently used for treatment, their active chemical components, and the inflammatory pathways that they inhibit.

333 citations

Journal ArticleDOI
TL;DR: The results of a great number of studies focusing on phytochemicals such as essential oils, saponins, flavonoids and phytosterols discussing their effects on productive traits and the putative mechanism of action are reviewed.
Abstract: There is a constant need to increase productivity in aquaculture, particularly to improve growth rate, feed utilization as well as stress resistance of fish. Because of consumer concerns and strict regulations in many countries, the use of synthetic chemicals, hormones and antibiotics is becoming unviable and natural compounds are more acceptable to the public. A wide variety of chemical compounds are found in plants, and many of them have been shown to have beneficial effects on appetite, growth and the immune status of fish acting through different mechanisms. Phytochemicals contained in herbs may enhance the innate immune system, possess antimicrobial capabilities, and are redox active molecules with antioxidant characteristics that may help to improve the general physiological condition of fish. Many studies have discussed the values of phytochemicals as feed additives. Another paramount concern related to phytochemicals is their endocrine modulator effect that can be applied both in aquaculture targeting the production of table fish and the growing sector of ornamental fish production. Different mechanisms such as the effects at the steroid receptor level, effects on steroid synthesis, distribution and excretion, actions on the hypothalamus–pituitary–gonad axis, as well as indirect mechanisms including thyroid and growth hormone disruption have been postulated for the reproductive endocrine disruption in fish populations by phytochemicals. This paper reviews the results of a great number of studies focusing on phytochemicals such as essential oils, saponins, flavonoids and phytosterols discussing their effects on productive traits and the putative mechanism of action.

257 citations