Curcumin, a yellow polyphenolic pigment from the Curcuma longa L. (turmeric) rhizome, has been used for centuries for culinary and food coloring purposes, and as an ingredient for various medicinal preparations, widely used in Ayurveda and Chinese medicine. In recent decades, their biological activities have been extensively studied. Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease prevention, with particular emphasis on its antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, and cardioprotective effects. Bioavailability, bioefficacy and safety features, side effects, and quality parameters of curcumin are also addressed. Finally, curcumin's multidimensional applications, food attractiveness optimization, agro-industrial procedures to offset its instability and low bioavailability, health concerns, and upcoming strategies for clinical application are also covered.

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Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications.

Caffeic acid (3,4-dihydroxy cinnamic acid) (CA) is naturally found in fruits, vegetables, olive oil, and coffee. This study was undertaken to evaluate the anticancer effect of caffeic acid on HT-1080 human fibrosarcoma cell line. The antiproliferative effect of caffeic acid was determined by MTT assay, and the oxidative stress was determined by lipid peroxidation, changes in the enzymatic, and non-enzymatic antioxidant status. To understand the mode of antiproliferative effect of CA, the authors observed intracellular ROS levels by DCFH-DA method, mitochondrial membrane potential alterations by Rh-123 staining, oxidative DNA damage by comet assay, and apoptotic morphological changes by AO/EtBr-staining method. The results show that caffeic acid enhances lipid peroxidative markers such as TBARS, CD, and LHP in HT-1080 cell line. Caffeic acid enhances the ROS levels, which is evidenced by the increased DCF fluorescence. Further, caffeic acid treatment altered the mitochondrial membrane potential in HT-1080 cells. Similarly, the authors observed increased oxidative DNA damage (% Tail DNA, % Tail length, Tail moment, and olive tail moment), and apoptotic morphological changes in caffeic acid-treated groups. These data suggest that caffeic acid exhibits potent anticancer effect in HT-1080 cell line, and that it may be used as an anticancer agent.

Inhibitory effect of caffeic acid on cancer cell proliferation by oxidative mechanism in human HT-1080 fibrosarcoma cell line

Members of the genus Curcuma L. have been used in traditional medicine for centuries for treating gastrointestinal disorders, pain, inflammatory conditions, wounds, and for cancer prevention and antiaging, among others. Many of the biological activities of Curcuma species can be attributed to nonvolatile curcuminoids, but these plants also produce volatile chemicals. Essential oils, in general, have shown numerous beneficial effects for health maintenance and treatment of diseases. Essential oils from Curcuma spp., particularly C. longa, have demonstrated various health-related biological activities and several essential oil companies have recently marketed Curcuma oils. This review summarizes the volatile components of various Curcuma species, the biological activities of Curcuma essential oils, and potential safety concerns of Curcuma essential oils and their components.

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Chemical Composition and Biological Activities of Essential Oils of Curcuma Species.

The rising burden of cancer worldwide calls for an alternative treatment solution. Herbal medicine provides a very feasible alternative to western medicine against cancer. This article reviews the selected plant species with active phytochemicals, the animal models used for these studies, and their regulatory aspects. This study is based on a meticulous literature review conducted through the search of relevant keywords in databases, Web of Science, Scopus, PubMed, and Google Scholar. Twenty plants were selected based on defined selection criteria for their potent anticancer compounds. The detailed analysis of the research studies revealed that plants play an indispensable role in fighting different cancers such as breast, stomach, oral, colon, lung, hepatic, cervical, and blood cancer cell lines. The in vitro studies showed cancer cell inhibition through DNA damage and activation of apoptosis-inducing enzymes by the secondary metabolites in the plant extracts. Studies that reported in vivo activities of these plants showed remarkable results in the inhibition of cancer in animal models. Further studies should be performed on exploring more plants, their active compounds, and the mechanism of anticancer actions for use as standard herbal medicine.

Anticancer Plants: A Review of the Active Phytochemicals, Applications in Animal Models, and Regulatory Aspects

Bioassay-guided isolation of the active hexane fractions of Curcuma zedoaria led to the identification of five pure compounds, namely, curzerenone (1), neocurdione (2), curdione (3), alismol (4), and zederone (5) and a mixture of sterols, namely, campesterol (6), stigmasterol (7), and β-sitosterol (8). Alismol has never been reported to be present in Curcuma zedoaria. All isolated compounds except (3) were evaluated for their cytotoxic activity against MCF-7, Ca Ski, and HCT-116 cancer cell lines and noncancer human fibroblast cell line (MRC-5) using neutral red cytotoxicity assay. Curzerenone and alismol significantly inhibited cell proliferation in human cancer cell lines MCF-7, Ca Ski, and HCT-116 in a dose-dependent manner. Cytological observations by an inverted phase contrast microscope and Hoechst 33342/PI dual-staining assay showed typical apoptotic morphology of cancer cells upon treatment with curzerenone and alismol. Both compounds induce apoptosis through the activation of caspase-3. It can thus be suggested that curzerenone and alismol are modulated by apoptosis via caspase-3 signalling pathway. The findings of the present study support the use of Curcuma zedoaria rhizomes in traditional medicine for the treatment of cancer-related diseases. Thus, two naturally occurring sesquiterpenoids, curzerenone and alismol, hold great promise for use in chemopreventive and chemotherapeutic strategies.

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In Vitro Morphological Assessment of Apoptosis Induced by Antiproliferative Constituents from the Rhizomes of Curcuma zedoaria.

Curcuma zedoaria belonging to the family Zingiberaceae has been used in the traditional system of medicine in India and Southwest Asia in treating many human ailments and is found to possess many biological activities. The rationale of the present study was to isolate, identify, and characterize antitumour principles from the rhizomes of Curcuma zedoaria, to assess its cytotoxic effects on human and murine cancer cells, to determine its apoptosis inducing capacity in cancer cells, and to evaluate its tumour reducing properties in in vivo mice models. Isocurcumenol was characterized as the active compound by spectroscopy and was found to inhibit the proliferation of cancer cells without inducing significant toxicity to the normal cells. Fluorescent staining exhibited the morphological features of apoptosis in the compound-treated cancer cells. In vivo tumour reduction studies revealed that a dose of 35.7 mg/kg body weight significantly reduced the ascitic tumour in DLA-challenged mice and increased the lifespan with respect to untreated control mice.

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Antitumour Effects of Isocurcumenol Isolated from Curcuma zedoaria Rhizomes on Human and Murine Cancer Cells

Herbal medicine has formed the basis of health care throughout the world since the dawn of civilization. Each plant is a unique chemical factory capable of synthesizing unlimited numbers of highly complex and unusual chemical substances whose structures could otherwise escape the imagination forever. Phytomedicines have been used as a treatment for many diseases, ranging from skin disease to cancer. Most of the anticancer drugs that we use today are derived from plants. The anticancer effect of plants is due to specific phytochemicals or the complex synergistic interactions among their various constituents. The aim of the present study was to evaluate the cytotoxic properties of an extract of the Curucuma zedoariae rhizome, a plant belonging to the family Zingeberaceae, and to determine its IC50 value. Various organic extracts were isolated using Soxhlet apparatus in order of increasing solvent polarity, namely petroleum ether, ethyl acetate, acetone, and methanol. Colorimetric [3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] assay (MTT assay) was done to determine the cytotoxicity against human cervical carcinoma cells (He La). Acridine orange–ethidium dromide dual staining and DNA fragmentation assays were done to detect apoptotic features. Among the various extracts studied, the petroleum ether extract was found to exhibit maximum cytotoxicity against He La cells. Our results suggest that the petroleum ether extract of the Curucuma zedoariae rhizome may have potential as an anticancer agent. Further steps have to be done to purify the compound and to elucidate the antitumor activity of the extract.

Inhibitory effect of an extract of Curcuma zedoariae on human cervical carcinoma cells

Alpinia galanga (A. galanga) of Zingiberaceae family has been widely studied for their potential biological and medicinal properties. In this study, chrysin, isolated from A. galanga, was screened for the presence of the flavonoid compound 5,7-dihydroxyflavone. Chrysin was found to induce cytotoxicity and apoptosis in human lung cancer cells and murine lymphoma cells at 25, 50, and 75 µg/ml concentrations sparing the normal fibroblast cells and lymphocytes. Cell cycle analysis using flow cytometry showed that there was a dose-dependent increase of accumulation of the S-phase cells, causing a G1/S-phase arrest induced by chrysin at these concentrations. Annexin V- and active caspase-3-positive cells were found to increase dose dependently in these cells as evidenced by flow cytometry. The ascetic tumor reduction studies in Dalton’s lymphoma ascites mice models revealed that a dose of 1.3 mg/kg body weight of chrysin decreased the tumor volume significantly and increased the lifespan of mice to 52.6%. Moreover, the compound showed chemoprotective effects when administered along with cyclophosphamide, thereby reducing the toxic effects. These observations were confirmed using the evaluations of hematological parameters and liver and kidney function tests from animal studies. The synergistic interaction of chrysin with cyclophosphamide in terms of reducing the tumor size and increasing the lifespan of mice compared with the individual treatments suggests the possibility of reducing cyclophosphamide concentrations in the combination treatment.

In vitro and in vivo studies of 5,7-dihydroxy flavones isolated from Alpinia galanga (L.) against human lung cancer and ascetic lymphoma

In a letter to the editor, Raineri SM et al. have given an insight of another dimension of procalcitonin (PCT) use as a diagnostic tool in invasive candidiasis. But based on our preliminary information, PCT is reported as unconventional modes of diagnosis approach which yet to prove its stand-alone biomarker properties for invasive candidiasis.

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S. Lakshmi

Papers

Antitumour Effects of Isocurcumenol Isolated from Curcuma zedoaria Rhizomes on Human and Murine Cancer Cells

Inhibitory effect of an extract of Curcuma zedoariae on human cervical carcinoma cells

In vitro and in vivo studies of 5,7-dihydroxy flavones isolated from Alpinia galanga (L.) against human lung cancer and ascetic lymphoma

Response of letter to the editor on Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy.