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Arora R. Glucosinolate Hydrolytic Products-A Multi-Arm Warrior. J AOAC Int 2024; 107:876-883. [PMID: 38964347 DOI: 10.1093/jaoacint/qsae054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 12/08/2023] [Accepted: 06/18/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND Glucosinolates (GSLs) are the most controversial yet ignored class of phytochemicals. These are the middleman phytochemicals that have low bioactivity. But once there is any injury in the plant-manmade, insect caused, or natural-magic happens. The compound is broken down into smaller phytochemicals referred to as glucosinolate hydrolytic products (GHPs; nitriles, isothiocyanates [ITCs], and thiocyanates). These hydrolytic products are like a showstopper of the fashion industry. These compounds have some of the highest bioactivity in nature. They have been associated with a varied range of bioactivities (anticancer, antioxidant, insecticidal, weedicide, etc.) by researchers across the globe. OBJECTIVE The objective of the current article is to provide a critical review to highlight some of the important bioactivities of these ignored compounds and for promoting researchers to at least give these compounds a chance-to glow in the dark. METHODS This review has been written from analysis of accessible literature, mostly from the last 5 years (2018-2023), with some critically essential exceptions. RESULTS The review highlighted a brief background of GSLs and its hydrolysis. Efforts were made to include most of the biological properties of the compound. Special emphasis has been given to the anticancer activities of the compound with details of the involved mechanism. CONCLUSIONS Considering the wide array of bioactivities of GHPs, it is essential to consider it as a prospective medicinal compound. More GHPs-in a similar manner as sulforaphane-can be proceeded to phase trials. HIGHLIGHTS The mechanistic pathway for production of GHPs and related biological activities have been discussed in detail. The bioactivities have been further explained using the involved mechanism.
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Affiliation(s)
- Rohit Arora
- Department of Women and Baby, Sunnybrook Research Institute, 2075 Bayview Ave, North York, Ontario, M4N 3M5, Canada
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Yamaguchi Y, Sugiki M, Shimizu M, Ogawa K, Kumagai H. Comparative analysis of isothiocyanates in eight cruciferous vegetables and evaluation of the hepatoprotective effects of 4-(methylsulfinyl)-3-butenyl isothiocyanate (sulforaphene) from daikon radish ( Raphanus sativus L.) sprouts. Food Funct 2024; 15:4894-4904. [PMID: 38597802 DOI: 10.1039/d4fo00133h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
The contributions of cruciferous vegetables to human health are widely recognised, particularly at the molecular level, where their isothiocyanates play a significant role. However, compared to the well-studied isothiocyanate 4-(methylsulfinyl)butyl isothiocyanate (sulforaphane) produced from broccoli sprouts, less is known about the pharmacological effects of other isothiocyanates and the stage of vegetables preferable to obtain their benefits. We analysed the quantity and quality of isothiocyanates produced in both the sprouts and mature stages of eight cruciferous vegetables using gas chromatography-mass spectrometry (GC-MS). Additionally, we investigated the hepatoprotective effects of isothiocyanates in a mouse model of acute hepatitis induced by carbon tetrachloride (CCl4). Furthermore, we explored the detoxification enzyme-inducing activities of crude sprout extracts in normal rats. Among the eight cruciferous vegetables, daikon radish (Raphanus sativus L.) sprouts produced the highest amount of isothiocyanates, with 4-(methylsulfinyl)-3-butenyl isothiocyanate (sulforaphene) being the dominant compound. The amount of sulforaphene in daikon radish sprouts was approximately 30 times that of sulforaphane in broccoli sprouts. Sulforaphene demonstrated hepatoprotective effects similar to sulforaphane in ameliorating CCl4-induced hepatic injury in mice. A crude extract of 3-day-old daikon radish sprouts upregulated the detoxifying enzyme glutathione S-transferase (GST) in the liver, whereas the crude extract of broccoli sprouts showed limited upregulation. This study highlights that daikon radish sprouts and sulforaphene have the potential to serve as functional food materials with hepatoprotective effects. Furthermore, daikon radish sprouts may exhibit more potent hepatoprotective effects compared to broccoli sprouts.
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Affiliation(s)
- Yusuke Yamaguchi
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
| | - Mikio Sugiki
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
| | - Motomi Shimizu
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
| | - Kazuki Ogawa
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
| | - Hitomi Kumagai
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
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Nakatake R, Okuyama T, Hashimoto Y, Ishizaki M, Yanagida H, Kitade H, Yoshizawa K, Nishizawa M, Sekimoto M. Sulforaphane Is Protective against Warm Ischemia/Reperfusion Injury and Partial Hepatectomy in Rats. Int J Mol Sci 2024; 25:579. [PMID: 38203749 PMCID: PMC10778753 DOI: 10.3390/ijms25010579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 12/27/2023] [Accepted: 12/30/2023] [Indexed: 01/12/2024] Open
Abstract
Sulforaphane (SFN) has various beneficial effects on organ metabolism. However, whether SFN affects inflammatory mediators induced by warm hepatic ischemia/reperfusion injury (HIRI) is unclear. To investigate the hepatoprotective effects of SFN using an in vivo model of HIRI and partial hepatectomy (HIRI + PH), rats were subjected to 15 min of hepatic ischemia with blood inflow occlusion, followed by 70% hepatectomy and release of the inflow occlusion. SFN (5 mg/kg) or saline was randomly injected intraperitoneally 1 and 24 h before ischemia. Alternatively, ischemia was prolonged for 30 min to evaluate the effect on mortality. The influence of SFN on the associated signaling pathways was analyzed using the interleukin 1β (IL-1β)-treated primary cultured rat hepatocytes. In the HIRI + PH-treated rats, SFN reduced serum liver enzyme activities and the frequency of pathological liver injury, such as apoptosis and neutrophil infiltration. SFN suppressed tumor necrosis factor-alpha (TNF-α) mRNA expression and inhibited nuclear factor-kappa B (NF-κB) activation by HIRI + PH. Mortality was significantly reduced by SFN. In IL-1β-treated hepatocytes, SFN suppressed the expression of inflammatory cytokines and NF-κB activation. Taken together, SFN may have hepatoprotective effects in HIRI + PH in part by inhibiting the induction of inflammatory mediators, such as TNF-α, via the suppression of NF-κB in hepatocytes.
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Affiliation(s)
- Richi Nakatake
- Department of Surgery, Kansai Medical University, Hirakata 573-1010, Osaka, Japan; (T.O.); (Y.H.)
| | - Tetsuya Okuyama
- Department of Surgery, Kansai Medical University, Hirakata 573-1010, Osaka, Japan; (T.O.); (Y.H.)
| | - Yuki Hashimoto
- Department of Surgery, Kansai Medical University, Hirakata 573-1010, Osaka, Japan; (T.O.); (Y.H.)
| | - Morihiko Ishizaki
- Department of Surgery, Kansai Medical University, Hirakata 573-1010, Osaka, Japan; (T.O.); (Y.H.)
| | - Hidesuke Yanagida
- Department of Surgery, Kansai Medical University, Hirakata 573-1010, Osaka, Japan; (T.O.); (Y.H.)
| | - Hiroaki Kitade
- Department of Surgery, Kansai Medical University, Hirakata 573-1010, Osaka, Japan; (T.O.); (Y.H.)
| | - Katsuhiko Yoshizawa
- Department of Innovative Food Sciences, School of Food Sciences and Nutrition, Mukogawa Women’s University, 6-46 Ikebiraki-cho, Nishinomiya 663-8558, Hyogo, Japan;
| | - Mikio Nishizawa
- Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu 525-8577, Shiga, Japan
| | - Mitsugu Sekimoto
- Department of Surgery, Kansai Medical University, Hirakata 573-1010, Osaka, Japan; (T.O.); (Y.H.)
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Singla RK, Wang X, Gundamaraju R, Joon S, Tsagkaris C, Behzad S, Khan J, Gautam R, Goyal R, Rakmai J, Dubey AK, Simal-Gandara J, Shen B. Natural products derived from medicinal plants and microbes might act as a game-changer in breast cancer: a comprehensive review of preclinical and clinical studies. Crit Rev Food Sci Nutr 2023; 63:11880-11924. [PMID: 35838143 DOI: 10.1080/10408398.2022.2097196] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Breast cancer (BC) is the most prevalent neoplasm among women. Genetic and environmental factors lead to BC development and on this basis, several preventive - screening and therapeutic interventions have been developed. Hormones, both in the form of endogenous hormonal signaling or hormonal contraceptives, play an important role in BC pathogenesis and progression. On top of these, breast microbiota includes both species with an immunomodulatory activity enhancing the host's response against cancer cells and species producing proinflammatory cytokines associated with BC development. Identification of novel multitargeted therapeutic agents with poly-pharmacological potential is a dire need to combat advanced and metastatic BC. A growing body of research has emphasized the potential of natural compounds derived from medicinal plants and microbial species as complementary BC treatment regimens, including dietary supplements and probiotics. In particular, extracts from plants such as Artemisia monosperma Delile, Origanum dayi Post, Urtica membranacea Poir. ex Savigny, Krameria lappacea (Dombey) Burdet & B.B. Simpson and metabolites extracted from microbes such as Deinococcus radiodurans and Streptomycetes strains as well as probiotics like Bacillus coagulans and Lactobacillus brevis MK05 have exhibited antitumor effects in the form of antiproliferative and cytotoxic activity, increase in tumors' chemosensitivity, antioxidant activity and modulation of BC - associated molecular pathways. Further, bioactive compounds like 3,3'-diindolylmethane, epigallocatechin gallate, genistein, rutin, resveratrol, lycopene, sulforaphane, silibinin, rosmarinic acid, and shikonin are of special interest for the researchers and clinicians because these natural agents have multimodal action and act via multiple ways in managing the BC and most of these agents are regularly available in our food and fruit diets. Evidence from clinical trials suggests that such products had major potential in enhancing the effectiveness of conventional antitumor agents and decreasing their side effects. We here provide a comprehensive review of the therapeutic effects and mechanistic underpinnings of medicinal plants and microbial metabolites in BC management. The future perspectives on the translation of these findings to the personalized treatment of BC are provided and discussed.
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Affiliation(s)
- Rajeev K Singla
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- iGlobal Research and Publishing Foundation, New Delhi, India
| | - Xiaoyan Wang
- Department of Pathology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Rohit Gundamaraju
- ER Stress and Mucosal Immunology Lab, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia
| | - Shikha Joon
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- iGlobal Research and Publishing Foundation, New Delhi, India
| | | | - Sahar Behzad
- Evidence-based Phytotherapy and Complementary Medicine Research Center, Alborz University of Medical Sciences, Karaj, Iran
- Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Johra Khan
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi Arabia
- Health and Basic Sciences Research Center, Majmaah University, Majmaah, Saudi Arabia
| | - Rupesh Gautam
- Department of Pharmacology, MM School of Pharmacy, MM University, Sadopur, Haryana, India
| | - Rajat Goyal
- Department of Pharmacology, MM School of Pharmacy, MM University, Sadopur, Haryana, India
| | - Jaruporn Rakmai
- Kasetsart Agricultural and Agro-Industrial Product Improvement Institute (KAPI), Kasetsart University, Bangkok, Thailand
| | | | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, Universidade de Vigo, Ourense, Spain
| | - Bairong Shen
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Yan L, Yan Y. Therapeutic potential of sulforaphane in liver diseases: a review. Front Pharmacol 2023; 14:1256029. [PMID: 37705537 PMCID: PMC10495681 DOI: 10.3389/fphar.2023.1256029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 08/11/2023] [Indexed: 09/15/2023] Open
Abstract
The burden of liver diseases such as metabolic-associated fatty liver diseases and hepatocellular carcinoma has increased rapidly worldwide over the past decades. However, pharmacological therapies for these liver diseases are insufficient. Sulforaphane (SFN), an isothiocyanate that is mainly found in cruciferous vegetables, has been found to have a broad spectrum of activities like antioxidation, anti-inflammation, anti-diabetic, and anticancer effects. Recently, a growing number of studies have reported that SFN could significantly ameliorate hepatic steatosis and prevent the development of fatty liver, improve insulin sensitivity, attenuate oxidative damage and liver injury, induce apoptosis, and inhibit the proliferation of hepatoma cells through multiple signaling pathways. Moreover, many clinical studies have demonstrated that SFN is harmless to the human body and well-tolerated by individuals. This emerging evidence suggests SFN to be a promising drug candidate in the treatment of liver diseases. Nevertheless, limitations exist in the development of SFN as a hepatoprotective drug due to its special properties, including instability, water insolubility, and high inter-individual variation of bioavailability when used from broccoli sprout extracts. Herein, we comprehensively review the recent progress of SFN in the treatment of common liver diseases and the underlying mechanisms, with the aim to provide a better understanding of the therapeutic potential of SFN in liver diseases.
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Affiliation(s)
- Liang Yan
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Chen SY, Kannan M. Neural crest cells and fetal alcohol spectrum disorders: Mechanisms and potential targets for prevention. Pharmacol Res 2023; 194:106855. [PMID: 37460002 PMCID: PMC10528842 DOI: 10.1016/j.phrs.2023.106855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 06/23/2023] [Accepted: 07/14/2023] [Indexed: 07/26/2023]
Abstract
Fetal alcohol spectrum disorders (FASD) are a group of preventable and nongenetic birth defects caused by prenatal alcohol exposure that can result in a range of cognitive, behavioral, emotional, and functioning deficits, as well as craniofacial dysmorphology and other congenital defects. During embryonic development, neural crest cells (NCCs) play a critical role in giving rise to many cell types in the developing embryos, including those in the peripheral nervous system and craniofacial structures. Ethanol exposure during this critical period can have detrimental effects on NCC induction, migration, differentiation, and survival, leading to a broad range of structural and functional abnormalities observed in individuals with FASD. This review article provides an overview of the current knowledge on the detrimental effects of ethanol on NCC induction, migration, differentiation, and survival. The article also examines the molecular mechanisms involved in ethanol-induced NCC dysfunction, such as oxidative stress, altered gene expression, apoptosis, epigenetic modifications, and other signaling pathways. Furthermore, the review highlights potential therapeutic strategies for preventing or mitigating the detrimental effects of ethanol on NCCs and reducing the risk of FASD. Overall, this article offers a comprehensive overview of the current understanding of the impact of ethanol on NCCs and its role in FASD, shedding light on potential avenues for future research and intervention.
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Affiliation(s)
- Shao-Yu Chen
- Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292, USA; University of Louisville Alcohol Research Center, Louisville, KY 40292, USA.
| | - Maharajan Kannan
- Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292, USA; University of Louisville Alcohol Research Center, Louisville, KY 40292, USA.
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Abstract
Liver fibrosis has a high incidence worldwide and is the common pathological basis of many chronic liver diseases. Liver fibrosis is caused by the excessive deposition of extracellular matrix and concomitant collagen accumulation in livers and can lead to the development of liver cirrhosis and even liver cancer. A large number of studies have provided evidence that liver fibrosis can be blocked or even reversed by appropriate medical interventions. However, the antifibrosis drugs with ideal clinical efficacy are still insufficient. The edible plant-derived natural compounds have been reported to exert effective antifibrotic effects with few side-effects, representing a kind of promising source for the treatment of liver fibrosis. In this article, we reviewed the current progress of the natural compounds derived from dietary plants in the treatment of liver fibrosis, including phenolic compounds (capsaicin, chlorogenic acid, curcumin, ellagic acid, epigallocatechin-3-gallate, resveratrol, sinapic acid, syringic acid, vanillic acid and vitamin E), flavonoid compounds (genistein, hesperidin, hesperetin, naringenin, naringin and quercetin), sulfur-containing compounds (S-allylcysteine, ergothioneine, lipoic acid and sulforaphane) and other compounds (betaine, caffeine, cucurbitacin B, lycopene, α-mangostin, γ-mangostin, ursolic acid, vitamin C and yangonin). The pharmacological effects and related mechanisms of these compounds in in-vivo and in-vitro models of liver fibrosis are focused.
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Gao L, Li H, Li B, Shao H, Yu X, Miao Z, Zhang L, Zhu L, Sheng H. Traditional uses, phytochemistry, transformation of ingredients and pharmacology of the dried seeds of Raphanus sativus L. (Raphani Semen), A comprehensive review. JOURNAL OF ETHNOPHARMACOLOGY 2022; 294:115387. [PMID: 35580770 DOI: 10.1016/j.jep.2022.115387] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/03/2022] [Accepted: 05/11/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Raphani Semen (Lai Fu-zi in Chinese, RS), the dried seeds of Raphanus sativus L., is a traditional Chinese herbal medicine. RS has long been used for eliminating bloating and digestion, antitussive, expectorant and anti-asthmatic in clinical treatment of traditional Chinese medicine. AIM OF THE STUDY This review provides a critical and comprehensive summary of traditional uses, phytochemistry, transformation of ingredients and pharmacology of RS based on research data that have been reported, aiming at providing a basis for further study on RS. MATERIALS AND METHODS The search terms "Raphani Semen", "the seeds of Raphanus sativus L." and "radish seed" were used to obtain the information from electronic databases such as Web of Science, China National Knowledge Infrastructure, PubMed and other web search instruments. Traditional uses, phytochemistry, transformation of ingredients and pharmacology of RS were summarized. RESULTS RS has been traditionally used to treat food dyspeptic retention, distending pain in the epigastrium and abdomen, constipation, diarrhea and dysentery, panting, and cough with phlegm congestion in the clinical practice. The chemical constituents of RS include glucosinolates and sulfur-containing derivatives, phenylpropanoid sucrosides, small organic acids and derivatives, flavone glycosides, alkaloids, terpenoids, steroids, oligosaccharides and others. Among them, glucosinolates can be transformated to isothiocyanates by plant myrosinase or the intestinal flora, which display a variety of activities, such as anti-tumor, anti-inflammatory, antioxidant, antibacterial, treatment of metabolic diseases, central nervous system protection, anti-osteoporosis. RS has a variety of pharmacological activities, including treatment of metabolic diseases, anti-inflammatory, anti-tumor, antioxidant, antibacterial, antihypertensive, central nervous system protection, anti-osteoporosis, etc. This review will provide useful insight for exploration, further study and precise medication of RS in the future. CONCLUSIONS According to its traditional uses, phytochemistry, transformation of ingredients and pharmacology, RS is regarded as a promising medical plant with various chemical compounds and numerous pharmacological activities. However, the material bases and mechanisms of traditional effect of RS need further study.
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Affiliation(s)
- Lei Gao
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Huan Li
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Bingqian Li
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Huili Shao
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Xinyue Yu
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Zhuang Miao
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Lizhen Zhang
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Liqiao Zhu
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
| | - Huagang Sheng
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
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Lee KD, Shim SY. Anti-Inflammatory Food in Asthma Prepared from Combination of Raphanus sativus L., Allium hookeri, Acanthopanax sessiliflorum, and Dendropanax morbiferus Extracts via Bioassay-Guided Selection. Foods 2022; 11:foods11131910. [PMID: 35804727 PMCID: PMC9265937 DOI: 10.3390/foods11131910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/17/2022] [Accepted: 06/19/2022] [Indexed: 12/10/2022] Open
Abstract
Asthma is a highly prevalent inflammatory disease of the respiratory airways and an increasing health risk worldwide. Hence, finding new strategies to control or attenuate this condition is necessary. This study suggests nutraceuticals that are a combination of herbal plant extracts prepared from Acanthopanax sessiliflorum (AS), Codonopsis lanceolate (CL), Dendropanax morbiferus (DM), Allium hookeri (AH), and Raphanus sativus L. (RS) that can improve immunomodulatory ability through the detoxification and diuresis of air pollutants. Herbal parts (AH whole plant, RS and CL roots, AS and DM stems, and DM leaves) were selected, and four types of mixtures using plant extracts were prepared. Among these mixtures, M2 and M4 exhibited antioxidant activities in potent 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) and 1,1-diphenyl-β-picrylhydrazine (DPPH) radical assays. Moreover, M4 exhibited a marked increase in glutathione S-transferase (GST) activity and significantly inhibited the inflammatory mediator, nitric oxide (NO) and proinflammatory cytokines, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α generation. Furthermore, M4 exhibited the strongest antioxidant, hepatoprotective, and anti-inflammatory effects and was selected to prepare the product. Before manufacturing the product, we determined that the active mixture, M4, inhibited gene expression and generation of proinflammatory cytokines IL-1β, IL-6 and TNF-α in ovalbumin (OVA)-, lipopolysaccharide (LPS)-, and particulate matter (PM)-induced asthmatic rat models. The granular product (GP) was manufactured using M4 along with additives, i.e., lactose, oligosaccharide, stevioside extract, and nutmeg seed essential oils (flavor masking), in a ratio of 1:4 using a granulation machine, dried and ultimately packaged. The GP inhibited the generation of proinflammatory cytokines IL-1β, IL-6 and TNF-α in OVA-, LPS- and PM-induced asthmatic rat models. These results suggest that GP prepared from a combination of herbal plants (AS, CL, DM, AH and RS) is a potent functional food with anti-inflammatory activity that can be used to treat asthma caused by ambient air pollutants.
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Affiliation(s)
- Kyung-Dong Lee
- Department of Companion Animal Industry, College of Health & Welfare, Dongshin University, Naju 58245, Korea;
| | - Sun-Yup Shim
- Department of Food Science and Technology, College of Life Science and Natural Resources, Sunchon National University, Suncheon 57922, Korea
- Correspondence: ; Tel./Fax: +82-61-750-3250
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Jayasuriya R, Dhamodharan U, Ali D, Ganesan K, Xu B, Ramkumar KM. Targeting Nrf2/Keap1 signaling pathway by bioactive natural agents: Possible therapeutic strategy to combat liver disease. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 92:153755. [PMID: 34583226 DOI: 10.1016/j.phymed.2021.153755] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 09/03/2021] [Accepted: 09/12/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Nuclear factor erythroid 2-related factor (Nrf2), a stress-activated transcription factor, has been documented to induce a defense mechanism against oxidative stress damage, and growing evidence considers this signaling pathway a key pharmacological target for the treatment of liver diseases. PURPOSE The present review highlights the role of phytochemical compounds in activating Nrf2 and mitigate toxicant-induced stress on liver injury. METHODS A comprehensive search of published articles was carried out to focus on original publications related to Nrf2 activators against liver disease using various literature databases, including the scientific Databases of Science Direct, Web of Science, Pubmed, Google, EMBASE, and Scientific Information (SID). RESULTS Nrf2 activators exhibited promising effects in resisting a variety of liver diseases induced by different toxicants in preclinical experiments and in vitro studies by regulating cell proliferation and apoptosis as well as an antioxidant defense mechanism. We found that the phytochemical compounds, such as curcumin, naringenin, sulforaphane, diallyl disulfide, mangiferin, oleanolic acid, umbelliferone, daphnetin, quercetin, isorhamnetin-3-O-galactoside, hesperidin, diammonium glycyrrhizinate, corilagin, shikonin, farrerol, and chenpi, had the potential to improve the Nrf2-ARE signaling thereby combat hepatotoxicity. CONCLUSION Nrf2 activators may offer a novel potential strategy for the prevention and treatment of liver diseases. More extensive studies are essential to identify the underlying mechanisms and establish future therapeutic potentials of these signaling modulators. Further clinical trials are warranted to determine the safety and effectiveness of Nrf2 activators for hepatopathy.
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Affiliation(s)
- Ravichandran Jayasuriya
- SRM Research Institute and Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India
| | | | - Daoud Ali
- Department of Zoology, College of Science, King Saud University P.O. Box 2455, Riyadh 11451 Saudi Arabia
| | - Kumar Ganesan
- Li Ka Shing Faculty of Medicine, School of Chinese Medicine, The University of Hong Kong, Hong Kong, China
| | - Baojun Xu
- Food Science and Technology Program, BNU-HKBU United International College, Zhuhai 519087, China.
| | - Kunka Mohanram Ramkumar
- SRM Research Institute and Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India.
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Ungureanu C, Fierascu I, Fierascu RC, Costea T, Avramescu SM, Călinescu MF, Somoghi R, Pirvu C. In Vitro and In Vivo Evaluation of Silver Nanoparticles Phytosynthesized Using Raphanus sativus L. Waste Extracts. MATERIALS 2021; 14:ma14081845. [PMID: 33917755 PMCID: PMC8068147 DOI: 10.3390/ma14081845] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 04/02/2021] [Accepted: 04/06/2021] [Indexed: 02/08/2023]
Abstract
The aim of the current paper is the development of phytosynthesized silver nanoparticles mediated by Raphanus sativus L. extracts obtained through two extraction methods (temperature and microwave) and to test their potential application for controlling apple crops pathogens. The phytosynthesized materials were characterized by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. All the materials were evaluated in terms of antioxidant and in vitro antimicrobial activity (against bacteria, molds, and yeast: Escherichia coli ATCC 8738, Staphylococcus aureus ATTC 25923, Pseudomonas aeruginosa ATCC 9027, Salmonella typhimurium ATCC 14028, Candida albicans ATCC 10231, Venturia inaequalis, Podosphaera leucotricha, Fusarium oxysporum ATCC 48112, Penicillium hirsutum ATCC 52323, and Aspergillus niger ATCC 15475). Considering the results obtained in the in vitro assays, formulations based on nanoparticles phytosynthesized using Raphanus sativus L. waste extracts (RS1N) were evaluated as potential antifungal agents for horticultural crops protection, against Venturia inaequalis and Podosphaera leucotricha through in vivo assays. For the DPPH assay, the inhibition (%) varied between 37.06% (for RS1N at 0.8 mg/mL concentration) and 83.72% (for RS1N at 7.2 mg/mL concentration) compared to 19.97% (for RS2N at 0.8 mg/mL) and only 28.91% (for RS2N at 7.2 mg/mL). Similar results were obtained for RS3N (85.42% inhibition at 7.2 mg/mL) compared with RS4N (21.76% inhibition at 7.2 mg/mL). Regarding the ABTS assay, the highest scavenger activity values were recorded for samples RS1N (91.43% at 1.6 mg/mL) and RS3N (96.62% at 1.6 mg/mL).
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Affiliation(s)
- Camelia Ungureanu
- Department of General Chemistry, University “Politehnica” of Bucharest, 011061 Bucharest, Romania;
- Correspondence: (C.U.); (R.C.F.)
| | - Irina Fierascu
- National Institute for Research & Development in Chemistry and Petrochemistry—ICECHIM, 060021 Bucharest, Romania; (I.F.); (R.S.)
- Faculty of Horticulture, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 011464 Bucharest, Romania
| | - Radu Claudiu Fierascu
- National Institute for Research & Development in Chemistry and Petrochemistry—ICECHIM, 060021 Bucharest, Romania; (I.F.); (R.S.)
- Department of Science and Engineering of Oxide Materials and Nanomaterials, University “Politehnica” of Bucharest, 011061 Bucharest, Romania
- Correspondence: (C.U.); (R.C.F.)
| | - Teodora Costea
- Phytotherapy Department, Faculty of Pharmacy, Pharmacognosy, Phytochemistry, University of Medicine and Pharmacy “Carol Davila”, 020956 Bucharest, Romania;
| | - Sorin Marius Avramescu
- Research Center for Environmental Protection and Waste Management, University of Bucharest, 050107 Bucharest, Romania;
| | | | - Raluca Somoghi
- National Institute for Research & Development in Chemistry and Petrochemistry—ICECHIM, 060021 Bucharest, Romania; (I.F.); (R.S.)
| | - Cristian Pirvu
- Department of General Chemistry, University “Politehnica” of Bucharest, 011061 Bucharest, Romania;
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Ishida K, Kaji K, Sato S, Ogawa H, Takagi H, Takaya H, Kawaratani H, Moriya K, Namisaki T, Akahane T, Yoshiji H. Sulforaphane ameliorates ethanol plus carbon tetrachloride-induced liver fibrosis in mice through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway. J Nutr Biochem 2021; 89:108573. [PMID: 33388347 DOI: 10.1016/j.jnutbio.2020.108573] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 11/25/2020] [Accepted: 12/03/2020] [Indexed: 02/07/2023]
Abstract
Alcoholic liver disease (ALD)-related fibrosis results from a variety of mechanisms including the accumulation of acetaldehyde, reactive oxygen species, and hepatic overload of endogenous lipopolysaccharide (LPS). Alcohol cessation is the therapeutic mainstay for patients with all stages of ALD, whereas pharmacological strategies for liver fibrosis have not been established. Sulforaphane, a phytochemical found in cruciferous vegetables, activates nuclear factor erythroid 2-related factor 2 (Nrf2) and exerts anticancer, antidiabetic, and antimicrobial effects; however, few studies investigated its efficacy in the development of ALD-related fibrosis. Herein, we investigated the effect of sulforaphane on acetaldehyde metabolism and liver fibrosis in HepaRG and LX-2 cells, human hepatoma and hepatic stellate cell lines, respectively, as well as in a mouse model of alcoholic liver fibrosis induced by ethanol plus carbon tetrachloride (EtOH/CCl4). Sulforaphane treatment induced the activity of acetaldehyde-metabolizing mitochondrial aldehyde dehydrogenase in HepaRG cells and suppressed the acetaldehyde-induced proliferation and profibrogenic activity in LX-2 cells with upregulation of Nrf2-regulated antioxidant genes, including HMOX1, NQO1, and GSTM3. Moreover, sulforaphane attenuated the LPS/toll-like receptor 4-mediated sensitization to transforming growth factor-β with downregulation of NADPH oxidase 1 (NOX1) and NOX4. In EtOH/CCl4-treated mice, oral sulforaphane administration augmented hepatic acetaldehyde metabolism. Additionally, sulforaphane significantly inhibited Kupffer cell infiltration and fibrosis, decreased fat accumulation and lipid peroxidation, and induced Nrf2-regulated antioxidant response genes in EtOH/CCl4-treated mice. Furthermore, sulforaphane treatment blunted hepatic exposure of gut-derived LPS and suppressed hepatic toll-like receptor 4 signaling pathway. Taken together, these results suggest sulforaphane as a novel therapeutic strategy in ALD-related liver fibrosis.
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Affiliation(s)
- Koji Ishida
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Kosuke Kaji
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan.
| | - Shinya Sato
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Hiroyuki Ogawa
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Hirotetsu Takagi
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Hiroaki Takaya
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Hideto Kawaratani
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Kei Moriya
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Tadashi Namisaki
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Takemi Akahane
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan
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He Q, Luo Y, Xie Z. Sulforaphane ameliorates cadmium induced hepatotoxicity through the up-regulation of /Nrf2/ARE pathway and the inactivation of NF-κB. J Funct Foods 2021. [DOI: 10.1016/j.jff.2020.104297] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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14
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Yu S, Zhang S, Li C, Zhu Y, Mak KK, Pichika MR, Zhou H. New Alkyl (E)-5-(Methylsulfinyl) Pent-4-Enoates from Raphanus sativus Seeds. REVISTA BRASILEIRA DE FARMACOGNOSIA 2020. [DOI: 10.1007/s43450-020-00097-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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15
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Natural Sulfur-Containing Compounds: An Alternative Therapeutic Strategy against Liver Fibrosis. Cells 2019; 8:cells8111356. [PMID: 31671675 PMCID: PMC6929087 DOI: 10.3390/cells8111356] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 10/25/2019] [Accepted: 10/26/2019] [Indexed: 12/12/2022] Open
Abstract
Liver fibrosis is a pathophysiologic process involving the accumulation of extracellular matrix proteins as collagen deposition. Advanced liver fibrosis can evolve in cirrhosis, portal hypertension and often requires liver transplantation. At the cellular level, hepatic fibrosis involves the activation of hepatic stellate cells and their transdifferentiation into myofibroblasts. Numerous pro-fibrogenic mediators including the transforming growth factor-β1, the platelet-derived growth factor, endothelin-1, toll-like receptor 4, and reactive oxygen species are key players in this process. Knowledge of the cellular and molecular mechanisms underlying hepatic fibrosis development need to be extended to find novel therapeutic strategies. Antifibrotic therapies aim to inhibit the accumulation of fibrogenic cells and/or prevent the deposition of extracellular matrix proteins. Natural products from terrestrial and marine sources, including sulfur-containing compounds, exhibit promising activities for the treatment of fibrotic pathology. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans are largely unknown. This review aims to provide a reference collection on experimentally tested natural anti-fibrotic compounds, with particular attention on sulfur-containing molecules. Their chemical structure, sources, mode of action, molecular targets, and pharmacological activity in the treatment of liver disease will be discussed.
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Effects of sulforaphane on D-galactose-induced liver aging in rats: Role of keap-1/nrf-2 pathway. Eur J Pharmacol 2019; 855:40-49. [PMID: 31039346 DOI: 10.1016/j.ejphar.2019.04.043] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Revised: 04/21/2019] [Accepted: 04/26/2019] [Indexed: 02/06/2023]
Abstract
Aging; a biological phenomenon characterized by progressive decline in cellular functions, is considered as a major risk factor of various liver diseases that plays as an adverse prognostic role, thus increasing mortality rate. However, diet is the main environmental factor that has a major impact on the aging process whereas; sulforaphane (SFN), an isothiocyanate organosulfur compound in cruciferous vegetables, has been reported with myriad biological effects. In the present study, SFN antiaging properties were evaluated on D-galactose (D-Gal)-induced liver aging in rats. For this purpose, forty adult male Wistar rats were divided into five groups. All animals, except the normal control, were intraperitoneally injected with D-Gal (300 mg/kg/day for 5 days a week) for six consecutive weeks. In the hepatoprotective groups, animals received oral SFN (0.5, 1.0 and 2.0 mg/kg) for 6 weeks concurrently with D-GAL. SFN administration improved liver biomarkers through decreasing serum levels of AST, ALT, total and direct bilirubin when compared to D-Gal-aging group. SFN significantly increased hepatic GSH level as well as catalase and glutathione-S-transferase activities while counteracted the elevation in hepatic oxidative stress markers; MDA, NO and protein carbonyl in aged rats. SFN abrogated the dysregulation in hepatic Keap-1, Nrf-2 and HO-1and limited the elevation of TNF-α and TGF-β concentrations in aging liver. Histopathologically, SFN decreased the intensity of hepatic fibrous proliferation in D-Gal-induced aging. In conclusion, SFN has shown hepatic anti-aging potential through promoting the antioxidant machinery via regulating Keap-1, Nrf-2 and HO-1 and antioxidant enzyme activities as well as ameliorating oxidative stress, hampering the inflammatory cytokines; TNF-ɑ and TGF-β, and limiting hepatic fibrosis in a dose dependent manner.
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Hu L, Fan H, Wu D, Wan J, Wang X, Huang R, Liu W, Shen F. Assessing bioaccessibility of Se and I in dual biofortified radish seedlings using simulated in vitro digestion. Food Res Int 2018; 119:701-708. [PMID: 30884706 DOI: 10.1016/j.foodres.2018.10.049] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 10/11/2018] [Accepted: 10/14/2018] [Indexed: 11/26/2022]
Abstract
Selenium (Se) and iodine (I) are essential elements for humans, and biofortification of vegetables with these elements is an effective way to amend their deficiencies in the diet. In this study, the distribution and transformation of Se and I species were investigated in radish seedlings that were simultaneously supplemented with these two elements; the fate and the bioaccessibility of Se and I species were dynamically surveyed in the oral, gastric and intestinal phases using a simulated in vitro digestion method. The radish seedlings were cultivated in hydroponic conditions with Se (IV), Se (VI), I- and IO3- (each 1 mg L-1). The results revealed that Se-methylselenocysteine (MeSeCys), selenocystine (SeCys2), selenomethionine (SeMet) and Se (VI) were present in radish, and MeSeCys was the dominant species in both gastric and intestinal extracts, comprising 32.7 ± 1.5% and 39.6 ± 1.1% of the total content, respectively. I- was also the dominant species, which accounted for 57.1 ± 2.1%, 46.6 ± 1.5% and 68.8 ± 1.8% of the total digested content respectively in the oral, gastric and intestinal extracts. Meanwhile, IO3- was absent and organic I accounted for approximately 20%. The bioaccessibility of Se and I in the intestinal phase reached 95.5 ± 2.5% and 85.8 ± 0.9%, respectively; although after dialysis through membranes, the data reduced to 60.1 ± 2.8% and 39.6 ± 0.8%, respectively. Contents of MeSeCys and I- increased from the oral to intestinal phase and the bioaccessibility of both Se and I in radish was above 85%. So radish is suitable as a potential dietary source of Se and I with biofortification.
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Affiliation(s)
- Liang Hu
- School of Resource, Environment and Chemical Engineering, Nanchang University, Nanchang 330031, China; Jiangxi Provincial Key Laboratory for Restoration of Degraded Ecosystems & Watershed Ecohydrology, Nanchang Institute of Technology, Nanchang 330099, China
| | - Houbao Fan
- Jiangxi Provincial Key Laboratory for Restoration of Degraded Ecosystems & Watershed Ecohydrology, Nanchang Institute of Technology, Nanchang 330099, China
| | - Daishe Wu
- School of Resource, Environment and Chemical Engineering, Nanchang University, Nanchang 330031, China.
| | - Jinbao Wan
- School of Resource, Environment and Chemical Engineering, Nanchang University, Nanchang 330031, China
| | - Xianglian Wang
- School of Resource, Environment and Chemical Engineering, Nanchang University, Nanchang 330031, China; Jiangxi Provincial Key Laboratory for Restoration of Degraded Ecosystems & Watershed Ecohydrology, Nanchang Institute of Technology, Nanchang 330099, China
| | - Rongzhen Huang
- Jiangxi Provincial Key Laboratory for Restoration of Degraded Ecosystems & Watershed Ecohydrology, Nanchang Institute of Technology, Nanchang 330099, China
| | - Wenfei Liu
- Jiangxi Provincial Key Laboratory for Restoration of Degraded Ecosystems & Watershed Ecohydrology, Nanchang Institute of Technology, Nanchang 330099, China
| | - Fangfang Shen
- Jiangxi Provincial Key Laboratory for Restoration of Degraded Ecosystems & Watershed Ecohydrology, Nanchang Institute of Technology, Nanchang 330099, China
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Iranshahy M, Iranshahi M, Abtahi SR, Karimi G. The role of nuclear factor erythroid 2-related factor 2 in hepatoprotective activity of natural products: A review. Food Chem Toxicol 2018; 120:261-276. [DOI: 10.1016/j.fct.2018.07.024] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 07/11/2018] [Accepted: 07/12/2018] [Indexed: 12/15/2022]
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19
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Antioxidative effects of aqueous extract of broccoli sprouts against Triazophos induced hepatic and renal toxicity in female Wistar rats. J Appl Biomed 2018. [DOI: 10.1016/j.jab.2017.11.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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20
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Protective effects of radish (Raphanus sativus L.) leaves extract against hydrogen peroxide-induced oxidative damage in human fetal lung fibroblast (MRC-5) cells. Biomed Pharmacother 2018; 103:406-414. [PMID: 29674276 DOI: 10.1016/j.biopha.2018.04.049] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Revised: 04/04/2018] [Accepted: 04/06/2018] [Indexed: 11/23/2022] Open
Abstract
Natural antioxidants play a critical role in the promotion of good health for its prevention of oxidative stress. The main purpose of this study is to investigate the protective effects of radish leaves extract on the oxidative damage in human fetal lung fibroblast (MRC-5) cells. F2, a fraction of radish leaves extracts, which was fractionated by different polarity solvents and AB-8 macroporous resins column shows the best free radical scavenging ability, the highest total polyphenol contents (TPC), and the most potent protective effects on H2O2-induced oxidative damage in MRC-5 cells. The results indicated that pretreatment with F2 before the exposure of cells to H2O2 led to a significant increase in cell viability and internal antioxidant enzyme activities, and a decrease in the content of malondialdehyde (MDA). Furthermore, F2 attenuated the increase in intracellular reactive oxygen species (ROS) level and restored the loss of mitochondria membrane potential (MMP) caused by H2O2. In addition, pretreatment of F2 down-regulated the pro-apoptosis protein (Bax) and up-regulated the anti-apoptosis protein (Bcl-2) suggested its preliminary mechanism of protective effect. In summary, F2 from radish leaves might be used as a source of antioxidant for protecting the oxidative damage of lung.
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Tian S, Li B, Lei P, Yang X, Zhang X, Bao Y, Shan Y. Sulforaphane Improves Abnormal Lipid Metabolism via Both ERS-Dependent XBP1/ACC &SCD1 and ERS-Independent SREBP/FAS Pathways. Mol Nutr Food Res 2018; 62:e1700737. [DOI: 10.1002/mnfr.201700737] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Revised: 01/14/2018] [Indexed: 12/15/2022]
Affiliation(s)
- Sicong Tian
- Department of Food Science and Engineering; School of Chemistry and Chemical Engineering; Harbin Institute of Technology; Harbin China
| | - Baolong Li
- Heilongjiang University of Chinese Medicine; Harbin China
| | - Peng Lei
- Department of Food Science and Engineering; School of Chemistry and Chemical Engineering; Harbin Institute of Technology; Harbin China
| | - Xiuli Yang
- Department of Food Science and Engineering; School of Chemistry and Chemical Engineering; Harbin Institute of Technology; Harbin China
| | - Xiaohong Zhang
- Institute of Preventative Medicine and Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology; School of Medicine; Ningbo University; Zhejiang China
| | - Yongping Bao
- Norwich Medical School; University of East Anglia; Norwich UK
| | - Yujuan Shan
- Department of Food Science and Engineering; School of Chemistry and Chemical Engineering; Harbin Institute of Technology; Harbin China
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Yuan F, Chen X, Liu J, Feng W, Cai L, Wu X, Chen SY. Sulforaphane restores acetyl-histone H3 binding to Bcl-2 promoter and prevents apoptosis in ethanol-exposed neural crest cells and mouse embryos. Exp Neurol 2018; 300:60-66. [PMID: 29069573 PMCID: PMC5745274 DOI: 10.1016/j.expneurol.2017.10.020] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 10/16/2017] [Accepted: 10/20/2017] [Indexed: 12/14/2022]
Abstract
Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables. SFN's cytoprotective properties have been demonstrated in several models associated with a variety of disorders. Our recent studies have shown that SFN protects against ethanol-induced oxidative stress and apoptosis in neural crest cells (NCCs), an ethanol-sensitive cell population implicated in Fetal Alcohol Spectrum Disorders (FASD). This study is designed to test the hypothesis that SFN can prevent ethanol-induced apoptosis in NCCs by inhibiting HDAC and increasing histone acetylation at the Bcl-2 promoter. We found that exposure to 50mM ethanol resulted in a significant increase in HDAC activities in NCCs. Treatment with SFN decreased the activities of HDAC in ethanol-exposed NCCs. We also found that SFN treatment significantly increased the expression of acetyl-histone H3 in NCCs treated with ethanol. ChIP-qPCR assay revealed that ethanol exposure significantly decreased acetyl-histone H3 binding to the Bcl-2 promoter while supplementing with SFN reversed the ethanol-induced reduction in acetyl-histone H3 binding to the Bcl-2 promoter. In addition, SFN treatment restored the expression of Bcl-2 in ethanol-exposed NCCs and diminished ethanol-induced apoptosis in NCCs. Treatment with SFN also significantly diminished apoptosis in mouse embryos exposed to ethanol in vivo. These results demonstrate that SFN can epigenetically restore the expression of Bcl-2 and attenuate ethanol-induced apoptosis by increasing histone acetylation at the Bcl-2 promoter and suggest that SFN may prevent FASD through epigenetic regulation of the expression of anti-apoptotic genes.
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Affiliation(s)
- Fuqiang Yuan
- Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA; University of Louisville, Alcohol Research Center, Louisville, KY 40202, USA
| | - Xiaopan Chen
- Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA; University of Louisville, Alcohol Research Center, Louisville, KY 40202, USA; Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou, Zhejiang 310014, China
| | - Jie Liu
- Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA; University of Louisville, Alcohol Research Center, Louisville, KY 40202, USA
| | - Wenke Feng
- University of Louisville, Alcohol Research Center, Louisville, KY 40202, USA; Department of Medicine, University of Louisville, Louisville, KY 40292, USA
| | - Lu Cai
- Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA
| | - Xiaoyang Wu
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA
| | - Shao-Yu Chen
- Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA; University of Louisville, Alcohol Research Center, Louisville, KY 40202, USA.
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Balaban YH, Aka C, Koca-Caliskan U. Liver immunology and herbal treatment. World J Hepatol 2017; 9:757-770. [PMID: 28660010 PMCID: PMC5474722 DOI: 10.4254/wjh.v9.i17.757] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 04/29/2017] [Accepted: 05/18/2017] [Indexed: 02/06/2023] Open
Abstract
Beyond the metabolic functions, the liver recently has been defined as an organ of immune system (IS), which have central regulatory role for innate and adaptive immunity. The liver keeps a delicate balance between hepatic screening of pathogenic antigens and immune tolerance to self-antigens. Herbal treatments with immunological effects have potential to alter this hepatic immune balance towards either therapeutic side or diseases side by inducing liver injury via hepatotoxicity or initiation of autoimmune diseases. Most commonly known herbal treatments, which have therapeutic effect on liver and IS, have proven via in vitro, in vivo, and/or clinical studies were summarized in this review.
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Affiliation(s)
- Yasemin H Balaban
- Yasemin H Balaban, Gastroenterology Unit, Private Etimed Hospital, 06790 Ankara, Turkey
| | - Ceylan Aka
- Yasemin H Balaban, Gastroenterology Unit, Private Etimed Hospital, 06790 Ankara, Turkey
| | - Ufuk Koca-Caliskan
- Yasemin H Balaban, Gastroenterology Unit, Private Etimed Hospital, 06790 Ankara, Turkey
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Ahn M, Kim J, Bang H, Moon J, Kim GO, Shin T. Hepatoprotective effects of allyl isothiocyanate against carbon tetrachloride-induced hepatotoxicity in rat. Chem Biol Interact 2016; 254:102-8. [DOI: 10.1016/j.cbi.2016.05.037] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 05/18/2016] [Accepted: 05/25/2016] [Indexed: 01/06/2023]
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25
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Yoshida K, Ushida Y, Ishijima T, Suganuma H, Inakuma T, Yajima N, Abe K, Nakai Y. Broccoli sprout extract induces detoxification-related gene expression and attenuates acute liver injury. World J Gastroenterol 2015; 21:10091-10103. [PMID: 26401074 PMCID: PMC4572790 DOI: 10.3748/wjg.v21.i35.10091] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 05/25/2015] [Accepted: 07/03/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of broccoli sprout extract (BSEx) on liver gene expression and acute liver injury in the rat.
METHODS: First, the effects of BSEx on liver gene expression were examined. Male rats were divided into two groups. The Control group was fed the AIN-76 diet, and the BSEx group was fed the AIN-76 diet containing BSEx. After a 10-d feeding period, rats were sacrificed and their livers were used for DNA microarray and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. Next, the effects of BSEx on acute liver injury were examined. In experiments using acute liver injury models, 1000 mg/kg acetaminophen (APAP) or 350 mg/kg D-galactosamine (D-GalN) was used to induce injury. These male rats were divided into four groups: Control, BSEx, Inducer (APAP or D-GalN), and Inducer+BSEx. The feeding regimens were identical for the two analyses. Twenty-four hours following APAP administration via p.o. or D-GalN administration via i.p., rats were sacrificed to determine serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, hepatic glutathione (GSH) and thiobarbituric acid-reactive substances accumulation and glutathione-S-transferase (GST) activity.
RESULTS: Microarray and real-time RT-PCR analyses revealed that BSEx upregulated the expression of genes related to detoxification and glutathione synthesis in normal rat liver. The levels of AST (70.91 ± 15.74 IU/mL vs 5614.41 ± 1997.83 IU/mL, P < 0.05) and ALT (11.78 ± 2.08 IU/mL vs 1297.71 ± 447.33 IU/mL, P < 0.05) were significantly suppressed in the APAP + BSEx group compared with the APAP group. The level of GSH (2.61 ± 0.75 nmol/g tissue vs 1.66 ± 0.59 nmol/g tissue, P < 0.05) and liver GST activity (93.19 ± 16.55 U/g tissue vs 51.90 ± 16.85 U/g tissue, P < 0.05) were significantly increased in the APAP + BSEx group compared with the APAP group. AST (4820.05 ± 3094.93 IU/mL vs 12465.63 ± 3223.97 IU/mL, P < 0.05) and ALT (1808.95 ± 1014.04 IU/mL vs 3936.46 ± 777.52 IU/mL, P < 0.05) levels were significantly suppressed in the D-GalN + BSEx group compared with the D-GalN group, but the levels of AST and ALT in the D-GalN + BSEx group were higher than those in the APAP + BSEx group. The level of GST activity was significantly increased in the D-GalN + BSEx group compared with the D-GalN group (98.04 ± 15.75 U/g tissue vs 53.15 ± 8.14 U/g tissue, P < 0.05).
CONCLUSION: We demonstrated that BSEx protected the liver from various types of xenobiotic substances through induction of detoxification enzymes and glutathione synthesis.
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Ambrecht LA, Perlman JI, McDonnell JF, Zhai Y, Qiao L, Bu P. Protection of retinal function by sulforaphane following retinal ischemic injury. Exp Eye Res 2015; 138:66-9. [PMID: 26142954 DOI: 10.1016/j.exer.2015.06.030] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 06/18/2015] [Accepted: 06/30/2015] [Indexed: 12/21/2022]
Abstract
Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury.
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Affiliation(s)
- Lindsay A Ambrecht
- Department of Ophthalmology, Loyola University Chicago, Maywood, IL 60153, USA
| | - Jay I Perlman
- Department of Ophthalmology, Loyola University Chicago, Maywood, IL 60153, USA; Department of Pathology, Loyola University Chicago, Maywood, IL 60153, USA; Surgery Service, Edward Hines, Jr. VA Hospital, Hines, IL 60141, USA
| | - James F McDonnell
- Department of Ophthalmology, Loyola University Chicago, Maywood, IL 60153, USA
| | - Yougang Zhai
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153, USA
| | - Liang Qiao
- Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153, USA
| | - Ping Bu
- Department of Ophthalmology, Loyola University Chicago, Maywood, IL 60153, USA; Research Service, Edward Hines, Jr. VA Hospital, Hines, IL 60141, USA.
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Li J, Shen F, Guan C, Wang W, Sun X, Fu X, Huang M, Jin J, Huang Z. Activation of Nrf2 protects against triptolide-induced hepatotoxicity. PLoS One 2014; 9:e100685. [PMID: 24988078 PMCID: PMC4079517 DOI: 10.1371/journal.pone.0100685] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2014] [Accepted: 05/26/2014] [Indexed: 11/25/2022] Open
Abstract
Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF), has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2) in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN), attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.
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Affiliation(s)
- Jia Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Pharmaceutical Department, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China
| | - Feihai Shen
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Cuiwen Guan
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Wenwen Wang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Xiaozhe Sun
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Xinlu Fu
- Center of Laboratory Animals, Sun Yat-sen University, Guangzhou, China
| | - Min Huang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Jing Jin
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Zhiying Huang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Center of Laboratory Animals, Sun Yat-sen University, Guangzhou, China
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Choi WJ, Kim SK, Park HK, Sohn UD, Kim W. Anti-Inflammatory and Anti-Superbacterial Properties of Sulforaphane from Shepherd's Purse. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2014; 18:33-9. [PMID: 24634594 PMCID: PMC3951821 DOI: 10.4196/kjpp.2014.18.1.33] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 12/09/2013] [Accepted: 12/31/2013] [Indexed: 01/08/2023]
Abstract
Shepherd's purse, Capsella bursa-pastoris (L.) Medik., has been considered a health food for centuries in Asia and is known to contain the isothiocyanate compound sulforaphane. In this study, we evaluated the anti-inflammatory and antibacterial properties of a sulforaphane-containing solution (SCS) isolated from shepherd's purse. SCS had significant anti-inflammatory activity indicated by the decreased levels of nitric oxide (NO), cytokines (interleukin 1β [IL-1β], IL-6, and IL-10), and prostaglandin E2 (PGE2) in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. In addition, SCS decreased the inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) levels, which confirmed the anti-inflammatory activity of SCS. Further, SCS inhibited vancomycin-resistant enterococci (VRE) and Bacillus anthracis. The minimal inhibitory concentration was 250 µg/ml for VRE and 1,000 µg/ml for B. anthracis. Taken together, these data indicate that SCS has potential anti-inflammatory and anti-superbacterial properties, and thus it can be used as a functional food or pharmaceutical.
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Affiliation(s)
- Woo Jin Choi
- Department of Microbiology, College of Medicine, Chung-Ang University, Seoul 156-861, Korea
| | - Seong Keun Kim
- Department of Microbiology, College of Medicine, Chung-Ang University, Seoul 156-861, Korea
| | - Hee Kuk Park
- Department of Microbiology, College of Medicine, Chung-Ang University, Seoul 156-861, Korea
| | - Uy Dong Sohn
- College of Pharmacy, Chung-Ang University, Seoul 156-861, Korea
| | - Wonyong Kim
- Department of Microbiology, College of Medicine, Chung-Ang University, Seoul 156-861, Korea
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Aqueous extract of purple Bordeaux radish, Raphanus sativus L. ameliorates ethanol-induced gastric injury in rats. ACTA ACUST UNITED AC 2013. [DOI: 10.1007/s13596-013-0131-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Choudhary SP, Oral HV, Bhardwaj R, Yu JQ, Tran LSP. Interaction of brassinosteroids and polyamines enhances copper stress tolerance in raphanus sativus. JOURNAL OF EXPERIMENTAL BOTANY 2012; 63:5659-75. [PMID: 22915739 PMCID: PMC3444278 DOI: 10.1093/jxb/ers219] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Brassinosteroids (BRs) and polyamines (PAs) regulate various responses to abiotic stress, but their involvement in the regulation of copper (Cu) homeostasis in plants exposed to toxic levels of Cu is poorly understood. This study provides an analysis of the effects of exogenously applied BRs and PAs on radish (Raphanus sativus) plants exposed to toxic concentrations of Cu. The interaction of 24-epibrassinolide (EBR, an active BR) and spermidine (Spd, an active PA) on gene expression and the physiology of radish plants resulted in enhanced tolerance to Cu stress. Results indicated that the combined application of EBR and Spd modulated the expression of genes encoding PA enzymes and genes that impact the metabolism of indole-3-acetic acid (IAA) and abscisic acid (ABA) resulting in enhanced Cu stress tolerance. Altered expression of genes implicated in Cu homeostasis appeared to be the main effect of EBR and Spd leading to Cu stress alleviation in radish. Ion leakage, in vivo imaging of H(2)O(2), comet assay, and improved tolerance of Cu-sensitive yeast strains provided further evidence for the ability of EBR and Spd to improve Cu tolerance significantly. The study indicates that co-application of EBR and Spd is an effective approach for Cu detoxification and the maintenance of Cu homeostasis in plants. Therefore, the use of these compounds in agricultural production systems should be explored.
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Affiliation(s)
- Sikander Pal Choudhary
- Department of Horticulture, Zhejiang UniversityHangzhou 310058, ZhejiangChina
- Department of Botany, University of JammuJammu 180003India
- To whom correspondence should be addressed. E-mail: or or
| | - H. Volkan Oral
- Jacob Blaustein Institutes for Desert Research, French Associates Institute for Agriculture and Biotechnology of Drylands, Ben-Gurion University of the Negev84990Israel
| | - Renu Bhardwaj
- Department of Botanical and Environmental Sciences, Guru Nanak Dev UniversityAmritsar 143001India
| | - Jing-Quan Yu
- Department of Horticulture, Zhejiang UniversityHangzhou 310058, ZhejiangChina
- To whom correspondence should be addressed. E-mail: or or
| | - Lam-Son Phan Tran
- Signaling Pathway Research Unit, RIKEN Plant Science CenterYokohama, KanagawaJapan
- To whom correspondence should be addressed. E-mail: or or
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Choudhary SP, Kanwar M, Bhardwaj R, Yu JQ, Tran LSP. Chromium stress mitigation by polyamine-brassinosteroid application involves phytohormonal and physiological strategies in Raphanus sativus L. PLoS One 2012; 7:e33210. [PMID: 22479371 PMCID: PMC3315560 DOI: 10.1371/journal.pone.0033210] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2011] [Accepted: 02/13/2012] [Indexed: 01/01/2023] Open
Abstract
Brassinosteroids (BRs) and polyamines (PAs) are well-established growth regulators playing key roles in stress management among plants. In the present study, we evaluated the effects of epibrassinolide (EBL, an active BR) and spermidine (Spd, an active PA) on the tolerance of radish to oxidative stress induced by Cr (VI) metal. Our investigation aimed to study the impacts of EBL (10(-9) M) and/or Spd (1 mM) on the biochemical and physiological responses of radish (Raphanus sativus L.) under Cr-stress. Applications of EBL and/or Spd were found to improve growth of Cr-stressed seedlings in terms of root length, shoot length and fresh weight. Our data also indicated that applications of EBL and Spd have significant impacts, particularly when applied together, on the endogenous titers of PAs, free and bound forms of IAA and ABA in seedlings treated with Cr-stress. Additionally, co-applications of EBL and Spd modulated more remarkably the titers of antioxidants (glutathione, ascorbic acid, proline, glycine betaine and total phenol) and activities of antioxidant enzymes (guaicol peroxidase, catalase, superoxide dismutase and glutathione reductase) in Cr-stressed plants than their individual applications. Attenuation of Cr-stress by EBL and/or Spd (more efficient with EBL and Spd combination) was also supported by enhanced values of stress indices, such as phytochelatins, photosynthetic pigments and total soluble sugars, and reduction in malondialdehyde and H(2)O(2) levels in Cr-treated seedlings. Diminution of ROS production and enhanced ROS scavenging capacities were also noted for EBL and/or Spd under Cr-stress. However, no significant reduction in Cr uptake was observed for co-application of EBL and Spd when compared to their individual treatments in Cr-stressed seedlings. Taken together, our results demonstrate that co-applications of EBL and Spd are more effective than their independent treatments in lowering the Cr-induced oxidative stress in radish, leading to improved growth of radish seedlings under Cr-stress.
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Affiliation(s)
- Sikander Pal Choudhary
- Department of Horticulture, Zhejiang University, Hangzhou, Zhejiang, China
- Department of Botany, University of Jammu, Jammu, India
- * E-mail: (SPC); (LPT)
| | - Mukesh Kanwar
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, India
| | - Renu Bhardwaj
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, India
| | - Jing-Quan Yu
- Department of Horticulture, Zhejiang University, Hangzhou, Zhejiang, China
| | - Lam-Son Phan Tran
- Signaling Pathway Research Unit, RIKEN Plant Science Center, Yokohama, Kanagawa, Japan
- * E-mail: (SPC); (LPT)
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Choudhary SP, Kanwar M, Bhardwaj R, Gupta BD, Gupta RK. Epibrassinolide ameliorates Cr (VI) stress via influencing the levels of indole-3-acetic acid, abscisic acid, polyamines and antioxidant system of radish seedlings. CHEMOSPHERE 2011; 84:592-600. [PMID: 21561640 DOI: 10.1016/j.chemosphere.2011.03.056] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2010] [Revised: 03/15/2011] [Accepted: 03/24/2011] [Indexed: 05/30/2023]
Abstract
The present investigation determined the effects of epibrassinolide (EBL) on the levels of indole-3-acetic acid (IAA), abscisic acid (ABA), and polyamine (PA) and antioxidant potential of 7-d old Raphanus sativus L. cv. 'Pusa chetki' seedlings grown under Cr (VI) metal stress. Reduced titers of free (0.767 μg g(-1) FW) and bound (0.545 μg g(-1) FW) IAA in Cr (VI) stressed seedlings were observed over untreated control. Supplementations of EBL to Cr (VI) stressed seedlings were able to enhance both free (2.14-5.68 μg g(-1) FW) and bound IAA (2.45-7.78 μg g(-1) FW) concentrations in comparison to Cr (VI) metal treatment alone. Significant rise in free (13.49 μg g(-1) FW) and bound (12.17 μg g(-1) FW) ABA contents were noticed for Cr (VI) stressed seedlings when compared to untreated control. No significant increase in ABA contents were recorded for Cr (VI) stressed seedlings upon supplementation with EBL over Cr (VI) treatment alone. A significant increase in Put (18.40 μg g(-1) FW) and Cad (9.08 μg g(-1) FW) contents were found for 10(-9)M EBL plus Cr (VI) metal treatments when compared to Cr (VI) treatment alone. Spermidine (Spd) contents were found to decline significantly for EBL treatment alone or when supplemented with Cr (VI) treatments over untreated controls and Cr (VI) treatment alone. Antioxidant levels were found to enhance, with glutathione (57.98 mg g(-1) FW), proline (4.97 mg g(-1) FW), glycinebetaine (39.01 μmol mL(-1)), ascorbic acid (3.17 mg g(-1) FW) and phytochelatins (65.69 μmol g(-1) FW) contents noted for EBL supplemented to Cr (VI) metal solution over Cr (VI) treatment alone. Reduced activities of guaiacol peroxidase (0.391 U mg(-1) protein) and catalase (0.221 U mg(-1) protein) and enhanced activities of glutathione reductase (7.14 U mg(-1) protein), superoxide dismutase (15.20 U mg(-1) protein) and ascorbate peroxidase (4.31 U mg(-1) protein) were observed in seedlings treated with EBL plus Cr (VI) over Cr metal treatment alone. Reduced MDA (2.55 μmol g(-1) FW) and H(2)O(2) (33.24 μmol g(-1) FW) contents were recorded for 10(-9)M EBL supplemented to Cr (VI) stress over Cr (VI) treatment alone. Enhancement in free radical scavenging potential as indicated by higher values of 1,1-diphenylpicrylhydrazyl, deoxyribose and reducing power activity assays, and increased levels of phenols and soluble sugars also showed significant influence of EBL in alleviating Cr (VI) stress in radish seedlings.
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Gaona-Gaona L, Molina-Jijón E, Tapia E, Zazueta C, Hernández-Pando R, Calderón-Oliver M, Zarco-Márquez G, Pinzón E, Pedraza-Chaverri J. Protective effect of sulforaphane pretreatment against cisplatin-induced liver and mitochondrial oxidant damage in rats. Toxicology 2011; 286:20-7. [PMID: 21575670 DOI: 10.1016/j.tox.2011.04.014] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Revised: 04/21/2011] [Accepted: 04/27/2011] [Indexed: 02/07/2023]
Abstract
In the present work was analyzed whether sulforaphane (SFN) may protect against cisplatin (CIS)-induced hepatic damage, oxidant stress and mitochondrial dysfunction. Four groups of male Wistar rats were studied: control, CIS, CIS+SFN and SFN. SFN was given i.p. (500 μg/kg/d × 3 days) before CIS administration (single i.p. injection, 10mg/kg). Rats were sacrificed 3 days after CIS injection to evaluate hepatic damage (histological analysis, liver/body weight ratio and serum activity of aspartate aminotransferase and alanine aminotransferase), oxidant stress (lipid peroxidation and protein carbonyl and glutathione content), antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and superoxide dismutase) in liver homogenates and isolated mitochondria and mitochondrial function (oxygen consumption using either malate/glutamate or succinate as substrates and the activity of mitochondrial complex I, II, II-III, IV and V). Furthermore it was evaluated if SFN is able to scavenge some reactive oxygen species in vitro. It was found that SFN prevents CIS-induced (a) hepatic damage, (b) oxidant stress and decreased activity of antioxidant enzymes in liver and mitochondria and (c) mitochondrial alterations in oxygen consumption and decreased activity of mitochondrial complex I. It was also found that the scavenging ability of SFN for peroxynitrite anion, superoxide anion, singlet oxygen, peroxyl radicals, hydrogen peroxide and hydroxyl radicals was very low or negligible. The hepatoprotective effect of SFN was associated to the preservation of mitochondrial function, antioxidant enzymes and prevention of liver and mitochondrial oxidant stress.
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Dried peel fraction of Citrus sinensis partially reverses pathological changes in rat model of liver cirrhosis. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2011. [DOI: 10.1007/s12349-010-0033-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Guerrero-Beltrán CE, Calderón-Oliver M, Pedraza-Chaverri J, Chirino YI. Protective effect of sulforaphane against oxidative stress: recent advances. ACTA ACUST UNITED AC 2010; 64:503-8. [PMID: 21129940 DOI: 10.1016/j.etp.2010.11.005] [Citation(s) in RCA: 238] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2010] [Revised: 10/19/2010] [Accepted: 11/01/2010] [Indexed: 12/14/2022]
Abstract
Sulforaphane [1-isothiocyanate-(4R)-(methylsulfinyl)butane] is a natural dietary isothiocyanate produced by the enzymatic action of the myrosinase on glucopharanin, a 4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables of the genus Brassica such as broccoli, brussel sprouts, and cabbage. Studies on this compound is increasing because its anticarcinogenic and cytoprotective properties in several in vivo experimental paradigms associated with oxidative stress such as focal cerebral ischemia, brain inflammation, intracerebral hemorrhage, ischemia and reperfusion induced acute renal failure, cisplatin induced-nephrotoxicity, streptozotocin-induced diabetes, carbon tetrachloride-induced hepatotoxicity and cardiac ischemia and reperfusion. This protective effect also has been observed in in vitro studies in different cell lines such as human neuroblastoma SH-SY5Y, renal epithelial proximal tubule LLC-PK1 cells and aortic smooth muscle A10 cells. Sulforaphane is considered an indirect antioxidant; this compound is able to induce many cytoprotective proteins, including antioxidant enzymes, through the Nrf2-antioxidant response element pathway. Heme oxygenase-1, NAD(P)H: quinone oxidoreductase, glutathione-S-transferase, gamma-glutamyl cysteine ligase, and glutathione reductase are among the cytoprotective proteins induced by sulforaphane. In conclusion, sulforaphane is a promising antioxidant agent that is effective to attenuate oxidative stress and tissue/cell damage in different in vivo and in vitro experimental paradigms.
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Choudhary SP, Bhardwaj R, Gupta BD, Dutt P, Gupta RK, Biondi S, Kanwar M. Epibrassinolide induces changes in indole-3-acetic acid, abscisic acid and polyamine concentrations and enhances antioxidant potential of radish seedlings under copper stress. PHYSIOLOGIA PLANTARUM 2010; 140:280-296. [PMID: 20681975 DOI: 10.1111/j.1399-3054.2010.01403.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
In the present study, the effects of epibrassinolide (EBL) on indole-3-acetic acid (IAA), abscisic acid (ABA) and polyamine (PA) tissue concentrations and antioxidant potential of 7-day-old Raphanus sativus L. cv. 'Pusa chetki' seedlings grown under Cu stress were investigated. EBL treatment alone or in combination with Cu enhanced free and bound IAA titers when compared with the metal alone. Modest increases in free and bound ABA contents were observed for EBL treatment alone. However, the combination of EBL with Cu caused major increases in both forms of ABA, over Cu alone. Among the PAs analyzed, only putrescine and cadaverine concentrations were enhanced by EBL treatment alone. By contrast, a significant decline in putrescine and spermine contents was found in seedlings treated with EBL plus Cu. EBL treatments alone or in combination with Cu enhanced activities of guaiacol peroxidase (EC1.11.1.7), catalase (EC 1.11.1.6), superoxide dismutase (EC 1.15.1.1) and glutathione reductase (EC 1.6.4.2) and protein contents in comparison with metal and control treatments. A major decrease in malondialdehyde content was also recorded for EBL treatments with or without Cu. An increase in phytochelatin content was also observed in seedlings treated with EBL alone or in combination with Cu. Major improvement in radical scavenging activities, as attested by the antioxidant activity assay using DPPH (1,1-diphenylpicrylhydrazyl), and elevated deoxyribose and reducing powers, along with increased contents of ascorbic acid, total phenols and proline, also suggest a major influence of EBL application in mitigating copper-induced oxidative stress in radish seedlings.
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Choudhary SP, Bhardwaj R, Gupta BD, Dutt P, Gupta RK, Kanwar M, Dutt P. Changes induced by Cu2+ and Cr6+ metal stress in polyamines, auxins, abscisic acid titers and antioxidative enzymes activities of radish seedlings. ACTA ACUST UNITED AC 2010. [DOI: 10.1590/s1677-04202010000400006] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Hanlon PR, Robbins MG, Hammon LD, Barnes DM. Aqueous extract from the vegetative portion of Spanish black radish (Raphanus sativus L. var. niger) induces detoxification enzyme expression in HepG2 cells. J Funct Foods 2009. [DOI: 10.1016/j.jff.2009.08.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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