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Messaad CE, Belhadj H. Nbeg, a Neglected Functional Fruit from Sedra (Ziziphus lotus L.) : A Mini Review. J Med Food 2025; 28:340-353. [PMID: 39778899 DOI: 10.1089/jmf.2024.0193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
Abstract
Ziziphus lotus L., or "Sedra" in North Africa, is a wild jujube from the Rhamnaceae family. Its fruit, "Nbeg," is used in traditional medicine to treat various ailments, such as tuberculosis, bronchitis, liver disorders, and gastrointestinal issues. This mini review highlights the main nutritional and medicinal properties of Nbeg and its potential application in human health and nutrition. Current scientific articles have recommended the use of Z. lotus-derived compounds to generate novel treatments due to their diverse biological functions (anti-ulcer, wound healing, litholytic, and antispasmodic effects). Z. lotus appears to be a good source for antioxidant compounds (phenolics and flavonoids, which are a diverse group of natural compounds belonging to the polyphenol family) and nutritional molecules (carbohydrates, amino acids, triacylglycerol, proteins, sterols, fibers, vitamins, lipids, and minerals), which made it a viable option for human nutrition and health promotion.
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Affiliation(s)
- Chemes ElHouda Messaad
- Laboratory of Applied Microbiology, Faculty of Sciences of Nature and Life, University Ferhat Abbes Sétif 1, Sétif, Algeria
- Laboratory of Biodiversity and Biotechnological Techniques for the Valuation of Plant Resources (BTB_VRV), Faculty of Science, SNV Department, Mohamed Boudiaf University, M'sila, Algeria
| | - Hani Belhadj
- Laboratory of Applied Microbiology, Faculty of Sciences of Nature and Life, University Ferhat Abbes Sétif 1, Sétif, Algeria
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Gugsa E, Molla TS, Bekele T, Dejenie TA. Hepatoprotective effect of hydromethanol extract of Otostegia integrifolia benth leaves in isoniazid and rifampicin induced Swiss albino mice. Metabol Open 2023; 20:100255. [PMID: 38115863 PMCID: PMC10728564 DOI: 10.1016/j.metop.2023.100255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/01/2023] [Accepted: 09/10/2023] [Indexed: 12/21/2023] Open
Abstract
Introduction Drug-induced liver injury is the most common cause of acute liver failure. Off-Target effect "hepatotoxicity "frequently detected during clinical examination of patients on anti-Tb medication particularly isoniazid (INH), and rifampin (RMP). However, there is no any treatment option against isoniazid and rifampicin induced hepatotoxicity. It is, therefore, necessary to search for effective affordable and safe drugs from medicinal plants for the prevention of liver toxicity caused by isoniazid and rifampicin. The aim the current study is to evaluate hepatoprotective effect of hydro methanol extract from Otostegia integrifolia leaves in isoniazid and rifampicin-induced hepatotoxicity in Swiss albino mice. Methods O. integrifolia leaves powder was macerated in hydromethanol and thirty Swiss albino mice 29.0-40.6 g were grouped in to five groups. Group I were given 20 ml/kg distilled water, group II were given 100 mg INH and 150 mg RIF per kg body weight. Group III, group IV, and group V were given 200 mg extract, 400 mg extract, and 100 mg of N-acetyl cysteine respectively per kg 1hr before induction with 100 mg INH plus 150 mg RIF per kg. The treatments were followed for 14 days. On the 15th day, all mice were anaesthetized with diethyl ether; blood samples were collected for the assessment liver enzyme and function test. Results Group II mice's serum ALT, AST and total bilirubin levels were significantly increased and serum total protein and albumin levels were significantly decreased as compared with group I mice. The groups of mice treated with O. integrifolia at a dose of 400 mg/kg and N-acetyl cysteine AST, ALT and total bilirubin level were significantly decreased; and total protein and albumin levels were significantly (P < 0.05) increased as compared with group II. The liver index of the group IV showed decreased (P < 0.05) as compared to the group II. Conclusion Evidence from our study revealed that the hydromethanol extract of O. integrifolia has a hepatoprotective effect against isoniazid and rifampicin-induced hepatotoxicity in Swiss Albino mice. This protective effect of O. integrifolia extract may be based on its metal ion reducing power, free radical scavenging activity, and anti-inflammatory activity and could be used as a potential therapeutic option.
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Affiliation(s)
- Endalkachew Gugsa
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Ethiopia
| | - Tewodros Shibabaw Molla
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Ethiopia
| | - Tesfahun Bekele
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Ethiopia
| | - Tadesse Asmamaw Dejenie
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Ethiopia
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Anjum V, Bagale U, Kadi A, Potoroko I, Sonawane SH, Anjum A. Unveiling Various Facades of Tinospora cordifolia Stem in Food: Medicinal and Nutraceutical Aspects. Molecules 2023; 28:7073. [PMID: 37894552 PMCID: PMC10609069 DOI: 10.3390/molecules28207073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 10/03/2023] [Accepted: 10/07/2023] [Indexed: 10/29/2023] Open
Abstract
Natural products with curative properties are gaining immense popularity in scientific and food research, possessing no side effects in contrast to other drugs. Guduchi, or Tinospora cordifolia, belongs to the menispermaceae family of universal drugs used to treat various diseases in traditional Indian literature. It has received attention in recent decades because of its utilization in folklore medicine for treating several disorders. Lately, the findings of active phytoconstituents present in herbal plants and their pharmacological function in disease treatment and control have stimulated interest in plants around the world. Guduchi is ethnobotanically used for jaundice, diabetes, urinary problems, stomachaches, prolonged diarrhea, skin ailments, and dysentery. The treatment with Guduchi extracts was accredited to phytochemical constituents, which include glycosides, alkaloids, steroids, and diterpenoid lactones. This review places emphasis on providing in-depth information on the budding applications of herbal medicine in the advancement of functional foods and nutraceuticals to natural product researchers.
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Affiliation(s)
- Varisha Anjum
- Department of Food and Biotechnology, South Ural State University, Chelyabinsk 454080, Russia; (U.B.); (A.K.); (I.P.)
| | - Uday Bagale
- Department of Food and Biotechnology, South Ural State University, Chelyabinsk 454080, Russia; (U.B.); (A.K.); (I.P.)
| | - Ammar Kadi
- Department of Food and Biotechnology, South Ural State University, Chelyabinsk 454080, Russia; (U.B.); (A.K.); (I.P.)
| | - Irina Potoroko
- Department of Food and Biotechnology, South Ural State University, Chelyabinsk 454080, Russia; (U.B.); (A.K.); (I.P.)
| | - Shirish H. Sonawane
- Department of Chemical Engineering, National Institute of Technology, Warangal 506004, India;
| | - Areefa Anjum
- Department of Ilmul Advia, School of Unani Medical Education and Research, Jamia Hamdard, New Delhi 110062, India;
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Potential use of Tinospora cordifolia as a herbal supplement in dairy animals: a review. Trop Anim Health Prod 2022; 55:4. [PMID: 36502455 DOI: 10.1007/s11250-022-03415-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/24/2022] [Indexed: 12/14/2022]
Abstract
Supplementation is an integral part of modern dairy-feeding practices which mainly emphasise on higher production. Different supplements have been utilized by the farmers according to the need and action of supplements. Tinospora cordifolia (TC) is one such herbal supplement which can be utilized to feed dairy animals either alone or in combination with other supplements. TC is a herb found in tropical countries and having number of medicinal properties. Beneficial health effects of TC include immunostimulation, protection against inflammation and bacterial action, hepatoprotection, antioxidant and antineoplastic effects. Available studies on TC supplementation in dairy animals have shown a positive effect on health, body parameters and production performance. Supplementing TC is economically feasible, and it can be adopted by farmers as it helps in improving their net income. However, more research is needed in the field of dairy animals to explore the full potential of this herb. This review is written with the objective of highlighting the possibilities of using TC in dairy animal rations and promoting research in the concerned field to fill the gaps in knowledge. Thorough knowledge about TC and its effect in dairy animals can add a new concept to the supplementation process and developments of dairy rations.
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Saifi M, Ashrafi K, Nasrullah N, Bhardwaj U, Abdin MZ. Integrated miRNA, target mRNA, and metabolome profiling of Tinospora cordifolia with reference to berberine biosynthesis. 3 Biotech 2022; 12:311. [PMID: 36276443 PMCID: PMC9535074 DOI: 10.1007/s13205-022-03342-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 08/29/2022] [Indexed: 11/01/2022] Open
Abstract
MicroRNAs play a central role in gene regulation and emerge as novel targets for secondary metabolites improvement in plants. The crops thus can be improved through knowledge obtained by the study of miRNAs because of their conserved nature in gene regulation. The present study has been carried out on Tinospora cordifolia (T. cordifolia), because of its illimitable application for the treatment of various diseases. This plant has tremendous medicinal properties, yet unexplored at the molecular level, and has not received much recognition in the scientific field. Thus, here computational analysis was performed to identify T. cordifolia miRNAs using EST database. Using these miRNAs, we predicted their targets which were found to be associated with the regulation of diverse gene networks including 433 berberine biosynthesis genes in T. cordifolia. Further, selected miRNAs were validated and their expression was detected in different T. cordifolia tissues followed by expression analysis of their target mRNAs. These data were then compared with the metabolic profile of T. cordifolia with an emphasis on therapeutically important compound berberine. In this study, we did simultaneous miRNA/target gene expression and metabolome analysis which opens a new way for initiating new proposition and prioritization of miRNAs/genes/metabolites for targeted follow‑up metabolic engineering experimentations. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03342-9.
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Affiliation(s)
- Monica Saifi
- Centre for Transgenic Plant Development, Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062 India
| | - Kudsiya Ashrafi
- Centre for Transgenic Plant Development, Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062 India
| | - Nazima Nasrullah
- Centre for Transgenic Plant Development, Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062 India
| | - Urvashi Bhardwaj
- Centre for Transgenic Plant Development, Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062 India
| | - M. Z. Abdin
- Centre for Transgenic Plant Development, Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062 India
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Arunachalam K, Yang X, San TT. Tinospora cordifolia (Willd.) Miers: Protection mechanisms and strategies against oxidative stress-related diseases. JOURNAL OF ETHNOPHARMACOLOGY 2022; 283:114540. [PMID: 34509604 DOI: 10.1016/j.jep.2021.114540] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 08/11/2021] [Accepted: 08/17/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Tinospora cordifolia (Willd.) Miers (Menispermaceae) is a Mediterranean herb, used in Ayurvedic, Siddha, Unani, and folk medicines. The herb is also used in conventional medicine to treat oxidative stress-related diseases and conditions, including inflammation, pain, diarrhea, asthma, respiratory infections, cancer, diabetes, and gastrointestinal disorders. AIM OF THE REVIEW The taxonomy, botanical classification, geographical distribution, and ethnobotanical uses of T. cordifolia, as well as the phytochemical compounds found in the herb, the toxicology of and pharmacological and clinical studies on the effects of T. cordifolia are all covered in this study. MATERIALS AND METHODS To gather information on T. cordifolia, we used a variety of scientific databases, including Scopus, Google Scholar, PubMed, and Science Direct. The information discussed focuses on biologically active compounds found in T. cordifolia, and common applications and pharmacological activity of the herb, as well as toxicological and clinical studies on its properties. RESULTS The findings of this study reveal a connection between the use of T. cordifolia in conventional medicine and its antioxidant, anti-inflammatory, antihypertensive, antidiabetic, anticancer, immunomodulatory, and other biological effects. The entire plant, stem, leaves, root, and extracts of T. cordifolia have been shown to have a variety of biological activities, including antioxidant, antimicrobial, antiviral, antiparasitic, antidiabetic, anticancer, anti-inflammatory, analgesic and antipyretic, hepatoprotective, and cardioprotective impact. Toxicological testing demonstrated that this plant may have medicinal applications. T. cordifolia contains a variety of biologically active compounds from various chemical classes, including alkaloids, terpenoids, sitosterols, flavonoids, and phenolic acids. Based on the reports researched for this review, we believe that chemicals in T. cordifolia may activate Nrf2, which leads to the overexpression of antioxidant enzymes such as CAT, GPx, GST, and GR, and thereby induces the adaptive response to oxidative stress. T. cordifolia is also able to reduce NF-κB signalling by inhibiting PI3K/Akt, activating AMPK and sirtuins, and downregulating PI3K/Akt. CONCLUSIONS Our findings indicate that the pharmacological properties displayed by T. cordifolia back up its conventional uses. Antimicrobial, antiviral, antioxidant, anticancer, anti-inflammatory, antimutagenic, antidiabetic, nephroprotective, gastroprotective, hepatoprotective, and cardioprotective activities were all demonstrated in T. cordifolia stem extracts. To validate pharmacodynamic targets, further research is needed to evaluate the molecular mechanisms of the known compounds against gastrointestinal diseases, inflammatory processes, and microbial infections, as immunostimulants, and in chemotherapy. The T. cordifolia safety profile was confirmed in a toxicological analysis, which prompted pharmacokinetic assessment testing to confirm its bioavailability.
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Affiliation(s)
- Karuppusamy Arunachalam
- Key Laboratory of Economic Plants and Biotechnology and the Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650 201, People's Republic of China; Southeast Asia Biodiversity Research Institute, Chinese Academy of Sciences, Yezin, Nay Pyi Taw, 05282, Myanmar.
| | - Xuefei Yang
- Key Laboratory of Economic Plants and Biotechnology and the Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650 201, People's Republic of China; Southeast Asia Biodiversity Research Institute, Chinese Academy of Sciences, Yezin, Nay Pyi Taw, 05282, Myanmar.
| | - Thae Thae San
- Key Laboratory of Economic Plants and Biotechnology and the Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650 201, People's Republic of China; Southeast Asia Biodiversity Research Institute, Chinese Academy of Sciences, Yezin, Nay Pyi Taw, 05282, Myanmar
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Rouf R, Ghosh P, Uzzaman MR, Sarker DK, Zahura FT, Uddin SJ, Muhammad I. Hepatoprotective Plants from Bangladesh: A Biophytochemical Review and Future Prospect. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:1633231. [PMID: 34504532 PMCID: PMC8423546 DOI: 10.1155/2021/1633231] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/17/2021] [Indexed: 12/14/2022]
Abstract
Liver diseases are quite prevalant in many densely populated countries, including Bangladesh. The liver and its hepatocytes are targeted by virus and microbes, as well as by chemical environmental toxicants, causing wide-spread disruption of metabolic fuctions of the human body, leading to death from end-stage liver diseases. The aim of this review is to systematically explore and record the potential of Bangladeshi ethnopharmacological plants to treat liver diseases with focus on their sources, constituents, and therapeutic uses, including mechanisms of actions (MoA). A literature survey was carried out using Pubmed, Google Scholar, ScienceDirect, and Scopus databases with articles reported until July, 2020. A total of 88 Bangladeshi hepatoprotective plants (BHPs) belonging to 47 families were listed in this review, including Euphorbiaceae, Cucurbitaceae, and Compositae families contained 20% of plants, while herbs were the most cited (51%) and leaves were the most consumed parts (23%) as surveyed. The effect of BHPs against different hepatotoxins was observed via upregulation of antioxidant systems and inhibition of lipid peroxidation which subsequently reduced the elevated liver biomarkers. Different active constituents, including phenolics, curcuminoids, cucurbitanes, terpenoids, fatty acids, carotenoids, and polysaccharides, have been reported from these plants. The hepatoameliorative effect of these constituents was mainly involved in the reduction of hepatic oxidative stress and inflammation through activation of Nrf2/HO-1 and inhibition of NF-κB signaling pathways. In summary, BHPs represent a valuable resource for hepatoprotective lead therapeutics which may offer new alternatives to treat liver diseases.
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Affiliation(s)
- Razina Rouf
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Puja Ghosh
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Md. Raihan Uzzaman
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Dipto Kumer Sarker
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Fatima Tuz Zahura
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Shaikh Jamal Uddin
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Ilias Muhammad
- National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA
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Affiliation(s)
- Sangeetha Nithiyanandam
- School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - Sabina Evan Prince
- School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
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Preclinical Evidence of Curcuma longa and Its Noncurcuminoid Constituents against Hepatobiliary Diseases: A Review. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:8761435. [PMID: 32802138 PMCID: PMC7411463 DOI: 10.1155/2020/8761435] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 06/29/2020] [Accepted: 07/06/2020] [Indexed: 02/06/2023]
Abstract
Hepatobiliary disease currently serves as an important public health issue due to the fact that it is one of the major causes of death among economically active individuals and can easily progress to chronic diseases. Despite the development of vaccines and numerous drugs, a definite treatment remains lacking owing to different stages of the disease itself, its intricate pathogenesis, an effect uncertainty for long-term use, resistance, and side effects. Curcuma longa (C. longa), which belongs to the family Zingiberaceae and the genus Curcuma, has long been used not only as spice for curry or dye but also as a constituent of herbal formula for the treatment of different diseases due to its bioactive activities. Recently, many studies on the experimental results of C. longa have been published relative to hepatobiliary diseases such as fatty liver, hepatitis, cirrhosis, and tumors. Therefore, in this review, we aimed to summarize the pharmacological effects and underlying molecular mechanisms of C. longa and its four compounds, β-elemene, germacrone, ar-turmerone, and bisacurone, against hepatobiliary diseases. C. longa exhibited antioxidant, hepatoprotective, antisteatotic, anti-inflammatory, antifibrotic, antitumor, and cholagogic effects by regulating apoptosis, CYP2E1, Nrf, lipid metabolism-related factors, TGF-β, NF-κB, CYP7A1, and so on. In particular, β-elemene could be an attractive compound owing to its remarkable hepatoprotective, anti-inflammatory, antifibrotic, and antitumor activities. Altogether, the present review provides a preclinical basis for the efficacy of C. longa as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases, despite the need for further studies to establish the extraction conditions and separation of active constituents with high bioavailability, and warrants further evaluation in clinical trials.
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Saeed M, Naveed M, Leskovec J, Ali Kamboh A, Kakar I, Ullah K, Ahmad F, Sharif M, Javaid A, Rauf M, Abd El-Hack ME, Abdel-Latif MA, Chao S. Using Guduchi (Tinospora cordifolia) as an eco-friendly feed supplement in human and poultry nutrition. Poult Sci 2019; 99:801-811. [PMID: 32029162 PMCID: PMC7587696 DOI: 10.1016/j.psj.2019.10.051] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 10/16/2019] [Accepted: 10/18/2019] [Indexed: 12/11/2022] Open
Abstract
Guduchi (Tinospora cordifolia) is a well-recognized and widely distributed traditional plant that is used successfully in Indian Ayurveda medicine. T. cordifolia has shown many promising biological activities, such as antioxidative, antimicrobial, antihyperglycemic, anti-inflammatory, osteoprotective, hepatoprotective, antidiarrheal, and antistress effects. Guduchi is a rich source of protein and micronutrients, such as iron, zinc, copper, calcium, phosphorus, and manganese. It also contains many secondary plant metabolites, such as terpenes, alkaloids, flavonoids, steroids, and glycosides. Based on previous studies in poultry, the supplementation levels of Guduchi range from 1 to 5 g/kg of diet (different sources, such as powder, extracts, roots, and leaves, have been used). It was suggested that this variation in supplementation levels depends on different factors, including the extraction method, the supplementation proposed, the method of supplementation (either in feed or drinking water), and the species and physiological status of the birds. Generally, dietary supplementation of poultry broilers with T. cordifolia yielded positive impacts on growth performance, body gains (increased by 4.8%), dressing percentage (increased by 7.1%), meat quality traits, and the shelf life of the meat. In addition, T. cordifolia exerted a palliative effect on the general health status of the birds through reducing live enzymes and plasma uric acids and enhancing the immune response, as indicated by the leukocyte count, hemagglutinin titer, interleukin activity, and mortality levels. Further investigations concluded that T. cordifolia showed strong antimicrobial effects against Escherichia coli and Salmonella enteritidis, with subsequent reductions in mortality. Moreover, T. cordifolia showed an ability to improve humoral and cell-mediated immunity against Newcastle disease, infectious anemia, gout, and aflatoxicosis. The current review discusses many beneficial properties of T. cordifolia, although the lack of pharmacological trials limits the use of this extract in poultry. Further research should be performed regarding the composition of the active compound, the possible mechanisms of action, and the effective doses to fully understand the activities and benefits of T. cordifolia as a growth performance improvement supplement.
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Affiliation(s)
- Muhammad Saeed
- College of Animal Sciences and Technology, Northwest A & F University, Yangling 712100, China; Department of Poultry Science, Faculty of Animal Production & Technology, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100, Pakistan
| | - Muhammad Naveed
- Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu Province 211166, China
| | - Jakob Leskovec
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia 1230 Domžale, Slovenia
| | - Asgahr Ali Kamboh
- Department of Microbiology, Sindh Agriculture University Tandojam, Sindh Province, Pakistan
| | - Ihsanullah Kakar
- Clinical Medicine and Surgery Department LUAWMS, Uthal, Balochistan, Pakistan
| | - Kifayat Ullah
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Park Road, Tarlai Kalan, Islamabad 45550, Pakistan
| | - Fawwad Ahmad
- Institute of Animal and Dairy Sciences, University of Agriculture, Faisalabad, Pakistan
| | - Muhammad Sharif
- Institute of Animal and Dairy Sciences, University of Agriculture, Faisalabad, Pakistan
| | - Asif Javaid
- Department of Animal Nutrition, Faculty of Animal Production & Technology, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100, Pakistan
| | - Mubasher Rauf
- Department of Pathology, Faculty of Veterinary Science, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, code 63100, Pakistan
| | - Mohamed E Abd El-Hack
- Department of Poultry, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt
| | - Mervat A Abdel-Latif
- Nutrition and Veterinary Clinical Nutrition, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt
| | - Sun Chao
- College of Animal Sciences and Technology, Northwest A & F University, Yangling 712100, China.
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Research Progress on the Animal Models of Drug-Induced Liver Injury: Current Status and Further Perspectives. BIOMED RESEARCH INTERNATIONAL 2019; 2019:1283824. [PMID: 31119149 PMCID: PMC6500714 DOI: 10.1155/2019/1283824] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 03/26/2019] [Indexed: 02/07/2023]
Abstract
Drug-induced liver injury (DILI) is a major concern in clinical studies as well as in postmarketing surveillance. It is necessary to establish an animal model of DILI for thorough investigation of mechanisms of DILI and searching for protective medications. This article reviews the current status and future perspective on establishment of DILI models based on different hepatotoxic drugs, as well as the underlying mechanisms of liver function damage induced by specific medicine. Therefore, information from this article can help researchers make a suitable selection of animal models for further study.
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Yoshioka H, Fukaya S, Tominaga S, Nagatsu A, Miura N, Maeda T. Protective effect of the Kampo formula “Juzen-taiho-to” on isoniazid- and rifampicin-induced hepatotoxicity in mice. ACTA ACUST UNITED AC 2019. [DOI: 10.2131/fts.6.25] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Affiliation(s)
- Hiroki Yoshioka
- Department of Pharmacy, College of Pharmacy, Kinjo Gakuin University
| | - Shiori Fukaya
- Department of Pharmacy, College of Pharmacy, Kinjo Gakuin University
| | - Sarah Tominaga
- Department of Pharmacy, College of Pharmacy, Kinjo Gakuin University
| | - Akito Nagatsu
- Department of Pharmacy, College of Pharmacy, Kinjo Gakuin University
| | - Nobuhiko Miura
- Division of Health Effects Research, Japan National Institute of Occupational Safety and Health
| | - Tohru Maeda
- Department of Pharmacy, College of Pharmacy, Kinjo Gakuin University
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John P, Kale PP. Prominence of Oxidative Stress in the Management of Anti-tuberculosis Drugs Related Hepatotoxicity. Drug Metab Lett 2019; 13:95-101. [PMID: 31333143 DOI: 10.2174/1872312813666190716155930] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 05/08/2019] [Accepted: 06/03/2019] [Indexed: 06/10/2023]
Abstract
Advanced medical services and treatments are available for treating Tuberculosis. Related prevalence has increased in recent times. Unfortunately, the continuous consumption of related drugs is also known for inducing hepatotoxicity which is a critical condition and cannot be overlooked. The present review article has focused on the pathways causing these toxicities and also the role of enzyme CYP2E1, hepatic glutathione, Nrf2-ARE signaling pathway, and Membrane Permeability Transition as possible targets which may help in preventing the hepatotoxicity induced by the drugs used in the treatment of tuberculosis.
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Affiliation(s)
- Preena John
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle, Mumbai-400056, Maharashtra, India
| | - Pravin P Kale
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle, Mumbai-400056, Maharashtra, India
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Huang WT, Tu CY, Wang FY, Huang ST. Literature review of liver injury induced by Tinospora crispa associated with two cases of acute fulminant hepatitis. Complement Ther Med 2018; 42:286-291. [PMID: 30670256 DOI: 10.1016/j.ctim.2018.11.028] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 11/30/2018] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION Species of Tinospora are used as herbal remedies for the treatment of various diseases with very few toxic effects having been reported. Tinospora cordifolia (TCF) has been reported to effectively prevent hepatotoxicity. However, there are an increasing number of cases revealing that Tinospora crispa (TCP) might have the negative effect of inducing hepatotoxicity. Because of the similar leaves, people may mistake TCP for TCF, and consume it with the purpose of protecting liver function. OBJECTIVE Find out the misusing level of TCP and TCF and which chemical compound in TCP might induce hepatotoxicity. METHODS We report two cases of acute fulminant hepatitis associated with chronic use of TCP. Given that the two herbs were misidentified in these two reports, we investigated the frequency of erroneous identification by using three keywords ("Guduchi", "Tinospora cordifolia", "Tinospora crispa") to search images from the Google Images database. To further clarify the influence of liver function between TCP and TCF, we searched PubMed (up to 29 July 2018) for relevant publications on clinical trials or case reports. RESULTS Based on web review, over 35 percent of websites failed to accurately identify these two herbs. The different effects on liver function between TCP and TCF were compared through literature review. It indicated that TCF exerted liver protection, TCP had a contrary effect, suggesting its cis-Clerodane-type furano-diterpenoids might be an important factor of inducing hepatotoxicity. CONCLUSIONS We concluded that people might cause hepatic injury or even death without correctly identifying these two Tinospora species.
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Affiliation(s)
- Wei-Te Huang
- Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Ching-Yeh Tu
- Department of Chinese Medicine pharmacy, China Medical University Hospital, Taichung, Taiwan
| | - Fen-Yu Wang
- Traditional Chinese Medicine Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Sheng-Teng Huang
- Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; Research Center for Chinese Herbal Medicine, China Medical University, Taichung, Taiwan.
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15
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Baskaran UL, Sabina EP. Clinical and experimental research in antituberculosis drug-induced hepatotoxicity: a review. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2018; 15:27-36. [PMID: 28088257 DOI: 10.1016/s2095-4964(17)60319-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs (ATDs). There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. This review would give a precise idea of ATD-induced hepatotoxicity, its underlying mechanisms and alternative therapies for the same.
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Affiliation(s)
| | - Evan Prince Sabina
- School of Biosciences and Technology, VIT University, Vellore-632014, Tamilnadu, India
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16
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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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17
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Sun W, Wang S, Zhao W, Wu C, Guo S, Gao H, Tao H, Lu J, Wang Y, Chen X. Chemical constituents and biological research on plants in the genus Curcuma. Crit Rev Food Sci Nutr 2017; 57:1451-1523. [PMID: 27229295 DOI: 10.1080/10408398.2016.1176554] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Curcuma, a valuable genus in the family Zingiberaceae, includes approximately 110 species. These plants are native to Southeast Asia and are extensively cultivated in India, China, Sri Lanka, Indonesia, Peru, Australia, and the West Indies. The plants have long been used in folk medicine to treat stomach ailments, stimulate digestion, and protect the digestive organs, including the intestines, stomach, and liver. In recent years, substantial progress has been achieved in investigations regarding the chemical and pharmacological properties, as well as in clinical trials of certain Curcuma species. This review comprehensively summarizes the current knowledge on the chemistry and briefly discusses the biological activities of Curcuma species. A total of 720 compounds, including 102 diphenylalkanoids, 19 phenylpropene derivatives, 529 terpenoids, 15 flavonoids, 7 steroids, 3 alkaloids, and 44 compounds of other types isolated or identified from 32 species, have been phytochemically investigated. The biological activities of plant extracts and pure compounds are classified into 15 groups in detail, with emphasis on anti-inflammatory and antitumor activities.
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Affiliation(s)
- Wen Sun
- a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China
| | - Sheng Wang
- b State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences , Beijing , China
| | - Wenwen Zhao
- a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China
| | - Chuanhong Wu
- a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China
| | - Shuhui Guo
- a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China
| | - Hongwei Gao
- a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China
| | - Hongxun Tao
- a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China
| | - Jinjian Lu
- a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China
| | - Yitao Wang
- a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China
| | - Xiuping Chen
- a State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao , China
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18
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Hassan HM, Guo HL, Yousef BA, Luyong Z, Zhenzhou J. Hepatotoxicity mechanisms of isoniazid: A mini-review. J Appl Toxicol 2015; 35:1427-32. [DOI: 10.1002/jat.3175] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 04/17/2015] [Indexed: 12/25/2022]
Affiliation(s)
- Hozeifa M. Hassan
- Jiangsu Key Laboratory of Drug Screening; China Pharmaceutical University; Nanjing China
- Department of Pharmacology, Faculty of Pharmacy; University of Gezira; Wad-Medani Sudan
| | - Hong-li Guo
- Jiangsu Key Laboratory of Drug Screening; China Pharmaceutical University; Nanjing China
| | - Bashir A. Yousef
- Jiangsu Key Laboratory of Drug Screening; China Pharmaceutical University; Nanjing China
- Department of Pharmacology, Faculty of Pharmacy; University of Khartoum; Khartoum Sudan
| | - Zhang Luyong
- Jiangsu Key Laboratory of Drug Screening; China Pharmaceutical University; Nanjing China
- Jiangsu Center for Pharmacodynamics Research and Evaluation; China Pharmaceutical University; Nanjing China
- Jiangsu Key Laboratory of TCM Evaluation and Translational Research; China Pharmaceutical University; Nanjing China
| | - Jiang Zhenzhou
- Jiangsu Key Laboratory of Drug Screening; China Pharmaceutical University; Nanjing China
- Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University); Ministry of Education; Nanjing China
- State Key Laboratory of Natural Medicines; China Pharmaceutical University; Nanjing China
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19
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Jatav SK, Kulshrestha A, Zacharia A, Singh N, Tejovathi G, Bisen PS, Prasad GBKS. Spirulina maxima Protects Liver From Isoniazid and Rifampicin Drug Toxicity. J Evid Based Complementary Altern Med 2014; 19:189-194. [DOI: 10.1177/2156587214530720] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Hepatotoxicity associated with isoniazid and rifampicin is one of the major impediments in antituberculosis therapy. The present study explored the prophylactic and therapeutic efficacies of Spirulina maxima in isoniazid and rifampicin induced hepatic damage in a rat model. Hepatic damage induced in Wistar rats by isoniazid and rifampicin resulted in significant alterations in biomarkers of liver function, namely, bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and oxidative stress markers such as superoxide dismutase, catalase, glutathione, and thiobarbituric acid reactive substances. Co-administration of Spirulina maxima along with antituberculosis drugs protected liver from hepatotoxicity due to isoniazid and rifampicin. Administration of Spirulina maxima consecutively for 2 weeks to hepatodamaged animals resulted in restoration of hepatic function as evident from normalization of serum markers of liver function. Thus, the present study revealed remarkable prophylactic and therapeutic potential of Spirulina maxima. Co-administration of Spirulina maxima and antituberculosis drugs is advantageous as it provides extra nutritional benefit.
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Affiliation(s)
| | | | | | | | - G. Tejovathi
- Boston College of Professional Studies, Gwalior, India
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Tabarsi P, Fahimi F, Heidarzadeh N, Haghgoo R, Kazempour M, Masjedi M, Velayati AA. The Effect of Garcin® in Preventing AntiTB-Induced Hepatitis in Newly Diagnosed Tuberculosis Patients. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2014; 13:169-76. [PMID: 24711843 PMCID: PMC3977067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Adverse effects of antituberculosis agents such as hepatotoxicity may reduce treatment effectiveness, because they significantly contribute to nonadherence and eventually result in treatment failure, relapse or the emergence of drug resistance. Garlic is an ancient herbal substance, which its effectiveness on isoniazid and rifampicin-induced hepatic injury in animal models has been demonstrated (1). In the present study a randomized, double blind, placebo-controlled, parallel group clinical trial was designed to assess the effect(s) of garlic tablets (1000 mg daily) administered for two weeks orally. Fifty eight newly diagnosed, smear positive pulmonary tuberculosis patients, with age ranges between 18-65 years old, were randomly allocated into two groups. Each patient received either garlic or placebo tablets for the first two weeks of tuberculosis treatment. Of total 58 patients, 31 received garlic tablets while 27 received placebo. No significant difference was found between the two groups regarding age, sex, nationality, smoking, underlying diseases and opium usage. During 8 weeks of anti-TB (antituberculosis) treatment, 8 (13.0%) patients developed drug-induced hepatotoxicity (DIH). Of them, 6 (75%) occurred in the first two weeks of treatment. Fifty percent of the patients who developed DIH were in garlic group. Results indicated no significant difference between groups in developing DIH (p=1.000). We could not show a significant role in preventing DIH by 1000 mg daily garlic administration.
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Affiliation(s)
- Payam Tabarsi
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Fanak Fahimi
- Clinical Pharmacy Department, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. ,Corresponding author:
E-mail:
| | - Nader Heidarzadeh
- Chemical Injuries Research Center, Baqiyatallah University of Medical sciences, Tehran, Iran.
| | - Roodabeh Haghgoo
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mehdi Kazempour
- Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammadreza Masjedi
- Telemedicine Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ali Akbar Velayati
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Mishra A, Kumar S, Pandey AK. Scientific validation of the medicinal efficacy of Tinospora cordifolia. ScientificWorldJournal 2013; 2013:292934. [PMID: 24453828 PMCID: PMC3885194 DOI: 10.1155/2013/292934] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2013] [Accepted: 10/07/2013] [Indexed: 02/05/2023] Open
Abstract
Present communication reports the scientific evaluation of Tinospora cordifolia for its medicinal efficacy which includes phytochemical screening, antimicrobial, antioxidant, and anticancer activities of the plant. Secondary metabolites including anthraquinones, terpenoids, and saponins were present in many extracts in addition to phenolics. Total phenol contents in various extracts were found in the range of 8.75-52.50 catechol equivalent per gram (CE/g). In disc diffusion assays, polar extracts exhibited considerable inhibition against Klebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains of E. coli, Pseudomonas spp., and Proteus spp. Minimum bactericidal concentration (MBC) values of potential extracts were found between 1.29 and 22.73 mg/mL. The lowest MBC (1.29 mg/mL) was recorded for acetone and ethyl acetate extracts against K. pneumoniae and Pseudomonas spp., respectively. The antioxidant activity of the extracts was comparable to that of standard antioxidants and concentration-dependent response was shown in reducing power assay. Aqueous extracts demonstrated substantial metal ion chelating activity (67-95%) at lower concentrations (10-40 μ g/mL). Other extracts also exhibited considerable metal chelating response. Most of the extracts revealed considerable inhibition of MCF-7 cancer cell line. The study established remarkable antibacterial, antioxidant, and anticancer potential in T. cordifolia stem extracts.
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Affiliation(s)
- Amita Mishra
- Department of Biochemistry, University of Allahabad, Allahabad 211002, India
| | - Shashank Kumar
- Department of Biochemistry, University of Allahabad, Allahabad 211002, India
| | - Abhay K. Pandey
- Department of Biochemistry, University of Allahabad, Allahabad 211002, India
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22
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Nabavi SF, Daglia M, Moghaddam AH, Habtemariam S, Nabavi SM. Curcumin and Liver Disease: from Chemistry to Medicine. Compr Rev Food Sci Food Saf 2013; 13:62-77. [DOI: 10.1111/1541-4337.12047] [Citation(s) in RCA: 117] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Accepted: 09/23/2013] [Indexed: 02/06/2023]
Affiliation(s)
- Seyed Fazel Nabavi
- Applied Biotechnology Research Center; Baqiyatallah Univ. of Medical Sciences; Tehran Iran
| | - Maria Daglia
- Dept. of Drug Sciences; Univ. of Pavia, Medicinal Chemistry and Pharmaceutical Technology Section; via Taramelli 12 27100 Pavia Italy
| | - Akbar Hajizadeh Moghaddam
- Amol Univ. of Special Modern Technologies; Amol Iran
- Dept. of Biology; Faculty of basic science; Univ. of Mazandaran; Babolsar Iran
| | - Solomon Habtemariam
- Pharmacognosy Research Laboratories; Medway School of Science, Univ. of Greenwich; Central Ave. Chatham-Maritime Kent ME4 4TB U.K
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center; Baqiyatallah Univ. of Medical Sciences; Tehran Iran
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Abdoul-Azize S, Bendahmane M, Hichami A, Dramane G, Simonin AM, Benammar C, Sadou H, Akpona S, El Boustani ES, Khan NA. Effects of Zizyphus lotus L. (Desf.) polyphenols on Jurkat cell signaling and proliferation. Int Immunopharmacol 2012; 15:364-71. [PMID: 23219580 DOI: 10.1016/j.intimp.2012.11.013] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2012] [Revised: 11/20/2012] [Accepted: 11/22/2012] [Indexed: 12/12/2022]
Abstract
We assessed the effects of Zizyphus lotus L. (Desf.) polyphenols (ZLP) on T-cell signaling and proliferation. Our results showed that ZLP exerted no effect on the increases in intracellular free calcium concentrations, [Ca(2+)]i, in human Jurkat T-cells. However, ZLP modulated the thapsigargin-induced increases in [Ca(2+)]i in these cells. ZLP treatment was found to decrease the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In addition, ZLP induced a rapid (t1/2=33s) and dose-dependent decrease in intracellular pH (pHi) in human Jurkat T-cells. Furthermore, ZLP significantly curtailed T-cell proliferation by diminishing their progression from S to G2/M phase of cell cycle, and the expression of interleukin-2 (IL-2) mRNA. Taken together, the results of the present study demonstrate that ZLP modulate cell signaling and exert immunosuppressive effects in human T-cells.
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Affiliation(s)
- Souleymane Abdoul-Azize
- INSERM U866, Physiologie de la Nutrition & Toxicologie (NuTox), Université de Bourgogne, Dijon, France
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Sharma J, Gairola S, Gaur RD, Painuli RM. The treatment of jaundice with medicinal plants in indigenous communities of the Sub-Himalayan region of Uttarakhand, India. JOURNAL OF ETHNOPHARMACOLOGY 2012; 143:262-291. [PMID: 22759701 DOI: 10.1016/j.jep.2012.06.034] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Revised: 06/12/2012] [Accepted: 06/12/2012] [Indexed: 05/27/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Inspite of tremendous advances made in allopathic medical practices, herbs still play an important role in the management of various liver diseases. A large number of plants and formulations have been claimed to have hepatoprotective activity. Jaundice is a symptom, indicative of the malfunctioning of the liver. This paper provides ethnomedicinal information on the plants used to treat jaundice by three important indigenous communities, i.e., nomadic Gujjars, Tharu and Bhoxa of Sub-Himalayan region, Uttarakhand, India. AIMS OF THE STUDY To record herbal preparations used by the studied indigenous communities in treatment of jaundice and discuss hepatoprotective properties of the recorded plants. RESEARCH STRATEGY AND METHODS The traditional knowledge of the studied indigenous communities on herbal preparations used for treating jaundice was collected through structured questionnaire and personal interviews. The interviews were conducted with 91 traditional healers (29 Bhoxa, 35 Tharu and 27 nomadic Gujjars) in Sub-Himalayan region of Uttarakhand, India. More than 250 research papers reporting ethnomedicinal information on the hepatoprotective plants used by various communities from different parts of India were extensively reviewed. RESULTS A total of 40 medicinal plants belonging to 31 families and 38 genera were recorded to be used by the studied communities in 45 formulations as a remedy of jaundice. Bhoxa, nomadic Gujjars and Tharu communities used 15, 23 and 9 plants, respectively. To our knowledge eight plants reported in the present survey viz., Amaranthus spinosus L., Cissampelos pareira L., Ehretia laevis Roxb., Holarrhena pubescens Wall., Ocimum americanum L., Physalis divaricata D. Don, Solanum incanum L. and Trichosanthes cucumerina L. have not been reported earlier as remedy of jaundice in India. Literature review revealed that a total of 214 (belonging to 181 genus and 78 families), 19 (belonging to 18 genus and 12 families) and 14 (belonging to 14 genus and 11 families) plant species are used as internal, external and magico-religious remedies for jaundice, respectively by various communities in different parts of India. Most widely used hepatoprotective plant species for treatment of jaundice in India is Boerhavia diffusa L. followed by Tinospora cordifolia (Willd.) Miers, Saccharum officinarum L., Phyllanthus amarus Schumach. & Thonn., Ricinus communis L., Andrographis paniculata (Burm. f.) Nees., Oroxylum indicum (L.) Kurz, Lawsonia inermis L. and Eclipta prostrata (L.) L. CONCLUSIONS The plants recorded in the present survey have also been discussed in relation to pharmacological studies and hepatoprotective phytoconstituents present in them. Most of the recorded plants have shown hepatoprotective effects on experimental animals in earlier studies but more studies are needed to assess hepatoprotective properties of some recorded medicinal plants viz., Averrhoa carambola L., Ehretia laevis Roxb., Holarrhena pubescens Wall., Mangifera indica L., Ocimum americanum L., Oroxylum indicum (L.) Kurz, Physalis divaricata D. Don, Solanum incanum L., Sphaeranthus senegalensis DC. and Tribulus terrestris L.. The plants enumerated in this study with high number of citations and wider distributions have given some useful leads for further biomedical research. Nevertheless more phytochemical, pharmaceutical and clinical studies are needed to evaluate hepatoprotective properties, efficacy and safety of all the claimed medicinal plants.
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Affiliation(s)
- Jyotsana Sharma
- Department of Botany, HNB Garhwal University, Srinagar Garhwal, Uttarakhand 246174, India.
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25
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Hussain T, Gupta RK, K S, Khan MS, Hussain MS, Arif M, Hussain A, Faiyazuddin M, Rao CV. Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents. Asian Pac J Trop Biomed 2012; 2:454-60. [PMID: 23569949 PMCID: PMC3609318 DOI: 10.1016/s2221-1691(12)60075-6] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2011] [Revised: 11/12/2011] [Accepted: 12/17/2011] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVE To assess the hepatoprotective effect of Solanum xanthocarpum (S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals. METHODS Ethanolic (50%) fruit extract of S. xanthocarpum (100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid (I) 7.5 mg/kg, rifampicin (R) 10 mg/kg and pyrazinamide (P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), total bilirubin (TBL), albumin (ALB), total protein (TP), lactate dehydroginase (LDH), and serum cholesterol (CHL). Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination. RESULTS The results demonstrated that treatment with S. xanthocarpum significantly (P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, S. xanthocarpum significantly (up to P<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpum attenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration. CONCLUSIONS The results of this study strongly indicate the protective effect of S. xanthocarpum against liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.
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Affiliation(s)
- Talib Hussain
- Pharmacognosy and Ethnopharmacology Division, National Botanical Research Institute, Lucknow, Uttar Pradesh 226001, India
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Integral University, Lucknow Uttar Pradesh 226001
| | - Ramesh K Gupta
- Pharmacognosy and Ethnopharmacology Division, National Botanical Research Institute, Lucknow, Uttar Pradesh 226001, India
- Department of Pharmacology, Royal College of Pharmacy and Health Sciences, Berhampur-760002 (Orissa)
| | - Sweety K
- Pharmacognosy and Ethnopharmacology Division, National Botanical Research Institute, Lucknow, Uttar Pradesh 226001, India
| | - Mohd Sajid Khan
- Department of Biotechnology, Integral University, Lucknow Uttar Pradesh 226001
| | - Md Sarfaraj Hussain
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Integral University, Lucknow Uttar Pradesh 226001
| | - Md Arif
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Integral University, Lucknow Uttar Pradesh 226001
| | - Arshad Hussain
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Integral University, Lucknow Uttar Pradesh 226001
| | - Md Faiyazuddin
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Integral University, Lucknow Uttar Pradesh 226001
| | - Chandana Venkateswara Rao
- Pharmacognosy and Ethnopharmacology Division, National Botanical Research Institute, Lucknow, Uttar Pradesh 226001, India
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26
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Application of HPLC fingerprints for defining in vivo safety profile of Tulsi (Ocimum Sanctum). Med Chem Res 2012. [DOI: 10.1007/s00044-012-0022-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Singh M, Sasi P, Gupta VH, Rai G, Amarapurkar DN, Wangikar PP. Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model. Hum Exp Toxicol 2012; 31:788-97. [PMID: 22318308 DOI: 10.1177/0960327111433901] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Tuberculosis (TB) is highly endemic in India. The first-line anti-TB therapy (ATT) involving isoniazid (INH), rifampicin and pyrazinamide causes hepatotoxicity in approximately 11.5% of Indian patients. Studies have shown that ATT-induced hepatotoxicity is primarily due to oxidative stress caused by the drugs and metabolites. Herbal drugs with antioxidative properties have been tested in animal studies and clinical trials for the management of hepatotoxicity. The objective of this study was to investigate the role of curcumin (CUR), silymarin (SILY) and N-acetylcysteine (N-ACET) on hepatotoxicity by ATT drugs using an in vitro model of human hepatocellular carcinoma cell line (HepG2). HepG2 cells were treated with ATT drugs alone or along with CUR, SILY or N-ACET for a 48-h duration. The cells were monitored for viability, morphology, respiring mitochondria and cell cycle. Our results suggest that the presence of hepatoprotective drugs during treatment of HepG2 cells with ATT drugs lowers the hepatotoxic effect of the latter. This is observed in terms of (a) increased cell viability, (b) healthy-looking cell morphology as revealed by phase contrast microscopy, (c) active respiring cells as observed with confocal microscopy upon staining with a mitochondrial membrane-specific dye, MitoTracker(®) Red, and reduction in the sub-G(1) peak in cell cycle analysis by flow cytometry. Our results suggest that these hepatoprotective drugs need to be further explored as potential adjuvant therapy along with ATT drugs.
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Affiliation(s)
- M Singh
- Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India
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Prabhu VV, Guruvayoorappan C. Evaluation of immunostimulant activity and chemoprotective effect of mangroveRhizophora apiculataagainst cyclophosphamide induced toxicity in BALB/c mice. Immunopharmacol Immunotoxicol 2012; 34:608-15. [DOI: 10.3109/08923973.2011.642883] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Abdelmeguid NE, Chmaisse HN, Abou Zeinab NS. Silymarin ameliorates cisplatin-induced hepatotoxicity in rats: histopathological and ultrastructural studies. Pak J Biol Sci 2011; 13:463-79. [PMID: 21848071 DOI: 10.3923/pjbs.2010.463.479] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The benefit of silymarin, a plant extract with strong antioxidant activity against hepatotoxicity induced by cisplatin in rats was investigated in this study. Cisplatin is one of the most effective chemotherapeutic drugs, yet it alone does not achieve a satisfactory therapeutic outcome and at high doses it can produce undesirable side effects. Five equal-sized groups (18 rats each) of male Sprague Dawley rats [control, vehicle; cisplatin; silymarin 2 h after cisplatin injection; and silymarin 2 h before cisplatin injection] were used. Histopathological and ultrastructural observation of livers were carried out using light and electron microscopy. Results documented that cisplatin produced behavioral, external features animal changes, as well as hazard pathological picture changes in liver where most hepatocytes appeared diminutive with vacuolated cytoplasm, sinusoids dilated and organelle disorganized. These results revealed that cisplatin may be toxic and terminates in complex liver damage. Administrations of silymarin 2 h after cisplatin, significantly increase the body weight returning it to normal, yet it failed in complete protection against the pathological alteration caused by cisplatin. Pretreatment with silymarin 2 h before cisplatin significantly decreased the pathological changes induced by cisplatin and appeared highly protective. These results suggested that silymarin possess protective effects against cisplatin hepatotoxic action in animal models. Since, no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anticancerous medications and might serve as a novel combination agent with cisplatin since it plays a significant role in reducing its toxicity.
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Affiliation(s)
- N E Abdelmeguid
- Department of Zoology, Faculty of Science, Alexandria University, Moharram Bey, Alexandria 2151, Egypt
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Ghosh N, Ghosh R, Mandal V, Mandal SC. Recent advances in herbal medicine for treatment of liver diseases. PHARMACEUTICAL BIOLOGY 2011; 49:970-988. [PMID: 21595500 DOI: 10.3109/13880209.2011.558515] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
CONTEXT Liver disease is a serious ailment and the scenario is worsened by the lack of precise therapeutic regimens. Currently available therapies for liver ailments are not apposite and systemic toxicity inhibits their long term use. Medicinal plants have been traditionally used for treating liver diseases since centuries as the toxicity factor appears to be on the lower side. OBJECTIVE Several phytochemials have been identified which have significant hepatoprotective activity with minimal systemic adverse effects which could limit their long term use. The scenario calls for extensive investigations which can lead to development of lead molecules for hepatoprotective molecules of future. This review deals with the biological activity, mode of action and toxicity and forthcoming application of some of these leads. METHODS These generally have strong antioxidative potential and cause induction of antioxidant enzymes like superoxide dismutase, reduced glutathione and catalase. Additional mechanisms of hepatoprotection include stimulation of heme oxygenase-1 activity, inhibition of nitric oxide production, hepatocyte apoptosis and nuclear factor-κB activation. RESULTS AND CONCLUSION Out of the several leads obtained from plant sources as potential hepatoprotective agents, silymarin, andrographolide, neoandrographolide, curcumin, picroside, kutkoside, phyllanthin, hypophyllanthin, and glycyrrhizin have been established as potent hepatoprotective agents. The hepatoprotective potential of several herbal medicines has been clinically evaluated. Significant efficacy has been seen with silymarin, glycyrrhizin and Liv-52 in treatment of hepatitis, alcoholic liver disease and liver cirrhosis.
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Affiliation(s)
- Nilanjan Ghosh
- Dr. BC Roy College of Pharmacy and Allied Health Sciences, Durgapur, India.
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Ulbricht C, Basch E, Barrette EP, Boon H, Chao W, Costa D, Higdon ER, Isaac R, Lynch M, Papaliodis G, Grimes Serrano JM, Varghese M, Vora M, Windsor R, Woods J. Turmeric(Curcuma longa): An Evidence-Based Systematic Review by the Natural Standard Research Collaboration. ACTA ACUST UNITED AC 2011. [DOI: 10.1089/act.2011.17409] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Catherine Ulbricht
- The Natural Standard Research Collaboration, in Somerville, Massachusetts, is a senior attending pharmacist at Massachusetts General Hospital, and is an adjunct/assistant clinical professor at many universities
| | - Ethan Basch
- The Natural Standard Research Collaboration, is a medical oncologist and professor at Memorial Sloan-Kettering Cancer Center in New York, New York, and is on the faculty at Weill Cornell Medical College in New York, New York
| | - Ernie-Paul Barrette
- The Division of Infectious Diseases at Washington University School of Medicine in St. Louis, Missouri
| | - Heather Boon
- The Leslie Dan Faculty of Pharmacy at the University of Toronto in Ontario, Canada, is a founding chair and principal investigator of the Canadian Interdisciplinary Network for CAM Research (IN-CAM) in Calgary, Alberta, Canada, and is co-chair of Health Canada’s Expert Advisory Committee for Natural Health Products in Ottawa, Ontario, Canada
| | | | | | | | | | | | - George Papaliodis
- The Immunology and Uveitis Service at Massachusetts Eye and Ear Infirmary in Boston, Massachusetts, and is on the faculty at Massachusetts General Hospital in Boston, Massachusetts
| | | | | | | | | | - Jen Woods
- A publications editor, all at the Natural Standard Research Collaboration
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Abstract
Hepatotoxic effects attributable to antituberculosis therapy are considered unique among drug-related liver problems because almost all first-line antituberculosis medications have such adverse effects, which vary in severity according to the drug and the regimen. In addition, all regimens for the treatment of active tuberculosis include a combination of medications that must typically be administered for at least 6 months to ensure complete cure of the disease and to minimize the development of drug-resistant bacterial strains. Hepatotoxic effects are a serious problem in patients who are undergoing treatment for tuberculosis, not only because of the morbidity and mortality they directly cause, but also because the liver symptoms can necessitate interruption of therapy or affect a patient's adherence to it, which can limit the efficacy of the antitubercular regimen.
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Affiliation(s)
- Bahaa E Senousy
- Internal Medicine Department, Ain Shams University, Abbassia 11566, Cairo, Egypt
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Benammar C, Hichami A, Yessoufou A, Simonin AM, Belarbi M, Allali H, Khan NA. Zizyphus lotus L. (Desf.) modulates antioxidant activity and human T-cell proliferation. Altern Ther Health Med 2010; 10:54. [PMID: 20868496 PMCID: PMC2955679 DOI: 10.1186/1472-6882-10-54] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2009] [Accepted: 09/24/2010] [Indexed: 01/28/2023]
Abstract
Background Zizyphus lotus L. (Desf.) also known as Jujube, is a deciduous shrub which belongs to Rhamnaceae family. This plant is used in Algerian traditional medicine for its anti-diabetic, sedative, analgesic, anti-inflammatory and hypoglycaemic activities. In the present study, we determined the concentrations of different vitamins (vitamin A, C and E) and fatty acids in root, stem, leaves, fruit pulp and seed of Zizyphus lotus L. (Desf.) and assessed the effects of their aqueous extracts on antioxidant status and human T-cell proliferation. Methods Aqueous filtrates from different parts, i.e, root, leaf, stem, fruit pulp and seed, of Zizyphus lotus L. (Desf.) were prepared. Vitamin C levels were determined by precipitating with 10% trichloroacetic acid and vitamin A and E were assessed by HPLC. Lipid composition of these extracts was determined by gas-liquid chromatography. Anti-oxidant capacity was evaluated by using anti-radical resistance kit [Kit Radicaux Libres (KRL@; Kirial International SA, Couternon, France)]. T-cell blastogenesis was assessed by the incorporation of 3H-thymidine. IL-2 gene expression was evaluated by RT-qPCR. Results Our results show that fruit pulp contained higher vitamin A and C contents than other parts of the plant. Furthermore, the fruit pulp was the richest source of linoleic acid (18:2n-6), a precursor of n-6 fatty acids. Fruit seeds possessed higher vitamin C levels than leaves, roots and stem. The leaves were the richest source of vitamin E and linolenic acid (18:3n-3), a precursor of n-3 fatty acids. The antioxidant capacity of the different extracts, measured by KRL@ test, was as follows: pulp < seed<leaf<root < stem. As far as T-cell proliferation is concerned, we observed that the different extracts of Zizyphus lotus L. (Desf.) exerted immunosuppressive effects. Conclusion Seed extracts exerted the most potent immunosuppressive effects on T cell proliferation and IL-2 mRNA expression. The results of the present study are discussed in the light of their use to modulate the immune-mediated diseases.
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Adhvaryu MR, Reddy NM, Vakharia BC. Prevention of hepatotoxicity due to anti tuberculosis treatment: A novel integrative approach. World J Gastroenterol 2008; 14:4753-62. [PMID: 18720535 PMCID: PMC2739336 DOI: 10.3748/wjg.14.4753] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the ability of Curcuma longa (CL) and Tinospora cordifolia (TC) formulation to prevent anti-tuberculosis (TB) treatment (ATT) induced hepatotoxicity.
METHODS: Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched (25%) CL and a hydro-ethanolic extract enriched (50%) TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result.
RESULTS: Incidence and severity of hepatotoxicity was significantly lower in trial group (incidence: 27/192 vs 2/316, P < 0.0001). Mean aspartate transaminase (AST) (195.93 ± 108.74 vs 85 ± 4.24, P < 0.0001), alanine transaminase (ALT) (75.74 ± 26.54 vs 41 ± 1.41, P < 0.0001) and serum bilirubin (5.4 ± 3.38 vs 1.5 ± 0.42, P < 0.0001). A lesser sputum positivity ratio at the end of 4 wk (10/67 vs 4/137, P = 0.0068) and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment (9/152 vs 2/278, P = 0.0037) was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group (P < 0.0001).
CONCLUSION: The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects.
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Eminzade S, Uras F, Izzettin FV. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutr Metab (Lond) 2008; 5:18. [PMID: 18601745 PMCID: PMC2491620 DOI: 10.1186/1743-7075-5-18] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2008] [Accepted: 07/05/2008] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs. METHODS Male Wistar albino rats weighing 250-300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg) and rifampicin (100 mg/kg); and intra-gastric administration of pyrazinamid (350 mg/kg) and silymarin (200 mg/kg). Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin. RESULTS Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs. CONCLUSION The active components of silymarin had protective effects against hepatotoxic actions of drugs used in the chemotherapy of tuberculosis in animal models. Since no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anti-tuberculosis medications.
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Affiliation(s)
- Sude Eminzade
- Department of Pharmacology, Marmara University, Faculty of Pharmacy, Haydarpasa, Istanbul, Turkey
| | - Fikriye Uras
- Department of Biochemistry, Marmara University, Faculty of Pharmacy, Haydarpasa, Istanbul, Turkey
| | - Fikret V Izzettin
- Department of Pharmacology, Marmara University, Faculty of Pharmacy, Haydarpasa, Istanbul, Turkey
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Adhvaryu MR, Reddy N, Parabia MH. Anti-tumor activity of four Ayurvedic herbs in Dalton lymphoma ascites bearing mice and their short-term in vitro cytotoxicity on DLA-cell-line. AFRICAN JOURNAL OF TRADITIONAL, COMPLEMENTARY, AND ALTERNATIVE MEDICINES : AJTCAM 2008; 5:409-18. [PMID: 20161965 PMCID: PMC2816583 DOI: 10.4314/ajtcam.v5i4.31297] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/27/2023]
Abstract
The anti-tumor activity and chemopreventive potential of four Ayurvedic herbs viz. Curcuma longa L., Ocimum sanctum L., Tinospora cordifolia (Wild) Miers ex Hook.f & Thomas and Zizyphus mauritiana Lam. were evaluated using Dalton Lymphoma ascites (DLA) tumor model in Swiss Albino mice. The outcome was assessed using survival time, peritoneal ascitic fluid (Tumor volume) and hematological indices as parameters. Animals were divided into five groups (n = 6) viz. one DLA control and four Herb + DLA treated groups. All the four herb + DLA groups were pre-treated with respective herbs for 7 days and hematological indices were measured for entire five groups. On day-8 animals were inoculated with 1x10(6) DLA cells i.p., and Herb + DLA groups were continued with oral herbal treatment for 21-days. Hematological parameters and tumor volume were assessed to find the effects of herbs. Short term in vitro cytotoxicity was determined by Trypan Blue exclusion method and LDH leakage assay using different concentrations of herbal extracts and 5-FU as a positive control and IC(50) for each herbal extract and 5-FU were determined. Oral administration of crude herb increased the survival time and decreased the peritoneal ascitic fluid content significantly. Hb, RBCs and total WBC which were altered by DLA inoculation were restored significantly by all the herbs except O. sanctum. All the four herbs showed in vitro cytotoxic activity against DLA cell-line. Moreover inter group comparison of all the four herbs for anti-tumor activity showed efficacy in the following order--T. cordifolia > Z. mauritiana > or = C. longa > O. sanctum respectively.
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Affiliation(s)
- Meghna R Adhvaryu
- Bapalal Vaidya Botanical Research Centre, Dept. of Biosciences, Veer Narmad South Gujarat University, Surat-395007, India
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