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Abdel-Hameed UK, Abualghaith AS, Aly SH, Soliman MM, Munshi LA, Mohammed SAA, Eldahshan OA, Abdelghffar EAR. GC/MS Analysis and Protective Effects of Mentha longifolia L. Essential Oil Against Antituberculosis Drug-Induced Organs Toxicity in Wistar Albino Rats. PLANTS (BASEL, SWITZERLAND) 2024; 13:3231. [PMID: 39599440 PMCID: PMC11598752 DOI: 10.3390/plants13223231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 11/02/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024]
Abstract
Mentha longifolia (L.) L., also known as wild mint, is a perennial herbaceous plant that belongs to the Lamiaceae family. This study aimed to investigate the effects of essential oil of M. longifolia (MLEO) on oxidative stress and inflammatory responses in the liver and kidneys in the context of drug-induced liver injury caused by the anti-TB drugs rifampicin, isoniazid, and pyrazinamide (INH-RIF-PZA). The chemical composition of MLEO was characterized using GC/MS analysis, which revealed the presence of pulegone, trans-p-menthan-3-one, piperitenone, and β-caryophyllene as its major volatile constituents. An INH/RIF/PZA mixture was administered to Wistar rats for 30 days, and silymarin was administered as a standard drug. MLEO was administered p.o. at doses of 50 mg and 100 mg/kg b.w. Both doses of the MLEO therapy effectively regulated all biochemical indicators of hepatic impairment and reduced the damage caused by the INH/RIF/PZA mixture. It may be deduced that MLEO has the ability to protect organs against INH/RIF/PZA-induced damage and could potentially be a valuable natural remedy for treating anti-TB-induced liver and kidney injuries.
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Affiliation(s)
- Usama K. Abdel-Hameed
- Biology Department, College of Science, Taibah University, Al-Madinah Al-Munawara 42353, Saudi Arabia; (U.K.A.-H.); (A.S.A.); (L.A.M.); (S.A.A.M.)
- Botany Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
| | - Abdulaziz S. Abualghaith
- Biology Department, College of Science, Taibah University, Al-Madinah Al-Munawara 42353, Saudi Arabia; (U.K.A.-H.); (A.S.A.); (L.A.M.); (S.A.A.M.)
| | - Shaza H. Aly
- Department of Pharmacognosy, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo 11829, Egypt;
| | - Mohamed Mostafa Soliman
- Department of Biology, College of Science, Jazan University, P.O. Box. 114, Jazan 45142, Saudi Arabia;
- Zoology Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
| | - Lamiaa Adnan Munshi
- Biology Department, College of Science, Taibah University, Al-Madinah Al-Munawara 42353, Saudi Arabia; (U.K.A.-H.); (A.S.A.); (L.A.M.); (S.A.A.M.)
| | - Safia A. A. Mohammed
- Biology Department, College of Science, Taibah University, Al-Madinah Al-Munawara 42353, Saudi Arabia; (U.K.A.-H.); (A.S.A.); (L.A.M.); (S.A.A.M.)
| | - Omayma A. Eldahshan
- Pharmacognosy Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt
- Center for Drug Discovery Research and Development, Ain Shams University, Cairo 11566, Egypt
| | - Eman A. R. Abdelghffar
- Biology Department, College of Science, Taibah University, Al-Madinah Al-Munawara 42353, Saudi Arabia; (U.K.A.-H.); (A.S.A.); (L.A.M.); (S.A.A.M.)
- Zoology Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
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Tiwana G, Cock IE, Cheesman MJ. Combinations of Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. Extracts with Selected Antibiotics Against Antibiotic-Resistant Bacteria: Bioactivity and Phytochemistry. Antibiotics (Basel) 2024; 13:994. [PMID: 39452260 PMCID: PMC11504310 DOI: 10.3390/antibiotics13100994] [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: 09/19/2024] [Revised: 10/16/2024] [Accepted: 10/18/2024] [Indexed: 10/26/2024] Open
Abstract
Antimicrobial resistance (AMR) has arisen due to antibiotic overuse and misuse. Antibiotic resistance renders standard treatments less effective, making it difficult to control some infections, thereby increasing morbidity and mortality. Medicinal plants are attracting increased interest as antibiotics lose efficacy. This study evaluates the antibacterial activity of solvent extracts prepared using Terminalia bellirica and Terminalia chebula fruit against six bacterial pathogens using disc diffusion and broth microdilution assays. The aqueous and methanol extracts of T. bellirica and T. chebula showed substantial zones of inhibition (ZOIs) against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The activity against those bacteria was strong, with minimum inhibitory concentrations (MIC) ranging from 94 µg/mL to 392 µg/mL. Additionally, the T. bellirica methanolic extract showed noteworthy antibacterial activity against Escherichia coli and an extended spectrum β-lactamase (ESBL) E. coli strain (MIC values of 755 µg/mL for both). The aqueous T. bellirica and T. chebula extracts also inhibited Klebsiella pneumoniae growth (MIC values of 784 µg/mL and 556 µg/mL, respectively). The corresponding methanolic extracts also inhibited ESBL K. pneumoniae growth (MIC values of 755 µg/mL and 1509 µg/mL, respectively). Eighteen additive interactions were observed when extracts were combined with reference antibiotics. Strong antagonism occurred when any of the extracts were mixed with polymyxin B. Liquid chromatography-mass spectroscopy (LC-MS) analysis of the extracts revealed several interesting flavonoids and tannins, including 6-galloylglucose, 1,2,6-trigalloyl-β-D-glucopyranose, 6-O-[(2E)-3-phenyl-2-propenoyl]-1-O-(3,4,5-trihydroxybenzoyl)-β-D-glucopyranose, propyl gallate, methyl gallate, sanguiin H4, hamamelitannin, pyrogallol, gallic acid, ellagic acid, chebulic acid, and chebuloside II. All extracts were nontoxic in brine shrimp assays. This lack of toxicity, combined with their antibacterial activities, suggests that these plant species may be promising sources of antibacterial compound(s) that warrant further study.
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Affiliation(s)
- Gagan Tiwana
- School of Pharmacy and Medical Sciences, Gold Coast Campus, Griffith University, Gold Coast 4222, Australia;
| | - Ian Edwin Cock
- School of Environment and Science, Nathan Campus, Griffith University, Brisbane 4111, Australia;
| | - Matthew James Cheesman
- School of Pharmacy and Medical Sciences, Gold Coast Campus, Griffith University, Gold Coast 4222, Australia;
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Islam MR, Rauf A, Alash S, Fakir MNH, Thufa GK, Sowa MS, Mukherjee D, Kumar H, Hussain MS, Aljohani ASM, Imran M, Al Abdulmonem W, Thiruvengadam R, Thiruvengadam M. A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways. Med Oncol 2024; 41:134. [PMID: 38703282 DOI: 10.1007/s12032-024-02333-5] [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: 12/08/2023] [Accepted: 02/13/2024] [Indexed: 05/06/2024]
Abstract
Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.
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Affiliation(s)
- Md Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, 23561, Khyber Pakhtunkhwa, Pakistan.
| | - Shopnil Alash
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Md Naeem Hossain Fakir
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Gazi Kaifeara Thufa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Mahbuba Sharmin Sowa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Dattatreya Mukherjee
- Raiganj Government Medical College and Hospital, Pranabananda Sarani, Raiganj, 733134, West Bengal, India
| | - Harendra Kumar
- Dow University of Health Sciences, Mission Rd, New Labour Colony Nanakwara, Karachi, 74200, Sindh, Pakistan
| | - Md Sadique Hussain
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, 302017, Rajasthan, India
| | - Abdullah S M Aljohani
- Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Muhammad Imran
- Chemistry Department, Faculty of Science, King Khalid University, P.O. Box 9004, 61413, Abha, Saudi Arabia
| | - Waleed Al Abdulmonem
- Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Rekha Thiruvengadam
- Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical & Technical Sciences (SIMATS), Saveetha University, Chennai, 600077, Tamil Nadu, India.
| | - Muthu Thiruvengadam
- Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul, 05029, South Korea
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Patil VS, Harish DR, Charla R, Vetrivel U, Jalalpure SS, Bhandare VV, Deshpande SH, Hegde HV, Roy S. Structural insights into modeling of hepatitis B virus reverse transcriptase and identification of its inhibitors from potential medicinal plants of Western Ghats: an in silico and in vitro study. J Biomol Struct Dyn 2023; 42:11731-11749. [PMID: 37811543 DOI: 10.1080/07391102.2023.2264400] [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: 07/07/2023] [Accepted: 09/21/2023] [Indexed: 10/10/2023]
Abstract
The present study was proposed to model full-length HBV-RT and investigate the intermolecular interactions of known inhibitor and libraries of phytocompounds to probe the potential natural leads by in silico and in vitro studies. Homology modeling of RT was performed by Phyre2 and Modeller and virtual screening of ligands implemented through POAP pipeline. Molecular dynamics (MD) simulation (100 ns) and MM-GBSA calculations were performed using Schrodinger Desmond and Prime, respectively. Phytocompounds probable host protein targets gene set pathway enrichment and network analysis were executed by KEGG database and Cytoscape software. Prioritized plant extracts/enriched fraction LC-MS analysis was performed and along with pure compound, RT inhibitory activity, time-dependent HBsAg and HBeAg secretion, and intracellular HBV DNA, and pgRNA by qRT-PCR was performed in HepG2.2.15 cell line. Among the screened chemical library of 268 phytocompounds from 18 medicinal plants, 15 molecules from Terminalia chebula (6), Bidens pilosa (5), and Centella asiatica (4)) were identified as potential inhibitors of YMDD and RT1 motif of HBV-RT. MD simulation demonstrated stable interactions of 15 phytocompounds with HBV-RT, of which 1,2,3,4,6-Pentagalloyl Glucose (PGG) was identified as lead molecule. Out of 15 compounds, 11 were predicted to modulate 39 proteins and 15 molecular pathways associated with HBV infection. TCN and TCW (500 µg/mL) showed potent RT inhibition, decreased intracellular HBV DNA, and pgRNA, and time-dependent inhibition of HBsAg and HBeAg levels compared to PGG and Tenofovir Disoproxil Fumarate. We propose that the identified lead molecules from T. chebula as promising and cost-effective moieties for the management of HBV infection.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Vishal S Patil
- ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, India
- KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India
| | | | - Rajitha Charla
- ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, India
| | - Umashankar Vetrivel
- ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, India
- ICMR-National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India
| | - Sunil S Jalalpure
- KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India
| | - Vishwambhar Vishnu Bhandare
- ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, India
- Department of Microbiology, Shivaji University, Kolhapur, Maharashtra, India
| | - Sanjay H Deshpande
- ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, India
- Regional Centre for Biotechnology, NCR-Biotech Science Cluster, Faridabad, India
| | - Harsha V Hegde
- ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, India
| | - Subarna Roy
- ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, India
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Ai L, Yang F, Hu W, Guo L, Liu W, Xue X, Li L, Sheng Z. Hepatotoxic Components Effect of Chebulae Fructus and Associated Molecular Mechanism by Integrated Transcriptome and Molecular Docking. Molecules 2023; 28:molecules28083427. [PMID: 37110661 PMCID: PMC10143891 DOI: 10.3390/molecules28083427] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/23/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Chebulae Fructus (CF) is a natural medicinal plant widely used for its various pharmacological properties. Natural products used to cure several diseases have been considered safe thanks to their little or no side effects. However, in recent years, a hepatotoxic effect has been found due to the abuse of herbal medicine. CF has been reported to have hepatotoxicity, but the mechanism is unclear. In this experiment, the toxic aspect and mechanism of CF action were evaluated by transcriptome analysis. Components of toxic CF fractions were identified by LC-MS, and hepatotoxic toxic components in toxic CF fractions were predicted by molecular docking. The results showed that the ethyl acetate part of CF was the main toxic fraction, and transcriptome analysis found that the toxic mechanism was highly related to lipid metabolism-related pathways, and CFEA could inhibit the PPAR signaling pathway. Molecular docking results showed that 3'-O-methyl-4-O-(n″-O-galloyl-β-d-xylopyranosyl) ellagic acid (n = 2, 3 or 4) and 4-O-(3″,4″-O-digalloyl-α-l-rhamnosyl) ellagic acid have better docking energies with PPARα protein and FABP protein than other components. In summary, 3'-O-methyl-4-O-(n″-O-galloyl-β-d-xylopyranosyl) ellagic acid (n = 2, 3 or 4) and 4-O-(3″,4″-O-digalloyl-α-l-rhamnosyl) ellagic acid were the main toxic components, which may play a toxic role by inhibiting the PPAR signaling pathway and affect lipid metabolism.
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Affiliation(s)
- Liwen Ai
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Fan Yang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Wanjun Hu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Liyang Guo
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Weixue Liu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Xuexue Xue
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Lulu Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
| | - Zunlai Sheng
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
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Kamal Z, Ebnalwaled AA, Al-Amgad Z, Said AH, Metwally AA, Zigo F, Ondrašovičová S, Rehan IF. Ameliorative effect of biosynthesized titanium dioxide nanoparticles using garlic extract on the body weight and developmental toxicity of liver in albino rats compared with chemically synthesized nanoparticles. Front Vet Sci 2022; 9:1049817. [PMID: 36590803 PMCID: PMC9800981 DOI: 10.3389/fvets.2022.1049817] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 11/11/2022] [Indexed: 12/23/2022] Open
Abstract
The application of metallic nanoparticles poses risks to human and animal health. Titanium dioxide nanoparticles (TiO2NPs) are the most commonly synthesized metallic oxides in the world. Exposure to TiO2NPs can cause toxicity in the target organisms. This study aimed to evaluate the effects of green and chemical TiO2NPs on maternal and embryo-fetal livers. Green TiO2NPs using garlic extract (GTiO2NPs) and chemical TiO2NPs (CHTiO2NPs) were synthesized and characterized by x-ray powder diffraction and high-resolution transmission electron microscopy. The cytotoxicity of both chemical and green TiO2NPs was determined against HepG2 cell lines. Fifty pregnant female Albino rats were equally and randomly divided into five groups. Group 1 was kept as a control. Groups 2 and 3 were orally treated with 100 and 300 mg/kg body weight of CHTiO2NPs, respectively. Groups 4 and 5 were orally treated with 100 and 300 mg/kg of GTiO2NPs, respectively, from day 6 to 19 of gestation. All dams were euthanized on gestation day 20. All live fetuses were weighed and euthanized. Blood and tissue samples were collected for biochemical, histopathological, and Bax-immunohistochemical expression analyses. Our results indicated that garlic could be used as a reducing agent for the synthesis of TiO2NPs, and the produced NPs have no toxic effect against HepG2 cells compared with CHTiO2NPs. The maternal and fetal bodyweights were greatly reduced among the chemically TiO2NPs induced animals. The mean serum level of AST and ALT activities and the total protein level significantly increased when TiO2NPs were administered at high doses. Histologically, the CHTiO2NPs-treated groups revealed vacuolated and necrotized hepatocytes with congested and dilated blood vessels in the fetal and maternal livers. The immunohistochemistry revealed distinct positive staining of Bax expressed in the hepatocytes. Nevertheless, the biosynthesis of TiO2NPs using garlic extract had a minimal effect on the normal architecture of the liver. It could be concluded that the bioactivity of TiO2NPs can be modified by green synthesis using garlic extract. Compared to the CHTiO2NPs, the exposure to GTiO2NPs showed reduced liver damage in maternal and embryo-fetal rats.
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Affiliation(s)
- Zeinab Kamal
- Zoology Department, Faculty of Science, South Valley University, Qena, Egypt
| | - A. A. Ebnalwaled
- Electronic and Nano Devise Lab, Faculty of Science, South Valley University, Qena, Egypt
| | - Zeinab Al-Amgad
- General Authority for Veterinary Services, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt
| | - Alaa H. Said
- Electronic and Nano Devise Lab, Faculty of Science, South Valley University, Qena, Egypt
| | - Asmaa A. Metwally
- Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Aswan University, Aswan, Egypt
| | - František Zigo
- Department of Nutrition and Animal Husbandry, University of Veterinary Medicine and Pharmacy in Košice, Košice, Slovakia
| | - Silvia Ondrašovičová
- Department of Biology and Physiology, University of Veterinary Medicine and Pharmacy in Košice, Košice, Slovakia
| | - Ibrahim F. Rehan
- Department of Husbandry and Development of Animal Wealth, Faculty of Veterinary Medicine, Menoufia University, Shebin Alkom, Egypt
- Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya-shi, Japan
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Terminalia chebula Medicinal Uses: A Review of in vitro and in vivo Studies. BIOTECHNOL BIOPROC E 2022. [DOI: 10.1007/s12257-022-0090-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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Hassan Bulbul MR, Uddin Chowdhury MN, Naima TA, Sami SA, Imtiaj MS, Huda N, Uddin MG. A comprehensive review on the diverse pharmacological perspectives of Terminalia chebula Retz. Heliyon 2022; 8:e10220. [PMID: 36051270 PMCID: PMC9424961 DOI: 10.1016/j.heliyon.2022.e10220] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 05/31/2022] [Accepted: 08/02/2022] [Indexed: 11/22/2022] Open
Abstract
Terminalia chebula Retz, commonly known as 'Haritaki/Myrobalan,' has been utilised as a traditional medicine for a long time. It has been extensively exercised in various indigenous medicine practices like Unani, Tibb, Ayurveda, and Siddha to remedy human ailments such as bleeding, carminative, dysentery, liver tonic, digestive, antidiarrheal, analgesic, anthelmintic, antibacterial and helpful in skin disorders. Studies on the pharmacological effects of T. chebula and its phytoconstituents documented between January, 1996 and December, 2021 were explored using various electronic databases. During the time mentioned above, several laboratory approaches revealed the biological properties of T. chebula, including antioxidative, antiproliferative, anti-microbial, proapoptotic, anti-diabetic, anti-ageing, hepatoprotective, anti-inflammatory, and antiepileptic. It is also beneficial in glucose and lipid metabolism and prevents atherogenesis and endothelial dysfunction. Different parts of T. chebula such as fruits, seeds, galls, barks extracted with various solvent systems (aqueous, ethanol, methanol, chloroform, ethyl-acetate) revealed major bioactive compounds like chebulic acid, chebulinic acid, and chebulaginic acid, which in turn proved to have valuable pharmacological properties through broad scientific investigations. There is a common link between chebulagic acid and chebulanin with its antioxidant property, antiaging activity, antiinflammatory, antidiabetic activity, and cardioprotective activity. The actions may be through neutralizing the free radicals responsible for producing tissue damage alongside interconnecting many other diseases. The current review summarises the scientifically documented literature on pharmacological potentials and chemical compositions of T. chebula, which is expected to investigate further studies on this subject.
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Affiliation(s)
| | | | - Taslima Anjum Naima
- Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong, 4331, Bangladesh
| | - Saad Ahmed Sami
- Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong, 4331, Bangladesh
| | - Md. Shakil Imtiaj
- Department of Chemistry, Government City College, National University, Gazipur, 1708, Bangladesh
| | - Nazmul Huda
- Department of Chemistry, University of Texas at Rio Grande Valley, Edinburg, Texas, 78539, USA
| | - Md. Giash Uddin
- Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong, 4331, Bangladesh
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Duan S, Cui XY, Wang XY, Shan CB, Ma CM. Combination of Ephedra sinica stems and Terminalia chebula fruits produces new ephedrine derivatives in vivo that diminish the permeability to BBB while retaining airway dilation and hepatoprotective effects. JOURNAL OF ETHNOPHARMACOLOGY 2022; 285:114837. [PMID: 34788644 DOI: 10.1016/j.jep.2021.114837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/22/2021] [Accepted: 11/11/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The stems of Ephedra sinica and the fruits of Terminalia chebula are combined using in traditional Mongolian medicine formula "Gurigumu-7" for liver diseases. E. sinica stems contains ephedrine with broncho-dilatory activity. However, ephedrine can pass through the blood-brain barrier (BBB) and excite the central nervous system (CNS) to cause insomnia and restlessness. AIM OF THE STUDY The present study was to investigate the structures and bioactivities of new compounds formed in vivo after co-administration of E. sinica stems and T. chebula fruits. MATERIALS AND METHODS Pharmacokinetic investigation was carried out in rats. A parallel artificial membrane permeability measurement system was used to determine BBB permeability. Ex vivo experiments using tracheal rings of guinea pig was performed to examine the tracheal relaxation effect. In vivo hepatoprotective tests were carried out in Tg (fabp10a: dsRed) liver transgenic zebrafish. The fluorescent probe, 2,7-dichlorodihydrofluorescein diacetate, was used to measure reactive oxygen species, and UHPLC-MS was used to determine glutathione concentrations after derivatization with N-ethylmaleimide. RESULTS New ephedrine derivatives (1 and 2) formed in vivo and reached their maximum serum concentrations at 0.5 h after administration of the two herbal drugs. Compounds 1 and 2 showed lower BBB permeability than ephedrine, suggesting that they have less adverse effects on the CNS. Compounds 1 and 2 relaxed the tracheal rings and had strong hepatoprotective effect on transgenic zebrafish with liver specific expression of RFP. Compounds 1 and 2 significantly reduced the level of reactive oxygen species while increasing that of glutathione in thioacetamide-treated zebrafish, which might be the hepatoprotective mechanism. CONCLUSION These results provided evidences that the chemical constituents in various herbal drugs in a medicinal formula can interact to generate new compounds with fewer side effects and increased or additive bioactivity.
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Affiliation(s)
- Shen Duan
- School of Life Sciences, Inner Mongolia University, Hohhot, 010070, China.
| | - Xue-Ying Cui
- School of Life Sciences, Inner Mongolia University, Hohhot, 010070, China.
| | - Xin-Yao Wang
- School of Life Sciences, Inner Mongolia University, Hohhot, 010070, China.
| | - Cheng-Bin Shan
- School of Life Sciences, Inner Mongolia University, Hohhot, 010070, China.
| | - Chao-Mei Ma
- School of Life Sciences, Inner Mongolia University, Hohhot, 010070, China.
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Patil VS, Harish DR, Vetrivel U, Roy S, Deshpande SH, Hegde HV. Hepatitis C Virus NS3/4A Inhibition and Host Immunomodulation by Tannins from Terminalia chebula: A Structural Perspective. Molecules 2022; 27:molecules27031076. [PMID: 35164341 PMCID: PMC8839135 DOI: 10.3390/molecules27031076] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 01/15/2022] [Accepted: 01/22/2022] [Indexed: 01/27/2023] Open
Abstract
Terminalia chebula Retz. forms a key component of traditional folk medicine and is also reported to possess antihepatitis C virus (HCV) and immunomodulatory activities. However, information on the intermolecular interactions of phytochemicals from this plant with HCV and human proteins are yet to be established. Thus, by this current study, we investigated the HCV NS3/4A inhibitory and host immune-modulatory activity of phytocompounds from T. chebula through in silico strategies involving network pharmacology and structural bioinformatics techniques. To start with, the phytochemical dataset of T. chebula was curated from biological databases and the published literature. Further, the target ability of the phytocompounds was predicted using BindingDB for both HCV NS3/4A and other probable host targets involved in the immune system. Further, the identified targets were docked to the phytochemical dataset using AutoDock Vina executed through the POAP pipeline. The resultant docked complexes with significant binding energy were subjected to 50 ns molecular dynamics (MD) simulation in order to infer the stability of complex formation. During network pharmacology analysis, the gene set pathway enrichment of host targets was performed using the STRING and Reactome pathway databases. Further, the biological network among compounds, proteins, and pathways was constructed using Cytoscape 3.6.1. Furthermore, the druglikeness, side effects, and toxicity of the phytocompounds were also predicted using the MolSoft, ADVERpred, and PreADMET methods, respectively. Out of 41 selected compounds, 10 were predicted to target HCV NS3/4A and also to possess druglike and nontoxic properties. Among these 10 molecules, Chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose exhibited potent HCV NS3/4A inhibitory activity, as these scored a lowest binding energy (BE) of −8.6 kcal/mol and −7.7 kcal/mol with 11 and 20 intermolecular interactions with active site residues, respectively. These findings are highly comparable with Asunaprevir (known inhibitor of HCV NS3/4A), which scored a BE of −7.4 kcal/mol with 20 key intermolecular interactions. MD studies also strongly suggest that chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose as promising leads, as these molecules showed stable binding during 50 ns of production run. Further, the gene set enrichment and network analysis of 18 protein targets prioritized 10 compounds and were predicted to potentially modulate the host immune system, hemostasis, cytokine levels, interleukins signaling pathways, and platelet aggregation. On overall analysis, this present study predicts that tannins from T. chebula have a potential HCV NS3/4A inhibitory and host immune-modulatory activity. However, further experimental studies are required to confirm the efficacies.
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Affiliation(s)
- Vishal S. Patil
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi 590010, India; (V.S.P.); (U.V.); (S.H.D.); (H.V.H.)
| | - Darasaguppe R. Harish
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi 590010, India; (V.S.P.); (U.V.); (S.H.D.); (H.V.H.)
- Correspondence: (D.R.H.); (S.R.)
| | - Umashankar Vetrivel
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi 590010, India; (V.S.P.); (U.V.); (S.H.D.); (H.V.H.)
- ICMR-National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, India
| | - Subarna Roy
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi 590010, India; (V.S.P.); (U.V.); (S.H.D.); (H.V.H.)
- Correspondence: (D.R.H.); (S.R.)
| | - Sanjay H. Deshpande
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi 590010, India; (V.S.P.); (U.V.); (S.H.D.); (H.V.H.)
- Regional Centre for Biotechnology, NCR-Biotech Science Cluster, Faridabad 121001, India
| | - Harsha V. Hegde
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi 590010, India; (V.S.P.); (U.V.); (S.H.D.); (H.V.H.)
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11
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Ponnusamy N, Arumugam M. Interaction of Host Pattern Recognition Receptors (PRRs) with Mycobacterium Tuberculosis and Ayurvedic Management of Tuberculosis: A Systemic Approach. Infect Disord Drug Targets 2022; 22:e130921196420. [PMID: 34517809 DOI: 10.2174/1871526521666210913110834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 04/15/2021] [Accepted: 06/11/2021] [Indexed: 06/13/2023]
Abstract
Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), infects the lungs' alveolar surfaces through aerosol droplets. At this stage, the disease progression may have many consequences, determined primarily by the reactions of the human immune system. However, one approach will be to more actively integrate the immune system, especially the pattern recognition receptor (PRR) systems of the host, which notices pathogen-associated molecular patterns (PAMPs) of Mtb. Several types of PRRs are involved in the detection of Mtb, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), Dendritic cell (DC) -specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), Mannose receptor (MR), and NOD-like receptors (NLRs) related to inflammasome activation. In this study, we focus on reviewing the Mtb pathophysiology and interaction of host PPRs with Mtb as well as adverse drug effects of anti-tuberculosis drugs (ATDs) and systematic TB treatment via Ayurvedic medicine.
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Affiliation(s)
- Nirmaladevi Ponnusamy
- Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India
| | - Mohanapriya Arumugam
- Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India
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12
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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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13
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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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14
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Nigam M, Mishra AP, Adhikari-Devkota A, Dirar AI, Hassan MM, Adhikari A, Belwal T, Devkota HP. Fruits of Terminalia chebula Retz.: A review on traditional uses, bioactive chemical constituents and pharmacological activities. Phytother Res 2020; 34:2518-2533. [PMID: 32307775 DOI: 10.1002/ptr.6702] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 02/29/2020] [Accepted: 03/28/2020] [Indexed: 11/12/2022]
Abstract
Fruits of Terminalia chebula Retz. (Combretaceae) are widely used as crude drugs in various traditional medicine systems. The aim of this article is to review the available scientific information regarding the traditional uses, bioactive chemical constituents and the pharmacological activities of T. chebula. Numerous researches conducted on T. chebula have confirmed the presence of wide range of the phytochemicals such as flavonoids, tannins, phenolic acids and other bioactive compounds. T. chebula is also widely studied regarding its pharmacological activities such as antioxidant, hepatoprotective, neuroprotective, cytotoxic, antidiabetic, anti-inflammatory activities among others. However, more in vivo and clinical studies for mechanism-based pharmacological evaluation should be conducted in future to provide stronger scientific evidences for their traditional uses.
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Affiliation(s)
- Manisha Nigam
- Department of Biochemistry, H. N. B. Garhwal University, Srinagar Garhwal, India
| | - Abhay P Mishra
- Department of Pharmaceutical Chemistry, H. N. B. Garhwal University, Srinagar Garhwal, India
| | | | - Amina Ibrahim Dirar
- Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
| | - Md Mahadi Hassan
- Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
| | - Achyut Adhikari
- Central Department of Chemistry, Tribhuwan University, Kritipur, Nepal
| | - Tarun Belwal
- Key Laboratory for Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - Hari Prasad Devkota
- Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.,Program for Leading Graduate Schools, Health Life Science: Interdisciplinary and Glocal Oriented (HIGO) Program, Kumamoto University, Kumamoto, Japan
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15
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Sieniawska E, Maciejewska-Turska M, Świątek Ł, Xiao J. Plant-based Food Products for Antimycobacterial Therapy. EFOOD 2020. [DOI: 10.2991/efood.k.200418.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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16
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Lou H, Zhang F, Lu L, Ding Y, Hao X. Xanthohumol from Humulus lupulus L. potentiates the killing of Mycobacterium tuberculosis and mitigates liver toxicity by the combination of isoniazid in mouse tuberculosis models. RSC Adv 2020; 10:13223-13231. [PMID: 35492081 PMCID: PMC9051424 DOI: 10.1039/c9ra10347c] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 03/22/2020] [Indexed: 11/21/2022] Open
Abstract
Anti-tuberculosis drug induced hepatotoxicity is the main problem in tuberculosis patients. Xanthohumol, a major prenyl chalcone present in hops, has diverse biological activities including antibacterial and hepatoprotective activities. The present research aimed to investigate the combined effect of xanthohumol with isoniazid against Mycobacterium tuberculosis-infected mice. The liver damage was induced by treatment with isoniazid daily for 8 weeks. During the experiment, the uninfected group and the normal control group received an equal volume of saline, the xanthohumol group received an equal volume of xanthohumol only, and the isoniazid group received an equal volume of isoniazid only. The combination therapy group received not only isoniazid but also the corresponding xanthohumol. Experimental results showed that isoniazid combined with xanthohumol resulted in the lowest lung and spleen colony-forming unit counts compared to other groups. Furthermore, other positive outcomes implied that isoniazid combined with xanthohumol obviously alleviated anti-tuberculosis drug induced liver damage as indicated by the declined levels of ALT, AST, ALP, bilirubin and MDA and the increased levels of SOD, GSH-Px and ATPases. The study of the mechanisms underlying the hepatoprotective activity showed that xanthohumol was able to activate the antioxidative defense system and protect the hepatocellular membrane. The combination of isoniazid and xanthohumol had more effective bacteriostatic and hepatoprotective activities on Mycobacterium tuberculosis-infected mice than isoniazid alone. In conclusion, xanthohumol has the potential to be an effective adjuvant in tuberculosis treatment. Anti-tuberculosis drug induced hepatotoxicity is the main problem in tuberculosis patients.![]()
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Affiliation(s)
- Hai Lou
- Department of Tuberculosis
- Shanghai Pulmonary Hospital
- Tongji University School of Medicine
- Shanghai
- China
| | - Fen Zhang
- Department of Respiratory
- Shanghai Pulmonary Hospital
- Tongji University School of Medicinec
- Shanghai
- China
| | - Liqin Lu
- Department of Respiratory
- Shanghai Pulmonary Hospital
- Tongji University School of Medicinec
- Shanghai
- China
| | - Yingying Ding
- Department of Medical Microbiology and Parasitology
- Basic Medical College
- Second Military Medical University
- Shanghai
- China
| | - Xiaohui Hao
- Department of Tuberculosis
- Shanghai Pulmonary Hospital
- Tongji University School of Medicine
- Shanghai
- China
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17
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Mangwani N, Singh PK, Kumar V. Medicinal plants: Adjunct treatment to tuberculosis chemotherapy to prevent hepatic damage. J Ayurveda Integr Med 2019; 11:522-528. [PMID: 31679802 PMCID: PMC7772497 DOI: 10.1016/j.jaim.2019.02.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 12/29/2018] [Accepted: 02/18/2019] [Indexed: 02/07/2023] Open
Abstract
The effectiveness of herbs for the management of chemically induced hepatotoxicity has been discussed by many researchers. However, there is a paucity of compressive literature on the significance of hepatoprotective plants for the management of anti-TB drug induced toxicity. Anti-TB drugs have been reported to causes hepatic damage, due to which, many patients across the globe discontinued the treatment. Medicinal plants have multiple therapeutic effects. The assessment of biological activity of plants against Mycobacterium and its use for hepatic recovery provides an effective treatment approach. Traditionally used medicinal plants are the rich source of phytochemicals and secondary metabolites. These compounds can restore normal function, enzymatic activity and structure of hepatic cells against anti-TB drug induced hepatotoxicity. The present review covers comprehensive details on different hepatoprotective and antimycobacterial plants studied during past few decades so that potential adjuvants can be studied for Tuberculosis chemotherapy.
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Affiliation(s)
- Neelam Mangwani
- Value Addition Research and Development-Human Health, National Innovation Foundation-India, Grambharti, Mahudi Road, Gandhinagar, 382650, Gujarat, India
| | - Pawan Kumar Singh
- Value Addition Research and Development-Human Health, National Innovation Foundation-India, Grambharti, Mahudi Road, Gandhinagar, 382650, Gujarat, India.
| | - Vipin Kumar
- Value Addition Research and Development-Human Health, National Innovation Foundation-India, Grambharti, Mahudi Road, Gandhinagar, 382650, Gujarat, India
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18
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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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19
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Abstract
Purpose of this Review In order to combat the development of drug resistance, the clinical treatment of tuberculosis requires the combined use of several anti-tuberculosis (anti-TB) drugs, including isoniazid and rifampicin. Combinational treatment approaches are suggested by the World Health Organization (WHO) and are widely accepted throughout the world. Unfortunately, a major side effect of the treatment is the development of anti-tuberculosis drug-induced liver injury (AT-DILI). Many factors contribute to isoniazid- and rifampicin-mediated AT-DILI and genetic variations are among the most common factors. The purpose of this review is to provide information on genetic variations associated with isoniazid- and rifampicin-mediated AT-DILI. Recent Findings The genetic variations associated with AT-DILI have been identified in the genomic regions within or near genes encoding proteins in the following pathways: drug metabolizing enzymes (NAT2, CYP2E1, and GSTs), accumulation of bile acids, lipids, and heme metabolites (CYP7A1, BSEP, UGTs, and PXR), immune adaptation (HLAs and TNF-α), and oxidant challenge (TXNRD1, SOD1, BACH1, and MAFK). Summary The information summarized in this review considers the genetic bases of risk factors contributing to AT-DILI and provides information that may help for future studies. Some of the implicated genetic variations can be used in the design of genetic tests and serve as biomarkers for the prediction of isoniazid- and rifampicin-mediated AT-DILI risk in personalized medicine.
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20
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Li Q, Li HJ, Xu T, Du H, Huan Gang CL, Fan G, Zhang Y. Natural Medicines Used in the Traditional Tibetan Medical System for the Treatment of Liver Diseases. Front Pharmacol 2018; 9:29. [PMID: 29441019 PMCID: PMC5797630 DOI: 10.3389/fphar.2018.00029] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 01/10/2018] [Indexed: 12/13/2022] Open
Abstract
Liver disease is one of the most risk factors threatening human health. It is of great significance to find drugs that can treat liver diseases, especially for acute and chronic hepatitis, non-alcoholic fatty liver disease, and liver cancer. The search for drugs with good efficacy from traditional natural medicines has attracted more and more attention. Tibetan medicine, one of the China's traditional medical systems, has been widely used by the Tibetan people for the prevention and treatment of liver diseases for hundreds of years. The present paper summarized the natural Tibetan medicines that have been used in Tibetan traditional system of medicine to treat liver diseases by bibliographic investigation of 22 Tibetan medicine monographs and drug standards. One hundred and ninety three species including 181 plants, 7 animals, and 5 minerals were found to treat liver diseases in traditional Tibetan medicine system. The most frequently used species are Carthamus tinctorius, Brag-zhun, Swertia chirayita, Swertia mussotii, Halenia elliptica, Herpetospermum pedunculosum, and Phyllanthus emblica. Their names, families, medicinal parts, traditional uses, phytochemicals information, and pharmacological activities were described in detail. These natural medicines might be a valuable gift from the old Tibetan medicine to the world, and would be potential drug candidates for the treatment of liver diseases. Further studies are needed to prove their medicinal values in liver diseases treatment, identify bioactive compounds, elucidate the underlying mechanism of action, and clarify their side effects or toxicity with the help of modern phytochemical, pharmacological, metabonomics, and/or clinical trial methods.
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Affiliation(s)
- Qi Li
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hai-Jiao Li
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Tong Xu
- College of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Huan Du
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chen-Lei Huan Gang
- College of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Gang Fan
- College of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,Characteristic National Medicine Innovation Research Center of Tibet-Qiang-Yi, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yi Zhang
- College of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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21
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Tewari D, Mocan A, Parvanov ED, Sah AN, Nabavi SM, Huminiecki L, Ma ZF, Lee YY, Horbańczuk JO, Atanasov AG. Ethnopharmacological Approaches for Therapy of Jaundice: Part II. Highly Used Plant Species from Acanthaceae, Euphorbiaceae, Asteraceae, Combretaceae, and Fabaceae Families. Front Pharmacol 2017; 8:519. [PMID: 28848436 PMCID: PMC5554347 DOI: 10.3389/fphar.2017.00519] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 07/24/2017] [Indexed: 12/18/2022] Open
Abstract
In many developing countries, jaundice is the common symptom of hepatic diseases which are a major cause of mortality. The use of natural product-based therapies is very popular for such hepatic disorders. A great number of medicinal plants have been utilized for this purpose and some facilitated the discovery of active compounds which helped the development of new synthetic drugs against jaundice. However, more epidemiological studies and clinical trials are required for the practical implementation of the plant pharmacotherapy of jaundice. The focus of this second part of our review is on several of the most prominent plants used against jaundice identified in the analysis performed in the first part of the review viz. Andrographis paniculata (Burm.f.) Nees, Silybum marianum (L.) Gaertn., Terminalia chebula Retz., Glycyrrhiza glabra L. and some species of genus Phyllanthus. Furthermore, we discuss their physiological effects, biologically active ingredients, and the potential mechanisms of action. Some of the most important active ingredients were silybin (also recommended by German commission), phyllanthin and andrographolide, whose action leads to bilirubin reduction and normalization of the levels of relevant serum enzymes indicative for the pathophysiological status of the liver.
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Affiliation(s)
- Devesh Tewari
- Department of Pharmaceutical Sciences, Faculty of Technology, Kumaun UniversityNainital, India
| | - Andrei Mocan
- Department of Pharmaceutical Botany, “Iuliu Haţieganu” University of Medicine and PharmacyCluj-Napoca, Romania
- ICHAT and Institute for Life Sciences, University of Agricultural Sciences and Veterinary MedicineCluj-Napoca, Romania
| | - Emil D. Parvanov
- Division BIOCEV, Institute of Molecular Genetics, Academy of Sciences of the Czech RepublicPrague, Czechia
| | - Archana N. Sah
- Department of Pharmaceutical Sciences, Faculty of Technology, Kumaun UniversityNainital, India
| | - Seyed M. Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical SciencesTehran, Iran
| | - Lukasz Huminiecki
- Institute of Genetics and Animal Breeding of the Polish Academy of SciencesJastrzebiec, Poland
| | - Zheng Feei Ma
- School of Medical Sciences, Universiti Sains MalaysiaKota Bharu, Malaysia
- Department of Public Health, Xi’an Jiaotong-Liverpool UniversitySuzhou, China
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains MalaysiaKota Bharu, Malaysia
| | - Jarosław O. Horbańczuk
- Institute of Genetics and Animal Breeding of the Polish Academy of SciencesJastrzebiec, Poland
| | - Atanas G. Atanasov
- Institute of Genetics and Animal Breeding of the Polish Academy of SciencesJastrzebiec, Poland
- Department of Pharmacognosy, University of ViennaVienna, Austria
- Department of Vascular Biology and Thrombosis Research, Centre for Physiology and Pharmacology, Medical University of ViennaVienna, Austria
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22
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Basheer AS, Siddiqui A, Paudel YN, Hassan MQ, Imran M, Najmi AK, Akhtar M. Hepatoprotective and antioxidant effects of fish oil on isoniazid-rifampin induced hepatotoxicity in rats. PHARMANUTRITION 2017. [DOI: 10.1016/j.phanu.2017.01.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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23
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Raghu R, Karthikeyan S. Zidovudine and isoniazid induced liver toxicity and oxidative stress: Evaluation of mitigating properties of silibinin. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2016; 46:217-226. [PMID: 27497728 DOI: 10.1016/j.etap.2016.07.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 07/18/2016] [Accepted: 07/23/2016] [Indexed: 06/06/2023]
Abstract
HIV/AIDS patients are more prone for opportunistic TB infections and they are administered the combined regimen of anti-retroviral drug zidovudine (AZT) and isoniazid (INH) for therapy. However, AZT+INH treatment has been documented to induce injury and remedial measures to prevent this adversity are not clearly defined. Silibinin (SBN) is a natural hepatoprotective principle isolated from medicinal plant Silybum marianum and is currently used for therapy of various liver diseases. This study investigate the hepatotoxic potentials of AZT alone, INH alone and AZT+INH treatments and the mitigating potentials of SBN against these drugs induced toxic insults of liver in rats. Separate groups of rats (n=6 in each group) were administered AZT alone (50mg/kg b.w.), INH alone (25mg/kg, b.w.), AZT+INH (50mg/kg, b.w. and 25mg/kg, b.w.), SBN alone (100mg/kg, b.w.) and SBN+AZT+INH daily for sub-chronic period of 45days orally. The control rats received saline/propylene glycol. INH alone and AZT+INH-induced parenchymal cell injury and cholestasis of liver was evidenced by highly significant increase in the activities of marker enzymes (aspartate and alanine transaminase, alkaline phosphatase, argino succinic acid lyase), bilirubin, protein, oxidative stress parameters (lipid peroxidation, superoxide dismutase, catalase, reduced glutathione, vitamins C and E) and membrane bound ATPases were evaluated in serum/liver tissue homogenates. Histopathological studies show ballooning degradation, inflammatory lesions, lipid deposition and hydropic changes in the liver tissue. All the above biochemical and pathological changes induced by AZT+INH treatments were mitigated in rats receiving SBN simultaneously with these hepatotoxins, indicating its hepatoprotective and antioxidant potentials against AZT+INH-induced hepatotoxicity. The moderate hepatoprotective and oxidant potentials of SBN could be due to its low bioavailability and this deficiency could be prevented by supplementation of phosphatidylcholines and studies are warranted on these lines to improve the therapeutic efficiency of SBN.
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Affiliation(s)
- Ramanathan Raghu
- Food and Hepatotoxicology Laboratory, Department of Pharmacology and Environmental Toxicology, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamilnadu, India
| | - Sivanesan Karthikeyan
- Food and Hepatotoxicology Laboratory, Department of Pharmacology and Environmental Toxicology, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamilnadu, India.
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Elmorsy E, Attalla SM, Fikry E, Kocon A, Turner R, Christie D, Warren A, Nwidu LL, Carter WG. Adverse effects of anti-tuberculosis drugs on HepG2 cell bioenergetics. Hum Exp Toxicol 2016; 36:616-625. [PMID: 27461009 DOI: 10.1177/0960327116660751] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Tuberculosis (TB) is an intractable chronic infection. Disease treatment with anti-TB drugs remains challenging due to drug-induced hepatotoxicity. The toxicity of the anti-TB drugs rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) either alone or in combination was investigated in HepG2 cells. Assays of intracellular adenosine triphosphate (ATP) levels at 4-, 24- and 48-h post-exposure to gradient concentrations of RIF, INH and PZA were conducted. Drug-induced effects on mitochondrial membrane potential (MMP), mitochondrial complex I and complex III activity, nicotinamide adenine dinucleotide (NAD+) levels and cellular lactate production were assessed. Decreased ATP levels were dose-dependent and correlated with drug exposure duration. Approximate 24-h IC50s were 0.5 mM, 70 mM and 84 mM for RIF, INH and PZA, respectively. Twenty-four hours post-drug treatment, reductions of MMP ( p = 0.0005), mitochondrial complex I and III activities ( p = 0.0001 and p = 0.0003, respectively), NAD+ levels ( p = 0.0057) and increased lactate production ( p < 0.0001) were observed. Drug combinations used to mimic cumulative drug treatments induced a synergistic inhibition of mitochondrial complex I activity. An assessment of cellular ultrastructure using transmission electron microscopy indicated drug-induced mitophagy. Collectively, our study suggests that hepatotoxicity of commonly employed anti-TB drugs is mediated by their curtailment of mitochondrial function.
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Affiliation(s)
- E Elmorsy
- 1 Departments of Forensic Medicine and Clinical Toxicology, Mansoura University, Mansoura, Egypt
| | - S M Attalla
- 1 Departments of Forensic Medicine and Clinical Toxicology, Mansoura University, Mansoura, Egypt
| | - E Fikry
- 1 Departments of Forensic Medicine and Clinical Toxicology, Mansoura University, Mansoura, Egypt
| | - A Kocon
- 2 School of Medicine, University of Nottingham, Nottingham, UK
| | - R Turner
- 2 School of Medicine, University of Nottingham, Nottingham, UK
| | - D Christie
- 3 School of Life Sciences, University of Nottingham, Nottingham, UK
| | - A Warren
- 2 School of Medicine, University of Nottingham, Nottingham, UK
| | - L L Nwidu
- 4 Department of Experimental Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Port Harcourt, Port Harcourt, Nigeria
| | - W G Carter
- 2 School of Medicine, University of Nottingham, Nottingham, UK
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Khan MA, Gupta A, Kumar S, Ahmad S, Sastry JLN. Hepatoprotective activity of a new polyherbal formulation against paracetamol and D-galactosamine induced hepatic toxicity. J Pharm Bioallied Sci 2015; 7:246-9. [PMID: 26681875 PMCID: PMC4678983 DOI: 10.4103/0975-7406.168018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE The present study was envisaged to evaluate the protective effect of polyherbal formulation, DRDC/AY/8060, developed by Dabur India Ltd., against paracetamol and D-galactosamine induced hepatic toxicities in Wistar rats. MATERIALS AND METHODS The study was carried out in two different experiments of 10 and 14 days against paracetamol and D-galactosamine, respectively. Animals were divided into different treatment groups (n = 6). The control group received normal saline, a toxicant group in two experiments received paracetamol 750 mg/kg p.o. every 72 h for 10 days and D-galactosamine 400 mg/kg i.p. single dose. The test formulation was used at the two dose levels of 120 and 240 mg/kg/day. Treatment groups treated with test formulations were also administered D-galactosamine as given in toxicant group. At the end of the dosing schedule, blood was withdrawn from the retrobulbar plexus of the animals for serum estimation of serum glutamate oxaloacetate transferase (SGOT), serum glutamate pyruvate trasnferase (SGPT), albumin, bilirubin, and alkaline phosphatase (ALP). Following the withdrawal of blood animals was sacrificed, and liver tissue was excised for estimation of thiobarbituric acid reactive substances (lipid peroxidation, malondialdehyde), tissue glutathione (GSH) and histopathological studies. RESULTS It was evident from the biochemical estimation that both paracetamol and galactosamine caused hepatotoxicity in the toxicant groups. However, treatment with DRDC/AY/8060 significantly (P < 0.001, vs. toxicant) reduced the levels of SGOT, SGPT, serum bilirubin, and ALP, as well as decreased lipid peroxidation. In addition, treatment with test formulation also significantly (P < 0.001, vs. toxicant) elevated serum albumin and GSH levels compared to toxicant groups. CONCLUSION On the basis of these studies and comparative evaluation it can be concluded that the formulation DRDC/AY/8060 showed hepatoprotective activity against paracetamol and D-galactosamine at 120 mg/kg and 240 mg/kg.
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Affiliation(s)
- Mohammad Ahmed Khan
- Department of Pharmacognosy and Phytochemistry Faculty of Pharmacy, Bioactive Natural Product Laboratory, Hamdard University, New Delhi, India
| | - Arun Gupta
- Dabur Research and Development Center, Dabur India Ltd., Sahibabad, Ghaziabad, Uttar Pradesh, India
| | - Satyendra Kumar
- Dabur Research and Development Center, Dabur India Ltd., Sahibabad, Ghaziabad, Uttar Pradesh, India
| | - Sayeed Ahmad
- Department of Pharmacognosy and Phytochemistry Faculty of Pharmacy, Bioactive Natural Product Laboratory, Hamdard University, New Delhi, India
| | - J L N Sastry
- Dabur Research and Development Center, Dabur India Ltd., Sahibabad, Ghaziabad, Uttar Pradesh, India
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Choudhary M, Kumar V, Malhotra H, Singh S. Medicinal plants with potential anti-arthritic activity. JOURNAL OF COMPLEMENTARY MEDICINE RESEARCH 2015; 4:147-79. [PMID: 26401403 PMCID: PMC4566784 DOI: 10.5455/jice.20150313021918] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 02/09/2015] [Indexed: 01/08/2023]
Abstract
ETHNO PHARMACOLOGICAL RELEVANCE Traditional medicinal plants are practiced worldwide for treatment of arthritis especially in developing countries where resources are meager. This review presents the plants profiles inhabiting throughout the world regarding their traditional usage by various tribes/ethnic groups for treatment of arthritis. MATERIALS AND METHODS Bibliographic investigation was carried out by analyzing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases from the last six decades. Plants/their parts/extracts/polyherbal formulations, toxicity studies for arthritis have been included in the review article. The profiles presented also include information about the scientific name, family, dose, methodology along with mechanism of action and toxicity profile. Research status of 20 potential plant species has been discussed. Further, geographical distribution of research, plants distribution according to families has been given in graphical form. RESULTS 485 plant species belonging to 100 families, traditionally used in arthritis are used. Among 100 plant families, malvaceae constitute 16, leguminasae 7, fabaceae 13, euphorbiaceae 7, compositae 20, araceae 7, solanaceae 12, liliaceae 9, apocynaceae, lauraceae, and rubiaceae 10, and remaining in lesser proportion. It was observed in our study that majority of researches are carried mainly in developing countries like India, China, Korea and Nigeria. CONCLUSION This review clearly indicates that list of medicinal plants presented in this review might be useful to researchers as well as practioners. This review can be useful for preliminary screening of potential anti-arthritis plants. Further toxicity profile given in the review can be useful for the researchers for finding the safe dose.
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Affiliation(s)
- Manjusha Choudhary
- Department of Pharmacology, Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India
| | - Vipin Kumar
- Department of Pharmacy, School of Chemical Science and Pharmacy, Central University of Rajasthan, Ajmer, Rajasthan, India
| | - Hitesh Malhotra
- Department of Pharmacology, Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India
| | - Surender Singh
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
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Choi MK, Kim HG, Han JM, Lee JS, Lee JS, Chung SH, Son CG. Hepatoprotective Effect of Terminalia chebula against t-BHP-Induced Acute Liver Injury in C57/BL6 Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2015; 2015:517350. [PMID: 25691908 PMCID: PMC4321673 DOI: 10.1155/2015/517350] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2014] [Revised: 12/23/2014] [Accepted: 12/29/2014] [Indexed: 12/25/2022]
Abstract
We aimed to identify the hepatoprotective effects of Terminalia chebula water extract (TCW) and its corresponding pharmacological actions using C57/BL6 mice model of tert-butylhydroperoxide-(t-BHP-) induced acute liver injury. Mice were orally administered with TCW (0, 50, 100, or 200 mg/kg) or gallic acid (100 mg/kg) for 5 days before t-BHP (2.5 mM/kg) injection. Liver enzymes, histopathology, oxidative stress parameters, antioxidant components, and inflammatory cytokines were examined 18 h after t-BHP injection. t-BHP injection caused dramatic elevation of serum AST, ALT, and LDH level, while TCW pretreatment notably attenuated these elevations. Inflammatory cytokines including TNF-α, IL-1β, and IL-6 were notably increased in hepatic tissues, and then these were efficiently attenuated by TCW pretreatment. t-BHP injection notably increased malondialdehyde, total reactive oxygen species, and nitric oxide in the liver tissue, while it markedly dropped the antioxidant activities including total antioxidant capacity, total glutathione contents, glutathione peroxidase, superoxide dismutase, and catalase. TCW pretreatment remarkably ameliorated these alterations, and these effects were relevant to gene expressions. Histopathological examinations supported the above findings. Collectively, these findings well prove that TCW beneficially prevents acute and severe liver injury and clarify its corresponding mechanisms involved in the inhibition of oxidative stress and inflammatory cytokines.
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Affiliation(s)
- Min-Kyung Choi
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea
| | - Hyeong-Geug Kim
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea
| | - Jong-Min Han
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea
| | - Jin-Seok Lee
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea
| | - Jong Suk Lee
- GyeongGi Bio-Center, GSTEP, 864-1 Iui-dong, Yeongtong-gu, Suwon, Gyeonggi-do 443-270, Republic of Korea
| | - Sun Ho Chung
- GyeongGi Bio-Center, GSTEP, 864-1 Iui-dong, Yeongtong-gu, Suwon, Gyeonggi-do 443-270, Republic of Korea
| | - Chang-Gue Son
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea
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Rifampicin Loaded Mannosylated Cationic Nanostructured Lipid Carriers for Alveolar Macrophage-specific Delivery. Pharm Res 2014; 32:1741-51. [DOI: 10.1007/s11095-014-1572-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 11/10/2014] [Indexed: 10/24/2022]
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Upadhyay A, Agrahari P, Singh D. A Review on the Pharmacological Aspects of Terminalia chebula. INT J PHARMACOL 2014. [DOI: 10.3923/ijp.2014.289.298] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Bag A, Kumar Bhattacharyya S, Kumar Pal N, Ranjan Chattopadhyay R. Anti-inflammatory, anti-lipid peroxidative, antioxidant and membrane stabilizing activities of hydroalcoholic extract of Terminalia chebula fruits. PHARMACEUTICAL BIOLOGY 2013; 51:1515-1520. [PMID: 24004166 DOI: 10.3109/13880209.2013.799709] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
CONTEXT Arthritis is inflammation of one or more joints. Terminalia chebula Retz. (Combretaceae) fruit is mentioned in Ayurveda as useful in treating arthritic disorders. OBJECTIVE This work was undertaken to evaluate the anti-inflammatory, antioxidant, anti-lipid peroxidative and membrane-stabilizing effects of hydroalcoholic extract of Terminalia chebula fruits and also to establish a possible association between them. MATERIALS AND METHODS In vivo anti-inflammatory activity of T. chebula fruit extract at different doses ranged from 50 to 500 mg/kg, p.o. was evaluated against carrageenin-induced inflammation in rats. Human erythrocyte hemolytic assay was used for in vitro anti-inflammatory activity testing with 50 to 500 µg/ml fruit extract. Antioxidant potential of test fruit extract (10 to 100 µg/ml) was evaluated using TBARS and DPPH methods. The fruit extract was standardized for total phenolic content using Folin-Ciocalteu method. RESULTS The standardized extract at 250 mg/kg, p.o. dose caused 69.96% reduction in carrageenin-induced rat paw edema and demonstrated 96.72% protective effect on human RBC membrane stability. Besides, T. chebula fruit extract significantly reduced the in vivo formation of TBARS in carrageenin-induced rat liver with IC50 94.96 mg/kg, p.o. and also in vitro radical scavenging activities in DPPH assay method with IC50 42.14 µg/ml. The standardized extract contains phenolics 118.5 mg gallic acid equivalent/g of extract. DISCUSSION AND CONCLUSION These promising findings support the traditional use of T. chebula fruits in the treatment of arthritic disorders and suggest that radical quenching may be one of the mechanisms for its anti-inflammatory activity.
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Affiliation(s)
- Anwesa Bag
- Agricultural and Ecological Research Unit, Indian Statistical Institute , Kolkata , India and
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Jaganathan R, Ravinayagam V, Panchanadham S, Palanivelu S. Potential therapeutic role of Tridham in human hepatocellular carcinoma cell line through induction of p53 independent apoptosis. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 13:323. [PMID: 24256980 PMCID: PMC4222730 DOI: 10.1186/1472-6882-13-323] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2013] [Accepted: 11/15/2013] [Indexed: 12/31/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths reported worldwide. The incidence is higher in Asia and Africa, where there is greater endemic prevalence of hepatitis B and C. The devastating outcome of cancer can be minimized only by the use of potent therapeutic agents. Tridham (TD) has been acknowledged since olden days for its wide spectrum of biological properties and was used by traditional practitioners of Siddha and other indigenous systems of medicine. The present study aims at investigating the mechanistic action of TD by assessing the antiproliferative and pro-apoptotic effects on human hepatocellular carcinoma cell line (Huh7). METHODS Cell viability and apoptosis assay using MTT analysis and trypan blue staining, DAPI staining, DNA fragmentation, cell cycle analysis, mitochondrial membrane potential, real-time reverse transcription-polymerase chain reaction, western blotting and immunofluorescence staining were determined in Huh7 cells. RESULTS Viability studies of TD treated Huh7 cells showed an inhibition in cell growth in time and dose dependent manner. Chromatin condensation, DNA fragmentation and apoptotic bodies, which are structural changes characteristic of apoptosis, were found following TD treatment of Huh7 cells. DAPI staining and agarose gel electrophoresis confirmed the induction of apoptosis by TD. Cell cycle analysis of Huh7 cells treated with TD exhibited a marked accumulation of cells in the sub-G1 phase of the cell cycle in a dose dependent manner. Immunofluorescent staining for Ki-67 showed a higher level of expression in untreated cells as compared to TD treated cells. We observed a significant loss in the mitochondrial membrane potential and the release of cytochrome c into the cytosol in TD treated cells. Down regulation of Bcl-2, up regulation of Bax and Bad as well as activation of caspases-3 and 9 were also observed. The p53 gene expression was found to be unaltered in TD treated cells. CONCLUSION These results suggest that TD induces apoptosis of Huh7 cells through activation of Bax and triggered caspase cascade, independent of p53 function. This study throws light on the mechanistic action of TD in triggering apoptosis in Huh 7 cells.
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Seo JB, Jeong JY, Park JY, Jun EM, Lee SI, Choe SS, Park DY, Choi EW, Seen DS, Lim JS, Lee TG. Anti-Arthritic and Analgesic Effect of NDI10218, a Standardized Extract of Terminalia chebula, on Arthritis and Pain Model. Biomol Ther (Seoul) 2013; 20:104-12. [PMID: 24116282 PMCID: PMC3792193 DOI: 10.4062/biomolther.2012.20.1.104] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2011] [Revised: 10/28/2011] [Accepted: 11/18/2011] [Indexed: 12/29/2022] Open
Abstract
The fruit of Terminalia chebula Retzius has been used as a panacea in India and Southeast Asia but its biological activities have not been fully elucidated. Here we report anti-arthritic and analgesic effect of NDI10218, a standardized ethanol extract of Terminalia chebula, on collagen-induced arthritis and acetic acid-induced writhing model, respectively. Arthritis was induced in DBA/1J mice by immunizing bovine type II collagen and mice were treated with NDI10218 daily for 5 weeks after the onset of the disease. NDI10218 reduced the arthritis index and blocked the synovial hyperplasia in a dose-dependent manner. The serum levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β were significantly reduced in mice treated with NDI10218. Production of the inflammatory IL-17, but not immunosuppressive IL-10, was also inhibited in splenocytes isolated from NDI10218-treated arthritis mice. Administration of NDI10218 markedly decreased the number of T cell subpopulations in the regional lymph nodes of the arthritis mice. Finally, NDI10218 reduced the number of abdominal contractions in acetic acid-induced writhing model, suggesting an analgesic effect of this extract. Taken together, these results suggest that NDI10218 can be a new therapeutic candidate for the treatment of rheuma-toid arthritis.
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Affiliation(s)
- Jong Bae Seo
- R&D Center, BRN Science Co., Ltd., Biotechnology Incubation Center, Golden Helix, Seoul 151-742
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Bag A, Bhattacharyya SK, Chattopadhyay RR. The development of Terminalia chebula Retz. (Combretaceae) in clinical research. Asian Pac J Trop Biomed 2013; 3:244-52. [PMID: 23620847 PMCID: PMC3631759 DOI: 10.1016/s2221-1691(13)60059-3] [Citation(s) in RCA: 144] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2013] [Accepted: 02/26/2013] [Indexed: 01/08/2023] Open
Abstract
Medicinal plants are part and parcel of human society to combat diseases from the dawn of civilization. Terminalia chebula Retz. (Fam. Combretaceae), is called the 'King of Medicine' in Tibet and is always listed at the top of the list of 'Ayurvedic Materia Medica' because of its extraordinary power of healing. The whole plant possesses high medicinal value and traditionally used for the treatment of various ailments for human beings. Some of the folklore people used this plant in the treatment of asthma, sore throat, vomiting, hiccough, diarrhea, dysentery, bleeding piles, ulcers, gout, heart and bladder diseases. The plant has been demonstrated to possess multiple pharmacological and medicinal activities, such as antioxidant, antimicrobial, antidiabetic, hepatoprotective, anti-inflammatory, antimutagenic, antiproliferative, radioprotective, cardioprotective, antiarthritic, anticaries, gastrointestinal motility and wound healing activity. But no systematic updated information on the therapeutic effectiveness of Terminalia chebula, a popular herbal remedy in India and South-East Asia has so far been reported. This review highlights an updated information particularly on the phytochemistry and various pharmacological and medicinal properties of Terminalia chebula Retz. and some of its isolated compounds, along with their safety evaluation. This may provide incentive for proper evaluation of the plant as medicinal agent against the human diseases and also to bridge the lacunae in the existing literature and future scope which may offer immense opportunity for researchers engaged in validation of the traditional claims and development of safe and effective botanical medicine.
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Affiliation(s)
| | | | - Rabi Ranjan Chattopadhyay
- *Corresponding author: Rabi Ranjan Chattopadhyay, Agricultural and Ecological Research Unit, Indian Statistical Institute 203, Barrackpore Trunk Road Kolkata-700 108, India. Tel: +91-33-2575 3275 Fax: +91-33-2577 3049 E-mail: ;
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Horani A, Shoseyov D, Ginsburg I, Mruwat R, Doron S, Amer J, Safadi R. Triphala (PADMA) extract alleviates bronchial hyperreactivity in a mouse model through liver and spleen immune modulation and increased anti-oxidative effects. Ther Adv Respir Dis 2012; 6:199-210. [PMID: 22763675 DOI: 10.1177/1753465812452194] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVES Triphala (TRP), a herbal extract from Tibetan medicine, has been shown to affect lymphocytes and natural killer T (NKT) cell function. We hypothesize that TRP could ameliorate bronchial hyperreactivity through immune-cell modulations. METHODS Asthma mouse models were generated through intraperitoneal (IP) injections of ovalbumin (OVA)/2 weeks followed by repeated intranasal OVA challenges. Mice were then treated with normal saline (OVA/NS) or Triphala (OVA/TRP). Data were compared with mice treated with inhaled budesonide. All groups were assessed for allergen-induced hyperreactivity; lymphocytes from lungs, livers and spleens were analyzed for OVA-induced proliferation and their alterations were determined by flow cytometry. Oxidative reactivity using chemiluminescence, serum anti-OVA antibodies level and lung histology were assessed. RESULTS Both TRP and budesonide significantly ameliorated functional and histological OVA-induced bronchial hyperreactivity. TRP had no effect on serum anti-OVA antibodies as compared with decreased levels following budesonide treatment. Furthermore, a significant increase in lung and spleen CD4 counts and a decrease in the liver were noted after TRP treatments. Bronchoalveolar fluid from TRP-treated animals but not from the budesonide-treated animals showed anti-oxidative effects. CONCLUSION TRP and budesonide caused a significant decrease in bronchial reactivity. TRP treatment altered immune-cell distributions and showed anti-oxidative properties. These findings suggest that immune-cell modulation with TRP can ameliorate lung injury.
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Affiliation(s)
- Amjad Horani
- Division of Allergy, Immunology and Pulmonary Medicine, Washington University in Saint Louis, Saint Louis, MO, USA
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Abstract
AIM: To evaluate the antimicrobial potential of Terminalia chebula (T. chebula) extracts against pathogens causing otitis externa and compare it with ear drops.
METHODS: Four different extracts, methanol, ethanol, acetone and aqueous (hot and cold) extracts, from the T. chebula were tested for their antimicrobial activity through the agar well diffusion method and minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) values were determined through the macrodilution broth method against six different microorganism, five bacterial (one gram positive and four gram negative) and one yeast.
RESULTS: Organic and aqueous fruit extracts displayed activity against all five tested bacterial ear pathogens with a maximum zone of inhibition of 31.6 mm against Staphylococcus aureus, followed by Acinetobacter sp. (24.6 mm), Pseudomonas aeruginosa (23.6 mm), Proteus mirabilis (21 mm) and Escherichia coli (19.3 mm). Of the four solvents evaluated, acetonic fruit extract of T. chebula was found to be best. The MIC values ranged between 0.78 mg/mL and 50 mg/mL for the different bacterial ear pathogens and MBC values ranged between 1.56 mg/mL and 50 mg/mL. The acetonic fruit extract showed larger inhibition zones compared to the herbal ear drops, Kan pip with lowest MIC of 0.78 mg/mL and MBC of 1.56 mg/mL.
CONCLUSION: Acetonic extract of T. chebula fruit may be used to treat otitis externa. However, more detailed studies, such as in vivo testing and pharmacokinetics properties, are needed to determine its therapeutic potential.
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Upadhyay A, Singh DK. Molluscicidal activity of Sapindus mukorossi and Terminalia chebula against the freshwater snail Lymnaea acuminata. CHEMOSPHERE 2011; 83:468-474. [PMID: 21215991 DOI: 10.1016/j.chemosphere.2010.12.066] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2010] [Revised: 12/08/2010] [Accepted: 12/13/2010] [Indexed: 05/30/2023]
Abstract
The molluscicidal activity of Sapindus mukorossi and Terminalia chebula fruit powder against the vector snail Lymnaea acuminata was time and concentration dependent. The molluscicidal activity of T. chebula fruit powder (96 h LC(50):93.59 mg L(-1)) was more pronounced than that of S. mukorossi fruit powder (96 h LC(50):119.57 mg L(-1)). Ethanolic extracts of S. mukorossi and T. chebula fruit powder were more toxic than their other organic solvent extracts. The molluscicidal activity of ethanolic extract of S. mukorossi fruit powder (24h LC(50):2.75 mg L(-1)) was more effective than the ethanolic extract of T. chebula fruit powder (24h LC(50):124.06 mg L(-1)). The 96 h LC(50) of column-purified fraction of S. mukorossi fruit powder was 5.43 mg L(-1) whereas those of T. chebula fruit powder was 7.49 mg L(-1). Column, thin layer and high performance liquid chromatography analysis demonstrates that the active molluscicidal component in S. mukorossi and T. chebula is saponin (96 h LC(50):1.31 mg L(-1)) and tannic acid (96 h LC(50):1.64 mg L(-1)), respectively. These plants may be used as potent source of molluscicides against the snail L. acuminata.
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Affiliation(s)
- Aparna Upadhyay
- Malacology Laboratory, Department of Zoology, DDU Gorakhpur University, Gorakhpur 273 009, UP, India
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Shah VN, Shah MB, Bhatt PA. Hepatoprotective activity of punarnavashtak kwath, an Ayurvedic formulation, against CCl4-induced hepatotoxicity in rats and on the HepG2 cell line. PHARMACEUTICAL BIOLOGY 2011; 49:408-415. [PMID: 21391842 DOI: 10.3109/13880209.2010.521162] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
OBJECTIVE Punarnavashtak kwath (PNK) is a classical Ayurvedic formulation, mentioned in Ayurvedic literature Bhaishajya Ratnavali, for hepatic disorders and asthma. This study investigated the hepatoprotective activity of PNK to validate the traditional use of this formulation. MATERIALS AND METHODS PNK was prepared in the laboratory according to the method given in Ayurvedic literature. Phytochemical screening was performed to determine the presence of phytoconstituents. Hepatoprotective activity was evaluated against CCl(4)-induced hepatotoxicity in rats and by its effect on the HepG2 cell line. RESULTS Preliminary phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, saponins, and a bitter principle in PNK. Administration of PNK produced significant hepatoprotective effect as demonstrated by decreased levels of serum liver marker enzymes such as aspartate transaminase, serum alanine transaminase, serum alkaline phosphatase, and serum bilirubin and an increase in protein level. Thiopentone-induced sleeping time was also decreased in the PNK-treated animals compared with the CCl(4)-treated group. It also showed antioxidant activity by increase in activity of glutathione, superoxide dismutase, and catalase and by a decrease in thiobarbituric acid reactive substance level compared with the CCl(4)-treated group. Results of a histopathological study also support the hepatoprotective activity of PNK. Investigation carried out on the HepG2 cell line depicted significant increase in viability of cells exposed to PNK as compared with CCl(4)-treated cells. DISCUSSION AND CONCLUSION It can be concluded that PNK protects hepatocytes from CCl(4)-induced liver damages due to its antioxidant effect on hepatocytes. An in vitro study on HepG2 cell lines also supports its protective effect.
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Affiliation(s)
- Vaishali N Shah
- Department of Pharmacognosy, APMC College of Pharmaceutical Education and Research, Himatnagar, India.
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Sharma P, Prakash T, Kotresha D, Ansari MA, Sahrm UR, Kumar B, Debnath J, Goli D. Antiulcerogenic activity of Terminalia chebula fruit in experimentally induced ulcer in rats. PHARMACEUTICAL BIOLOGY 2011; 49:262-268. [PMID: 21323478 DOI: 10.3109/13880209.2010.503709] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
CONTEXT Terminalia chebula Retz. (Combretaceae) is a medium-sized tree that grows in the wild throughout India. T. chebula has been extensively used in Ayurveda, Unani, and homoeopathic medicine. The fruit has been used as a traditional medicine for a household remedy against various human ailments. Traditionally T. chebula is used to cure chronic ulcer, gastritis, and stomach cancers. OBJECTIVE The present study is to evaluate the antiulcer effect of hydroalcoholic (70%) extract of Terminalia chebula fruit. MATERIALS AND METHODS Aspirin, ethanol and cold restraint stress-induced ulcer methods in rats were used for the study. The effects of the extract on gastric secretions, pH, total and free acidity using pylorus ligated methods were also evaluated. RESULTS Animals pretreated with doses of 200 and 500 mg/kg hydroalcoholic extract showed significant reduction in lesion index, total affected area and percentage of lesion in comparison with control group (P < 0.05 and P < 0.01) in the aspirin, ethanol and cold restraint stress-induced ulcer models. Similarly extracts increased mucus production in aspirin and ethanol-induced ulcer models. At doses of 200 and 500 mg/kg of T. chebula extract showed antisecretory activity in pylorus ligated model, which lead to a reduction in the gastric juice volume, free acidity, total acidity, and significantly increased gastric pH. DISCUSSION AND CONCLUSION These findings indicate that hydroalcoholic extract of the fruit T. chebula displays potential antiulcerogenic activity. This activity thus lends pharmacological credence to the suggested use of the plant as a natural remedy in the treatment or management of ulcer.
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Affiliation(s)
- Praveen Sharma
- Department of Pharmacology and Toxicology, Acharya & B.M. Reddy College of Pharmacy, Bangalore
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Ginsburg I, Koren E, Horani A, Mahamid M, Doron S, Muhanna N, Amer J, Safadi R. Amelioration of hepatic fibrosis via Padma Hepaten is associated with altered natural killer T lymphocytes. Clin Exp Immunol 2009; 157:155-64. [PMID: 19659781 DOI: 10.1111/j.1365-2249.2009.03936.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatic fibrosis is the end-stage consequence of chronic liver disease, affecting many people worldwide. Unlike the anti-fibrotic effect of natural killer (NK) cells, CD8 and NK T subsets are considered as profibrogenic subsets. Padma Hepaten is a multi-compound herbal preparation derived from Tibetan medicine and has proven efficacy in some clinical trials and tests at the cellular level. In this study, we evaluate the immune efficacy of Padma Hepaten administered intraperitoneally (i.p.) and/or orally in a mice model of hepatic fibrosis. Hepatic fibrosis was induced by 6 weeks of biweekly i.p. carbon tetrachloride (CCl4) injections in male C57Bl6 mice. There were four groups, including naive mice, non-treated fibrotic mice and fibrotic mice treated by Padma Hepaten at weeks 5-6 of fibrosis induction either orally or by i.p. injections. Padma Hepaten was prepared at 10 mg/ml in saline and 250 microl (2.5 mg) were administered four times per week. After week 6, animals were killed. To isolate a Padma Hepaten-associated effect on lymphocytes, splenocytes were harvested from either naive or Padma Hepaten-treated non-fibrotic donors. Isolated splenocytes were therefore reconstituted into two groups of irradiated recipients. Recipients were then administered the same CCl4 regimen. Hepatic fibrosis was determined by sirius red staining of liver sections and by assessment of alpha smooth muscle actin expression compared with beta-actin (both by mRNA as well as the protein liver extract western blotting). Hepatic fibrosis and alanine aminotransferase serum levels were decreased significantly in both Padma Hepaten-treated groups compared with the non-treated fibrotic group. Padma Hepaten treatment was associated with attenuation of lymphocyte subsets in both treated groups. Using a chemiluminescence technique to assess total anti-oxidant capacities (TAC), it was found that both the plasmas and livers of mice treated by CCl4 had significantly higher TAC compared with controls. However, the levels of TAC in animals treated either by CCl4 alone or CCl4 with Padma Hepaten were similar. Adoptive transfer of Padma Hepaten-treated lymphocytes was associated with fibrosis amelioration compared with recipients with naive lymphocytes. CCl4 generates higher levels of anti-oxidant capacities, probably as a response to oxidative stress. Padma Hepaten administration attenuated hepatic fibrogenesis significantly, accompanied by attenuation of lymphocyte but not anti-oxidant capacities.
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Affiliation(s)
- I Ginsburg
- Institute of Dental Research, Faculty of Dental Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
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Kaiser P, Youssouf MS, Tasduq SA, Singh S, Sharma SC, Singh GD, Gupta VK, Gupta BD, Johri RK. Anti-allergic effects of herbal product from Allium cepa (bulb). J Med Food 2009; 12:374-82. [PMID: 19459740 DOI: 10.1089/jmf.2007.0642] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Allium cepa (Family Liliaceae) is a reputed Indian medicinal herb that is prescribed as an effective remedy for several ailments in the Ayurvedic system of medicine. The aim of this study was to evaluate its efficacy against various events responsible for Type I allergic reactions. A herbal fraction (ALC-02) from A. cepa (bulb) inhibited histamine release and attenuated intracellular calcium levels in Compound 48/80-induced rat peritoneal mast cells. It also prevented Compound 48/80-mediated systemic anaphylaxis while lowering histamine levels in plasma. ALC-02 suppressed carrageenan-induced rat paw edema. It inhibited eosinophil peroxidase activity and protein content in bronchoalveolar lavage fluid (BALF) of ovalbumin-challenged mice. In this experiment ALC-02 also caused a substantial reduction in lipid peroxidation in BALF/lung tissue and augmented superoxide dismutase activity in lung tissue. ALC-02 suppressed erythrocytic lysis caused by Triton X-100. A significant quenching of 1,1-diphenyl-2-picrylhydrazyl radical by ALC-02 was observed. The results have shown a promising anti-allergic profile of ALC-02 that could be attributed to its potential antihistaminic, anti-inflammatory, and antioxidant activities.
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Affiliation(s)
- P Kaiser
- Division of Pharmacology and Natural Products Chemistry, Indian Institute of Integrative Medicine, Jammu-Tawi, India
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Mukherjee PK, Sahoo AK, Narayanan N, Kumar NS, Ponnusankar S. Lead finding from medicinal plants with hepatoprotective potentials. Expert Opin Drug Discov 2009; 4:545-76. [DOI: 10.1517/17460440902911433] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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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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Evaluation of the antimicrobial, antioxidant, and anti-inflammatory activities of hydroxychavicol for its potential use as an oral care agent. Antimicrob Agents Chemother 2008; 53:216-22. [PMID: 18573934 DOI: 10.1128/aac.00045-08] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Hydroxychavicol isolated from the chloroform extraction of aqueous extract of Piper betle leaves showed inhibitory activity against oral cavity pathogens. It exhibited an inhibitory effect on all of the oral cavity pathogens tested (MICs of 62.5 to 500 microg/ml) with a minimal bactericidal concentration that was twofold greater than the inhibitory concentration. Hydroxychavicol exhibited concentration-dependent killing of Streptococcus mutans ATCC 25175 up to 4x MIC and also prevented the formation of water-insoluble glucan. Interestingly, hydroxychavicol exhibited an extended postantibiotic effect of 6 to 7 h and prevented the emergence of mutants of S. mutans ATCC 25175 and Actinomyces viscosus ATCC 15987 at 2x MIC. Furthermore, it also inhibited the growth of biofilms generated by S. mutans and A. viscosus and reduced the preformed biofilms by these bacteria. Increased uptake of propidium iodide by hydroxychavicol-treated cells of S. mutans and A. viscosus indicated that hydroxychavicol probably works through the disruption of the permeability barrier of microbial membrane structures. Hydroxychavicol also exhibited potent antioxidant and anti-inflammatory activities. This was evident from its concentration-dependent inhibition of lipid peroxidation and significant suppression of tumor necrosis factor alpha expression in human neutrophils. Its efficacy against adherent cells of S. mutans in water-insoluble glucan in the presence of sucrose suggests that hydroxychavicol would be a useful compound for the development of antibacterial agents against oral pathogens and that it has great potential for use in mouthwash for preventing and treating oral infections.
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Tasduq SA, Kaiser P, Sharma SC, Johri RK. Potentiation of isoniazid-induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: A toxicity profile study. Hepatol Res 2007; 37:845-53. [PMID: 17573957 DOI: 10.1111/j.1872-034x.2007.00129.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM Biochemical characterization of long-term toxic manifestations of anti-tubercular (anti-TB) drugs - rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) - individually and in two combinations: (i) RIF + INH, and (ii) RIF + INH + PZA in Wistar rats. METHODS Animals received anti-TB drugs - alone or in combination - once daily p.o. for up to 90 days (doses, in mg/kg: RIF, 250; INH, 50; PZA, 100). Assays for alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (serum) and lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), catalase, Na+K+-ATPase and CYP 2E1 (liver) were performed to assess liver toxicity. Clinical biochemistry was done by commercial kits. Determinations were made at 0, 15, 30 and 90 days of treatment schedule. RESULTS Anti-TB drugs-treated animals showed abnormal rises or falls (>1.5-2 fold) in the serum/liver parameters. Mild hyperlipidemia, hypercholesterolemia and hyperuricemia were the other pathologies. Of all the treated groups, INHalone or in combination with other drugs produced a progressive enhancement of toxicity over 15-90 days. The in vivo results were further supported by in vitro results (MTT assay, GSH and LPO) in primary cultures of rat hepatocyte. RESULTS indicated that anti-TB drugs in combination: (i) caused membrane damage resulting in leakage of ALT, ALP and bilirubin; (ii) caused imbalance in endogenous enzymatic oxidant-antioxidant defense via increased lipid peroxidation and in glutathione homeostasis; and (iii) enhanced the CYP 2E1-mediated bioactivation mechanism. CONCLUSION Toxicity manifestations seemed to be heptocytic injury targeted at hepatocytes, bile ducts or sinusoidal cells related to hepatitis and primary biliary cholestasis.
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Affiliation(s)
- Sheikh Abdullah Tasduq
- Pharmacology Division, Indian Institute of Integrative Medicine (formerly Regional Research Laboratory), Jammu, India
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Adhvaryu MR, Reddy N, Parabia MH. Effects of four Indian medicinal herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury and immunosuppression in guinea pigs. World J Gastroenterol 2007; 13:3199-205. [PMID: 17589898 PMCID: PMC4436605 DOI: 10.3748/wjg.v13.i23.3199] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate and compare the hepatoprotective and immunomodulatory effects of Curcuma longa (CL), Ocimum sanctum (OS), Tinospora cordifolia (TC) and Zizyphus mauritiana (ZM) on liver injury and immunosuppression induced by Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA).
METHODS: Duncan Hartley guinea pigs, weighing 700-1050 g, were treated orally with 50 mg/kg of INH, 100 mg/kg of RIF and 300 mg/Kg of PZA for 21-d. 200 mg/kg (bw) of each herb crude extract was administered to the herb control group and 2-h previous to INH + RIF + PZA (AKT) doses to the Herb + AKT groups. Serum alanine aminotransferase (ALT), aspertate aminotransferase (AST) bilirubin and Alkaline Phosphatase (ALP) were assessed on d 0 and 21 in all the groups. Phagocytic % (P%), Phagocytic Index (PI) and Chemotactic Index (CI) were also measured as immunologic parameters. Histological analysis was carried out to assess injury to the liver.
RESULTS: The AKT treated control group showed hepatotoxicity as judged by elevated serum AST 5-fold, AST/ALT ratio 4-fold, ALP 2-fold and hepatological changes, such as focal necrosis, portal triaditis and steatosis. Immune function was suppressed as judged by decreased P% (51.67 ± 1.68 vs 40.61 ± 1.28, P < 0.01), PI (2.0725 ± 0.05 vs 0.61 ± 0.05, P < 0.001) and CI (1.8525 ± 0.04 vs 0.695 ± 0.07, P < 0.001). All four herb treated groups showed normal liver histology, enzyme levels and increased P%, while PI and CI were enhanced in the TC and ZM treated groups, respectively. CL + AKT, TC + AKT and ZM + AKT showed nearly normal histology with minimal inflammation and microvesicular steatosis, while OS + AKT showed partial protection. Hepatotoxicity was prevented by restricting the rise of AST by 2-fold in CL + AKT and TC + AKT groups and by 3-fold in OS + AKT and ZM + AKT groups, AST/ALT by 2-fold and ALP to normal levels in all four groups. All four herb + AKT groups showed normal to enhanced neutrophil function.
CONCLUSION: All four herbs showed hepatoprotective potential and prevented immunosuppression. CL and TC showed the highest hepatoprotective activity, while TC and ZM showed strong immunostimulatory activity.
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Affiliation(s)
- Meghna-R Adhvaryu
- Bapalal Vaidya Botanical Research Centre, Department of Biosciences, Veer Narmad South Gujarat University, 110, Nehru Nagar Society, Ichchhanath Road, Surat 395007, India.
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Sachin BS, Sharma SC, Sethi S, Tasduq SA, Tikoo MK, Tikoo AK, Satti NK, Gupta BD, Suri KA, Johri RK, Qazi GN. Herbal modulation of drug bioavailability: enhancement of rifampicin levels in plasma by herbal products and a flavonoid glycoside derived fromCuminum cyminum. Phytother Res 2007; 21:157-63. [PMID: 17128432 DOI: 10.1002/ptr.2046] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The bioavailability of rifampicin (RIF) in a fixed dose combination (FDC) used for the treatment of tuberculosis remains an area of clinical concern and several pharmaceutical alternatives are being explored to overcome this problem. The present study presents a pharmacological approach in which the bioavailability of a drug may be modulated by utilizing the herb-drug synergism. The pharmacokinetic interaction of some herbal products and a pure molecule isolated from Cuminum cyminum with RIF is shown in this paper. An aqueous extract derived from cumin seeds produced a significant enhancement of RIF levels in rat plasma. This activity was found to be due to a flavonoid glycoside, 3',5-dihydroxyflavone 7-O-beta-D-galacturonide 4'-O-beta-D-glucopyranoside (CC-I). CC-I enhanced the Cmax by 35% and AUC by 53% of RIF. The altered bioavailability profile of RIF could be attributed to a permeation enhancing effect of this glycoside.
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Affiliation(s)
- B S Sachin
- Division of Pharmacology, Regional Research Laboratory (CSIR), Canal Road, Jammu-Tawi, 180016 India
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