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Ma CF, Yang L, Degen AA, Ding LM. The water extract of Rheum palmatum has antioxidative properties and inhibits ROS production in mice. JOURNAL OF ETHNOPHARMACOLOGY 2024; 335:118602. [PMID: 39084270 DOI: 10.1016/j.jep.2024.118602] [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: 04/29/2024] [Revised: 07/15/2024] [Accepted: 07/19/2024] [Indexed: 08/02/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rheum palmatum (RP) is a widely used traditional herb, which possesses antioxidant properties, inhibits ROS production and reduces fever. AIM OF THE STUDY The aim of this study was to examine the antioxidative properties of the water extract of RP on oxidative-stressed mice. MATERIALS & METHODS Forty mice were administered with DL-homocysteine (DL-Hcy) to induce oxidative stress and were divided into four groups: 1) CK: NaCl and water; 2) DL-Hcy: DL-Hcy and water; 3) DL-Hcy+50RP: DL-Hcy with 50 mg kg-1 body weight (BW) d-1 RP; and 4) DL-Hcy+150RP: DL-Hcy with 150 mg kg-1 BW d-1 RP. Rhein (0.3 mg g-1 dry matter) was the main active ingredient in RP. RESULTS When compared with Dl-Hcy mice, the mice with supplementary RP mitigated oxidative stress by reducing the liver concentrations of superoxide dismutase (SOD) by 27% and glutathione peroxidase (GSH-Px) by 32%, and the reactive oxygen species (ROS) in the kidney and spleen. These responses were more pronounced in DL-Hcy+150RP than DL-Hcy+50RP mice. RP also exhibited therapeutic effects on liver steatosis, chronic kidney nephritis and intestinal villus width shortening caused by oxidative stress, and concomitantly decreased the serum glucose concentration (RP vs. DL-HCY, 2.3 vs. 4.1 mmol L-1). CONCLUSION It was concluded that RP possesses antioxidant and therapeutic properties that can mitigate lesions on organs and prevent diabetes in oxidative-stressed mice. This study highlights the potential of RP as a medicinal supplement for animals in the future.
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Affiliation(s)
- Cheng-Fang Ma
- Sichuan Provincial Forest and Grassland Key Laboratory of Alpine Grassland Conservation and Utilization of Tibetan Plateau, College of Grassland Resources, Institute of Qinghai-Tibet Plateau, Southwest Minzu University, Chengdu, 610041, China; Sate Key Laboratory of Herbage Improvement and Grassland Agro-ecosystem, College of Ecology, Lanzhou University, Lanzhou, 730000, China
| | - Li Yang
- Sate Key Laboratory of Herbage Improvement and Grassland Agro-ecosystem, College of Ecology, Lanzhou University, Lanzhou, 730000, China
| | - Abraham Allan Degen
- Desert Animal Adaptations and Husbandry, Wyler Department of Dryland Agriculture, Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Beer Sheva, 84105, Israel
| | - Lu-Ming Ding
- Sichuan Provincial Forest and Grassland Key Laboratory of Alpine Grassland Conservation and Utilization of Tibetan Plateau, College of Grassland Resources, Institute of Qinghai-Tibet Plateau, Southwest Minzu University, Chengdu, 610041, China.
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Carmo HRP, Castillo AR, Bonilha I, Gomes EIL, Barreto J, Moura FA, Davanzo GG, de Brito Monteiro L, Muraro SP, Fabiano de Souza G, Morari J, Galdino FE, Brunetti NS, Reis-de-Oliveira G, Carregari VC, Nadruz W, Martins-de-Souza D, Farias AS, Velloso LA, Proenca-Modena JL, Mori MA, Loh W, Bhatt DL, Yellon DM, Davidson SM, De Oliveira PG, Moraes-Vieira PM, Sposito AC. Diacerein reduces inflammasome activation and SARS-CoV-2 virus replication: a proof-of-concept translational study. Front Pharmacol 2024; 15:1402032. [PMID: 39434905 PMCID: PMC11491754 DOI: 10.3389/fphar.2024.1402032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 09/06/2024] [Indexed: 10/23/2024] Open
Abstract
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein's influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection. Methods Human peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and infected in vitro with SARS-CoV-2. Additionally, we carried out a pilot randomized, double-blind, placebo-controlled study with 14 participants allocated to diacerein (n = 7) or placebo (n = 7) therapies every 12 h for 10 days. The primary endpoint was change in plasma markers of inflammasome activation (NLRP3, caspase-1, and gasdermin-D). Results In vitro protocols have shown that rhein, diacerein's primary metabolite, decreased IL-1β secretion caused by SARS-CoV-2 infection in human PBMCs (p < 0.05), and suppressed viral replication when administered either before or after the virus incubation (p < 0.05). This later effect was, at least partially, attributed to its inhibitory effect on 3-chymotrypsin-like protease (SARS-CoV-2 3CLpro) and papain-like protease in the SARS-CoV-2 (SARS-CoV-2 PLpro) virus and in the phosphorylation of proteins related cytoskeleton network (p < 0.05). Diacerein-treated COVID-19 patients presented a smaller area under the curve for NLRP3, caspase-1 and GSDM-D measured on days 2, 5, and 10 after hospitalization compared to those receiving a placebo (p < 0.05). Conclusion The indicated mechanisms of action of diacerein/rhein can reduce viral replication and mitigate the inflammatory response related to SARS-CoV-2. These findings are preliminary and require confirmation in clinical trials.
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Affiliation(s)
- Helison R. P. Carmo
- Laboratory of Vascular Biology and Atherosclerosis (Aterolab), State University of Campinas (UNICAMP), Campinas, Brazil
| | - Alejandro Rossel Castillo
- Laboratory of Vascular Biology and Atherosclerosis (Aterolab), State University of Campinas (UNICAMP), Campinas, Brazil
| | - Isabella Bonilha
- Laboratory of Vascular Biology and Atherosclerosis (Aterolab), State University of Campinas (UNICAMP), Campinas, Brazil
| | - Erica I. L. Gomes
- Laboratory of Vascular Biology and Atherosclerosis (Aterolab), State University of Campinas (UNICAMP), Campinas, Brazil
| | - Joaquim Barreto
- Laboratory of Vascular Biology and Atherosclerosis (Aterolab), State University of Campinas (UNICAMP), Campinas, Brazil
| | - Filipe A. Moura
- Brigham and Women’s Hospital, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Gustavo Gastão Davanzo
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | - Lauar de Brito Monteiro
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | - Stéfanie Primon Muraro
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | - Gabriela Fabiano de Souza
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | - Joseane Morari
- Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Campinas, Brazil
| | - Flávia Elisa Galdino
- Institute of Chemistry, University of Campinas (UNICAMP), Campinas, Brazil
- Brazilian Synchrotron Light Laboratory (LNLS), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil
| | - Natália S. Brunetti
- Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | | | | | - Wilson Nadruz
- Laboratory of Vascular Biology and Atherosclerosis (Aterolab), State University of Campinas (UNICAMP), Campinas, Brazil
| | - Daniel Martins-de-Souza
- Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Campinas, Brazil
- Laboratory of Neuroproteomics, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- D’Or Institute for Research and Education (IDOR), São Paulo, Brazil
- Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil
| | - Alessandro S. Farias
- Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Campinas, Brazil
- Autoimmune Research Laboratory, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil
| | - Licio A. Velloso
- Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Campinas, Brazil
| | - José Luiz Proenca-Modena
- Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil
| | - Marcelo A. Mori
- Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Campinas, Brazil
- Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil
- Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil
| | - Watson Loh
- Institute of Chemistry, University of Campinas (UNICAMP), Campinas, Brazil
| | - Deepak L. Bhatt
- Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Derek M. Yellon
- The Hatter Cardiovascular Institute, University College London, London, United Kingdom
| | - Sean M. Davidson
- The Hatter Cardiovascular Institute, University College London, London, United Kingdom
| | - Pedro G. De Oliveira
- Instituto de Ortopedia e Traumatologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, Brazil
- Sport Traumatology Group, Department of Orthopaedics and Traumatology, Santa Casa de São Paulo School of Medical Sciences, São Paulo, Brazil
| | - Pedro M. Moraes-Vieira
- Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Campinas, Brazil
- Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, Brazil
| | - Andrei C. Sposito
- Laboratory of Vascular Biology and Atherosclerosis (Aterolab), State University of Campinas (UNICAMP), Campinas, Brazil
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Qi Y, Liu Y, Zhang B, Wang M, Cao L, Song L, Jin N, Zhang H. Comparative antibacterial analysis of the anthraquinone compounds based on the AIM theory, molecular docking, and dynamics simulation analysis. J Mol Model 2022; 29:16. [PMID: 36547745 DOI: 10.1007/s00894-022-05406-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 12/04/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Hydroxyanthraquinones and anthraquinone glucoside derivatives are always considered as the active antibacterial components. METHODS Comparison of structure characteristics and antibacterial effect of these compounds was performed by applying quantum chemical calculations, atoms in molecules theory, molecular docking, and dynamics simulation procedure. Density functional theory calculation with B3LYP using 6-31G (d, p) basis set has been used to determine ground state molecular geometries. RESULTS The molecular geometric stability, electrostatic potential, frontier orbital energies, and topological properties were analyzed at the active site. Once glucose ring is introduced into the hydroxyanthraquinone rings, almost all of the positive molecular potentials are distributed among the hydroxyl hydrogen atoms of the glucose rings. In addition, low electron density ρ (r) and positive Laplacian value of the O-H bond of the anthraquinone glucoside are the evidences of the highly polarized and covalently decreased bonding interactions. The anthraquinone glucoside compounds have generally higher intermolecular binding energies than the corresponding aglycones due to the strong interaction between the glucose rings and the surrounding amino acids. Molecular dynamics simulations further explored the stability and dynamic behavior of the anthraquinone compound and protein complexes through RMSD, RMSF, SASA, and Rg. CONCLUSION The type of carboxyl, hydroxyl, and hydroxymethyl groups on phenyl ring and the substituent glucose rings is important to the interactions with the topoisomerase type II enzyme DNA gyrase B.
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Affiliation(s)
- Yanjiao Qi
- Key Laboratory of Environment-Friendly Composite Materials of the State Ethnic Affairs Commission, 730000, Lanzhou, People's Republic of China.,Key Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in Universities of Gansu Province, 730000, Lanzhou, People's Republic of China
| | - Yue Liu
- Key Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in Universities of Gansu Province, 730000, Lanzhou, People's Republic of China
| | - Bo Zhang
- Key Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in Universities of Gansu Province, 730000, Lanzhou, People's Republic of China
| | - Mingyang Wang
- Key Laboratory of Environment-Friendly Composite Materials of the State Ethnic Affairs Commission, 730000, Lanzhou, People's Republic of China
| | - Long Cao
- Department of Chemical Engineering, Northwest Minzu University, 730124, Lanzhou, People's Republic of China
| | - Li Song
- Gansu Hualing Dairy Co. LTD., Lanzhou, People's Republic of China
| | - Nengzhi Jin
- Gansu Province Computing Center, 730000, Lanzhou, People's Republic of China
| | - Hong Zhang
- Key Laboratory of Environment-Friendly Composite Materials of the State Ethnic Affairs Commission, 730000, Lanzhou, People's Republic of China.
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Ntemafack A, Singh RV, Ali S, Kuiate JR, Hassan QP. Antiviral potential of anthraquinones from Polygonaceae, Rubiaceae and Asphodelaceae: Potent candidates in the treatment of SARS-COVID-19, A comprehensive review. SOUTH AFRICAN JOURNAL OF BOTANY : OFFICIAL JOURNAL OF THE SOUTH AFRICAN ASSOCIATION OF BOTANISTS = SUID-AFRIKAANSE TYDSKRIF VIR PLANTKUNDE : AMPTELIKE TYDSKRIF VAN DIE SUID-AFRIKAANSE GENOOTSKAP VAN PLANTKUNDIGES 2022; 151:146-155. [PMID: 36193345 PMCID: PMC9519529 DOI: 10.1016/j.sajb.2022.09.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 09/03/2022] [Accepted: 09/26/2022] [Indexed: 06/16/2023]
Abstract
Medicinal plants are being used as an alternative source of health management to cure various human ailments. The healing role is attributed to the hidden dynamic groups of various phytoconstituents, most of which have been recorded from plants and their derivatives. Nowadays, medicinal plants have gained more attention due to their pharmacological and industrial potential. Aromatic compounds are one of the dynamic groups of secondary metabolites (SM) naturally present in plants; and anthraquinones of this group are found to be attractive due to their high bioactivity and low toxicity. They have been reported to exhibit anticancer, antimicrobial, immune-suppressive, antioxidant, antipyretic, diuretic and anti-inflammatory activities. Anthraquinones have been also shown to exhibit potent antiviral effects against different species of viruses. Though, it has been reported that a medicinal plant with antiviral activity against one viral infection may be used to combat other types of viral infections. Therefore, in this review, we explored and highlighted the antiviral properties of anthraquinones of Polygonaceae, Rubiaceae and Asphodelaceae families. Anthraquinones from these plant families have been reported for their effects on human respiratory syncytial virus and influenza virus. They are hence presumed to have antiviral potential against SARS-CoV as well. Thus, anthraquinones are potential candidates that need to be screened thoroughly and developed as drugs to combat COVID-19. The information documented in this review could therefore serve as a starting point in developing novel drugs that may help to curb the SARS-COVID-19 pandemic.
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Affiliation(s)
- Augustin Ntemafack
- Department of Biochemistry, University of Dschang, Dschang, Cameroon
- Department of Biochemistry and Molecular Biology, Indiana University-Purdue University Indianapolis, Indiana, USA
| | - Rahul Vikram Singh
- Department of Dietetic and Nutrition Technology, CSIR-Institute of Himalayan Bioresource Technology, Palampur, India
| | - Sabeena Ali
- Molecular Biology and Plant Biotechnology Division, CSIR - Indian Institute of Integrative Medicine, Sanat Nagar, Srinagar, India
| | | | - Qazi Parvaiz Hassan
- Molecular Biology and Plant Biotechnology Division, CSIR - Indian Institute of Integrative Medicine, Sanat Nagar, Srinagar, India
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Yu X, Xu Q, Chen W, Mai Z, Mo L, Su X, Ou J, Lan Y, Zheng H, Xue Y. Rhein inhibits Chlamydia trachomatis infection by regulating pathogen-host cell. Front Public Health 2022; 10:1002029. [PMID: 36238249 PMCID: PMC9552556 DOI: 10.3389/fpubh.2022.1002029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Accepted: 09/07/2022] [Indexed: 01/27/2023] Open
Abstract
The global incidence of genital Chlamydia trachomatis infection increased rapidly as the primary available treatment of C. trachomatis infection being the use of antibiotics. However, the development of antibiotics resistant stain and other treatment failures are often observed in patients. Consequently, novel therapeutics are urgently required. Rhein is a monomer derivative of anthraquinone compounds with an anti-infection activity. This study investigated the effects of rhein on treating C. trachomatis infection. Rhein showed significant inhibitory effects on the growth of C. trachomatis in multiple serovars of C. trachomatis, including D, E, F and L1, and in various host cells, including HeLa, McCoy and Vero. Rhein could not directly inactivate C. trachomatis but could inhibit the growth of C. trachomatis by regulating pathogen-host cell interactions. Combined with azithromycin, the inhibitory effect of rehin was synergistic both in vitro and in vivo. Together these findings suggest that rhein could be developed for the treatment of C. trachomatis infections.
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Affiliation(s)
- Xueying Yu
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China,Department of Clinical Laboratory, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
| | - Qingqing Xu
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Wentao Chen
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China,Guangzhou Key Laboratory for Sexually Transmitted Diseases Control, Guangzhou, China
| | - Zhida Mai
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Lijun Mo
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Xin Su
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Jiangli Ou
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Yinyuan Lan
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Heping Zheng
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China,Guangzhou Key Laboratory for Sexually Transmitted Diseases Control, Guangzhou, China,*Correspondence: Heping Zheng
| | - Yaohua Xue
- Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China,Guangzhou Key Laboratory for Sexually Transmitted Diseases Control, Guangzhou, China,Yaohua Xue
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Das D, Bihari Jena A, Banerjee A, Kumar Radhakrishnan A, Duttaroy AK, Pathak S. Can plant-derived anti-HIV compounds be used in COVID-19 cases? Med Hypotheses 2022; 166:110926. [PMID: 35935095 PMCID: PMC9347142 DOI: 10.1016/j.mehy.2022.110926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 07/30/2022] [Indexed: 01/08/2023]
Abstract
People living with HIV are more exposed to the adverse health effects of the worldwide COVID-19 pandemic. The pandemic's health and social repercussions may promote drug abuse and inadequate HIV management among this demographic. The coronavirus pandemic of 2019 (COVID-19) has caused unprecedented disruption worldwide in people's lives and health care. When the COVID-19 epidemic was identified, people with HIV faced significant obstacles and hurdles to achieving optimal care results. The viral spike protein (S-Protein) and the cognate host cell receptor angiotensin-converting enzyme 2 (ACE2) are both realistic and appropriate intervention targets. Calanolides A, Holy Basil, Kuwanon-L, and Patentiflorin have anti-HIV effects. Our computational biology study investigated that these compounds all had interaction binding scores related to S protein of coronavirus of -9.0 kcal /mol, -7.1 kcal /mol, -9.1 kcal /mol, and -10.3 kcal/mol/mol, respectively. A combination of plant-derived anti-HIV compounds like protease inhibitors and nucleoside analogs, which are commonly used to treat HIV infection, might be explored in clinical trials for the treatment of COVID-19.
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Key Words
- ACE2
- ACE2, Angiotensin-converting enzyme-2
- AIDS, Acquired immunodeficiency syndrome
- AZT, Azidothymidine
- CD4, Cluster of Differentiation 4
- Calanolides A
- Covid-19
- HAART, Highly active antiretroviral therapy, ART, Antiretroviral therapy
- HIV
- HIV, Human Immunodeficiency Virus
- Holy Basil
- IN, Integrase
- Kuwanon-L
- NETs, neutrophil extracellular traps
- NNTRIs, Non-nucleoside analogs transcriptase reverse inhibitor
- NRTIs, nucleoside analog reverse transcriptase inhibitor
- Patentiflorin A
- RT, Reverse Transcriptase
- S protein
- SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2
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Affiliation(s)
- Diptimayee Das
- Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai 603103, India
| | - Atala Bihari Jena
- Centre of Excellence in Integrated Omics and Computational Biology, Utkal University, Bhubaneswar 751004, Odisha, India
| | - Antara Banerjee
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Arun Kumar Radhakrishnan
- Department of Pharmacology, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Asim K Duttaroy
- Department of Nutrition, Institute of Medical Sciences, Faculty of Medicine, University of Oslo, Norway
| | - Surajit Pathak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
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Saleh-E-In MM, Choi YE. Anethum sowa Roxb. ex fleming: A review on traditional uses, phytochemistry, pharmacological and toxicological activities. JOURNAL OF ETHNOPHARMACOLOGY 2021; 280:113967. [PMID: 33640440 DOI: 10.1016/j.jep.2021.113967] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 02/15/2021] [Accepted: 02/21/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Anethum sowa Roxb. ex Fleming (Syn. Peucedanum sowa Roxb. ex Fleming, Family: Apiaceae) is a pharmacologically important as aromatic and medicinal plant. Various parts of this plant are used in traditional medicine systems for carminative, uterine and colic pain, digestion disorder, flatulence in babies, appetite-stimulating agent and used to treat mild flue and cough. The essential oil is used for aromatherapy. It is also used as a spice for food flavouring and culinary preparations in many Asian and European countries. AIM OF THE REVIEW This review aims to provide a comprehensive and critical assessment from the reported traditional and pharmaceutical uses and pharmacological activities of the extracts, essential oil and phytoconstituents with emphasis on its therapeutic potential as well as toxicological evaluation of A. sowa. MATERIALS AND METHODS Online search engines such as SciFinder®, GoogleScholar®, ResearchGate®, Web of Science®, Scopus®, PubMed and additional data from books, proceedings and local prints were searched using relevant keywords and terminologies related to A. sowa for critical analyses. RESULTS The literature studies demonstrated that A. sowa possesses several ethnopharmacological activities, including pharmaceutical prescriptions, traditional applications, and spice in food preparations. The phytochemical investigation conducted on crude extracts has been characterized and identified various classes of compounds, including coumarins, anthraquinone, terpenoids, alkaloid, benzodioxoles, phenolics, polyphenols, phenolic and polyphenols, fatty acids, phthalides and carotenoids. The extracts and compounds from the different parts of A. sowa showed diverse in vitro and in vivo biological activities including antioxidant, antiviral, antibacterial, analgesic and anti-inflammatory, Alzheimer associating neuromodulatory, cytotoxic, anticancer, antidiabetes, insecticidal and larvicidal. CONCLUSION A. sowa is a valuable medicinal plant which is especially used in food flavouring and culinary preparations. This review summarized the pertinent information on A. sowa and its traditional and culinary uses, as well as potential pharmacological properties of essential oils, extracts and isolated compounds. The traditional uses of A. sowa are supported by in vitro/vivo pharmacological studies; however, further investigation on A. sowa should be focused on isolation and identification of more active compounds and establish the links between the traditional uses and reported pharmacological activities with active compounds, as well as structure-activity relationship and in vivo mechanistic studies before integrated into the medicine. The toxicological report confirmed its safety. Nonetheless, pharmacokinetic evaluation tests to validate its bioavailability should be encouraged.
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Affiliation(s)
- Md Moshfekus Saleh-E-In
- Division of Forest Resources, College of Forest and Environmental Sciences, Kangwon National University, Chunchon, 200-701, Republic of Korea
| | - Yong Eui Choi
- Division of Forest Resources, College of Forest and Environmental Sciences, Kangwon National University, Chunchon, 200-701, Republic of Korea.
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Ethnobotanical Uses, Phytochemistry and Pharmacology of Different Rheum Species (Polygonaceae): A Review. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1308:309-352. [PMID: 33861453 DOI: 10.1007/978-3-030-64872-5_22] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Today, there is an increased tendency to use herbal remedies. Rhubarb refers to several species of the genus Rheum L. in the Polygonaceae family. This species-rich genus is mainly distributed in Asian countries. Several medicinal effects have been attributed to the Rheum spp. in the traditional and modern medicine such as healing lungs, liver, kidney, womb and bladder diseases, cancer, diabetes, insect bites, relapsing fevers, diarrhea and constipation. Various in vitro, in vivo and clinical studies have investigated the therapeutic effect of extracts, fractions and pure compounds isolated from different species of this genus. Considering the positive findings, several pharmaceutical formulations containing rhubarb extract like capsules, drops, mouthwashes and different topical formulations are now present in the market. However, there are other traditional therapeutic effects of rhubarb that have not been studied yet and it is of great importance to perform confirmatory experiments or clinical investigations. The current review summarizes general information regarding botany, phytochemistry, ethnobotany and pharmacological aspects of Rheum spp. It is hoped that the present review could motivate subsequent research on the other medicinal properties of these plants that have been neglected until today.
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de Oliveira PG, Termini L, Durigon EL, Lepique AP, Sposito AC, Boccardo E. Diacerein: A potential multi-target therapeutic drug for COVID-19. Med Hypotheses 2020; 144:109920. [PMID: 32534337 PMCID: PMC7263256 DOI: 10.1016/j.mehy.2020.109920] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 05/28/2020] [Indexed: 02/07/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 19 (COVID-19), was declared pandemic by the World Health Organization in March 2020. SARS-CoV-2 binds its host cell receptor, angiotensin-converting enzyme 2 (ACE2), through the viral spike (S) protein. The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. In addition, cardiac symptoms, including fulminant myocarditis, are frequent in patients in a severe state of illness. Diacerein (DAR) is an anthraquinone derivative drug whose active metabolite is rhein. Different studies have shown that this compound inhibits the IL-1, IL-2, IL-6, IL-8, IL-12, IL-18, TNF-α, NF-κB and NALP3 inflammasome pathways. The antiviral activity of rhein has also been documented. This metabolite prevents hepatitis B virus (HBV) replication and influenza A virus (IAV) adsorption and replication through mechanisms involving regulation of oxidative stress and alterations of the TLR4, Akt, MAPK, and NF-κB signalling pathways. Importantly, rhein inhibits the interaction between the SARS-CoV S protein and ACE2 in a dose-dependent manner, suggesting rhein as a potential therapeutic agent for the treatment of SARS-CoV infection. Based on these findings, we hypothesize that DAR is a multi-target drug useful for COVID-19 treatment. This anthraquinone may control hyperinflammatory conditions by multi-faceted cytokine inhibition and by reducing viral infection.
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Affiliation(s)
- Pedro Gonçalves de Oliveira
- Instituto de Ortopedia e Traumatologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, SP 01246-903, Brazil; Sport Traumatology Group, Department of Orthopaedics and Traumatology, Santa Casa de São Paulo School of Medical Sciences , São Paulo, SP 01221-020, Brazil.
| | - Lara Termini
- Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 01246-000, Brazil
| | - Edison Luiz Durigon
- Department of Microbiology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-900, Brazil
| | - Ana Paula Lepique
- Department of Immunology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-900, Brazil
| | - Andrei C Sposito
- Laboratório de Biologia Vascular e Aterosclerose (Aterolab), Faculdade de Ciências Médicas da UNICAMP, Campinas, SP 13083-887, Brazil
| | - Enrique Boccardo
- Department of Microbiology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-900, Brazil
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10
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Piccolella S, Crescente G, Faramarzi S, Formato M, Pecoraro MT, Pacifico S. Polyphenols vs. Coronaviruses: How Far Has Research Moved Forward? Molecules 2020; 25:molecules25184103. [PMID: 32911757 PMCID: PMC7570460 DOI: 10.3390/molecules25184103] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/03/2020] [Accepted: 09/07/2020] [Indexed: 12/20/2022] Open
Abstract
The epidemic, caused by SARS-CoV-2 at the beginning of 2020, led us to a serious change in our lifestyle that for about three months has confined us to our homes, far from our laboratory routine. In this period, the belief that the work of a researcher should never stop has been the driving force in writing the present paper. It aims at reviewing the recent scientific knowledge about in vitro experimental data that focused on the antiviral role of phenols and polyphenols against different species of coronaviruses (CoVs), pointing up the viral targets potentially involved. In the current literature scenario, the papain-like and the 3-chymotrypsin-like proteases seem to be the most deeply investigated and a number of isolated natural (poly)phenols has been screened for their efficacy.
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11
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Naik B, Gupta N, Ojha R, Singh S, Prajapati VK, Prusty D. High throughput virtual screening reveals SARS-CoV-2 multi-target binding natural compounds to lead instant therapy for COVID-19 treatment. Int J Biol Macromol 2020; 160:1-17. [PMID: 32470577 PMCID: PMC7250083 DOI: 10.1016/j.ijbiomac.2020.05.184] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 05/21/2020] [Accepted: 05/22/2020] [Indexed: 12/21/2022]
Abstract
The present-day world is severely suffering from the recently emerged SARS-CoV-2. The lack of prescribed drugs for the deadly virus has stressed the likely need to identify novel inhibitors to alleviate and stop the pandemic. In the present high throughput virtual screening study, we used in silico techniques like receptor-ligand docking, Molecular dynamic (MD), and ADME properties to screen natural compounds. It has been documented that many natural compounds display antiviral activities, including anti–SARS-CoV effect. The present study deals with compounds of Natural Product Activity and Species Source (NPASS) database with known biological activity that probably impedes the activity of six essential enzymes of the virus. Promising drug-like compounds were identified, demonstrating better docking score and binding energy for each druggable targets. After an extensive screening analysis, three novel multi-target natural compounds were predicted to subdue the activity of three/more major drug targets simultaneously. Concerning the utility of natural compounds in the formulation of many therapies, we propose these compounds as excellent lead candidates for the development of therapeutic drugs against SARS-CoV-2.
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Affiliation(s)
- Biswajit Naik
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India
| | - Nidhi Gupta
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India
| | - Rupal Ojha
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India
| | - Satyendra Singh
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India
| | - Vijay Kumar Prajapati
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India
| | - Dhaneswar Prusty
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India.
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12
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Zhuang T, Gu X, Zhou N, Ding L, Yang L, Zhou M. Hepatoprotection and hepatotoxicity of Chinese herb Rhubarb (Dahuang): How to properly control the "General (Jiang Jun)" in Chinese medical herb. Biomed Pharmacother 2020; 127:110224. [PMID: 32559851 DOI: 10.1016/j.biopha.2020.110224] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 04/29/2020] [Accepted: 04/30/2020] [Indexed: 02/06/2023] Open
Abstract
Chinese herb Rhubarb (Dahuang), one of the most widely used traditional Chinese medicine in clinical application for over a thousand years and known as the "General (Jiang Jun)" in Chinese medical herb, currently used clinically for long-term treatment of gastrointestinal diseases and chronic liver diseases. Through previous researches, it has been identified that Rhubarb possessed a good hepatoprotective effect, which primarily protected liver from oxidation, fibrosis and cirrhosis, liver failure, hepatocellular carcinoma and various types of hepatitis. Meanwhile, it has been recently reported that long-term administration of Rhubarb preparation may undertake the risk of liver damage, which has aroused worldwide doubts about the safety of Rhubarb. Therefore, how to correctly understand the "two-way" effect of Rhubarb on liver protection and liver toxicity provides a basis for scientific evaluation of Rhubarb's efficacy on liver and side effects, as well as guiding clinical rational drug use. In this review, the mechanisms of Rhubarb how to play a role in hepatoprotection and why it causes hepatotoxic potential will be elaborated in detail and critically. In addition, some positive clinical guidances are also advised on how to reduce its hepatotoxicity in medical treatment.
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Affiliation(s)
- Tongxi Zhuang
- Center for Chinese Medicine Therapy and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xinyi Gu
- Center for Chinese Medicine Therapy and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Nian Zhou
- Center for Chinese Medicine Therapy and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lili Ding
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Li Yang
- Center for Chinese Medicine Therapy and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Mingmei Zhou
- Center for Chinese Medicine Therapy and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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13
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Zhang XH, Long Y, Yu QH, Cao T, Chen XX, Yu JA, Gao XX. Characterisation of the complete chloroplast genome of an endemic herb plant species, Rheum palmatum (Polygonaceae) in China. MITOCHONDRIAL DNA PART B-RESOURCES 2019; 4:3725-3726. [PMID: 33366161 PMCID: PMC7707442 DOI: 10.1080/23802359.2019.1681319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Rheum palmatum has a long history in medicine, which is one of the main export medicinal herb in China. The complete chloroplast genome of R. palmatum was assembled and reported in this study. The R. palmatum chloroplast genome was 161,541 bp in length as the circular and consisted a large single-copy (LSC) region of 86,519 bp, a small single-copy (SSC) region of 13,112 bp and a pair of inverted-repeat (IR) regions of 30,955 bp. The nucleotide composition was asymmetric 31.2% A (Adenine), 31.5% T (Thymine), 19.0% C (Cytosine), and 18.3% G (Guanine) with an overall G + C content of 37.3%. It encoded 131 genes, including 86 protein-coding genes (76 PCG species), 37 transfer RNA genes (26 tRNAs species), and eight ribosomal RNA genes (four rRNAs species). The Phylogenetic relationships used neighbour-joining (NJ) method and the result showed that R. palmatum and Rheum officinale are phylogenetically related to each other in the family Polygonaceae. This study will be very important for Chinese medicinal herb research value and clinical drug development for future in China.
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Affiliation(s)
- Xiu-Hang Zhang
- Department of Burn Surgery, The First Hospital of Jilin University, Changchun, China
| | - Yu Long
- Department of Biological and Pharmaceutical Engineering, Wuhan, Hubei, China
| | - Qing-Hua Yu
- Department of Burn Surgery, The First Hospital of Jilin University, Changchun, China
| | - Tianyi Cao
- Zhejiang Integrated Traditional Chinese and Western Medicine Hospital, Hangzhou, China
| | - Xin-Xin Chen
- Department of Burn Surgery, The First Hospital of Jilin University, Changchun, China
| | - Jia-Ao Yu
- Department of Burn Surgery, The First Hospital of Jilin University, Changchun, China
| | - Xin-Xin Gao
- Department of Burn Surgery, The First Hospital of Jilin University, Changchun, China
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14
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Pan Y, Ke Z, Ye H, Sun L, Ding X, Shen Y, Zhang R, Yuan J. Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis. Inflamm Res 2019; 68:1025-1034. [PMID: 31531682 PMCID: PMC7079752 DOI: 10.1007/s00011-019-01284-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 09/03/2019] [Accepted: 09/07/2019] [Indexed: 02/06/2023] Open
Abstract
Objective Saikosaponin c (SSc), a compound purified from the traditional Chinese herb of Radix Bupleuri was previously identified to exhibit anti-HBV replication activity. However, the mechanism through which SSc acts against HBV remains unknown. In this study, we investigated the mechanism of SSc mediated anti-HBV activity. Methods HepG2.2.15 cells were cultured at 37 ℃ in the presence of 1–40 μg/mL of SSc or DMSO as a control. The expression profile of HBV markers, cytokines, HNF1α and HNF4α were investigated by real-time quantitative PCR, Elisa, Western blot and Dot blotting. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells was mediated by two small siRNAs specifically targeting HNF1α or HNF4α. Results We found that SSc stimulates IL-6 expression, leading to attenuated HNF1α and HNF4α expression, which further mediates suppression of HBV pgRNA synthesis. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells by RNA interference abrogates SSc’s anti-HBV role. Moreover, SSc is effective to both wild-type and drug-resistant HBV mutants. Conclusion SSc inhibits pgRNA synthesis by targeting HNF1α and HNF4α. These results indicate that SSc acts as a promising compound for modulating pgRNA transcription in the therapeutic strategies against HBV infection. Electronic supplementary material The online version of this article (10.1007/s00011-019-01284-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yanchao Pan
- Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People's Hospital, Shenzhen, 518112, China.
| | - Zhiyi Ke
- Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People's Hospital, Shenzhen, 518112, China
| | - Hong Ye
- Anhui Academy of Medical Sciences, Hefei, 230061, China
| | - Lina Sun
- Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People's Hospital, Shenzhen, 518112, China
| | - Xiaoyan Ding
- Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People's Hospital, Shenzhen, 518112, China
| | - Yun Shen
- Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People's Hospital, Shenzhen, 518112, China
| | - Runze Zhang
- Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People's Hospital, Shenzhen, 518112, China
| | - Jing Yuan
- Diagnosis and Treatment of Infectious Diseases Research Laboratory, Shenzhen Third People's Hospital, Shenzhen, 518112, China.
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15
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Tan ZB, Fan HJ, Wu YT, Xie LP, Bi YM, Xu HL, Chen HM, Li J, Liu B, Zhou YC. Rheum palmatum extract exerts anti-hepatocellular carcinoma effects by inhibiting signal transducer and activator of transcription 3 signaling. JOURNAL OF ETHNOPHARMACOLOGY 2019; 232:62-72. [PMID: 30553869 DOI: 10.1016/j.jep.2018.12.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 12/06/2018] [Accepted: 12/12/2018] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Hepatocellular carcinoma (HCC) is among the most common malignancies. Signal transducer and activator of transcription 3 (STAT3), with abnormal expression and constitutive activation, has been reported to promote proliferation, metastasis, survival and angiogenesis of HCC cells. Rheum palmatum (RP), a traditional Chinese medicinal herb, exhibited tumor-suppressing effects in multiple human cancers, but its potential functions in HCC remain unexplored. AIM OF THE STUDY This study aimed to examine the involvement of STAT3 signaling in the anti-HCC effects of RP extract. MATERIALS AND METHODS SMMC-7721 and HepG2 HCC cell lines were treated with RP extract for 24 h, and then viability, migration, and invasion of HCC cells and angiogenesis of human umbilical vein endothelial cells (HUVECs) were analyzed using MTS, wound-healing, Transwell invasion and tube formation assays, respectively. Western blotting and immunohistochemistry (IHC) were used to examine the activation of key molecules in STAT3 signaling, including STAT3, JAK2, and Src. Additionally, we explored the in vivo antitumor effects of RP extract in a xenograft tumor nude mouse model of HCC. RESULTS The result showed that RP extract reduced viability, migration, and invasion of SMMC-7721 and HepG2 cells and angiogenesis of HUVECs. It suppressed the phosphorylation of STAT3 and its upstream kinases including JAK2 and Src. In addition, RP extract treatment downregulated STAT3 target genes, including survivin, Bcl-xL, Mcl-1, Bcl-2, MMP-2, MMP-9, Cyclin D1, CDK4, c-Myc, and VEGF-C. Furthermore, RP extract suppressed the xenograft tumor growth and activation of STAT3 in xenograft tumor mice. CONCLUSION Collectively, the results showed that RP extract prevented HCC progression by inhibiting STAT3, and might be useful for the treatment of HCC.
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MESH Headings
- Animals
- Antineoplastic Agents, Phytogenic/pharmacology
- Antineoplastic Agents, Phytogenic/therapeutic use
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/metabolism
- Carcinoma, Hepatocellular/pathology
- Cell Line, Tumor
- Cell Movement/drug effects
- Cell Survival/drug effects
- Human Umbilical Vein Endothelial Cells/drug effects
- Human Umbilical Vein Endothelial Cells/physiology
- Humans
- Liver Neoplasms/drug therapy
- Liver Neoplasms/metabolism
- Liver Neoplasms/pathology
- Male
- Mice, Inbred BALB C
- Mice, Nude
- Neovascularization, Pathologic/drug therapy
- Neovascularization, Pathologic/metabolism
- Plant Extracts/pharmacology
- Plant Extracts/therapeutic use
- Rheum
- STAT3 Transcription Factor/metabolism
- Signal Transduction/drug effects
- Wound Healing/drug effects
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Affiliation(s)
- Zhang-Bin Tan
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Hui-Jie Fan
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Yu-Ting Wu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Ling-Peng Xie
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Yi-Ming Bi
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Hong-Lin Xu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Hong-Mei Chen
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Jun Li
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Bin Liu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Guangzhou Institute of Cardiovascular Disease, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
| | - Ying-Chun Zhou
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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16
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Zhang Y, Ma H, Mai X, Xu Z, Yang Y, Wang H, Ouyang L, Liu S. Comparative Pharmacokinetics and Metabolic Profile of Rhein Following Oral Administration of Niuhuang Shang Qing Tablets, Rhubarb and Rhein in Rats. INT J PHARMACOL 2018. [DOI: 10.3923/ijp.2019.19.30] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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17
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Rapid Determination of Total Content of Five Major Anthraquinones in Rhei Radix et Rhizoma by NIR Spectroscopy. CHINESE HERBAL MEDICINES 2017. [DOI: 10.1016/s1674-6384(17)60101-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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18
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Arbab AH, Parvez MK, Al-Dosari MS, Al-Rehaily AJ. In vitro evaluation of novel antiviral activities of 60 medicinal plants extracts against hepatitis B virus. Exp Ther Med 2017; 14:626-634. [PMID: 28672977 PMCID: PMC5488430 DOI: 10.3892/etm.2017.4530] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 03/03/2017] [Indexed: 02/06/2023] Open
Abstract
Currently, >35 Saudi Arabian medicinal plants are traditionally used for various liver disorders without a scientific rationale. This is the first experimental evaluation of the anti-hepatitis B virus (HBV) potential of the total ethanolic and sequential organic extracts of 60 candidate medicinal plants. The extracts were tested for toxicity on HepG2.2.15 cells and cytotoxicity concentration (CC50) values were determined. The extracts were further investigated on HepG2.2.15 cells for anti-HBV activities by analyzing the inhibition of HBsAg and HBeAg production in the culture supernatants, and their half maximal inhibitory concentration (IC50) and therapeutic index (TI) values were determined. Of the screened plants, Guiera senegalensis (dichloromethane extract, IC50=10.65), Pulicaria crispa (ethyl acetate extract, IC50=14.45), Coccinea grandis (total ethanol extract, IC50=31.57), Fumaria parviflora (hexane extract, IC50=35.44), Capparis decidua (aqueous extract, IC50=66.82), Corallocarpus epigeus (total ethanol extract, IC50=71.9), Indigofera caerulea (methanol extract, IC50=73.21), Abutilon figarianum (dichloromethane extract, IC50=99.76) and Acacia oerfota (total ethanol extract, IC50=101.46) demonstrated novel anti-HBV activities in a time- and dose-dependent manner. Further qualitative phytochemical analysis of the active extracts revealed the presence of alkaloids, tannins, flavonoids and saponins, which are attributed to antiviral efficacies. In conclusion, P. crispa, G. senegalensis and F. parviflora had the most promising anti-HBV potentials, including those of C. decidua, C. epigeus, A. figarianum, A. oerfota and I. caerulea with marked activities. However, a detailed phytochemical study of these extracts is essential to isolate the active principle(s) responsible for their novel anti-HBV potential.
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Affiliation(s)
- Ahmed Hassan Arbab
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.,Department of Pharmacognosy, College of Pharmacy, Omdurman Islamic University, Omdurman 14415, Republic of the Sudan
| | - Mohammad Khalid Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia
| | - Mohammed Salem Al-Dosari
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia
| | - Adnan Jathlan Al-Rehaily
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia
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19
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Ma J, Li T, Han X, Yuan H, Liang H, Wang Y, Wang X, Duan Y, Li A, Song H, Yang D. Discovery and mechanism of action of Novel Baicalein modified derivatives as potent antihepatitis agent. Virology 2017; 507:199-205. [PMID: 28453983 DOI: 10.1016/j.virol.2017.04.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 03/30/2017] [Accepted: 04/04/2017] [Indexed: 12/28/2022]
Abstract
Anti-hepatitis B virus (HBV) activity was evaluated in HepG2 2.2.15 cells by novel Baicalein derivatives. The result showed that compounds 4k and 4h was found to be effective anti-HBV agent. Further, the effect of compounds 4k and 4h showed dose-dependent inhibition of HBV-DNA as compared to control together with significant inhibition of HbeAG and HbsAG expression in the tested dose. Both compounds showed considerable affinity against the HepG2.2.15 cells. Moreover, the docking study of compound 4k was carried out with HLA molecule showing excellent intermolecular interactions with the receptor via creation of numerous bonds with Ser5, Thr27, Asp29 and Phe8. The compound 4k showed significant effect on the HO-1 expression in HepG2.2.15 cells together with excellent anti-HBV activity in transgenic mouse confirmed by biochemical and histopathological parameters. Compound 4k also showed excellent pharmacokinetic profile in experimental animal and thus, provide a novel class of potent anti-HBV agents.
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Affiliation(s)
- Ji Ma
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou university, Zhengzhou City, Henan 450000, China.
| | - Tengfei Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou university, Zhengzhou City, Henan 450000, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou university, Zhengzhou City, Henan 450000, China
| | - Huifeng Yuan
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou university, Zhengzhou City, Henan 450000, China
| | - Haijun Liang
- Department of Infection, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan 453100, China
| | - Yanping Wang
- Department of Infection, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan 453100, China
| | - Xinwei Wang
- Department of Infection, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan 453100, China
| | - Yuxiu Duan
- Department of Infection, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan 453100, China
| | - Aihui Li
- Department of Infection, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan 453100, China
| | - Huilian Song
- Department of Infection, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan 453100, China
| | - Daokun Yang
- Department of Infection, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan 453100, China
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Wu WJ, Yan R, Li T, Li YP, Zhou RN, Wang YT. Pharmacokinetic alterations of rhubarb anthraquinones in experimental colitis induced by dextran sulfate sodium in the rat. JOURNAL OF ETHNOPHARMACOLOGY 2017; 198:600-607. [PMID: 28214059 DOI: 10.1016/j.jep.2017.01.049] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Revised: 12/20/2016] [Accepted: 01/26/2017] [Indexed: 06/06/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rhubarb (Rhei Rhizoma et Radix) is used for the treatment of digestive diseases in traditional medicinal practice in China. Recent studies also support its beneficial activities in alleviating ulcerative colitis (UC). AIM OF THE STUDY This study aimed to characterize the oral pharmacokinetics of rhubarb anthraquinones, the main bioactive components of this herb, in the experimental chronic colitis rat model induced by dextran sulfate sodium (DSS) and to identify the factors causing the pharmacokinetic alterations. MATERIALS AND METHODS Rats received drinking water (normal group) or 5% DSS for the first 7 days and 3% DSS for additional 14 days (UC group). On day 21 both groups received an oral dose of the rhubarb extract (equivalent to 5.0g crude drug/kg body weight). Plasma anthraquinone aglycones levels were determined directly by an LC-MS/MS method and the total of each anthraquinone (aglycone+conjugates) was quantified after β-glucuronidases hydrolysis. RESULTS Rhubarb anthraquinones predominantly existed as conjugates in plasma samples from both groups and only free aloe-emodin, rhein and emodin were detected. Compared to the normal rats, both Cmax and AUC of the three free anthraquinones were increased, while the systemic exposure (AUC) of the total (aglycone+conjugates) of most anthraquinones decreased by UC accompanied by the disappearance of multiple-peak phenomenon in the plasma concentration-time profiles. Gut bacteria from UC rats exhibited a decreased activity in hydrolyzing anthraquinone glycosides to form respective aglycone and there were significant decreases in microbial β-glucosidases and β-glucuronidases activities. Moreover, the intestinal microsomes from UC rats catalyzed glucuronidation of free anthraquinones with higher activities, while the activities of hepatic microsomes were comparable to normal rats. CONCLUSIONS The decreases of β-glucuronidases activity in DSS-induced chronic rat colitis should mainly account for the decreases in systemic exposure and abrogation of enterohepatic recirculation of most rhubarb anthraquinones after oral intake.
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Affiliation(s)
- Wen-Jin Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Ru Yan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Ting Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Ya-Ping Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Rui-Na Zhou
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Yi-Tao Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
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Xia J, Inagaki Y, Song P, Sawakami T, Kokudo N, Hasegawa K, Sakamoto Y, Tang W. Advance in studies on traditional Chinese medicines to treat infection with the hepatitis B virus and hepatitis C virus. Biosci Trends 2016; 10:327-336. [PMID: 27350107 DOI: 10.5582/bst.2016.01110] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Traditional Chinese medicine (TCM), as a type of complementary and alternative medicine (CAM), is a sophisticated and time-honored form of healthcare in China. Many TCMs are widely used to treat hepatitis B and hepatitis C in countries like China, Japan, and South Korea. Since conventional clinical preparations like interferon-α cause obvious dose-dependent adverse reactions and drug resistance, TCMs and related bioactive compounds have garnered increasing attention from physicians and medical researchers. Thus far, a number of TCMs and compounds have been used to inhibit the hepatitis B virus (HBV) or hepatitis C virus (HCV) in vitro, in vivo, and even in clinical trials. The current review summarizes TCMs and related compounds that have been used to inhibit HBV or HCV. Most of these medicines are derived from herbs. HepG2.2.15 cells have been used to study HBV in vitro and Huh7.5 cells have been similarly used to study HCV. Ducks have been used to study the anti-HBV effect of new medication in vivo, but there are few animal models for anti-HCV research at the present time. Thus far, a number of preclinical studies have been conducted but few clinical trials have been conducted. In addition, a few chemically modified compounds have displayed greater efficacy than natural products. However, advances in TCM research are hampered by mechanisms of action of many bioactive compounds that have yet to be identified. In short, TCMs and related active compounds are a CAM that could be used to treat HBV and HCV infections.
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Affiliation(s)
- Jufeng Xia
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
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Wu YH. Naturally derived anti-hepatitis B virus agents and their mechanism of action. World J Gastroenterol 2016; 22:188-204. [PMID: 26755870 PMCID: PMC4698485 DOI: 10.3748/wjg.v22.i1.188] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 10/03/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus (HBV) are available for HBV patients, HBV infection is still a severe public health problem in the world. All the approved therapeutic drugs (including interferon-alpha and nucleoside analogues) have their limitations. No drugs or therapeutic methods can cure hepatitis B so far. Therefore, it is urgently needed to discover and develop new anti-HBV drugs, especially non-nucleoside agents. Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms. In this review, the natural products against HBV are discussed according to their chemical classes such as terpenes, lignans, phenolic acids, polyphenols, lactones, alkaloids and flavonoids. Furthermore, novel mode of action or new targets of some representative anti-HBV natural products are also discussed. The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20 years, especially novel skeletons and mode of action. Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date, scarcely any of them are found in the list of conventional anti-HBV drugs worldwide. Additionly, in anti-HBV mechanism of action, only a few references reported new targets or novel mode of action of anti-HBV natural products.
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Arbab AH, Parvez MK, Al-Dosari MS, Al-Rehaily AJ, Al-Sohaibani M, Zaroug EE, AlSaid MS, Rafatullah S. Hepatoprotective and antiviral efficacy of Acacia mellifera leaves fractions against hepatitis B virus. BIOMED RESEARCH INTERNATIONAL 2015; 2015:929131. [PMID: 25950002 PMCID: PMC4407411 DOI: 10.1155/2015/929131] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 03/25/2015] [Indexed: 01/29/2023]
Abstract
The present study investigated the hepatoprotective and anti-HBV efficacy of Acacia mellifera (AM) leaves extracts. The crude ethanolic-extract, including organic and aqueous fractions, were tested for cytotoxicity on HepG2 and HepG2.2.15 cells (IC50=684 μg/mL). Of these, the ethyl acetate and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-toxicated cells at 48 h. In CCl4-injured rats, oral administration of AM ethanol extract (250 and 500 mg/kg·bw) for three weeks significantly normalized the sera aminotransferases, alkaline phosphatase, bilirubin, cholesterol, triglycerides, and lipoprotein levels and elevated tissue nonprotein sulphydryl and total protein. The histopathology of dissected livers also revealed that AM cured the tissue lesions. The phytochemical screening of the fractions showed presence of alkaloids, flavonoids, tannins, sterols, and saponins. Further, anti-HBV potential of the fractions was evaluated on HepG2.2.15 cells. Of these, the n-butanol and aqueous fractions exhibited the best inhibitory effects on HBsAg and HBeAg expressions in dose- and time-dependent manner. Taken together, while the ethyl acetate and aqueous fractions exhibited the most promising antioxidant/hepatoprotective and anti-HBV activity, respectively, the n-butanol partition showed both activities. Therefore, the therapeutic potential of AM extracts warrants further isolation of the active principle(s) and its phytochemical as well as biological studies.
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Affiliation(s)
- Ahmed H. Arbab
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
- Department of Pharmacognosy, College of Pharmacy, Omdurman Islamic University, Khartoum 14415, Sudan
| | - Mohammad K. Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mohammed S. Al-Dosari
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Adnan J. Al-Rehaily
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Mohammed Al-Sohaibani
- Department of Pathology, King Khalid University Hospital, King Saud University, Riyadh 11461, Saudi Arabia
| | - Elwaleed E. Zaroug
- Department of Pharmacognosy, College of Pharmacy, Omdurman Islamic University, Khartoum 14415, Sudan
| | - Mansour S. AlSaid
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
- Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Syed Rafatullah
- Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
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In vitro glucuronidation of five rhubarb anthraquinones by intestinal and liver microsomes from humans and rats. Chem Biol Interact 2014; 219:18-27. [DOI: 10.1016/j.cbi.2014.05.006] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Revised: 05/05/2014] [Accepted: 05/11/2014] [Indexed: 11/23/2022]
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Shih KN, Huang WT, Chang CL, Feng CC. Effects of Ixeris Chinensis (Thunb.) Nakai boiling water extract on hepatitis B viral activity and hepatocellular carcinoma. AFRICAN JOURNAL OF TRADITIONAL, COMPLEMENTARY, AND ALTERNATIVE MEDICINES 2014; 11:187-93. [PMID: 24653576 DOI: 10.4314/ajtcam.v11i1.30] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection and hepatocellular carcinoma are major diseases that affect the Taiwanese population. Therefore, the development of an alternative herbal medicine that can effectively treat these diseases is a research target. In this study, we tested Ixeris Chinensis (Thunb.) Nakai boiling water extract (ICTN BWE) in vitro and analysed its effects on the HBV and liver cancer. MATERIALS AND METHODS We used a human liver cancer cell line (Hep3B, a cell line that continuously secretes HBV particles into a medium) as an experimental model for the screening of various ICTN BWE concentrations and their effects on the HBV in vitro. RESULTS Our results showed that 75 µg/mL ICTN BWE downregulated the relative expression of the hepatitis B virus surface antigens (HBsAg) to 77.1%. Using the human liver cancer cell lines HuH-7 and HepG2, and 3-(4,5-dimethylthiazol-zyl)-2,5-diphenyl tetrazolium bromide (MTT) and tumour clonogenic assays, we then showed that ICTN BWE inhibits hepatocellular carcinoma growth. CONCLUSION Fluorescent microscopy of DAPI(4',6-Diamidino-2-phenylindole)-stained nuclei and DNA fragmentation assays confirmed the inhibitory effects of ICTN BWE on liver tumour cell growth through induction of apoptosis.
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Affiliation(s)
- Ko-Nien Shih
- Department of Radiological Technology, College of Medical Sciences and Technology, Yuanpei University, HsinChu City 30015, Taiwan
| | - Wen-Tao Huang
- Department of Radiological Technology, College of Medical Sciences and Technology, Yuanpei University, HsinChu City 30015, Taiwan
| | - Chung-Liang Chang
- Department of Environmental Engineering and Health, College of Health Sciences, Yuanpei University, HsinChu City 30015, Taiwan
| | - Chih-Chung Feng
- Cardiovascular Internal Medicine Department, Changhua Christian Hospital, Changhua, 50006, Taiwan
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Zhang F, Wang G. A review of non-nucleoside anti-hepatitis B virus agents. Eur J Med Chem 2014; 75:267-81. [PMID: 24549242 DOI: 10.1016/j.ejmech.2014.01.046] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Revised: 01/12/2014] [Accepted: 01/17/2014] [Indexed: 12/14/2022]
Abstract
Hepatitis B Virus is the most common cause of chronic liver disease worldwide. Currently approved agents of chronic HBV infection treatment include interferon and nucleoside analogues. However, the side effects of interferon and the viral resistance of nucleoside analogues make the current treatment far from satisfactory. Therefore, new drugs with novel structures and mechanisms are needed. Recently, a number of non-nucleoside HBV inhibitors have been obtained from natural sources or prepared by synthesis/semi-synthesis. Some of them exhibited potent anti-HBV activity with novel mechanisms. These compounds provide useful information for the medicinal chemist to develop novel non-nucleoside compounds as anti-HBV agents.
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Affiliation(s)
- Fan Zhang
- School of Pharmacy, Liaoning Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou 121001, PR China.
| | - Gang Wang
- School of Pharmacy, Liaoning Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou 121001, PR China
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Antiviral activity of Rheum palmatum methanol extract and chrysophanol against Japanese encephalitis virus. Arch Pharm Res 2014; 37:1117-23. [PMID: 24395532 PMCID: PMC7091366 DOI: 10.1007/s12272-013-0325-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2013] [Accepted: 12/24/2013] [Indexed: 11/13/2022]
Abstract
Rheum palmatum, Chinese traditional herb, exhibits a great variety of anti-cancer and anti-viruses properties. This study rates antiviral activity of R. palmatum extracts and its components against Japanese encephalitis virus (JEV) in vitro. Methanol extract of R. palmatum contained higher levels of aloe emodin, chrysophanol, rhein, emodin and physcion than water extract. Methanol extract (IC50 = 15.04 μg/ml) exhibited more potent inhibitory effects on JEV plaque reduction than water extract (IC50 = 51.41 μg/ml). Meanwhile, IC50 values determined by plaque reduction assay were 15.82 μg/ml for chrysophanol and 17.39 μg/ml for aloe-emodin, respectively. Virucidal activity of agents correlated with anti-JEV activity, while virucidal IC50 values were 7.58 μg/ml for methanol extract, 17.36 μg/ml for water extract, 0.75 μg/ml for chrysophanol and 0.46 μg/ml for aloe-emodin, respectively. In addition, 10 μg/ml of extract, chrysophanol or aloe emodin caused 90 % inhibition of JEV yields in cells and significantly activated gamma activated sequence-driven promoters. Hence, methanol extract of R. palmatum and chrysophanol with high therapeutic index might be useful for development of antiviral agents against JEV.
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Wu W, Yan R, Yao M, Zhan Y, Wang Y. Pharmacokinetics of anthraquinones in rat plasma after oral administration of a rhubarb extract. Biomed Chromatogr 2013; 28:564-72. [PMID: 24136708 DOI: 10.1002/bmc.3070] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Revised: 09/09/2013] [Accepted: 09/20/2013] [Indexed: 11/12/2022]
Abstract
A sensitive and specific LC-MS/MS method was developed for simultaneous determination of aloe-emodin, rhein, emodin, chrysophanol and physcion and their conjugates in rat plasma. The lower limit of quantitation of each anthraquinone was 0.020-0.040 µm. Intra-day and inter-day accuracies were 90.1-114.3% and the precisions were <14.6%. The matrix effects were 104.0-113.2%. The method was successfully applied to a pharmacokinetic study in rats receiving a rhubarb extract orally. The area under the concentration-time curve (AUC0-t ) and peak concentration (Cmax ) of free aloe-emodin and emodin in rat plasma were much lower than those of rhein. The amounts of chrysophanol and physcion were too low to be continuously detected. After treating the plasma samples with β-glucuronidases, each anthraquinone was detectable throughout the experimental period (36 h) and showed much higher plasma concentrations and AUC0-t . The free/total ratios of aloe-emodin, rhein and emodin were 6.5, 49.0 and 1.7% for Cmax and 3.7, 32.5 and 1.1% for AUC0-t , respectively. The dose-normalized AUC0-t and Cmax of the total of each anthraquinone were in the same descending order: rhein > emodin > chrysophanol > physcion > aloe-emodin. These findings reveal phase II conjugates as the dominant in vivo existing forms of rhubarb antharquinones and warrant a further study to evaluate their contribution to the herbal activity.
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Affiliation(s)
- Wenjin Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
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Xu H, Wu Q, Peng C, Zhou L. Study on the antiviral activity of San Huang Yi Gan Capsule against hepatitis B virus with seropharmacological method. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 13:239. [PMID: 24073917 PMCID: PMC3849434 DOI: 10.1186/1472-6882-13-239] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/10/2012] [Accepted: 09/24/2013] [Indexed: 12/22/2022]
Abstract
Background Seropharmacology arising recently is a novel method of in vitro pharmacological study on Chinese herb using drug-containing animal serum. As seropharmacology possesses the advantages of experiments in vitro and in vivo, it is increasingly applied in pharmacological research on Chinese medicine. However, some issues of seropharmacology remain controversial and need to be clearly defined. San Huang Yi Gan Capsule (SHYGC) is a Chinese herbal formula with antiviral property against hepatitis B virus (HBV), but little is known about the mechanism underlying its anti-HBV activity. The aim of the present study was to elucidate the action mechanism of SHYGC using seropharmacological method and systematically address the methodology of preparing drug-containing serum. Methods New Zealand rabbits were orally administrated SHYGC with various regimens, followed by preparation of SHYGC-containing rabbit sera with a variety of methods. After HBV-producing HepG2 2.2.15 cells were treated with SHYGC-containing sera or entecavir for 9 days, the levels of hepatitis B surface antigen (HBsAg) and HBV DNA and the activity of DNA Polymerase were determined in HepG2 2.2.15 cells-conditioned media. Results An optimally standardized method of preparing drug-containing serum was raised for seropharmacology, with which SHYGC was demonstrated to suppress HBsAg expression, HBV DNA replication and DNA Polymerase activity in a dose-dependent fashion. Conclusions This seropharmacological study shows SHYGC is a potentially powerful anti-HBV agent. Additionally, seropharmacology is a promising pharmacological method with a broad range of advantages, and it can be widely used in biomedical research, if combined with pharmacokinetics.
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Chen Y, Zhu J. Anti-HBV effect of individual traditional Chinese herbal medicine in vitro and in vivo: an analytic review. J Viral Hepat 2013; 20:445-52. [PMID: 23730837 DOI: 10.1111/jvh.12112] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Accepted: 04/17/2013] [Indexed: 01/05/2023]
Abstract
Traditional Chinese herbal medicine (TCHM) has been widely used in the treatment of chronic hepatitis B (CHB) in China. The systematic analysis of clinical research of TCHM against CHB revealed its potential but not confirmed its therapeutic effect. To understand the detailed antiviral effect of TCHM against HBV infection, we systematically analysed the anti-HBV effect of individual Chinese herbs on the basis of the research on individual TCHM in vitro and in vivo, which were published from 1995 to 2012. Among 171 herbal components isolated from 76 Chinese herbs, we found 13 compounds and 9 extracts isolated from 18 Chinese herbs showing strong inhibitory effect on HBV DNA, HBeAg or HBsAg release with low cytotoxicity in HepG2.2.15 cells, and agents from 12 Chinese herbs showing the highest inhibition rates of plasma DHBV DNA of more than 50% in DHBV-infected ducks. In addition, the two compounds chrysophanol 8-O-beta-D-glucoside isolated from Rheum palmatum and wogonin isolated from Scutellaria baicalensis were found to display strong anti-HBV activity. Interestingly, compounds isolated from 5 of these effective anti-HBV Chinese herbs were found to show strong antibacterial or antifungal activity also. This review summarizes and analyses the studies on the anti-HBV effect of individual TCHM in cell and animal models, providing potential perspective in the understanding of TCHM in the treatment of hepatitis B and the development of new anti-HBV drugs from TCHM.
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Affiliation(s)
- Y Chen
- The China Institute for History of Medicine and Medical Literature, China Academy of Chinese Medical Sciences, Beijing, China
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Anti-hepatitis B virus lignans from the root of Streblus asper. Bioorg Med Chem Lett 2013; 23:2238-44. [PMID: 23434030 DOI: 10.1016/j.bmcl.2013.01.046] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2012] [Revised: 01/09/2013] [Accepted: 01/15/2013] [Indexed: 12/13/2022]
Abstract
Four new lignans, strebluslignanol F (1), (7'R,8'S,7″R,8″S)-erythro-strebluslignanol G (2), isomagnaldehyde (3) and isostrebluslignanaldehyde (4), along with 12 known lignans (5-16) were isolated from the ethyl acetate-soluble part of MeOH extract of the root of Streblus asper. Their structures were elucidated through various spectroscopic methods, including 1D NMR ((1)H NMR, (13)C NMR), 2D NMR (HMQC, HMBC and NOESY) and HRMS. The stereochemistry at the chiral centers was determined using CD spectra, as well as analyses of coupling constants and optical rotation data. The isolated lignans were evaluated for their anti-HBV activities in vitro using the HBV transfected HepG2.2.15 cell line. The most active lignans, (7'R,8'S,7″R,8″S)-erythro-strebluslignanol G, magnolol, isomagnolol and isolariciresinol, exhibited significant anti-HBV activities with IC50 values of 1.58, 2.03, 10.34 and 3.67 μM, respectively, for HBsAg with no cytotoxicity, and of 3.24, 3.76, 8.83 and 14.67 μM, respectively, for HBeAg with no cytotoxicity. (7'R,8'S,7″R,8″S)-erythro-Strebluslignanol G and magnolol showed significant anti-HBV activities to inhibit the replication of HBV DNA with the IC50 values of 9.02 and 8.67 μM, respectively.
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Qiu LP, Chen KP. Anti-HBV agents derived from botanical origin. Fitoterapia 2012; 84:140-57. [PMID: 23164603 DOI: 10.1016/j.fitote.2012.11.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 10/29/2012] [Accepted: 11/04/2012] [Indexed: 01/16/2023]
Abstract
There are 350,000 hepatitis B virus (HBV) carriers all over the world. Chronic HBV infection is at a high risk of developing liver cirrhosis and hepatocelluar carcinoma (HCC), and heavily threatened people's health. Two kinds of drugs approved by FDA for anti-HBV therapy are immunomodulators (interferon α, pegylated-interferon α) and nucleos(t)ide analogues (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate). These drugs have been proved to be far from being satisfactory due to their low specificity, side effects, and high rate of drug resistance. There is an urgent need to discover and develop novel effective anti-HBV drugs. With vast resources, various structures, diverse biological activities and action mechanisms, as well as abundant clinical experiences, botanical agents become a promising source of finding new anti-HBV drugs. This review summarizes the recent research and development of anti-HBV agents derived from botanical origin on their sources and active components, inhibitory effects and possible toxicities, as well as action targets and mechanisms, and also addresses the advantages and the existing shortcomings in the development of botanical inhibitors. This information may not only broaden the knowledge of anti-HBV therapy, and offer possible alternative or substitutive drugs for CHB patients, but also provides considerable information for developing new safe and effective anti-HBV drugs.
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Affiliation(s)
- Li-Peng Qiu
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, 212013, China
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Esposito F, Corona A, Zinzula L, Kharlamova T, Tramontano E. New anthraquinone derivatives as inhibitors of the HIV-1 reverse transcriptase-associated ribonuclease H function. Chemotherapy 2012; 58:299-307. [PMID: 23128501 DOI: 10.1159/000343101] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Accepted: 08/31/2012] [Indexed: 02/02/2023]
Abstract
BACKGROUND The degradative activity of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), termed ribonuclease H (RNase H), which hydrolyzes the RNA component of the heteroduplex RNA:DNA replication intermediate, is an excellent target for drug discovery. Anthraquinones (AQs) and their derivatives, which are common secondary metabolites occurring in bacteria, fungi, lichens and a large number of families in higher plants, have been reported to have several biological activities including that of inhibiting HIV-1 RT activities in biochemical assays. METHODS We have assayed new AQ derivatives on HIV-1 RNase H activities in biochemical assays. RESULTS Six series of new AQ derivatives with various substituents at positions 1, 2, 3 and 4 of the AQ ring were tested, and new analogs able to inhibit HIV-1 RT-associated RNase H activity in the low micromolar range were found. CONCLUSIONS Our results demonstrate that AQ derivatives are promising anti-RNase H inhibitors.
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Affiliation(s)
- Francesca Esposito
- Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy.
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VanMen C, Jang YS, Zhu HM, Lee JH, Trung TN, Ngoc TM, Kim YH, Kang JS. Chemical-based species classification of rhubarb using simultaneous determination of five bioactive substances by HPLC and LDA analysis. PHYTOCHEMICAL ANALYSIS : PCA 2012; 23:359-364. [PMID: 22009582 DOI: 10.1002/pca.1365] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2011] [Revised: 09/04/2011] [Accepted: 09/07/2011] [Indexed: 05/31/2023]
Abstract
INTRODUCTION Rhubarb is a traditional Chinese medicine derived from the rhizome of three species: Rheum tanguticum, Rheum palmatum and Rheum officinale. There are several species that are often misidentified as rhubarb. Taxonomical identification of these various species can be challenging. We have developed an HPLC-based species classification to identify rhubarb. OBJECTIVE The objective of this study was to develop a simple HPLC method for the simultaneous determination of bioactive compounds and identification of medicinal rhubarb rhizome and non-medicinal species. METHODOLOGY Quantitative analysis was performed on a C₁₈-column using 0.05 M aqueous phosphoric acid and acetonitrile as the mobile phase under gradient conditions with ultraviolet detection at 280 nm. The method was validated with respect to linearity, accuracy, precision, and recovery. Statistical analysis was used to classify different groups of species. RESULTS All calibration curves showed good linearity (r ≥ 0.9995). The method showed good repeatability with intra- and inter-day standard deviations of less than 1.13% and 1.32%, respectively. The accuracy and recovery of all marker compounds were in the ranges of 98.0 to 102.6% and 99.21 to 102.04%, respectively. Seventeen peaks were selected, and 39 known and 57 unknown samples were classified into five species based on linear discriminant analysis with an accuracy of 100%. CONCLUSION A chemical-based species classification method of rhubarb using simultaneous determination of bioactive compounds by HPLC was developed with 39 known samples of five different species and successfully applied to identify 57 unknown samples collected from Korea and China.
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Affiliation(s)
- Chu VanMen
- College of Pharmacy, Chungnam National University, Daejeon, Korea
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Diversity of Pharmacological Properties in Chinese and European Medicinal Plants: Cytotoxicity, Antiviral and Antitrypanosomal Screening of 82 Herbal Drugs. DIVERSITY-BASEL 2011. [DOI: 10.3390/d3040547] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Xing XY, Zhao YL, Kong WJ, Wang JB, Jia L, Zhang P, Yan D, Zhong YW, Li RS, Xiao XH. Investigation of the "dose-time-response" relationships of rhubarb on carbon tetrachloride-induced liver injury in rats. JOURNAL OF ETHNOPHARMACOLOGY 2011; 135:575-581. [PMID: 21463673 DOI: 10.1016/j.jep.2011.03.053] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2010] [Revised: 02/23/2011] [Accepted: 03/27/2011] [Indexed: 05/30/2023]
Abstract
AIM OF THE STUDY The present study investigated the liver protection and toxicity of rhubarb against carbon tetrachloride (CCl4)-induced chronic liver injury in rats. MATERIALS AND METHODS The rats were treated by intraperitoneal injection of 10% CCl4 for 12 weeks. At the end of week 4, rhubarb at doses of 40 g kg(-1) (high-dose group), 20 g kg(-1) (medium-dose group) and 10 g kg(-1) (low-dose group) was intragastrically administered to CCl4-treated rats once a day for three weeks. At the end of week 16, all rats were maintained for 1 month without any administration. At the end of weeks 8, 12, 16 and 20, the general status of rats, histopathology of liver, serum alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), total bilirubin (TBIL) and hyaluronic acid (HA) levels were observed, respectively. Combined with clustering analysis and correspondence analysis, the "dose-time-response" relationships of rhubarb on the liver injury rats were synthetically investigated. RESULTS High dose (40 g kg(-1)) of rhubarb exhibited a significant protective effect on injured liver by reversing the biochemical parameters and histopathological changes. But, this hepatoprotective effect will be weakened, even be transferred to toxicity with increasing the administration dose and time of rhubarb. These results were consistent with the histopathological observation and the determination of serum levels. CONCLUSIONS The safety should be considered simultaneously in the long-term and high dose use of rhubarb, the liver function and change should be regularly detected. This study provided some useful references for the clinical rational use of rhubarb and other herbal medicinal products.
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Affiliation(s)
- Xiao-yan Xing
- China Military Institute of Chinese Materia Medica, 302 Military Hospital of China, Beijing 100039, PR China
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Jang YS, Chu VM, Lee KJ, Seo EY, Kim DH, Kang JS. Effects of the decoction water on the extraction of the bioactive compounds from rhubarb. ANALYTICAL SCIENCE AND TECHNOLOGY 2011. [DOI: 10.5806/ast.2011.24.1.038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Zhang L, Wang G, Hou W, Li P, Dulin A, Bonkovsky HL. Contemporary clinical research of traditional Chinese medicines for chronic hepatitis B in China: an analytical review. Hepatology 2010; 51:690-8. [PMID: 20101751 PMCID: PMC2930399 DOI: 10.1002/hep.23384] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
UNLABELLED Chronic hepatitis B (CHB) is major global health problem. In China, where about 120,000,000 persons are chronically infected, CHB has been treated for centuries with traditional Chinese medicines (TCMs). This review summarizes and meta-analyzes the results of randomized controlled trials (RCTs) of TCM formulations reported in China in 1998-2008 for treatment of CHB. RCTs comparing either TCM formulations alone or in combination with interferon (IFN) or lamivudine (LAM) versus IFN or LAM were included. Chinese electronic databases were searched. The methodological quality of RCTs was assessed using the Jadad scale. TCMs had a greater beneficial effect (P = 0.0003) than IFN and a slightly better effect (P = 0.01) than LAM on the normalization of serum alanine aminotransferase. TCMs had a similar beneficial effect when compared with IFN or LAM for CHB on antiviral activity as evidenced by the loss of serum hepatitis B e antigen and hepatitis B virus (HBV) DNA. TCMs enhanced IFN and LAM antiviral activities and improvements of liver function. The quality of many studies was poor; reports often lacked information regarding methods of randomization or blinding and adverse events. CONCLUSION Some TCMs seem effective as alternative remedies for patients with CHB, suggesting that further study of TCMs in the treatment of CHB is warranted, both in preclinical models of HBV infection and in higher quality RCTs worldwide.
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Affiliation(s)
- Lingyi Zhang
- The Liver-Biliary-Pancreatic Center and the Liver, Digestive Diseases and Metabolism Laboratory, Carolinas Medical Center, Charlotte, NC, USA
| | - Guqi Wang
- The Liver-Biliary-Pancreatic Center and the Liver, Digestive Diseases and Metabolism Laboratory, Carolinas Medical Center, Charlotte, NC, USA
,McColl-Lockwood Laboratory, Carolinas Medical Center, Charlotte, NC, USA
| | - Weihong Hou
- The Liver-Biliary-Pancreatic Center and the Liver, Digestive Diseases and Metabolism Laboratory, Carolinas Medical Center, Charlotte, NC, USA
| | - Ping Li
- Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, China
| | - Andrea Dulin
- The Liver-Biliary-Pancreatic Center and the Liver, Digestive Diseases and Metabolism Laboratory, Carolinas Medical Center, Charlotte, NC, USA
| | - Herbert L. Bonkovsky
- The Liver-Biliary-Pancreatic Center and the Liver, Digestive Diseases and Metabolism Laboratory, Carolinas Medical Center, Charlotte, NC, USA
,Department of Biology, The University of North Carolina at Charlotte, Charlotte, NC
,Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC
,Departments of Medicine and Molecular, Microbial & Structural Biology, The University of Connecticut Health Center, Farmington, Connecticut, USA
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Song J, Yao H, Li Y, Li X, Lin Y, Liu C, Han J, Xie C, Chen S. Authentication of the family Polygonaceae in Chinese pharmacopoeia by DNA barcoding technique. JOURNAL OF ETHNOPHARMACOLOGY 2009; 124:434-9. [PMID: 19505556 DOI: 10.1016/j.jep.2009.05.042] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2008] [Revised: 04/30/2009] [Accepted: 05/28/2009] [Indexed: 05/22/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Medicinal plants belonging to the family Polygonaceae in Chinese pharmacopoeia possess important medicinal efficacy in traditional Chinese medicines. AIM OF THE STUDY DNA barcodes are first used to discriminate the Polygonaceae in Chinese pharmacopoeia and their adulterants. MATERIALS AND METHODS DNA samples, extracted from thirty-eight specimens belonging to eighteen species in Polygonaceae, were used as templates. Eight candidate barcodes were amplified by polymerase chain reaction. Sequence analysis was accomplished by CodonCode Aligner V 2.06 and DNAman V 6. Species identification was performed using MEGA V 4.0. RESULTS The amplification efficiency of six candidate DNA barcodes (rbcL, trnH-psbA, ndhJ, rpoB, rpoC1, accD) was 100%, while the efficiency of YCF5 and nrITS was 56% and 44%, respectively. The interspecific divergence was highest for the trnH-psbA (20.05%), followed by the nrITS (14.01%) across all species pairs, while intraspecific variation both within populations and between populations was absent (0.0%). The trnH-psbA can not only distinguish ten species of Polygonaceae in Chinese pharmacopoeia, but also recognize eight other species of Polygonaceae including their adulterants. CONCLUSION Our findings show that DNA barcoding is an efficient tool for identification of Polygonaceae in Chinese pharmacopoeia and their adulterants.
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Affiliation(s)
- Jingyuan Song
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, 151 Malianwa North Road, Haidian District, Beijing 100193, PR China
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Abstract
Hepatitis B virus (HBV) or hepatitis C virus (HCV) infections are a major threat worldwide. Combination therapy of interferon-alpha and ribavirin is currently the treatment of choice for HCV-infected patients. However, this regimen is only effective in approximately 50% of patients and provokes severe side-effects. Numerous natural alternatives for treating HCV have been suggested. Deoxynojirimycin and its derivatives are iminosugars which exert anti-HCV activity by inhibiting alpha-glucosidases. A non-immunosuppressive derivate of cyclosporine A, NIM811, exerts anti-HCV activity by binding to cyclophilin. Other natural products with promising anti-HCV activity are 2-arylbenzofuran derivatives, Mellein, and pseudoguaianolides. For HBV treatment, several drugs are available, specifically targeting the virus polymerase (lamivudine, entecavir, telbivudine, and adefovir dipivoxil). The efficacy of these drugs is hampered by the development of resistance due to point mutations in the HBV polymerase. Due to drug resistance and adverse side-effects, the search for novel drugs is mandatory. Wogonin, ellagic acid, artemisinin and artesunate, chrysophanol 8-O-beta-D-glucoside, saikosaponin C, and protostane triterpenes are active against HBV. Natural products need to be investigated in more detail to explore their potential as novel adjuncts to established HBV or HCV therapy.
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