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Li Z, Lin Y, Zou Y, Liang Y, Zeng L, Wang Y, Li Y, Zong Y, Zhang Y, Zheng Y, Cui Y, Huang L, Chen Z, Pan X, Zhu L. Zuogui pills ameliorate chemotherapy-induced ovarian aging by improving stemness, regulating cell cycle and reducing apoptosis of oogonial stem cells via the Notch1/Nrf2 pathway. JOURNAL OF ETHNOPHARMACOLOGY 2025; 339:119105. [PMID: 39580130 DOI: 10.1016/j.jep.2024.119105] [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: 10/03/2024] [Revised: 11/12/2024] [Accepted: 11/12/2024] [Indexed: 11/25/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Zuogui Pills (ZGP) is a classic traditional Chinese herbal formula originating from the Ming Dynasty. It has been widely used in the treatment of kidney deficiency-related diseases, including ovarian aging. AIM OF THE STUDY To investigate the effects and potential mechanisms of ZGP on ovarian aging induced by the chemotherapeutic agent cyclophosphamide (CTX), as well as its impact on the therapeutic target, oogonial stem cells (OSCs), involving the Notch1/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. MATERIALS AND METHODS This study utilized High-Performance Liquid Chromatography (HPLC) to analyze the active components of Zuogui Pills (ZGP). In vivo experiments involved the establishment of an ovarian aging model in female rats through intraperitoneal injection of CTX, followed by an 8-week treatment with ZGP and dehydroepiandrosterone (DHEA). The Notch pathway inhibitor DAPT was administered via intraperitoneal injection, followed by ZGP intervention to validate its therapeutic effects. Transcriptomic sequencing was used to analyze the differential genes before and after ZGP treatment of CTX-induced ovarian aging, and KEGG and GO analyses were applied to assess the changes in relevant signaling pathways and biological processes. In vitro experiments included the extraction, separation, and purification of ovarian germ stem cells, followed by transfection with a Notch1 overexpression plasmid. The CTX active component 4-Hydroxycyclophosphamide (4HC) was used for model intervention, and ZGP, DHEA-containing serum, and DAPT were applied to intervene with the oogonial stem cells. The effects of CTX modeling, the therapeutic efficacy of ZGP, and the general condition of the rats were observed. H&E staining was employed to assess ovarian morphology and follicle counting at various stages. Serum hormone levels were measured using ELISA, while qPCR, Western blot, flow cytometry, immunofluorescence, and IHC were utilized to analyze the expression of the Notch1/Nrf2 pathway, cell cycle proteins, and stemness-related indicators. Flow cytometry, TUNEL fluorescence, and CCK8 assays were conducted to evaluate changes in cell cycle composition, apoptosis, and proliferation. Finally, ChIP-qPCR was employed to validate the transcriptional regulation of the target gene NFE2L2 by Notch1. RESULTS ZGP improved serum sex hormones in ovarian aging rats, enhanced ovarian index, and optimized ovarian and uterine morphology, as well as follicle quantity composition. After transcriptome sequencing, KEGG analysis enriched the Notch signaling pathway and cell cycle, while GO analysis highlighted enrichment in the Notch pathway and stem cell population maintenance. Various experiments validated that ZGP significantly improved the expression of cell cycle-related proteins Cyclin D1 (CCND1), Cyclin E1 (CCNE1), cyclin-dependent kinase inhibitor 1a (CDKN1A), stemness markers Mouse Vasa Homolog (MVH), Octamer-binding Transcription Factor 4 (Oct4), Fragilis, 5-Bromo-2'-deoxyuridine (BrdU), as well as Notch1 and Nrf2 in aging ovarian tissues and OSCs. Additionally, ZGP promoted the proliferation of 4HC-damaged OSCs, optimized OSCs cell cycle composition, reduced G0/G1 phase arrest, and decreased early and late apoptosis. ZGP could reverse the detrimental effects on stemness and cell cycle of OSCs caused by blocking the Notch pathway. Furthermore, ZGP may activate the regulation of its target gene NFE2L2 by upregulating Notch1 expression in OSCs, thereby exerting therapeutic effects. CONCLUSION ZGP protects ovarian function in CTX-induced ovarian aging rats by regulating the Notch1/Nrf2 pathway. It restores serum sex hormone levels, maintains normal follicle development, promotes the proliferation of aged OSCs, optimizes the cell cycle, reduces apoptosis, and preserves stemness, thereby alleviating ovarian aging.
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Affiliation(s)
- Zuang Li
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yuewei Lin
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yuxin Zou
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yunyi Liang
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Lihua Zeng
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yixuan Wang
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yucheng Li
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yun Zong
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yuying Zhang
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yunling Zheng
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yixuan Cui
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Liuqian Huang
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Zhuoting Chen
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Xinyi Pan
- Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Ling Zhu
- Department of Gynecology, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
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Ribeiro IC, de Moraes JVB, Mariotini-Moura C, Polêto MD, da Rocha Torres Pavione N, de Castro RB, Miranda IL, Sartori SK, Alves KLS, Bressan GC, de Souza Vasconcellos R, Meyer-Fernandes JR, Diaz-Muñoz G, Fietto JLR. Synthesis of new non-natural L-glycosidic flavonoid derivatives and their evaluation as inhibitors of Trypanosoma cruzi ecto-nucleoside triphosphate diphosphohydrolase 1 (TcNTPDase1). Purinergic Signal 2024; 20:399-419. [PMID: 37975950 PMCID: PMC11303637 DOI: 10.1007/s11302-023-09974-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 10/20/2023] [Indexed: 11/19/2023] Open
Abstract
Trypanosoma cruzi is the pathogen of Chagas disease, a neglected tropical disease that affects more than 6 million people worldwide. There are no vaccines to prevent infection, and the therapeutic arsenal is very minimal and toxic. The unique E-NTPDase of T. cruzi (TcNTPDase1) plays essential roles in adhesion and infection and is a virulence factor. Quercetin is a flavonoid with antimicrobial, antiviral, and antitumor activities. Its potential as a partial inhibitor of NTPDases has also been demonstrated. In this work, we synthesized the non-natural L-glycoside derivatives of quercetin and evaluated them as inhibitors of recombinant TcNTPDase1 (rTcNTPDase1). These compounds, and quercetin and miquelianin, a natural quercetin derivative, were also tested. Compound 16 showed the most significant inhibitory effect (94%). Quercetin, miquelianin, and compound 14 showed inhibition close to 50%. We thoroughly investigated the inhibitory effect of 16. Our data suggested a competitive inhibition with a Ki of 8.39 μM (± 0.90). To better understand the interaction of compound 16 and rTcNTPDase1, we performed molecular dynamics simulations of the enzyme and docking analyses with the compounds. Our predictions show that compound 16 binds to the enzyme's catalytic site and interacts with important residues for NTPDase activity. As an inhibitor of a critical T. cruzi enzyme, (16) could be helpful as a starting point in the developing of a future treatment for Chagas disease. Furthermore, the discovery of (16) as an inhibitor of TcNTPDase1 may open new avenues in the study and development of new inhibitors of E-NTPDases.
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Affiliation(s)
- Isadora Cunha Ribeiro
- Biochemistry and Molecular Biology Department, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | | | - Christiane Mariotini-Moura
- General Biology Department, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
- Medicine and Nursing Department, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | - Marcelo Depolo Polêto
- Biochemistry and Molecular Biology Department, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | | | - Raissa Barbosa de Castro
- Biochemistry and Molecular Biology Department, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | - Izabel Luzia Miranda
- Exact Science Institute, Chemistry Department, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Suélen Karine Sartori
- Exact Science Institute, Chemistry Department, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Kryssia Lohayne Santos Alves
- Exact Science Institute, Chemistry Department, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Gustavo Costa Bressan
- Biochemistry and Molecular Biology Department, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | | | - José Roberto Meyer-Fernandes
- Laboratory of Cellular Biochemistry, Institute of Medical Biochemistry Leopoldo de Meis, Health Sciences Center, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gaspar Diaz-Muñoz
- Exact Science Institute, Chemistry Department, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Juliana Lopes Rangel Fietto
- Biochemistry and Molecular Biology Department, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
- General Biology Department, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
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To DC, Hoang LM, Nguyen HT, Hoa TTV, Thuy NTT, Tran MH, Nguyen PH, Nguyen PDN, Nhan NT, Tram NTT. Dataset on the compounds from the leaves of Vietnamese Machilus thunbergii and their anti-inflammatory activity. Data Brief 2023; 51:109713. [PMID: 37965621 PMCID: PMC10641128 DOI: 10.1016/j.dib.2023.109713] [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: 09/18/2023] [Revised: 10/19/2023] [Accepted: 10/19/2023] [Indexed: 11/16/2023] Open
Abstract
Machilus thunbergii has a history of traditional applications including treating dyspepsia, apoplexy, headaches, abdominal pain, abdominal distension, and leg edema [1]. It is also employed for alleviating allergies, inflammation, pain relief, promoting blood circulation, addressing costal chondritis, and sinusitis [2]. Research into the chemical composition of M. thunbergii has revealed the presence of lignans, flavonoids, lactones, and essential oils [1,[3], [4], [5]. While some investigations have explored the inhibitory effects of extracts and lignan compounds from this species on NO production [6], [7], [8], there has been no research into the flavonoids isolated from this plant and their potential for inhibiting NO production, given our reachable referencing. The ethyl acetate (EtOAc) soluble fraction of M. thunbergii leaves was subjected to column chromatography (CC) using silica gel and Sephadex LH-20 for compound isolation. Nuclear magnetic resonance (NMR) data primarily facilitated the determination of isolated compound structures. Anti-inflammatory activity was evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells. Anti-inflammatory activity-guided fractionation led to the isolation of twelve secondary metabolites (1-12). The compounds were identified as quercetin (1), kaempferol (2), rhamnetin (3), quercitrin (4), hyperoside (5), reynoutrin (6), guaijaverin (7), afzelin (8), astragalin (9), rutin (10), kaempferol-3-O-rutinoside (11), and rhamnetin-3-O-rutinoside (12). Compounds 3, 5, 6, 9, 11, and 12 were isolated from M. thunbergii for the first time. Evaluation against LPS-induced NO production in macrophage RAW264.7 cells showed that 1-3 exhibited potent inhibitory activity with IC50 values of 15.45, 25.44, and 19.82 µM, respectively. Compounds 4-9 demonstrated IC50 values ranging from 42.15 to 67.42 µM, while 10-12 exhibited inactivity (IC50 > 100 µM).
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Affiliation(s)
- Dao Cuong To
- Phenikaa University Nano Institute (PHENA), Phenikaa University, Yen Nghia, Ha Dong, Hanoi 12116, Vietnam
| | - Le Minh Hoang
- Phenikaa University Nano Institute (PHENA), Phenikaa University, Yen Nghia, Ha Dong, Hanoi 12116, Vietnam
| | - Hoa Thi Nguyen
- Phenikaa University Nano Institute (PHENA), Phenikaa University, Yen Nghia, Ha Dong, Hanoi 12116, Vietnam
| | - Truong Thi Viet Hoa
- Phenikaa University Nano Institute (PHENA), Phenikaa University, Yen Nghia, Ha Dong, Hanoi 12116, Vietnam
| | - Nhung Truong Thi Thuy
- Phenikaa University Nano Institute (PHENA), Phenikaa University, Yen Nghia, Ha Dong, Hanoi 12116, Vietnam
| | - Manh Hung Tran
- School of Medicine & Pharmacy, The University of Danang, Hoa Quy, Ngu Hanh Son, Da Nang City 550000, Vietnam
| | - Phi Hung Nguyen
- Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi 122100, Vietnam
| | | | - Ngu Truong Nhan
- Tay Nguyen University, 567 Le Duan, Buon Ma Thuot, Dak Lak 630000, Vietnam
| | - Nguyen Thi Thu Tram
- Faculty of Basic Sciences, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu, An Khanh Ward, Ninh Kieu District, Can Tho 94000, Vietnam
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Iftikhar N, Hussain AI, Fatima T, Alsuwayt B, Althaiban AK. Bioactivity-Guided Isolation and Antihypertensive Activity of Citrullus colocynthis Polyphenols in Rats with Genetic Model of Hypertension. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1880. [PMID: 37893598 PMCID: PMC10608828 DOI: 10.3390/medicina59101880] [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: 09/08/2023] [Revised: 10/10/2023] [Accepted: 10/16/2023] [Indexed: 10/29/2023]
Abstract
Background and Objectives: Citrullus colocynthis belongs to the Cucurbitaceae family and is a wild medicinal plant used in folk literature to treat various diseases. The purpose of the current study was to explore the antihypertensive and antioxidant potentials of Citrullus colocynthis (CC) polyphenol-rich fractions using a spontaneous hypertensive rat (SHR) model. Materials and Methods: The concentrated aqueous ethanol extract of CC fruit was successively fractioned using solvents of increasing polarity, i.e., hexane, chloroform, ethyl acetate and n-butanol. The obtained extracts were analyzed for total phenolic content (TPC), total flavonoid content (TFC) and total flavonol content (TOF). Moreover, the CC extracts were further evaluated for radical scavenging capacity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays and antioxidant activity using inhibition of linoleic acid peroxidation and determination of reducing potential protocols. The phytochemical components were characterized by HPLC-MWD-ESI-MS in positive ionization mode. Results: The results showed that ethyl acetate fraction (EAF) exhibited a higher content of phenolic compounds in term of TPC (289 mg/g), TFC (7.6 mg/g) and TOF (35.7 mg/g). EAF showed higher antioxidant and DPPH and ABTS scavenging activities with SC50 values of 6.2 and 79.5 µg/mL, respectively. LCMS analysis revealed that twenty polyphenol compounds were identified in the EAF, including phenolic acids and flavonoids, mainly myricetin and quercetin derivatives. The in vivo antihypertensive activity of EAF of CC on SHR revealed that it significantly decreased the mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressures (DBP) and pulse pressure (PP) as compared to normal and hypertensive control groups. Moreover, EAF of CC significantly reduced the oxidative stress in the animals in a dose-dependent manner by normalizing the levels of superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NOx) and total antioxidant capacity (TAC). Furthermore, the treatment groups, especially the 500 mg of EAF per kg body weight (EA-500) group, significantly (p ≤ 0.05) improved the electrocardiogram (ECG) pattern and pulse wave velocity (PWV). Conclusion: It was concluded that the EAF of CC is a rich source of polyphenols and showed the best antioxidant activity and antihypertensive potential in SHR.
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Affiliation(s)
- Neelam Iftikhar
- Natural Product and Synthetic Chemistry Laboratory, Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan;
| | - Abdullah Ijaz Hussain
- Natural Product and Synthetic Chemistry Laboratory, Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan;
- Central Hi-Tech Laboratory, Government College University Faisalabad, Faisalabad 38000, Pakistan
| | - Tabinda Fatima
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hafr Al Batin, Hafar Al Batin 39524, Saudi Arabia;
| | - Bader Alsuwayt
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafar Al Batin 39524, Saudi Arabia; (B.A.); (A.K.A.)
| | - Abdullah K. Althaiban
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafar Al Batin 39524, Saudi Arabia; (B.A.); (A.K.A.)
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Sang YL, Dai L, Wang P, Chen LJ, Jiao ML, Liu JY, Zhang NZ, Fan GW, Hao YJ, Wang XL. Investigation of insecticidal activity of two Rhododendron species on stored-product insects. JOURNAL OF PLANT DISEASES AND PROTECTION : SCIENTIFIC JOURNAL OF THE GERMAN PHYTOMEDICAL SOCIETY (DPG) 2023; 130:371-382. [PMID: 35965943 PMCID: PMC9361267 DOI: 10.1007/s41348-022-00654-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 07/20/2022] [Indexed: 05/03/2023]
Abstract
This study was designed to investigate the insecticidal activity of the essential oils (EOs) and extracts from Rhododendron rufum and Rhododendron przewalskii. The EOs were extracted from the leaves of R. Rufum and R. przewalskii by hydro-distillation and their chemical components were analyzed by gas chromatography-mass spectrometry (GC-MS). The repellency, contact toxicity and antifeedant activity of the EOs and extracts were evaluated against Sitophilus oryzae and Tribolium castaneum along with those of their main components. A total of nine compounds were identified from the EO of R. Rufum, and the most abundant component was myristicin (79.72%). The EO of R. Rufum exhibited repellent activities at different levels and its main compound myristicin showed contact toxicity and repellent effects against S. oryzae and T. castaneum. Meanwhile, by bioassay-guided fractionation, four compounds with strong antifeedant activities against T. castaneum, 24-methylenecycloartanyl-2'E, 4'Z-tetradecadienoate (1), methyl thyrsiflorin B acetate (2), friedelin (3) and Excoecarin R1 methyl ester (4) were separated and identified from the ethanol extract of R. przewalskii for the first time. Considering the significant anti-insect activities, the EOs and extracts of R. Rufum and R. przewalskii might be used in integrated pest strategies, establishing a good perspective for the comprehensive use of natural plant resources of Rhododendron genus.
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Affiliation(s)
- Yu-Li Sang
- College of Pharmacy, Liaoning University, No.66 Middle Chongshan Road, Shenyang, 110036 Liaoning China
| | - Lu Dai
- College of Pharmacy, Liaoning University, No.66 Middle Chongshan Road, Shenyang, 110036 Liaoning China
| | - Pei Wang
- College of Pharmacy, Liaoning University, No.66 Middle Chongshan Road, Shenyang, 110036 Liaoning China
| | - Li-Jiang Chen
- College of Pharmacy, Liaoning University, No.66 Middle Chongshan Road, Shenyang, 110036 Liaoning China
| | - Mei-Ling Jiao
- College of Pharmacy, Liaoning University, No.66 Middle Chongshan Road, Shenyang, 110036 Liaoning China
| | - Jing-Yu Liu
- College of Pharmacy, Liaoning University, No.66 Middle Chongshan Road, Shenyang, 110036 Liaoning China
| | - Nai-Zhi Zhang
- College of Pharmacy, Liaoning University, No.66 Middle Chongshan Road, Shenyang, 110036 Liaoning China
| | - Guang-Wen Fan
- College of Pharmacy, Liaoning University, No.66 Middle Chongshan Road, Shenyang, 110036 Liaoning China
| | - Yan-Jun Hao
- Liaoning Academy of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, No.79 East Chongshan Road, Shenyang, 110032 Liaoning China
| | - Xiu-Lan Wang
- Inner Mongolia Institute of Mongolian Medicine Engineering Technology, Inner Mongolia University for Nationalities, No.536 West Huolinhe Street, Tongliao, 028000 China
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Ansari P, Hannan JMA, Choudhury ST, Islam SS, Talukder A, Seidel V, Abdel-Wahab YHA. Antidiabetic Actions of Ethanol Extract of Camellia sinensis Leaf Ameliorates Insulin Secretion, Inhibits the DPP-IV Enzyme, Improves Glucose Tolerance, and Increases Active GLP-1 (7-36) Levels in High-Fat-Diet-Fed Rats. MEDICINES (BASEL, SWITZERLAND) 2022; 9:medicines9110056. [PMID: 36422117 PMCID: PMC9698069 DOI: 10.3390/medicines9110056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 11/04/2022] [Accepted: 11/09/2022] [Indexed: 05/14/2023]
Abstract
Camellia sinensis (green tea) is used in traditional medicine to treat a wide range of ailments. In the present study, the insulin-releasing and glucose-lowering effects of the ethanol extract of Camellia sinensis (EECS), along with molecular mechanism/s of action, were investigated in vitro and in vivo. The insulin secretion was measured using clonal pancreatic BRIN BD11 β cells, and mouse islets. In vitro models examined the additional glucose-lowering properties of EECS, and 3T3L1 adipocytes were used to assess glucose uptake and insulin action. Non-toxic doses of EECS increased insulin secretion in a concentration-dependent manner, and this regulatory effect was similar to that of glucagon-like peptide 1 (GLP-1). The insulin release was further enhanced when combined with isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, but was decreased in the presence of verapamil, diazoxide and Ca2+ chelation. EECS also depolarized the β-cell membrane and elevated intracellular Ca2+, suggesting the involvement of a KATP-dependent pathway. Furthermore, EECS increased glucose uptake and insulin action in 3T3-L1 cells and inhibited dipeptidyl peptidase IV (DPP-IV) enzyme activity, starch digestion and protein glycation in vitro. Oral administration of EECS improved glucose tolerance and plasma insulin as well as inhibited plasma DPP-IV and increased active GLP-1 (7-36) levels in high-fat-diet-fed rats. Flavonoids and other phytochemicals present in EECS could be responsible for these effects. Further research on the mechanism of action of EECS compounds could lead to the development of cost-effective treatments for type 2 diabetes.
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Affiliation(s)
- Prawej Ansari
- Department of Pharmacy, School of Pharmacy and Public Health, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
- School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK
- Correspondence:
| | - J. M. A. Hannan
- Department of Pharmacy, School of Pharmacy and Public Health, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
| | - Samara T. Choudhury
- Department of Pharmacy, School of Pharmacy and Public Health, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
| | - Sara S. Islam
- Department of Pharmacy, School of Pharmacy and Public Health, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
| | - Abdullah Talukder
- Department of Pharmacy, School of Pharmacy and Public Health, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
| | - Veronique Seidel
- Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
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Thuy Linh NT, Thuy TT, Tam NT, Cham BT, Tai BH, Thao DT, Thien DG, Chinh VT, Hoang Anh NT. Chemical constituents of Impatiens parvisepala and their α-glucosidase inhibition activity. Nat Prod Res 2022:1-6. [PMID: 36154790 DOI: 10.1080/14786419.2022.2127705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
The first chemical study of the whole Impatiens parvisepala S. X. Yu & Y. T. Hou led to the isolation of a new triterpene saponin, named Iparvisepala-1 (6) along with ten known compounds, which cover three flavonoid glycosides (1-3), one dihydrochalcone glucoside (4), one triterpenoid saponin (5), one triterpene (7) and four miscellaneous compounds (8-11). Their structures were elucidated by MS, NMR spectroscopic analyses as well as by comparisons of spectra data with those of the related published literatures. Additionally, flavonoid glucoside 2 showed impressive effect on α-glucosidase inhibition with the IC50 value of 12.53 ± 0.39 µM, much better than that of the positive control acabose (IC50 = 197.53 ± 2.68 µM).
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Affiliation(s)
- Nguyen Thi Thuy Linh
- Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam.,Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam
| | - Trinh Thi Thuy
- Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam.,Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam
| | - Nguyen Thanh Tam
- Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam
| | - Ba Thi Cham
- Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam.,Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam
| | - Bui Huu Tai
- Institute of Marine Biochemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam
| | - Do Thi Thao
- Institute of Biotechnology, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam
| | - Dinh Gia Thien
- Nguyen Binh Khiem specialized high school, Tam Ky, Quang Nam, Vietnam
| | - Vu Tien Chinh
- Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam.,Vietnam National Museum of Nature, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam
| | - Nguyen Thi Hoang Anh
- Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam.,Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam
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Hyperoside improves learning and memory deficits by amyloid β1-42 in mice through regulating synaptic calcium-permeable AMPA receptors. Eur J Pharmacol 2022; 931:175188. [DOI: 10.1016/j.ejphar.2022.175188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 08/02/2022] [Accepted: 08/03/2022] [Indexed: 11/20/2022]
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Antibacterial Activity of Prenylated Flavonoids Isolated from Hop against Fish Pathogens Streptococcus iniae and Vibrio vulnificus. BIOTECHNOL BIOPROC E 2022. [DOI: 10.1007/s12257-021-0247-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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10
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Wang Q, Wei HC, Zhou SJ, Li Y, Zheng TT, Zhou CZ, Wan XH. Hyperoside: A review on its sources, biological activities, and molecular mechanisms. Phytother Res 2022; 36:2779-2802. [PMID: 35561084 DOI: 10.1002/ptr.7478] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 04/01/2022] [Accepted: 04/11/2022] [Indexed: 12/22/2022]
Abstract
Hyperoside is a natural flavonol glycoside in various plants, such as Crataegus pinnatifida Bge, Forsythia suspensa, and Cuscuta chinensis Lam. Medical research has found that hyperoside possesses a broad spectrum of biological activities, including anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects. These pharmacological properties lay the foundation for its use in treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers. Hyperoside is obtained from the plants and chemical synthesis. This study aims to provide a comprehensive overview of hyperoside on its sources and biological activities to provide insights into its therapeutic potential, and to provide a basis for high-quality studies to determine the clinical efficacy of this compound.
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Affiliation(s)
- Qi Wang
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, China
| | - Hao-Cheng Wei
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, China
| | - Sheng-Jun Zhou
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, China
| | - Ying Li
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, China
| | - Ting-Ting Zheng
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, China
| | - Chang-Zheng Zhou
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, China
| | - Xin-Huan Wan
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, China
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Tsiftsoglou OS, Stefanakis MK, Kalpourtzi EN, Hadjipavlou-Litina DI, Lazari DM. Chemical constituents isolated from the aerial parts of Helleborus cyclophyllus (A. Braun) Boiss. (Ranunculaceae), evaluation of their antioxidant and anti-inflammatory activity in vitro and virtual screening of molecular properties and bioactivity score. Nat Prod Res 2022; 36:6031-6038. [DOI: 10.1080/14786419.2022.2041009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Olga St. Tsiftsoglou
- Laboratory of Pharmacognosy, Faculty of Health sciences, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Michalis K. Stefanakis
- Laboratory of Organic Chemistry, School of Sciences and Engineering, Department of Chemistry, University of Crete, Heraklion, Greece
| | - Eirini N. Kalpourtzi
- Laboratory of Pharmacognosy, Faculty of Health sciences, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitra I. Hadjipavlou-Litina
- Department of Pharmaceutical Chemistry, Faculty of Health Sciences, School of Pharmacy, Aristotle University of Thessaloniki, Greece
| | - Diamanto M. Lazari
- Laboratory of Pharmacognosy, Faculty of Health sciences, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Elkousy RH, Said ZNA, Abd El-Baseer MA, Abu El Wafa SA. Antiviral activity of castor oil plant (Ricinus communis) leaf extracts. JOURNAL OF ETHNOPHARMACOLOGY 2021; 271:113878. [PMID: 33515683 DOI: 10.1016/j.jep.2021.113878] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 01/19/2021] [Accepted: 01/20/2021] [Indexed: 02/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ricinus communis L., commonly known as castor oil plant, is a precious traditional medicine with a history of thousands of years in the world. Castor oil plant has high traditional and medicinal values for treating liver infections, stomach ache, flatulence, constipation, inflammation, warts, colic, enteritis, fever, headache, and as a counter irritant. Its diverse phytochemicals have a wide range of valuable medicinal activities including hepatoprotective, anti-nociceptive, antioxidant, antiulcer, anticancer, anti-inflammatory, central analgesic, antidiabetic, antimicrobial, antiviral, and wound healing activity. AIM OF THE WORK To provide a complete characterization of the composition of Ricinus communis leaves using ultra-performance liquid chromatography coupled with hybrid triple time-of-flight mass spectrometry (UPLC-Triple TOF-MS/MS) and different chromatographic techniques and to evaluate its antiviral potential using three mechanisms against three common viruses. MATERIALS AND METHODS R. communis leaves were extracted with 70% methanol and further partitioned with solvents of increasing polarities: petroleum ether, dichloromethane (CH2Cl2), ethyl acetate, and n-butanol. The CH2Cl2 and n-butanol fractions were subjected to repeated chromatographic separation to isolate the phytochemicals, and their structures were elucidated using nuclear magnetic resonance spectroscopy. UPLC-Triple TOF-MS/MS was performed to determine the different phytochemicals in the ethyl acetate fraction. The antiviral activity of the extracts was investigated using the maximum nontoxic concentration of each against the challenge dose of the virus (CDV) and 1/10 and 1/100 dilutions of the CDV for Coxsackie B virus type 4 (COXB4), herpes simplex virus type 1 (HSV1), and hepatitis A virus (HAV) using Vero cell cultures that were treated according to three protocols to test for anti-replicative, protective, and anti-infective antiviral activity. Cell viability was evaluated using the MTT colorimetric assay and each experiment is repeated three times independently of each other. RESULTS R. communis leaves possessed antiviral activity. Evaluation of the anti-replicative activity showed that all extracts possessed high anti-replicative activity against HAV especially methanol and methylene chloride fractions and moderate activity against COXB4; butanol > methylene chloride and ethyl acetate > methanol. All extracts showed protective activity against HAV, especially butanol extract, while methanol extracts showed higher non-significant antiviral protective activity against HSV1 vs Acyclovir. Almost no anti-infective effects were recorded for any extract against the studied viruses. CONCLUSION The discriminatory effect against each virus by different mechanisms suggests the presence of different chemical compounds. The alkaloid and phenolic derivatives of the extracts of R. communis leaves may help develop a drug to prevent or treat common viral infections. Further investigations are recommended to define the bioactive antiviral properties of R. communis leaves.
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Affiliation(s)
- Rawah H Elkousy
- Department of Pharmacognosy, Faculty of Pharmacy (for Girls), Al-Azhar University, P.O. Box 11651, Nasr City, Cairo, Egypt
| | - Zeinab N A Said
- Department of Microbiology, Faculty of Medicine (for Girls), Al-Azhar University, P.O. Box 11754, Nasr City, Cairo, Egypt
| | - Mohamed A Abd El-Baseer
- Department of Microbiology, Faculty of Science (for Boys), Al-Azhar University, P.O. Box 13129, Nasr City, Cairo, Egypt
| | - Salwa A Abu El Wafa
- Department of Pharmacognosy, Faculty of Pharmacy (for Girls), Al-Azhar University, P.O. Box 11651, Nasr City, Cairo, Egypt.
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Park HJ, Kim HN, Kim CY, Seo MD, Baek SH. Synergistic Protection by Isoquercitrin and Quercetin against Glutamate-Induced Oxidative Cell Death in HT22 Cells via Activating Nrf2 and HO-1 Signaling Pathway: Neuroprotective Principles and Mechanisms of Dendropanax morbifera Leaves. Antioxidants (Basel) 2021; 10:antiox10040554. [PMID: 33918248 PMCID: PMC8066007 DOI: 10.3390/antiox10040554] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/28/2021] [Accepted: 03/31/2021] [Indexed: 01/18/2023] Open
Abstract
Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial superoxide generation, Ca2+ dysregulation, mitochondrial dysfunction, and nuclear translocation of apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin and quercetin, both of whom showed prominent synergism, as assessed by drug–drug interaction analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway.
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Affiliation(s)
- Hye-Jin Park
- College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Korea; (H.-J.P.); (H.-N.K.)
| | - Ha-Neul Kim
- College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Korea; (H.-J.P.); (H.-N.K.)
- Department of Molecular Science and Technology, Ajou University, Suwon 16499, Korea
| | - Chul Young Kim
- College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan-si 15588, Korea;
| | - Min-Duk Seo
- College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Korea; (H.-J.P.); (H.-N.K.)
- Department of Molecular Science and Technology, Ajou University, Suwon 16499, Korea
- Correspondence: (M.-D.S.); (S.-H.B.)
| | - Seung-Hoon Baek
- College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Korea; (H.-J.P.); (H.-N.K.)
- Correspondence: (M.-D.S.); (S.-H.B.)
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Ahmed AH. Phytochemical and Cytotoxicity Studies of Callistemon viminalis Leaves Extract Growing in Egypt. Curr Pharm Biotechnol 2020; 21:219-225. [PMID: 31696815 DOI: 10.2174/1389201020666191107110341] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 09/24/2019] [Accepted: 09/30/2019] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To isolate and identify new compounds from the methanolic extract of Callistemon viminalis leaves collected in Cairo, Egypt and evaluate its cytotoxic and hepatoprotective potentials. METHODS The methanolic extract of Callistemon viminalis leaves was fractionated and subjected to different chromatographic techniques to isolate pure, new compounds which were identified by nuclear magnetic resonance (NMR), spectroscopic analysis and mass spectrometric methods. The methanolic extract of the leaves was assessed for its cytotoxic and hepatoprotective activities against Hepatocellular carcinoma cells (Hep G-2 cell line) by estimating the viability of the HepG2 cells by the MTT reduction assay. RESULTS Six compounds were isolated and identified for the first time from the methanolic extract of Callistemon viminalis leaves, three compounds are new flavonoids namely; 3-O-[α-L-arabinopyranosyl- (1→2)-α-L-arabinopyranosyl)]-3'-O-methylquercetin (C1); 5,7,3',4' tetrahydroxy isoflavone-7-O-α- L-1C4- rhamnopyranosyl (1'''-6'')-O-β-D-4C1-glucopyranoside (C2) and 6-methyl-5,7-dihydroxy-4'- methoxyflavone (C6) along with the three known ones; hyperoside (C3), rutin (C4) and isoquercitrin (C5). CONCLUSION The methanolic extract of the leaves showed strong cytotoxic activity against Hepatocellular carcinoma cells (Hep G-2 cell line) and weak hepatoprotective effect.
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Affiliation(s)
- Amal H Ahmed
- Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
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15
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Targeting staphylocoagulase with isoquercitrin protects mice from Staphylococcus aureus-induced pneumonia. Appl Microbiol Biotechnol 2020; 104:3909-3919. [PMID: 32130467 DOI: 10.1007/s00253-020-10486-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 02/10/2020] [Accepted: 02/18/2020] [Indexed: 10/24/2022]
Abstract
Staphylocoagulase (Coa) is a virulence factor of Staphylococcus aureus (S. aureus) that promotes blood coagulation by activating prothrombin to convert fibrinogen to fibrin. Coa plays a crucial role in disease pathogenesis and is a promising target for the treatment of S. aureus infections. Here, we identified that isoquercitrin, a natural flavonol compound, can markedly reduce the activity of Coa at concentrations that have no effect on bacterial growth. Mechanistic studies employing molecular dynamics simulation revealed that isoquercitrin binds to Coa by interacting with Asp-181 and Tyr-188, thereby affecting the binding of Coa to prothrombin. Importantly, in vivo studies showed that isoquercitrin treatment significantly reduced the bacterial burden, pathological damage, and inflammation of lung tissue and improved the percentage of survival of mice infected with S. aureus Newman strain. These data suggest that isoquercitrin is a promising inhibitor of Coa that can be used for the development of therapeutic drugs to combat S. aureus infections.Key Points• Staphylocoagulase plays a key role in the pathogenesis of S. aureus infection.• We identified that isoquercitrin is a direct inhibitor of staphylocoagulase.• Isoquercitrin treatment can significantly attenuate S. aureus virulence in vivo.
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da Costa Cordeiro BMP, de Lima Santos ND, Ferreira MRA, de Araújo LCC, Junior ARC, da Conceição Santos AD, de Oliveira AP, da Silva AG, da Silva Falcão EP, dos Santos Correia MT, da Silva Almeida JRG, da Silva LCN, Soares LAL, Napoleão TH, da Silva MV, Paiva PMG. Hexane extract from Spondias tuberosa (Anacardiaceae) leaves has antioxidant activity and is an anti-Candida agent by causing mitochondrial and lysosomal damages. Altern Ther Health Med 2018; 18:284. [PMID: 30340567 PMCID: PMC6194709 DOI: 10.1186/s12906-018-2350-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 10/09/2018] [Indexed: 12/18/2022]
Abstract
Background Spondias tuberosa is a plant that produces a fruit crop with high economic relevance at Brazilian Caatinga. Its roots and leaves are used in folk medicine. Methods Chemical composition of a hexane extract from S. tuberosa leaves was evaluated by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and 1H nuclear magnetic resonance (NMR). Antioxidant potential was investigated by DPPH and ABTS assays. Antifungal action on Candida species was evaluated determining the minimal inhibitory concentration (MIC50) and putative mechanisms were determined by flow cytometry analysis. In addition, hemolytic activity on human erythrocytes was assessed and the concentration required to promote 50% hemolysis (EC50) was determined. Results Phytochemical analysis by TLC showed the presence of flavonoids, hydrolysable tannins, saponins and terpenes. The HPLC profile of the extract suggested the presence of gallic acid (0.28 ± 0.01 g%) and hyperoside (1.27 ± 0.01 g%). The representative 1H NMR spectrum showed saturated and unsaturated fatty acids among the main components. The extract showed weak and moderate antioxidant activity in DPPH (IC50: 234.00 μg/mL) and ABTS (IC50: 123.33 μg/mL) assays, respectively. It was able to inhibit the growth of C. albicans and C. glabrata with MIC50 of 2.0 and 0.078 mg/mL, respectively. The treatment of C. glabrata cells with the extract increased levels of mitochondrial superoxide anion, caused hyperpolarization of mitochondrial membrane, and compromised the lysosomal membrane. Weak hemolytic activity (EC50: 740.8 μg/mL) was detected. Conclusion The results demonstrate the pharmacological potential of the extract as antioxidant and antifungal agent, aggregating biotechnological value to this plant and stimulating its conservation.
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Effect of isoquercitrin on membrane dynamics and apoptosis-like death in Escherichia coli. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2017; 1860:357-363. [PMID: 29155212 DOI: 10.1016/j.bbamem.2017.11.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 11/09/2017] [Accepted: 11/15/2017] [Indexed: 12/11/2022]
Abstract
Minimum inhibitory concentration (MIC) is defined as the lowest concentration of a compound that completely inhibits microbial growth. Antibacterial mechanisms of compounds have been investigated at their sub-MICs as well as at their MIC. In this study, the effects of sub-MIC and MIC of isoquercitrin on Escherichia coli were investigated. The antibacterial effect of isoquercitrin was tested using the microdilution method. Sub-MICs of isoquercitrin induced the production of reactive oxygen species and depletion of glutathione. The oxidative effects induced by sub-MICs of isoquercitrin could be prolonged, finally resulting in apoptosis-like death. DNA fragmentation and phosphatidylserine externalization, which are regarded as the hallmarks of apoptosis, were evaluated using the TUNEL assay and Annexin V staining, respectively. Furthermore, isoquercitrin induced the peroxidation of membrane lipids and inner membrane permeabilization at both its sub-MIC and MIC. This suggested membrane damage in response to lipid oxidation. The uptake of membrane impermeable dyes, propidium iodide and calcein, demonstrated that isoquercitrin damaged the cell membrane at concentrations higher than its MIC. Thus, isoquercitrin induced apoptosis-like death and dysregulation of cell membrane dynamics.
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Zhang Y, Wang M, Dong H, Yu X, Zhang J. Anti-hypoglycemic and hepatocyte-protective effects of hyperoside from Zanthoxylum bungeanum leaves in mice with high-carbohydrate/high-fat diet and alloxan-induced diabetes. Int J Mol Med 2017; 41:77-86. [PMID: 29115390 PMCID: PMC5746319 DOI: 10.3892/ijmm.2017.3211] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Accepted: 10/17/2017] [Indexed: 12/12/2022] Open
Abstract
The development of diabetes mellitus (DM) is accompanied by hyperglycemia-induced oxidative stress. Hyperoside is a major bioactive component in Zanthoxylum bungeanum leaves (HZL) and is a natural antioxidant. However, the effects of HZL on DM and its mechanisms of action remain undefined. The present study evaluated the anti-hypoglycemic and hepatocyte-protective effects of HZL in mice with diabetes induced by a high-carbohydrate/high-fat diet (HFD) and alloxan. We also aimed to eludicate the underlying mechanisms. Our resutls demonstrated that the administration of HZL significantly reduced body weight gain, serum glucose levels and insulin levels in diabetic mice compared with the vehicle-treated mice. In addition, the levels of dyslipidemia markers including total cholesterol, triglyceride and low-density lipoprotein cholesterol in the HFD-treated mice were markedly decreased. Further experiments using hepatocytes from mice revealed that HZL significantly attenuated liver injury associated with DM compared with vehicle treatment, as evidenced by lower levels of alanine aminotransferase and aspartate aminotransferase in serum and by lower levels of lipid peroxidation, nitric oxide content and inducible nitric oxide synthase activity in liver tissues. Nuclear factor-κB (NF-κB) and mitogen-associated protein kinase (MAPK) signaling pathways were investigated to elucidate the molecular mechanisms responsible for the protective effects of HZL against diabetic liver injury. The results indicated that HZL inhibited the phosphorylation of p65/NF-κB, MAPK (including p38, JNK and ERK1/2) and activating transcription factor 3 protein expression, with an additional suppression of Bax, cytochrome c, caspase-9 and caspase-3 in the liver tissues of diabetic mice. Taken together, our findings suggest that HZL, which was effective in inhibiting oxidative stress-related pathways may be beneficial for use in the treatment of DM.
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Affiliation(s)
- Yali Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China
| | - Mimi Wang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China
| | - Huanhuan Dong
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China
| | - Xiaomin Yu
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China
| | - Jingfang Zhang
- College of Forestry, Northwest A&F University, Xianyang, Shaanxi 712100, P.R. China
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Yang Y, Tantai J, Sun Y, Zhong C, Li Z. Effect of hyperoside on the apoptosis of A549 human non‑small cell lung cancer cells and the underlying mechanism. Mol Med Rep 2017; 16:6483-6488. [PMID: 28901459 PMCID: PMC5865815 DOI: 10.3892/mmr.2017.7453] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 11/29/2016] [Indexed: 12/15/2022] Open
Abstract
Hyperoside (HY) is a major pharmacologically active component from Prunella vulgaris L. and Hypericum perforatum. The present study aimed to determine the anticancer effect of HY and determine the underlying mechanisms involved. Human A549 cells were treated with HY (10, 50 and 100 µM), and cell viability was detected by an MTT assay. Cell apoptosis and mitochondrial membrane potential were determined by flow cytometry. Western blot analysis was used to identify the expression of apoptosis-associated proteins and phosphorylation of MAPK. The present study demonstrated that HY significantly inhibited the viability of A549 cells in a time- and dose-dependent manner, and enhanced the percentage of apoptotic cells. HY also significantly increased the protein phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), disrupted mitochondrial membrane penetrability, and triggered the release of mitochondrial cytochrome c and apoptosis-inducing factor into the cytosol. Treatment with HY also activated the expression of caspase-9 and caspase-3. These results suggested that HY-induced apoptosis was associated with activation of the p38 MAPK- and JNK-induced mitochondrial death pathway. HY may offer potential for clinical applications in treating human non-small cell lung cancer and improving cancer chemotherapy.
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Affiliation(s)
- Yu Yang
- Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, P.R. China
| | - Jicheng Tantai
- Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, P.R. China
| | - Yifeng Sun
- Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, P.R. China
| | - Chenxi Zhong
- Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, P.R. China
| | - Zhigang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, P.R. China
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Živković JČ, Barreira JCM, Šavikin KP, Alimpić AZ, Stojković DS, Dias MI, Santos-Buelga C, Duletić-Laušević SN, Ferreira ICFR. Chemical Profiling and Assessment of Antineurodegenerative and Antioxidant Properties of Veronica teucrium L. and Veronica jacquinii Baumg. Chem Biodivers 2017; 14. [PMID: 28488389 DOI: 10.1002/cbdv.201700167] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023]
Abstract
Neuroprotective potential of V. teucrium and V. jacquinii methanol extracts was analyzed. Chemical analysis of investigated extracts showed the presence of phenolic acid derivatives, flavonoids and one secoiridoid. The detected flavonoids derived from flavones (luteolin and isoscutellarein in V. jacquinii; apigenin, isoscutellarein and luteolin in V. teucrium) and flavonol (quercetin in V. jacquinii). Acteoside was the dominant compound in V. jacquinii, while plantamajoside and isoscutellarein 7-O-(6‴-O-acetyl)-β-allosyl (1‴→2‴)-β-glucoside were the major phenolics in V. teucrium. Additionally, the antineurodegenerative activity was tested at concentrations of 25, 50, and 100 μg/ml using acetylcholinesterase (AChE) and tyrosinase (TYR) assays. The inhibition of both enzymes was achieved with the investigated extracts, ranging from 22.78 to 35.40% for AChE and from 9.57 to 16.38% for TYR. There was no statistical difference between the activities of the analyzed extracts. Our data indicate that V. teucrium and V. jacquinii may have beneficial effects against Alzheimer's and Parkinson's disease.
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Affiliation(s)
- Jelena Č Živković
- Institute for Medicinal Plants Research "Dr. Josif Pančić", Tadeuša Košćuška 1, RS-11000, Belgrade, Serbia
| | - João C M Barreira
- CIMO/Escola Superior Agrária, Instituto Politécnico de Bragança, Apartado 1172, PT-5301-855, Bragança
- REQUIMTE/Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, no. 228, PT-4050-313, Porto
| | - Katarina P Šavikin
- Institute for Medicinal Plants Research "Dr. Josif Pančić", Tadeuša Košćuška 1, RS-11000, Belgrade, Serbia
| | - Ana Z Alimpić
- Institute of Botany and Botanical Garden "Jevremovac", Faculty of Biology, University of Belgrade, Takovska 43, RS-11000, Belgrade
| | - Dejan S Stojković
- Department of Plant Physiology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Bulevar Despota Stefana 142, RS-11000, Belgrade
| | - Maria Inês Dias
- CIMO/Escola Superior Agrária, Instituto Politécnico de Bragança, Apartado 1172, PT-5301-855, Bragança
- REQUIMTE/Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, no. 228, PT-4050-313, Porto
| | - Celestino Santos-Buelga
- GIP-USAL, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, ES-37007, Salamanca
| | - Sonja N Duletić-Laušević
- Institute of Botany and Botanical Garden "Jevremovac", Faculty of Biology, University of Belgrade, Takovska 43, RS-11000, Belgrade
| | - Isabel C F R Ferreira
- CIMO/Escola Superior Agrária, Instituto Politécnico de Bragança, Apartado 1172, PT-5301-855, Bragança
- REQUIMTE/Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, no. 228, PT-4050-313, Porto
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Zhang Y, Dong H, Zhang J, Zhang L. Inhibitory effect of hyperoside isolated from Zanthoxylum bungeanum leaves on SW620 human colorectal cancer cells via induction of the p53 signaling pathway and apoptosis. Mol Med Rep 2017; 16:1125-1132. [PMID: 29067453 PMCID: PMC5562015 DOI: 10.3892/mmr.2017.6710] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 04/06/2017] [Indexed: 12/13/2022] Open
Abstract
The present study aimed to demonstrate the antiproliferative effect of hyperoside from Zanthoxylum bungeanum leaves (HZL) and explain the underlying molecular mechanisms in the SW620 human colorectal cancer cell line. The cytotoxic effects of HZL were determined using a3‑(4,5‑dimethylthiazol‑2‑yl)2,5‑diphenyltetrazolium bromide assay. Apoptosis and cell cycle were detected using flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (∆Ψm) were assessed using 2',7'‑dichlorofluorescin diacetate and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl carbocyanine iodide fluorescence spectrophotometry, respectively. Western blot analysis was used to quantify the expression levels of apoptosis‑associated proteins. Reverse transcription‑quantitative polymerase chain reaction analysis was used to determine the mRNA expression of glutathione peroxidase (GSH‑Px) and catalase (CAT). HZL had a marked anti‑proliferative effect on the SW620 human colorectal cancer cells by inducing cell cycle G2/M phase arrest and apoptosis, which was associated with an increase in the expression of p53 and p21. Further mechanistic investigations revealed that the induction of apoptosis was associated with increased generation of ROS, reduced ∆Ψm, and upregulation of B‑cell lymphoma 2‑associated X protein, cytochrome c, caspase‑9, apoptotic protease activating factor 1 and caspase‑3. The antitumor potency of HZL was also attributed to inhibition of the mRNA expression levels of GSH‑Px and CAT. These data indicated that HZL may be involved in the pro‑apoptotic signaling of SW620 human colorectal cancer cells via induction of the caspase‑dependent apoptosis and p53 signaling pathways.
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Affiliation(s)
- Yali Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China
| | - Huanhuan Dong
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China
| | - Jingfang Zhang
- College of Forestry, Northwest A&F University, Xianyang, Shaanxi 712100, P.R. China
| | - Liyu Zhang
- Shaanxi Institute of Pediatric Diseases, Xi'an Children's Hospital, Xi'an, Shaanxi 710002, P.R. China
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22
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Li H, Liu Y, Yi Y, miao Q, Liu S, Zhao F, Cong W, Wang C, Xia C. Purification of quercetin-3- O -sophoroside and isoquercitrin from Poacynum hendersonii leaves using macroporous resins followed by Sephadex LH-20 column chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2017; 1048:56-63. [DOI: 10.1016/j.jchromb.2017.01.041] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 01/24/2017] [Accepted: 01/29/2017] [Indexed: 10/20/2022]
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Nawrot-Hadzik I, Granica S, Abel R, Czapor-Irzabek H, Matkowski A. Analysis of Antioxidant Polyphenols in Loquat Leaves using HPLC-based Activity Profiling. Nat Prod Commun 2017. [DOI: 10.1177/1934578x1701200205] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Leaves of Eriobotrya japonica (loquat) have been used in Traditional Chinese Medicine with beneficial effects in numerous diseases. Extracts from loquat leaves are rich in antioxidants, containing among others: triterpenes, sesquiterpenes, flavonoids, tannins, and megastigmane glycosides. However, there is no conclusive study revealing which of these compounds are the main bioactive principles. The goal of this study was to pinpoint compounds responsible for strong antioxidant activity. Eriobotryae folium was extracted and fractionated between solvents of increasing polarity. All extracts and fractions were screened for total polyphenols and tannins, and antioxidant activity was checked by DPPH, phosphomolybdenum and linoleic acid tests. The ethyl acetate fraction demonstrated the highest antioxidant activity and contained the largest amount of polyphenols. Applying HPLC-based activity profiling to localize antioxidants revealed that cinchonain IIb, as well as flavonoid glycosides such as hyperoside, isoquercitrin, kaempferol glycosides, quercetin-rhamnoside, as well as two tentatively identified protocatechuic acid derivatives are the main substances responsible for the strong antioxidant activity of the ethyl acetate fraction.
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Affiliation(s)
- Izabela Nawrot-Hadzik
- Department of Pharmaceutical Biology and Botany, Medical University, ul. Borowska 211, 50-556 Wroclaw, Poland
| | - Sebastian Granica
- Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University, ul. S. Banacha 1, Warsaw, Poland
| | - Renata Abel
- Department of Pharmaceutical Biology and Botany, Medical University, ul. Borowska 211, 50-556 Wroclaw, Poland
| | - Hanna Czapor-Irzabek
- Laboratory of Elemental Analysis and Structural Research, Medical University, ul. Borowska 211A, 50-556 Wroclaw, Poland
| | - Adam Matkowski
- Department of Pharmaceutical Biology and Botany, Medical University, ul. Borowska 211, 50-556 Wroclaw, Poland
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Orfali GDC, Duarte AC, Bonadio V, Martinez NP, de Araújo MEMB, Priviero FBM, Carvalho PO, Priolli DG. Review of anticancer mechanisms of isoquercitin. World J Clin Oncol 2016; 7:189-199. [PMID: 27081641 PMCID: PMC4826964 DOI: 10.5306/wjco.v7.i2.189] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 10/19/2015] [Accepted: 02/16/2016] [Indexed: 02/06/2023] Open
Abstract
This review was based on a literature search of PubMed and Scielo databases using the keywords “quercetin, rutin, isoquercitrin, isoquercitin (IQ), quercetin-3-glucoside, bioavailability, flavonols and favonoids, and cancer” and combinations of all the words. We collected relevant scientific publications from 1990 to 2015 about the absorption, bioavailability, chemoprevention activity, and treatment effects as well as the underlying anticancer mechanisms of isoquercitin. Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom. The subclass of flavonols receives special attention owing to their health benefits. The main components of this class are quercetin, rutin, and IQ, which is a flavonoid and although mostly found as a glycoside, is an aglycone (lacks a glycoside side chain). This compound presents similar therapeutic profiles to quercetin but with superior bioavailability, resulting in increased efficacy compared to the aglycone form. IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant, antiproliferative, anti-inflammatory, anti-hypertensive, and anti-diabetic. The protective effects of IQ in cancer may be due to actions on lipid peroxidation. In addition, the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway, mixed-lineage protein kinase 3, mitogen-activated protein kinase, apoptotic pathways, as well proinflammatory protein signaling. This review contributed to clarifying the mechanisms of absorption, metabolism, and actions of IQ and isoquercitrin in cancer.
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Xie W, Chen C, Jiang Z, Wang J, Melzig MF, Zhang X. Apocynum venetum Attenuates Acetaminophen-Induced Liver Injury in Mice. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2015; 43:457-76. [DOI: 10.1142/s0192415x15500299] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Apocynum venetum L. (A. venetum) has long been used in oriental folk medicine for the treatment of some liver diseases; however, the underlying mechanisms remain to be fully elucidated. Acetaminphen (APAP) is a widely used analgesic drug that can cause acute liver injury in overdose situations. In this study, we investigated the potential protective effect of A. venetum leaf extract (ALE) against APAP-induced hepatotoxicity. Mice were intragastrically administered with ALE once daily for 3 consecutive days prior to receiving a single intraperitoneal injection of APAP. The APAP group showed severe liver injury characterized by the noticeable fluctuations in the following parameters: serum aminotransferases; hepatic malondialdehyde (MDA), 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione (GSH). These liver damages induced by APAP were significantly attenuated by ALE pretreatments. A collective analysis of histopathological examination, DNA laddering and western blot for caspase-3 and cytochrome c indicated that the ALE is also capable of preventing APAP-induced hepatocyte death. Hyperoside, isoquercitrin and their derivatives have been identified as the major components of ALE using HPLC-MS/MS. Taken together, the A. venetum possesses hepatoprotective effects partially due to its anti-oxidant action.
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Affiliation(s)
- Wenyan Xie
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China
| | - Chen Chen
- College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China
| | - Zhihui Jiang
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China
| | - Jian Wang
- College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China
| | - Matthias F. Melzig
- College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China
- Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195, Berlin, Germany
| | - Xiaoying Zhang
- College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China
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