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Attah CO, Alhaji UI, Ameh DA, Forcados GE, Muhammad A, Bashir M, Ibrahim S. In Vivo Chemosuppressive Effects of Kolaviron on 7,12-Dimethylbenzanthracene-Induced Mammary Lesions are Associated with Changes in Levels of Estrogen Receptor-α, CYP 1A1, Proinflammatory Cytokines, and Alterations to Metabolic Pathways Implicated in Mammary Carcinogenesis. J Med Food 2024; 27:940-950. [PMID: 39093123 DOI: 10.1089/jmf.2023.0158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024] Open
Abstract
Garcinia kola is a medicinal food commonly consumed in Sub-Sahara Africa, for which Kolaviron (KV) is the active portion. As a follow-up to our earlier chemopreventive studies, we investigated the chemotherapeutic effects of KV on experimentally induced mammary carcinogenesis in female Wistar rats. Mammary carcinogenesis was induced using 80 mg/kg of 7,12-dimethylbenzanthracene (DMBA) administered by oral gavage. One hundred-fifty days post-DMBA induction, estrogen receptor-α (ER-α) levels were determined in the experimental rats before treatment with KV commenced. Treatment was done using 50, 100, and 200 mg/kg KV thrice a week for 4 weeks, after which the experiment was terminated. Significantly higher levels of estrogen receptor-α, CYP 1A1, malondialdehyde, formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased cytokine (interleukin-6 and tumor necrosis factor-α) activity were observed in DMBA-induced rats, which were attenuated in KV-treated rats. Tyrosine metabolism was exclusively enriched in DMBA-induced rats in contrast to KV-treated rats. Collectively, the results point to the chemotherapeutic potential of KV.
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Affiliation(s)
- Catherine Ojebbah Attah
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
| | - Umar Ismail Alhaji
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
| | - Danladi Amodu Ameh
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
| | | | - Aliyu Muhammad
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
| | - Musa Bashir
- Center for Dryland Agriculture, Bayero University, Kano, Nigeria
| | - Sani Ibrahim
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
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Prayoga DK, Aulifa DL, Budiman A, Levita J. Plants with Anti-Ulcer Activity and Mechanism: A Review of Preclinical and Clinical Studies. Drug Des Devel Ther 2024; 18:193-213. [PMID: 38318501 PMCID: PMC10840521 DOI: 10.2147/dddt.s446949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 01/23/2024] [Indexed: 02/07/2024] Open
Abstract
Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), histamine H2 receptor antagonists (H2RAs), and cytoprotective agents have drawbacks like mucosal injury, diminish gastric acid secretion, and interact with concurrent medications. Therefore, alternative therapeutic approaches are needed to tackle this health concern. Plants are rich in active metabolites in the bark, roots, leaves, fruits, and seeds, and have been utilized for medicinal purposes since ancient times. The use of herbal therapy is crucial, and regulations are necessary to ensure the quality of products, particularly in randomized studies, to assess their efficacy and safety in treating ulcer disorders. This study aims to explore the anti-ulcer activity of medicinal plants in treating peptic ulcer disease, ulcerative colitis, and aphthous ulcers. Articles were searched in Scopus and PubMed, and filtered for publication from 2013 to 2023, resulting in a total of 460 from Scopus and 239 from PubMed. The articles were further screened by title and abstract and resulted in 55 articles. Natural products, rich in active metabolites, were described to manage ulcer disease by protecting the mucosa, reducing ulcer effects, inhibiting pro-inflammatory factors, and reducing bacterial load, thus improving patients' quality of life. Natural extracts have proven effective in managing other health problems, including ulcers by reducing pain and decreasing lesions. This review provides an overview of preclinical and clinical studies on medicinal plants, focusing on their effectiveness in treating conditions like peptic ulcers, ulcerative colitis, and aphthous ulcers.
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Affiliation(s)
- Deshanda Kurniawan Prayoga
- Master Program in Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 45363, Indonesia
| | - Diah Lia Aulifa
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Sumedang, 45363, Indonesia
| | - Arif Budiman
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, Sumedang, 45363, Indonesia
| | - Jutti Levita
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, 45363, Indonesia
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Althagafi HA. The Potential Anticancer Potency of Kolaviron on Colorectal Adenocarcinoma (Caco-2) Cells. Anticancer Agents Med Chem 2024; 24:1097-1108. [PMID: 38835121 DOI: 10.2174/0118715206288807240527165444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 04/17/2024] [Accepted: 05/10/2024] [Indexed: 06/06/2024]
Abstract
BACKGROUND Globally, colorectal cancer (CRC) is categorized as the third type of cancer associated with mortalities. Chemotherapeutic drugs such as cisplatin can be used to treat cancer-affected patients. However, several adverse effects are associated with its application. This motivated the researchers to search for alternatives that are more efficient and have fewer undesirable effects. Kolaviron is a bioflavonoid that has been reported to have antioxidant and anti-inflammatory properties. AIM This study aimed to compare the anticancer effects of kolaviron and cisplatin on Caco-2 cells. The IC50 of kolaviron and cisplatin were calculated, and redox status, apoptotic-related proteins and the cell cycle were also examined. METHODS Caco-2 cells were treated with kolaviron ( ⅓, and ½ of IC50 dose) and cisplatin (IC50 dose) for 24 h and 48 h. Cell viability was assessed using the MTT protocol. Redox status and apoptotic-related proteins, in addition to the cell cycle, were examined. RESULTS The MTT assay showed the IC50 of kolaviron is 9.49 μg/mL, and that of cisplatin is 2.71 μg/ml against Caco-2 cells. Further, both doses of kolaviron significantly increased the leakage of lactate dehydrogenase (LDH), the production of reactive oxygen species (ROS), and lipoperoxidation (LPO), besides decreasing the antioxidant potency of tumor cells as revealed by the diminished reduced glutathione (GSH). At the molecular level, a significant increase in the levels of p53, cytochrome c, Bax, and caspase 3 was recorded, coupled with a decrease in the level of Bcl2, after treating the Caco-2 cells with kolaviron and cisplatin. Furthermore, kolaviron demonstrated asserted more effects on apoptosis and increased cell percentage in the subG1 phase. In addition, a notable decrease in the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 is associated with an increase in the expression of tumor protein P53 (TP53) in kolaviron-treated Caco-2 cells cancerous cells. CONCLUSION Conclusively, these data suggest that kolaviron has a potential antitumor capacity against colorectal cancer via multiple pathways, including enhancement of ROS production, redox status, p53 pathway, and apoptosis. Therefore, this study authenticated the capability of kolaviron as a valuable chemotherapeutic agent.
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Affiliation(s)
- Hussam A Althagafi
- Department of Biology, Faculty of Science, Al-Baha University, Al-Baha, Saudi Arabia
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Sun Y, Zheng C, Li T, He X, Yang F, Guo W, Song J, Gao Y, Deng C, Huang X. GB1a Activates SIRT6 to Regulate Lipid Metabolism in Mouse Primary Hepatocytes. Int J Mol Sci 2023; 24:ijms24119540. [PMID: 37298491 DOI: 10.3390/ijms24119540] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/18/2023] [Accepted: 05/26/2023] [Indexed: 06/12/2023] Open
Abstract
Lipid accumulation, oxidative stress, and inflammation in hepatocytes are features of nonalcoholic fatty liver disease (NAFLD). Garcinia biflavonoid 1a (GB1a) is a natural product capable of hepatic protection. In this study, the effect of GB1a on anti-inflammatory, antioxidant, and regulation of the accumulation in HepG2 cells and mouse primary hepatocytes (MPHs) was investigated, and its regulatory mechanism was further explored. The result showed that GB1a reduced triglyceride (TG) content and lipid accumulation by regulating the expression of SREBP-1c and PPARα; GB1a reduced reactive oxygen species (ROS) and improved cellular oxidative stress to protect mitochondrial morphology by regulating genes Nrf2, HO-1, NQO1, and Keap1; and GB1a reduced the damage of hepatocytes by inhibiting the expression of inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65. The activities of GB1a were lost in liver SIRT6-specific knockout mouse primary hepatocytes (SIRT6-LKO MPHs). This indicated that activating SIRT6 was critical for GB1a to perform its activity, and GB1a acted as an agonist of SIRT6. It was speculated that GB1a may be a potential drug for NAFLD treatment.
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Affiliation(s)
- Yongzhi Sun
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Congmin Zheng
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Ting Li
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Xinqian He
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Fan Yang
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Wenfeng Guo
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
- Institute of Science and Technology Park, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Jianping Song
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
- Institute of Science and Technology Park, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Yong Gao
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Changsheng Deng
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
- Institute of Science and Technology Park, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Xinan Huang
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
- Institute of Science and Technology Park, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
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Farombi EO, Ajayi BO, Opata EK, Fafioye AO, Akinade AT. Kolaviron modulates angiogenesis, apoptosis and inflammatory signaling in rat model of testosterone propionate-induced benign prostate hyperplasia. Inflammopharmacology 2023:10.1007/s10787-023-01171-7. [PMID: 36881348 DOI: 10.1007/s10787-023-01171-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 02/19/2023] [Indexed: 03/08/2023]
Abstract
Benign prostatic hyperplasia (BPH) is a non-malignant disease of the prostate characterized by uncontrolled proliferation of the prostate gland. Inflammation and oxidative stress have been reported to play a role in the development of BPH. Kolaviron, a bioflavonoid complex of Garcinia kola seed, has been shown to possess anti-inflammatory effect. In this study, we investigated the effect of Kolaviron on testosterone propionate (TP)-induced BPH in rats. Fifty male rats were assigned in 5 groups. Groups 1 and 2 were orally exposed to corn oil (2 ml/kg) and Kolaviron (200 mg/kg/day, p.o) for 28 days. Group 3 rats received TP (3 mg/kg/day, s.c) for 14 days while Groups 4 and 6 were treated with Kolaviron (200 mg/kg/day, p.o) and Finasteride (5 mg/kg/day, p.o), respectively, for 14 days prior to TP (3 mg/kg, s.c) co-exposure for the remaining 14 days. Administration of Kolaviron to TP-treated rats reverted histological alteration and significantly decreased prostate weight, prostate index, 5α-reductase, dihydrotestosterone, androgen receptor expression, tumor necrosis factor α, interleukin-1β, cyclooxygenase-2, prostaglandin E2, 5-lipoxygenase leukotriene B4, inducible nitric oxide synthase and nitric oxide concentration. In addition, Kolaviron alleviated TP-induced oxidative stress and reduced the expression of Ki-67, VEGF, and FGF to almost control levels. Furthermore, Kolaviron promoted apoptosis in TP-treated rats through downregulation of BCL-2 and upregulation of P53 and Caspase 3 expressions. Overall, Kolaviron prevented BPH via regulation of androgen/androgen receptor signaling, anti-oxidative and anti-inflammatory mechanisms.
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Affiliation(s)
- Ebenezer O Farombi
- Molecular Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
| | - Babajide O Ajayi
- Molecular Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Edward K Opata
- Molecular Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Abisoye O Fafioye
- Molecular Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Adetomilola T Akinade
- Molecular Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
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Ajeigbe OF, Maruf OR, Anyebe DA, Opafunso IT, Ajayi BO, Farombi EO. 6- shogaol suppresses AOM/DSS-mediated colorectal adenoma through its antioxidant and anti-inflammatory effects in mice. J Food Biochem 2022; 46:e14422. [PMID: 36125935 DOI: 10.1111/jfbc.14422] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 08/31/2022] [Accepted: 09/06/2022] [Indexed: 01/13/2023]
Abstract
Colorectal adenoma appears as benign lesions and is a precursor of colorectal adenocarcinoma. The effect of 6-Shogaol (6-[S]), a bioactive agent from ginger, in early colonic adenoma growth is unknown. As a result, this study examines the effect of 6-[S] in a mouse colorectal adenoma model induced by Azoxymethane (AOM) and dextran sulfate sodium (DSS). Adult male mice served as control in Group 1. Group 2 was treated orally with 6-[S] extract (20 mg/kg BW). Group 3 was exposed to AOM (25 mg/kg BW, ip) and one cycle of DSS (2.5%) in drinking water alone while Group 4 was co-treated with 6-[S] for twenty-one (21) days. The body weight gain, organ weight and length, oxidative stress indices, inflammatory markers and histological examination were estimated. Our findings show that 6-[S] co-treatment reversed AOM/DSS-induced elevation in colon weight, colon length, nitric oxide (NO), myeloperoxidase (MPO), hydrogen peroxidase (H2 O2 ), and tumor necrosis factor-alpha (TNF-α). However, the antioxidant enzyme activities measured namely catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione-S-transferase were significantly increased in 6-[S] treated mice. Taken together, the protective effect of 6-[S] on oxidative burden, inflammation, and histological aberration observed in the colon of the AOM/DSS model of adenoma growth in mice is mediated primarily owing to its anti-inflammatory and anti-oxidative properties. Thus, this study reveals 6-[S] as a useful agent in the possible clinical intervention of colorectal adenoma. PRACTICAL APPLICATIONS: Certain spices have been reported to have numerous phytochemicals with numerous medicinal purposes. However, no studies have been conducted to investigate the role of 6-[S], a phytochemical found in ginger, in the treatment of colorectal adenoma. The study's findings show that 6-[S] is protective in early colonic cancer development, as it manages colorectal adenoma cancer models of AOM/DSS. As a result, 6-[S]'s ability to reduce oxidative stress and inflammation in the colon may be a potential nutritional therapeutic adjuvant for colorectal adenoma.
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Affiliation(s)
- Olufunke Florence Ajeigbe
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Opeyemi Rabiat Maruf
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Daniel Abu Anyebe
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Ifeoluwa Tobi Opafunso
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Babajide Oluwaseun Ajayi
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Ebenezer Olatunde Farombi
- Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
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Grace AG, Usman MA, Ochayi MO, Adams MD, Umar HD, Obalum CD, Akunna GG, Meraiyebu AB, Onwuchekwa C. Elucidating the anti-oxidant and anti-inflammatory potentials of Triticum aestivum against ulcerative colitis: An in vivo and in silico study. PHYTOMEDICINE PLUS 2022; 2:100350. [DOI: 10.1016/j.phyplu.2022.100350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Rajagopal M, Paul AK, Lee MT, Joykin AR, Por CS, Mahboob T, Salibay CC, Torres MS, Guiang MMM, Rahmatullah M, Jahan R, Jannat K, Wilairatana P, de Lourdes Pereira M, Lim CL, Nissapatorn V. Phytochemicals and Nano-Phytopharmaceuticals Use in Skin, Urogenital and Locomotor Disorders: Are We There? PLANTS 2022; 11:plants11091265. [PMID: 35567266 PMCID: PMC9099949 DOI: 10.3390/plants11091265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 04/29/2022] [Accepted: 04/30/2022] [Indexed: 12/02/2022]
Abstract
Nanomedicines emerged from nanotechnology and have been introduced to bring advancements in treating multiple diseases. Nano-phytomedicines are synthesized from active phytoconstituents or plant extracts. Advancements in nanotechnology also help in the diagnosis, monitoring, control, and prevention of various diseases. The field of nanomedicine and the improvements of nanoparticles has been of keen interest in multiple industries, including pharmaceutics, diagnostics, electronics, communications, and cosmetics. In herbal medicines, these nanoparticles have several attractive properties that have brought them to the forefront in searching for novel drug delivery systems by enhancing efficacy, bioavailability, and target specificity. The current review investigated various therapeutic applications of different nano-phytopharmaceuticals in locomotor, dermal, reproductive, and urinary tract disorders to enhance bioavailability and efficacy of phytochemicals and herbal extracts in preclinical and in vitro studies. There is a lack of clinical and extensive preclinical studies. The research in this field is expanding but strong evidence on the efficacy of these nano-phytopharmaceuticals for human use is still limited. The long-term efficacy and safety of nano-phytopharmaceuticals must be ensured with priority before these materials emerge as common human therapeutics. Overall, this review provides up-to-date information on related contemporary research on nano-phytopharmaceuticals and nano-extracts in the fields of dermatological, urogenital, and locomotor disorders.
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Affiliation(s)
- Mogana Rajagopal
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia; (M.R.); (M.-T.L.); (A.R.J.); (C.-S.P.)
| | - Alok K. Paul
- School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7001, Australia;
| | - Ming-Tatt Lee
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia; (M.R.); (M.-T.L.); (A.R.J.); (C.-S.P.)
| | - Anabelle Rose Joykin
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia; (M.R.); (M.-T.L.); (A.R.J.); (C.-S.P.)
| | - Choo-Shiuan Por
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia; (M.R.); (M.-T.L.); (A.R.J.); (C.-S.P.)
| | - Tooba Mahboob
- School of Allied Health Sciences and World Union for Herbal Drug Discovery (WUHeDD), Walailak University, Nakhon Si Thammarat 80160, Thailand;
| | - Cristina C. Salibay
- Biologica Sciences Department, College of Science and Computer Studies, De La Salle University, Dasmarinas 4114, Philippines; (C.C.S.); (M.S.T.)
| | - Mario S. Torres
- Biologica Sciences Department, College of Science and Computer Studies, De La Salle University, Dasmarinas 4114, Philippines; (C.C.S.); (M.S.T.)
| | - Maria Melanie M. Guiang
- Department of Biology, College of Arts and Sciences, Central Mindanao University, Bukidnon 8710, Philippines;
- Center of Biodiversity Research and Extension in Mindanao (CEBREM), Central Mindanao University, Bukidnon 8710, Philippines
| | - Mohammed Rahmatullah
- Department of Biotechnology & Genetic Engineering, University of Development Alternative, Lalmatia, Dhaka 1207, Bangladesh; (M.R.); (R.J.); (K.J.)
| | - Rownak Jahan
- Department of Biotechnology & Genetic Engineering, University of Development Alternative, Lalmatia, Dhaka 1207, Bangladesh; (M.R.); (R.J.); (K.J.)
| | - Khoshnur Jannat
- Department of Biotechnology & Genetic Engineering, University of Development Alternative, Lalmatia, Dhaka 1207, Bangladesh; (M.R.); (R.J.); (K.J.)
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
- Correspondence: (P.W.); (V.N.)
| | - Maria de Lourdes Pereira
- CICECO—Aveiro Institute of Materials, Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal;
| | - Chooi Ling Lim
- Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur 57000, Malaysia;
| | - Veeranoot Nissapatorn
- School of Allied Health Sciences and World Union for Herbal Drug Discovery (WUHeDD), Walailak University, Nakhon Si Thammarat 80160, Thailand;
- Correspondence: (P.W.); (V.N.)
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Adoga JO, Channa ML, Nadar A. Type-2 diabetic rat heart: The effect of kolaviron on mTOR-1, P70S60K, PKC-α, NF-kB, SOD-2, NRF-2, eNOS, AKT-1, ACE, and P38 MAPK gene expression profile. Biomed Pharmacother 2022; 148:112736. [PMID: 35202911 DOI: 10.1016/j.biopha.2022.112736] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 11/02/2022] Open
Abstract
It has been established that genetic factors partially contribute to type-2 diabetes and vascular disease development. This study determined the effect of kolaviron on the expression profile of genes associated with the insulin signaling pathway and involved in regulating glucose and lipid metabolism, oxidative stress, inflammation, vascular functions, pro-survival and the apoptosis pathway in the heart of type-2 diabetic rats. After induction and confirmation of type-2 diabetes seven days after, the rats were treated with kolaviron for twenty-eight days before being euthanized. Organs were harvested and stored at - 80 °C in a biofreezer. Total RNA was extracted from the ventricle, reverse transcribed to cDNA followed by a real-time quantitative polymerase chain reaction (RT-qPCR) analysis of the expression of mTOR-1, P70S60K, PKC-α, NF-kB, SOD-2, NRF-2, eNOS, AKT-1, ACE, p38 MAPK and the reference gene (GAPDH), after which they were normalized/standardized. The results show an increase in the relative mRNA expression of mTOR/P70S60K/PKCα /P38MAPK/NF-KB/ACE and a decrease in the relative mRNA expression of NRF2/SOD/AKT/eNOS in the heart of the diabetic rats. Nevertheless, kolaviron modulated the expression profile of these genes, which suggest a therapeutic effect and target for vascular dysfunction and complications in type-2 diabetes through the activation of the NRF-2/AKT-1/eNOS signaling pathway and suppression of the NF-kB/PKC signaling pathway.
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Affiliation(s)
- Jeffrey O Adoga
- Department of Physiology, School of Laboratory Medicine and Medical Science, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa.
| | - Mahendra L Channa
- Department of Physiology, School of Laboratory Medicine and Medical Science, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa
| | - Anand Nadar
- Department of Physiology, School of Laboratory Medicine and Medical Science, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa
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Tesi EP, Ben‐Azu B, Mega OO, Mordi J, Knowledge OO, Awele ED, Rotu RA, Emojevwe V, Adebayo OG, Eneni OA. Kolaviron, a flavonoid‐rich extract ameliorates busulfan‐induced chemo‐brain and testicular damage in male rats through inhibition of oxidative stress, inflammatory, and apoptotic pathways. J Food Biochem 2022; 46:e14071. [DOI: 10.1111/jfbc.14071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 12/19/2021] [Accepted: 12/20/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Edesiri P. Tesi
- Department of Science Laboratory Technology Delta State Polytechnic Ogwashi‐Uku Nigeria
| | - Benneth Ben‐Azu
- Department of Pharmacology Faculty of Basic Medical Science, College of Health Sciences Delta State University Abraka Nigeria
| | - Oyovwi O. Mega
- Department of Basic Medical Sciences Achievers University Owo Nigeria
| | - Joseph Mordi
- Department of Biochemistry Faculty of Basic Medical Science, College of Health Sciences Delta State University Abraka Nigeria
| | - Obed O. Knowledge
- Department of Science Laboratory Technology Delta State Polytechnic Ogwashi‐Uku Nigeria
| | - Egbuchua D. Awele
- Department of Science Laboratory Technology Delta State Polytechnic Ogwashi‐Uku Nigeria
| | - Rume A. Rotu
- Department of Physiology Faculty of Basic Medical Science College of Medicine University of Ibadan Ibadan Nigeria
| | - Victor Emojevwe
- Department of Physiology Faculty of Basic Medical Science University of Medical Sciences Ondo Nigeria
| | - Olusegun G. Adebayo
- Neurophysiology Unit, Department of Physiology PAMO University of Medical Sciences Port‐Harcourt Nigeria
| | - Okubo Aya‐Ebi Eneni
- Department of Pharmacology and Toxicology Faculty of Pharmacy Niger Delta University Amassoma Nigeria
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Elgalil Mohamed Ahmed A, Attia MA, Abd-Elaziz MEE, Abd Ellatif R. Histological study of the effect of quercetin on experimentally induced ulcerative colitis in adult male albino rats. TANTA MEDICAL JOURNAL 2022; 50:285. [DOI: 10.4103/tmj.tmj_101_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Alrazi IMD, Ogunwa TH, Kolawole AO, Elekofehinti OO, Omotuyi OI, Miyanishi T, Maruta S. Kolaflavanone, a biflavonoid derived from medicinal plant Garcinia, is an inhibitor of mitotic kinesin Eg5. J Biochem 2021; 170:611-622. [PMID: 34264310 DOI: 10.1093/jb/mvab083] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/05/2021] [Indexed: 11/14/2022] Open
Abstract
Mitotic kinesin Eg5 remains a validated target in antimitotic therapy because of its essential role in the formation and maintenance of bipolar mitotic spindles. Although numerous Eg5 inhibitors of synthetic origin are known, only a few inhibitors derived from natural products have been reported. In our study, we focused on identifying novel Eg5 inhibitors from medicinal plants, particularly Garcinia species. Herein, we report the inhibitory effect of kolaflavanone (KLF), a Garcinia biflavonoid, on the ATPase and microtubule-gliding activities of mitotic kinesin Eg5. Additionally, we showed the interaction mechanism between Eg5 and KLF via in vitro and in silico analyses. The results revealed that KLF inhibited both the basal and microtubule-activated ATPase activities of Eg5. The inhibitory mechanism is allosteric, without a direct competition with adenosine-5'-diphosphate for the nucleotide-binding site. KLF also suppressed the microtubule gliding of Eg5 in vitro. The Eg5-KLF model obtained from molecular docking showed that the biflavonoid exists within the α2/α3/L5 (α2: Lys111-Glu116 and Ile135-Asp149, α3: Asn206-Thr226; L5: Gly117-Gly134) pocket, with a binding pose comparable to known Eg5 inhibitors. Overall, our data suggest that KLF is a novel allosteric inhibitor of mitotic kinesin Eg5.
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Affiliation(s)
- Islam M D Alrazi
- Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan
| | - Tomisin H Ogunwa
- Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan
| | - Ayodele O Kolawole
- Department of Biochemistry, The Federal University of Technology, Akure, Ondo State, PMB 704, Nigeria
| | - Olusola O Elekofehinti
- Department of Biochemistry, The Federal University of Technology, Akure, Ondo State, PMB 704, Nigeria
| | - Olaposi I Omotuyi
- Centre for Biocomputing and Drug Design, Biochemistry Department, Adekunle Ajasin University, Akungba-Akoko, Ondo State, PMB 001, Nigeria
| | - Takayuki Miyanishi
- Graduate School of Fisheries and Environmental Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan
| | - Shinsaku Maruta
- Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo 192-8577, Japan
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13
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Attah OC, Umar IA, Ameh DA, Forcados GE, Muhammad A, Sani I. Kolaviron pre-treatment suppresses 7, 12 dimethylbenzanthracene-induced alterations in estrogen receptor-α, CYP 1A1, oxidative stress and inflammation in female Wistar rats. J Food Biochem 2021; 46:e13984. [PMID: 34936107 DOI: 10.1111/jfbc.13984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 10/04/2021] [Accepted: 10/17/2021] [Indexed: 11/30/2022]
Abstract
Due to the need to develop locally available, cheaper, and efficacious treatment regimens for breast cancer, the chemopreventive effect of kolaviron (KV), an extract of Garcinia kola seeds was examined. Fifty (50) female Wistar rats (120-180 g) were assigned to five groups (control group, 7, 12 dimethylbenzanthracene [DMBA] groups, tamoxifen group) of 10 rats each. They were pre-treated with KV thrice a week for four weeks except control. Estrogen receptor-α (ER-α) levels were determined in the pre-treated rats before induction of mammary carcinogenesis. After the four weeks pre-treatment period, 80 mg/kg of DMBA was used for induction. A hundred and fifty (150) days after induction, the rats were sacrificed humanely. Significantly higher levels of ER-α, formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, increased cytokines (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]), CYP1A1 activity and malondialdehyde (MDA) with a corresponding decrease in superoxide dismutase (SOD), catalase and glutathione peroxidase were observed in DMBA-induced rats. Pre-treatment with KV at 200 mg/kg body weight significantly (p < .05) decreased ER-α levels by 19.01% and 37.52%, [IL-6] by 36.37% and 20.55%, TNF-α by 42.2% and 12.33% in serum and mammary tissue respectively. Also, a significant (p < .05) decrease in serum CYP1A1 activity, MDA with concomitant increase in SOD, catalase and glutathione peroxidase activities were observed in serum and mammary tissue respectively. Collectively, the results suggest that KV could be further explored in targeting chemoprevention of DMBA-induced mammary damage. PRACTICAL APPLICATIONS: Garcinia kola is widely cultivated in West and Central Africa with kolaviron (KV) as its major constituents. The seeds which have a bitter astringent taste are widely consumed by people in the region. Locals claim that consumption of the seeds provides relief for the management of several ailments including cancer. However, scientific investigations that provide a basis for these claims are still needed. This study provides evidence that points to the ameliorative potential of KV on breast cancer model. The results will be beneficial to local communities who hitherto had no knowledge on the potential of G. kola in chemoprevention. The results from this study will also attract further research attention from the international scientific community to examine the anti-cancer benefits of G. kola. This will also be beneficial to the global community due to the increasing number of breast cancer cases recorded annually.
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Affiliation(s)
- O C Attah
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - I A Umar
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - D A Ameh
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - G E Forcados
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - A Muhammad
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - I Sani
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria
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14
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Adoga JO, Channa ML, Nadar A. Kolaviron attenuates cardiovascular injury in fructose-streptozotocin induced type-2 diabetic male rats by reducing oxidative stress, inflammation, and improving cardiovascular risk markers. Biomed Pharmacother 2021; 144:112323. [PMID: 34656062 DOI: 10.1016/j.biopha.2021.112323] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 10/02/2021] [Accepted: 10/08/2021] [Indexed: 01/01/2023] Open
Abstract
The prevalence of cardiovascular disease among type-2 diabetic patients has become a source of major concern world over. This study explored the protective effect of kolaviron, a bioflavonoid, against oxidative cardiovascular injury in fructose- streptozotocin-induced type 2 diabetic male Sprague Dawley rats. After acclimatization, induction, and confirmation of type-2 diabetes, kolaviron was administered for 28days, after which the animals were anesthetized with Isofor and euthanized. Blood from each rat were collected, and blood samples were then centrifuged for serum and plasma. Cardiac troponin I (cTnI), creatine kinase myocardial band (CK-MB), Creatine phosphokinase (CK), and insulin levels were immediately determined in serum, while remaining samples (serum, plasma, and organs) were stored in the bio-freezer at - 80 °C and 10% formalin for enzyme-link immunosorbent assay (ELISA), biochemical, molecular, and histopathological studies. The results show that type-2 diabetes induction with fructose and streptozotocin led to increased blood glucose levels, decreased insulin levels and cardiac antioxidant enzyme activities, increased malondialdehyde levels, cardiac biomarkers and pro-inflammatory cytokines levels, resulted in abnormal lipid profile, increased blood pressure and angiotensin-converting enzyme (ACE) activity, and decreased plasma endothelial nitric oxide synthase (eNOS) concentration. The histopathological examination of the cardiac tissue revealed severe lesion, hypertrophy, and myofibrils degeneration. However, administration of kolaviron for 28days remarkably improved these conditions. Hence the result from the study validates the potency of kolaviron, and suggests it could serve as an alternative to existing remedy in ameliorating or protecting against cardiovascular injury in type-2 diabetes.
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MESH Headings
- Animals
- Anti-Inflammatory Agents/pharmacology
- Antioxidants/pharmacology
- Biomarkers/blood
- Blood Glucose/drug effects
- Blood Glucose/metabolism
- Blood Pressure/drug effects
- Diabetes Mellitus, Experimental/chemically induced
- Diabetes Mellitus, Experimental/drug therapy
- Diabetes Mellitus, Experimental/metabolism
- Diabetes Mellitus, Type 2/chemically induced
- Diabetes Mellitus, Type 2/drug therapy
- Diabetes Mellitus, Type 2/metabolism
- Diabetic Cardiomyopathies/etiology
- Diabetic Cardiomyopathies/metabolism
- Diabetic Cardiomyopathies/pathology
- Diabetic Cardiomyopathies/prevention & control
- Flavonoids/pharmacology
- Fructose
- Inflammation Mediators/blood
- Insulin/blood
- Lipids/blood
- Male
- Myocytes, Cardiac/drug effects
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- Oxidative Stress/drug effects
- Peptidyl-Dipeptidase A/blood
- Rats, Sprague-Dawley
- Streptozocin
- Rats
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Affiliation(s)
- Jeffrey O Adoga
- Department of Physiology, School of Laboratory Medicine and Medical Science, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa.
| | - Mahendra L Channa
- Department of Physiology, School of Laboratory Medicine and Medical Science, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa
| | - Anand Nadar
- Department of Physiology, School of Laboratory Medicine and Medical Science, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa
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15
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Abd Rashid N, Abd Halim SAS, Teoh SL, Budin SB, Hussan F, Adib Ridzuan NR, Abdul Jalil NA. The role of natural antioxidants in cisplatin-induced hepatotoxicity. Biomed Pharmacother 2021; 144:112328. [PMID: 34653753 DOI: 10.1016/j.biopha.2021.112328] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 10/05/2021] [Accepted: 10/08/2021] [Indexed: 12/13/2022] Open
Abstract
Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses. In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver. Various natural products, plant extracts and oil rich in flavonoids, terpenoids, polyphenols, and phenolic acids were able to minimize oxidative stress by restoring the level of antioxidant enzymes and acting as an anti-inflammatory agent. Likewise, treatment with honey and royal jelly was demonstrated to decrease serum transaminases and scavenge free radicals in the liver after cisplatin administration. Medicinal properties of these natural products have a promising potential as a complementary therapy to counteract cisplatin-induced hepatotoxicity. This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.
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Affiliation(s)
- Norhashima Abd Rashid
- Department of Biomedical Science, Faculty of Applied Science, Lincoln University College, Selangor, Malaysia.
| | | | - Seong Lin Teoh
- Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
| | - Siti Balkis Budin
- Center for Diagnostic, Therapeutic and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
| | - Farida Hussan
- Human Biology Department, School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia.
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16
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Yu Y, Zheng C, Lu X, Deng C, Xu Q, Guo W, Wu Q, Wang Q, Liu C, Huang X, Song J. GB1a Ameliorates Ulcerative Colitis via Regulation of the NF-κB and Nrf2 Signaling Pathways in an Experimental Model. Front Med (Lausanne) 2021; 8:654867. [PMID: 34557497 PMCID: PMC8452853 DOI: 10.3389/fmed.2021.654867] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Accepted: 08/09/2021] [Indexed: 11/13/2022] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease. The intake of African Garcinia Kola nuts has been reported as a therapy for diarrhea and dysentery in the African population. However, the mechanism of action through which Garcinia Kola nuts act to ameliorates UC remains unknown. GB1a is the main active component of Garcinia Kola nuts. In this study, we explored the therapeutic effects and underlying mechanism of GB1a on dextran sodium sulfate (DSS)-induced UC. Human Colonic Epithelial Cells (HCoEpic) were challenged with TNF-α to test the effects of GB1a in protecting against oxidative stress and inflammation in vitro. Our data showed that GB1a significantly attenuated DSS-induced colonic inflammatory injury manifested as reversed loss of body weight and disease activity index (DAI) scores in UC mice. We also showed that GB1a improved the permeability of the intestinal epithelium by modulating the expression of tight junction proteins (ZO-1, Occludin). Mechanistically, GB1a may activate the Nrf2 antioxidant signaling pathway and suppress the nuclear translocation of NF-κB in reduced oxidative stress and expression of inflammatory genes induced by TNF-α in HCoEpic cells. Our study suggests that GB1a alleviates inflammation, oxidative stress and the permeability of the colonic epithelial mucosa in UC mice via the repression of NF-κB and activation of Nrf2 signaling pathway.
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Affiliation(s)
- Yuanyuan Yu
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Congmin Zheng
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xu Lu
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Changsheng Deng
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital and The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qin Xu
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital and The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wenfeng Guo
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital and The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qingye Wu
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qi Wang
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Changhui Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xinan Huang
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital and The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jianping Song
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital and The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
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17
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Adewole KE, Ishola AA, Omolaso BO. Identification of potential histone deacetylase inhibitory biflavonoids from Garcinia kola (Guttiferae) using in silico protein-ligand interaction. PHYSICAL SCIENCES REVIEWS 2021. [DOI: 10.1515/psr-2020-0099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
Overactivity of histone deacetylases (HDACs) is the underlying cause of some cancers, thus, inhibiting their overactivities is a rational treatment option. However, endeavors to employ current anti-HDACs agents in cancer treatment have yielded limited success. Consequently, there is need to explore anti-HDACs natural products, especially from plants sources, because of the intimate relationship plant products and drug discovery have enjoyed over the centuries. To identify possible HDACs inhibitors, Garcinia kola (Guttiferae) seed-derived compounds were screened in silico for HDAC-inhibitory tendencies because of their reported anticancer potentials. Fifteen G. kola-derived compounds and givinostat were docked with five selected HDACs using AutodockVina, while the binding interactions of the compounds with high binding affinities for the five HDACs were viewed with Discovery Studio Visualizer BIOVIA, 2016. Results indicated that four of the compounds studied, including amentoflavone, Garcinia biflavonoid 1, Garcinia biflavonoid 2 and kolaflavanone have higher binding propensity for all the five HDACs relative to givinostat, the standard HDAC inhibitor. This study indicated that inhibition of HDAC might be another key mechanism accountable for the bioactivities of G. kola and its intrinsic compounds. The results from this study implied that the compounds could be further investigated as drugable HDAC inhibitors with potential pharmacological applications in the treatment of cancers.
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Affiliation(s)
- Kayode E. Adewole
- Department of Biochemistry, Faculty of Basic Medical Sciences , University of Medical Sciences , Ondo City , Ondo State , Nigeria
| | - Ahmed A. Ishola
- Central Research Laboratories Limited , University Road , Ilorin , Kwara State , Nigeria
| | - Blessing O. Omolaso
- Department of Physiology, Faculty of Basic Medical Sciences , University of Medical Sciences , Ondo City , Ondo State , Nigeria
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18
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Wang C, Han Z, Wu Y, Lu X, Tang X, Xiao J, Li N. Enhancing stability and anti-inflammatory properties of curcumin in ulcerative colitis therapy using liposomes mediated colon-specific drug delivery system. Food Chem Toxicol 2021; 151:112123. [PMID: 33744379 DOI: 10.1016/j.fct.2021.112123] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 03/04/2021] [Accepted: 03/09/2021] [Indexed: 02/07/2023]
Abstract
Curcumin liposomes (CUR-LPs) was identified by evaluating morphology, appearance, zeta potential, particle diameter, and drug encapsulation efficiency. The results indicated that particle diameter, surface charge and polydispersity index (PDI) of curcumin (CUR)-loaded anionic liposomes were 167 nm, -34 mV and 0.09, respectively. CUR-LPs is high stable pseudo-pH-sensitive nanoparticles system which has a favorable stability in simulated gastric fluid and slower degradation rate allowing CUR sustained release for prolonged times in simulated intestinal fluid. Within 1 h, the CUR consumption was 21.82% in simulated gastric fluid (SGF) and 27.32% in simulated intestinal fluid (SIF), respectively. CUR-LPs could attenuate clinical symptoms including weight loss, diarrhea and fecal bleeding. Especially, it could also prevent dextran sulfate sodium salt (DSS)-inducedcolon tissue damage and colon shortening, and reduce the production of malondialdehyde (MDA), colonic myeloperoxidase (MPO), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in animal model. Our study illustrated that liposomes (LPs) was a potential carrier to develop the colon-specific drug delivery system incorporating CUR for treating ulcerative colitis.
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Affiliation(s)
- Chaofan Wang
- Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Tai'an, Shandong Province, 271018, PR China.
| | - Zhenlin Han
- Department of Molecular Biosciences and Bioengineering, University of Hawaii at 10Manoa, Honolulu, HI, 96822, USA.
| | - Yuhao Wu
- Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Tai'an, Shandong Province, 271018, PR China.
| | - Xiaoming Lu
- Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Tai'an, Shandong Province, 271018, PR China.
| | - Xiaozhen Tang
- Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Tai'an, Shandong Province, 271018, PR China.
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food 12Science, Faculty of Food Science and Technology, University of Vigo -Ourense Campus, E-32004, Ourense, Spain; International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, 212013, China.
| | - Ningyang Li
- Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Tai'an, Shandong Province, 271018, PR China.
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Erukainure OL, Salau VF, Chukwuma CI, Islam MS. Kolaviron: A Biflavonoid with Numerous Health Benefits. Curr Pharm Des 2021; 27:490-504. [PMID: 33185157 DOI: 10.2174/1381612826666201113094303] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 07/23/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND The increasing interests on the healing properties of medicinal plants have led to a paradigm shift from the use of synthetic drug to the search of natural medicines for the treatment and management of several diseases. Like other phenolics flavonoids have been continuously explored for their medicinal benefits, with their potent antioxidant activity being a major interest. Kolaviron (KVN) is a biflavonoid isolated from Garcinia kola Heckel, which has been reported for its potent antioxidant and anti-inflammatory properties. These properties have been explored in several disease models including reproductive toxicity, cardiotoxicity, diabetes mellitus, gastrotoxicity and hepatotoxicity. OBJECTIVES The present study was aimed to review the reported medicinal properties of KVN in order to provide some guidelines and direction to researchers on KVN research. METHODS A literature search was conducted with the aim of identifying peer-reviewed published data on KVN and their biological activities. Different academic and/or scientific search engines were utilized including but not limited to Google Scholar, PubMed, ScienceDirect and so on. RESULTS Among all the studied disease models obtained from the literatures, the effect of KVN on reproductive toxicity was the most studied as it represented 25% of all the studies, followed by neuroprotective, cardioprotective and hepatoprotective activities of Kolaviron. From our identified studies, KVN has been shown to have antidiabetic, cardioprotective, neuroprotective, hematoprotective, nephroprotective, gastroprotective, hepatoprotective activities. KVN also has effects on malaria and reproductive health, which can be explored for novel drug and nutraceutical developments for related ailments. Unfortunately, while toxicity data are lacking, most studies are limited to in vitro and/or in vivo models, which may impede translation in this area of research. CONCLUSION Based on data gathered from the literature search, it is evident that KVN possesses numerous health benefits, which can be attributed to its potent antioxidant and anti-inflammatory activities. However, more studies are required in this area of research to validate the medicinal value of kolaviron, which may positively influence the economic value of plant, Garcinia kola.
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Affiliation(s)
- Ochuko L Erukainure
- Department of Biochemistry, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa
| | - Veronica F Salau
- Department of Biochemistry, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa
| | - Chika I Chukwuma
- Center on Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, 9300, Free State, South Africa
| | - Md Shahidul Islam
- Department of Biochemistry, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa
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20
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Suleiman RB, Muhammad A, Umara IA, Ibrahima MA, Erukainure OL, Forcados GE, Katsayal SB. Kolaviron Ameliorates 7, 12-Dimethylbenzanthracene - Induced Mammary Damage in Female Wistar Rats. Anticancer Agents Med Chem 2021; 22:181-192. [PMID: 34225638 DOI: 10.2174/1871520621666210322101232] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 12/27/2020] [Accepted: 01/25/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Kolaviron (KV) is a flavonoid rich portion obtained from Garcinia kola seeds with a number of reported pharmacological effects. However, its ameliorative effects on 7,12-Dimethylbenzanthracene (DMBA)-induced mammary damage has not been fully investigated, despite the reported use of the seeds in the treatment of inflammatory related disorders. OBJECTIVE To evaluate the ameliorative effects of KV on DMBA-induced mammary damage in female Wistar rats. METHODS Forty-nine (49) female Wistar rats were randomly assigned into seven groups of seven rats each. DMBA was administered orally to rats in five of the groups as a single dose of 80 mg/kg body wt while the remaining two groups received the vehicle. The rats were palpated weekly for 3 months to monitor tumor formation. After 3 months of DMBA administration, 1 ml of blood was collected to assay for estrogen receptor- α (ER-α) level. Thereafter, the vehicle (dimethyl sulfoxide) was daily administered to the negative control and positive control groups for the 14 days duration of the experiment while three groups were each given a daily oral dose of 50, 100 and 200 mg/kg body wt of KV for the duration of the experiment. The last DMBA-induced group received 10 mg/kg body wt of the standard drug tamoxifen twice in a week and the remaining DMBA-free group received 200 mg/kg body wt KV. Subsequently, the animals were humanly sacrificed and ER-α, sialic acids, sialidase, sialyltransferase levels were assay for in blood and mammary tissues followed by histopathological examinations. RESULTS Significantly higher levels of estrogen receptor-α (ER-α), formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration and increased sialylation were detected in DMBA-induced rats. Treatment with KV at 50, 100 and 200 mg/kg body weight resulted in a significant (p<0.05) decrease in ER-α level, significantly (p<0.05) lower free serum sialic acid (21.1%), total sialic acid level of the mammary tissue (21.57%), sialyltransferase activity (30.83%) as well as mRNA level of the sialyltransferase gene (ST3Gal1) were observed after KV interventions. CONCLUSION The findings suggest that KV could be further explored in targeting DMBA-induced mammary damage implicated in mammary carcinogenesis.
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Affiliation(s)
- Rabiatu B Suleiman
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Aliyu Muhammad
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Ismaila A Umara
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Mohammed A Ibrahima
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Ochuko L Erukainure
- Department of Pharmacology, University of the Free State, Bloemfontein 9300. South Africa
| | - Gilead E Forcados
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Sanusi B Katsayal
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
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21
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Omayone TP, Olaleye SB. Biochemical and histopathological effects of low dose vanadium in the healing of acetic acid-induced colitis in male wistar rats. J Basic Clin Physiol Pharmacol 2021; 33:273-283. [PMID: 33592685 DOI: 10.1515/jbcpp-2020-0246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 10/31/2020] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Vanadium has been reported to possess relevant therapeutic properties such as anti-diabetic and anti-tumoral. This study aimed at determining the effects of vanadium on experimentally induced colitis in rats. METHODS Forty-five male Wistar rats (103 ± 3.90 g, n=15) were used for this study and were divided into three groups. Group 1 (Untreated control) had nothing added to their drinking, while groups 2 and 3 received sodium metavanadate at a dose of 50 and 200 mg/L respectively in their drinking water for 10 weeks. Colitis was thereafter induced by intra colonic administration of 1.50 mL of 6% acetic acid. Animals were sacrificed on day 0 (pre-induction), three- and seven-days post induction. Blood samples were collected for haematological variables and the distal 8 cm of the colon was collected for macroscopic, histological and biochemical (malondialdehyde-MDA, superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase- GPx and nitrite concentration- NO) assessment. RESULTS Low dose vanadium proved beneficial in ameliorating acetic acid-induced colitis by improving both histopathological and haematological changes. Gross observation showed a faster healing rate in vanadium treated groups (50 and 200 mg/L) compared with untreated control at day 3 (40 and 26.20 vs. 2.50%) and day 7 (80 and 66.70 vs. 42%) respectively. Vanadium also appears to exert its beneficial effects on acetic acid-induced colitis via up regulation of antioxidant enzymes (SOD, CAT, GPx) and NO while decreasing the over production of MDA. CONCLUSIONS Vanadium at small concentration functions as an essential trace element and may be able to promote healing process during ulcerative colitis.
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Affiliation(s)
- Tosan Peter Omayone
- Gastrointestinal Secretion and Inflammation Research Unit, Department of Physiology, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Oyo State, Nigeria.,Department of Physiology, School of Health and Health Technology, Federal University of Technology Akure, Akure, Nigeria
| | - Samuel Babafemi Olaleye
- Gastrointestinal Secretion and Inflammation Research Unit, Department of Physiology, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Oyo State, Nigeria
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22
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Farombi EO, Awogbindin IO, Olorunkalu PD, Ogbuewu E, Oyetunde BF, Agedah AE, Adeniyi PA. Kolaviron protects against nigrostriatal degeneration and gut oxidative damage in a stereotaxic rotenone model of Parkinson's disease. Psychopharmacology (Berl) 2020; 237:3225-3236. [PMID: 32651640 DOI: 10.1007/s00213-020-05605-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 06/29/2020] [Indexed: 12/16/2022]
Abstract
The asymptomatic and clinical stages of Parkinson's disease (PD) are associated with comorbid non-motor symptoms including gastrointestinal (GI) dysfunction. Although the neuroprotective and gastroprotective roles of kolaviron (KV) have been reported independently, whether KV-mediated GI-protective capacity could be beneficial in PD is unknown. We therefore investigated the modulatory effects of KV on the loss of dopaminergic neurons, locomotor abnormalities, and ileal oxidative damage when rats are lesioned in the nigrostriatal pathway. KV treatment markedly suppressed the behavioral deficit and apomorphine-induced rotations associated with rotenone lesioning. KV attenuated the loss of nigrostriatal dopaminergic neurons and perturbations in the striatal glucose-regulated protein (GRP78) and X-box binding protein 1 (XBP1) levels. Ileal epithelial injury following stereotaxic rotenone infusion was associated with oxidative stress and marked inhibition of acetylcholine esterase activity and reduced expression of occludin in the crypt and villi. While KV treatment attenuated the redox imbalance in the gut and enhanced occludin immunoreactivity, acetylcholinesterase activity was not affected. Our data demonstrate ileal oxidative damage as a characteristic non-motor gut dysfunction in PD while showing the potential dual efficacy of KV in the attenuation of both neural defects and gut abnormalities associated with PD.
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Affiliation(s)
- Ebenezer O Farombi
- Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria.
| | - Ifeoluwa O Awogbindin
- Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria
| | - Precious D Olorunkalu
- Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria
| | - Emmanuel Ogbuewu
- Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria
| | - Bisola F Oyetunde
- Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria
| | - Alberta E Agedah
- Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria
| | - Philip A Adeniyi
- Cell Biology and Neurotoxicity Unit, Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado Ekiti, Ekiti State, Nigeria
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23
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Shin DW, Lim BO. Nutritional Interventions Using Functional Foods and Nutraceuticals to Improve Inflammatory Bowel Disease. J Med Food 2020; 23:1136-1145. [PMID: 33047999 DOI: 10.1089/jmf.2020.4712] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal tract, the second largest organ in the body, plays an important role in nutrient and mineral intake through the intestinal barrier. Dysfunction of intestinal permeability and related disorders commonly occur in patients with inflammatory bowel disease (IBD), one of the health problems in the Western societies that are considered to be mainly due to the Western diet. Although the exact etiology of IBD has not been elucidated, environmental and genetic factors may be involved in its pathogenesis. Many synthetic or biological drugs, such as 5-aminosalicylic acid corticosteroids as anti-inflammatory drugs, have been used clinically to treat IBD. However, their long-term use exhibits some adverse health consequences. Therefore, many researchers have devised alternative therapies to overcome this problem. Many studies have revealed that some functional nutrients in nature can relieve gastrointestinal inflammation by controlling proinflammatory cytokines. In this study, we review the ability of functional nutraceuticals such as phytochemicals, fatty acids, and bioactive peptides in improving IBD by regulating its underlying pathogenic mechanisms.
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Affiliation(s)
- Dong Wook Shin
- College of Biomedical and Health Science, Konkuk University, Chungju, Korea
| | - Beong Ou Lim
- College of Biomedical and Health Science, Konkuk University, Chungju, Korea.,Research Institute of Inflammatory Disease, Konkuk University, Chungju, Korea
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24
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Anticolitic Effect of Berberine in Rat Experimental Model: Impact of PGE2/p38 MAPK Pathways. Mediators Inflamm 2020; 2020:9419085. [PMID: 33061833 PMCID: PMC7542536 DOI: 10.1155/2020/9419085] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 07/24/2020] [Accepted: 08/01/2020] [Indexed: 12/13/2022] Open
Abstract
Berberine (BER), a natural isoquinoline alkaloid, has been demonstrated to have appreciable anticolitis effects. Nevertheless, the protective mechanism of BER in ulcerative colitis (UC) is barely understood. The present study was aimed at exploring the therapeutic efficacy of BER on UC in experimental colitis rat model. Rats were orally administered with BER for seven days at low and high doses (25 and 50 mg/kg/day) before AcOH intracolonic instillation. BER significantly retrieved colon inflammation and mucosal damage indicated by inhibition of macroscopic score and lessened the levels of inflammatory biomarkers (IL-1β, IL-6, TNF-α, MPO, and PGE2). Notable downregulation of mRNA expression of p38 MAPK and increased protein expression of TGF-β were achieved by BER treatment. The anti-inflammatory potential of BER was supported by the histopathological screening of colon mucosa. In addition, BER restored colonic antioxidant capacity through elevation of GSH level and antioxidant enzymatic activities (SOD, CAT, GPx, and GR) together with reductions of both MDA and NO levels. Marked downregulation of Nos2 mRNA expression is accompanied by increased Nrf2 and Hmox-1 expressions in colon specimens treated by BER. Furthermore, BER exhibited noticeable antiapoptotic activities through decreasing proapoptotic proteins (Bax and caspase-3) and lessening antiapoptotic Bcl-2 protein in the colon mucosa. Based on these findings, BER may improve colitis markedly which may be mediated by its striking antioxidant, anti-inflammatory, and antiapoptotic properties.
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25
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Dozie-Nwakile OC, Dozie NC, Kingsley UI, Catherine OF, Felicia ON. Effects of Kolaviron on Pneumonia-like Infection Induced in Albino Wistar Rats. Antiinflamm Antiallergy Agents Med Chem 2020; 20:219-227. [PMID: 32933465 DOI: 10.2174/1871523019666200915085729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 08/11/2020] [Accepted: 08/21/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Pneumonia is an acute or chronic inflammatory disorder of the lungs, affecting the mucosal areas of the lung. It can be caused by bacteria, viruses or fungi. In some cases, it may be caused by physical or chemical irritants. Kolaviron, a natural bioflavonoid extract from Garcinia kola seeds, has been shown to possess anti-inflammatory properties in Flu-like conditions which are associated with cough. There has been a paucity of information on the likelihood of the effectiveness of kolaviron against pneumonia infections. OBJECTIVE To evaluate the antibacterial and anti-inflammatory effects of kolaviron on albino Wistar rats induced with pneumonia using Klebsiella pneumonia. MATERIALS AND METHODS Powdered Garcinia kola seeds were extracted with n-hexane and 100% methanol as solvents by using Soxhlet extractor. A standard method was used to obtain kolaviron from the seed extracts. A total of 24 albino Wistar rats were randomly divided into six groups A to F, each comprising four rats. The rats were allowed to acclimatize for 1 hour in very cold environments using ice packs. A standardized 1.0 x10 -5 mg/ml culture suspension was intranasally inoculated to the rats for 10 days to induce pneumonia-like symptoms. Thereafter, the kolaviron was administered to the rats such that a 500mg/kg kolaviron extract was given once daily to groups A (male rats) and B (female rats). Groups C (male rats) and D (female rats) received 250mg/kg of kolaviron extract once daily, while group E rats were given 0.5 ml of dimethyl sulfoxide (DMSO) once daily, which served as the negative control. The rats in Group F received 2.86 mg/kg of ofloxacin once daily and served as the positive control. All the treatments were done for a period of 5 days. Then 10 days after the treatments, the animals were sacrificed and the lungs were harvested for hydrostatic lung test and histopathological examination. An overnight broth culture of Klebsiella pneumonia was streaked in sterile molten nutrient agar maintained at 37°C for 24hrs. Later, a stock of 500mg/ml of kolaviron was prepared in DMSO. Two-fold dilutions were performed to obtain the following concentrations of 100%, 50%, 25%, 12.5%, 6.25%, 3.125%, and 1.565% with the stock. The anti-Klebsiella pneumonia activity of the kolaviron extract was determined using agar well diffusion methods and incubation was done at 37 o C for 24 hrs. Student t-test and Oneway Analysis of variance (ANOVA) were used for comparison of mean differences between and among the groups. RESULTS AND DISCUSSION The sensitivity of Klebsiella pneumonia to kolaviron was concentration- dependent. There was an increase in anti-Klebsiella pneumonia activity with a decrease in kolaviron concentration. Kolaviron (KV), at 500mg/kg concentration, was efficacious and showed significant anti-inflammatory effects (P<0.0001). This was also confirmed in the histopathological examinations. The 3.125% concentration of the kolaviron gave IZDs that ranged from 25.68±3.33 mm on day 1 to 27.33±2.78 mm on day 5. Treatment with kolaviron showed to be sex-dependent with a significant difference (p<0.0001), when pre-treatment and post-treatment effects were compared between male and female rats. CONCLUSION Kolaviron can be used as an agent in the treatment of pneumonia as it possesses anti- inflammatory and anti-Klebsiella pneumonia activities.
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Affiliation(s)
- Ogechukwu Calista Dozie-Nwakile
- Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, College of Medicine, University of Nigeria, Enugu Campus, Nsukka, Enugu State, Nigeria
| | - Nwakile Calistus Dozie
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences Nnamdi Azikiwe University, Awka, Anambra State, Nigeria
| | - Uchendu Ikenna Kingsley
- Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, College of Medicine, University of Nigeria, Enugu Campus, Nsukka, Enugu State, Nigeria
| | - Okonkwo Francis Catherine
- Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, College of Medicine, University of Nigeria, Enugu Campus, Nsukka, Enugu State, Nigeria
| | - Onyemelukwe Ngozi Felicia
- Department of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, College of Medicine, University of Nigeria, Enugu Campus, Nsukka, Enugu State, Nigeria
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26
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Omotoso GO, Mutholib NY, Abdulsalam FA, Bature AI. Kolaviron protects against cognitive deficits and cortico-hippocampal perturbations associated with maternal deprivation in rats. Anat Cell Biol 2020; 53:95-106. [PMID: 32274254 PMCID: PMC7118269 DOI: 10.5115/acb.19.160] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 09/23/2019] [Accepted: 10/04/2019] [Indexed: 11/27/2022] Open
Abstract
Prolonged separation of pups from their mother in early postnatal period can interfere with normal growth and development, resulting in different behavioral changes similar to features of schizophrenia in man. This study explored the cytoprotective action of kolaviron, a biflavonoid, on the prefrontal cortex and hippocampus of maternally deprived Wistar rats. Eight months old female rats were time-mated, and after delivery their pups were randomly assigned into four groups; group A received 0.5 ml of normal saline, group B received kolaviron orally (200 mg/kg/bw) on postnatal days (PND) 21–35, group C were maternally deprived on PND 9 for 24 hours, while group D were also maternally deprived on PND 9 for 24 hours, and then received kolaviron orally (200 mg/kg/bw) on PND 21–35. Behavioral studies (open field test, Morris water test, and Y-maze test) were conducted after the experiment prior to sacrifice. Some of the rats were anesthetized with ketamine and perfusion-fixed with 0.1 M phosphate buffered saline and 4% paraformaldehyde, while others were sacrificed by cervical dislocation for enzyme studies. The hippocampus and prefrontal cortex were excised from the brain and processed for tissue histology, histochemistry, and enzymatic analysis. Results revealed behavioral deficits, oxidative stress, degenerative changes, and astrocytosis in the prefrontal cortex and hippocampus of maternally deprived rats, but intervention with kolaviron caused significant improvement in neurobehavior, morphology, and neurochemistry in these brain areas. We concluded that kolaviron could protect the brain against neurological consequences of nutritional and environmental insults arising from maternal separation in early postnatal period.
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Affiliation(s)
- Gabriel Olaiya Omotoso
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | | | | | - Abdulkabir I Bature
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
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27
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Kim M, Chung KS, Hwang SJ, Yoon YS, Jang YP, Lee JK, Lee KT. Protective Effect of Cicer arietinum L. (Chickpea) Ethanol Extract in the Dextran Sulfate Sodium-Induced Mouse Model of Ulcerative Colitis. Nutrients 2020; 12:nu12020456. [PMID: 32059355 PMCID: PMC7071501 DOI: 10.3390/nu12020456] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/07/2020] [Accepted: 02/10/2020] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a major risk factor of colorectal cancer. Drugs currently used for IBD exhibit adverse effects including vomiting, nausea, and diarrhea. Naturally derived novel alternative therapies are required to overcome these limitations. In this study, we investigated the protective effects of ethanol extract of Cicer arietinum (CEE) in a dextran sodium sulfate (DSS)-induced mouse model of colitis. CEE markedly improved DSS-induced clinical symptoms and histological status, such as the disease activity index, spleen weight, and colon length. Moreover, CEE-treated mice showed significant recovery of DSS-induced crypt damage and cell death. CEE suppressed myeloperoxidase (MPO) activity and macrophage marker F4/80 mRNA expression in colonic tissue of mice with DSS-induced colitis, indicating neutrophil infiltration and macrophage accumulation, respectively. Although DSS upregulated pro-inflammatory mediators and activated transcription factors, CEE downregulated the mRNA expression of cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α, protein expression of cyclooxygenase-2 and inducible nitric oxide synthase, as well as activation of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Hence, our findings reveal that the anti-inflammatory properties of CEE, involving the downregulation of the expression of pro-inflammatory mediators by inactivating NF-κB and STAT3 in DSS-induced colitis mice.
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Affiliation(s)
- Mia Kim
- Department of Cardiovascular and Neurologic Disease (Stroke Center), College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea;
| | - Kyung-Sook Chung
- Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea; (K.-S.C.); (S.-J.H.)
| | - Se-Jung Hwang
- Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea; (K.-S.C.); (S.-J.H.)
| | - Ye Seul Yoon
- Department of Basic Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea;
| | - Young Pyo Jang
- Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea;
- Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea
| | - Jong Kil Lee
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea;
| | - Kyung-Tae Lee
- Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea; (K.-S.C.); (S.-J.H.)
- Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea;
- Correspondence: ; Tel.: +82-2-961-0860; Fax: +82-2-966-3885
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28
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Xu K, Yang C, Xu Y, Li D, Bao S, Zou Z, Kang F, Tan G, Li SM, Yu X. Selective geranylation of biflavonoids by Aspergillus terreus aromatic prenyltransferase (AtaPT). Org Biomol Chem 2020; 18:28-31. [DOI: 10.1039/c9ob02296a] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Regio-selective geranylation of natural biflavonoids using Aspergillus terreus aromatic prenyltransferase (AtaPT) as an efficient catalyst.
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Affiliation(s)
- Kangping Xu
- School of Pharmaceutical Sciences
- Central South University
- Changsha
- People's Republic of China
| | - Can Yang
- School of Pharmaceutical Sciences
- Central South University
- Changsha
- People's Republic of China
| | - Yuanyuan Xu
- School of Pharmaceutical Sciences
- Central South University
- Changsha
- People's Republic of China
| | - Dan Li
- School of Pharmaceutical Sciences
- Central South University
- Changsha
- People's Republic of China
| | - Shumin Bao
- School of Pharmaceutical Sciences
- Central South University
- Changsha
- People's Republic of China
| | - Zhenxing Zou
- School of Pharmaceutical Sciences
- Central South University
- Changsha
- People's Republic of China
| | - Fenghua Kang
- School of Pharmaceutical Sciences
- Central South University
- Changsha
- People's Republic of China
| | - Guishan Tan
- School of Pharmaceutical Sciences
- Central South University
- Changsha
- People's Republic of China
- Xiangya Hospital of Central South University
| | - Shu-Ming Li
- Institut für Pharmazeutische Biologie und Biotechnologie
- Philipps-Universität Marburg
- 35037 Marburg
- Germany
| | - Xia Yu
- School of Pharmaceutical Sciences
- Central South University
- Changsha
- People's Republic of China
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29
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El-Mahdy NA, Saleh DA, Amer MS, Abu-Risha SES. Role of allopurinol and febuxostat in the amelioration of dextran-induced colitis in rats. Eur J Pharm Sci 2019; 141:105116. [PMID: 31654756 DOI: 10.1016/j.ejps.2019.105116] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 10/20/2019] [Accepted: 10/21/2019] [Indexed: 12/24/2022]
Abstract
Ulcerative colitis is a chronic auto-inflammatory disorder confined to the colorectal region. It is challenging to find an absolute treatment and current therapy aims to ameliorate symptoms, decrease relapses and prevent prognosis of colorectal cancer. In the present study, we investigated the possible action of xanthine oxidase inhibitors in murine colitis model by measuring different indicative parameters and comparing the results to those of the reference sulfasalazine. Also, we compared the effects of combining sulfasalazine and allopurinol to each drug alone. Dextran Sodium Sulfate (DSS) is used in this study to induce ulcerative colitis in male wistar rats as it is known to be the closest model that mimics human ulcerative colitis. Allopurinol was given prior to colitis induction by four days and febuxostat for six days before induction with DSS (5% w/v) and continue to give them concomitantly during the induction.Il-1β, malondialdehyde, reduced glutathione (GSH), xanthine oxidase, and superoxide dismutase were measured in colonic tissue. We also measured concentrations of IL-1β, Il-6 and uric acid in serum. Allopurinol dose-dependently ameliorated biochemical injuries. Febuxostat has shown better results than allopurinol and sulfasalazine, and this is the first study to demonstrate this.
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Affiliation(s)
- Nageh Ahmed El-Mahdy
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Dina Ali Saleh
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
| | - Magdy Salah Amer
- Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
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30
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Hormetic and Mitochondria-Related Mechanisms of Antioxidant Action of Phytochemicals. Antioxidants (Basel) 2019; 8:antiox8090373. [PMID: 31487950 PMCID: PMC6769633 DOI: 10.3390/antiox8090373] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 08/11/2019] [Accepted: 08/28/2019] [Indexed: 12/12/2022] Open
Abstract
Antioxidant action to afford a health benefit or increased well-being may not be directly exerted by quick reduction-oxidation (REDOX) reactions between the antioxidant and the pro-oxidant molecules in a living being. Furthermore, not all flavonoids or polyphenols derived from plants are beneficial. This paper aims at discussing the variety of mechanisms underlying the so-called "antioxidant" action. Apart from antioxidant direct mechanisms, indirect ones consisting of fueling and boosting innate detox routes should be considered. One of them, hormesis, involves upregulating enzymes that are needed in innate detox pathways and/or regulating the transcription of the so-called vitagenes. Moreover, there is evidence that some plant-derived compounds may have a direct role in events taking place in mitochondria, which is an organelle prone to oxidative stress if electron transport is faulty. Insights into the potential of molecules able to enter into the electron transport chain would require the determination of their reduction potential. Additionally, it is advisable to know both the oxidized and the reduced structures for each antioxidant candidate. These mechanisms and their related technical developments should help nutraceutical industry to select candidates that are efficacious in physiological conditions to prevent diseases or increase human health.
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31
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Zhou X, Liu Y, Huang Y, Ma Y, Lv J, Xiao B. Mucus-penetrating polymeric nanoparticles for oral delivery of curcumin to inflamed colon tissue. J Drug Deliv Sci Technol 2019. [DOI: 10.1016/j.jddst.2019.04.030] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Omotoso GO, Olajide OJ, Gbadamosi IT, Adebayo JO, Enaibe BU, Akinola OB, Owoyele BV. Cuprizone toxicity and Garcinia kola biflavonoid complex activity on hippocampal morphology and neurobehaviour. Heliyon 2019; 5:e02102. [PMID: 31367687 PMCID: PMC6646876 DOI: 10.1016/j.heliyon.2019.e02102] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 05/08/2019] [Accepted: 07/15/2019] [Indexed: 12/16/2022] Open
Abstract
Cuprizone-induced neurotoxicity has been employed to study the biology of remyelination in experimental models of multiple sclerosis. This study was aimed at determining the role of kolaviron, a biflavonoid from Garcinia kola, in mitigating the damaging effects of cuprizone on behaviour and the hippocampus. Twenty-four male albino mice aged 6–8 weeks were categorised into 4 equal groups: Group A (Control) received regular diet; Group B received 200 mg/kg/d of kolaviron in addition to their regular diet; Group C received 0.2% cuprizone diet only, while Group D received both kolaviron and cuprizone diet. The treatment lasted for 35 days after which behavioural tests (Morris water maze, Y maze and open field tests) were conducted and brain tissues were processed for histology, histochemistry (Nissl staining), immunohistochemistry (glial fibrillary acidic protein) and biochemistry (malondialdehyde, superoxide dismutase and glutathione peroxidase). Results showed that cuprizone toxicity led to weight loss, impairment in memory and exploratory drive, oxidative stress, chromatolysis and reactive astrocytosis; meanwhile administration of kolaviron prevented cuprizone-induced weight loss, memory decline, oxidative stress and neuromorphological alterations. In conclusion, administration of kolaviron might be useful in limiting the effects of cuprizone toxicity on the morphology and functions of the hippocampus.
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Affiliation(s)
- G O Omotoso
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, P.M.B. 1515, Ilorin 240003, Nigeria
| | - O J Olajide
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, P.M.B. 1515, Ilorin 240003, Nigeria
| | - I T Gbadamosi
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, P.M.B. 1515, Ilorin 240003, Nigeria
| | - J O Adebayo
- Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, P.M.B. 1515, Ilorin 240003, Nigeria
| | - B U Enaibe
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, P.M.B. 1515, Ilorin 240003, Nigeria
| | - O B Akinola
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, P.M.B. 1515, Ilorin 240003, Nigeria
| | - B V Owoyele
- Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, P.M.B. 1515, Ilorin 240003, Nigeria
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33
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Mileo AM, Nisticò P, Miccadei S. Polyphenols: Immunomodulatory and Therapeutic Implication in Colorectal Cancer. Front Immunol 2019; 10:729. [PMID: 31031748 PMCID: PMC6470258 DOI: 10.3389/fimmu.2019.00729] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Accepted: 03/19/2019] [Indexed: 12/12/2022] Open
Abstract
Polyphenolic compounds, widely present in fruits, vegetables, and cereals, have potential benefits for human health and are protective agents against the development of chronic/degenerative diseases including cancer. More recently these bioactive molecules have been gaining great interest as anti-inflammatory and immunomodulatory agents, mainly in neoplasia where the pro-inflammatory context might promote carcinogenesis. Colorectal cancer (CRC) is considered a major public healthy issue, a leading cause of cancer mortality and morbidity worldwide. Epidemiological, pre-clinical and clinical investigations have consistently highlighted important relationships between large bowel inflammation, gut microbiota (GM), and colon carcinogenesis. Many experimental studies and clinical evidence suggest that polyphenols have a relevant role in CRC chemoprevention, exhibit cytotoxic capability vs. CRC cells and induce increased sensitization to chemo/radiotherapies. These effects are most likely related to the immunomodulatory properties of polyphenols able to modulate cytokine and chemokine production and activation of immune cells. In this review we summarize recent advancements on immunomodulatory activities of polyphenols and their ability to counteract the inflammatory tumor microenvironment. We focus on potential role of natural polyphenols in increasing the cell sensitivity to colon cancer therapies, highlighting the polyphenol-based combined treatments as innovative immunomodulatory strategies to inhibit the growth of CRC.
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Affiliation(s)
- Anna Maria Mileo
- Tumor Immunology and Immunotherapy Unit, Department of Research, Advanced Diagnostic and Technological Innovation, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Paola Nisticò
- Tumor Immunology and Immunotherapy Unit, Department of Research, Advanced Diagnostic and Technological Innovation, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Stefania Miccadei
- Tumor Immunology and Immunotherapy Unit, Department of Research, Advanced Diagnostic and Technological Innovation, IRCCS Regina Elena National Cancer Institute, Rome, Italy
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Fasunla AJ, Nwankwo U, Onakoya PA, Oladokun A, Nwaorgu OG. Gustatory Function of Pregnant and Nonpregnant Women in a Tertiary Health Institution. EAR, NOSE & THROAT JOURNAL 2019; 98:143-148. [PMID: 30864460 DOI: 10.1177/0145561319833914] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Physiological changes in pregnancy may cause taste dysfunction. The aim of this study was to determine and compare gustatory function of pregnant women with nonpregnant women and also to investigate the effect of pregnancy on gustatory function. It was a case-control study of consecutive 70 healthy pregnant women (cases) and 70 healthy nonpregnant women (control). Participants scored their taste perception on a visual analogue scale (1-10) and their gustatory function was assessed using "taste strips" impregnated with graded concentration of sweet, sour, salty, and bitter taste substances applied on tongue surfaces. Subjective mean gustatory score, correct identification of taste in the strips and total taste strip (TTS) score were compared between both groups and analysis was done using appropriate statistics. The mean age of pregnant women (30.5 [3.9]) and controls (28.5 [6.6]) were comparable. Twenty-one (30%) pregnant women changed their diet in first trimester due to change in taste sensation. Almost all cases developed craving for spicy and salty foods and, aversions to fish, beans, and vegetables. There was a significant difference in the subjective rating of taste perception between the 2 groups ( P = .037). About 2.9% of pregnant women have hypogeusia. There was a significant difference between pregnant and nonpregnant women in sour taste ( P = .006; 2.90 [0.71] vs 3.92 [0.82]) and TTS ( P = .02; 27.50 [3.48] vs 29.21 [2.69]) scores, respectively. In conclusion, gustatory function was reduced in pregnancy compared to nonpregnant women and this led to dietary change in some pregnant women.
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Affiliation(s)
- Ayotunde James Fasunla
- 1 Department of Otorhinolaryngology, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria
| | - Ukamaka Nwankwo
- 1 Department of Otorhinolaryngology, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria
| | - Paul Adekunle Onakoya
- 1 Department of Otorhinolaryngology, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria
| | - Adesina Oladokun
- 2 Department of Obstetrics and Gynaecology, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria
| | - Onyekwere George Nwaorgu
- 1 Department of Otorhinolaryngology, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria
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Somade OT, Adedokun AH, Adeleke IK, Taiwo MA, Oyeniran MO. Diallyl disulfide, a garlic-rich compound ameliorates trichloromethane-induced renal oxidative stress, NFkB activation and apoptosis in rats. CLINICAL NUTRITION EXPERIMENTAL 2019. [DOI: 10.1016/j.yclnex.2018.10.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Lian L, Zhang S, Yu Z, Ge H, Qi S, Zhang X, Long L, Xiong X, Chu D, Ma X, Li X, Gao H. The dietary freeze-dried fruit powder of Actinidia arguta ameliorates dextran sulphate sodium-induced ulcerative colitis in mice by inhibiting the activation of MAPKs. Food Funct 2019; 10:5768-5778. [DOI: 10.1039/c9fo00664h] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Oral administration freeze-dried Actinidia arguta powder could ameliorate ulcerative colitis disease via inhibiting the activation of MAPKs pathway.
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Ajayi BO, Adedara IA, Farombi EO. Protective mechanisms of 6-gingerol in dextran sulfate sodium-induced chronic ulcerative colitis in mice. Hum Exp Toxicol 2018; 37:1054-1068. [PMID: 29350052 DOI: 10.1177/0960327117751235] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Abstract
Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon, with an increasing incidence worldwide. 6-Gingerol (6G) is a bioactive constituent of Zingiber officinale, which has been reported to possess various biological activities. This study was designed to evaluate the role of 6G in chronic UC. Chronic UC was induced in mice by three cycles of 2.5% dextran sulfate sodium (DSS) in drinking water. Each cycle consisted of 7 days of 2.5% DSS followed by 14 days of normal drinking water. 6G (100 mg/kg) and a reference anti-colitis drug sulfasalazine (SZ) (100 mg/kg) were orally administered daily to the mice throughout exposure to three cycles of 2.5% DSS. Administration of 6G and SZ significantly prevented disease activity index and aberrant crypt foci formation in DSS-treated mice. Furthermore, 6G and SZ suppresses immunoexpression of tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, Regulated on activation, normal T cell expressed and secreted (RANTES), and Monocyte chemoattractant protein-1 (MCP-1) in the DSS-treated mice. 6G effectively protected against colonic oxidative damage by augmenting the antioxidant status with marked decrease in lipid peroxidation levels in DSS-treated mice. Moreover, 6G significantly inhibited nuclear factor kappa B (P65), p38, cyclooxygenase-2, and β-catenin whereas it enhanced IL-10 and adenomatous polyposis coli expression in DSS-treated mice. In conclusion, 6G prevented DSS-induced chronic UC via anti-inflammatory and antioxidative mechanisms and preservation of the Wnt/β-catenin signaling pathway.
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Affiliation(s)
- B O Ajayi
- Department of Biochemistry, Drug Metabolism & Toxicology Research Laboratories, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - I A Adedara
- Department of Biochemistry, Drug Metabolism & Toxicology Research Laboratories, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - E O Farombi
- Department of Biochemistry, Drug Metabolism & Toxicology Research Laboratories, College of Medicine, University of Ibadan, Ibadan, Nigeria
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Ajayi BO, Adedara IA, Ajani OS, Oyeyemi MO, Farombi EO. [6]-Gingerol modulates spermatotoxicity associated with ulcerative colitis and benzo[a]pyrene exposure in BALB/c mice. J Basic Clin Physiol Pharmacol 2018; 29:247-256. [PMID: 29902912 DOI: 10.1515/jbcpp-2017-0140] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 12/13/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND The deterioration of male reproductive health may represent an outcome of an active disease and environmental factors. The present study investigated the modulatory role of [6]-gingerol in spermatotoxicity resulting from colitis and benzo[a]pyrene (B[a]P), an environmental and food-borne pollutant. METHODS Group I (control) mice received corn oil alone, while group II ([6]-gingerol alone) mice orally received [6]-gingerol alone at 100 mg/kg body weight. Group III [benzo[a]pyrene+dextran sulfate sodium (BDS) alone] mice were orally exposed to B[a]P at 125 mg/kg for 7 days followed by three cycles of 4% dextran sulfate sodium (DSS) in drinking water. A cycle consisted of seven consecutive days of exposure to DSS-treated water followed by 14 consecutive days of normal drinking water. Group IV (BDS+[6]-gingerol) mice were orally treated daily with 100 mg/kg of [6]-gingerol during exposure to B[a]P and DSS in the same manner as those of group III. RESULTS [6]-Gingerol significantly abrogated BDS-mediated increase in disease activity index and restored the colon wet weight, colon length and colon mass index to near normal when compared to BDS alone group. Moreover, [6]-gingerol significantly prevented BDS-induced decreases in the daily sperm production (DSP), testicular sperm number (TSN), epididymal sperm number, sperm progressive motility and sperm membrane integrity when compared with the control. [6]-Gingerol markedly increased the sperm antioxidant enzymes activities and decreased the sperm head, mid-piece and tail abnormalities as well as suppressed oxidative stress and inflammatory biomarkers in BDS-exposed mice. CONCLUSIONS [6]-Gingerol protected against spermatotoxicity in experimental model of interaction of colitis with environmental pollutant B[a]P.
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Affiliation(s)
- Babajide O Ajayi
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Isaac A Adedara
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Olumide S Ajani
- Department of Veterinary Surgery and Reproduction, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
| | - Matthew O Oyeyemi
- Department of Veterinary Surgery and Reproduction, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
| | - Ebenezer O Farombi
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
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Kolawole AN, Akinladejo VT, Elekofehinti OO, Akinmoladun AC, Kolawole AO. Experimental and computational modeling of interaction of kolaviron-kolaflavanone with aldehyde dehydrogenase. Bioorg Chem 2018. [DOI: 10.1016/j.bioorg.2018.02.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Mijan MA, Lim BO. Diets, functional foods, and nutraceuticals as alternative therapies for inflammatory bowel disease: Present status and future trends. World J Gastroenterol 2018; 24:2673-2685. [PMID: 29991873 PMCID: PMC6034142 DOI: 10.3748/wjg.v24.i25.2673] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 05/19/2018] [Accepted: 06/09/2018] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a serious health concern among western societies. The disease is also on the rise in some East Asian countries and in Australia. Health professionals and dietitians around the world are facing an unprecedented challenge to prevent and control the increasing prevalence of IBD. The current therapeutic strategy that includes drugs and biological treatments is inefficient and are associated with adverse health consequences. In this context, the use of natural products is gaining worldwide attention. In vivo studies and clinical evidence suggest that well-planned dietary regimens with specific nutrients can alleviate gastrointestinal inflammation by modulating inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), IL-6, IL-1β, and IL-10. Alternatively, the avoidance of high-fat and high-carbohydrate diets is regarded as an effective tool to eliminate the causes of IBD. Many functional foods and bioactive components have received attention for showing strong therapeutic effects against IBD. Both animal and human studies suggest that bioactive functional foods can ameliorate IBD by downregulating the pro-inflammatory signaling pathways, such as nuclear factor κB, STAT1, STAT6, and pro-inflammatory cytokines, including IL-1β, IL-4, IL-6, COX-2, TNF-α, and interferon γ. Therefore, functional foods and diets have the potential to alleviate IBD by modulating the underlying pathogenic mechanisms. Future comprehensive studies are needed to corroborate the potential roles of functional foods and diets in the prevention and control of IBD.
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Affiliation(s)
- Mohammad Al Mijan
- Department of Integrated Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, South Korea
| | - Beong Ou Lim
- Department of Integrated Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, South Korea
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Omotoso GO, Olajide OJ, Gbadamosi IT, Rasheed MA, Izuogu CT. Kolaviron Protects the Prefrontal Cortex and Hippocampus against Histomorphological and Neurobehavioural Changes in Cuprizone Model of Multiple Sclerosis. Malays J Med Sci 2018; 25:50-63. [PMID: 30918455 PMCID: PMC6422579 DOI: 10.21315/mjms2018.25.2.6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 02/06/2018] [Indexed: 12/18/2022] Open
Abstract
Background This study explored the efficacy of kolaviron-a biflavonoid complex isolated from the seeds of Garcinia kola-in protecting against cuprizone (CPZ)-induced demyelination in both the prefrontal cortex and the hippocampus of Wistar rats. Methodology Thirty rats were treated to receive 0.5 mL phosphate-buffered saline (group A, control), 0.5 mL corn oil (group B), 0.2% CPZ (group C), for 6 weeks, 0.2% CPZ for 3 weeks and then 200 mg/kg of Kv for 3 weeks (group D), or 200 mg/kg of Kv for 3 weeks followed by 0.2% CPZ for 3 weeks (group E). Rats were assessed for exploratory functions and anxiety-like behaviour before being euthanised and perfused transcardially with 4% paraformaldehyde. Prefrontal and hippocampal thin sections were stained in hematoxylin and eosin and cresyl fast violet stains. Results CPZ-induced demyelination resulted in behavioural impairment as seen by reduced exploratory activities, rearing behaviour, stretch attend posture, center square entry, and anxiogenic characteristics. Degenerative changes including pyknosis, karyorrhexis, neuronal hypertrophy, and reduced Nissl integrity were also seen. Animals treated with Kv showed significant improvement in behavioural outcomes and a comparatively normal cytoarchitectural profile. Conclusion Kv provides protective roles against CPZ-induced neurotoxicity through prevention of ribosomal protein degradation.
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Affiliation(s)
- Gabriel Olaiya Omotoso
- Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
| | - Olayemi Joseph Olajide
- Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.,International Center for Genetic Engineering and Biotechnology, Padriciano 99, Trieste-Italy
| | - Ismail Temitayo Gbadamosi
- Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
| | - Mikail Abiodun Rasheed
- Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
| | - Chiazokam Tochukwu Izuogu
- Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
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Alabi QK, Akomolafe RO, Omole JG, Adefisayo MA, Ogundipe OL, Aturamu A, Sanya JO. Polyphenol-rich extract of Ocimum gratissimum leaves ameliorates colitis via attenuating colonic mucosa injury and regulating pro-inflammatory cytokines production and oxidative stress. Biomed Pharmacother 2018; 103:812-822. [PMID: 29684860 DOI: 10.1016/j.biopha.2018.04.071] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 04/09/2018] [Accepted: 04/09/2018] [Indexed: 12/13/2022] Open
Abstract
Colitis is a chronic inflammation and ulcer on the inner lining of the large intestine. For many centuries Ocimum gratissimum (OG) leaves have been used in folk medicine in Nigeria to treat inflammatory bowel diseases, however, to date, the anti-colitis effects of OG have not been scientifically proven. In this study we investigated the effects of polyphenol rich extract of Ocimum gratissimum (PREOG) leaf on colonic mucosa injury in colitis, its mechanisms, initial administration time and dosage. Dextran sodium sulfate (DSS)-induced rat colitis models was used. PREOG administration was initiated at 3 and 7 d after the model was established at doses of 200, 400 and 800 mg/kg for 7 d. 5-aminosalicylic acid (5-ASA) was used as a reference drug. The disease activity index (DAI), vascular permeability, markers of oxidative stress, granulocyte infiltration, inflammation and histopathological alteration were evaluated. Obvious colonic inflammation and mucosa injuries were observed in DSS-induced colitis groups. PREOG administration promoted repair of colonic mucosa injuries, attenuated inflammation, and decreased DAI scores in rats with colitis. PREOG also decreased the plasma concentrations of Interleukin-(IL)-6 and tumor necrosis factor (TNF)-α, and concentrations of myeloperoxidase, nitric oxide, cyclooxygenase-2 and malondialdehyde in the colon, and increased the plasma concentrations of IL-4 and IL-10 as well as the concentration of superoxide dismutase, catalase and reduced glutathione in the colon. The efficacy of PREOG was dosage dependent. In conclusion, OG repairs colonic mucosa injury in experimental colitis through its ant-inflammatory and ant-oxidant. Its efficacy related to initial administration time and dose.
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Affiliation(s)
- Quadri K Alabi
- Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria; Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, Afe Babalola University, Ado Ekiti, Ekiti State, Nigeria.
| | - Rufus O Akomolafe
- Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Joseph G Omole
- Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Modinat A Adefisayo
- Department of Physiology, Faculty of Basic Medical Sciences, University of Medical Sciences,Ondo State, Nigeria
| | - Olaofe L Ogundipe
- Department of Public Health and Community Medicine, Afe Babalola University, Ado Ekiti, Ekiti State, Nigeria
| | - Ayodeji Aturamu
- Health Center College of Education, Ikere Ekiti, Ekiti State, Nigeria
| | - Joseph O Sanya
- Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, Afe Babalola University, Ado Ekiti, Ekiti State, Nigeria
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Oyagbemi AA, Omobowale TO, Olopade JO, Farombi EO. Kolaviron and Garcinia kola attenuate doxorubicin-induced cardiotoxicity in Wistar rats. ACTA ACUST UNITED AC 2018; 15:/j/jcim.ahead-of-print/jcim-2016-0168/jcim-2016-0168.xml. [DOI: 10.1515/jcim-2016-0168] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Accepted: 06/06/2017] [Indexed: 01/06/2023]
Abstract
AbstractBackgroundTheMethodsSixty male rats (Wistar strain) were used in this study. They were divided into 6 groups (A-F) each containing 10 animals. Group A was the control. Rats in Groups B, C, D, E and F were treated with doxorubicin at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in groups C, D, E and F were pre-treated orally with Kolaviron at the dosage of 100 mg/kg and 200 mg/kg, andResultsThe results show that doxorubicin caused a significant increase in heart rate and prolonged QT, reduced antioxidant status, increased oxidative stress, inflammation and markers of cardiac damage which were reversed by pre-treatment with Kolaviron andConclusionsOverall, pre-treatment with Kolaviron or
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Gabriela Vogt A, Perin G, Luchese C, da Silva PC, Antunes Wilhelm E, Santos Silva M. Organylselanyl α-Amino Phosphonates: Synthesis, NMR Spectroscopic Study, and Antioxidant and Antinociceptive Activities. European J Org Chem 2018. [DOI: 10.1002/ejoc.201701565] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- Ane Gabriela Vogt
- Programa de Pós-Graduação em Bioquímica e Prospecção; Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio); Grupo de Pesquisa em Neurobiotecnologia - GPN, CCQFA; Universidade Federal de Pelotas - UFPel; 96010-900 Capão do Leão RS Brazil
| | - Gelson Perin
- Programa de Pós-Graduação em Química; Laboratório de Síntese Orgânica Limpa - LASOL, CCQFA; Universidade Federal de Pelotas - UFPel; 96010-900 Capão do Leão RS Brazil
| | - Cristiane Luchese
- Programa de Pós-Graduação em Bioquímica e Prospecção; Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio); Grupo de Pesquisa em Neurobiotecnologia - GPN, CCQFA; Universidade Federal de Pelotas - UFPel; 96010-900 Capão do Leão RS Brazil
| | - Patrícia Cecília da Silva
- Centro de Ciências Naturais e Humanas - CCNH; Universidade Federal do ABC - UFABC; 09210-180 Santo André SP Brazil
| | - Ethel Antunes Wilhelm
- Programa de Pós-Graduação em Bioquímica e Prospecção; Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio); Grupo de Pesquisa em Neurobiotecnologia - GPN, CCQFA; Universidade Federal de Pelotas - UFPel; 96010-900 Capão do Leão RS Brazil
| | - Márcio Santos Silva
- Centro de Ciências Naturais e Humanas - CCNH; Universidade Federal do ABC - UFABC; 09210-180 Santo André SP Brazil
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Catalán-Latorre A, Pleguezuelos-Villa M, Castangia I, Manca ML, Caddeo C, Nácher A, Díez-Sales O, Peris JE, Pons R, Escribano-Ferrer E, Fadda AM, Manconi M. Nutriosomes: prebiotic delivery systems combining phospholipids, a soluble dextrin and curcumin to counteract intestinal oxidative stress and inflammation. NANOSCALE 2018; 10:1957-1969. [PMID: 29319093 DOI: 10.1039/c7nr05929a] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Nutriosomes, new phospholipid nanovesicles specifically designed for intestinal protection were developed by simultaneously loading a water-soluble dextrin (Nutriose® FM06) and a natural antioxidant (curcumin). Nutriosomes were easily fabricated in a one-step, organic solvent-free procedure. The stability and delivery performances of the vesicles were improved by adding hydroxypropyl methylcellulose. All the vesicles were small in size (mean diameter ∼168 nm), negatively charged (zeta potential ∼-38 mV, irrespective of their composition), and self-assembled predominantly in unilamellar vesicles stabilized by the presence of Nutriose®, which was located in both the inter-lamellar and inter-vesicle media, as confirmed by cryo-TEM and SAXS investigation. The dextrin acted also as a cryo-protector, avoiding vesicle collapse during the lyophilization process, and as a protector against high ionic strength and pH changes encountered in the gastrointestinal environment. Thanks to the antioxidant properties of curcumin, nutriosomes provided an optimal protective effect against hydrogen peroxide-induced oxidative stress in Caco-2 cells. Moreover, these innovative vesicles showed promising efficacy in vivo, as they improved the bioavailability and the biodistribution of both curcumin and dextrin upon oral administration, which acted synergically in reducing colonic damage chemically induced in rats.
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Affiliation(s)
- Ana Catalán-Latorre
- Dept. of Scienze della Vita e dell'Ambiente, University of Cagliari, Cagliari, Italy.
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Adedara IA, Ajayi BO, Awogbindin IO, Farombi EO. Interactive effects of ethanol on ulcerative colitis and its associated testicular dysfunction in pubertal BALB/c mice. Alcohol 2017; 64:65-75. [PMID: 28965657 DOI: 10.1016/j.alcohol.2017.06.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 05/02/2017] [Accepted: 06/08/2017] [Indexed: 01/01/2023]
Abstract
Available epidemiological reports have indicated an increase in the incidence of ulcerative colitis, as well as alcohol consumption, globally. The present study investigated the possible interactive effects of ethanol consumption on ulcerative colitis and its associated testicular dysfunction using six groups of 12 pubertal mice each. Group I (Control) mice received drinking water alone. Group II mice received ethanol alone at 5 g/kg body weight. Group III mice received 2.5% dextran sulphate sodium (DSS) in drinking water followed by normal drinking water. Groups IV, V, and VI mice received DSS followed by ethanol at 1.25, 2.5, and 5 g/kg, respectively. Administration of ethanol to mice with ulcerative colitis intensified the disease-activity index with marked reduction in colon length, colon mass index, body weight gain, and organo-somatic indices of testes and epididymis when compared with the DSS-alone group. Moreover, ethanol exacerbated colitis-mediated decrease in enzymatic and non-enzymatic antioxidants but increased the oxidative stress and inflammatory biomarkers in the testes and epididymis. The diminution in luteinizing hormone, follicle stimulating hormone, and testosterone levels was intensified following administration of ethanol to mice with ulcerative colitis that were administered 5 g/kg ethanol alone. The decrease in sperm functional parameters and testicular spermatogenic indices as well as histopathological damage in colon, testes, and epididymis was aggravated following administration of ethanol to mice with ulcerative colitis. In conclusion, the exacerbating effects of ethanol on ulcerative colitis-induced testicular dysfunction are related to increased oxidative stress and inflammation in the treated mice.
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Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis. ASIAN PAC J TROP MED 2017; 10:864-870. [PMID: 29080614 DOI: 10.1016/j.apjtm.2017.08.017] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 07/15/2017] [Accepted: 08/17/2017] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). METHODS The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE2, COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting. RESULTS Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE2 in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment. CONCLUSIONS The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.
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Olajide OJ, Asogwa NT, Moses BO, Oyegbola CB. Multidirectional inhibition of cortico-hippocampal neurodegeneration by kolaviron treatment in rats. Metab Brain Dis 2017; 32:1147-1161. [PMID: 28405779 DOI: 10.1007/s11011-017-0012-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Accepted: 04/06/2017] [Indexed: 01/09/2023]
Abstract
Earliest signs of neurodegenerative cascades in the course of Alzheimer's disease (AD) are seen within the prefrontal cortex (PFC) and hippocampus, with pathological evidences in both cortical structures correlating with manifestation of behavioural and cognitive deficits. Despite the enormous problems associated with AD's clinical manifestations in sufferers, therapeutic advances for the disorder are still very limited. Therefore, this study examined cortico-hippocampal microstructures in models of AD, and evaluated the possible beneficial roles of kolaviron (Kv)-a biflavonoid complex in rats. Nine groups of rats were orally exposed to sodium azide (NaN3) or aluminium chloride (AlCl3) solely or in different combinations with Kv. Sequel to sacrifice and transcardial perfusion (using buffered saline then 4% paraformaldehyde), PFC and hippocampal tissues were harvested and processed for: spectrophotometric assays of oxidative stress and neuronal bioenergetics parameters, histological demonstration of cytoarchitecture and immunohistochemical evaluation of astrocytes and neuronal cytoskeleton. Results showed alterations in mitochondrial functions, which led to compromised neuronal antioxidant system, dysfunctional neural bioenergetics, hypertrophic astrogliosis, cytoskeletal dysregulation and neuronal death within the PFC and hippocampus. These degenerative events were associated with NaN3 and AlCl3 toxicity in rats. Furthermore, Kv inhibited cortico-hippocampal degeneration through multiple mechanisms that primarily involved halting of biochemical cascades that activate proteases which destroy molecules expedient for cell survival, and others that mediate a program of cell suicide in neuronal apoptosis. In conclusion, Kv showed important neuroprotective roles within cortico-hippocampal cells through multiple mechanisms, and particularly has prominent prophylactic activity than regenerative potentials.
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Affiliation(s)
- Olayemi Joseph Olajide
- Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria.
| | - Nnaemeka Tobechukwu Asogwa
- Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin, Nigeria
- Central Research Laboratories Ltd, 132b University Road, Ilorin, Nigeria
| | - Blessing Oluwapelumi Moses
- Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | - Christiana Bidemi Oyegbola
- Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
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Olajide OJ, Ugbosanmi AT, Enaibe BU, Ogunrinola KY, Lewu SF, Asogwa NT, Akapa T, Imam A, Ibrahim A, Gbadamosi IT, Yawson EO. Cerebellar Molecular and Cellular Characterization in Rat Models of Alzheimer's Disease: Neuroprotective Mechanisms of Garcinia Biflavonoid Complex. Ann Neurosci 2017; 24:32-45. [PMID: 28827919 DOI: 10.1159/000464421] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 10/04/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Recent evidences suggest that cerebellar degeneration may be associated with the development of Alzheimer's disease (AD). However, previous reports were mainly observational, lacking substantial characterization of cellular and molecular cerebellar features during AD progression. PURPOSE This study is aimed at characterizing the cerebellum in rat models of AD and assessing the corresponding neuroprotective mechanisms of Garcinia biflavonoid complex (GBc). METHODS Male Wistar rats were grouped and treated alone or in combination with PBS (ad libitum)/day, corn oil (CO; 2 mL/kgBw/day), GBc (200 mg/kgBw/day), sodium azide (NaN3) (15 mg/kgBw/day) and aluminium chloride (AlCl3) (100 mg/kgBw/day). Groups A and B received PBS and CO, respectively; C received GBc; D received NaN3; E received AlCl3; F received NaN3 then GBc subsequently; G received AlCl3 then GBc subsequently; H received NaN3 and GBc simultaneously while I received AlCl3 and GBc simultaneously. Following treatments, cerebellar cortices were processed for histology, immunohistochemistry and colorimetric assays. RESULTS Our data revealed that cryptic granule neurons and pyknotic Purkinje cell bodies (characterized by short dendritic/axonal processes) correspond to indistinctly demarcated cerebellar layers in rats treated with AlCl3 and NaN3. These correlates, with observed hypertrophic astrogliosis, increased the neurofilament deposition, depleted the antioxidant system-shown by expressed superoxide dismutase and glutathione peroxidase, and cerebellar glucose bioenergetics dysfunction-exhibited in assayed lactate dehydrogenase and glucose-6-phosphate dehydrogenase. We further showed that GBc reverses cerebellar degeneration through modulation of neurochemical signaling pathways and stressor molecules that underlie AD pathogenesis. CONCLUSION Cellular, molecular and metabolic neurodegeneration within the cerebellum is associated with AlCl3 and NaN3-induced AD while GBc significantly inhibits corresponding neurotoxicity and is more efficacious when pre-administered.
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Affiliation(s)
- Olayemi Joseph Olajide
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | - Anita Temi Ugbosanmi
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | - Bernard Ufuoma Enaibe
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | - Kehinde Yomi Ogunrinola
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | - Susan Folashade Lewu
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | | | - Tosan Akapa
- Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin, Nigeria
| | - Aminu Imam
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | - Abdulmumin Ibrahim
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | | | - Emmanuel Olusola Yawson
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
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Farombi EO, Adedara IA, Ajayi BO, Idowu TE, Eriomala OO, Akinbote FO. 6-Gingerol improves testicular function in mice model of chronic ulcerative colitis. Hum Exp Toxicol 2017; 37:358-372. [DOI: 10.1177/0960327117703689] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- EO Farombi
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - IA Adedara
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - BO Ajayi
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - TE Idowu
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - OO Eriomala
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - FO Akinbote
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
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